Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

ObjectiveThe potential suitable area for ecological planting， key ecological factors， and suitable range of Polygonatum odoratum in China were analyzed to provide theoretical and scientific guidance for the artificial planting of P. odoratum. MethodA total of 454 geographical distribution records of P. odoratum in China and 118 ecological factors were used in this study. The maximum entropy model （MaxEnt） was adopted to predict the suitable areas of P. odoratum. The key ecological factors and their suitable ranges were analyzed by the jackknife method， contribution rates of ecological factors， and response curves. ResultThe suitable areas of P. odoratum were mainly located in the northwest， north， and northeast of China， the highly suitable areas of which were concentrated in Shaanxi， Shanxi， Gansu， etc. Solar radiation in November （Srad11）， precipitation in July （Prec7）， percentage of evergreen/deciduous needleleaf trees （Class1）， silt content （2-50 μm） mass fraction （SLTPPT）， and annual average temperature （Bio1） were found to be the key ecological factors affecting the suitable distribution of P. odoratum in China. The cumulative contribution rate of solar radiation factors （31.29%）>vegetation factors （25.61%）>soil factors （19.52%）>precipitation factors （11.38%）>temperature factors （8.57%）>topography factors （3.63%）. ConclusionIt is suggested to carry out ecological planting of P. odoratum mainly in Shaanxi （such as Baoji and Ankang Cities and Ningshan， Liuba， and Hua Counties）， Gansu （such as Tianshui City， Gannan Tibetan Autonomous Prefecture， and Liangdang and Huating Counties）， and Shanxi （such as Yangquan， Taiyuan， Fenyang， and Jinzhong Cities， as well as Xingxian County） of China. Solar radiation factors should be given priority in the planting process， followed by vegetation， soil， precipitation， temperature， and topography factors. The range of key ecological factors， namely Srad11， Prec7， Class1， SLTPPT， and Bio1 should be controlled within 8 095.21-10 334.98 （optimum 8 787.50） kJ·m^-2·d^-1， 109.99-223.60 （146.91） mm， 1.00%-9.45% （6.76%-10.68%）， 41.73%-50.35% （46.53%）， and 3.29-16.33 （13.57） °C， respectively.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.

To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑₂OPs, ∑₂PYRs, and ∑₂NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑₂OPs, ∑₂PYRs, and ∑₂NEOs in this study were 419.77, 2.95, and 20.36 nmol·g⁻¹, respectively. The multiple linear regression results showed that the urinary concentration of ∑₂OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑₂PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑₂NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑₂PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑₂NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑₂NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑₂NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.

Objective To investigate the effect of multi-sided foramen ultrafine drainage tube with metal support on the formation of thoracic residual cavity after uniportal video-assisted thoracoscopic (VATS) upper lobectomy. Methods The clinical data of the patients who underwent uniportal VATS upper lobectomy for lung cancer in the Department of Thoracic Surgery of the First Hospital of Lanzhou University from January 2021 to April 2022 were retrospectively analyzed. According to the type of ultrafine drainage tube used in the surgery, the patients were divided into a test group (using metal-supported multi-sided foramen ultrafine drainage tube) and a control group (using ordinary 12F ultrafine drainage tube). The incidence of postoperative thoracic residual cavity and operation-related data were compared between the two groups. Results A total of 200 patients were enrolled, including 126 males and 74 females, with a mean age of 57.52 years. There were 90 patients in the test group, and 110 patients in the control group. The incidence of postoperative thoracic residual cavity in the test group was lower than that in the control group (P=0.045). The differences in the postoperative bedtime, postoperative visual analogue scale, postoperative analgesic pump using time, postoperative hospitalization time, times of postoperative thoracentration and drainage, postoperative drainage time and hospitalization cost between the two groups were statistically significant (P<0.05). The incidences of postoperative lung infection, pleural effusion and atelectasis complications were lower in the test group than those in the control group (P<0.05). The differences in the preoperative anesthesia time, operation time, intraoperative bleeding and postoperative lung leakage were not statistically significant (P>0.05). Conclusion The use of multi-sided foramen ultrafine drainage tube with metal support can reduce the incidence of thoracic residual cavity after uniportal VATS upper lobectomy, and can reduce pain and economical burdens and the incidence of operation-related complications, accelerating the recovery of patients after surgery. The application of multi-sided foramen ultrafine drainage tube with metal support in uniportal VATS upper lobectomy can be widely used in the clinic.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Objective:To investigate the predictive value of systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and CT perfusion imaging (CTP) parameters for early neurological deterioration (END) in patients with mild stroke duo to anterior circulation large vessel occlusion.Methods:Patients with minor stroke duo to anterior circulation large vessel occlusion admitted to the First People's Hospital of Suqian from November 2021 to December 2023 were included. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5, and END was defined as an increase of ≥ 4 in NIHSS score within 24 hours of admission compared to the baseline. SIRI and SII were calculated based on the findings of blood routine examination. According to CTP at admission, the cerebral blood volume (CBV) index, infarct core volume, and early infarct growth rate (EIGR) were obtained. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each predictor on END. Results:A total of 132 patients were included, with 85 males (64.4%) and a median age of 68 years (interquartile range, 58-77 years). Thirty-nine patients (29.5%) experienced END. The baseline NIHSS score, fasting blood glucose, neutrophil count, lymphocyte count, SIRI, SII, infarct core volume, and EIGR in the END group were significantly higher than those in the non-END group, while the CBV index was significantly lower than that in the non-END group (all P<0.05). Multivariate logistic regression analysis showed that SIRI (odds ratio [ OR] 3.672, 95% confidence interval[ CI] 1.838-6.326; P<0.001), SII ( OR 4.824, 95% CI 2.057-7.135; P<0.001), CBV index ( OR 0.968, 95% CI 0.947-0.986; P<0.001), and EIGR ( OR 2.527, 95% CI 1.918-3.589; P<0.001) were the independent predictive factors of END. ROC curve analysis showed that the area under the curves of SIRI, SII, CBV index, and EIGR for predicting END were 0.780 (95% CI 0.692-0.863), 0.798 (95% CI 0.709-0.888), 0.775 (95% CI 0.697-0.853), and 0.772 (95% CI 0.732-0.829), respectively. Conclusion:SIRI, SII, CBV index, and EIGR are the independent predictive factors of END in patients with minor stroke duo to anterior circulation large vessel occlusion, and have certain predictive value for END.