OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To explore clinical efficacy of osteoplasty combined with percutaneous vertebroplasty(PVP)and percutaneous kyphoplasty(PKP)alone in treating osteoporosis vertebral compression fractures(OVCFs).Methods The clini-cal data of 80 patients with single-level OVCFs treated from January 2021 to June 2022 were retrospectively analyzed,and were divided into treatment group and control group according to different surgical methods,40 patients in each group.In treatment group,there were 24 males and 16 females,aged from 60 to 83 years old with an average of(70.43±7.31)years old;bone min-eral density ranged from-3.30 to-2.50 SD with an average of(-2.84±0.24)SD;1 patient with T10,4 patients with T11,11 pa-tients with T12,7 patients with L1,7 patients with L2,5 patients with L3,3 patients with L4,2 patients with L5;bone setting tech-nique combined with PVP were performed.In control group,there were 27 males and 13 females,aged from 60 to 82 years old with an average of(68.98±6.94)years old;bone mineral density ranged from-3.40 to-2.50 SD with an average of(-2.76±0.23)SD;2 patients with T10,3 patients with T11,13 patients with T12,11 patients with L1,5 patients with L2,3 patients with L3,2 patients with L4,1 patient with L5;simple PKP were peformed.Visual analogue scale(VAS)and lumbar Oswestry disability in-dex(ODI)were compared between two groups before operation,3 days,3 and 12 months after operation.The changes of local kyphotic angle,vertebral wedge angle and vertebral anterior margin height ratio were compared between two groups before op-eration,3 days and 12 months after operation.Results All patients were successfully completed operation.Treatment group were followed up from 13 to 22 months with an average of(16.82±2.14)months,and control group were followed up from 13 to 23 months with an average of(16.45±2.56)months.Three patients were occurred bone cement leakage in treatment group,while 1 patient were occurred bone cement leakage and 1 patient occurred sensory disturbance of lower limb skin in control group;there were no significant difference in complications between two groups(P＞0.05).There were no significant difference in preoperative VAS and ODI between two groups(P＞0.05).At 3 days after operation,VAS of treatment group 3.68±0.62 was significantly higher than that of control group 4.00±0.72(P＜0.05).There were no significant difference in VAS and ODI be-tween two groups at 3 and 12 months after operation(P＞0.05).There were no significant difference in local kyphotic angle,vertebral wedge angle and vertebral anterior margin height between two groups at 3 days and 12 months after operation(P＞0.05).Conclusion Compared with PKP,bone setting manipulation combined with PVP for the treatment of OVCFs has advan-tages in early postoperative pain relief.In terms of vertebral height recovery,bone setting manipulation combined with PVP and PKP alone have similar clinical effects.

Objective To understand the infection status of patients with maintenance hemodialysis(MHD)in Guizhou Province,and provide basis for the prevention and control of hemodialysis-related infection.Methods MHD patients in hemodialysis centers of 124 secondary and or higher grade medical institutions in Guizhou Province from July to December 2022 were surveyed.Survey content included the general conditions of patients,hemodialysis-related conditions,infection of pathogens of blood-borne diseases,and other infection-related conditions.Results A total of 15 114 MHD patients were surveyed,with age mainly ranging from 36 to＜60 years old(55.83％).Hemodialysis history ranged mainly from 1 year to＜5 years(59.37％),and the frequency of hemodi-alysis was mainly 3 times per week(73.91％).Autologous arteriovenous fistula(AVF)was the major vascular access for dialysis,with a total of 12 948 cases(85.77％).The main primary disease was chronic renal failure(99.89％).The infection rates of hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency vi-rus(HIV),and Treponema pallidum in MHD patients were 5.29％,0.64％,0.24％,and 1.70％,respectively.HBV infection rates among MHD patients of different ages,different numbers of dialysis hospitals,and dialysis in-stitutions of different scales showed statistically significant differences(all P＜0.05).HCV infection rates among MHD patients of different ages,with different dialysis times and from institutions of different scales were signifi-cantly different(all P＜0.05).TP infection rates among MHD patients of different ages and different numbers of dialysis hospitals were all significantly different(all P＜0.05).Infection rates of HBV and HCV in MHD patients aged from 36 to 60 years old(not included)were relatively higher(6.10％and 