OBJECTIVE To know about the perception and current status of drug risk management among pharmacists in Chinese medical institutions， providing insights and recommendations for enhancing the drug risk management system in medical institutions. METHODS A questionnaire survey was conducted across 28 provinces， cities， and autonomous regions； stratified radom sampling was employed to study the population of medical workers and pharmaceutical professionals in medical institutions nationwide. The survey included information on the survey population， the current status of drug risk management implementation in medical institutions， the cognition， definition and process of drug risk management related concepts， and the content and mode of drug risk management work in medical institutions. Finally， suggestions were collected from various medical institutions on the system construction of drug risk management. Descriptive statistical analysis was adopted to summarize the obtained data. RESULTS A total of 446 questionnaires were collected in this survey， including 420 valid questionnaires and 26 invalid questionnaires. The questionnaire collection rate was 100%，and the effective rate was 94.17%. 51.19% of the respondents No.2020YFC2009001）。 based their understanding of drug risk management on Management Measures for Adverse Drug Reaction Reports and Monitoring， while 87.38% recognized the need for drug risk management throughout the drug use process. 63.33% of the participants stated that their medical institutions had dedicated positions related to drug risk management， with the highest proportion （72.17%） was in third-grade class A medical institutions. 66.43% reported implementing risk management across all drug use stages. Suggestions for the development of drug risk management systems in medical institutions by the research participants focused on enhancing guiding documents， clarifying concepts， establishing information-sharing mechanisms. CONCLUSIONS The overall awareness of drug risk management in China’s medical institutions is high， with practices in place across various stages in multiple forms. However， there remains a need to strengthen institutional documents， management regulations， system development， and information-sharing mechanisms to improve collaborative governance， improve drug management levels， and ensure patient safety.

OBJECTIVE To evaluate the efficacy， safety and economy of inclisiran in the treatment of atherosclerotic cardiovascular disease with hypercholesterolemia. METHODS A rapid health technology assessment （HTA） approach was employed. HTA reports， systematic reviews（SR）/meta-analyses， and pharmacoeconomic studies related to inclisiran were systematically identified through comprehensive searches of Chinese and English databases， including PubMed， Embase， the Cochrane Library， CNKI and Wanfang database， supplemented by HTA institutional repositories. The search timeframe spanned from database inception to April 2025. The results of the studies were descriptively analysed and summarized through literature screening， data extraction and literature quality assessment. RESULTS The final analysis included 22 studies， comprising one HTA report， 15 SR/meta-analyses， and 6 pharmacoeconomic evaluations. Regarding therapeutic efficacy， compared with control group， inclisiran could significantly reduce the levels of low-density lipoprotein cholesterol， proprotein convertase subtilisin/kexin type 9， total cholesterol， triacylglycerol， apolipoprotein B， and lipoprotein（a）， increase the level of high-density lipoprotein cholesterol， and reduce the risk of adverse cardiovascular events. In terms of safety， the inclisiran group showed no significant difference compared with the control group in the risk of total adverse events， serious adverse events， or non-serious adverse events； however， an increased incidence of injection site reactions was observed， most of which were mild. In terms of cost-effectiveness， there were discrepancies in research conclusions both domestically and internationally. More studies indicated that inclisiran did not demonstrate cost-effectiveness advantage and would require an appropriate price reduction to meet cost-effectiveness criteria. CONCLUSIONS Inclisiran demonstrates favorable efficacy and acceptable safety in treating atherosclerotic cardiovascular disease with hypercholesterolemia， though its economic profile requires improvement.

The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

Retrieving keyframes most relevant to text from small intestine videos with given labels can efficiently and accurately locate pathological regions. However, training directly on raw video data is extremely slow, while learning visual representations from image-text datasets leads to computational inconsistency. To tackle this challenge, a small bowel video keyframe retrieval based on multi-modal contrastive learning (KRCL) is proposed. This framework fully utilizes textual information from video category labels to learn video features closely related to text, while modeling temporal information within a pretrained image-text model. It transfers knowledge learned from image-text multimodal models to the video domain, enabling interaction among medical videos, images, and text data. Experimental results on the hyper-spectral and Kvasir dataset for gastrointestinal disease detection (Hyper-Kvasir) and the Microsoft Research video-to-text (MSR-VTT) retrieval dataset demonstrate the effectiveness and robustness of KRCL, with the proposed method achieving state-of-the-art performance across nearly all evaluation metrics.
Humans ; Video Recording ; Intestine, Small/diagnostic imaging* ; Machine Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

OBJECTIVES: To assess the changes in body composition and nutritional risks faced by children with different stages of acute leukemia (AL). METHODS: Bioelectrical impedance analysis combined with anthropometric measurements was used to detect body composition. This prospective study was conducted from August 2023 to July 2024 at Shandong Provincial Hospital, examining the body composition and physical balance of children with various stages of AL and healthy children. RESULTS: The non-fat components of children with AL and healthy children both showed a linear increase with age. In the younger age group, there were no significant differences in body composition between children with AL and healthy children. However, in the older age group, the body composition of children undergoing chemotherapy for AL was significantly lower than that of healthy children (P<0.05), and muscle mass recovered first after the completion of AL chemotherapy. The proportion of children with increased trunk fat in AL children who completed chemotherapy was significantly lower than that in healthy children (P<0.05), while the incidence rate of severe left-right imbalance in body composition was significantly higher (P<0.05). Muscle distribution in children with AL primarily showed insufficient limb and overall muscle mass, whereas healthy children mainly exhibited insufficient upper limb muscle mass. CONCLUSIONS The body composition of children with AL varies at different treatment stages, indicating that nutritional status is affected by both the disease itself and the treatment. Early screening can provide a basis for reasonable nutritional intervention.
Humans ; Child ; Male ; Female ; Child, Preschool ; Body Composition ; Prospective Studies ; Adolescent ; Leukemia/metabolism* ; Infant ; Nutritional Status ; Acute Disease ; Electric Impedance

