OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

Objective The molding process of compound Shexiang Huangqi dropping pills was optimized by central composite design and response surface method,the determination of volatile components in the compound by gas chromatography was established in order to improve the quality standard of the compound.Methods Single factor method was used to select the optimum range of matrix type,the ratio of matrix to liquid,and drop distance of compound Shexiang Huangqi dropping pills;Appearance traits,a difference of pill weight,and dissolution time were used as evaluation indexes,the optimum forming process conditions of compound Shexiang Huangqi dropping pills were optimized by central composite design and response surface method;Three batches of compound Shexiang Huangqi dropping pills were taken as test samples and determined by gas chromatography;The gas chromatographic column was HP-5 sillica capillary column,the inlet temperature was 260 ℃,the temperature was programmed,and the detector temperature was 300 ℃,the split ratio was 10∶1,nitrogen was selected as the carrier gas with a flow rate of 1.0 mL·min-1.Results The optimum forming process conditions of compound Shexiang Huangqi dropping pills were selected by central composite design and response surface method as a matrix:matrix=0.99,drug:matrix=0.55,drop distance=6.00,and the comprehensive score were 0.845 2.Under these conditions,the quality of the prepared dropping pills was the best;The chromatographic peaks of borneol,muscone,and ligustilide reached the baseline separation;the linear ranges of the three components were 0.327-1.962,0.140-0.840,0.710 5-4.263 μg(all r＞0.999);The average recoveries were 92.30％(RSD=1.65％,n=6),101.28％(RSD=0.81％,n=6)and 98.99％(RSD=0.65％,n=6);The average contents of the three components were 0.201 7,0.084 7 and 1.382 9 mg·g-1,respectively.Conclusions The forming process is stable and feasible,which can provide a reference for the development and application of compound Shexiang Huangqi dropping pills;The gas chromatography method established can simultaneously determine the contents of borneol,muscone,and ligustilide in compound Shexiang Huangqi dropping pills,which can be used for quality control of compound Shexiang Huangqi dropping pills.

Objective To construct a Framingham risk score(FRS)tool for predicting poor prognosis after mechanical thrombec-tomy(MT)in patients with middle cerebral artery(MCA)acute ischemic stroke(AIS)based on logistic regression model.Methods A retrospective analysis was conducted on the imaging and clinical data of 126 patients with MCA-AIS.Categorical data were com-pared between groups using the chi-square test or continuity-corrected chi-square test,while normally distributed continuous data were analyzed using the independent samples t-test.Multivariate logistic regression analysis was used to screen the risk factors for poor prognosis after MT in patients with MCA-AIS.The Framingham risk assessment model was used to establish a FRS tool for poor prognosis after MT in patients with MCA-AIS.Results The independent risk factors for poor prognosis after MT in patients with MCA-AIS were the Alberta stroke program early CT score(ASPECTS)before the operation,the baseline National Institute of Health Stroke Scale(NIHSS)score,and the time from femoral artery puncture to recanalization.The FRS tool ranges from-7 to 12 points,with a risk prediction rate of 0.044 7 to 0.970 1.Conclusion The FRS tool can calculate the risk probability of poor prognosis sim-ply and quickly,and has high predictive value for the prognosis after MT in MCA-AIS patients.

Objective To construct a Framingham risk score(FRS)tool for predicting poor prognosis after mechanical thrombec-tomy(MT)in patients with middle cerebral artery(MCA)acute ischemic stroke(AIS)based on logistic regression model.Methods A retrospective analysis was conducted on the imaging and clinical data of 126 patients with MCA-AIS.Categorical data were com-pared between groups using the chi-square test or continuity-corrected chi-square test,while normally distributed continuous data were analyzed using the independent samples t-test.Multivariate logistic regression analysis was used to screen the risk factors for poor prognosis after MT in patients with MCA-AIS.The Framingham risk assessment model was used to establish a FRS tool for poor prognosis after MT in patients with MCA-AIS.Results The independent risk factors for poor prognosis after MT in patients with MCA-AIS were the Alberta stroke program early CT score(ASPECTS)before the operation,the baseline National Institute of Health Stroke Scale(NIHSS)score,and the time from femoral artery puncture to recanalization.The FRS tool ranges from-7 to 12 points,with a risk prediction rate of 0.044 7 to 0.970 1.Conclusion The FRS tool can calculate the risk probability of poor prognosis sim-ply and quickly,and has high predictive value for the prognosis after MT in MCA-AIS patients.

