Background The moderation role of environmental factors in the spread of hand-foot-and-mouth disease (HFMD) has attracted much attention, but the existing conclusions are inconsistent. For example, some scholars believe that high temperature, high humidity, and high concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) increase the risk of HFMD, but other scholars have reached the opposite conclusion, or believe that there is no significant relationship. Objective Based on distributed lag nonlinear model (DLNM), to investigate the relationship between the incidence of HFMD and meteorological and air pollutant variables in Lianyungang City, and to provide scientific basis for early warning. Methods Daily data of meteorological factors and air pollutants in Lianyungang City from 2021 to 2024 were retrieved. Meteorological factors included average daily temperature, average wind speed, average air pressure, and relative humidity. Air pollutant indicators included PM_2.5, inhalable particulate matter (PM₁₀), carbon monoxide (CO), sulfur dioxide (SO₂), NO₂, and ozone (O₃). Spearman correlation analysis was used to analyze their correlations with HFMD, and the R package (version 4.3.1) dlnm was used to construct a DLNM model. Results During the study period, a total of 10503 cases were reported, with a male to female ratio of 1.47∶1 and the highest proportion of scattered children (49.97%). The Spearman correlation analysis results showed that daily average temperature (r=0.40), relative humidity (r=0.17) and O₃ (r=0.14) were positively correlated with the incidence of HFMD (all Ps<0.01), while average air pressure (r=−0.34), PM_2.5 (r=−0.24), PM₁₀ (r=−0.24), CO (r=−0.22), and NO₂ (r=−0.06) were negatively correlated with it (all Ps<0.05). There was no statistical relationship of SO₂ and average wind speed with the incidence of HFMD (both Ps>0.05). The cumulative risk effect was greatest when the daily average temperature was 28.50 ℃ (CRR=4.63, 95%CI: 2.68, 8.01). The average wind speed below 0.50 m·s⁻¹ and in the range of 2.50-3.50 m·s⁻¹ showed an acute risk effect, and low pressure (below 1016.00 hPa) could immediately increase the risk of the disease. The cumulative risk effect was greatest when the relative humidity was 100% (CRR=3.16, 95%CI: 1.77, 5.65). The greatest cumulative protective effects of PM_2.5 and PM₁₀ were present at concentrations of 158.00 μg·m⁻³ (CRR=0.12, 95%CI: 0.01, 0.99) and 561.50 μg·m⁻³ (CRR=0.01, 95%CI: 0.01, 0.99) respectively. The protective effect of CO was the strongest at the highest concentration (67.00 μg·m⁻³) (RR=0.67, 95%CI: 0.34, 0.64). The cumulative protective effects of SO₂ and NO₂ were both most significant at the concentration of 0.50 μg·m⁻³. Low concentrations of O₃ (below 48.00 μg·m⁻³) showed a risk effect, and the single-day protective effect was significant when the concentration was 141.00 μg·m⁻³. Conclusion There is a nonlinear and hysteretic relationship between environmental factors and the incidence of HFMD. A rational and efficient early warning and prevention and control system can be constructed accordingly.

Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P ＜ 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P＜ 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.

Objective To analyze the overall characteristics, research hotspots, and development trends of immune cell-related studies in radiotherapy for rectal cancer. Methods A systematic search was conducted by using Web of Science Core Collection to retrieve articles related to radiation therapy and immune cells in rectal cancer published from 1991 to 2024. Advanced bibliometric tools, such as VOSviewer and CiteSpace, were utilized to facilitate analysis and describe publication trends, geographic contributions, institutional affiliations, journal prominence, author collaboration, and prominent keywords. Results The annual number of relevant publications has increased steadily, showing remarkable growth over the past five years. Studies focusing on adaptive immune cells (T and B cells) account for the largest proportion of works and form the most extensive collaboration networks, reflecting the central role of T cell–mediated antitumor immunity in radiotherapy. Meanwhile, innate immune cells, including myeloid-derived suppressor cells, macrophages, monocytes, and neutrophils, are increasingly investigated for their regulatory roles in shaping the tumor immune microenvironment and influencing therapeutic responses. Among countries, China and the United States have contributed the highest number of publications and demonstrated strong academic influence. While several stable research groups have been formed, intergroup collaboration remains limited. Keyword analysis revealed that radiotherapy-induced immune modulation, tumor immune microenvironment remodeling, and treatment response have emerged as major research hotspots. Conclusion Research on immune cells in rectal cancer radiotherapy has progressed rapidly in recent years. The emphasis of this field has gradually shifted from single-treatment approaches to mechanistic studies investigating the interaction between radiotherapy and the tumor immune microenvironment. The field still demonstrates considerable potential for future research and clinical translational applications.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy in China,with cervical lymph node metastasis being a frequent and critical clinical feature that directly affects patient prognosis and recurrence risk.In recent years,with the rapid increase in the prevalence of overweight and obesity in China,the role of body mass index(BMI)in various tumors has attracted growing attention.This study aimed to investigate the association between overweight and cervical LNM in PTC,analyze sex-specific differences and influencing factors,and provide evidence for precise clinical management.Methods:A retrospective analysis was conducted on the clinicopathologic data of 1 445 patients with classical PTC treated at Xiangya Hospital of Central South University between August 2021 and June 2022.Patients were divided into groups based on the presence or absence of lymph node metastasis.Restricted cubic spline analysis explored the nonlinear relationship between BMI and lymph node metastasis risk.Univariate and multivariate Logistic regression analyses were applied to identify independent risk factors.Furthermore,sex-stratified analysis was performed among overweight patients(BMI≥24 kg/m2)to determine sex-specific risk factors for lymph node metastasis.Results:Among all patients,716(49.6%)had lymph node metastasis.Univariate analysis showed that BMI,sex,age,tumor diameter,multifocality,and extrathyroidal extension were significantly associated with cervical lymph node metastasis in PTC patients(all P<0.05).A nonlinear positive correlation was observed between BMI and lymph node metastasis risk,which was more pronounced in male patients.Additionally,BMI was positively correlated with triglyceride levels and negatively correlated with high-density lipoprotein cholesterol.Sex-stratified analysis revealed that in overweight male patients,younger age(OR=0.954),larger tumor diameter(OR=1.085),and multifocality(OR=2.776)were independent risk factors for LNM;in overweight female patients,younger age(OR=0.943)and larger tumor diameter(OR=1.074)were the main influencing factors.Conclusion:Overweight is closely associated with cervical lymph node metastasis in PTC,and the high-risk factors for LNM differ between male and female overweight patients.Young age,larger tumor size,and multifocality in overweight males,and young age and larger tumors in overweight females indicate a higher risk of metastasis.It is recommended that high-risk populations receive enhanced preoperative evaluation and individualized lymph node dissection strategies to achieve precise treatment and improved risk control.

