Relationship Between Peripheral Blood T Lymphocyte Subsets and Prognosis of Patients with Advanced Non-small Cell Lung Cancer Treated with Camrelizumab / 肿瘤防治研究

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Finite element analysis of 14-year-old adolescent after spinal foraminoplasty at L / 解剖学报

Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M

Erythrocyte membrane-associated protein inhibiting Th17 cell differentiation via IL-6 / STAT3 / ROR-γt signaling pathway in experimental autoimmune encephalomyelitis mice / 解剖学报

Objective To explore the effect of exogenous and endogenous erythrocyte membrane-associated protein (ERMAP) on helper T cell 17 (Th17) cell differentiation through interleukin 6 / signal transducers and activators of transcription 3 / retionoid-related orphan nuclear receptor-γt(IL-6 / STAT3 / ROR-γt) signal pathway in the mouse model of experimental autoimmune encephalomyelitis (EAE) . Methods Using flow cytometry to verify the function of ERMAP-Ig fusion protein at different concentrations; Agarose gel electrophoresis was performed to identify ERMAP knockout mice. Flow cytometry was performed to detect the effect of ERMAP-Ig fusion protein on Th17 cell differentiation in vitro. Forty 6-week-old normal C57BL / 6 mice were randomly divided into 2 groups to establish EAE models, control-Ig and ERMAP-Ig groups, with 20 mice in each group; Clinical scores were recorded; Flow cytometry was performed to detect Th17 cell differentiation in EAE mice in vivo. Forty 6-week-old identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models. Identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models, ERMAP

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on paraquat-induced lung fibrosis in rats / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and epithelial-mesenchymal transition of alveolar epithelial cells in lung fibrosis model rats caused by paraquat (PQ). Methods Lung fibrosis model was constructed by a single intraperitoneal injection of PQ (30 mg·kg

The Anterior Insula and its Projection to the Prelimbic Cortex are Involved in the Regulation of 5-HT-Induced Itch / 神经科学通报·英文版

Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.

Diagnosis and treatment recommendations of dialysis patients with SARS-CoV-2 infection for primary care clinicians / 西安交通大学学报(医学版)

End-stage renal disease (ESRD) patients undergoing outpatient hemodialysis (HD) and home peritoneal dialysis (PD) are high risk population of severe and critical types caused by SARS-CoV-2 infection. In order to improve the quality of diagnosis and treatment in dialysis patients with SARS-CoV-2 infection, we wrote this recommendation for primary care clinicians. During the epidemic period of SARS-CoV-2 infection, all patients should be instructed to strengthen self-management. Once the SARS-CoV-2 infection was found in dialysis patients, early stratified management should be carried out within 72 hours after the first positive nucleic acid or antigen test results, which includes early antiviral therapy, early recognition, and transferring severe patients from community or primary hospital to a referral hospital promptly. Guidance for dietary and sports rehabilitation after SARS-CoV-2 infection should also be started as soon as possible.

Mechanism of TRPC in promoting extracellular matrix deposition of glomerular mesangial cells / 西安交通大学学报(医学版)

【Objective】 To explore the role and mechanism of TRPC in promoting extracellular matrix (ECM) deposition in rat glomerular mesangial cells (HBZY-1). Methods Immunofluorescence staining was performed to observe the distribution and expression of TRPC1 and TRPC6 in HBZY-1 cells. After AngⅡ stimulation, qRT-PCR and Western blotting were used to detect the mRNA and protein expressions of Gαq/PLCβ4/TRPC signaling pathway main proteins and ECM deposition indicators (α-SMA, collagenⅢ and fibronectin). By silencing the expressions of TRPC1 and TRPC6 by RNA interference, the expressions of ECM deposition indicators were detected. Changes in [Ca2+]i influx were determined through Fluo-4AM Ca2+ imaging. 【Results】 Both TRPC1 and TRPC6 were expressed in HBZY-1, and were mainly located in cell membrane and cytoplasm. After AngⅡ stimulation, Gαq/PLCβ4/TRPC signaling pathway was activated, and the mRNA and protein expressions of Gαq, PLCβ4, TRPC1 and TRPC6 were all increased (P<0.05). [Ca2+]i influx also increased (P<0.01), and the mRNA and protein expressions of ECM deposition indicators (α-SMA, ColⅢ and Fn) were upregulated (P<0.05). Silencing the expressions of TRPC1 and TRPC6 by RNA interference led to decreased [Ca2+]i influx (P<0.05), and downregulated mRNA and protein expressions of ECM deposition indicators in HBZY-1 cells (P<0.05). The results suggested that inhibition of TRPC expressions could inhibit AngⅡ induced ECM deposition in HBZY-1 cells, which might be associated with decreased [Ca2+]i influx. 【Conclusion】 TRPC may be a novel therapeutic target of renal fibrosis.