Based on the previous transcriptomic experimental data of Trichinella spiralis(T.spira-lis)in this study,the larval stage specific gene TP12446 was screened and its identity in the ubiq-uitin ligase RNF family was predicted.In the study,bioinformatics methods were used to analyze its physicochemical properties and its activity to lay the foundation for further exploring the func-tion of TP12446 gene.The physicochemical properties and protein structure of TP12446 protein were predicted by bioinformatics.Its ubiquitin ligase activity was also verified by ubiquitination re-actions in vitro.The expression characteristics of TP12446 protein in different stage of T.spiralis infection were analyzed by qPCR and Western blot.Bioinformatics analysis showed that TP12446 protein was composed of 453 amino acids and its molecular weight was 51.48 kDa.The protein had a transmembrane structure and contained signal peptides.The results indicated that it was a secre-tory protein and mainly located in the cytoplasmic membrane.The protein structure analysis re-vealed that the protein contained RING and PA domain,its secondary structure was mainly com-posed of α-helix and irregular crimp and there were 10 B cell epitopes on TP12446 protein.The prediction of glycosylation and phosphorylation sites indicated that TP12446 protein contained 38 potential phosphorylation sites.Results of PPI interaction protein prediction showed that TP12446 protein had strong interaction with Usp8,Tmem37,Otub1,Otub2,Ubox5 and CD151.The results of qPCR and Western blot showed that TP12446 gene expression was the highest in the larva stage of T.spiralis,the activity of ubiquitin ligase was verified by ubiquitination reaction in vitro.TP12446 protein was a secretory hydrophobic protein with E3 ubiquitin ligase activity,which was involved in regulating cell cycle and apoptosis.

Objective The molding process of compound Shexiang Huangqi dropping pills was optimized by central composite design and response surface method,the determination of volatile components in the compound by gas chromatography was established in order to improve the quality standard of the compound.Methods Single factor method was used to select the optimum range of matrix type,the ratio of matrix to liquid,and drop distance of compound Shexiang Huangqi dropping pills;Appearance traits,a difference of pill weight,and dissolution time were used as evaluation indexes,the optimum forming process conditions of compound Shexiang Huangqi dropping pills were optimized by central composite design and response surface method;Three batches of compound Shexiang Huangqi dropping pills were taken as test samples and determined by gas chromatography;The gas chromatographic column was HP-5 sillica capillary column,the inlet temperature was 260 ℃,the temperature was programmed,and the detector temperature was 300 ℃,the split ratio was 10∶1,nitrogen was selected as the carrier gas with a flow rate of 1.0 mL·min-1.Results The optimum forming process conditions of compound Shexiang Huangqi dropping pills were selected by central composite design and response surface method as a matrix:matrix=0.99,drug:matrix=0.55,drop distance=6.00,and the comprehensive score were 0.845 2.Under these conditions,the quality of the prepared dropping pills was the best;The chromatographic peaks of borneol,muscone,and ligustilide reached the baseline separation;the linear ranges of the three components were 0.327-1.962,0.140-0.840,0.710 5-4.263 μg(all r＞0.999);The average recoveries were 92.30％(RSD=1.65％,n=6),101.28％(RSD=0.81％,n=6)and 98.99％(RSD=0.65％,n=6);The average contents of the three components were 0.201 7,0.084 7 and 1.382 9 mg·g-1,respectively.Conclusions The forming process is stable and feasible,which can provide a reference for the development and application of compound Shexiang Huangqi dropping pills;The gas chromatography method established can simultaneously determine the contents of borneol,muscone,and ligustilide in compound Shexiang Huangqi dropping pills,which can be used for quality control of compound Shexiang Huangqi dropping pills.

