OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

OBJECTIVE To study the differences in toxicity between intravenous(iv)administration and aqueous solution exposure of Dichroa alkali salt(DAS)in zebrafish.METHODS ① Well-devel-oped zebrafish larvae of 2 d post fertilization(2 dpf)were randomly divided into the normal control(no treatment),solvent control(saline,iv),and DAS groups(0.125,0.25,0.50,1.00 and 2.00 mg·kg-1,iv)before being observed for 3 consecutive days after administration.A heart rate of 0 was determined as death of zebrafish,and the mortality rate,maximum non-lethal dose(MNLD),and 10 percent lethal dose(LD10)were calculated.The incidence of venous sinus congestion,pericardial edema,slowing heart rate and blood flow of zebrafish in the 0.50 and 2.00 mg·kg-1 groups were observed and calculated by somatoscopic microscopy at 4 h after drug administration.Zebrafish larvae were iv given DAS at doses of 0.041,0.136,0.412,and 0.452 mg·kg-1 while the malformation phenotypes of zebrafish larvae development were observed under a stereomicroscope for 3 consecutive days,including pericardial edema,abnormal heart rate,slow blood flow,loss of circulation,eye abnormalities,brain malforma-tions,jaw abnormalities,loss/degeneration of the liver,delayed yolk sac absorption,intestinal abnormal-ities,abnormal body coloration,body edema,curvature of the trunk/tail/nodal cord and muscle degener-ation before the incidence was calculated.②Zebrafish larvae were randomly divided into a normal control group and DAS aqueous solution exposure groups at concentrations of 2.5,5.0,10.0,25.0,50.0,75.0,and 100.0 mg·L-1,observed for 3 d until the mortality rate,LD10,and MNLD were calculated.Zebrafish were exposed to DAS aqueous solutions at concentrations of 0.32,1.06,3.20,and 11.00 mg·L-1,and the malformation phenotypes of zebrafish larvae development were observed under a stereomicro-scope for 3 consecutive days to calculate the incidence.RESULTS ① The MNLD and LD10 of DAS iv administered to zebrafish larvae were 0.412 and 0.452 mg·kg-1,respectively.Compared with the solvent control group,4 h after DAS iv administration,the incidence of sinus congestion,slow heart rate and pericardial edema in the 0.50 and 2.00 mg·kg-1 groups significantly increased(P<0.05,P<0.01),so was the incidence of slow blood flow in the 2.00 mg·kg-1 group(P<0.01).The rate of delayed yolk sac absorption was significantly increased in the 0.041,0.136,0.412,and 0.452 mg·kg-1 groups(P<0.05,P<0.01),so was the mortality rate in the 0.452 mg·kg-1 group(P<0.05),with pericardial edema observed in the dead zebrafish.② The MNLD and LD10 of DAS aqueous solution exposure for zebrafish larvae were 3.20 and 11.00 mg·L-1,respectively.Compared with the normal control group,the incidence of decreased heart rate and slow blood flow was significantly increased in the 3.20 and 11.00 mg·L-1 groups(P<0.01),so was the incidence of significantly darkened intestines in the 1.06,3.20,and 11.00 mg·L-1 groups(P<0.01).The incidence of delayed yolk sac absorption was significantly increased in the 0.32,1.06,3.20,and 11.00 mg·L-1 groups(P<0.05,P<0.01),so was the incidence of trunk curvature and lower jaw malformation in the 11.00 mg·L-1 group(P<0.01).CONCLUSION The toxic phenotypes of DAS are different between iv administration and aqueous solution exposure in zebrafish larvae.DAS aqueous solution exposure can not only lead to slow heart rate,slow blood rheology,delayed yolk sac absorption and intestinal blackening,but also induce neurodevelopmental toxicity.However,iv adminis-tration can effectively ward off significant gastrointestinal damage and neurodevelopmental toxicity.