TRPC6 involves in endoplasmic reticulum stress induced apoptosis of glomerular mesangial cells / 西安交通大学学报(医学版)

【Objective】 To explore the role and mechanism of TRPC6 in apoptosis of glomerular mesangial cells (HBZY-1) induced by endoplasmic reticulum stress (ERS). 【Methods】 The experiment groups were classified as follows: normal control (NC), thapsigargin (TG), TG+SKF96365, and TG+TRPC6 siRNA groups. Transcription and protein expressions of TRPC6 and ERS related proteins (GRP78 and Caspase12) were detected by qRT-PCR and Western blotting. Additionally, cell apoptosis was measured by flow cytometry and Hoechst33258. Finally, Fluo-4 AM Ca2+ imaging technique was used to determine changes of intracellular calcium ( [Ca2+] i) by laser scanning confocal microscope. 【Results】 Morphological changes of apoptotic cells were characterized by nuclear enrichment or nuclear fragmentation, and the apoptosis rate was increased after TG stimulation. The expressions of TRPC6 and ERS related proteins (GRP78 and Caspase12) were elevated in TG group compared with NC group (P<0.05). Pre-incubation of HBZY-1 cells with SKF96365 and TRPC6 siRNA decreased cell apoptosis (P<0.05). The entry of [Ca2+] i also increased after TG stimulation (P<0.05). The expressions of TRPC6, GRP78 and Caspase12 were downregulated compared with TG group after treatment with SKF96365 and TRPC6 siRNA accompanied by decreased [Ca2+] i (P<0.05). 【Conclusion】 Taken together, this study suggests that inhibition of TRPC6 can alleviate TG-induced HBZY-1 cell apoptosis.

Macrophage MED1 deficiency promotes the development of atherosclerosis in female ApoE and LDLR knockout mice / 西安交通大学学报(医学版)

【Objective】 To study the effect of macrophage mediator 1 (MED1) deficiency on atherosclerosis in female mice. 【Methods】 ApoE knockout (ApoE-/-), LDLR knockout (LDLR-/-), MED1fl/fl, and macrophage MED1 knockout (MED1△Mac) mice were recruited in the study. Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout (MED1△Mac/ApoE-/-) mice and their littermate controls (MED1fl/fl/ApoE-/-). ② LDLR knockout (LDLR-/-) mice receiving bone marrow from MED1△Mac (MED1△Mac→LDLR-/-) or MED1fl/fl (MED1fl/fl→LDLR-/-) mice. Female mice from these two models were fed a Western diet (21% fat and 0.15% cholesterol) for 12 weeks to promote the development of atherosclerosis. Body weight, total cholesterol (TC), and total triglyceride (TG) content in plasma were measured dynamically. After Western diet feeding for 12 weeks, aortic tree and aortic root were collected and hematoxylin-eosin (H&E) and oil red O staining were performed. 【Results】 Plasma TC and TG did not significantly differ between MED1fl/fl/ApoE-/- control group and MED1△Mac/ApoE-/-experimental group. However, the plaque area in aortic tree and aortic root was significantly increased in MED1△Mac/ApoE-/-mice. Moreover, compared with that in MED1fl/fl→LDLR-/- control group, the plaque area of aortic tree and aortic root had an increasing trend in MED1△Mac→LDLR-/- mice group. 【Conclusion】 MED1 deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.

