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.

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 clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Glaucoma is a neurodegenerative disease characterized by progressive and irreversible necrosis and apopto-sis of retinal ganglion cells.The abnormal activation of microglia,astrocytes and Müller cells in the central nervous system of the retina and macrophages,T/B lymphocytes and regulatory T cells in the peripheral immune system is involved in the pathogenesis of glaucoma,and the secretion of inflammatory factors such as interleukin 6 and interleukin 8 is closely relat-ed to the development of glaucoma.In this paper,the role of immune cells of the central nervous system and peripheral im-mune system of the retina and the inflammatory factors they secreted in the development of glaucoma is reviewed,in order to understand the pathogenesis of glaucoma at the cellular and molecular levels and to provide ideas for exploring new treatment methods.

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

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.