Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

ObjectiveTo establish a mouse model of hypoxic pulmonary hypertension (HPH) through intermittent hypoxia induction, and to develop a comprehensive and reliable evaluation system for the HPH model, thereby providing experimental evidence for mechanistic studies and translational applications related to this disease. MethodsTwenty-four male specific pathogen-free (SPF) BALB/c mice were randomly divided into a control group and a model group, with 12 mice per group. Mice in the model group were placed in a hypobaric oxygen chamber control system to establish the HPH model, whereas mice in the control group received no intervention. After 28 days of modeling, a comprehensive evaluation of the pathophysiological characteristics of both groups was performed using a general condition scoring scale, echocardiography, hemodynamic measurements, blood gas analysis, hematological tests, organ coefficient determination, histopathological examination, and enzyme-linked immunosorbent assay (ELISA). In addition, correlation analyses were conducted among echocardiographic parameters, the contents of endothelin‑1 (ET‑1) and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) in lung tissue, and other measured indices. ResultsWith prolonged modeling duration time, body weight, water intake, and activity level of mice in the model group were significantly decreased compared with the control group (P<0.05). Echocardiography showed that, compared with the control group, the model group exhibited increased right ventricular dimensions (P<0.01), right ventricular anterior wall thickening (P<0.01), and widened main pulmonary artery diameter (P<0.01), whereas the peak systolic velocity across the pulmonary valve, tricuspid annular plane systolic excursion, and peak systolic velocity of the tricuspid annulus were significantly decreased (P<0.001); tricuspid regurgitation was observed in some model animals. Hemodynamic results revealed that right ventricular systolic pressure was elevated in the model group compared with the control group (P<0.001). Blood gas analysis showed that pH, partial pressure of oxygen, oxygen saturation, actual bicarbonate, and total carbon dioxide were all decreased in the model group compared with the control group (P<0.01). Hematological indices demonstrated that lymphocyte counts (P<0.05) and reticulocyte counts (P<0.001) were decreased in the model group compared with the control group. Compared with the control group, the organ coefficients of heart and lung in the model group were significantly increased (P<0.05 and P<0.001). Pathological examination revealed that the right ventricular hypertrophy index was significantly increased in the model group (P<0.001), with varying degrees of damage to the right ventricle, pulmonary artery, and pulmonary vessels; both the pulmonary artery wall thickness percentage and the pulmonary wall area percentage were significantly elevated (P<0.001). ELISA results showed that the levels of ET‑1 and NT‑proBNP in lung tissues were significantly increased in the model group compared with the control group (P<0.05 and P<0.001, respectively). Correlation analysis indicated that some echocardiographic parameters were highly correlated with multiple indices in the development of HPH (P<0.05). ConclusionEchocardiography can accurately assess a series of hemodynamic changes in HPH, including right ventricular structural, functional impairment, and pulmonary hypertension. Laboratory tests not only help verify whether the model has been successfully established, but also provide deeper insights into the pathogenesis of HPH, evaluate the effects of interventions, and offer scientific evidence for clinical outcomes. Pathological examination can further confirm the alterations in pulmonary vascular remodeling and increased right heart load. This multimodal analysis provides a reliable animal model and evaluation paradigm for both basic and translational research on HPH, and is of great significance for exploring disease mechanisms and developing precision therapeutic strategies.

Objective:To determine the median effective dose (ED 50) of oliceridine inhibiting the responses to the laryngeal mask airway insertion when combined with ciprofol in elderly patients. Methods:In this sequential trial, American Society of Anesthesiologists Physical Status classificationⅠ-Ⅲ elderly patients of either sex, aged ≥65 yr, with a body mass index of 18-30 kg/m 2, undergoing elective urological surgery under general anesthesia with laryngeal mask airway, were included in this study. Ciprofol 0.4 mg/kg was intravenously injected, the dose of oliceridine was determined by using modified Dixon′s up-and-down method (increment or decrement of 0.005 mg/kg), and the initial dose of oliceridine was 0.01 mg/kg. A positive response was defined as an increase in maximum mean arterial pressure or heart rate ≥20% within 3 min after inserting the laryngeal mask airway or occurrence of any one of these signs such as movement, coughing, frowning, mouth corner twitching, tearing, laryngospasm, or bispectral index value failing to drop below 60. The trial was terminated upon observing 7 positive-to-negative transition points, starting from the first occurrence of an alternation between positive and negative responses to laryngeal mask airway insertion. The ED 50 and 95% confidence interval of oliceridine inhibiting the responses to the laryngeal mask airway insertion was calculated when combined with ciprofol in elderly patients. Results:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion was 0.027 mg/kg, and the 95% confidence interval was 0.008-0.048 mg/kg when combined with ciprofol 0.4 mg/kg. Conclusions:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion is 0.027 mg/kg when combined with ciprofol 0.4 mg/kg in elderly patients.

