AIM:To evaluate the immediate effect of vocal training on tear film stability in patients with dry eye disease.METHODS:A prospective crossover controlled study. From April 1 to April 20, 2026, volunteers with mild-to-moderate dry eye [Ocular Surface Disease Index-6(OSDI-6)score: 4-8] were enrolled. Participants were randomly allocated into two groups to receive two interventions in different sequences. Group A underwent a 50-min standardized vocal training session during the first intervention, while Group B served as a blank control; The two groups crossed over to the alternative intervention for the second session, with a 1-week washout period between the two interventions. The immediate post-intervention changes in Dry Eye Symptoms Questionnaire(CDES-Q)score, pre-and post-intervention non-invasive tear film breakup time(NIBUT), including first NIBUT and average NIBUT, as well as tear meniscus height(TMH), were recorded for each session.RESULTS:A total of 32 eligible participants(64 eyes)were enrolled and completed the study per protocol. The participants were randomly assigned to two groups with different intervention sequences. Group A(16 participants, 32 eyes)comprised 3 males and 13 females, with a mean age of 61.69±4.56 y and a mean OSDI-6 score of 5.750±1.183. Group B(16 participants, 32 eyes)comprised 3 males and 13 females, with a mean age of 63.19±1.56 y and a mean OSDI-6 score of 5.250±1.438.There were no significant differences in baseline characteristics between the two groups(P>0.05). After vocal training intervention, the net effect size for first NIBUT was 1.883 s(P=0.042), and for average NIBUT was 2.076 s(P=0.019). No significant change was observed in TMH(P=0.652). The CDES-Q score difference was -47.188(P<0.001). Further individual data analysis revealed that 59% of participants exhibited prolonged first NIBUT and 50% exhibited prolonged average NIBUT after vocal training.CONCLUSION: Vocal training can immediately improve tear film stability. This therapeutic approach shows promise for dry eye management and provides a reference for future large scale and long-term investigations.

AIM: To investigate the prevalence of dry eye symptoms among computer professionals in different climate zones and to identify the risk factors associated with dry eye disease.METHODS: A cross-sectional study was conducted by distributing questionnaires from December 2023 to January 2024 to computer professionals in six prefecture-level cities located in three distinct climate zones. Mixed-effects logistic regression analysis was employed to explore the relationship between environmental factors and the severity of dry eye disease. Environmental factors, including meteorological parameters and air pollutant concentrations, were obtained from the National Meteorological Information Center and the China Air Quality Online Monitoring and Analysis Platform, respectively. The annual mean values of environmental parameters served as independent variables, while the participants' Ocular Surface Disease Index(OSDI)scores were used as the dependent variable in the regression analysis.RESULTS:A total of 364 male participants aged 18-50 y were enrolled in this study. Among them, 80 participants presented with dry eye symptoms, corresponding to a detection rate of 22.0%.There was a significant difference in the detection rate of dry eye symptoms across different regions(P<0.05). Mixed-effects logistic regression analysis identified the following risk factors: daily eye use time(P<0.001, OR=1.669), relative humidity(P=0.047,OR=1.237), NO2 concentration(P=0.042, OR=1.283), PM2.5 concentration(P=0.006,OR=1.485), and CO concentration(P=0.018, OR=1.388). Temperature was found to be a protective factor(P=0.003, OR=0.701).CONCLUSION: Meteorological conditions and air quality significantly influence the occurrence of dry eye symptoms in male computer professionals. Prevention and treatment strategies for dry eye diseases should be tailored to the environmental characteristics of different regions to protect the ocular surface health of this occupational group.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