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective:To compare the survival outcomes in patients of small cell lung cancer (SCLC) with brain-single metastasis and brain with organs-multiple metastasis.Methods:Using the US surveillance, epidemiology and final results database, 5 520 SCLC patients with complete clinical information from 2004 to 2015 were selected. SCLC patients were adjusted, stratified or matched according to the metastasis site after the stratification or matching of the propensity scores, and the lung cancer-specific survival (CSS) rate and overall survival (OS) rate were compared between brain-single metastasis group and brain with organs-multiple metastasis group. In addition, the effects of chemotherapy and radiotherapy in CSS between brain-single metastasis group and brain with organs-multiple metastasis group were compared.Results:Of the 5 520 SCLC patients, 2 658 cases was in the brain-single metastasis group, and 2 862 cases was in brain with organs-multiple metastasis group. After the stratification or matching of the propensity scores, the median survival time in brain-single metastasis group was significantly longer than that in brain with organs-multiple metastasis group (6 months vs. 4 months), and there was statistical difference ( P<0.05). The fatality rate in brain-single metastasis group was significantly lower than that in brain with organs-multiple metastasis group (80.66% vs. 85.96%), and there was statistical difference ( P<0.01). Kaplan-Meier survival curve analysis result showed that the OS rate and CSS rate in brain-single metastasis group were significantly higher than those in brain with organs-multiple metastasis group (14.72% vs. 9.50% and 19.34% vs. 14.04%), and there were statistical differences ( P<0.05). Cox analysis result showed that age, race, T stage, gender, N stage, radiotherapy, chemotherapy, tumor diameter, marriage and metastasis were the influencing factors of CSS rate in SCLC patients with brain metastasis ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that radiotherapy and chemotherapy can significantly improve the CSS rate ( HR = 0.668 and 0.671, 95% CI 0.570 to 0.783 and 0.573 to 0.786, P < 0.01). Conclusions:The survival rate in SCLC patients with brain-single metastasis is higher than that of SCLC patients with brain with organs-multiple metastasis; chemotherapy and radiotherapy can improve the survival rate in SCLC patients with brain metastasis.

Objective To explore the effect of antimicrobial use density (AUD) on the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) and antimicrobial resistance rate of healthcare-associated Staphylococcus aureus (HA-SA) half a year later.Methods From 2012 to 2015,all types of AUD,detection rate of MRSA,and antimicrobial resistance rate of HA-SA were calculated semiannually,correlation between antimicrohial resistance rate of HA-SA and all types of AUD in the same first half of year were analyzed with correlation analysis and multiple linear regression.Results From the first half of 2012 to the latter half of 2015,the total AUD declined from 128.2 to 49.0,except the AUD of carbapenems rose,AUD of other antimicrobial agents declined.From the latter half of 2012 to the latter half of 2015,104 249 patients were admitted to the hospital,and 1 008 strains of SA were isolated from 40 884 specimens,857 (85.02％) of which were community-associated SA(CA SA) and 151 (14.98％) were HA-SA.Isolation rate of HA-MRSA declined from 31.25％ in the latter half of 2012 to 12.50％ in the latter half of 2015;isolation rate of CA-MRSA rose from 7.08％ to 16.08％,resistance rate of HA-SA was generally higher than that of CA-SA.Antimicrobial resistance rate of HA-SA to ciprofloxacin remained the same,to levofloxacin increased,to 8 other antimicrobial agents all declined;resistance rates of CA-SA to oxacillin,ciprofloxacin,clindamycin,gentamicin,and levofloxacin increased,but to other antimicrobial agents declined;no SA strains was found to be resistant to vancomycin and linezolid.The resistance rate of HA-SA to azithromycin and erythrocin was correlated with the AUD of macrolides,resistance rate of HA-SA to clindamycin was correlated wvith the AUD of aminoglycosides,to gentamicin was correlated with the AUD of macrolides and the total AUD.Conclusion The selective pressure of antimicrobial agents is still the important cause of the occurrence of antimicrobial resistance,decreasing the AUD of antimicrobial agents will help for reducing the detection rate of HA-MRSA and drug resistance rate of HA-SA.