Epidemiological characteristics of sexually transmitted diseases in Dehong Prefecture， Yunnan Province from 2010 to 2022 / 上海预防医学

ObjectiveTo understand the epidemiological characteristics and trends of sexually transmitted diseases （STDs） in Dehong Prefecture， Yunnan Province from 2010 to 2022， so as to provide a basis for the prevention and control of STDs in Dehong Prefecture. MethodsThe 2010‒2022 epidemic cards of STD cases in Dehong Prefecture were downloaded from the China Disease Control and Prevention Information System， and descriptive analysis of the incidence rate and demographic characteristics by disease type was conducted. The syphilis screening data of various populations in Dehong Prefecture between 2014 and 2022 were obtained from the National STD Control and Management Information System， and the syphilis positivity rates of key populations were calculated. ResultsA total of 18 225 STD cases were reported in Dehong Prefecture from 2010 to 2022， and the reported incidence rate increased from 17.1/105 in 2010 to 172.0/105 in 2022， showing an increasing trend （χ2trend=42.9， P<0.001）. The number of reported cases of gonorrhea， syphilis， condyloma acuminatum， genital chlamydia infection， and genital herpes were 7 801 （42.8%）， 4 563 （25.0%）， 3 462 （18.8%）， 1 660 （9.1%）， and 775 （4.3%）， respectively. The majority of the reported STD cases were males （12 336 cases， 67.7%）， young adults aged 15 to <45 years （15 839 cases， 87.2%）， and farmers （9 230 cases， 50.7%）. The elderly group aged 65 years and over accounted for 10.5% of syphilis cases. Among different types of key populations， the highest syphilis positivity rate was found among men who have sex with men （10.1%）， followed by STD clinic attendees （8.1%）， and the syphilis positivity rates among clandestine prostitutes， voluntary counseling and testing population， drug addicts， and drug rehabilitation center/re-education through labor center population were 2.2%， 1.6%， 1.4%， and 1.3%， respectively. ConclusionFrom 2010 to 2022， the STD epidemic in Dehong Prefecture showed a rapidly increasing trend， with a higher incidence of gonorrhea and syphilis， and a higher syphilis positivity rate among men who have sex with men， drug addicts， clandestine prostitutes， and STD clinic patients. In the future， publicity， education and behavioral interventions for these groups should be strengthened to reduce the prevalence and transmission of STDs.

Health-related quality of life in patients with type 2 diabetes based on the European 5-Dimensional Health Scale / 公共卫生与预防医学

Objective To evaluate the quality of life of patients with type 2 diabetes mellitus in Weifang City, Shandong Province and to explore its influencing factors. Methods A multistage stratified random sampling method was used to investigate patients in endocrine outpatient clinics in four medical institutions in Weifang from July to September 2022. The survey included general information, multi-dimensional evaluation of quality of life with the EQ-5D-5L scale, calculation of health utility values, and analysis of influencing factors using Tobit regression models. Results A total of 397 patients with type 2 diabetes were included in the present investigation, with health utility value of 0.82±0.21 points and visual analogue scale (VAS) score of 79.47±12.81 points. Pain or discomfort, anxiety or depression were more prominent in the study population. Age, diabetic complications, BMI, daily need for care, social support, and daily level of glycemic control were factors influencing health-related quality of life in patients with type 2 diabetes. Conclusion In the actual treatment of type 2 diabetes patients, an emphasis should be placed on protecting elderly type 2 diabetic patients, preventing and controlling the occurrence and development of diabetic complications, and improving daily blood glucose control to further improve the health-related quality of life of the population.

Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α-MMP9-mediated HIF1α signaling pathway / 药学学报

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens.@*RESULTS@#The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05).@*CONCLUSION@#PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.

Ultrasound-guided continuous fascia iliaca compartment block for perioperative pain management in elderly patients undergoing hip fracture surgery / 中国骨伤

OBJECTIVE@#To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures.@*METHODS@#A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed.@*RESULTS@#The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05).@*CONCLUSION@#Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.

