Background: s/Aims: The critical view of safety (CVS) prevents bile duct injury, but severe inflammation hinders its achievement.This study evaluated the parkland grading scale (PGS) as a real-time intraoperative predictor of CVS attainment in a Southeast Asian population, establishing standardized clinical data for future artificial intelligence applications. Methods: This prospective observational study (January–June 2025) included 88 consecutive patients undergoing laparoscopic cholecystectomy by a single surgeon. PGS was assessed upon initial laparoscopic inspection. We analyzed correlations between PGS, CVS attainment (Strasberg’s criteria), operative time, and bail-out procedures using Spearman’s correlation and multivariate logistic regression. Results: Severe inflammation (PGS grade 4–5) was observed in 31.8% of patients. PGS exhibited a strong negative correlation with CVS score (p = −0.652; p < 0.001) and strong positive correlations with operative time and blood loss. A PGS threshold of 4 accurately predicted CVS failure (area under the curve = 0.863). Bail-out procedures were necessary in 11 cases (12.5%), all occurring in the PGS ≥ 4 group. Advanced age and diabetes mellitus were independent risk factors for CVS failure. Conclusions The PGS serves as a precise intraoperative early warning system. A score ≥ 4 indicates a significant risk of CVS failure, prompting safer bail-out strategies. Additionally, this study provides a standardized dataset vital for training future autonomous surgical risk assessment models.

OBJECTIVE: To explore the effects of electroacupuncture (EA) on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells (GCs) in patients with polycystic ovary syndrome (PCOS) and phlegm-dampness syndrome. METHODS: In this randomized controlled trial, 90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022. Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment, with 45 in in each group. Both groups underwent the ovarian stimulation protocol. The patients in the EA group received EA therapy including Zhongwan (CV 12), Qihai (CV 6), bilateral Xuehai (SP 10), Sanyinjiao (SP 6), Yinlingquan (SP 9), Tianshu (ST 25), Zusanli (ST 36), and Fenglong (ST 40), and the patients in the control group was treated with pseudo-acupuncture. The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval. The primary outcomes were clinical pregnancy rate (CPR) and the number of high-quality embryos. The secondary outcomes were (1) pregnancy-related indicators, including fresh embryo transfer rate (ETR), ovarian hyperstimulation syndrome (OHSS) rate, early pregnancy loss rate (ePLR), ectopic pregnancy rate, live birth rate (LBR), and cumulative CPR; (2) mitochondrial autophagy and mitochondrial membrane potential (MMP) in GCs; and (3) scoring for Chinese medicine syndrome. Adverse events to assess clinical safety were also monitored. RESULTS: The cumulative CPR was significantly higher in the EA group (42/45, 93.3%) than in the control group (38/45, 84.4%, P=0.036). The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group (3.80±1.65 vs. 2.44±1.34, P<0.001; 46.7% vs 24.4%, P=0.028). Ectopic pregnancies were not observed in either group. There were no significant differences in the fresh CPR, OHSS rate, ePLR or LBR between the two groups (P>0.05). Compared with the control group, the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio (all P<0.01). The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group (P<0.01). CONCLUSIONS EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome. Mechanistically, this effect may be related to EA in decreasing miR-146a-5p mRNA expression, promoting mitochondrial autophagy in GCs, and improving mitochondrial function, which may contribute to improved oocyte quality. (Trial registration No. ChiCTR2200062915).
