ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L^-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

ObjectiveTo investigate the effect of Yishen Tongluo prescription （YSTLP） on apoptosis of renal tubular epithelial cells and explore the mechanism based on endoplasmic reticulum stress pathway of protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4）/transcription factor C/EBP homologous protein （CHOP）. MethodThe db/db mice were randomly divided into model group， valsartan group （10 mg·kg^-1）， and low， middle， high-dose YSTLP groups （1， 2.5， 5 g·kg^-1）. Samples were collected after eight weeks of drug intervention. In addition， db/m mice in the same litter served as the control group. Human renal tubular epithelial cells （HK-2） were cultured in vitro and divided into the control group， advanced glycated end-product （AGE） group， and AGE + low， middle， and high-dose YSTLP groups （100， 200， 400 mg·L^-1）. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect the apoptosis rate of HK-2 cells. Methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay was conducted to detect the viability of HK-2 cells. Calcium fluorescence probe staining and luciferase reporter gene method were adopted to detect the luciferase activity of folded protein response element （UPRE） and endoplasmic reticulum stress. Immunohistochemical （IHC） analysis was carried out to measure the protein expressions of phosphorylated PKR （p-PERK）， CHOP， and ATF4. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of CHOP and X-box binding protein 1 （XBP1） in mouse kidney and HK-2 cells. Western blot was used to detect the protein expression level of p-PERK， PERK， CHOP， ATF4， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and cleaved Caspase-3 in mouse kidney and HK-2 cells. ResultIn the cellular assay， HK-2 cell viability was significantly reduced， and the apoptosis rate was elevated in the AGE group compared with the control group （P<0.01）. The mRNA and protein expression levels of apoptosis-related factor Bcl-2 were significantly reduced （P<0.01）， and those of Bax were significantly increased （P<0.01）. The protein expression level of cleaved Caspase-3 was significantly increased （P<0.01）. Compared with the AGE group， YSTLP administration treatment resulted in elevated cell viability and reduced apoptosis rate （P<0.01）. The mRNA and protein expression levels of Bcl-2 were significantly elevated in a time- and dose-dependent manner （P<0.01）， and those of Bax were significantly reduced in a time- and dose-dependent manner. The protein expression level of cleaved Caspase-3 was significantly reduced in a time- and dose-dependent manner （P<0.01）. The intracellular Ca²⁺ imbalance and UPRE luciferase fluorescence intensity were increased in the AGE group compared with the control group （P<0.01）. The mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 were significantly increased （P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the AGE group， YSTLP effectively improved intracellular Ca²⁺ imbalance in HK-2 cells and decreased UPRE luciferase fluorescence intensity in a dose-dependent manner （P<0.01）. It reduced the mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 （P<0.01） and the protein expression levels of intracellular p-PERK， CHOP， and ATF4 in a dose- and time-dependent manner （P<0.01）. In animal experiments， the protein expression level of Bcl-2 was significantly reduced（P<0.01）， and that of cleaved Caspase-3 and Bax was significantly increased in the model group compared with the control group （P<0.05）. The protein expression level of Bcl-2 was dose-dependently elevated， and that of cleaved Caspase-3 and Bax was dose-dependently decreased in the YSTLP groups compared with the model group （P<0.01）. Compared with the control group， the mRNA expression levels of CHOP and XBP1 were significantly elevated in the model group （P<0.05， P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the model group， YSTLP significantly decreased the mRNA expression levels of CHOP and XBP1 （P<0.01） and the protein expression levels of p-PERK， CHOP， and ATF4 （P<0.01）. ConclusionYSTLP can effectively inhibit endoplasmic reticulum stress and improve apoptosis of renal tubular epithelial cells， and its mechanism may be related to the regulation of the PERK/AFT4/CHOP pathway.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

Objective To investigate the clinical efficacy of Shenling Weixiao capsules combined with XELOX(oxaliplatin+capecitabine)chemotherapy regimen in the treatment of patients with spleen-qi deficient colorectal cancer.Methods Eighty patients with spleen-qi deficient colorectal cancer treated at the Cangzhou Hospital of Integrated TCM-WM·Hebei from January 2020 to May 2022 were selected as the research subjects.The patients were divided into the control group and the observation group by using the random number table,with 40 patients in each group.The patients in the control group were treated with XELOX regimen,and the patients in the observation group were treated XELOX regimen and Shenling Weixiao capsules.The patients in both groups were treated for 4 treatment cycles,with 21 days as one treatment cycle.After treatment,the clinical efficacy of patients in the two groups was evaluated according to the evaluation criteria in solid tumors,and the traditional Chinese medicine(TCM)syndrome score was recorded.The quality of life of patients in the two groups was assessed by using the functional assessment of cancer theraphy-colorectal(V4.0).Serum levels of tumor markers like squamous cell carcinoma antigen(SCC-Ag),carcinoembryonic antigen(CEA),and carbohydrate antigen 199(CA199)were measured by using the electrochemiluminescence immunoassay.Serum levels of inflammatory factors like tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP),and vascular endothelial growth factor(VEGF)were measured by using the enzyme-linked immunosorbent assay.The levels of CD3+,CD4+and CD8+T lymphocyte subpopulations in blood were detected by using the flow cytometry,and the CD4+/CD8+ratio was calculated.The incidence of adverse reactions was recorded.Results The overall effective rate of patients in the observation group[75.0％(30/40)]was significantly higher than that of patients in the control group[52.5％(21/40)](x2=4.381,P＜0.05).There was no statistically significant difference in the TCM syndrome score and the quality of life score between the two groups before treatment(P＞0.05).Compared with before treatment,there was a significant decrease in the TCM symptom score and a significant increase in the quality of life score in the two groups after treatment(P＜0.05).After treatment,the TCM symptom score of patients in the observation group was significantly lower than that in the control group,while the quality of life score was significantly higher than that in the control group(P＜0.05).There was no statistically significant difference in serum SCC-Ag,CEA and CA199 levels of patients between the two groups before treatment(P＞0.05).Compared with before treatment,the serum SCC-Ag,CEA and CA199 levels of patients in the two groups were significantly reduced after treatment(P＜0.05).After treatment,the serum SCC-Ag,CEA and CA199 levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).There was no statistically significant difference in the serum levels of TNF-α,IL-6,CRP and VEGF of patients between the two groups before treatment(P＞0.05).Compared with before treatment,the serum levels of TNF-α,IL-6,CRP and VEGF of patients were significantly reduced in the two groups after treatment(P＜0.05).The serum levels of TNF-α,IL-6,CRP and VEGF of patients in the observation group were significantly lower than those in the control group after treatment(P＜0.05).There was no statistically significant difference in the CD3+,CD4+and CD8+levels and the CD4+/CD8+ratio of patients between the two groups before treatment(P＞0.05).Compared with before treatment,the CD3+and CD4+levels and the CD4+/CD8+ratio of patients increased and the CD8+level decreased in the two groups after treatment(P＜0.05).The CD3+and CD4+levels and the CD4+/CD8+ratio were significantly higher and the CD8+level was significantly lower in the observation group than those in the control group after treatment(P＜0.05).The incidence of adverse reactions in the control group and observation group was 32.50％(13/40)and 12.50％(5/40),respectively,and the incidence of adverse reactions in the observation group was significantly lower than that in the control group(x2=4.588,P=0.032).Conclusion Shenling Weixiao capsules combined with XELOX chemotherapy regimen can improve clinical symptoms,reduce inflammatory responses,and enhance the immune function of patients with spleen-qi deficient colorectal cancer.