Eosinophil-to-neutrophil ratio predicts outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis / 国际脑血管病杂志

Objective:To investigate the predicting value of eosinophil-to-neutrophil ratio (ENR) for outcomes at 3 months after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai'an First People's Hospital from July 2019 to July 2022 were included retrospectively. Multivariate logistic regression model was used to determine the independent correlation between ENR and outcomes at 3 months after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of ENR levels for poor outcomes at 3 months after intravenous thrombolysis. Results:A total of 352 patients with AIS receiving intravenous thrombolysis were enrolled, including 240 men (68.1%), age 66.46±12.00 years old. The median National Institutes of Health Stroke Scale score was 8 (interquartile range, 5-13). At 3 months after onset, 215 patients (61.0%) had good outcomes, 137 (38.9%) had poor outcomes. Univariate analysis showed that the median ENR×10 2 level of the poor outcome group was significantly lower than that of the good outcome group ( Z= –7.305, P<0.01). Multivariate logistic regression analysis showed that lower ENR×10 2 was an independent risk factor for poor outcomes at 3 months after intravenous thrombolysis (odds ratio 0.619, 95% confidence interval 0.514-0.745; P<0.01). ROC curve analysis showed that the area under the curve for ENR×10 2 predicting the poor outcomes after intravenous thrombolysis was 0.731 (95% confidence interval 0.678-0.784; P<0.01). The optimal cutoff value was 0.625 and the corresponding sensitivity and specificity were 94% and 40%, respectively. Conclusion:Lower ENR before intravenous thrombolysis in patients with AIS is independently associated with the poor outcomes at 3 months.

Systemic immune-inflammation index predicts hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the predictive value of systemic immune-inflammatory index (SII) for hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai’an First People’s Hospital from July 2019 to July 2022 were included retrospectively. The head CT was performed at 24 h after intravenous thrombolysis and determined whether HT existed. sICH was defined as brain parenchymal hematoma, and the National Institutes of Health Stroke Scale (NIHSS) scores increased by ≥4 compared with the baseline, or the patient died within 36 h after onset. Multivariate logistic regression analysis was used to determine the independent correlation between SII and HT and sICH after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of SII for HT and sICH after intravenous thrombolysis. Results:A total of 352 patients with AIS received intravenous thrombolysis were enrolled, including 240 males (68.1%), aged 66.46±12.00 years. The median baseline NIHSS score was 8 (interquartile range, 5-13), and the median SII is 531.91×10 9/L (interquartile range, 351.20-896.91×10 9/L). HT occurred in 62 patients (17.6%) and sICH occurred in 27 patients (7.7%). Univariate analysis showed that the SII of the HT group was significantly higher than that of the non-HT group ( Z=–2.731, P=0.006), and the SII of the sICH group was significantly higher than that of non-sICH group ( Z=–4.125, P<0.01). Multivariate logistic regression analysis showed that the increased SII was the independent risk factor for HT (odds ratio [ OR] 1.001, 95% confidence interval [ CI] 1.000-1.001; P=0.004) and sICH ( OR 1.001, 95% CI 1.001-1.002; P<0.01). ROC curve analysis shows that the area under curve of SII predicting HT was 0.610 (95% CI 0.535-0.686; P=0.006), and the best cutoff value was 488.48×10 9/L. The corresponding sensitivity and specificity were 69% and 47% respectively. The area under the curve of SII predicting sICH was 0.739 (95% CI 0.636-0.842; P<0.01), and the best cutoff value was 846.56×10 9/L, the corresponding sensitivity and specificity were 70% and 77% respectively. Conclusion:The increased SII at admission can predict the risks of HT and sICH in patients with AIS after intravenous thrombolysis.

