Empagliflozin ameliorates renal tissue damage in diabetic nephropathy mice through autophagy-lysosome pathway / 中国药理学通报

Aim To investigate the effeots of empagliflozin on kidney tissue and autophagy-lysosome pathway in diabetio kidney disease (DKD) mice. Methods The db/m group as the control group, the db/db mice were randomly divided into the model group and empagliflozin group. After 8 weeks of administration, the levels of 24 h urine protein (24 h-UTP), fasting blood glucose (FBG), glycosylated hemoglobin (HBAlc), total cholestérol (TC), triglycéride (TG), blood urea nitrogen (BUN), serum creatinine (Scr), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β, and monocyte chemoattractant protein-1 (MCP-1) were detected. The expression of p62, LC3B, Beclinl, Agt7, LAMP1, Bcl-2, caspase-3 and Bax in kidney tissue was measured by Western blot. The pathological changes of kidney were observed under light microscope. Results Compared with the control group, the model group showed thickening of basement membrane, increased extracellular matrix, interstitial inflammatory cell infiltration and interstitial fibrosis (P < 0. 01). Moreover, the model group had higher content of FBG, HBAlc, 24h-UTP, TC, TG, BUN, Scr, TNF-α, IL-1β, and MCP-1 (P < 0. 01), higher expression of LC3B-/LC3B- I, Beclinl, LAMP1, Agt7 and Bcl-2 (P<0. 01), and lower expression of p62, caspase-3 and Bax in rénal tissue (P < 0. 01) than those in the control group. Compared with the model group, empagliflozin alleviated the pathological injury in kidney (P < 0. 01), and the changes in the above indicators were reversed. Conclusion By irepairing autophagy-lysosomal pathway in renal tissue, empagliflozin can promote the degradation of autophagy substrates, inhibit the production of inflammatory factors and apoptosis, thereby protecting the kidney.

Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia / 中西医结合学报

OBJECTIVE@#Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment.@*METHODS@#The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.@*RESULTS@#According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.@*CONCLUSION@#JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

Predictive Value of Complete Blood Count and Inflammation Marker on Risk of Recurrence in Children with Henoch-Schönlein Purpura / 中国实验血液学杂志

OBJECTIVE@#To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP).@*METHODS@#One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed.@*RESULTS@#In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%.@*CONCLUSION@#Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.

Comparison of chemical compositions of different parts of Xanthoceras sorbifolium seeds based on UHPLC-Q-Orbitrap HRMS / 中国中药杂志

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.

Effect and mechanism of Danggui Buxue Decoction-containing serum in mitigating H9c2 cell injury caused by exposure to intermittent low oxygen / 中国中药杂志

This study aims to explore the effect and mechanism of Danggui Buxue Decoction(DBD)-containing serum in alleviating the H9c2 cell injury caused by the exposure to intermittent low oxygen. H9c2 cells were assigned into five groups: control(CON) group, intermittent low oxygen(IH) group, intermittent low oxygen plus DBD-containing serum(IH+DBD) group, intermittent low oxygen plus the autophagy enhancer rapamycin(IH+RAPA) group, and intermittent low oxygen plus DBD-containing serum and the autophagy inhibitor 3-methyladenine(IH+DBD+3-MA) group. Monodansylcadaverine(MDC) staining was employed to detect the changes of autophagosomes. Cell counting kit-8(CCK-8) assay was employed to determine the activity of myocardial cells, and lactate dehydrogenase(LDH) and creatine kinase(CK) kits were used to measure the LDH and CK levels in the cell culture, which would reflect the degree of cell damage. TdT-mediated dUTP nick-end labeling(TUNEL) staining was used to detect the apoptosis of myocardial cells, and JC-1 fluorescence probe to detect the changes in mitochondrial membrane potential. Western blot was employed to determine the expression levels of the autophagy-related proteins microtubule-associated proteins light chain 3Ⅱ(LC3Ⅱ), microtubule-associated proteins light chain 3Ⅰ(LC3Ⅰ), P62, Parkin and apoptosis related proteins pro caspase-3, caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax). The results showed that compared with the CON group, the IH group showed decreased fluorescence intensity of MDC staining, decreased LC3Ⅱ/LC3Ⅰ ratio, down-regulated Parkin expression, and up-regulated expression of P62. In addition, the IH group showed decreased cell survival rate, increased content of LDH and CK in the culture medium, increased number of TUNEL positive cells, and decreased pro caspase-3/caspase-3 and Bcl-2/Bax ratios and mitochondrial membrane potential. Compared with the IH group, the IH+DBD and IH+RAPA groups showed increased fluorescence intensity of MDC staining, increased LC3Ⅱ/LC3Ⅰ ratio, up-regulated Parkin expression, and down-regulated P62 expression. In addition, the two groups showed increased cell survival rate, reduced content of LDH and CK in the culture medium, decreased number of TUNEL positive cells, and increased pro caspase-3/caspase-3 and Bcl-2/Bax ratios and mitochondrial membrane potential. The IH+DBD+3-MA and IH groups showed no significant differences in the above indicators. Compared with the IH+DBD group, the IH+DBD+3-MA group showed decreased fluorescence intensity of MDC staining, decreased LC3Ⅱ/LC3Ⅰ ratio, down-regulated Parkin expression, and up-regulated P62 expression. In addition, the group had decreased cell survival rate, increased content of LDH and CK in the culture medium, increased number of TUNEL positive cells, decreased pro caspase-3/caspase-3 and Bcl-2/Bax ratios, and declined mitochon-drial membrane potential. To sum up, DBD could promote the mitophagy, inhibit the apoptosis, and alleviated the injury of H9c2 cells exposed to low oxygen.

