The study aims to explore the herb-drug interaction between Xuefu Zhuyu Decoction(XFZY) and atorvastatin(AT). Reverse transcription polymerase chain reaction(RT-PCR) was used to analyze the transcription levels of proteins related to drug metabolism and transport in LS174T cells, detect the intracellular drug uptake under various substrate concentrations and incubation time, and optimize the model reaction conditions of transporter multidrug resistance protein 1(MDR1)-specific probe Rhodamine 123 and AT to establish a cell model for investigating the human intestinal drug interaction. The cell counting kit-8(CCK-8) method was adopted to evaluate the cytotoxicity of XFZY on LS174T cells. After a single and continuous 48 h culture with XFZY, AT or Rhodamine 123 was added for co-incubation. The effect and mechanism of XFZY on human intestinal absorption of AT were analyzed by measuring the intracellular drug concentrations and transcription levels of related transporters and metabolic enzymes. The results of in vitro experiments show that a single co-culture with a high concentration of XFZY significantly increases the intracellular concentrations of Rhodamine 123 and AT. A high concentration of XFZY co-culture for 48 h increases the AT uptake level, significantly induces the CYP3A4 and UGT1A1 gene expression levels, and inhibits the OATP2B1 gene expression level. To compare with the evaluation results of the in vitro human cell model, the pharmacokinetic experiment of XFZY combined with AT was carried out in rats. Sprague-Dawley(SD) rats were randomly divided into a blank control group and an XFZY group. After 14 days of continuous intragastric administration, AT was given in combination. The liquid chromatography-mass spectrometry(LC-MS)/MS method was used to detect the concentrations of AT and metabolites 2-hydroxyatorvastatin acid(2-HAT), 4-hydroxyatorvastatin acid(4-HAT), atorvastatin lactone(ATL), 2-hydroxyatorvastatin lactone(2-HATL), and 4-hydroxyatorvastatin lactone(4-HATL) in plasma samples, and the pharmacokinetic parameters were calculated. Pharmacokinetic analysis in rats shows that continuous administration of XFZY does not significantly change the pharmacokinetic characteristics of AT in rats, but the AUC_(0-6 h) values of AT and metabolites 2-HAT, 4-HAT, and 2-HATL increase by 21.37%, 14.94%, 12.42%, and 6.68%, respectively. The metabolic rate of the main metabolites shows a downward trend. The study indicates that administration combined with XFZY can significantly increase the uptake level of AT in human intestinal cells and increase the exposure level of AT and main metabolites in rats to varying degrees. The mechanism may be mainly due to the inhibition of intestinal MDR1 transport activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atorvastatin/administration & dosage* ; Humans ; Rats ; Rats, Sprague-Dawley ; Male ; Intestines/cytology* ; Intestinal Mucosa/metabolism* ; Herb-Drug Interactions ; Cytochrome P-450 CYP3A/metabolism* ; Intestinal Absorption/drug effects*

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

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

High-voltage pulsed electric field(HV-PEF)ablation technology has demonstrated promising applications in the clinical treatment of chronic obstructive pulmonary disease(COPD).However,its use has been limited to exploratory applications in a small number of cases,and the underlying mechanisms remain largely undefined.To facilitate broader clinical implementation,comprehensive molecular mechanism studies via extensive animal experimentation are essential.Rats,due to their ease of modeling COPD and the availability of comprehensive molecular reagents,serve as an optimal model for such studies.Consequently,the development of electrodes specifically designed for HV-PEF respiratory ablation in SD rats is of significant importance.In this study,we meticulously examined the anatomical structure of rat airways and investigated various equipment parameters,including material composition,rigidity,diameter,electrode ring dimensions,spacing between positive and negative poles,insulation coating for the catheters,welding techniques between the guidewire and electrode ring,and the design of vent holes in the catheter.Based on these considerations,we fabricated PVC ablation electrode catheters with integrated ventilation functionality.Subsequently,we employed finite element simulation to estimate the field strengths that could be applied by these electrodes.The simulation results were then validated in normal rats to assess the electrical safety and efficacy of the electrodes.These findings laid the groundwork for further investigation into the mechanisms of HV-PEF treatment for COPD.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To design a nurse-driven intelligent individualized medication management system to enhance the whole-course patient management efficiency.Methods The system consisted of an in-hospital PC terminal,a mobile patient terminal and a mobile medical terminal.The in-hospital PC terminal was developed with B/S architecture and.NET;the patient and medical terminals both were realized with Java.The patient terminal was made up of a personal information module,a data reporting module and a message center module,and the in-hospital PC and medical terminals were composed of several modules for patient management,data management,statistical analysis and system management.Results The system developed provided whole-course intelligent management for out-of-hospital patients comprehensively,continuously and actively,lowering acute morbidity and nurses'workload for follow-up.Conclusion The system developed enhances patients'awareness of self-health management and improves nurses'efficiency for individualized medication management.[Chinese Medical Equipment Journal,2024,45(11):44-48]