ObjectiveTo investigate the value of liver stiffness measurement （LSM） and spleen stiffness measurement （SSM） measured by two-dimensional shear wave elastography （2D-SWE） in the diagnosis of severe portal hypertension （SPH） and high-risk varices （HRV）， and to provide a basis for noninvasive assessment of portal hypertension. MethodsA prospective study was conducted among 78 patients with cirrhotic portal hypertension who were treated in Liver Research Center of Beijing Friendship Hospital， Capital Medical University， from December 2019 to April 2023. According to hepatic venous pressure gradient （HVPG）， the patients were divided into 6 mmHg≤HVPG<12 mmHg group， 12 mmHg≤HVPG<20 mmHg group， and HVPG ≥20 mmHg group. All patients underwent gastroscopy and 2D-SWE within 1 week after HVPG measurement， and SWE-LSM and SWE-SSM measured by 2D-SWE were recorded. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. With HVPG and gastroscopy findings as the gold standard， the receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to evaluate diagnostic performance， while the DeLong test was used for comparison of AUC. The Pearson or Spearman correlation analysis was used to investigate the correlation between variables， and the linear regression analysis and the Logistic regression analysis were used to investigate the influencing factors for HVPG and HRV. ResultsThe mean HVPG was 18.1±6.4 mmHg for the patients enrolled in this study， and HRV was observed in 62 patients （79.5%）. Both SWE-LSM and SWE-SSM were significantly positively correlated with HVPG （r=0.413 and 0.633， both P<0.001）， with an AUC of 0.812 and 0.902， respectively， in the diagnosis of HVPG≥12 mmHg and an AUC of 0.804 and 0.789， respectively， in the diagnosis of HVPG≥20 mmHg （all P>0.05）. The multivariate linear regression analysis showed that SWE-SSM was an independent influencing factor for HVPG （β=0.17， P<0.001）. In the diagnosis of HRV， only SWE-SSM showed a significant positive correlation with HRV （r=0.432， P<0.001）， with a better diagnostic performance than SWE-LSM in terms of AUC （0.808 vs 0.642， Z=2.775， P=0.006）. The multivariate Logistic regression analysis showed that platelet count was an independent influencing factor for HRV （odds ratio=0.97， P=0.014）. ConclusionSWE-SSM is closely correlated with both HVPG and HRV， showing a good performance in the diagnosis of SPH and HRV， and therefore， it is expected to become an effective noninvasive tool for assessing portal hypertension.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective:To retrieve, evaluate and summarize the best evidence for the management of oral intake in stroke patients with dysphagia.Methods:A systematic search was conducted in Chinese and English databases and subject-specific professional websites for clinical decisions, best practices, guidelines, systematic reviews, expert consensuses and evidence summaries on the management of oral intake in stroke patients with dysphagia. The retrieval time limit was from the establishment of the database to March 31, 2024. The included literatures were screened, quality-evaluated, and evidence was extracted and summarized.Results:A total of 16 articles were included, including three clinical decisions, four guidelines, four expert consensuses, four evidence summaries and one systematic review. A total of 28 pieces of evidence were summarized from eight aspects, namely, swallowing function screening, nutritional risk screening, feeding management, oral medication management, water drinking management, oral care, aspiration management, and training and education.Conclusions:This study systematically summarizes the best evidence for the management of oral intake in stroke patients with dysphagia, providing scientific guidance and strategic support for the improvement of patients' long-term quality of life.

Objective To investigate the therapeutic effects and mechanisms of Xuefu Zhuyu Mixture(XFZY)in rats with coronary heart disease(CHD).Methods A CHD rat model was established.Successfully modeled rats were randomly divided into five groups(n=12 each):model group,Lipitor group,low-dose XFZY group(7.02 g·kg-1·d-1),high-dose XFZY group(14.04 g·kg-1·d-1),and high-dose XFZY+RS09[Toll-like receptor 4(TLR4)agonist]group(14.04 g·kg-1·d-1 XFZY+intraperitoneal RS09),with an additional normal control group(n=12).After treatment,following treatment completion,all rats underwent echocardiography to assess left ventricular end-diastolic diameter(LVDd),end-systolic diameter(LVDs),ejection fraction(LVEF),and fractional shortening(FS).Myocardial histopathology and vascular remodeling indices were evaluated via hematoxylin-eosin(HE)staining,while myocardial fibrosis was examined using Masson's trichrome staining.