Humans ; Female ; Polycystic Ovary Syndrome/therapy* ; Pregnancy ; Electroacupuncture ; Granulosa Cells/metabolism* ; Adult ; Mitochondria/metabolism* ; Pregnancy Outcome ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Infertility, Female/therapy*

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Objective:To develop and externally validate a nomogram prediction model for assessing the risk of treatment dropout in allergic rhinitis (AR) patients undergoing sublingual immunotherapy (SLIT).Methods:Between February 2016 and December 2019, data from 358 and 259 AR patients undergoing SLIT were collected from Guizhou Provincial People′s Hospital and Huangshi Central Hospital, respectively. The data included general patient information, dust mite sIgE levels, allergen types, and 22 other clinical variables. Data from Guizhou Provincial People′s Hospital were used as the training set, while data from Huangshi Central Hospital were served as the external validation set. A multivariable Cox regression model was used to identify independent factors associated with SLIT dropout and to develop a nomogram prediction model.Results:Multivariate Cox regression analysis identified several significant factors influencing SLIT dropout, including dust mite sIgE levels (Grade Ⅱ-Ⅳ; HR=1.48, 95% CI: 1.16-1.88), presence of other allergic diseases ( HR=0.47, 95% CI: 0.37-0.61), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score ( HR=0.98, 95% CI: 0.97-1.00), WeChat management ( HR=0.77, 95% CI: 0.60-0.98), treatment efficacy ( HR=0.72, 95% CI: 0.56-0.92), age (5-17 years, HR=0.50, 95% CI: 0.36-0.71;≥60 years, HR=1.42, 95% CI: 1.08-1.87), household income (<5 000 CNY, HR=1.44, 95% CI: 1.09-1.90;>20 000 CNY, HR=0.66, 95% CI: 0.44-0.99), allergen types (single dust mite, HR=0.70, 95% CI: 0.49-0.93; and combined pollen or mold, HR=1.45, 95% CI: 1.02-2.04), and time to efficacy <3 months ( HR=0.73, 95% CI: 0.56-0.94), all P<0.05. At the third-year follow-up, the area under curve (AUC) for the nomogram model was 0.913 (95% CI: 0.881-0.943) in the training group and 0.886 (95% CI: 0.838-0.933) in the validation group. Calibration and decision curve analyses demonstrated the model′s consistency with actual dropout rates and clinical benefit in both groups. Additionally, a Brier score of 0.29 further confirmed the model′s predictive accuracy. Conclusion:We successfully develop a nomogram-based prediction model for SLIT dropout in AR patients, which could assist healthcare professionals in effectively identifying high-risk patients and facilitate the development of more personalized and timely treatment plans aimed at enhancing patient compliance.

Objective:To develop and externally validate a nomogram prediction model for assessing the risk of treatment dropout in allergic rhinitis (AR) patients undergoing sublingual immunotherapy (SLIT).Methods:Between February 2016 and December 2019, data from 358 and 259 AR patients undergoing SLIT were collected from Guizhou Provincial People′s Hospital and Huangshi Central Hospital, respectively. The data included general patient information, dust mite sIgE levels, allergen types, and 22 other clinical variables. Data from Guizhou Provincial People′s Hospital were used as the training set, while data from Huangshi Central Hospital were served as the external validation set. A multivariable Cox regression model was used to identify independent factors associated with SLIT dropout and to develop a nomogram prediction model.Results:Multivariate Cox regression analysis identified several significant factors influencing SLIT dropout, including dust mite sIgE levels (Grade Ⅱ-Ⅳ; HR=1.48, 95% CI: 1.16-1.88), presence of other allergic diseases ( HR=0.47, 95% CI: 0.37-0.61), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score ( HR=0.98, 95% CI: 0.97-1.00), WeChat management ( HR=0.77, 95% CI: 0.60-0.98), treatment efficacy ( HR=0.72, 95% CI: 0.56-0.92), age (5-17 years, HR=0.50, 95% CI: 0.36-0.71;≥60 years, HR=1.42, 95% CI: 1.08-1.87), household income (<5 000 CNY, HR=1.44, 95% CI: 1.09-1.90;>20 000 CNY, HR=0.66, 95% CI: 0.44-0.99), allergen types (single dust mite, HR=0.70, 95% CI: 0.49-0.93; and combined pollen or mold, HR=1.45, 95% CI: 1.02-2.04), and time to efficacy <3 months ( HR=0.73, 95% CI: 0.56-0.94), all P<0.05. At the third-year follow-up, the area under curve (AUC) for the nomogram model was 0.913 (95% CI: 0.881-0.943) in the training group and 0.886 (95% CI: 0.838-0.933) in the validation group. Calibration and decision curve analyses demonstrated the model′s consistency with actual dropout rates and clinical benefit in both groups. Additionally, a Brier score of 0.29 further confirmed the model′s predictive accuracy. Conclusion:We successfully develop a nomogram-based prediction model for SLIT dropout in AR patients, which could assist healthcare professionals in effectively identifying high-risk patients and facilitate the development of more personalized and timely treatment plans aimed at enhancing patient compliance.