Objective To investigate the potential of polylactic acid glycolic acid copolymer (PLGA) composite ordered multi tunnel collagen scaffold in fabricating a biomimetic artificial nerve graft to repair the sciatic nerve defects in rats.Methods The ordered multi tunnel collagen scaffold was prepared by vacuum freeze-drying and directional drawing method to simulate the epineurium;the outer conduit was prepared by PLGA to simulate the epineurium;and then,the ordered multi tunnel collagen scaffolds were loaded in the PLGA conduit (5∶1) under a stereomicroscope to develop a novel biomimetic artificial nerve.Sixty-four rats were randomly divided into four groups:artificial nerve group,PLGA group,peripheral nerve group,and non-graft control group (n=16);rats in the artificial nerve group,PLGA group,and peripheral nerve group were repaired with artificial nerve graft,hollow PLGA conduit and allogeneic sciatic nerve to bridge the sciatic nerve defect,while the sciatic nerve with the gap in rats of the control group was without any grafting.After 11 weeks of operation,the hind limbs of rats in each group were detected by behavioral test,electrophysiological examination and Fluoro-Gold retrograde tracing method.The changes of muscle tissues (gastrocnemius) were observed by hematoxylin staining and TMR-α-BTX staining,and the regenerated axons were observed by immunohistochemical staining with NF200 and the regenerative spinal anterior horn motor neurons were observed by Nissl fluorescence staining 12 weeks after operation.Results After 11 weeks of operation,the recoveries of the motor functions (the distance between the injured hindlimb and forelimb,the rotation angle of the injured foot) in the peripheral nerve group,artificial nerve group,PLGA group and control group were significantly deteriorated in turn,and the differences were statistically significant (P＜0.05).Electrophysiological examination showed that the recovery effect of peripheral nerve group was the best in both latency and amplitude of the compound muscle action potential,followed by artificial nerve group.The latency of PLGA group was the longest and the amplitude of compound action potential was the smallest;significant differences were noted between each two groups (P2＜0.05).At 12 weeks after operation,the wet weight ratio of muscle fibers,area of muscle fibers and neuromuscular junction area were significantly different between each two groups (P＜0.05);the degree of gastrocnemius atrophy in the artificial nerve group was significantly improved than that in the PLGA group,but not yet reached the level of peripheral nerve group.NF200 immunohistochemical staining showed that a large number of NF200-positive axons were seen in the grafts of the artificial nerve group,but the number was slightly smaller than that of the peripheral nerve group;the number of regenerated axons in the PLGA group was the smaller and mainly distributed near the proximal side.In the PLGA group,only (19.33 ±6.73)％ regenerated spinal anterior horn motor neurons were labeled with Fluoro-Gold,while the positive rates of Fluoro-Gold in the artificial nerve group and peripheral nerve group were (42.67±7.45)％ and (50.13±4.33)％;the differences between each two groups were statistically significant (P＜0.05).Conclusion The biomimetic artificial nerve made of PLGA conduit and ordered multi tunnel collagen scaffold can efficiently reconstruct the defected peripheral nerve with guiding axonal regeneration and promoting functional restoration in rats;however,its effect is poor than peripheral nerve grafting.

[Summary] To investigate the difference in serum pigment epithelium-derived factor ( PEDF) among type 2 diabetic patients before and after use of dipeptidyl peptidase-4 inhibitors linagliptin for treatment, and to explore the correlation of serum PEDF with lipids, body mass index, and HbA1C . 39 patients with recently diagnosed type 2 diabetes and 30 healthy individuals were enrolled. Baseline weight, waist circumference, body mass index, fasting plasma glucose, HbA1C , serum glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, total cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol ( LDL-C) , and PEDF measured by enzyme linked immunosorbant assay were determined both in the diabetic and control subject. The treatment group was treated with oral linagliptin 5 mg/d for six month, serum PEDF and clinical parameters were determined in the diabetic group during 6 months of treatment. ( 1 ) PEDF levels were found to be comparable with the controls ( P=0. 584);LDL-C and waist circumference showed positive correlation with PEDF(P<0. 05 or P<0. 01). (2) PEDF level was significantly increased in patients with type 2 diabetes after linagliptin treatment [(3. 21 ± 1. 91 vs 2. 45 ± 1.53)μg/ml,P<0.01]. SerumPEDFlevelinpatientswithtype2diabeteswassimilartothatofhealthycontrolswith associated LDL-C and waist circumference. After linagliptin treatment, serum PEDF level was raised, suggesting that it may have certain protective effect for diabetic vascular complications.

