Protective Effect of Modified Shengmaisan on Cardiac Function in Elderly Patients with Myocardial Infarction Based on NF-κB/iNOS/NO Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the protective effect of modified Shengmaisan on cardiac function in elderly patients with myocardial infarction based on the nuclear factor-κB/induction nitric oxide synthase/nitric oxide （NF-κB/iNOS/NO） signaling pathway. MethodA total of 136 elderly patients with myocardial infarction treated in Qinghai Hospital of Traditional Chinese Medicine from december 2019 to december 2021 were included. They were randomly divided into an observation group and a control group， with 68 cases in each group. The control group was treated with conventional western medicine， and the observation group was treated with conventional western medicine + modified Shengmaisan. Both groups were treated with percutaneous coronary intervention for revascularization. The indexes related to cardiac function and levels of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and matrix metalloproteinase-9 （MMP-9） were analyzed and compared between the two groups. The echocardiographic index， cardiac function classification， changes in the NF-κB/iNOS/NO signaling pathway， oxidative stress indexes， and major adverse cardiovascular events （MACE） of the two groups were compared. ResultCompared with those before treatment， the levels of N-terminal B-type natriuretic peptide （NT-pro BNP）， serum inflammatory indexes， left ventricular end systolic volume （LVESV）， left ventricular end diastolic volume （LVEDV）， NO， iNOS， NF-κB p65， and methane dicarboxylic aldehyde （MDA） were significantly reduced （P<0.05，P<0.01）， and the left ventricular ejection fraction （LVEF） and superoxide dismutase (SOD） were significantly increased （P<0.05）. After treatment， as compared with the control group， the levels of NT-pro BNP， serum inflammatory indexes， LVESV， LVEDV， NO， iNOS， NF-κB p65， and MDA in the observation group were significantly reduced （P<0.05）， and those of LVEF and SOD were significantly increased （P<0.05）. There was no significant difference in the New York Heart Association (NYHA) cardiac function classification between two groups. The incidence of MACE in the observation group was significantly lower than that in the control group （P<0.05）. ConclusionModified Shengmaisan can significantly reduce NT-pro BNP and levels of serum inflammatory indexes in elderly patients with myocardial infarction， improve echocardiographic indexes， regulate the NF-κB/iNOS/NO signaling pathway， and reduce the oxidative stress index and the incidence of MACE， which has a good protective effect on cardiac function.

Roles and perspectives of inflammatory factors in diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is the leading cause of blindness in the working-age population, in which diabetic macular edema(DME)is the most common reason resulting in the vision impairment. Studies showed that inflammation factors play an important role in the pathogenesis and development of DME. Chronic hyperglycemia activates several biochemical pathways, leading to retinal hypoxia, oxidative stress and chronic inflammation. Intraretinal inflammation-related cells, such as microglia, monocytes/macrophages, Müller cells and retinal pigment epithelial cells, become activated and release a large number of inflammation-related factors and mediators, including the complement system, vascular endothelial growth factor(VEGF), placental growth factor(PlGF), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6 and IL-8, etc., resulting in the breakdown of the blood-retinal barrier and neuronal degeneration. In addition, up-regulatethe expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)by retinal vascular endothelial cells increased the adhesion of leukocyte and leukostasis, further aggravating retinal hypoxia and breakdown of the blood-retinal barrier, leading to the increased retinal vascular leakage and macular edema. Therefore, early treatment with anti-VEGF and anti-inflammatory are pivotal for the treatment of DME. In this review, we will discuss the role of inflammation factors in the pathogenesis of DME and the research status of the targeted drugs targeting inflammation, so as to provide reference for the treatment of DME.

Clinical study on 3% Diquafosol Sodium eye drops in treatment of meibomian gland dysfunction-related dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical effect of 3% diquafosol sodium eye drops in treatment of meibomian gland dysfunction-related dry eye.METHODS: The study involved 280 patients totally with meibomian gland dysfunction-related dry eye in the ophthalmology department, Hangzhou Hospital of Traditional Chinese Medicine from May 2020 to May 2021. Patients were divided into the treatment group(160 cases with 320 eyes)and the control group(120 cases with 240 eyes)according to the randomized number table method. The control group was treated with YangXueRunMu formula combined with 0.3% sodium hyaluronate eye drops, the treatment group was treated with YangXueRunMu formula combined with 3% diquafosol sodium eye drops. Both groups were administered for 4wk. The following indicators were measured before and after treatment at 2 and 4wk, respectively: the ocular surface disease index(OSDI)score, Schirmer I test( SⅠt), comprehensive analysis of tear meniscus height(TMH), non-invasive tear film break-up time(NITBUT), meibomian gland lipid secretion of smooth degree scoring and meibomian gland loss rate score, the determination of interleukin-6(IL-6)in tears and the level of tumor necrosis factor-alpha(TNF-α). The efficacy of these tests results was evaluated among these indicators.RESULTS: The overall effective rates of the treatment group and the control group were 95.6% and 81.7% respectively(P<0.05). After 2, 4wk of treatment, the ocular surface disease index(OSDI), NITBUT, meibomian gland lipid secretion scoring, meibomian gland loss rate score and the levels of IL-6 and TNF-α in tears of two groups were significantly different than before treatment(P<0.05). and the treatment group was better than the control group; there was no difference between the SⅠt and TMH groups before and after treatment in the two groups(P>0.05).CONCLUSION: The 3% diquafosol sodium eye drops can promote the normal secretion of meibomian gland by prolonging the homeostasis of the tear membrane, and it can also inhibit the release of inflammatory factors in tears in the treatment of blebomian gland dysfunction-related dry eye.