Objective:To study the growth inhibition of Thunberg Fritillary extract on non-small cell lung cancer.Methods:The Thunberg Fritillary extract was prepared and characterized by UPLC-QE/MS.Replicated Lewis lung carcinoma ectopic tumor-bear-ing mouse model,yeast injection induced acute inflammation,compared the effect of Thunberg Fritillary extract combination with acute inflammation on the growth,tumor volume and tumor suppression rate of Lewis lung carcinoma mice,and determine the content of inflammatory factors by the flow CBA method(IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,IL-23,TNF-α,IFN-γ,IFN-β,GM-CSF,MCP-1).Results:The inhibition of Lewis lung carcinoma mice was similar to that of cisplatin alone,and the tumor suppression rate was 35%;the tumor suppression rate of Thunberg Fritillary extract combined with acute inflammatory stimulation of yeast was 62%,1.8 times that of cisplatin alone.The decrease in the expressions of cytokines IL-23,MCP-1 after acute inflammatory stimulation in yeast was associated with tumor suppression;while the increased expressions of IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,TNF-α,IFN-γ,IFN-β and GM-CSF cytokines were associated with tumor suppression.Conclusion:The Thun-berg Fritillary extract combination with acute inflammation can play a positive role against non-small cell lung cancer,which will pro-vide new research ideas and methods for the prevention and treatment of non-small cell lung cancer.

Objective To investigate the mechanism of luteolin(LUT)in inhibiting inflammatory aging for treating diabetic retinopathy(DR).Methods Through preliminary experiments,high glucose(HG)and LUT concentrations were established to induce ARPE-19 cells for the experiment.Cells were divided into:Control group(5.5 mmol·L-1 glu-cose),HG group(35 mmol·L-1 glucose),HG+low LUT group(35 mmol·L-1 glucose+20 μmol·L-1 LUT),HG+high LUT group(35 mmol·L-1 glucose+40 μmol·L-1 LUT).Cell viability was measured by CCK-8 assay;Cell migration abil-ity was assessed by scratch assay;ELISA detected inflammatory aging factors[senescence-associated β-galactosidase(SA-β-Gal),interleukin(IL)-1β,IL-6];DCFDA measured intracellular ROS levels;β-galactosidase activity staining identi-fied cellular senescence;TUNEL assay determined apoptosis rate;Western blot and RT-PCR analyzed protein and mRNA expression of silent information regulator 1(SIRT1),nuclear factor(NF)-κB,NOD-like receptor family pyrin domain con-taining 3(NLRP3),and Thioredoxin.Results Compared with the Control group,the cell viability and migration ability of the HG group decreased,and the difference was statistically significant(both P＜0.01);Compared with the HG group,both the HG+low LUT group and the HG+high LUT group showed an increase in cell viability and migration ability,and the differences were statistically significant(both P＜0.05).Compared with the Control group,the expression levels of SA-β-Gal,IL-1 β,and IL-6 in HG group cells were all increased,and the differences were statistically significant(all P＜0.01);Compared with the HG group,the expression levels of SA-β-Gal in the HG+low LUT group and SA-β-Gal,IL-1β,and IL-6 in the HG+high LUT group decreased,and the differences were statistically significant(all P＜0.05).Compared with the Control group,the HG group showed an increase in the number of senescent cells,apoptosis rate,and ROS content in the cells,with statistically significant differences(all P＜0.01);Compared with the HG group,the number of senescent cells,apoptosis rate,and ROS content in the HG+low LUT group and HG+high LUT group were all reduced,and the differences were statistically significant(all P＜0.05).Compared with the Control group,the expression levels of SIRT1 protein and mRNA in HG group cells decreased,while the expression levels of NF-κB,NLRP3,and Thioredoxin protein and mRNA in-creased,and the differences were statistically significant(all P＜0.01);Compared with the HG group,the expression lev-els of SIRT1 protein and mRNA in the HG+low LUT group and HG+high LUT group increased,while the expression levels of NF-κB,NLRP3,and Thioredoxin protein and mRNA decreased,and the differences were statistically significant(all P＜0.05).Conclusion LUT improves cell viability,migration,senescence and apoptosis levels induced by HG while sup-pressing the expression of inflammatory aging factors,which may be related to its regulation of the SIRT1/NF-κB/NLRP3 signaling pathway.