Effect of Rheb1 in the Development of Mouse Megakaryocyte-Erythroid Progenitor Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Rheb1 in the development of mouse megakaryocyte-erythroid progenitor cells and its related mechanism.@*METHODS@#Rheb1 was specifically knocked-out in the hematopoietic system of Vav1-Cre;Rheb1fl/fl mice(Rheb1Δ/Δ mice). Flow cytometry was used to detect the percentage of red blood cells in peripheral blood and erythroid cells in bone marrow in Vav1-Cre;Rheb1fl/fl mice and control mice. The CFC assay was used to detect the differentiation ability of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Real-time fluorescence quantification PCR was used to detect the relative expression of PU.1,GATA-1,GATA-2,CEBPα and CEBPβ of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Rapamycin was added to the culture medium, and it was used to detect the changes in cloning ability of megakaryocyte-erythroid progenitor cells from wild-type mice in vitro.@*RESULTS@#After Rheb1 was knocked out, the development and stress response ability of megakaryocyte-erythroid progenitor cells in mice were weaken and the differentiation ability of megakaryocyte-erythroid progenitor cells in vitro was weaken. Moreover, the expression of GATA-1 of megakaryocyte-erythroid progenitor cells was decreased. Further, rapamycin could inhibit the differentiative capacity of megakaryocyte-erythroid progenitor cells in vitro.@*CONCLUSION@#Rheb1 can regulate the development of megakaryocyte-erythroid progenitor cells probably through the mTOR signaling pathway in mice.

Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation / 中国天然药物

Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.

Progress on correlation between intestinal flora and mental diseases / 中国药理学通报

The impact of intestinal flora on human and animal health and diseases has attracted much attention both at home and abroad in recent years. The intestinal flora constitutes the intestinal microecosystem and plays an important role in physiological activities such as nutrition, metabolism, growth and development, barrier protection, and immunity. In this article, the relationship between intestinal dysbiosis and psychiatric diseases has been reviewed from two aspects:metagenomic characterization of intestinal microflora diversity in neurological diseases and validation of the relationship between intestinal flora and psychiatric diseases by fecal bacteria transplantation in germ-free mice. In addition, the microbial-gut-brain axis theory has been proposed in recent years, which links the nerve-endocrine-immune system to form a two-way signaling pathway. Intestinal flora plays an important role in regulating the central nervous system by promoting neurotransmitter release, endocrine, and immunity. The system plays an important role. Changes in intestinal flora mainly affect the host's nervous system through vagus nerve pathways, endocrine pathways, immune pathways, etc, thereby triggering or aggravating depression, autism, Alzheimer's disease, schizophrenia, Parkinson's disease, etc. This article reviews the relationships between host-related neurological abnormalities, intestinal flora imbalance and mental diseases, and discusses the research methods, research progress, and mechanism of the correlation between intestinal flora imbalance and mental diseases to research progress on microbe-gut-brain axis.