M1 macrophages promote non-alcoholic steatohepatitis / 中华消化杂志

Objective:To investigate the function, mechanism and therapeutic potential of macrophages in non-alcoholic steatohepatitis (NASH).Methods:Eight-week-old male foz/ foz (Alms mutant) mice were fed with a high fat diet (HFD) for 6, 8 and 10 weeks and 8-week-old male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet for 7 d, 3 weeks and 4 weeks to establish NASH models. The mice of control group were fed with normal diet or MCD control diet. The expression of F4/80 mRNA level in the livers of mice of NASH model group and control group was detected by fluorescence quantitative polymerase chain reaction. Macrophages in the livers of mice of NASH group and control group were determined by immunofluorescence staining. After transgenic lysM-Cre/DTR mice were fed with MCD diet for 5 weeks, they were divided into transgenic experimental group (ablation of macrophages induced by diphtheria-toxin (DTox) injection) and transgenic control group (phosphate buffer saline injection). The levels of triglyceride and lipid peroxide in the livers of transgenic experimental group and transgenic control group were detected, and the inflammation of the livers of the mice was scored. The mechanism of macrophages regulating inflammation in NASH was investigated by cytokine profiliny analysis and Western blotting. The interaction between hepatocytes and macrophages were determined by co-culturing the conditional medium of hepatocytes AML-12 and macrophages RAW264.7. Macrophages of mice of control group and NASH model group were depleted by liposomal clodronate to confirm its value in NASH prevention. Independent sample t-test was used for statistical analysis. Results:F4/80 mRNA level in the livers of NASH model foz/ foz mice fed with HFD for 6 weeks, 8 weeks and 10 weeks was higher than that of control group (1.49±0.19, 1.70±0.15 and 1.93±0.04 vs.1.05±0.22), and the differences were statistically significant ( t=3.06, 4.92 and 7.92, all P<0.05). The expression of F4/80 mRNA level of the livers of NASH model mice fed with MCD for 7 d and 3 weeks was higher than that of control group (2.70±0.99 and 3.08±1.71 vs.1.00±0.83), and the differences were statistically significant ( t=3.43 and 3.54, both P<0.01). The results of immunofluorescence demonstrated that compared with that of control group, the number of F4/80 + inducible nitric oxide synthase (iNOS) + M1 macrophages were significantly increased, while F4/80 + CD206 + M2 macrophages were significantly decreased in the livers of NASH model mice fed with MCD for 4 weeks. After macrophages depletion, the inflammation score, the levels of triglyceride and lipid peroxide in the liver of transgenic experimental mice were all lower than those of transgenic control mice (0.69±0.32 vs. 1.95±0.74, (43.97±13.24) g/mg vs. (63.09±14.85) g/mg, (24.84±6.21) nmol/mg vs.(37.91±8.91) nmol/mg), and the differences were statistically significant ( t =3.14, 2.72 and 2.41, all P<0.05). The results of cytokine profiling analysis showed that macrophage depletion could lower the levels of interleukin (IL)-12 and macrophages inflammatory protein-1α (the difference between multiples: -3.98, -2.74, both P<0.05). CCAAT/enhancer binding protein β was defected in the nuclear of transgenetic experimental mice. In vitro study showed that RAW264.7 macrophages conditional medium could promote lipid accumulation in AML-12 hepatocytes, while conditional medium from MCD medium-treated AML-12 hepatocytes could promote RAW264.7 macrophages to M1 polarization. After treated with liposomal clodronate, the levels of triglyceride and lipid peroxidation in the liver of control mice were both lower than those of MCD-induced NASH model mice((45.33±14.59) g/mg vs. (63.10±16.02) g/mg, (2.11±0.48) nmol/mg vs. (2.73±0.17) nmol/mg), and the differences were statistically significant ( t=2.84 and 2.73, both P<0.05). The results of Western blotting indicated that after treating with liposomal clodronate, the relative content of phosphorylated protein kinase R-like endoplasmic reticulum kinase, inositol requiring enzyme-1α, protein disulfide isomerase, glucose regulatory protein 78, phosphorylated eukaryotic initiation factor 2α in the liver of NASH model mice were all lower than those of NASH model mice without liposomal clodronate treatment (1.84±0.36 vs. 3.05±0.83, 1.50±0.84 vs. 6.65±1.47, 0.87±0.12 vs. 2.28±0.52, 1.68±0.43 vs. 4.76±1.13, 1.42±0.19 vs. 2.75±0.79), and the differences were statistically significant( t=2.32, 5.28, 4.56, 4.41 and 2.85, all P<0.05). Conclusions:Macrophages are polarized into M1 phenotype in NASH. M1 macrophages contributed to NASH progression by interacting with hepatocyets to promote the secretion of inflammatory cytokines, up-regulation of lipogenic factors, oxidative stress and endoplasmic reticulum stress, resulting in the progression of NASH. Macrophages depletion by liposomal clodronate is a potential noval approach for NASH prevention.

Serum levels of sST2 and inflammatory factors in patients with acute left ventricular ejection fraction reduction heart failure treated with sacubitril/valsartan / 中华全科医师杂志

Objective:To investigate the serum levels of soluble growth stimulation expression gene 2 protein (sST2) and inflammatory factors in patients with acute left ventricular ejection fraction reduction heart failure (HFrEF) treated with sacubitril/valsartan.Methods:Ninety six patients with acute HFrEF admitted in The Affiliated Hospital of Qingdao University from March 2020 to March 2021 were enrolled. The patients were treated with sacubitril/valsartan,the dose was gradually increased from 50 mg b.i.d to the target dose of 200 mg b.i.d according to hemodynamics. After 12 weeks, the target dose was achieved in 72 cases (compliance group), and did not achieved in 24 cases (non-compliance group). The serum levels of sST2, IL-1β, IL-6, TNF-αand IL-10 were measured and compared between the two groups. The changes in left atrial anteroposterial diameter (LA), left ventricular end-diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) values were assessed with echocardiography. The adverse reactions, readmission rate and all-cause death within 3 months after discharge were compared between the two groups.Results:A total of 96 patients with acute HFrEF completed the follow-up, including 72 patients (75.0%) in the compliance group and 24 (25.0%) in the non-compliance group; aged 50-75 (66.1±6.7) years old, and 68 (70.8%) males. After treatment, the serum levels of sST2, IL-1β, IL-6 and TNF-α were decreased, and the IL-10 level was increased in both groups ( P<0.05); while the improvement of serum indicators in the compliance group was more marked ( P<0.05). Echocardiography showed that the LA, LVDd, and LVEF were significantly increased after treatment ( P<0.05) in compliance group, while there was no significant changes before and after treatment in the non-compliance group. SST2, inflammatory factors and echocardiographic measurements of patients in the standard group had statistical significance before and after treatment ( P<0.05), and the difference showed a downward trend. No deterioration of renal function and angioedema were observed in both groups, and there was no significant difference in hyperkalemia (two in compliance group and one in non-compliance group), symptom hypotension (each in two groups) between the two groups (χ 2=0.12, 0.68; P>0.05). In the non-compliance group, 10 patients (41.7%) were readmitted due to heart failure, and 6 patients (25.0%) died; while there were no readmitted cases or fatal cases in compliance group (χ 2=33.49, 19.20; P<0.05). Conclusion:Early application of sacubitril and valsartan sodium in patients with acute HFrEF after hemodynamic stabilization can significantly improve left ventricular remodeling, for those with earlier escalation to the target dose, it is more beneficial. The changes of serum sST2 and inflammatory factor level after treatment may predict the efficacy of sacubitril/valsartan therapy.