Objective:To explore the characteristics of nutrition self-management of home-based elderly chronic obstructive pulmonary disease (COPD) patients based on user persona, in order to provide reference for accurate home nutrition management.Methods:From July to December 2023, home-based elderly COPD patients in the Department of Respiratory and Critical Care Medicine of General Hospital of Ningxia Medical University were selected by convenience sampling method. The Mini Nutritional Assessment, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Physical Activity Rating Scale-3, COPD Patients Self-Management Scale were used to conduct questionnaire survey. The SPSS 26.0 software was used to analyze the influencing factors of patients′ self-management of nutrition. Attributes with statistical significance ( P<0.05) were extracted as labels, and the visualization of patients′ self-management of nutrition portraits was completed in the form of pictures combined with labels. Results:A total of 320 questionnaires were distributed, and 309 valid questionnaires were collected. Among 309 home-based elderly COPD patients, there were 210 males and 99 females with an age of (69.14 ± 6.84) years old. According to the data analysis results, three dimensions of natural attributes, social attributes, and behavioral tracks were artificially extracted to construct three types of nutritional self-management user persona for home-based elderly COPD patients, respectively namely blind management type, independent attempt type, and powerless type.Conclusions:There are great differences in the nutritional status and self-management of home-based elderly patients with COPD. Accurate management measures can be developed based on user persona analysis to improve their nutritional status.

Objective:To explore the characteristics of potential categories of chronic disease co-morbid patients' learned helplessness, and to analyze the differential characteristics of different categories of chronic disease co-morbid patients.Methods:Convenience sampling method was used to select patients with chronic disease co-morbidities who attended The NO.1 People's Hospital of Xiangyang, Hubei University of Medicine, from June to December 2023 as survey respondents. General information questionnaire, Learned Helplessness Scale, Health Questionnaire Somatic Symptom Cluster Scale, Kessler Psychological Distress Scale, and Comprehension Social Support Scale were used for the cross-sectional survey. The potential profile of learned helplessness, and the influencing factors of potential categories of learned helplessness was analyzed.Results:A total of 810 patients with chronic co-morbidities were investigated. There were 453 males and 357 females, aged (65.03±10.89) years old. The learned helplessness of these patients was categorized into three different potential categories, which were named as low-level learned helplessness group, medium-level learned helplessness group, high-level learned helplessness, accounting for 17.5% (142/810), 23.5% (190/810), and 59.0% (478/810), respectively. Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe physical symptoms ( OR=1.456, 1.391, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe the psychological distress ( OR=1.359, 1.917, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with lower levels of social support ( OR=0.928, 0.874, both P<0.01). Compared with the low-level learned helplessness group, patients with a duration of illness >5 years were used as controls, patients with a duration of illness 2-5 years were more likely to belong to the medium-level learned helplessness group and high-level learned helplessness group ( OR=74.586, 62.620, both P<0.01). Compared with the low-level learned helplessness group, patients with neutral personalities were compared, patients with extroverted personalities had a lower probability of belonging to the medium-level learned helplessness group ( OR=0.105, P<0.05), while patients with introverted personalities had a lower probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group ( OR=0.052, 0.046, both P<0.01). Conclusions:Patients with chronic disease co-morbidities have higher levels of learned helplessness during disease treatment and have more distinctive categorical characteristics. Healthcare professionals should adopt targeted nursing interventions according to different categories of chronic disease co-morbid patients to reduce the level of learned helplessness.