Objective To investigate changes in serum sclerostin (SO) in postmenopausal women before and after treatment with recombinant human parathyroid hormone (1-34) [rhPTH (1-34)],and to explore the relationship of serum SO with estradiol (E2),and bone mineral density (BMD).Methods Ninety-five postmenopausal women were divided into normal BMD group (n =41) and osteoporosis group (n =54).Body mass index,alkaline phosphatase (ALP),serum E2,calcium,phosphate,and SO were determined in both groups.The patients in osteoporosis group were treated with rhPTH (1-34) 20 μg/d by subcutaneous injection and oral calcium 500 mg/d for 12 months.Serum calcium,serum phosphate,BMD,serum ALP,serum E2,and sclerostin were determined in osteoporosis group by 6 months and 12 months of treatment.Results (1) Serum level of SO in osteoporosis group was raised significantly as compared with normal BMD group (P ＜ 0.05) ; E2 and BMD were negatively correlated with SO; age and postmenopausal years were positively correlated with SO (P ＜ 0.05).(2) Serum SO was reduced gradually with treatment of rhPTH (1-34) by 6 months and 12 months (P ＜ 0.05).Conclusions Serum SO was increased in postmenopausal women,which was related to E2 and BMD,and was reduced gradually with treatment of rhPTH (1-34).SO may participate in the development of postmenopausal osteoporosis.

ObjectiveTo investigate the effect of rhPTH (1-34) and elcatonin on bone metabolism and serum secreted protein acidic and rich in cysteine ( SPARC ) in postmenopausal women with osteoporosis.Methods One hundred and twenty-four postmenopausal women with osteoporosis were randomly divided into 2 groups:One group was treated with recombinant human parathyroid hormone ( 1-34 ) [ rhPTH ( 1-34 ) ] 200 U/d by subcutaneous injection (PTH group,n =89 )and another group was treated with elcatonin 20 U/week by intramuscular injection (CT group,n =35 ) for 12 months.All patients received a basic therapy with oral calcium ( Ca 600 mg+ Vit D3125 U,q..d.).The bone mineral density ( BMD ) of lumbar spine( L2-4 ),the left femoral neck,greater trochanter,and Ward's triangle,serum calcium and phosphate were measured by baseline,6 months' and 12 months.Levels of serum bone-specific alkaline phosphatase( BSAP),serum secreted protein acidic and rich in cysteine (SPARC)were determined by an ELISA assay.ResultsBy 12 months,rhPTH ( 1-34 ) treatment significantly increased the lumbar spine L2-4 BMD 7.9％ (P＜0.05),serum calcium 8.3 ％ ( P＜ 0.05 ),serum BSAP 93.4％ ( P＜ 0.05 ),serum SPARC by 12.6％[ ( 195.68±59.57 vs 173.81 ±81.33 ) pμg/L,P＜0.05 ].Elcatonin therapy increased the lumbar spine L2-4 BMD by 3.2％ (P＜0.05) at the end of 12 months,but elcatonin did not influence serum calcium,BSAP and SPARC.The rhPTH( 1-34 ) increased lumbar spine L2-4 BMD more than elcatonin did at 12 months( P＜0.05 ).ConclusionrhPTH (1-34) could promote the bone anabolism more effectively than elcatonin did.Serum SPARC may play an important role in promoting osteogenesis by rhPTH.