Role of long non-coding RNA 068 in the migration of melanoma cells / 中华皮肤科杂志

Objective:To investigate the effect of long non-coding RNA 068 (lncRNA 068) on the migration of a melanoma cell line A375, and to explore its mechanism of action.Methods:From December 2015 to November 2020, 21 patients with pathologically confirmed cutaneous melanoma were collected from Department of Dermatology, Affiliated Hospital of Nantong University, and quantitative PCR (qPCR) was performed to determine the expression of lncRNA 068 in melanoma and paracancerous tissues. LncRNA 068 was overexpressed or knocked down via lentiviral transfection in A375 human melanoma cells in the following experiments. Specifically, A375 cells were divided into lentiviral vector (LV) -green fluorescent protein (GFP) group and LV-lncRNA 068 group to be transfected with a GFP-expressing LV and a LV containing lncRNA 068 respectively in the overexpression experiment, and were divided into LV-LacZ short hairpin RNA (shRNA) group and LV-lncRNA 068 shRNA group to be transfected with a LV containing the reporter gene LacZ-specific shRNA and a LV containing the lncRNA 068-targeting shRNA respectively in the low-expression experiment, with the LV-GFP group and LV-LacZ shRNA group serving as the control groups. Transwell and scratch assays were performed to evaluate cell migration, EdU cell proliferation assay and cell counting kit-8 (CCK8) assay to determine the proportion of proliferative cells and cell viability respectively, and immunofluorescence staining was conducted to evaluate epithelial-mesenchymal transformation in the above groups. Lentivirus-transfected A375 cells from the above groups were inoculated into the axillae of BALB/c nude mice, and tumor volume was measured and calculated every 3 days. After 30 days, all mice were sacrificed, and tumor tissues were resected to measure the tumor volume and weight. Cultured B16F10 cells were subcutaneously inoculated into the back and foot of BALB/c nude mice to construct mouse models of subcutaneously transplanted B16F10 melanoma. After 2 weeks, the mice were sacrificed, and qPCR and Western blot analysis were performed to determine the mRNA expression of inflammatory factors in transplanted B16F10 melanoma and paracancerous tissues, and expression of IκB kinase (IKK) /P65 signaling pathway-related proteins, respectively. Comparisons between 2 groups were done by t test, and comparisons of tumor volume and weight at different time points among groups were done by repeated measures analysis of variance. Results:qPCR showed that the relative expression of lncRNA 068 was significantly lower in human melanoma tissues and transplanted B16F10 murine melanoma tissues (0.414 ± 0.109, 0.717 ± 0.041, respectively) than in the corresponding paracancerous tissues (1.050 ± 0.103, 1.011 ± 0.023, t = 19.48, 10.83, respectively, both P < 0.001). Transwell and scratch assays both showed that the cellular migratory ability was significantly lower in the LV-lncRNA 068 group than in the LV-GFP group (both P < 0.01), and significantly higher in the LV-lncRNA 068 shRNA group than in the LV-LacZ shRNA group (both P < 0.05). Immunofluorescence assay showed significantly increased fluorescence intensity of E-cadherin and decreased fluorescence intensity of N-cadherin in the LV-lncRNA 068 group compared with the LV-GFP group (both P < 0.001), but significantly decreased fluorescence intensity of E-cadherin and increased fluorescence intensity of N-cadherin in the LV-lncRNA 068 shRNA group compared with the LV-LacZ shRNA group (both P < 0.05). In vivo tumor formation experiment in nude mice showed that there were no significant differences in the volume or weight of melanoma between the LV-lncRNA 068 group and LV-GFP group (both P > 0.05), as well as between the LV-lncRNA 068 shRNA group and LV-LacZ shRNA group (both P > 0.05). As qPCR and Western blot analysis showed, the mRNA and protein expression of interleukin-10 (IL-10) and claudin-1 in A375 cells were significantly higher in the LV-lncRNA 068 group than in the LV-GFP group (both P < 0.05), but significantly lower in the LV-lncRNA 068 shRNA group than in the LV-LacZ shRNA group (both P < 0.05). Compared with the paracancerous tissues, B16F10 melanoma tissues showed significantly decreased mRNA expression of IL-10 ( P < 0.01), but significantly increased mRNA expression of IL-6 and tumor necrosis factor-α, as well as protein expression of phosphorylated P65 and phosphorylated IKK ( P < 0.01) . Conclusion:Overexpression of lncRNA 068 can inhibit the migration of A375 melanoma cells, and may affect the development of inflammation and inhibit the epithelial-mesenchymal transformation by inhibiting the IKK/P65 signaling pathway.

Clinical Efficacy of Negative Pressure Sealing Drainage Combined with Compound Huangbai Liquid on Diabetic Foot and Effect on Serum Inflammatory Factors / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of negative pressure sealing drainage combined with compound Huangbai liquid on diabetic foot and effects on serum inflammatory factors. MethodA total of 168 patients with diabetic foot treated in Rizhao Hospital of Traditional Chinese Medicine from January 2019 to December 2021 were enrolled and randomly divided into a control group （84 cases） and an experimental group （84 cases）. All patients received basic treatment such as blood glucose control and anti-infection. The patients in the control group were treated with negative pressure drainage combined with normal saline，while those in the experimental group were treated with negative pressure drainage combined with compound Huangbai liquid. The ulcer areas，Visual Analogue Scale （VAS） scores，ankle-brachial index （ABI），CT angiography of the lower extremities （diameter of the dorsalis pedis artery，average blood velocity，and blood flow），and serum inflammatory factors［C-reactive protein （CRP），interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）］ of the two group were compared before and after treatment，and the quality of life，satisfaction，and clinical efficacy of patients in the two groups were assessed after treatment. ResultCompared with the conditions before treatment，the two groups showed reduced ulcer areas，VAS scores，mean blood flow rate of dorsal foot artery，CRP，IL-6，and TNF-α levels （P<0.05），increased ABI，dorsum arterial blood flow，and lumen diameter（P<0.05），and improved quality of life （P<0.05）. Compared with the control group after treatment，the experimental group showed superior improvement in the ulcer area，VAS score，ABI，mean blood flow rate of dorsal foot artery，blood flow，and serum inflammatory factors（P<0.05），better quality of life，and higher satisfaction of treatment effect （P<0.05）. Under different treatment protocols，the total clinical effective rate of the experimental group was 92.86%（78/84），higher than 71.43%（60/84） in the control group （χ2=13.070，P<0.05）. ConclusionNegative pressure sealing drainage combined with compound Huangbai liquid for the treatment of diabetic foot can effectively relieve the clinical symptoms in patients，reduce ulcer area and VAS score，improve the blood circulation in dorsalis pedis artery，and decrease the levels of CRP，IL-6，and TNF-α，thereby inhibiting the occurrence of inflammatory reaction.