Objective:To explore the relationship between autistic trait and pain empathy among college students, as well as the mediating role of personal pain perception.Methods:From October to December 2023, a cross-sectional survey was conducted among 1 195 college students using the autism spectrum quotient, pain sensitivity questionnaire, fear of pain questionnaire, pain catastrophizing scale and empathy for pain scale.SPSS 27.0 software was used for descriptive statistics and correlation analysis.A structural equation model was constructed using Mplus 8.3 to examine the mediating effect of personal pain perception, which was composed of pain sensitivity, fear and catastrophizing cognition.Results:Autistic trait(22.00(18.00, 26.00))was significantly positively correlated with pain sensitivity (55.00(43.00, 70.00)), fair of pain (69.00(60.00, 78.00)), and pain catastrophizing cognition (16.00(8.00, 23.00)) ( r=0.112, 0.154, 0.204, all P<0.001).Autistic trait was also significantly positively correlated with affective distress(62.00(46.00, 80.00), r=0.162, P<0.001) and vicarious pain (14.00(8.00, 20.00), r=0.096, P<0.001) of pain empathy.Pain sensitivity, fear of pain and pain catastrophizing cognition were significantly positively correlated with affective distress( r=0.244, 0.332, 0.375, all P<0.001) and vicarious pain ( r=0.210, 0.232, 0.285, all P<0.001) of pain empathy.The effects of autistic trait on affective distress and vicarious pain dimensions of pain empathy were fully mediated by personal pain perception, with the mediating effects of 0.115( P<0.001, 95% CI=0.073-0.165) and 0.085( P<0.001, 95% CI=0.053-0.124). Conclusions:The autistic trait of college students can predict the affective distress and vicarious pain of pain empathy indirectly through personal pain perception.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Objective:To explore the current status of quality of life of rheumatoid arthritis (RA) patients and its influencing factors based on the health ecology model (HEM) , and to provide a scientific basis for the development of health education programs for RA patients.Methods:From November 2023 to April 2024, 230 RA patients in the Department of Rheumatology and Immunology, General Hospital of Ningxia Medical University, were selected for the study using convenience sampling method. Patients were surveyed using the General Information Questionnaire, Quality of Life Instruments for Chronic Diseases in RA (QLICD-RA) , Health Literacy Management Scale, Social Support Rate Scale, Brief Illness Perception Questionnaire, 8-item Morisky Medication Adherence Scale, Pain Catastrophizing Scale, Chronic Disease Self-Management Study Measures, Fear of Progression Questionnaire-Short Form, Tampa Scale for Kinesiophobia and Visual Analogue Scale. Pearson and Spearman correlation was used to analyze the correlation between quality of life and health literacy, social support, disease perception, self-management behaviors, fear of disease progression, fear of exercise, medication adherence, pain catastrophizing, and pain in RA patients. Multiple linear regression was used to analyze the factors influencing the quality of life of RA patients.Results:A total of 230 questionnaires were distributed and 228 valid questionnaires were recovered, with a valid recovery rate of 99.13% (228/230) . The total QLICD-RA score of 228 RA patients was (137.53±27.57) . Duration of disease, disease perception, pain, pain catastrophizing, self-management behavior, joint deformity, morning stiffness duration, gastrointestinal response, sleep, social support, and main economic sources were the factors influencing the quality of life of RA patients ( P<0.05) , explaining 83.6% of the total variance. Conclusions:The quality of life of RA patients is moderate, and its influencing factors are distributed at all levels of HEM. Healthcare professionals can optimize the health education program for the main influencing factors of each layer, focusing on guiding patients to correctly understand the disease, stimulating the subjective initiative of patients, enhancing the ability of patients to actively manage the disease, and improving the quality of life of patients.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Objective:To evaluate the efficacy of rhomboid inter-costal and sub-serratus (RISS) block with ropivacaine-dexmedetomidine-dexamethasone for analgesia after thoracoscopic lobectomy.Methods:This study was a prospective, randomized, double-blind, controlled trial. From January 2021 to November 2023, 46 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, undergoing elective video-assisted thoracoscopic lobectomy at the Second Affiliated Hospital of Nanjing Medical University, were selected and assigned into 2 groups ( n=23 each) using simple randomization: ropivacaine group (R group) and ropivacaine-dexmedetomidine-dexamethasone group (RDA group). RISS block was performed preoperatively, with 20 ml of the drug solution injected at the target points of the rhomboid-intercostal muscle and the serratus anterior-intercostal muscle. R group received 0.375% ropivacaine 40 ml, while RDA group received 40 ml of the mixture containing 0.375% ropivacaine, dexmedetomidine 1 μg/kg, and dexamethasone 8 mg. Postoperative analgesia was performed with oxycodone (When the patient′s numerical rating scale [NRS] score >4 in post-anesthesion care unit, oxycodone 2 mg was intravenously administered as needed until the NRS score <4, and then a patient-controlled analgesia pump was initiated). The time of the first postoperative analgesic requirement, NRS scores at rest and during coughing at 1, 3, 6, 12, 24 and 48 h postoperatively, cumulative consumption of oxycodone in the periods of 0-12 h, >12-24 h, and >24-48 h, time to first ambulation, and incidence of related adverse reactions within 48 h postoperatively were recorded. Results:Compared with R group, the time to the first analgesic requirement was significantly prolonged, the cumulative consumption of oxycodone in the first 0-12 h postoperatively was reduced ( P<0.001), and no statistically significant changes were found in the time to first ambulation, NRS scores at rest and during coughing, or the incidence of postoperative adverse reactions in RDA group ( P>0.05). Conclusions:RISS block using a combination of ropivacaine, dexmedetomidine and dexamethasone can significantly prolong block duration, reduce postoperative opioid analgesic consumption, and provide good safety for the patients undergoing thoracoscopic lobectomy.