Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.

Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.

Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Mitral valve prolapse is one of the common causes of mitral regurgitation.Mitral valve prolapse complicated with leaflet cleft is rare in clinical practice,which most often undergo surgical mitral valve repair or mitral valve replacement.We report a case of mitral valve prolapse with posterior leaflet cleft treated by transcatheter edge-to-edge mitral valve repair,in order to provide a model for similar cases.

Objective:To investigate the impacts of galangin(Gal)on the immune inflammatory response in preeclampsia(PE)rats by regulating the IL-6/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Pregnant rats were injected subcutaneously with L-arginine methyl ester(L-NAME 125 mg/kg)to establish a PE model.After successful modeling,they were randomly grouped into Model group,low,medium and high doses Gal groups(10,30,and 60 mg/kg)and activator group(60 mg/kg Gal+0.05 mg/kg IL-6/STAT3 pathway activator rIL-6).Twelve pregnant rats of the same period were randomly selected as the control group,and each group was given corresponding drugs by gavage and intraperitoneal injection,once a day for a continuous week.The levels of mean caudal artery pressure(MAP)and 24-hour urinary protein and blood urea nitrogen(BUN)in rats during the third trimester of pregnancy were measured using a blood pressure tester and a fully automated biochemical analyzer;the number and weight of the average offspring of pregnant mice in each group were calculated,and the pregnancy outcome was analyzed;HE staining was applied to observe the pathological damage of rat placenta;ELISA was applied to detect the levels of IL-6,IL-1β and TNF-α in the placenta of rats in each group;the proportion of T lymphocytes in rat peripheral blood was detected by flow cytometry;Western blot was applied to detect the expression of IL-6/STAT3 pathway protein in rat placenta.Results:Compared with control group,the lev-els of MAP,24-hour urinary protein,BUN,IL-6,IL-1β,TNF-α,the CD8+T cells,and the expression levels of IL-6 and p-STAT3/STAT3 proteins in Model group were obviously increased,the placenta tissue was severely damaged,the mean offspring number and mean offspring weight,the proportions of CD3+T,CD4+T,and CD4+/CD8+T cells were decreased(P<0.05);compared with Model group,the levels of MAP,24-hour urinary protein,BUN,IL-6,IL-1β,TNF-α,the CD8+T cells,and the expression levels of IL-6 and p-STAT3/STAT3 proteins in Gal low,medium and high doses groups were obviously decreased,the damage to placental tissue was reduced,the mean offspring number and mean offspring weight,the proportions of CD3+T,CD4+T,and CD4+/CD8+T cells were in-creased(P<0.05);compared with Gal high-dose group,the levels of MAP,24-hour urinary protein,BUN,IL-6,IL-1β,TNF-α,the CD8+T cells,and the expression levels of IL-6 and p-STAT3/STAT3 proteins in activator group were obviously increased,the placenta tissue was aggravated,the mean offspring number and mean offspring weight,the proportions of CD3+T,CD4+T and CD4+/CD8+T cells were decreased(P<0.05).Conclusion:Gal may play a role in alleviating PE symptoms and improving pregnancy outcomes by inhibit-ing the IL-6/STAT3 pathway,inhibiting inflammatory reactions,and regulating cellular immunity.

Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.