0.84％,respectively).Patients with dialysis time ≥10 years had a higher HCV infection rate(1.64％).Infection rates of HCV,HIV,and TP in pa-tients dialyzed in medical institutions with ≥90 dialysis beds were relatively higher(0.74％,0.28％,and 1.94％,respectively).Medical institutions with＜30 dialysis beds had the highest HBV infection rate(18.64％).There were 9 cases(0.06％)of vascular puncture infection,12 cases(0.08％)of bloodstream infection,7 cases(0.05％)of vascular access-related bloodstream infection,and 30 cases(0.20％)of pulmonary infection.Vascular access-re-lated bloodstream infection rate and pulmonary infection rate among MHD patients with different types of vascular access showed statistically significant difference(all P＜0.05).Vascular access-related bloodstream infection rate(0.37％)and pulmonary infection rate(1.10％)of patients with non-cuffed catheters vascular access were higher than those of other types.Conclusion MHD patients in Guizhou Province are mainly middle-aged and young peo-ple,with more males than females.The dialysis frequency is mostly 3 times per week,and AVF is the major vascu-lar access.MHD patients are prone to complications such as infections of HBV,HCV,HIV,and TP,as well as bloodstream infection and pulmonary infection.

Objective To conduct risk assessment analysis through risk assessment model for postoperative pneu-monia(POP)in surgical departments constructed according to analytic hierarchy process(AHP)-risk matrix,and evaluate the application effectiveness of the model.Methods Taking a tertiary comprehensive teaching hospital as an example,a risk assessment was conducted on the occurrence of POP in 15 surgical departments in 2022.The ap-plication effect of POP risk assessment model for the surgical departments constructed based on the AHP-risk ma-trix was evaluated,and the POP risk level of the surgical departments was determined.Results Through applica-tion of risk assessment model,the POP risk level of the surgical departments was divided into 5 levels,namely ex-tremely high risk(n=3),high risk(n=1),medium risk(n=5),low risk(n=4),and extremely low risk(n=2).Conclusion The application effect of the surgical POP risk assessment model based on AHP-risk matrix method is good,achieving quantitative assessment of healthcare-associated infection risk,and providing data basis and support for further targeted risk control.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate a suspected outbreak of carbapenem-resistant Klebsiella pneumoniae(CRKP)healthcare-associated bloodstream infection(HA-BSI),provide reference for effective control of CRKP in-fection.Methods The characteristics of CRKP infected patients and the risk factors for the event transmission in an adult hematology department of a teaching hospital in June 2022 were obtained by field epidemiological investigation.The specimens of environmental target strains were co-llected by blood nutrient agar inoculation,the removal status of environmental microorganisms and the effect of infection control after implementing control measures were com-pared.Results There were a total of 6 cases of CRKP HA-BSI,with an attacking rate of 1.29％(6/464),which was significantly higher than 0 during the same period in 2021,and difference was statistically significant(P=0.011).In environmental hygiene monitoring,the detection rate of CRKP was 2.27％(1/44),which was from the surface of bed curtain in the living unit of infected patients,homology analysis with CRKP detected from 2 patients revealed that the 16s RNA of 3 CRKP strains was completely identical,with a similarity of 100％.Seven house-keeping genes of 3 CRKP strains were all identical and belonged to the ST11 type.Comprehensive control measures were taken:appropriate closure of the ward,centralized isolation of patients,terminal disinfection of the ward,reg-ular health care workers and relative restriction of their activity areas.After the measures were taken,the qualified rate of microbial colony count in the ward increased compared to before taking the measures(2.27％vs 68.89％,P＜0.001),with a statistically significant difference,there were no more CRKP infected cases after the intervention,indicating that the control measures were effective.Conclusion This outbreak was caused by ST11 type of common CRKP in China,and laminar bed curtains are carriers of pathogen transmission.It is speculated that non-standard cleaning and disinfection,as well as inadequate implementation of hand hygiene are the main causes for transmis-sion.Adopting an appropriate strategy of closing the ward and concentrating patient isolation can quickly and effec-tively prevent the transmission of the event.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.