Establishment of Feedforward Control Model for Dry Granulation of Polysaccharide Components Based on Quality by Design / 中国实验方剂学杂志

ObjectiveA feedforward control model for dry granulation of polysaccharide components was established to guide the adjustment and optimization of critical process parameters （CPPs） in the design space， so as to reduce the impact of fluctuations in raw materials properties on the quality of medicines. MethodTaking Astragali Radix extract powder as the model drug， the design space of dry granulation CPPs was determined by Box-Behnken design. Astragali Radix mixed powder with different powder properties were prepared by mixture design， the variance inflation factor （VIF） was used to diagnose the multicollinearity of the powder properties， and principal component analysis （PCA） was used to extract the characteristic data of the model. Radial basis function neural network （RBFNN） was used to establish a feedforward control model for reflecting the relationship between the powder properties of polysaccharide components， dry granulation CPPs and one-time molding rate. ResultThe design space for dry granulation CPPs of polysaccharide components was 16-35 Hz for feeding speed， 10-23 Hz for roller speed， and 10-46 kg·cm-2 for roller pressure. The established RBFNN feedforward control model had a good predictive effect on the one-time molding rate of dry granulation of polysaccharide components， which could be used to guide the adjustment and optimization of CPPs in the design space， the relative error was 0.38%-6.73%， and the average relative error was 3.42%. ConclusionThe established feedforward control model can well reflect the relationship between the powder properties of the polysaccharide components， the dry granulation CPPs and the one-time molding rate of the granules， which can be used to guide the adjustment and optimization of CPPs in the design space， reduce the impact of material property fluctuation on product quality， and provide ideas for promoting the quality of traditional Chinese medicine from passive control to active control.

Effects of MCC950 on nerve injury in rats with intracerebral hemorrhage / 中国应用生理学杂志

Objective: To investigate the effects of the pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950 on nerve injury in rats with intracerebral hemorrhage(ICH). Methods: Seventy-two SD rats were randomly divided into three groups (n=24): Sham group, ICH group and MCC950 group. ICH group and MCC950 group rats were injected with autogenous non-anticoagulant blood to establish ICH model, and then the rats in MCC950 group were intraperitoneally injected with MCC950 at the dose of 10 mg/kg(2 mg/ml) for 3 days after ICH model was established. Seventy-two hours after the establishment of the model, the forelimb placement test, the corner test and mNSS score were performed to observe the neurological function of the rats with ICH. The volume of hematoma was observed in fresh brain tissue sections. HE staining was used to observe the pathological changes of brain tissue. The dry-wet weight ratio was calculated to evaluate the changes of brain tissue edema. The degeneration of neurons was observed by FJC staining. The neuronal apoptosis was observed by TUNEL staining. The protein expression and activation levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD were determined by Western blot. Results: Compared with sham group, the percentage of successful placement of left forelimb and left turn was decreased significantly (P＜0.01, P＜0.05), mNSS score was increased significantly (P＜0.01) in ICH group. Hematoma volume was increased significantly, the number of microglial cells around the hematoma was increased, the number of neurons was decreased, nerve cell swelled, some cells showed pyknotic necrosis, and the staining was deepened. The water content of the right base was increased significantly (P＜0.05). The number of FJC positive and TUNEL positive cells around the hematoma was increased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were increased significantly (P＜0.01, P＜ 0.05). Compared with ICH group, the percentage of successful placement of left forelimb and left turn was increased significantly in MCC950 group (P＜0.05), while the mNSS score and the volume of hematoma were decreased significantly (P＜0.01), the swelling degree of nerve cells around the hematoma was reduced significantly, and the number of pyrotic necrotic cells was decreased. The water content of the right base was decreased significantly (P＜0.05), and the number of FJC positive and TUNEL positive cells around the hematoma was decreased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were decreased significantly (P＜0.05). Conclusion: MCC950 can ameliorate nerve injury after ICH by inhibiting NLRP3 inflammasome mediated inflammation and pyroptosis.

YU Tian-yuan's experience in the clinical application of Danzhong (CV 17) for mental illness / 中国针灸

To summarize YU Tian-yuan's experience of applying Danzhong (CV 17) for mental illness in acupuncture and tuina. YU Tian-yuan uses Danzhong (CV 17) alone or in combination with other acupoints to treat mental illnesses such as insomnia, palpitation and chest distress. Professor YU emphasizes 4 tips when treating diseases, nourishing the heart to tranquilize by light stimulation; regulating spirit by combined stimulation; leaving the acupoints and holding on the meridian for a wide range of stimulation; using rubbing and pushing manipulation in several directions for regulating qi to soothe the chest. And in clinical practice, formed a unique therapy to treat mental illness.

