Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

The pathogenesis of metabolic dysfunction-associated steatotic liver disease （MASLD） is fundamentally rooted in spleen deficiency and is closely associated with phlegm turbidity， damp-heat and blood stasis. Clinically， liver constraint with spleen deficiency and internal retention of damp turbidity represent the predominant traditional Chinese medicine （TCM） syndrome patterns. Researches have indicated intrinsic connections between the syndrome patterns and biological indicators such as gut microbiota and metabolic profiles. Regarding treatment， classical famous formulas， modern empirical formulas， and newly developed TCM drugs show positive effects in regulating glucose and lipid metabolism， improving insulin resistance， and alleviating metabolic inflammation， exhibiting multi-target mechanisms of action； acupuncture and other external therapies also provide adjunctive value. Nevertheless， current researches still have limitations such as the lack of high-quality clinical evidence and insufficient systematic elucidation of the uncerlying mechanisms. Future efforts should focus on conducting high-quality TCM clinical trials with hard endpoint outcomes such as hepatic histology outcomes， and utilizing modern technologies like multi-omics to elucidate TCM's mechanisms of action， thereby advancing the position of TCM as a first-line therapeutic strategy for MASLD.

ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To investigate the risk factors for postoperative recurrence and metastasis in patients with T1 stageⅢ/Ⅳ clear cell renal cell carcinoma(ccRCC), and to analyze the influence of surgical methods on prognosis, so as to provide prognostic evaluation and treatment guidance for clinical practice. Methods A retrospective analysis was conducted on 398 patients diagnosed with T1 stage Ⅲ/Ⅳ ccRCC who underwent either partial nephrectomy(PN)or radical nephrectomy(RN)at Jiangsu Province Hospital during Jan. 2008 and Sep. 2022. The patients were divided into recurrence group(n=49)and non-recurrence group(n=349)according to whether the tumor recurred during the follow-up period. The general, clinical data and prognosis were compared between the two groups. Univariate and multivariate Cox regression analyses were used to explore the factors influencing disease-free survival(DFS)and overall survival(OS)after surgery. Subgroup analysis using Kaplan-Meier curves was performed for T1a and T1b patients. Results During the median follow-up of 67(42, 98)months, the recurrence group was characterized by older age, larger tumor diameter, higher proportion of T1b stage, and more complex tumor anatomy. Univariate and multivariate Cox regression analyses showed that age ≥55 years and R.E.N.A.L. score ≥7 were independent risk factors for poorer DFS and OS(P＜0.05). Subgroup analysis revealed that PN or RN did not significantly affect DFS or OS in T1a patients and OS in T1b patients, while RN significantly improved DFS in T1b patients(P＜0.05). Conclusion Age ≥55 years and R.E.N.A.L. score ≥7 are independent risk factors for poor DFS and OS in highgrade T1 ccRCC patients. For T1b patients, RN may improve DFS.

ObjectiveTo examine factors associated with breast cancer among adult women in suburban Shanghai and develop a risk stratification model, and to provide a basis for the identification of high-risk populations. MethodsA cross-sectional study was conducted using baseline data from the Shanghai Suburban Adult Cohort and Biobank. A total of 39 683 women aged 20-74 years, comprising 249 breast cancer cases and 39 434 non-breast cancer cases, were included. Information on demographic characteristics, reproductive health, lifestyle, chronic diseases, and psychological status was collected. Missing data were handled using multiple imputation. Multivariable Firth logistic regression analyses were used to identify factors associated with breast cancer, and restricted cubic spline analyses were performed to assess the dose-response relationship between glycated hemoglobin and breast cancer. With breast cancer as the outcome variable, the data were randomly split into a training set and a test set at a ratio of 7∶3. A logistic regression model was developed for risk stratification and further calibrated using Platt scaling. Model performance was evaluated using the area under receiver operating characteristic curve (ROC-AUC), area under the precision-recall curve (PR-AUC), Brier score, calibration intercept, and calibration slope, to assess discrimination, overall prediction error, and calibration. Given that breast cancer was a low-prevalence outcome, the model’s precision, recall, and lift for the top 5% and top 10% of high-risk individuals were further calculated, to evaluate the model’s ability to identify and stratify risk in high-risk screening scenarios. ResultsIn the fully adjusted multivariable Firth logistic regression model, increasing age was associated with a higher risk of breast cancer (OR=1.050, 95%CI: 1.033-1.067), whereas older age at menarche (OR=0.921, 95%CI: 0.859-0.987) and a greater number of pregnancies (OR=0.875, 95%CI: 0.770-0.986) were associated with a lower risk of breast cancer. Women with a history of estrogen use had a higher risk of breast cancer than those without such a history (OR=3.098, 95%CI: 1.481-5.728). Hyperglycemia was associated with an increased risk of breast cancer (OR=1.754, 95%CI: 1.305-2.334). Compared with women without anxiety or depression, those with mild (OR=2.239, 95%CI: 1.484-3.266) or severe (OR=10.104, 95%CI: 1.106-32.798) anxiety or depression had a higher risk of breast cancer. Restricted cubic spline analyses showed a nonlinear association between glycated hemoglobin and breast cancer (P=0.003). The logistic regression-based risk stratification model showed moderate discriminative ability (ROC-AUC=0.730, 95%CI: 0.673-0.784) and a low overall prediction error (Brier score=0.006, 95%CI: 0.006-0.006). The lift values were 4.261 for the top 5% high-risk group and 3.199 for the top 10% high-risk group, identifying 21.3% and 32.0% of breast cancer cases, respectively. ConclusionBreast cancer among adult women in suburban Shanghai is associated with older age, earlier age at menarche, fewer pregnancies, history of estrogen use, hyperglycemia, and mild and severe anxiety or depression, suggesting that greater attention should be paid to reproductive hormone-related factors, metabolic abnormalities, and psychological health in community-based women’s health management. The logistic regression-based model using routine epidemiological indicators shows moderate discriminative ability and potential for enriching high-risk populations and might help support initial screening and stratified management of women at high risk of breast cancer in resource-limited community settings.

