To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

OBJECTIVE To explore and predict the quality markers （Q-markers） of Compound xiebai capsules for the treatment of chronic obstructive pulmonary disease （COPD） by constituents analysis combined with network pharmacology and molecular docking studies， and to establish the quality standard of Compound xiebai capsules. METHODS UHPLC-TOF-MS was used for qualitative analysis of Compound xiebai capsules， and the candidate Q-markers of Compound xiebai capsules were screened by combining network pharmacology and molecular docking technology. Further， HPLC was applied to establish the fingerprints of 15 batches of Compound xiebai capsules and to conduct quantitative analysis of the main components. RESULTS A total of 51 components were identified from Compound xiebai capsules. Among them， 15 components， namely oxyberberine， methylworenine， coptisine， tetrahydroberberine， epiberberine， berberine， magnoflorine， gandensin， cucurbitacin D， hydroxygenkwan， jatrorrhizine， columbamine， quercetin， cucurbitacin R， and palmatine， were determined as the candidate Q-markers for Compound xiebai capsules in the treatment of COPD. A total of 13 common peaks were calibrated in the fingerprints of 15 batches of Compound xiebai capsules for COPD treatment， with similarity values ranging from 0.976 to 0.999 compared to the reference fingerprint. Seven components were identified among these peaks， namely peak 5 （magnoflorine）， peak 8 （jatrorrhizine）， peak 9 （epiberberine）， peak 10 （columbamine）， peak 11 （coptisine）， peak 12 （palmatine）， and peak 13 （berberine）. Their respective contents were （0.267±0.048）， （0.453±0.084）， （0.572±0.160）， （0.392±0.074）， （1.076±0.273）， （1.477±0.271）， and （6.664±1.249） mg/g （ n ＝3）. CONCLUSIONS This study predicted 15 candidate Q-markers of Compound xiebai capsules in the treatment of COPD and established the fingerprint along with a quantitative determination method for seven major components.

Background Per- and poly-fluoroalkyl substances (PFAS) can influence gestational diabetes mellitus (GDM); however, current studies on their association are limited and have yielded inconsistent findings. Objective To investigate the association between maternal exposure to PFAS, as measured by urinary concentrations in early pregnancy, and the risk of developing GDM. Methods Based on the Wuhu Birth Cohort in Anhui Province conducted between 2020 and 2023, this study included 1910 pregnant women. Urine samples were collected during the first trimester, and a 75 g oral glucose tolerance test (OGTT) was completed at 24–28 gestational weeks. The concentrations of six PFAS in urine were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Participants were categorized into low, medium, and high exposure groups according to tertiles of individual PFAS concentrations. Logistic regression analysis was employed to assess the potential impact of early-pregnancy PFAS exposure levels on the risk of GDM, with stratified analyses by maternal age and fetal sex. A generalized weighted quantile sum regression (gWQS) model was applied to evaluate the relative weight distribution of the six PFAS in their mixture effect. Results The logistic regression results revealed that both medium exposure to perfluorohexane sulfonate (PFHxS) (OR=1.475, 95%CI: 1.040, 2.093) and high exposure to perfluorononanoic acid (PFNA) (OR=1.430, 95%CI: 1.013, 2.018) were positively associated with diagnosed GDM. This association was more pronounced among women older than 28 years. Among pregnant women carrying male fetuses, high-level exposures to per fluorohexanoic acid (PFHxA) (OR=1.708, 95%CI: 1.006, 2.899) and PFHxS (OR=2.116, 95%CI: 1.247, 3.584) showed positive associations with diagnosed GDM. In contrast, among those carrying female fetuses, moderate perfluorooctanesulfonic acid (PFOS) exposure was associated with a lower risk of GDM (OR=0.542, 95%CI: 0.311, 0.946). The gWQS results demonstrated that PFOS (0.48) and perfluorobutane sulfonate (PFBS) (0.34) contributed the most to the mixture effect. Conclusion Early-pregnancy exposure to PFAS (particularly PFHxS and PFNA) may be an etiological factor for GDM, with maternal age and fetal sex potentially acting as effect modifiers in this association.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Objective To assess the effectiveness of the Regulations on Medical Dispute Prevention and Resolution(hereafter referred to as the Regulations)and to provide evidence-based recommendations for enhancing the legal governance sys-tem of medical dispute management.Methods A cross-sectional study was conducted involving physicians,nurses,techni-cians,clinical department directors,and head nurses.The investigation was conducted through literature review,questionnaire surveys,and expert interviews.Factor analysis and chi-square tests were employed for statistical analysis.Results Significant differences(P＜0.01)were observed among healthcare practitioners in Guangxi concerning their understanding of the Regula-tions,preferences for dispute resolution methods,implementation of informed consent,and risk intervention practices.However,no significant differences emerged in medical quality and safety evaluations or recommendations for surgical accident insurance.Conclusion This study suggests it is a need to refine the legal framework for medical dispute prevention and resolution.It is rec-ommended to strengthen medical personnel's compliance with informed consent obligations and deepen their understanding of rel-evant laws and regulations.Efforts should be intensified to promote third-party mediation mechanisms such as the Medical Dispute Mediation Committee(MedMC)and medical accident insurance coverage.Additionally,pre-dispute risk assessments should be enhanced,and a risk early intervention model integrating artificial intelligence,healthcare practices,and legal regulations should be established.