Role of M2 isoform of pyruvate kinase in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Diabetic retinopathy(DR), one of the most common diabetes-specific microvascular complications, is classically described by intraretinal microvascular abnormalities and neovascularization. It is the main reason why visual impairment and blindness in people aged 20-65 years worldwide. Glycolysis can provide energy by converting glucose into pyruvate. Endothelial cells mainly utilize glycolysis to produce ATP to maintain the function, including forming tight junctions and barrier functions. Pyruvate kinase(PK)M2(M2 isoform of pyruvate kinase)is a key enzyme of glycolysis and is widely expressed in most tissues. As major cellular components in the retina, endothelial cells and photoreceptor cells play a crucial role in the occurrence and development of DR. Studies have shown that PKM2 takes part in the development of DR by regulating the function of endothelial cells and photoreceptors in metabolic and non-metabolic ways. Therefore, this article overviews the role of PKM2 in DR from the direction of endothelial cells and photoreceptor cells and provides new insight into the diagnosis and treatment of DR.

Optimization of supercritical CO 2 extraction of red ginseng polysaccharide by response surface methodology and its antioxidant activity in vitro / 国际中医中药杂志

Objective:Response surface methodology was used to optimize the optimal extraction conditions of red ginseng polysaccharide and to study the antioxidant activity of red ginseng polysaccharide.Methods:Supercritical CO 2 extraction method was used to extract polysaccharides from red ginseng. The effects of solid-liquid ratio, extraction time, extraction temperature and extraction pressure on the extraction of polysaccharides from red ginseng were investigated. Box-behnken Design method was used to optimize the extraction process of red ginseng polysaccharide, and Logit method was used to calculate the semi-inhibitory concentration of red ginseng polysaccharide on DPPH clearance (half maximal inhibitory concentration, IC 50). Results:The optimal extraction conditions were as follows: extraction temperature 61.12 ℃, extraction pressure 20.64 MPa, extraction time 128.37 min, solid-liquid ratio 1∶25.61 g/ml, and the extraction yield of red ginseng polysaccharide was 36.89%. The results of three groups of repeatability tests showed that the relative error of polysaccharide yield of red ginseng was in the range of 5%. When the mass concentration of red ginseng polysaccharide was 25 μg/ml, it had better antioxidant activity and IC 50 was 10.97 μg/ml. Conclusion:The optimized extraction conditions of red ginseng polysaccharide were reasonable and reliable, and the antioxidant activity of red ginseng polysaccharide was strong, which could provide reference for the follow-up research.

Prediction of Disintegration Time of Traditional Chinese Medicine Tablets Based on Generalized Regression Neural Network / 中国实验方剂学杂志

Objective:This paper constructs a generalized regression neural network （GRNN） model to predict the disintegration time of traditional Chinese medicine （TCM） tablets. Method:Taking Astragali Radix as a model drug， the mixed Astragali Radix powders with different powder properties were prepared by mixing Astragali Radix extract powders with microcrystalline cellulose and lactose， which were made to Astragali Radix tablets by direct compression method. The powder properties of mixed Astragali Radix powders and the disintegration time of Astragali Radix tablets were determined， respectively. The correlation between the original data was eliminated by principal component analysis （PCA）. The principal component factors were used as the input layer of the GRNN model， and the disintegration time was used as the output layer for network training. Finally， the verification group data was used to predict the disintegration time， and the network prediction accuracy was calculated by comparing with the actual value. Result:Three principal component factors were obtained through PCA by analyzing the original nine variables that were correlated with each other （Hausner ratio， true density， tap density， compression degree， angle of repose， bulk density， porosity， water content and total dissolved solids）， which reduced the complexity of the network. The prediction value of the disintegration time based on this prediction method was in good agreement with the actual value， the error of disintegration time was 0.01-1.34 min and the average relative error was 3.16%. Conclusion:Based on the GRNN mathematical model， the physical properties of Astragali Radix extract powders can be used to accurately predict the disintegration time of Astragali Radix tablets， which provides a reference for studying the disintegration time of TCM tablets.

