Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P＜0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P＜0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.

BACKGROUND:Studies have shown that there is a close relationship between pyroptosis,inflammatory factors and osteoporosis.OBJECTIVE:To review the effects of pyroptosis and inflammatory factors on the pathogenesis of osteoporosis from the perspectives of osteogenic differentiation and osteoclastic differentiation,based on an overview of pyroptosis in relation to the interaction of relevant inflammatory factors.METHODS:The first author used the computer to search the literature published by each database until 2024,and searched CNKI,WanFang,VIP and PubMed databases with the search terms of"pyroptosis,inflammatory factors,osteoporosis,osteoblast,osteoclast,bone metabolism,signaling pathway,review"in Chinese and English.A total of 79 papers were finally included according to the inclusion criteria.RESULTS AND CONCLUSION:The progression of osteoporosis is closely related to inflammation,in which pyroptosis plays a key role.Immune cells induce pyroptosis through apoptosis pathway,promote the secretion of inflammatory factors such as interleukin-18,interleukin-1β and NLRP3,build an inflammatory immune microenvironment,and regulate bone metabolism through complex signaling pathways,resulting in enhanced bone absorption and reduced bone formation,thereby leading to osteoporosis.Previous studies have shown that inhibiting pyroptosis is anti-inflammatory and slows the progression of osteoporosis,and it has been shown to improve inflammatory bone loss in vitro and in animal models.At present,research on pyroptosis and osteoporosis is limited.On the one hand,the exact mechanism of osteoporosis and the pathogenesis of pyroptosis are unknown,and the specific pathways and regulatory mechanisms remain to be understood.On the other hand,therapeutic strategies targeting pyroptosis are still theoretical,not clinically proven,and drug side effects are unknown.In the future,the research focus is to further explore the pathogenesis,especially the mechanism of pyroptosis,identify potential therapeutic targets,further study the pyroptosis signaling pathway and Gasdermin protein,and develop new drugs to improve the therapeutic effect in patients with osteoporosis.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods， and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction （PPI） network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets， clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia， 48 mice were randomly divided into a blank group， a model group， an allopurinol group （5 mg·kg^-1）， and low-dose （10 mg·kg^-1）， medium-dose （30 mg·kg^-1）， and high-dose （90 mg·kg^-1） luteolin groups. For the first three days， the blank and model groups were gavaged with an equal volume of normal saline， while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards， modeling was performed by intraperitoneal injection at 12：00 daily （normal saline for the blank group， and oxonic acid potassium-hypoxanthine mixture for other groups， with 300 mg·kg^-1 for each group）. Gavage intervention was administered at 18：00 daily （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） until day 7. After sampling， levels of serum uric acid （UA）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were measured. Levels of xanthine oxidase （XO） in the liver and kidney， ATP-binding cassette transporter G2 （ABCG2） and malondialdehyde （MDA） in the kidney， and superoxide dismutase （SOD） in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis， 36 rats were randomly divided into a blank group， a model group， a colchicine group （0.315 mg·kg^-1）， and low-dose （7 mg·kg^-1）， medium-dose （21 mg·kg^-1）， and high-dose （63 mg·kg^-1） luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L^-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint （the blank group was injected with an equal volume of normal saline）， with repeated injections every two days for reinforcement. From day 2 after modeling， daily gavage administration was performed （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） for a total of 16 days. During the experiment， ankle swelling and pain threshold were measured regularly. After sampling， levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined. Ankle joints were subjected to HE， Masson， and safranin O-fast green staining， and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets， such as XO， ABCG2， nuclear factor erythroid 2-related factor 2 （Nrf2）， and SOD， through acting on signaling pathways including NF-κB， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， and ABC transporters， thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model， compared with the blank group， the model group showed significantly increased serum UA level， liver and kidney XO activity， renal ABCG2 expression， and liver SOD activity （P<0.01）. Compared with the model group， the high-dose luteolin group significantly reduced serum UA level （P<0.01）， inhibited liver and kidney XO activity （P<0.01）， and significantly increased renal ABCG2 expression and liver SOD activity （P<0.01）， effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model， compared with the blank group， the model group showed significant ankle swelling， decreased pain threshold， and significantly increased levels of IL-6， IL-1β， and TNF-α in serum and synovial tissue （P<0.01）. The high-dose luteolin group significantly reduced ankle swelling， prolonged hot plate pain threshold， effectively decreased the levels of the above inflammatory factors in serum and synovial tissue （P<0.01）， and significantly improved ankle pathological damage， showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis， and its potential mechanism may be related to inhibiting XO activity， increasing ABCG2 and SOD levels， and regulating Nrf2-mediated oxidative stress-related pathways.

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.