Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Continuing medical education for general practitioners is an important measure to upgrade the quality of primary health care services in China, which is still facing various challenges and need to be further developed and improved. This article analyzes the status quo and existing problems of continuing medical education for general practitioners in China, and proposes suggestions based on the concept of people centered and integrated health care (PCIC), including faculty development, training contents, assessment methods, and experience learning, to provide references for the improvement of continuing medical education for general practitioners.

Osteoarthritis （OA） is characterized by articular cartilage degeneration， synovial hyperplasia， hyperosteogeny， and narrowing of joint space， which can be caused by trauma， inflammation， and other factors. With the increasing global population aging， the incidence of OA is rising year by year， making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex， including oxidative stress， autophagy， and apoptosis. Recent studies have found that ferroptosis， a new type of cell death， is also an important pathogenic factor in OA， characterized by a series of complex changes such as iron ion accumulation， glutathione （GSH） depletion， and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation， delay extracellular matrix （ECM） degradation， and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement， but there are limitations. Traditional Chinese medicine （TCM） has been widely used in the treatment of various diseases because of its low cost， low drug resistance， and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets， multiple levels， and aspects， but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism， lipid peroxidation， cysteine/glutamate transporter system Xc^- （system Xc^-）/GSH/glutathione peroxidase 4 （GPX4） pathway， nicotinamide adenine dinucleotide phosphate（NADPH）/ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀） pathway， tumor protein p53 in OA， and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Liver Diseases/drug therapy* ; Antioxidants ; Polysaccharides/therapeutic use* ; Medicine, Chinese Traditional

Programmed cell death protein-1(PD-1)/programmed cell death ligand-1(PD-L1)has been considered to be one of the most promising targets for tumor immunotherapy.At present,both monoclonal antibody drugs and small molecule inhibitors targeting PD-1/PD-L1 are facing bottlenecks.Numerous researchers have tried to explore different strategies to block the PD-L1/PD-L1 pathway,hoping to improve the effects of tumor immunotherapy.This review focuses on the degraders,bifunctional molecules and covalent inhibitors that target PD-L1,aiming to provide inspiring insights for the development of anti-PD-1/PD-L1 drugs.

Objective:To investigate the feasibility of oblique overlap anastomosis plus single flap valvuloplasty (OSF) for reconstruction after laparoscopic proximal gastrectomy.Methods:The C-shaped seromuscular flap (2.5 × 3.5 cm), which was 2 cm from the top of the remnant stomach, was extracorporeally created on the anterior wall of the remnant stomach. The stomach was opened approximately 1.0 cm above the lower edge of the mucosal flap. Four supporting stitches were sutured around the hole and the right wall of the esophageal stump was incised with a support suture to prevent the linear stapler from entering the submucosa. Liner stapler was inclined to the left side of the esophagus at an angle of about 30 degrees to the longitudinal axis of the esophagus for oblique anastomosis between the dorsal side of the esophagus and the anterior stomach and then esophagogastrostomy was performed with the length of anastomosis was 4 cm. Entry hole was suture with 3 stitches and then the linear stapler was used for closing the entry hole. Finally, the seromuscular flap was closed using barbed sutures.Results:Clinical data of 11 patients with Siewert type II esophagogastric junction adenocarcinoma who underwent radical gastrectomy and reconstruction by OSF between January 2022 and May 2023 were retrospectively collected. There were 7 males and 4 females. The average age was (69.9±7.8) years, the BMI was (21.7±7.2) kg/m 2 and the tumor size was (2.1±0.6) cm. OSF reconstruction was successfully completed in all 11 patients. The median operative time was 275 (270-428) minutes, the time for OSF reconstruction was 112 (80-140) minutes, and the blood loss was 50 (20-400) ml. The pathological stage was 0-I in 7 cases and II-III in 4 cases. The patients were fed on the 4th day (4-7 days) and discharged from hospital on the 7th day (6-9 days) after surgery. No patient had gastroesophageal reflux symptoms of grade B and above, and no patient took anti-reflux medicine. Conclusions:OSF is a safe and feasible treatment for Siewert type II esophagogastric junction adenocarcinoma.

Objective:To investigate the feasibility of oblique overlap anastomosis plus single flap valvuloplasty (OSF) for reconstruction after laparoscopic proximal gastrectomy.Methods:The C-shaped seromuscular flap (2.5 × 3.5 cm), which was 2 cm from the top of the remnant stomach, was extracorporeally created on the anterior wall of the remnant stomach. The stomach was opened approximately 1.0 cm above the lower edge of the mucosal flap. Four supporting stitches were sutured around the hole and the right wall of the esophageal stump was incised with a support suture to prevent the linear stapler from entering the submucosa. Liner stapler was inclined to the left side of the esophagus at an angle of about 30 degrees to the longitudinal axis of the esophagus for oblique anastomosis between the dorsal side of the esophagus and the anterior stomach and then esophagogastrostomy was performed with the length of anastomosis was 4 cm. Entry hole was suture with 3 stitches and then the linear stapler was used for closing the entry hole. Finally, the seromuscular flap was closed using barbed sutures.Results:Clinical data of 11 patients with Siewert type II esophagogastric junction adenocarcinoma who underwent radical gastrectomy and reconstruction by OSF between January 2022 and May 2023 were retrospectively collected. There were 7 males and 4 females. The average age was (69.9±7.8) years, the BMI was (21.7±7.2) kg/m 2 and the tumor size was (2.1±0.6) cm. OSF reconstruction was successfully completed in all 11 patients. The median operative time was 275 (270-428) minutes, the time for OSF reconstruction was 112 (80-140) minutes, and the blood loss was 50 (20-400) ml. The pathological stage was 0-I in 7 cases and II-III in 4 cases. The patients were fed on the 4th day (4-7 days) and discharged from hospital on the 7th day (6-9 days) after surgery. No patient had gastroesophageal reflux symptoms of grade B and above, and no patient took anti-reflux medicine. Conclusions:OSF is a safe and feasible treatment for Siewert type II esophagogastric junction adenocarcinoma.