Glucuronic acid metabolites of phenolic acids target AKT-PH domain to improve glucose metabolism / 中草药·英文版

OBJECTIVE@#Phenolic acids widely exist in the human diet and exert beneficial effects such as improving glucose metabolism. It is not clear whether phenolic acids or their metabolites play a major role in vivo. In this study, caffeic acid (CA) and ferulic acid (FA), the two most ingested phenolic acids, and their glucuronic acid metabolites, caffeic-4'-O-glucuronide (CA4G) and ferulic-4'-O-glucuronide (FA4G), were investigated.@*METHODS@#Three insulin resistance models in vitro were established by using TNF-α, insulin and palmitic acid (PA) in HepG2 cells, respectively. We compared the effects of FA, FA4G, CA and CA4G on glucose metabolism in these models by measuring the glucose consumption levels. The potential targets and related pathways were predicted by network pharmacology. Fluorescence quenching measurement was used to analyze the binding between the compounds and the predicted target. To investigate the binding mode, molecular docking was performed. Then, we performed membrane recruitment assays of the AKT pleckstrin homology (PH) domain with the help of the PH-GFP plasmid. AKT enzymatic activity was determined to compare the effects between the metabolites with their parent compounds. Finally, the downstream signaling pathway of AKT was investigated by Western blot analysis.@*RESULTS@#The results showed that CA4G and FA4G were more potent than their parent compounds in increasing glucose consumption. AKT was predicted to be the key target of CA4G and FA4G by network pharmacology analysis. The fluorescence quenching test confirmed the more potent binding to AKT of the two metabolites compared to their parent compounds. The molecular docking results indicated that the carbonyl group in the glucuronic acid structure of CA4G and FA4G might bind to the PH domain of AKT at the key Arg-25 site. CA4G and FA4G inhibited the translocation of the AKT PH domain to the membrane, while increasing the activity of AKT. Western blot analysis demonstrated that the metabolites could increase the phosphorylation of AKT and downstream glycogen synthase kinase 3β in the AKT signaling pathway to increase glucose consumption.@*CONCLUSION@#In conclusion, our results suggested that the metabolites of phenolic acids, which contain glucuronic acid, are the key active substances and that they activate AKT by targeting the PH domain, thus improving glucose metabolism.

Structural Characterization of Vaginal Microbiota in Threatened Abortion Patients with Syndrome of Kidney Deficiency by 16S rRNA Sequencing / 中国实验方剂学杂志

ObjectiveTo investigate the structural features of vaginal microbiota in the early threatened abortion patients with the syndrome of kidney deficiency. MethodThirty-one patients with early threatened abortion of kidney deficiency syndrome （DK-TA group） and 116 women with normal early pregnancy （NP group） attending the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2018 to December 2020 were selected. The vaginal secretions were collected for 16S rRNA sequencing， which can reveal the vaginal microbiota composition and differential bacteria between the two groups. ResultThe DK-TA group had higher abundance and diversity of vaginal microbiota than the NP group. The Binary jaccard and unweighted_unifrac distance matrix analysis showed that the similarity， dispersion， abundance， and phylogenetic relationship of vaginal microbiota were significantly different between the two groups. At the phylum level， the DK-TA group had lower relative abundance of Bacteroidetes and Fusobacteria and higher relative abundance of Proteobacteria and Gemmatimonadetes than the NP group. At the genus level， the DK-TA group had lower relative abundance of Sneathia and Bifidobacterium and higher relative abundance of Escherichia-Shigella and Shuttleworthia than the NP group. Linear discriminant analysis Effect Size（LEfSe）revealed that Bacteroidetes， Fusobacteria， and Bifidobacteria were dominant in the NP group and Proteobacteria and Firmicutes in the DK-TA group. The function prediction found that DK-TA was closely associated with 38 functional pathways， including cyclic adenosine monophosphate signaling pathway and regulation of tryptophan channels by inflammatory mediators. In addition， the vaginal differential bacteria between the two groups had significant positive or negative association with the differential metabolic pathways. ConclusionProteobacteria， Gemmatimonadetes， and Bacteroidetes in the vaginal microbiota may be biomarkers for threatened abortion of kidney deficiency syndrome.