Signal transducer and activator of transcription 3(STAT3)is known to modulate the expression of genes related to cell transformation,proliferation,and survival,making it a significant target for cancer therapy.Recent research has also highlighted the crucial involvement of aberrant STAT3 activation in the pathogenesis of diabetic kidney disease(DKD).Accordingly,this article focuses on the therapeutic potential of targeting STAT3 in DKD.The structure of STAT3,its mechanisms of activity regulation,mechanisms of abnormal STAT3 activation in DKD,and a summary of the current research is provided.The review aims provide a reference for research into the pathogenesis of DKD and the development of new drugs.

Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.

OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.

Objective:To investigate the diagnostic value of cardiac magnetic resonance (CMR) contrast medium perfusion and delayed contrast enhancement for early myocardial ischemia.Methods:Ninety-one patients with coronary artery stenosis diagnosed by coronary angiography (CAG) between March 2020 and March 2022 in Yiwu Central Hospital were included in this study. These patients underwent first-pass perfusion cardiac magnetic resonance imaging and delayed enhancement examination. Arrival time ( t0), accumulative signal intensity (ASI), relative peak enhancement rate (SI%), maximum intensity of signal enhancement (SIp), and maximum curve slope (α) were statistically analyzed in the CMR contrast agent normal-dose perfusion and low-dose perfusion segments. The diagnostic value of CMR contrast agent perfusion versus CAG for early myocardial ischemia was determined. The signal intensity was compared between enhanced and non-enhanced areas of CMR contrast agent perfusion. Results:There were significant differences in ASI, SI%, SIp, and Slope (α) between normal perfusion and low perfusion segments ( t = 9.62, 10.65, 8.67, 6.93, all P < 0.05). There was no significant difference in the detection rate of lesioned vessels in early myocardial ischemia between CMR contrast agent perfusion and CAG [50.42% (120/238) vs. 51.68% (123/238), χ2 = 1.32, P = 0.163). There was a significant difference in the detection rate of lesioned vessels in myocardial ischemia between CMR contrast agent perfusion and CAG ( χ2 = 15.31, P < 0.001, r = 0.71). The signal intensity value in the delayed enhancement segment was significantly higher than that in the non-delayed enhancement segment [(598.43 ± 40.19) vs. (298.64 ± 70.58), t =19.85, P = 0.001). Conclusion:CMR contrast agent perfusion can effectively evaluate the severity of early myocardial ischemia and locate the diseased blood vessels. Delayed enhancement can determine the location and area of early myocardial ischemia, and can objectively reflect the severity of myocardial ischemia.

Fibrosis refers to the final outcome of damage in multiple-type tissue and the imbalance of tissue repair especially in the process of chronic inflammatory response diseases.Fibrosis can occur in various organ tissues.Its continuous progression may lead to organ dysfunction and failure,which is a huge threat to human health.Traditional Chinese medicine has significant therapeutic effects in preventing and treating fibrosis.Due to its characteristics of multiple components,pathways,and targets,it has become a hot research topic in the field of fibrosis.Astragali Radix,a Chinese medicinal for supplementing qi,is the root of Astragalus membranaceus(Fisch.)Bge.var.mongholicus Hisao or Astragalus membranaceus(Fisch.)Bge.It has the effects of replenishing qi and elevating yang,generating fluid and nourishing blood,expelling toxin and draining pus,astringing sore and promoting granulation.It has found that Astragali Radix contains many chemical components such as polysaccharides,saponins,and flavonoids,which have good anti-inflammatory and antioxidant effects.Astragali Radix can effectively intervene in the fibrosis process of multiple organ tissues such as the heart,kidney,liver,and lung.Therefore,this article reviews the anti-fibrotic effects and mechanisms of Astragali Radix and its chemical components,hoping to provide ideas and references for the development and utilization of Astragali Radix.