Objective To improve the underwater technique during the start phase of breaststroke swimmers through swimming flume training and assess its effectiveness in enhancing competitive performance.Methods The participants were 14 male swimmers in the short-distance Level 4 category from the Shanghai Swimming Team,and they were randomly divided into the experimental group(n=7)and control group(n=7).The experimental group underwent swimming flume start training,while the control group underwent regular pool start training,and both groups received the training twice a week for 16 weeks.Before and after the 16-week training,a 15-m breaststroke start test was conducted.Repeated measures analysis of variance and paired t-tests were used to compare the changes in kinematic parameters(time,speed,and entry angle)between and within groups.Results After 16 weeks of specialized training,the 15-m performance at the start for the experimental group and control group(F(1,12)=6.52,P＜0.05,η2=0.39)showed an interaction,with the experimental group performing better after training compared to the control group before training(P＜0.05).In the experimental group,the duration of the pull-out phase(F(1,12)=10.28,P＜0.01,η2=0.46)and the second sliding phase(F(1,12)=4.81,P＜0.05,η2=0.22)was improved;the distance of the pull-out phase(F(1,12)=4.71,P＜0.05,η2=0.21)and the second sliding phase(F(1,12)=4.90,P＜0.05,η2=0.21)was improved;the speed of the pull-out phase(F(1,12)=4.77,P＜0.05,72=0.20)was significantl improved.The within-group statistics showed that the experimental group significantly improved their exit speed(P＜0.05).The hand entry angle was optimized(P＜0.05),while changes in other joint angles were not significant.Conclusions Swimming flume training reduced the time spent in the pull-out and second gliding phases during the breaststroke start,effectively preventing the speed loss during underwater gliding.This provides an experimental evidence for enhancing start performance and optimizing training method for breaststroke swimmers.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective:To analyze the cost-effectiveness of administering two doses of different types of human papillomavirus (HPV) vaccines to 12-year-old female adolescents.Methods:A decision tree Markov model with genital warts and cervical cancer as target diseases was established to analyze the effects, costs, and Quality Adjusted Life Years (QALY) of strategies such as no vaccination, two doses of bivalent HPV (HPV-2), two doses of quadrivalent HPV (HPV-4), and two doses of nine-valent HPV (HPV-9) in a 12-year-old female adolescent cohort in 2023 using 50% of the procurement price or self-funded vaccination price in pilot provinces. The number of avoided cases of cervical cancer and genital warts and the incremental cost-utility ratio (ICUR) were compared between different strategies.Results:Compared with non-vaccination, female adolescents who received two doses of HPV-2, HPV-4 and HPV-9 were able to avoid 55.2% of cervical cancer cases with HPV-2, 77.11% and 78.68% of genital warts with HPV-4, and 54.99% and 73.46% of cervical cancer with HPV-9, respectively. The ICUR of strategies HPV-2, HPV-4, and HPV-9 was -28 470.44 yuan/QALY, 29 328.26 yuan/QALY and 48 106.85 yuan/QALY, respectively. HPV-2 was the most economical strategy and could achieve net cost savings. Single-factor sensitivity analysis showed that the results were robust, and the most influential factors were discount rate, vaccine prices and direct medical costs for low-grade precancerous lesions. The probability sensitivity analysis showed that compared with the national gross domestic product (GDP) per capita in 2023, the probability of cost-utility of HPV-2, HPV-4 and HPV-9 compared with non-vaccination was 99.51%, 89.03% and 67.81%, respectively. Only when the price of a single dose of HPV-4 and HPV-9 vaccines was lower than 26.12% and 20.68% of the current self-funded vaccination price, respectively, could there be a net cost saving.Conclusion:In the case where HPV-2 adopts the pilot province procurement price and the multivalent vaccine adopts a 50% self-funded vaccination price, the vaccination of 12-year-old female adolescents with HPV-2, HPV-4 and HPV-9 has cost-effectiveness, and HPV-2 is the most economical strategy.