Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

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.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Objective To investigate the association between extensive perivascular space(EPVS)burden in different locations and ischemic stroke(IS),its subtypes,and transient ischemic attack(TIA)through Mendelian randomization(MR)analysis.Methods The summary data from large-scale Genome-wide Association Studies(GWAS)and various MR methods were employed.We applied multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness.Subsequently,meta-analysis was utilized to integrate causal relationships between EPVS burden in different locations and IS from various sources.Additionally,reverse MR was employed to observe the impact of various IS types on EPVS burden.Finally,linkage disequilibrium score regression was conducted to assess genetic correlations between exposures and outcomes.Results EPVS burden in both the white matter(OR=1.12,95％CI:1.01-1.25;P=0.04)and basal ganglia(OR=1.57,95％CI:1.30-1.89;P＜0.01)are significant risk factors for IS.EPVS burden in the basal ganglia is also a risk for IS(small-vessel)(OR=4.56,95％CI:2.57-8.27;P=5.95× 10-7).After IS and TIA there seems to be a potential increase in extensive basal ganglia perivascular space burden.Conclusions Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators to predict IS.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

Objective:To investigate the application value of exercise rehabilitation mode based on cardiopulmonary exercise testing(CPET)in the treatment and rehabilitation of coronary heart disease(CHD).Methods:This ran-domized controlled study enrolled 260 CHD patients admitted in Hai'an People's Hospital between January 2021 and June 2022.They were divided into control group(n=130,routine nursing)and intervention group(n=130,addi-tional exercise rehabilitation training nursing).After 6-month intervention,scores of Heart Health-Self-Effica-cy and Self-Management(HH-SESM)scale,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC),peak oxygen uptake(VO2peak),percentage of peak oxygen uptake in predicted maximum(VO2peak％Pred),peak metabolic equivalent(peak Mets),cardiac function indexes,and incidence of adverse events were com-pared between two groups.Results:After intervention,compared with patients in control group,those in interven-tion group had significant higher scores of HH-SESM[(76.57±5.88)points vs.(64.51±5.16)points]and CQQC[(111.66±7.93)points vs.(84.16±6.96)points],VO2peak[(1.41±0.11)L/min vs.(1.19±0.26)L/min],VO2peak％Pred[(59.32±3.51)％vs.(51.27±3.11)％],peak Mets[(7.89±1.86)vs.(5.22±1.16)],6MWD[(473.53±18.12)m vs.(354.27±23.11)m],and significant lower serum N-terminal pro brain natri-uretic peptide(NT-proBNP)[(5.13±2.17)pg/ml vs.(13.81±2.22)pg/ml],cardiac troponin Ⅰ(cTnⅠ)[(2.90±0.51)ng/ml vs.(4.76±1.32)ng/ml](P＜0.001 all).Intervention group had significant lower incidence of adverse events comparing to control group(3.85％vs.13.85％,P=0.005).Conclusion:Exercise rehabilitation treatment based on cardiopulmonary exercise test could effectively improve self-efficacy and self-management,quality of life,cardiopulmonary function and reduce risk of adverse events in patients with coronary heart disease.

Objective:To analyze the preferences of medical staff in TCM hospitals in Beijing regarding the achievements transformation of hospital traditional Chinese medicine preparations,and to provide a reference for formulating incentive policies.Methods:233 medical staff from five TCM hospitals in Beijing were taken as the research objects,and surveyed with a questionnaire designed based on the discrete choice experiment(DCE).Mixed logit models and latent class models were then used to analyze their transformation preferences.Results:The mixed Logit model revealed that seven key attributes significantly influenced medical staff's preferences for the achievements transformation of traditional Chinese medicine preparations(P<0.05).Latent class analysis identified three distinct preference groups among respondents:an organization-dependent group(27.0%),a pro-transformation group(61.4%),and a conservative group(11.6%).Conclusions:Medical Staff preferred transformation conditions that increased monthly income;utilized"human use+re-experimentation";involved the hospital's achievements transformation department as the entity;were funded by the hospital;offered a 70%profit share;enabled promotion three years earlier,and assigned patents to the hospital.The study recommends implementing diverse incentive measures and developing differentiated strategies tailored to the distinct Medical Staff categories to facilitate the transformation of hospital traditional Chinese medicine preparations into new drugs.