Effect of Wudan Pill on Polarization of Macrophages in Endometriosis with Cold Congeal and Blood Stasis Syndrome Based on p38 MAPK Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Wudan pill on the polarization of macrophages in the rat model of endometriosis （EMT） with cold congeal and blood stasis syndrome based on p38 mitogen-activated protein kinases （p38 MAPK）. MethodFemale SD rats with regular motility cycles were selected and randomly divided into sham-operated group， model group， Wudan pill high， medium， and low-dose groups （2.4， 1.2， and 0.6 g⋅kg-1）， Chinese patent medicine group， and western medicine group by the random number table method. The method of ice water bath + autologous endometrial transplantation was used to establish the rat model of EMT with cold congeal and blood stasis， and the rats were executed after 4 weeks of continuous drug administration to collect materials. Expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-4， and transforming growth factor-β （TGF-β） were determined by enzyme-linked immunosorbent assay （ELISA） to assess inflammation. The real-time quantitative polymerase chain reaction （Real-time PCR） was performed to determine the inducible nitric oxide synthase （iNOS）， TNF-α， arginase 1 （Arg1）， and human mannose receptor （CD206） transcriptional levels to evaluate macrophage polarization. Western blot （WB） and immunofluorescence （IF） assays were used to determine the protein expression levels of iNOS and Arg1 to corroborate macrophage polarization. WB and Real-time PCR were used to determine the protein expression levels of the p38 MAPK pathway. ResultAs compared with sham-operated group， the levels of serum TNF-α， IL-1β， TGF-β， and IL-4 of rats in the model group were significantly higher （P<0.05）. In the model group， the protein levels of iNOS， TNF-α， p-p38 MAPK， and phosphorylated-extracellular signal-regulated kinase （p-ERK） in endothelial tissues were significantly higher， the mRNA levels of iNOS， TNF-α， MAPK， and ERK were significantly higher， and the mRNA and protein expression levels of Arg1 and CD206 were significantly lower （P<0.05， P<0.01）. The number of iNOS positive cells in endothelial tissues was significantly increased， and the number of Arg1 positive cells in endothelial tissues in the model group was significantly decreased （P<0.05， P<0.01）. As compared with the model group， the expression of TNF-α， IL-1β， TGF-β， and IL-4 in each administration group was reduced to different degrees， which was especially significant in the Wudan pill high and medium-dose groups and the western medicine group （P<0.05）. The protein expression levels of iNOS， TNF-α， p-p38 MAPK， and p-ERK in endometrial tissues of rats in the Wudan pill high and medium-dose groups， the Chinese patent medicine group， and the western medicine group were significantly lower， the mRNA expression levels of iNOS， TNF-α， MAPK， and ERK were significantly lower， and the protein expression levels of Arg1 and CD206 were significantly higher （P<0.05， P<0.01）. The number of iNOS positive cells in endometrial tissues of rats was significantly decreased in the Wudan pill high and medium-dose groups， the Chinese patent medicine group， and the western medicine group， whereas the number of Arg1 positive cells was increased （P<0.05， P<0.01）. The low， medium， and high doses of Wudan pill were dose-dependent， and the efficacy of the Wudan pill high-dose group was similar to that of the western medicine group. ConclusionWudan pill reduces the inflammatory response in rat model of EMT with cold congeal and blood stasis syndrome and decreases expression levels of TNF-α， IL-1β， IL-4， and TGF-β， thereby prompting polarization of macrophages from M1 to M2 type. The mechanism is presumedly related to p38 MAPK signaling pathway.

Effect of Activating Blood Therapy of Traditional Chinese Medicine on Inflammatory Factors in Patients with Acute Cerebral Infarction： A Review / 中国实验方剂学杂志

Acute cerebral infarction （ACI）， also known as ischemic stroke， is a disease with a high disability rate， which brings heavy burdens to society and families. Its pathogenesis is related to many factors， of which the inflammatory theory is one of the important mechanisms. In the early stage of ACI， microglia are activated， and the inflammatory mediators， such as interleukins and tumor necrosis factor-α （TNF-α）， released by them induce vascular endothelial cells to express adhesion molecules. The circulating leukocytes （neutrophils， monocyte-macrophages， etc.） are promoted to roll and adhere to the injured vascular endothelium， migrate and cross the blood-brain barrier， penetrate and infiltrate the brain parenchyma， and further expand the local inflammatory response by releasing a variety of proinflammatory mediators， thus exacerbating the tissue injury at the injury site and ischemic penumbra. Traditional Chinese medicine （TCM） has advantages in treating the disease. TCM believes that the occurrence of stroke is related to blood stasis caused by various reasons， which block the brain vessel. This article reviewed the research progress on the effect of activating blood therapy on inflammatory factors in patients with ACI in recent years and discussed its regulation of inflammatory factors in ACI such as interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， TNF-α， C reactive protein （CRP）， and monocyte chemotactic protein-1 （MCP-1）， hoping to elucidate the scientific connotation of TCM treatment of ACI and lay the foundation for further research.

