Objective To explore the risk factors of adverse pregnancy outcomes in the patients with cervical incompetence(CI),and to establish a risk warning model of adverse pregnancy outcomes in CI pa-tients based on decision tree model.Methods The clinical data of 159 patients with CI admitted and treated in this hospital from February 2022 to April 2023 were retrospectively analyzed,and the risk factors for adverse pregnancy outcomes were screened and the decision tree model for postoperative adverse pregnancy outcomes was constructed.The internal verification method was 5-fold cross-validation.Results The incidence rate of adverse pregnancy outcome was 22.64%.The pregnant weeks of cervical cerclage,amniotic cystocele,multiple cervical cerclage,preoperative cervical length and amniotic fluid sediment were all influential factors for ad-verse pregnancy outcome occurrence(P＜0.05).The amniotic fluid sediment was the most important factor affecting the postoperative adverse pregnancy outcome in CI patients,and the preoperative cervical length had little influence on the postoperative adverse pregnancy outcomes in CI patients.The area under the curve(AUC)value of logistic regression model was slightly higher than that of the decision tree model.The accura-cy rate of the 5-fold cross-validation model was 78.3%.Conclusion During clinical treatment,the above two models can be combined to find the influencing factors of postoperative adverse pregnancy outcomes in CI pa-tients from different aspects,and provide references for clinical medical staff to evaluate the disease condition of CI patients and formulate the intervention plans.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Breast cancer is the most common malignant tumor in women worldwide,and its incidence rate is increasing annually.Early dia-gnosis is essential for improving patient prognosis.In recent years,artificial intelligence(AI)technology has emerged as a transformative tool,providing new directions for accurate diagnostic and prognostic assessments.This article systematically reviews research progress in the ap-plication of AI to breast cancer screening,multimodal imaging techniques for diagnosis,pathological diagnosis,treatment,and prognostic modeling.Through machine learning and deep learning algorithms,AI has demonstrated significant advantages in the enhancement of dia-gnostic accuracy,efficiency,and accessibility,including improvement of the detection rate of small lesions,reduction in the radiologists'workload,and optimization of treatment decisions.Despite challenges,including the integration of explainable technology in clinical trans-formation,lack of data standardization,complexity of multimodal data,and risk of model generalization,AI is expected to play a more prom-inent role in the precise diagnosis and intelligent therapy for breast cancer,thereby contributing to the full realization of the goal of preci-sion medicine.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective:To investigate the current status and related factors of antiviral treatment for chronic hepatitis B virus (HBV) infection in rural communities in China.Methods:In 2023, 866 chronic HBV-infected individuals from rural communities in Zhangqiu District, Jinan City, were included in the study. Basic information, disease status and antiviral treatment conditions of the infected individuals were collected through questionnaires, specimen collection and laboratory tests. Univariate and multivariate logistic regression were used to analyze the related factors of the antiviral treatment rate of those who met the indications for hepatitis B antiviral treatment.Results:The median age ( Q1, Q3) of subjects was 56 (48, 66) years old, among which 436 (50.4%) were males. There were 712 (82.2%) individuals who met the indications for hepatitis B antiviral treatment, and 110 individuals received antiviral treatment with a rate of 15.5%. Multivariate logistic regression analysis showed that compared with males, families with an average monthly income per capita of <1 000 yuan, no alcohol consumption, no smoking, and a family history of HBV infection, females ( OR=4.66, 95% CI: 2.88-7.53), families with an average monthly income per capita of 1 000-1 999 yuan ( OR=1.64, 95% CI: 1.00-2.68) and ≥2 000 yuan ( OR=2.78, 95% CI: 1.54-5.03), alcohol consumption ( OR=6.42, 95% CI: 2.80-14.7), smoking ( OR=1.98, 95% CI: 1.04-3.77), and no family history of HBV infection ( OR=1.90, 95% CI: 1.16-3.09) had a lower antiviral treatment rate for chronic HBV infection. Conclusion:The antiviral treatment rate of chronic HBV-infected individuals in rural communities of Zhangqiu District, Jinan City is low, and the related factors are female, high monthly income per capita, alcohol consumption, smoking, and no family history of HBV infection.

Objective To investigate the impact of inhibiting GATA binding protein 4(GATA4)on the susceptibility to atrial fibrillation in elderly individuals and to elucidate the underlying mecha-nisms.Methods Fifteen 3-month-old young SD rats and 45 18-month-old SD rats were selected.According to the age and the injection of adeno-associated virus,the rats were divided into young group,elderly group,negative control group and interfering GATA4 group,with 15 rats in each group.Based on age and AAV injection,the rats were categorized into four groups:young group,elderly group,negative control group,and GATA4 interference group,with 15 rats in each group.Left atrial anteroposterior diameter was assessed via echocardiography.The extent of atrial fibro-sis was evaluated using Masson staining.Western blot analysis was employed to examine the ex-pression levels of GATA4,calcium cycling-related proteins,and NOD-like receptor pyrin domain-containing protein 3(NLRP3).Mouse atrial myocytes(HL-1 cells)were divided into five groups according to viral infection:control group,knockdown negative control group,GATA4 knock-down group,overexpression negative control group,and GATA4 overexpression group.The expression of GATA4 and NLRP3 was analyzed using Western blotting.Results The incidence of atrial fibrillation in the elderly group was significantly higher than that in the young group(80.0％vs 11.1％,P＜0.01).Compared with the negative control group,the induction rate of atrial fibrillation in the GATA4 interference group was significantly decreased(22.2％vs 80.0％,P＜0.05).Compared with the young group,the left atrial diameter,percentage of collagen vol-ume,activation time,absolute value of conduction dispersion,and expression of NLPR3 in the aged group were significantly increased,and the expression of calcium cycling protein was disor-dered(P＜0.05,P＜0.01).Compared with the negative control group,the left atrial diameter,per-centage of collagen volume,activation time,absolute value of conduction dispersion,and expres-sion of NLPR3 in the GATA4 interference group were significantly decreased,and the disturbance of calcium circulation was alleviated(P＜0.05,P＜0.01).Compared with the negative group of knockdown and overexpression,the expression of GATA4 and NLRP3 in HL1 cells in GATA4 knockdown group was significantly decreased,and the expression of GATA4 and NLPR3 in HL-1 cells in GATA4 overexpression group was significantly increased(P＜0.01).Conclusion GATA4 inhibition decreases the susceptibility to atrial fibrillation and mitigates age-related structural remodeling,electrical remodeling,and inflammation in the atrium by regulating calcium cycling disorders and myocardial cell senescence via the NLRP3 pathway.