Background Irritable bowel syndrome with diarrhea(IBS-D)is a common gastrointestinal dysfunction disease,but currently,single Western medicine treatments have significant side effects and are prone to recurrence.Probiotics and traditional Chinese medicine have certain therapeutic effects on IBS-D,but the exact treatment mechanism is still unclear,and there is limited research on the combination of the two.Objective To investigate the effects of Chongkang Capsules combined with Bifidobacterium on gut microbiota,mucosal barrier function,and neurotransmitter levels in patients with IBS-D and comorbid anxiety and depression,and to analyze its therapeutic mechanisms.Methods A total of 150 patients with irritable bowel syndrome with diarrhea(IBS-D)and anxiety and depression who were treated in the gastroenterology department of our hospital from January 2021 to June 2022,were selected as the study subjects.A randomized controlled trial was designed with three treatment groups:50 patients in the observation group received Chongkang Capsules combined with Bifidobacterium for 4 weeks;50 patients in the positive control group received Rifaximin combined with Bifidobacterium for 4 weeks;and 50 patients in the blank control group received Bifidobacterium alone for 4 weeks(to exclude interference from the bacterial species in the Bifidobacterium capsules in intestinal flora detection).The changes in IBS-D symptom severity,stool consistency,anxiety and depression scores(HAM-A/HAM-D),intestinal flora(lactobacilli,Bifidobacterium,bacteroides,enterobacteria),intestinal barrier markers(serum D-lactic acid,DAO),inflammatory factors(IL-6,IL-8,TNF-α),intestinal tight junction proteins(Occludin,ZO-1),neurotransmitters(5-HT),and recurrence rates were compared among the three groups before and after treatment.Results Symptom improvement:the improvement in IBS-SSS scores,stool classification,and HAM-A/HAM-D scores in the observation and positive control groups was significantly better than that in the blank control group(all P<0.001),but there was no significant difference between the two groups(P>0.05).Flora regulation:after treatment,the observation and positive control groups showed a significant increase in beneficial bacteria(lactobacilli and Bifidobacterium)and a significant decrease in pathogenic bacteria(bacteroides and enterobacteria)compared to the blank control group(all P<0.001).The improvement in flora persisted up to 6 months after treatment(P<0.001).Barrier and inflammation:the reduction in serum D-lactic acid,DAO,and IL-6/IL-8/TNF-α levels was significantly greater in the observation and positive control groups than in the blank control group(all P<0.001).The expression of intestinal barrier proteins(Occludin and ZO-1)was significantly upregulated(P<0.001).Neurotransmitters:the increase in serum 5-HT levels were significantly higher in the two groups than in the blank control group(P<0.001).Recurrence rate:the 3-month recurrence rates in the observation group(8.0%)and positive control group(10.0%)were significantly lower than that in the blank control group(30.0%).The 6-month recurrence rates(14.0%vs.16.0%vs.44.0%)also showed significant differences(all P<0.05).Conclusion Chongkang Capsules combined with Bifidobacterium can effectively alleviate clinical symptoms in patients with IBS-D and comorbid anxiety and depression.The mechanism may be related to regulating intestinal flora balance,repairing the intestinal mucosal barrier,suppressing inflammatory responses,and increasing 5-HT levels.Additionally,the low recurrence rate suggests its clinical application value.