Effect of Shenling Guchang Prescription on Gestational Diabetes Rats Based on Intestinal Microecology / 中国实验方剂学杂志

ObjectiveTo study the mechanism of Shenling Guchang prescription on blood glucose of gestational diabetes mellitus rats by regulating intestinal flora and short chain fatty acids. MethodThe 30 pregnant rats were randomly selected from 36 pregnant rats which were successfully pregnant. The model rats were fed with high-fat and high-sugar diet for 1 week， and 35 mg·kg-1 streptozotocin （ STZ ） was given for 3 consecutive days to construct a gestational diabetes model. After successful modeling， the rats were randomly divided into model group， metformin group， Shenling Guchang prescription low-， medium- and high-dose group. The high dose group of Shenling Guchang prescription was given 18 mg·kg-1， the middle dose group was given 9 mg·kg-1， the low dose group was given 4.5 mg·kg-1 drug solution by gavage， the metformin group was given 52.5 mg·kg-1 drug solution by gavage， the blank group and the model group were given equal volume of normal saline by gavage.At 24 h after the last administration， blood samples were collected from the tail tip of the rats to measure the blood glucose， and blood samples were collected from the abdominal aorta under anesthesia to measure the levels of triglyceride （TG）， total cholesterol （TC）， high density lipoprotein cholesterol （HDL-C） and low density lipoprotein cholesterol （LDL-C）. Lipopolysaccharides （LPS）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and insulin （INS） were detected by enzyme-linked immunosorbent assay （ELISA）.The intestinal tissue of rats was taken， and the pathological changes of intestinal tissue were observed by hematoxylin-eosin （HE） staining. Fecal samples were collected from rats， 16S rRNA sequencing was used to detect intestinal flora， and short-chain fatty acids were detected by gas chromatography. ResultCompared with the blank group， the incidence of adverse pregnancy outcomes in the model group was significantly increased （P<0.05）. Compared with the model group， the incidence of adverse pregnancy outcomes in the Shenling Guchang prescription groups and the metformin group was significantly decreased （P<0.05）. Compared with the blank group， the levels of blood glucose， TG， TC， HDL-C， LDL-C， LPS， IL-1β， IL-6 and TNF-α in the model group were significantly increased （P<0.05）， and the intestinal tissues had different degrees of inflammatory changes and mucosal damage. Compared with the model group， the levels of blood glucose， TG， TC， HDL-C， LDL-C， LPS， IL-1β， IL-6 and TNF-α in each group of Shenling Guchang prescription and metformin group were down-regulated （P<0.05）， and intestinal inflammation and intestinal mucosal damage were improved. Compared with the blank group， the functional structure and diversity of intestinal flora in the model group changed （P<0.05）. Compared with the model group， the functional structure and diversity of intestinal flora in the Shenling Guchang prescription groups and the metformin group were reversed， and the trend was close to the blank group （P<0.05）.Compared with the blank group， the abundance of pathogenic bacteria such as Escherichia coli， Enterococcus， Klebsiella， and Dustella in the model group was significantly increased， and the abundance of probiotics such as Prevotella， Prevotella， Akmania， Rombustella， and Lachnospiraceae was decreased （P<0.05）. Compared with the model group， the abundance of pathogenic bacteria such as Escherichia coli， Enterococcus， Klebsiella， and Dustella was decreased （P<0.05）， and the abundance of probiotic bacteria such as Prevotella， Akmanella， Rombustella， and Lachnospira was increased （P<0.05） in the Shenling Guchang prescription groups and the metformin group. Compared with the blank group， the content of short-chain fatty acids in the model group was significantly decreased （P<0.05）. Compared with the model group， the content of short-chain fatty acids in each group of Shenling Guchang prescription and metformin group increased （P<0.05）. Correlation analysis showed that Proteobacteria was positively correlated with inflammatory factors， blood glucose and blood lipid in gestational diabetes mellitus （P<0.05）. ConclusionShenling Guchang prescription has a good regulatory effect on blood glucose， blood lipids and adverse pregnancy outcomes in rats with gestational diabetes mellitus. Its efficacy is comparable to that of metformin sustained-release tablets. Its mechanism may be related to regulating the structure of intestinal flora， increasing the content of short-chain fatty acids， reducing LPS， IL-1β， IL-6， TNF-α， and improving intestinal inflammation.

Effect of segmentectomy versus lobectomy under single utility port video-assisted thoracic surgery on inflammatory factors and immune cells in peripheral blood of non-small cell lung cancer patients: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To evaluate the clinical effects of segmentectomy versus lobectomy under single utility port video-assisted thoracic surgery on inflammatory factors and immune cells in peripheral blood of non-small cell lung cancer patients, and to analyze the effect of changes of postoperative inflammatory factors and immune cells on the prognosis of the patients. Methods    The clinical data of 256 patients who underwent segmentectomy or lobectomy under single utility port video-assisted thoracic surgery for non-small cell lung cancer in the First Affiliated Hospital of Hebei North University from January 2016 to October 2020 were retrospectively collected. According to the operation method, they were divided into a segmentectomy group (126 patients with 79 males and 47 females at an age of 63.4±6.2 years) and a lobectomy group (130 patients with 91 males and 39 females at an age of 62.9±5.6 years). The change of inflammatory factors (C reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-α) and immune cells (CD4+T cells, CD8+T cells and natural killer cells) were recorded and analyzed before operation (T0) and 1 day (T1), 3 days (T2), 7 days (T3), 1 month (T4) after the operation between the two groups. According to postoperative recurrence situations, they were divided into a recurrence group and a non-recurrence group, multivariate logistic regression analysis was used to analyze the relationship between the change of postoperative inflammatory factors, immune cells, and the prognosis of patients with non-small cell lung cancer. Results    (1) There was no statistical difference in sex ratio, underlying diseases, body mass index, levels of preoperative inflammatory factors or immune cells between the two groups (all P>0.05). (2) The changes of postoperative inflammatory factors in the segmentectomy group were significantly less than those in the lobectomy group at T1-T3 (all P<0.05), and the changes of postoperative immune cells in the segmentectomy group were significantly less than those in the lobectomy group at T1-T4 (all P<0.05). (3) The changes of postoperative inflammatory factors and immune cells on postoperative day 3 in the recurrence group were significantly more than those in the non-recurrence group (all P<0.05). (4) Multivariate logistic regression analysis showed that the changes of postoperative inflammatory factors and immune cells on postoperative day 3 may be the risk factors for postoperative recurrence and metastasis in patients with non-small cell lung cancer (all P<0.05). Conclusion    Single utility port video-assisted thoracic surgery segmentectomy for the treatment of non-small cell lung cancer can reduce the inflammatory response and protect body's immune function, and the change of postoperative inflammatory factors and immune cells in postoperative day 3 may be the risk factors for postoperative recurrence and metastasis in patients with non-small cell lung cancer.

