Objective:To investigate the mechanism of Coptidis rhizoma in the treatment of gastritis based on network pharmacology. Methods:The main components and targets of Coptidis rhizoma were screened by TCMSP and TCMID database. GeneCards were used to select the target genes related to gastritis from the human gene database, and the target genes related to gastritis were screened by Genemap in the OMIM database. We used R language VennDiagram package to crosse the gene targets of drugs and diseases, and screen the target of the main components of Coptidis rhizoma in the treatment of gastritis, and to use Cytoscape software to map the gene regulatory network of galangal in the treatment of gastritis, and to use the String database to construct the gene-protein of Coptidis rhizoma. The interaction visualization network map for protein- protein interaction (PPI) were screened out the core genes, and the Bioconductor in the R language was used to analyze the GO and KEGG pathways for the selected gene targets. Results:Fourteen main active compounds of Coptidis rhizoma were screened, and 71 gene targets may be involved in the treatment of gastritis. The results of GO and KEGG pathway analysis indicated that berberine mainly involves cytokine receptor binding, regulation of cytokine activity, and biological processes such as binding to heme, by regulating AGE-RAGE, IL-17, TNF, NF-kappa B and HIF-1. The signaling pathway acts to treat gastritis. Conclusions:This study constructed the role of berberine in the treatment of gastritis with multi-active component, multi-gene, multi-target pathway through network pharmacology. It comprehensively predicted the gene target and signaling pathway of Coptidis rhizoma in the treatment of gastritis, in order to further study the treatment of berberine. The mechanism of action of gastritis provides a reference basis.

OBJECTIVE: To screen potential traditional Chinese medicine and their active monomer ingredients for treatment of diabetic nephropathy (DN) through the mechanism of caspase-1-mediated pyroptosis. METHODS: Using the Chinese Medicine System Pharmacology Analysis Platform (TCMSP), we screened traditional Chinese drugs and their active monomer components targeting caspase-1, and searched for the potential gene targets of the monomer components using GeneCards database. Cytoscape was used to construct the monomer compound-gene target network. Gene ontology (GO) functional enrichment analysis and Kyoto Gene and Gene Encyclopedia (KEGG) pathway enrichment analysis were used to predict the molecular mechanism of the screened traditional Chinese medicine and monomers. In SD rat models of diabetic mellitus (DM), we tested the therapeutic effect of ginsenoside Rh2 (daily dose of 20 mg/kg for 12 weeks) by examining renal pathology with HE staining and detecting the expressions of pyroptosis marker proteins caspase-1, GSDMD, IL-1β and IL-18 in the renal tissues using Western blotting, the serum levels of IL-1β and IL-18 and activities of cathepsin B and cathepsin L. RESULTS: Ginsenoside Rh2 could effectively dock with caspase-1 molecule. Fourteen targets were identified in ginsenoside Rh2 target network. GO function enrichment analysis revealed 27 GO terms associated with molecular function (4 terms), cell component (10 terms) and biological process (13 terms). KEGG pathyway enrichment analysis identified 4 signaling pathways involving lysosomes, glycosaminoglycan degradation, galactose metabolism, and sphingolipid metabolism pathways. In the animal experiment, treatment with ginsenoside Rh2 significantly alleviated renal pathologies and down-regulated the expressions of pyroptosis marker proteins (cleaved caspase-1, GSDMD-N, IL-1β and IL-18) ( < 0.05 or 0.01), lowered serum levels of IL-1β and IL-18 ( < 0.01), and enhanced the activities of cathepsin B and cathepsin L in the serum of the diabetic rats. CONCLUSIONS Ginsenoside Rh2 may inhibit caspase-1-mediated pyroptosis through the lysosome pathway to improve kidney damages in rat models of DN.

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes.However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

Clinical pharmacists participated in the antithrombotic diagnosis and treatment of a child with severe pneumonia complicated with intraventricular thrombosis,pulmonary embolism and high renal excretion rate.The child was admitted to the hospital due to"severe pneumonia".Based on the initial coagulation routine indicators,it was considered that the coagulation dysfunction was caused by severe pneumonia.Later,it progressed to right ventricular thrombus and multiple embolisms in both pulmonary arteries.The clinical pharmacist evaluated the risk of thrombus and bleeding by considering the child's age,weight,dynamic changes in disseminated intravascular coagulation and platelet count indicators,as well as liver and kidney function changes.They assisted the clinician in developing an individualized antithrombotic treatment plan.During hospitalization,the child's D-dimer level increased progressively,which was considered to be related to the child's high renal excretion rate.The clinical pharmacist promptly suggested adjusting the frequency and dosage of the antithrombotic medication.The clinician adopted the suggestion,and the child's thrombus masses reduced and dissipated.The child recovered well during hospitalization and was discharged smoothly,follow-up showed no recurrence of thrombus.Clinical pharmacists assisted physicians in developing individualized antithrombotic regimens for children through full pharmacological monitoring,which improved the prognosis of the children,ensured the effectiveness and safety of antithrombotic medication use,and could also provide a reference for antithrombotic therapy for similar children.