Objective: To retrospectively analyze the supply and demand of RhD-negative red blood cell (RBC) components, explore the dynamic changes in clinical demand and application trends of RhD-negative RBC products, and provide evidence for optimizing the preparation and supply management of various RhD-negative RBCs products. Methods: The total supply of RBCs and the demand and supply of RhD-negative RBC products from 2021 to 2025 were retrieved from the information management system. The trend chi-square test was performed using SPSS 22.0 statistical software to analyze the annual supply rate and repeat reservation rate of RhD-negative RBC products. Meanwhile, the clinical transfusion indications for RhD-negative RBC products in 2025 were further analyzed. Results: From 2021 to 2025, the supply rate of RhD-negative RBC products gradually increased from 0.42% (1 904.5 U/448 787 U) to 0.48% (1945U/402088.5U), showing an upward trend across years (P<0.05). The actual demand and supply of RhD-negative RBC products remained balanced, while the repeat reservation rate increased significantly from 29.73% (804 U/2 704 U) to 43.62% (1 505 U/3 450 U), showing an upward trend year by year (P<0.05). Fresh RhD-negative RBC products accounted for 87.09% (8 270 U/9 495.5 U) of the total supply, while RhD-negative frozen RBC products accounted for 12.91% (1 225.5 U/9 495.5 U). In 2025, therapeutic transfusion, elective surgery (including obstetric transfusion), and emergency transfusion accounted for 55.40% (1 077.5 U/1 945 U), 38.56% (750 U/1 945 U), and 6.04% (117.5 U/1 945 U) of the total supply of RhD-negative RBC products, respectively. RhD-negative frozen RBC products accounted for 67.23% (79 U/117.5 U) of emergency use and 29.47% (221 U/750 U) of elective surgery (including obstetrics) use; fresh RhD-negative RBC suspensions accounted for 93.92% (1 012 U/1 077.5 U) of therapeutic use and 70.56% (529 U/750 U) of elective surgery (including obstetrics) use. In recent years, RhD-negative washed RBC products and concentrated washed RBC products have been introduced as new products, and their clinical utilization has shown an increasing trend. Conclusion: Despite a decline in total blood collection volume, the security management system of RhD-negative RBC components in Guangzhou Blood Center has functioned largely meeting clinical demand. Advances in hospital technology had led to the routine application of RhD-negative concentrated washed RBCs. It is recommended that concentrated washed RBCs should be standardized with a formal definition and corresponding national quality standards should be established.