Objective To compare the effectiveness of cobalt chloride test papers and borescope in evaluating the drying of endoscopes,providing a reference for clinical selection of appropriate assessment tools.Methods 10 gastroscopes and 10 colonoscopes procedures were selected from November 2023 to March 2024 for circulation experiments.After endoscope reprocessing,they were randomly divided into five groups with different drying times(30 s,3 min,6 min,9 min,and 12 min)with 200 samples.Cobalt chloride test paper and borescope were used to evaluate the drying effectiveness.Results The qualified rate of gastrointestinal endoscope by borescope was significantly higher than that by cobalt chloride test paper,but cobalt chloride test paper was obviously better than that by borescope in convenience and cost-effectiveness.The borescope had the function of visualization,and the quantitative positioning observation of residual droplets showed that there were a large number of droplets left after gastrointestinal endoscope drying for 30 s,and the number of droplets was obviously reduced after drying for 3 min.Among them,the gastroscope was mainly light(1～5 drops/strip)and none(0 drops/strip),and the colonoscope was mainly moderate(6～10 drops/strip)and light droplets.Compared with different drying times,there was a significant statistical difference in the number of residual droplets in the endoscope(P<0.01),and the localized droplets mainly remained in the distal bending part and the proximal bifurcation part of the lumen.Conclusion Both cobalt chloride test papers and borescope are important methods for assessing endoscope drying efficacy,each with its own advantages and limitations.Clinicians can use both methods in combination to comprehensively evaluate the overall dryness of endoscopes,thereby ensuring the safety and effectiveness of the endoscope reprocessing process.

