BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Objective To analyze the combined effect of body mass index(BMI)and age with cancer occurrence among a hypertensive population in Minhang District,Shanghai.Methods Participants of this study were 212 394 hypertensive patients without cancer in Minhang District,Shanghai,registered in the electronic health information system from 2007 to 2015.Age and BMI were included as smoothing functions in the generalized additive Cox proportional risk model.The bivariate response model was constructed to visualize results using surface plots and to comprehensively analyze the association of BMI and age with the risk of cancer occurrence.Results A total of 22 141 participants developed cancer by Dec 31,2018.The association between age and the risk of cancer incidence showed an overall linear trend while the association between BMI and the risk of cancer incidence showed an overall"U"shape.BMI at about 26 kg/m2 showed the lowest risk of cancer incidence.The risk of cancer occurrence increased with increasing age in people with different BMIs.The associations between BMI and the risk of cancer incidence were different at different age groups:there was no significant association between BMI and the risk of cancer incidence in the young people(20-44 years).While in the middle-aged and older people aged over 45 years,BMI was associated with the risk of cancer incidence in a"U"shape.The lowest risk of cancer incidence was around the BMI of 26 kg/m2.Conclusion BMI among the population with hypertension should be controlled in a reasonable range,especially in the middle-aged and older population,to prevent cancer occurrence.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Chalcone/analogs & derivatives* ; Quinones/pharmacology* ; Pyroptosis/drug effects* ; Caspase 1/metabolism* ; Glucose ; Phosphate-Binding Proteins/metabolism* ; Signal Transduction/drug effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Oxygen/metabolism* ; Cytokines/metabolism* ; Gasdermins

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.
Humans ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B/drug therapy* ; Hepatitis B virus ; Antiviral Agents/therapeutic use* ; Gastroenterology

Objective To investigate the hotspots and trends in research related to nanotechnology applications in sepsis from 1996 to 2023.Methods Sepsis-related nanotechnology literature was sourced from the Web of Science core databases,with key metrics like publication count,citations,and various collaborations(author,institutional,national)analyzed.The data,including co-occurring keywords,were visualized using the CiteSpace tool.Results From 1996 to 2023,a total of 1 271 publications on nanotechnology in sepsis were retrieved,demonstrating a significant increase in both studies and citations,with the annual publication rate growing from 1 in 1996 to 205 in 2022,averaging an 23.7％ growth rate.From 1996 to 2006,the number of articles issued showed a slow upward trend,and the overall trend tends to be stable.From 2006 to 2023,a rapid growth in publications peaked in 2022 with 205 articles.The Chinese Academy of Sciences(CAS)leads the list of institutions with the highest number of publications,with a total of 32 papers.While the most prolific author was Amin with 14 publications.China was the most productive country with 430 publications(33.8％)and 7 539 citations,followed by the United States with 276 publications and 9 859 citations.India,South Korea and Germany followed.The research hotspots,indicated by keyword clusters like "composites""activation""capture""infection""drug delivery""sensor" and "biomarkers".The research hotspots are mainly in the diagnostic and therapeutic areas.Conclusions Nanotechnology holds great promise in facilitating sepsis treatment,and research hotspots nanomaterials are shifting from traditional antimicrobial and immunomodulatory properties of nanomaterials to the development of multifunctional nanocomplexes targeting diverse pathological mechanisms in sepsis.This transition underlines the expanding role of nanomaterials in this field.Despite their growing influence,current research is predominantly led by independent scholars,lacking extensive national and inter-institutional collaborations,which limits its impact.It is recommended to strengthen the cooperation and communication between domestic and foreign researchers to promote the scientific and standardized development of nanotechnology application in sepsis.

Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ²=3.663，P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ²=8.711, P=0.003 and χ²=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ²=3.386，P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ²=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ²=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.
Humans ; Anastomosis, Roux-en-Y ; Retrospective Studies ; Cohort Studies ; Esophagitis, Peptic ; Quality of Life ; Propensity Score ; Gastrectomy/methods* ; Esophagogastric Junction/surgery* ; Anastomosis, Surgical/methods* ; Adenocarcinoma/pathology* ; Stomach Neoplasms/pathology* ; Postoperative Complications ; Treatment Outcome