Effect of Gegen Qinliantang-medicated Serum on Nonalcoholic Steatohepatitis Based on Nrf2/TXNIP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Gegen Qinliantang （GGQLT）-medicated serum on free fatty acid （FFA）-induced nonalcoholic steatohepatitis （NASH） in vitro model of human hepatoma cells HepG2. MethodNASH model of HepG2 cells was established in vitro， and the cells were intervened with different volume fractions of GGQLT-medicated serum and resveratrol. Intracellular lipid deposition in each group was detected by oil red O staining， the level of reactive oxygen species （ROS） in each group were detected by flow cytometry， the levels of glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， triglyceride （TG） and malondialdehyde （MDA） in each group were detected by kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of nuclear transcription factor （NF）E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （NQO1）， Kelch-like epichlorohydrin-associated protein-1 （Keap1）， NF-κB， thioredoxin interacting protein （TXNIP）， interleukin-1β （IL-1β） in HepG2 cells of each group. The protein expression of Nrf2， TXNIP in cells of each group was detected by Western blot. ResultFFA induced large accumulation of intracellular lipids. Compared with the normal group， the activities of GSH-Px and SOD were significantly decreased （P<0.01） and the contents of TG， ROS and MDA were significantly increased （P<0.05， P<0.01） in the model group. Compared with the model group， all GGQLT groups and resveratrol group could elevate intracellular SOD activity to different degrees （P<0.05， P<0.01） and significantly reduce the levels of intracellular ROS and MDA （P<0.05， P<0.01）， GGQLD high- and medium-dose groups and resveratrol group significantly elevated GSH-Px activity （P<0.01）， GGQLD medium- and low-dose groups and resveratrol group significantly decreased TG content （P<0.05， P<0.01）. Compared with the model group， GGQLT high- and medium-dose groups and resveratrol group could significantly upregulate the mRNA expression levels of Nrf2， HO-1 and NQO1 （P<0.01）， all GGQLT groups and resveratrol group could significantly downregulate the TXNIP protein expression level， as well as significantly downregulate the mRNA expression levels of Keap1， NF-κB （P<0.05， P<0.01）. Nrf2-siRNA transfection of cells revealed that Nrf2 expression was significantly downregulated （P<0.01） in the Nrf2-siRNA group of cells by comparing with NC-siRNA group at the corresponding dose of drugs， and the inhibitory effects of GGQLT and resveratrol on TXNIP， IL-1β were attenuated. ConclusionFFA induces the production of ROS and inflammatory factors in HepG2 cells， and GGQLT can improve the anti-inflammatory and antioxidant capacities of cells， and its mechanism may be related to the regulation of Nrf2/TXNIP signaling pathway， so as to improve NASH.

Indirubin relieves inflammatory injury of chondrocytes in a mouse model of osteoarthritis / 南方医科大学学报

OBJECTIVE@#To investigate the effect of indirubin for relieving joint inflammation and injury in a rat model of osteoarthritis.@*METHODS@#Articular cartilage chondrocytes were isolated from adult rat knee joint and cultured in the presence of interleukin-1β (IL-1β) and 0.1, 0.5, 1.0, or 2.0 μmol/L indirubin. The cells were transfected with NPAS2 siRNA or a non-specific siRNA, and the cell proliferation and apoptosis were evaluated using tetramethylthiazole blue staining and flow cytometry. The protein expression levels of Bax, Bcl-2, ACAN, COL2A1, MMP-13 and NPAS2 were detected with Western blotting, and the levels of NO, PGE2 and TNF-α in the culture supernatant were determined with ELISA. The mRNA expression levels of NPAS2, ACAN, COL2A1 and MMP-13 were detected using fluorescence quantitative PCR. In a C57BL/6 mouse model of osteoarthritis, the effect of indirubin on BAX, Bcl-2, ACAN and MMP-13 protein expressions in the bone and joint tissues were evaluated with Western blotting.@*RESULTS@#Treatment with 0.1 μmol/L indirubin produced no significant changes in chondrocyte proliferation, apoptosis, caspase-3 activity, or BAX and Bcl-2 protein expressions. At higher doses (0.5, 1.0 and 2.0 μmol/L), indirubin significantly promoted cell proliferation, increased Bcl-2 protein expression, and lowered cell apoptosis rate, caspase-3 activity and Bax protein expression (P < 0.05). Indirubin treatment at 0.5 μmol/L up-regulated the protein and mRNA expressions of NPAS2, ACAN and COL2A1, and down-regulated the expressions of MMP-13, NO, PGE2 and TNF-α (P < 0.05). Interference of NPAS2 expression significantly attenuated the protective effect of 0.5 μmol/L indirubin against IL-1β-induced chondrocyte injury. The mouse model of osteoarthritis showed obviously increased protein levels of BAX and MMP-13 (P < 0.01) and decreased levels of Bcl-2 (P < 0.05) and ACAN (P < 0.01) in the knee joint, and indirubin treatment of the mouse models significantly inhibited the increase of BAX and MMP-13 protein expressions (P < 0.01) and up-regulated the protein expressions of Bcl-2 and ACAN (P < 0.05).@*CONCLUSION@#Indirubin has a protective effect on osteoarthritis tissue and alleviates inflammation and damage of osteoarthritis chondrocytes possibly through NPAS2.

Analysis of current status and influencing factors of inflammatory factors among electrical workers in Hainan province / 中华劳动卫生职业病杂志

Objective: To analyze the level and influence factors of inflammatory factors among electrical workers in Hainan Province. Methods: A total of 509 electrical workers were selected as the research subjects with random cluster sampling in September 2020. Basic information was collected by questionnaire, the serum IL-6, IL-8 and TNF-α levels of the subjects were detected by Luminex.Mann-Whitney U test and Kruskal-wallis H test were used for univariate analysis. Ordinal logistic regression analysis was used for potential influencing factors of the level of inflammatory factors. Results: The median concentrations of IL-6, IL-8 and TNF-α in serum were 2.78, 9.77 and 8.18 pg/ml. Compared with women, male was a risk factor for the increase of IL-6 levels (OR=1.80, 95%CI: 1.08~3.00, P=0.024) . Compared with 51-60 years old, 21-31 years old (OR=0.27, 95%CI: 0.18~0.42, P<0.001) , 31-41 years old (OR=0.27, 95%CI: 0.17~0.43, P<0.001) and 41-51 years old (OR=0.64, 95%CI: 0.41~0.99, P=0.043) were protective factors for the increase of IL-8 level. Compared with day shift workers, shift work was a risk factor for the increase of IL-8 level (OR=1.73, 95%CI: 1.21~2.48, P=0.003) . Compared with women, male was a risk factor for the increase of TNF-α levels (OR=2.87, 95%CI: 1.70~4.86, P<0.001) . Compared with workers who exposed to 7 or more occupational hazard factors, exposed to 1~3 (OR=0.53, 95%CI: 0.30~0.92, P=0.024) occupational hazard factors were protective factors for the increase of TNF-α levels. Conclusion: The level of inflammatory factors was related to sex, age, work system and occupational environment, which can provide basic data for follow-up research on occupational population.