Objective:To investigate the expression and clinical significance of angiomotin-like protein 1 (AMOTL1) and downstream related molecules of Hippo signaling pathway yes-associated protein (YAP) and TAZ in different cervical tissues.Methods:From January 2017 and July 2018 ,102 cervical cancer tissues, 50 cervical squamous epithelial high-grade lesions (HSIL) tissues, 45 low-grade lesions (LSIL) tissues and 50 chronic cervicitis tissues, all of which underwent surgical treatment and pathological diagnosis at Xuzhou Medical University Affiliated Hospital from January 2017 to July 2018, were selected. The expression of AMOTL1 and Hippo pathway downstream related proteins YAP and TAZ were evaluated by immunohistochemistry and their relationship with the clinicopathological parameters of cervical cancer were examined in the cervical tissues of each group. The comparison of inter group rates in count data was conducted using the chi square test. Adopting Spearman correlation analysis method to analyze the relationship between AMOTL1, YAP, and TAZ. Single factor survival analysis was performed using Kaplan Meier curves. Kaplan Meier method and multivariate Cox regression analysis were used to investigate the factors affecting the prognosis of cervical cancer patients.Results:The immunohistochemical results showed that the positive rates of AMOTL1 in chronic cervicitis, LSIL, HSIL, and cervical cancer were 12.00% (6/50), 17.78% (8/45), 28.00% (14/50), and 76.47% (78/102), respectively. The positive expression status of AMOTL1 in chronic cervicitis, LSIL, HSIL and cervical cancer were 12.00%(6/50), 17.78%(8/45), 28.00%(14/50), 76.47%(78/102). The positive rates of YAP in chronic cervicitis, LSIL, HSIL, and cervical cancer were 10.00% (5/50), 15.56% (7/45), 30.00% (15/50), and 63.73% (65/102), respectively. The positive expression of YAP in cervical cancer tissues was higher than that in other groups ( χ2=56.66, P<0.001). The positive rates of TAZ in chronic cervicitis, LSIL, HSIL, and cervical cancer were 8.00% (4/50), 17.78% (8/45), 30.00% (15/50), and 71.57% (73/102), respectively. The positive expression of TAZ in cervical cancer tissues was higher than that in other groups ( χ2=74.71, P<0.001), AMOTL1 positive expression is associated with the International Federation of Gynecology and Obstetrics (FIGO) staging ( χ2=16.28, P=0.001), tissue differentiation degree ( χ2=30.16, P<0.001), and lymph node metastasis ( χ2=5.81, P=0.016), YAP positive expression is associated with FIGO staging ( χ2=15.99, P<0.001), differentiation degree ( χ2=25.06, P<0.001), tumor diameter ( χ2=13.63, P=0.003), and lymph node metastasis ( χ2=5.78, P=0.016), and TAZ positive expression is associated with FIGO staging ( χ2=14.49, P<0.001). tissue differentiation degree ( χ2=25.32, P<0.001), and the presence or absence of lymph node metastasis ( χ2=4.95, P=0.026) are related. Spearman correlation analysis showed a positive correlation between AMOTL1 and YAP expression ( r=0.65, P<0.001), and a positive correlation between AMOTL1 and TAZ expression ( r=0.72, P<0.001), There was a positive correlation between YAP and TAZ expression ( r=0.68, P<0.001). Kaplan Meier survival analysis showed that individuals with positive expression of AMOTL1, YAP, and TAZ proteins had shorter survival times than those with negative expression ( χ2 values were 9.84, 8.64, and 18.57, respectively; P values were 0.002, 0.003, and <0.001, respectively). Multivariate Cox regression analysis showed that FIGO staging ( HR=3.18, 95% CI 1.09-9.29, P=0.034), lymph node metastasis ( HR=16.74, 95% CI 3.20-87.45, P=0.010), AMOTL1 positive expression ( HR=13.06, 95% CI 1.41-121.08, P=0.024), and YAP positive expression ( HR=9.75, 95% CI 1.59-59.52, P=0.014) were risk factors for poor prognosis in cervical cancer patients. Conclusion:AMOTL1, YAP, and TAZ may jointly participate in the malignant transformation process of cervical cancer. AMOTL1 and YAP are closely related to prognosis and may become potential prognostic indicators for cervical cancer.

Objective:This study retrospectively analyzed the clinical characteristics of patients newly diagnosed with acute myeloid leukemia (AML) who were admitted to the hematology intensive care unit (HCU) with critical illness. It also examined factors associated with critical illness and early mortality in these patients.Methods:Clinical data were collected from 91 newly diagnosed AML patients admitted to the HCU of the Department of Hematology, First Affiliated Hospital of Soochow University, from October 2020 to 2024. Reasons for HCU admission, major therapeutic interventions, and risk factors for critical illness and early mortality were analyzed.Results:The median time from diagnosis to HCU admission was 3 days ( IQR: 3–9 days), and the median HCU stay was 10 days ( IQR: 3–23 days). Of the 91 patients, 71 were admitted to the HCU before induction chemotherapy, while 20 were transferred to the HCU after its initiation. The leading causes of HCU admission were pulmonary infection (78.0% ), respiratory failure (44.0% ), hepatic insufficiency (28.6% ), renal insufficiency (27.5% ), disseminated intravascular coagulation (DIC; 25.3% ), and sepsis (23.1% ). Median Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and SOFA scores at HCU admission were 14 ( IQR: 11–18) and the median Sepsis Related Organ Failure Assessment (SOFA) score was 7 ( IQR: 4, 10). Major HCU interventions included vasoactive drugs, noninvasive and invasive mechanical ventilation, continuous renal replacement therapy, therapeutic leukocyte clearance, and cardiopulmonary resuscitation. Among patients receiving induction chemotherapy, the composite complete remission rate was 65.4%, and the overall remission rate was 88.5%. Thirty-five (38.5% ) patients died within 28 days of HCU admission. Independent risk factors for 28-day mortality were DIC ( OR=9.350, 95% CI 1.999–43.745, P=0.005), sepsis ( OR=6.817, 95% CI 1.571–29.582, P=0.010), and cardiac insufficiency ( OR=12.281, 95% CI 2.385–63.254, P=0.003) . Conclusion:The main reason for HCU admission in newly diagnosed critically ill AML patients was pulmonary infection. Nearly 40% of patients experisenced early death, and DIC, sepsis, and heart failure were factors influencing early mortatlity.

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph + ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.