OBJECTIVE: To investigate the correlation of seminal plasma oxidation reduction potential (ORP), normalized oxidation-reduction potential (nORP) and sperm DNA fragmentation index (DFI) to sperm motion parameters, and their clinical predictive value for oligoasthenozoospermia (OAZ). METHODS: This study included 433 male subjects visiting the Clinic of Andrology in our hospital from March to May 2024. According to sperm concentration and the percentage of progressively motile sperm (PMS), we divided them into a normal control (n = 119), an oligozoospermia (OZ, n = 118), an athenozoospermia (AZ, n = 119) and an OAZ group (n = 77). Using the electrode method, we measured the seminal plasma ORP, calculated nORP=ORP/sperm concentration (mV/［10⁶/ml］), and determined DFI and high DNA chromatin sperm (HDS) by flow cytometry based on sperm chromatin structure assay (SCSA), followed by comparison among the four groups in age, abstinence days, semen volume, total sperm count, sperm concentration, PMS, non-progressively motile sperm (NPMS), immotile sperm (IMS), curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), straightness(STR), wobble (WOB), DFI, HDS, ORP and nORP. Using the receiver operating characteristic (ROC) curve, we assessed the predictive value of DFI, ORP and nORP for OAZ, and analyzed the correlation of DFI, ORP and nORP to sperm motion parameters by Pearson and Spearman analyses. RESULTS: Statistical analysis revealed statistically significant differences among the four groups in semen volume, abstinence days, total sperm count, sperm concentration, PMS, NPMS, IMS, total sperm motility, VCL, VSL, VAP, STR, DFI, HDS, ORP and nORP (P < 0.05), but not in age, LIN and WOB (P > 0.05). The area under the ROC curve (AUC) for the predictive value of DFI for OAZ was 0.880, with the critical value of 8.920, sensitivity of 74.8% and specificity of 88.2%; that of ORP for AZ was 0.698, with the critical value of 155.375, sensitivity of 70.6% and specificity of 64.7%; and that of nORP for OZ was 0.999, with the critical value of 9.844, sensitivity of 98.3% and specificity of 99.2%. Pearson and Spearman correlation analyses showed that DFI was correlated positively with age, abstinence days, semen volume, IMS, HDS and ORP, but negatively with PMS, NPMS, total sperm motility, VCL, VSL, VAP and STR; ORP positively with abstinence days, semen volume, IMS, DFI and nORP, but negatively with PMS, NPMS, total sperm motility, VSL, LIN and STR; and nORP positively with HDS, but negatively with abstinence days, total sperm count, sperm concentration, PMS and NPMS. CONCLUSION Oxidative stress (OS) may be an important pathological factor for elevated ORP, increased DFI and changes of routine sperm motion parameters, consequently leading to OAZ. As OS markers, DFI and ORP have a high predictive value for OS-induced OAZ.
Male ; Humans ; DNA Fragmentation ; Semen/metabolism* ; Sperm Motility ; Spermatozoa ; Oxidation-Reduction ; Adult ; Oligospermia ; Sperm Count ; Semen Analysis ; Asthenozoospermia

OBJECTIVE: To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. METHODS: Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. CONCLUSIONS Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans ; Acupuncture Therapy ; Neoplasms/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

Ischemia-reperfusion (I/R) injury following skin flap transplantation is a critical factor leading to flap necrosis and transplant failure. Antagonizing inflammatory responses and oxidative stress are regarded as crucial targets for mitigating reperfusion injury and enhancing flap survival. In this study, caffeic acid-vanadium metal polyphenol nanoparticles (CA-V NPs) were prepared for the treatment of skin flap ischemia and reperfusion. This study was conducted using a one-step method to prepare new types of CA-V NPs with uniform sizes and stable structures. In vitro, the CA-V NPs exhibited CAT-like and SOD-like activities and could effectively scavenge ROS, generate oxygen, and alleviate oxidative stress. In the H₂O₂-induced cellular oxidative stress model, CA-V NPs effectively reduced ROS levels and inhibited apoptosis through the XIAP/Caspase-3 pathway. In the cellular inflammation model induced by LPS combined with IFN-γ, CA-V NPs reprogrammed macrophage polarization toward the M2 phenotype and reduced inflammatory responses by reducing the expression of the chemokines CCL4 and CXCL2. In addition, animal experiments have shown that CA-V NPs can alleviate oxidative stress in skin flap tissues, inhibit apoptosis, promote angiogenesis, and ultimately improve the survival rate of skin flaps. CA-V NPs provide a new target and strategy for the treatment of flap I/R injury.