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify inflammatory cytokine levels[tumor necrosis factorα(TNF-α),interleukin(IL)-1β,and IL-6]in myocardial tissues.Immunohistochemical analysis determined protein expression of B-cell lymphoma-2(Bc12)and Caspase 3 in myocardial tissues.Western Blot was performed to measure myocardial protein expression levels of TLR4,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-AKT),total AKT,phosphorylated mammalian target of rapamycin(p-mTOR),and total mTOR.Results Compared with the normal group,rats in the model group exhibited severe myocardial tissue damage,along with significantly elevated collagen volume fraction,LVDs,LVDd,myocardial levels of IL-6,TNF-α and IL-1β,cardiomyocyte apoptosis ratio,aortic media thickness,and protein expression of Caspase 3,TLR4,PI3K,p-AKT/AKT and p-mTOR/mTOR in myocardial tissue(P＜0.05).Conversely,LVEF,FS,aortic luminal diameter,and Bcl-2 protein content were significantly reduced,the difference being statistically significant(P＜0.05).Compared to the model group,both low-and high-dose XFZY groups as well as the Lipitor group demonstrated attenuated myocardial lesions,with significant reductions in collagen volume fraction,LVDs,LVDd,myocardial IL-6,TNF-α,IL-1β levels,cardiomyocyte apoptosis ratio,aortic media thickness,and protein expression of Caspase 3,TLR4,PI3K,p-AKT/AKT and p-mTOR/mTOR(P＜0.05).Concurrently,LVEF,FS,aortic luminal diameter,and Bcl-2 protein content were significantly increased,the difference being statistically significant(P＜0.05).No statistically significant differences were observed between the high-dose XFZY group and the Lipitor group for any aforementioned parameters(P＞0.05).However,rats treated with high-dose XFZY plus RS09 showed aggravated myocardial injury with manifested interstitial fibrosis,alongside significantly intensified inflammatory response,cardiomyocyte apoptosis,and vascular remodeling compared to the high-dose XFZY alone group(all P＜0.05).Conclusion XFZY alleviates CHD symptoms by suppressing TLR4/PI3K/AKT/mTOR pathway activation,thereby reducing myocardial inflammation,fibrosis,apoptosis,and vascular remodeling.

ObjectiveTo understand the prevalence of tobacco use among residents aged 15 years old and above in Jiading District of Shanghai, and to provide a scientific basis for formulating effective regional tobacco control policies. MethodsThe Probability Proportional to Size (PPS) sampling method was employed to select one neighborhood committee (village) from each of Jiading District’s 11 subdistricts as survey monitoring sites. From the household registry of each selected neighborhood committee (village), 50 residential households were randomly sampled, resulting in a total of 550 households surveyed. Within each selected household, one permanent resident aged 15 years old or above was randomly chosen to complete the questionnaire. The content covered general information, exposure to secondhand smoke, awareness of tobacco related health hazards, etc. Statistical analyses were performed using SPSS 27.0 software. ResultsA total of 550 questionnaires were distributed, with 549 valid responses collected, and the effective response rate was 99.82%. The survey findings revealed that in 2023, the current smoking rate among individuals aged 15 years old and above in Jiading District of Shanghai was 18.76%, with males accounting for 38.93% and females accounting for 2.62%. Male gender was identified as a relative factor for smoking (OR=34.108, 95%CI: 14.440‒80.722), whereas higher education attainment emerged as a protective factor against smoking (OR=0.388, 95%CI: 0.184‒0.820). Among non-smokers aged 15 years old and above in Jiading District, the secondhand smoke exposure rate was 46.86%, with statistically significant differences observed across different age groups and occupations (P<0.001). Restaurants exhibited the highest secondhand smoke exposure rate of 42.14%, followed by households bearing (36.79%). The overall awareness rate among individuals aged 15 years old and above in Jiading District regarding four smoking-related diseases, namely stroke, heart disease, lung cancer, and impotence, was 48.45%, while the awareness rate for three secondhand smoke-induced diseases, namely adult heart disease, pediatric pulmonary disease, and adult lung cancer, was 64.29%. ConclusionThere is still room for reduction in the prevalence of tobacco use among individuals aged 15 yeas old and above in Jiading District. The exposure to secondhand smoke is severe, and residents have low awareness of the harm of tobacco. Tobacco control law enforcement should be strengthened, smoke-free-home health education should be included in tobacco control efforts, and targeted health education should be carried out.