Based on Theory of "Deficiency of Qi and Stagnation" to Explore Pathogenesis of Chronic Renal Failure "Micro-inflammatory State" and Progress of Traditional Chinese Medicine Prevention and Treatment / 中国实验方剂学杂志

Chronic renal failure （CRF） is generally characterized by micro-inflammatory state， which can aggravate the CRF process in severe cases， leading to the deterioration of renal function， malnutrition， anemia and other complications. Therefore， it is of great significance to improve the micro-inflammatory state of CRF. "Deficiency of Qi and stagnation" is the basic pathogenesis of the micro-inflammatory state of CRF， which runs through the whole process of the disease and affects the formation and outcome of CRF in different forms. Traditional Chinese medicine （TCM） has unique advantages in improving the micro-inflammatory state and enhancing the immunity of the body due to its advantages of syndrome differentiation and treatment， strengthening the righteousness and eliminating pathogenic factors. Therefore， the author systematically sorted out the relationship between micro-inflammatory state and CRF， understanding of micro-inflammatory state of CRF and its prevention and treatment of TCM by referring to relevant literature， based on the theory of "deficiency of Qi and stagnation"， and proposed that spleen and kidney failure （deficiency of Qi） is the origin of micro-inflammatory state of CRF， and blood stasis and poisonous evil （stagnation） is the target of its onset. Deficiency of Qi and stagnation adhered to each other， acted as cause and effect， and developed in a spiral manner throughout the development of the disease. TCM has the effects of nourishing the spleen and kidney， removing blood stasis and turbidity. By down-regulating C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor alpha （TNF-α） and other micro-inflammatory indicators， it can eliminate the pathological wastes derived from spleen and kidney deficiency， reduce the micro-inflammatory state， restore the balance of Yin and Yang in the body to achieve the purpose of eliminating pathogens and protecting renal function， providing guidance for the clinical treatment of CRF.

Effect of Mankuining Decoction on Expression of Inflammatory Factors and Intestinal Flora in Mice with Ulcerative Colitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect and the possible mechanism of Mankuining decoction on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） in mice. MethodA total of 90 male SPF C57BL/6 mice were randomly classified into normal group， model group， mesalazine group （0.266 g·kg-1）， and high-， and medium-， low-dose （20， 10， 5 g·kg-1） Mankuining decoction groups， with 15 rats in each group. Mice， except the normal group， drank 3% DSS solution for 7 days to induce UC， and administration （ig） started on the day of modeling. The model group and the normal group were given equivalent amount of 0.9% normal saline once a day for 7 days. The general conditions of mice were recorded every day and the disease activity index （DAI） was calculated. On the 8th day， mice were killed by cervical dislocation. All the colons and feces were collected. The length of colon was recorded， and the histopathological changes of colon were observed based on hematoxylin-eosin （HE） staining. The content of inflammatory factors in colon was detected by enzyme-linked immunosorbent assay （ELISA）， and the changes of intestinal flora in mouse feces were determined based on 16SrRNA sequencing. ResultCompared with the normal group， the model group had severe colon damage， reduction in colon length （P<0.01）， increase in DAI （P<0.01）， decrease in interleukin-10 （IL-10） and transforming growth factor-β1 （TGF-β1） in colon（P<0.01）， rise of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-17α （IL-17α）， and tumor necrosis factor-α （TNF-α） in colon （P<0.05， P<0.01）， and decrease in abundance and diversity of intestinal flora. Compared with the model group， mesalazine and high-， medium-， low-dose Mankuining decoction alleviated the colon injury， recovered the length of colon （P<0.01）， decreased DAI （P<0.01）， increased IL-10 and TGF-β1 in colon （P<0.01）， and decreased IL-1β， IL-6， IL-17α， and TNF-α in colon （P<0.01）. Moreover， they raised the abundance and diversity of intestinal flora compared with the model group， as manifested by the increase in the abundance of Firmicutes， Akkermansia， Dubosiella， and Blautia and the decrease in the abundance of Bacteroidetes， Muribaculaceae， Clostridia_UCG-014， and Alistipes. ConclusionMankuining decoction has definite effect in treating UC mice， and the effect is positively correlated with the concentration. In addition， different concentration has different influence on the structure of flora. The mechanism is the likelihood that it alleviates the disorder of intestinal flora to restore intestinal immune balance and further promote the recovery of colonic mucosa.

Effect of Jiedu Huayu Granules on Inflammatory State of Patients with Chronic Hepatic Failure with Toxic Heat and Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

Ameliorative Effect of Gramine on 2，4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of gramine on 2，4-dinitrochlorobenzene （DNCB）-induced atopic dermatitis （AD） in mice and its potential mechanism. MethodThe mice were divided into the normal control group， model group， dexamethasone （0.05 g·kg-1） group， and high- and low-dose （0.12，0.06 g·kg-1） gramine groups. Mice in all groups except for the normal control group were stimulated with DNCB， followed by medication 13 d later. The changes in skin lesions were then observed， and the skin thickness， moisture content， and transepidermal water loss （TWEL） in each group were measured. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining， and the effects of drugs on CD4+/CD8+T-cell ratio in the spleen were detected by flow cytometry. The levels of immunoglobulin E （IgE）， interleukin （IL）-4， and IL-6 in serum were detected by enzyme-linked immunosorbent assay （ELISA）， and the changes in serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （CRE） by microplate method. The mRNA expression levels of inflammatory cytokines γ-interferon（IFN-γ）， IL-13， IL-17， IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in skin lesions were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of nuclear transcription factor -κB (NF-κB) and NF-κB inhibitory protein α (IκBα) in skin lesions by Western blot. ResultCompared with the normal control group， the model group showed skin edema， erythema， scab， scratch， and lymphocyte and neutrophil infiltration， decreased skin moisture content， as well as increased skin thickness， TWEL （P<0.01）， spleen index， CD4+/CD8+ T-cell ratio in the spleen （P<0.05）， mRNA expression of IFN-γ， IL-13， IL-17， IL-1β， IL-6， and TNF-α in the skin lesions （P<0.05）， serum contents of IgE， IL-4， and IL-6 （P<0.05）， and protein expression of IκBα and NF-κB in skin lesions （P<0.05）. Compared with the model group， dexamethasone and gramine at different doses alleviated skin erythema， scale， scab， and inflammatory cell infiltration， elevated skin moisture content， inhibited skin thickening and TWEL， and decreased spleen index， CD4+/CD8+T-cell ratio in the spleen， mRNA expression of inflammatory factors in the skin lesions， serum contents of IgE and inflammatory factors， and protein expression of IκBα and NF-κB in skin lesions， especially in the dexamethasone group and the high- dose gramine group（P<0.05，P<0.01）. ConclusionGramine can inhibit the expression of related inflammatory factors and regulate the immune function of AD mice via the IκBα/NF-κB pathway， enabling it become a potential drug for treating AD.

