The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective:To explore the role and the intervention effect of emodin in intestinal neuropathy in rats with severe acute pancreatitis (SAP) through the nucleotide binding oligomerization domain like receptor protein 3/cysteine containing aspartic acid protease-1 (NLRP3/Caspase-1) pathway.Methods:Forty male healthy SD rats aged 6-8 weeks with a weight of approximately 200g were randomly divided into control group, SAP model group, emodin treatment (EMO) group, and NLRP3 knockdown group. SAP were induced by retrograde injection of sodium deoxycholate into the pancreatic duct of rats and serum amylase of which were detected. The effective NLRP3 knockdown sequence was screened for NLRP3 knockdown animal experiments. Fluorescence quantitative polymerase chain reaction was used to detect the expression of NLRP3, Caspase-1, gasdermin-D (GSDMD), interleukin (IL)-1β, IL-18 and tumor necrosis factor-α(TNF-α) in the small intestine of each group. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) in the small intestine of each group.Results:The amylase levels of the control group, SAP group, EMO group, and NLRP3 knockdown group were (277.73±24.92) U/L, (1018.57±282.89) U/L, (625.43±134.40) U/L, and (391.01±27.63) U/L, respectively. The SAP and EMO groups were significantly higher than the control group ( P<0.001), while the EMO and NLRP3 knockdown groups were significantly lower than the SAP group (all P<0.001). Compared with control group, the expression levels of NLRP3, Caspase-1, IL-1β, IL-18, TNF-α and GSDMD in SAP group were increased, with statistical significance (all P<0.001). Compared with SAP group, the NLRP3 knockdown group showed the expressionlevels of the above 6 genes were all decreased, and EMO group showed decreased gene expressing levels of NLRP3, IL-1β, IL-18 and TNF-α, with statistical significance (all P<0.05). The relative expression of GFAP in small intestine of control group, SAP group, EMO group and NLRP3 knockdown group were (1.00±0), (1.66±0.11), (1.13±0.02) and (1.13±0.02), respectively. Among them, the expression of GFAP in SAP group was increased compared with the control group; The expression of GFAP in EMO group and NLRP3 knockdown group was lower than that in model group, and the differences were statistically significant (all P<0.05). Conclusions:Emodin and knocking down NLRP3 can both promote the repair of SAP small intestine injury through the NLRP3/Caspase-1 signaling pathway, and thus play a protective role in the intestine.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

AIM To investigate the effects and mechanism of Shenxiao Jiedu Tongluo Recipe on renal AIM 2-mediated pyroptosis of a golden hamster model of diabetic nephropathy(DN).METHODS Fifty male golden hamsters of SPF grade were randomly divided into the control group and the model group.The golden hamsters of the model group successfully developed into DN models by feeding of high glucose and high fat diet and intraperitoneal injection of STZ were further randomly assigned into the model group,the enagliflozin group(10 mg/kg),and the low-dose and the high-dose Shenxiao Jiedu Tongluo Recipe groups(12.8,25.6 g/kg)for 8 weeks gavage of the corresponding administration.The golden hamsters had their levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,and Sur detected by automatic biochemical analyzer;their serum SOD activity and MDA level detected by biochemical method;their serum levels of IL-1β,IL-18,and TNF-α detected by ELISA method;their pathomorphological changes of kidney tissue observed by HE and PAS staining;their protein expressions of ROS and γH2AX detected by immunofluorescence or immunohistochemistry;and their renal protein expressions of AIM 2,caspase-1 and GSDMD detected by Western blot and immunohistochemistry.RESULTS Compared with the control group,the model group showed atrophic glomeruli;enlarged glomerular capsule cavity;mesangial expansion;edema and necrosis in the dilated renal tubules;increased levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.01);and decreased serum SOD activity(P＜0.01).Compared with the model group,the high-dose Shenxiao Jiedu Tongluo Recipe group and the enagliflozin group displayed improved renal histopathology,decreased levels of 24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.05,P＜0.01);and increased serum SOD activity(P＜0.01).CONCLUSION Shenxiao Jiedu Tongluo Recipe can inhibit AIM 2-mediated cell death and alleviate renal inflammatory damage in golden hamsters by inhibiting their expression of ROS-dsDNA-AIM 2 signal pathway to attain reduction of their renal ROS level,DNA damage of renal intrinsic cells,and synthesis of AIM 2 inflammatory corpuscles as well.

Bile acids (BAs) are a group of endogenous steroid molecules that regulate lipid, glucose and energy metabolism. They play an important role in maintaining body homeostasis and physiological functions as key signaling molecules for host and gut microbial metabolism. The accurate characterization and quantification of BAs in vivo is of great importance in basic and clinical research. Over the past decades, enzymatic assay, enzyme-linked immunoassay, nuclear magnetic resonance (NMR), chromatography, and other related techniques have been developed and applied to the detection of BAs. The diverse structures of BAs, the existence of isomers and the complex matrix of biological samples pose great challenges for the detection of endogenous BAs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is a robust analytical technique that combines the rapid separation capacities of UPLC with the powerful structural identification capabilities of MS/MS, facilitating the more rapid separation, characterization and accurate quantitative of target analytes in biological samples. UPLC-MS/MS has been widely used in the quantitative analysis of BAs in recent years for its high selectivity, high sensitivity, and high accuracy. This paper summarized the biosynthetic pathways of BAs, sample pretreatment methods, common analytical detection techniques, and highlights the current status of the application of UPLC-MS/MS technology in the analysis of endogenous BAs over the past five years, to provide a reference for the accurate detection of endogenous BAs and further research development and application.

OBJECTIVE To investigate the improvement effect mechanism of Xibining prescription （XBN） on knee osteoarthritis （KOA） model rats based on AMP-activated protein kinase（AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Totally 36 rats were randomly divided into blank group， model group， XBN group （12.56 g/kg）， XBN+metformin （AMPK agonist） group （12.56 g/kg XBN+100 mg/kg metformin）， with 9 rats in each group. Except for blank group， KOA model was induced by anterior cruciate ligament transection in other groups. After modeling， each group was given relevant medicine/normal saline， XBN and normal saline intragastrically， once a day， and metformin intraperitoneally， every other day， for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage， mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS-4）， ADAMTS-5， matrix metalloproteinase 3 （MMP-3） and MMP- 13， and the phosphorylation level of AMPK and mTOR proteins were detected. RESULTS Compared with blank group， the structure of cartilage tissue in the model group was disordered， the matrix of cartilage layer was lightly stained，the tide line was distorted or interrupted， and Mankin score was significantly increased （P＜0.05）. The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly （P＜0.05）； mRNA and protein expressions of ADAMTS-4， ADAMTS-5， MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues （P＜0.05）. Compared with model group， the pathological morphology of cartilage was improved significantly in each administration group， and above score or indexes were reversed significantly （P＜0.05）. Compared with XBN group， the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group， and the levels of above score or indicators were further improved （P＜0.05）. CONCLUSIONS XBN can ameliorate cartilage injury in KOA model rats， promote cartilage synthesis and reduce cartilage degradation， the mechanism of which may be associated with activating AMPK/mTOR signaling pathway.

Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).

We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg^-1), medium (8 g·kg^-1) and high (16 g·kg^-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.