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by anorexia.Methods:This cross-sectional study included patients registered in the RealDTC study from May 2023 to December 2023. Demographic data, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnea questionnaire score, Clinical COPD Questionnaire (CCQ) score, forced expiratory volume in one second (FEV 1), forced expiratory volume in the first second predicted of percentage (FEV 1%pred), FEV 1/forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, GOLD group, number of acute exacerbations and hospitalizations in the past year, and score of the Functional Assessment of Anorexia Cachexia Therapy-Anorexia/Cachexia Subscale-12 (FAACT-A/CS-12) were collected. Patients with a FAACT-A/CS-12 score ≤30 were diagnosed as having anorexia. Multivariate logistic regression analysis was used to evaluate the influencing factors of anorexia in COPD patients. Results:A total of 617 COPD patients were included, of whom 109(17.7%) had anorexia. Compared with non-anorexia patients, COPD patients with anorexia had higher age, CAT, mMRC and CCQ scores, and more acute exacerbations and hospitalizations in the past year, while body mass index, FEV 1, FEV 1%pred and FEV 1/FVC were lower (all P<0.05). The proportions of patients with primary education or below, GOLD 3-4 grade and GOLD E group were higher in COPD patients with anorexia (all P<0.05). Logistic regression analysis showed that a CAT score of 10-<20 [odds ratio ( OR)=4.017, 95% confidence interval ( CI): 1.673-59.645], a CAT score of 20-<30 ( OR=9.686, 95% CI: 3.777-24.842), a CAT score of ≥30 ( OR=78.286, 95% CI: 7.654-800.689) and ≥1 hospitalization in the past year ( OR=2.050, 95% CI: 1.292-3.254) were independent risk factors for anorexia in COPD patients (all P<0.05). Conclusions:COPD patients with anorexia have poor lung function, high symptom burden and high risk of acute exacerbation. Clinicians should pay attention to the management of COPD patients with anorexia and take corresponding intervention measures.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by anorexia.Methods:This cross-sectional study included patients registered in the RealDTC study from May 2023 to December 2023. Demographic data, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnea questionnaire score, Clinical COPD Questionnaire (CCQ) score, forced expiratory volume in one second (FEV 1), forced expiratory volume in the first second predicted of percentage (FEV 1%pred), FEV 1/forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, GOLD group, number of acute exacerbations and hospitalizations in the past year, and score of the Functional Assessment of Anorexia Cachexia Therapy-Anorexia/Cachexia Subscale-12 (FAACT-A/CS-12) were collected. Patients with a FAACT-A/CS-12 score ≤30 were diagnosed as having anorexia. Multivariate logistic regression analysis was used to evaluate the influencing factors of anorexia in COPD patients. Results:A total of 617 COPD patients were included, of whom 109(17.7%) had anorexia. Compared with non-anorexia patients, COPD patients with anorexia had higher age, CAT, mMRC and CCQ scores, and more acute exacerbations and hospitalizations in the past year, while body mass index, FEV 1, FEV 1%pred and FEV 1/FVC were lower (all P<0.05). The proportions of patients with primary education or below, GOLD 3-4 grade and GOLD E group were higher in COPD patients with anorexia (all P<0.05). Logistic regression analysis showed that a CAT score of 10-<20 [odds ratio ( OR)=4.017, 95% confidence interval ( CI): 1.673-59.645], a CAT score of 20-<30 ( OR=9.686, 95% CI: 3.777-24.842), a CAT score of ≥30 ( OR=78.286, 95% CI: 7.654-800.689) and ≥1 hospitalization in the past year ( OR=2.050, 95% CI: 1.292-3.254) were independent risk factors for anorexia in COPD patients (all P<0.05). Conclusions:COPD patients with anorexia have poor lung function, high symptom burden and high risk of acute exacerbation. Clinicians should pay attention to the management of COPD patients with anorexia and take corresponding intervention measures.