Effect of Fufang Shelong Capsules on Rats with Membranous Nephropathy Based on p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the nephroprotective and anti-inflammatory effects of Fufang Shelong capsules （FFSL） in rats with membranous nephropathy （MN）， and the role of the p38 mitogen-activated protein kinase （MAPK） signaling pathway. MethodMale SD rats of SPF grade were divided into a normal group and an experimental group. The MN model was induced by tail vein injection of cationized bovine serum albumin in the experimental group. After screening， the eligible model rats were included and divided into a positive control group （tripterygium glycosides tablets） and low-， medium-， and high-dose FFSL groups （0.375， 0.75， 1.5g·kg-1）. The rats were treated correspondingly for eight weeks， and urine protein was detected during drug intervention. Renal function and inflammation-related indicators were detected after drug intervention. The changes in 24-hour urine total protein （24 h UP）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， creatinine （Cr）， blood urea nitrogen （BUN）， total protein （TP）， albumin （Alb）， and total cholesterol （TC） were detected. Flow cytometry was used to detect CD4+/CD8+ changes. Kidney tissues were collected to observe pathological changes under a light microscope and an electron microscope. The protein expression of p38 MAPK and phosphorylated p38 MAPK （p-p38 MAPK） in kidney tissues was detected by Western blot. ResultCompared with the normal group， the model group showed increased 24 h UP （P<0.01）， elevated serum Cr， BUN， TC， IL-6， IL-8， and TNF-α （P<0.05，P<0.01）， decreased serum Alb and TP levels （P<0.05，P<0.01）， increased CD4+/CD8+ in the peripheral blood （P<0.01）， and up-regulated protein expression of p38 MAPK and p-p38 MAPK in kidney tissues （P<0.05）. Additionally， in the model group， immune complex deposition and foot process fusion， accompanied by infiltration of inflammatory cells， were observed on the epithelial side of the basement membrane in the pathological kidney tissues. Compared with the model group， the groups with drug intervention showed declining 24 h UP levels at six weeks （P<0.05，P<0.01）， decreased serum Cr， BUN， TC， IL-6， IL-8， and TNF-α （P<0.05，P<0.01）， increased serum Alb and TP levels （P<0.05，P<0.01）， reduced CD4+/CD8+ in the peripheral blood （P<0.01）， improved renal pathological damage， and down-regulated p38 MAPK and p-p38 MAPK in kidney tissues （P<0.05，P<0.01）. ConclusionFFSL can decrease the expression of inflammatory factors， reduce proteinuria， delay kidney damage， and protect kidney function by inhibiting the expression of the p38 MAPK signaling pathway.

Analysis of Crucial Transcription Factors of Berberine Against Cerebral Ischemia Based on Transcriptomics and Proteomics / 中国实验方剂学杂志

ObjectiveOn the basis of determining the protective effect of berberine （BBR） on cerebral ischemia， crucial transcription factors （TFs） of BBR against cerebral ischemia was identified by using transcriptome and proteome sequencing. MethodThe model of middle cerebral artery occlusion （MCAO） was established by thread embolization. The sham operation group， model group， low-dose group of BBR （dose of 37.5 mg·kg-1·d-1） and high-dose group of BBR （75 mg·kg-1·d-1） were set up. The rats were killed after continuous intragastric administration for 7 days. The pharmacodynamics was evaluated by Longa score and cerebral infarction rate， and the expressions of inflammatory cytokines， such as interleukin （IL）-1β， tumor necrosis factor （TNF）-α and monocyte chemotactic protein-1 （MCP-1） were measured by enzyme-linked immunosorbent assay （ELISA）. Then， RNA-Seq technique was used to detect the differentially expressed genes （DEGs） before and after BBR intervention， and DAVID 6.8 was used for enrichment analysis of DEGs. CatTFREs technique was used to detect differential TFs before and after BBR intervention， and DAVID 6.8 and STRING 11.0 were used for enrichment analysis and TFs association analysis. Finally， by integrating the activity of TFs and the changes of downstream target genes， crucial TFs were identified and the related regulatory network was constructed by Cytoscape 3.7.1. ResultCompared with the sham operation group， the neurological impairment was significant in the model group （P<0.01）， and compared with the model group， the low and high dose BBR groups could significantly reduce the neurological function damage （P<0.01） and decrease the rate of cerebral infarction （P<0.01）. Transcriptome data analysis showed that BBR was involved in the recovery process after cerebral ischemia mainly by affecting cell adhesion， brain development， neuron migration， calcium signaling pathway， cyclic adenosine monophosphate （cAMP） signaling pathway， inflammatory response and other related functions and signaling pathways. Proteomic data analysis showed that the differentially expressed TFs after BBR intervention interfered with cerebral ischemia mainly by regulating cell differentiation， immune system process， cell proliferation and other biological processes. In addition， integration analysis of TFs and DEGs revealed that transcription factor CP2-like 1 （TFCP2L1）， nuclear factor erythroid-2 like 1 （NFE2L1）， neurogenic differentiation protein 6 （NeuroD6） and POU domain， class 2， transcription factor 1 （POU2F1） were crucial TFs against cerebral ischemia-reperfusion injury mediated by BBR. ConclusionBBR has obvious protective effect on cerebral ischemia-reperfusion injury and its crucial TFs include TFCP2L1， NFE2L1， NeuroD6 and POU2F1.