Effect of Danggui Shaoyaosan on Diminished Ovarian Reserve in Model Rats： An Exploration Based on TGF-β1/ Smads Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the improving effect of Danggui Shaoyaosan on diminished ovarian reserve （DOR） in rats triggered by Tripterygia wilfordii polyglycoside tablet combined with stress， and to explore the role of transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁）/Smads signaling pathway in such improvement. Method:Forty-eight female SD rats with normal sexual cycle were selected and randomly divided into a normal group （<italic>n</italic>=8） and a modeling group （<italic>n</italic>=40）， and the ones in the modeling group were given Tripterygium wilfordii polyglycoside tablets （50 mg·kg^-1） combined with random stress for 15 d. After successful modeling， the rats were randomized into the model group， low-， medium-， and high-dose （3.96， 7.92， 15.84 g·kg^-1） Danggui Shaoyaosan groups， and estradiol valerate group （0.09 mg·kg^-1）， with eight in each group. Under the premise of stress exposure， they were separately gavaged with the normal saline， low-， medium- and high-dose Danggui Shaoyaosan， and estradiol valerate for 15 successive days. The estrous cycle of rats in each group was observed daily. After intervention， the rats were sacrificed and the ovarian visceral index was calculated. The pathological changes in ovarian tissues were observed by hematoxylin eosin （HE） staining. The protein expression levels of TGF-<italic>β</italic>₁ and TGF-<italic>β</italic>₁receptor （TGF-<italic>β</italic>₁R） in the ovarian tissues of rats were measured by immunohistochemistry （IHC）， and the mRNA expression levels of Smad2， Smad3， and Smad7 in the ovarian tissues by real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， the model group exhibited disordered estrus cycle （<italic>P</italic><0.05）， reduced visceral index （<italic>P</italic><0.01）， and down-regulated TGF-<italic>β</italic>₁ and TGF-<italic>β</italic>₁R protein and Smad2 and Smad3 mRNA expression in the ovarian tissues （<italic>P</italic><0.01）， and up-regulated Smad7 mRNA expression （<italic>P</italic><0.01）. Compared with the model group， Danggui Shaoyaosan at the low， medium， and high doses and estradiol valerate improved the estrus cycle of rats to varying degrees （<italic>P</italic><0.05） and increased the visceral index， with better effects observed in the medium-group and high-dose Danggui Shaoyaosan groups （<italic>P</italic><0.05，<italic>P</italic><0.01）. Besides， the protein expression levels of TGF-<italic>β</italic>₁ and TGF-<italic>β</italic>₁R and the mRNA expression levels of Smad2 and Smad3 in the ovarian tissues were elevated to varying degrees （<italic>P</italic><0.01）， and the Smad7 mRNA expression declined （<italic>P</italic><0.01）. The improvements in TGF-<italic>β</italic>₁ and TGF-<italic>β</italic>₁R protein expression of the medium-dose Danggui Shaoyaosan group and estradiol valerate group were more obvious. Conclusion:Danggui Shaoyaosan significantly improves ovarian reserve in DOR rats， which is closely related to the regulation of TGF-<italic>β</italic>₁/Smads signaling pathway.

The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students

Objective@#The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders. @*Methods@#Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors. @*Results@#We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups. @*Conclusion@#IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.

Effect and Safety of Penetrating Moxibustion in Treatment of Migraine without Aura: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To observe the clinical effect of penetrating moxibustion on migraine without aura (MO) patients.@*METHODS@#Totally 60 MO patients from the Acupuncture Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine were collected from November 2015 to February 2017. All patients were assigned to a treatment group and a control group using a random number table, 30 cases in each group. The treatment group was treated with penetrating moxibustion, and the control group was treated with mild moxibustion, thrice a week for 4 consecutive weeks. The total effective rate, Visual Analogue Scale (VAS) scores, headache intensity, and Migraine Specific Quality of Life Questionnaire (MSQ) scores of patients after treatment were compared between the two groups. The moxibustion sensation and reaction after moxibustion were observed, and the adverse reactions were evaluated. All patients were followed up at 4 and 16 weeks after treatment.@*RESULTS@#The total effective rate of the treatment group was significantly higher than that of the control group (93.33% vs. 80.00%, P0.05).@*CONCLUSIONS@#Penetrating moxibustion can significantly relieve pain and improve quality of life of MO patients. After penetrating moxibustion, flushing and sweating of patients were obvious, and the curative effect was superior to the mild moxibustion.

Detection of peripheral blood circulating tumor cells in oral squamous cell carcinoma and its clinical significance / 华西口腔医学杂志

OBJECTIVES@#This study aims to investigate the diagnostic value of peripheral blood circulating tumor cells (CTCs) in oral squamous cell carcinoma (OSCC) and its correlation with the clinicopathological features of OSCC.@*METHODS@#Ninety-three patients diagnosed as OSCC in the First Affiliated Hospital of Zhengzhou University from May 2019 to May 2020 were selected as the experimental group, and 20 healthy volunteers were employed as the control group. The CTCs value of peripheral blood of the patients were measured by CTCs detection technology, and its clinical significance was analyzed.@*RESULTS@#The CTCs values in the experimental group were higher than those in the control group, and the difference was statistically significant (@*CONCLUSIONS@#Peripheral blood CTCs has important clinical value for early screening, auxiliary diagnosis, evaluation of metastasis, and determination of malignant degree, progression, and pathological grade of OSCC and a relatively reliable tumor detection indicator.

Prevention and control of HIV/AIDS in China: lessons from the past three decades / 中华医学杂志(英文版)

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.