Objective: To explore the expression of IQGAP1 (Ras GTPase-activating-like protein containing IQ domain) in esophageal squamous cell carcinoma (ESCC) tissues and cell lines and its effect on the proliferation and invasion of TE-2 cell. Methods: Totally 125 pairs of cancer tissues and para-cancerous tissues from ESCC patients, who underwent surgical resection inAffiliated Tumor Hospital of Zhengzhou University from January 2015 to December 2016, were included in this study; in addition, ESCC cell lines (TE-2, TE3, ECA109) and normal esophageal epithelial cell line Het-1A were also collected. The expression of IQGAP1 was detected by immunohistochemical staining and its relationship with cliniopathological features was also analyzed. IQGAP1 mRNA and protein expressions in ESCC cell lines were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively. TE-2 cells were transfected with si-IQGAP1 (positive transfection group) and si-CTRL (negative control group) plasmids, and the effects of IQGAP1 silencing on the proliferation and invasion of TE-2 cells were detected by MTT and Transwell assay. The expressions of E-cadherin and Ncadherin were detected by Western blotting. Results: The positive expression rate of IQGAP1 in ESCC tissues was significantly higher than that in para-cancerous tissues (P<0.05), which was closely related to tumor stage and histologic grade (all P<0.05). The mRNAand protein expressions of IQGAP1 in TE-2, TE-3 and ECA109 cells were significantly higher than those in Het-1Acells (all P<0.05).After IQGAP1 was silenced, compared with the negative control group and the blank group, the expression of IQGAP1 mRNAand protein in the positive transfection group significantly decreased (all P<0.05); the proliferation and invasiveness of TE-2 cells significantly decreased (all P<0.05); E-cardherin was up-regulated while N-cardherin was down-regulated (all P<0.05) in the positive interference group. Conclusion: IQGAP1 is highly expressed in ESCC tissues, and si-IQGAP1 can inhibit the proliferation and invasion of TE-2 cells, which plays an important role in the occurrence and development of ESCC.

Objective To discuss the rationality of stage pT3 in the AJCC 8th TNM criteria of gallbladder carcinoma. Methods A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage:tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure;(2) pT3b stage:tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females,aged 36 to 80 years,with a median age of 59 years;43 patients with pT3b, including 24 males and 19 females,aged 41 to 78 years old,median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t?test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non?normally distributed measurement data.The comparison of the count data was performed by χ2 test or Fisher exact probability method. Survival analysis was performed using Kaplan?Meier method, and survival rate was compared using Log?rank test.Results (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19?9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816,-1.966,-3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days)(P<0.05).(2) The 1?,3?, 5?year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ2=5.117, P=0.024). (3)The 1?, 3?year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ2=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.

Objective To discuss the rationality of stage pT3 in the AJCC 8th TNM criteria of gallbladder carcinoma. Methods A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage:tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure;(2) pT3b stage:tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females,aged 36 to 80 years,with a median age of 59 years;43 patients with pT3b, including 24 males and 19 females,aged 41 to 78 years old,median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t?test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non?normally distributed measurement data.The comparison of the count data was performed by χ2 test or Fisher exact probability method. Survival analysis was performed using Kaplan?Meier method, and survival rate was compared using Log?rank test.Results (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19?9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816,-1.966,-3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days)(P<0.05).(2) The 1?,3?, 5?year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ2=5.117, P=0.024). (3)The 1?, 3?year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ2=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.

Objective: To discuss the rationality of stage pT3 in the AJCC 8^th TNM criteria of gallbladder carcinoma. Methods: A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage: tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure; (2) pT3b stage: tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females, aged 36 to 80 years, with a median age of 59 years; 43 patients with pT3b, including 24 males and 19 females, aged 41 to 78 years old, median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t-test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non-normally distributed measurement data.The comparison of the count data was performed by χ² test or Fisher exact probability method. Survival analysis was performed using Kaplan-Meier method, and survival rate was compared using Log-rank test. Results: (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19-9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816, -1.966, -3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days) (P<0.05). (2) The 1-, 3-, 5-year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ²=5.117, P=0.024). (3)The 1-, 3-year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ²=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8^th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.