Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

In recent years, the "Room Escape" industry in China is booming, and this real live game has become popular. However, health threatening events such as fire, trauma, coma, and lung infection in the game venues have been reported at home and abroad. If these venues are not supervised in time, there will be great potential public safety and health hazards. In this review, we summarized the hidden dangers of public safety and health in such venues, including fire and safety hazards, persistent stress state, indoor ventilation problems, risk of contagious infection, non-player characters’ health risk, special film effects of 4D cinemas, mosquito problems, light pollution and noise, and food safety. Meanwhile, health management recommendations for the game venues were proposed from the aspects of formulating health management standards, improving health security measures, and strengthening related health education to players, so as to improve the hygiene levels of such venues and protect players and staff from injuries or diseases.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*

Objective To evaluate the prognostic value of preoperative neutrophil-to lymphocyte ratio (NLR) in invasive breast carcinomas of no special type.Methods we retrospectively analyzed the clinical and pathological data of all breast cancer patients at Shanghai Huangpu District Cental Hospital from Jan.2012 to Dec.2012.The optimal cutoff value was obtained by ROC.The difference among variables was calculated by chi-square test.DFS and OS were estimated using Kaplan-Meier method.Cox analysis was performed to analyze clinical parameters for their prognostic relevance.Results A total of 493 were eligible.The optimal cutoff value of NLR was 2.057.The sensitivity was 0.767 and specifity was 0.327 at the optimal cutoff point.Univariate analysis showed that patients with NLR higher than 2.057 had significantly lower DFS (P=-0.001) than patients with NLR equal or lower than 2.057,while the overall survival rate was not statistically different (P=0.131).The Cox proportional multivariate hazard model revealed that higher NLR was independently related with poor DFS with hazard ratio 5.649(95％ confidence interval 3.128-10.201,P=0.002).Conclusions Preoperative NLR is an independent predictor of DFS in breast cancer patients.Further validation and a feasibility study are required before it can be considered for clinical use.

Based on link control concepts, the life cycle of science and technology projects was divided into five stages,, such as project application, selection, implementation, output and assessment.All the science misconducts that might occur among these five stages were listed.Finally, different precautions were made to prevent different misconducts during different stage..

Objective To promote the idea and practice of truthful conduct of research among fellow researchers by creating a research integrity training mode for Chinese postgraduates.Methods Based on the RCR (Responsible Conduct of Research) training module,a common research education initiative adopted by many American research institutes,and through literature review and social science study,this paper explored the idea of develop a research integrity training mode for Chinese postgraduates.Results A thorough explanation and analysis was given to the five major aspect of research integrity training mode,including theoretical basis,training objectives,operational procedure,neces sary conditions for application and training evaluation.Conclusion Research integrity training is one of the most important contents of graduate education,and a well designed training mode is the first and foremost step of developing a responsible and credible environment in academia of China.

Objective To investigate the therapeutic effect of Xuebijing injection on stroke associated pneu monia the changes of plasma C-reactive protein level .Methods 80 cases of post-stroke patients with pneumonia were randomly divided into Xuebijing injection treatment group 40 cases and control group of 40 cases, two groups were given conventional antibiotics and anti-inflammatory treatment ,treated with Xuebijing injection group was dealed with Xuebijing injection 50ml plus 0.9% sodium chloride solution 100ml intravenous drip on the basis of conventional therapy,2/d,for 7d,changes before and after treatment in the two groups were evaluated the body temperature ,periph-eral white blood cell count ,neutrophil percentage ,C-reactive protein index .Results The treatment group after treat-ment for 7d body temperature,blood routine,neutrophils and C-reactive protein were compared before treatment were significantly improved(t=9.99,24.09,12.44,43.98;all P<0.05),all of the indexes in the control group compared before treatment were significantly improved,the differences were significant(t=15.95,20.12,4.14,16.53;all P<0.05),after treatment the observation index except temperatrue decreased significantly ,with statistically significant differences compared with control group (t=4.83,6.15,7.93,all P<0.05).Conclusion Xuebijing injection syner-gistic effect of stroke-associated pneumonia antibiotic treatment significantly , more effective than antibiotic therapy alone,has the very good application and promotion of clinical value .

Depending on the performance,Type of management of medical scientific research managers is divided into four basic management types of positive push type,upload issued type,passive type,the individual barrier type.In addition,factors of management,management performance and the quality of recruits are resolved corresponding to the management type,and have proposed the corresponding practice and management recommendations from two angles of medical research managers and the upper decision makers.

Objective To analyze the causes of medical disputes and to find an effective way to reduce medical malpractice and medical dispute.Methods The complete identification files of 251 cases of medical malpractice obtained from corresponding Offices of Technical Identification of Medical Malpractice in three cities at prefecture level in Shandong province were analyzed to compare the cause of medical malpractice identified by patients with that identified by experts.Results The main causes that identified by patients included violation(36.41%),default(35.60%),illegality(13.05%),tort(11.89%),and absence of management(3.05%).Among the litigation claims,58.53%were identified as existed factors causing disputes.Among the identified factors,72.66%should have been prevented and controlled.Conclusion Medical malpractice and medical dispute can be effectively prevented and controlled by putting management site forward,ensuring the implemention of the policies,and strengthening the substantive responsibility of the leadership.