ObjectiveTo analyze the microbial culture positivity rate， pathogen spectrum， prevalence of multidrug-resistant organisms （MDROs）， and differences among donor procurement sources in corneas from the Eye Bank of Guangdong Province， and to provide evidence for eye bank quality control and the prevention of post-keratoplasty infections. MethodsThis retrospective study included 7 442 donor corneas procured by the Eye Bank of Guangdong Province and used for keratoplasty at Zhongshan Ophthalmic Center， Sun Yat-sen University， between 2018 and 2025. During surgery， donor corneoscleral rim tissue was excised for bacterial and fungal culture. Culture-positive specimens underwent microbial identification and antimicrobial susceptibility testing （AST）. Culture-positive corneas were compared across study years， pathogen categories， and donor procurement sources. ResultsOf the 7 442 donor corneas， 251 were culture-positive， corresponding to an overall culture positivity rate of 3.37%， with annual rates ranging from 1.50% to 5.31%. Among culture-positive corneas， 178 （70.92%） yielded bacteria alone， 72 （28.68%） yielded fungi alone， and 1 （0.40%） yielded both bacteria and fungi. Candida spp. and Aspergillus spp. were the predominant fungal isolates. Gram-negative bacteria were more frequently isolated than Gram-positive bacteria. The most common bacterial isolates were Acinetobacter baumannii， Staphylococcus epidermidis， Stenotrophomonas maltophilia， Enterococcus faecium， and Pseudomonas fluorescens. MDROs accounted for 75.47% of bacterial isolates， predominantly Acinetobacter baumannii， Staphylococcus epidermidis， and Enterococcus faecium， and demonstrated an increasing trend over the study period. Donor corneas procured through the Hospital Cornea Retrieval Program （HCRP） had a higher culture positivity rate than those obtained through Organ Procurement Organization （OPO） （P＜0.000 1）. Among culture-positive donor corneas， the proportion of fungal culture-positive corneas was significantly higher in the HCRP group than in the OPO group （P=0.001 5）， whereas the proportion of MDROs among bacterial culture-positive corneas was significantly higher in the OPO group than that in the HCRP group （P=0.005 2）. ConclusionsThe overall culture positivity rate of donor corneas from the Eye Bank of Guangdong Province is relatively low， indicating that the risk of microbial contamination is controlled. However， pathogen profiles and antimicrobial resistance patterns varies by procurement source. Ongoing microbiological and antimicrobial resistance surveillance， together with optimized donor risk assessment and timely reporting of culture results， may further improve eye bank quality management and help inform strategies for preventing post-keratoplasty infections.

ObjectiveTo analyze the microbial culture positivity rate， pathogen spectrum， prevalence of multidrug-resistant organisms （MDROs）， and differences among donor procurement sources in corneas from the Eye Bank of Guangdong Province， and to provide evidence for eye bank quality control and the prevention of post-keratoplasty infections. MethodsThis retrospective study included 7 442 donor corneas procured by the Eye Bank of Guangdong Province and used for keratoplasty at Zhongshan Ophthalmic Center， Sun Yat-sen University， between 2018 and 2025. During surgery， donor corneoscleral rim tissue was excised for bacterial and fungal culture. Culture-positive specimens underwent microbial identification and antimicrobial susceptibility testing （AST）. Culture-positive corneas were compared across study years， pathogen categories， and donor procurement sources. ResultsOf the 7 442 donor corneas， 251 were culture-positive， corresponding to an overall culture positivity rate of 3.37%， with annual rates ranging from 1.50% to 5.31%. Among culture-positive corneas， 178 （70.92%） yielded bacteria alone， 72 （28.68%） yielded fungi alone， and 1 （0.40%） yielded both bacteria and fungi. Candida spp. and Aspergillus spp. were the predominant fungal isolates. Gram-negative bacteria were more frequently isolated than Gram-positive bacteria. The most common bacterial isolates were Acinetobacter baumannii， Staphylococcus epidermidis， Stenotrophomonas maltophilia， Enterococcus faecium， and Pseudomonas fluorescens. MDROs accounted for 75.47% of bacterial isolates， predominantly Acinetobacter baumannii， Staphylococcus epidermidis， and Enterococcus faecium， and demonstrated an increasing trend over the study period. Donor corneas procured through the Hospital Cornea Retrieval Program （HCRP） had a higher culture positivity rate than those obtained through Organ Procurement Organization （OPO） （P＜0.000 1）. Among culture-positive donor corneas， the proportion of fungal culture-positive corneas was significantly higher in the HCRP group than in the OPO group （P=0.001 5）， whereas the proportion of MDROs among bacterial culture-positive corneas was significantly higher in the OPO group than that in the HCRP group （P=0.005 2）. ConclusionsThe overall culture positivity rate of donor corneas from the Eye Bank of Guangdong Province is relatively low， indicating that the risk of microbial contamination is controlled. However， pathogen profiles and antimicrobial resistance patterns varies by procurement source. Ongoing microbiological and antimicrobial resistance surveillance， together with optimized donor risk assessment and timely reporting of culture results， may further improve eye bank quality management and help inform strategies for preventing post-keratoplasty infections.

BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.