PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.

Objective To rapidly identify and assign the chemical components in Sugemule-4 decoction by using UPLC Orbitrap Exploris MS/MS,and then conduct network pharmacological analysis,and clarify the anti-insomnia effect of Sugmule-4 decoction.Methods ACQUITY UPLC BEH C18(2.1 mm×100 mm,1.7 μm)Chromatographic column,with 0.1％formic acid aqueous solution(A)-0.1％formic acid acetonitrile solution(B)as mobile phase gradient elution.Flow rate:0.5 mL·min-1,injection volume:5 μL.Under the control of the control software(Xcalibur,Thermo Fisher Scientific),the primary and secondary mass spectrometry data are collected based on the FullScan-ddMS2 function.Combined with the self-built database and online database,the chemical components in Sugemule-4 decoction are identified by accurate relative molecular weight,fragment ion information,pyrolysis pattern and comparison of control samples.The identified chemical components were analyzed by network pharmacology,and the targets of drug and insomnia were obtained from TCMSP,SwissTargetPrediction,GeneCards,OMIM,TTD,DrugBank and DisGeNET databases respectively,and the intersection target was obtained;Protein interaction analysis was performed through STRING database.Use Metascape platform to analyze GO function and KEGG pathway,and predict the mechanism of Sugmule-4 decoction in treating insomnia.To determine the anti-insomnia effect of Sugmule-4 decoction,SD rats were divided into normal control group(K),model group(M),Sugmule-4 decoction group(S)and Anshenbunao liquid group(A).After chronic unpredictable mild stress and PCPA were used for modeling,the rats were given corresponding drugs by gavage for 7 days,then the open field text was conducted to observe the general state and behavioral changes,and detection of AChE,5-HT,and GABA levels in serum and brain tissue of rats in each group using ELISA method.Results 136 components were identified from Sugemule-4 decoction,including 37 terpenoids,34 alkaloids,26 flavonoids,20 phenylpropanoids,14 phenolic acids and 5 amino acids.The results of network pharmacology analysis show that the mechanism of Sugemule-4 decoction in treating insomnia is mainly achieved by its components such as Romucosine D,Nornantenine,Nuciferine,and(R)-ar Turbone acting on targets such as ACHE,ADORA2A,and CHRM1 through signal pathways such as Neuroactive ligand-receptor interaction,synaptic signaling,and trans synaptic signaling.This is a multi component-multi target-multi signal pathway joint implementation process.The results of pharmacodynamic experiment showed that Sugmule-4 decoction and Anshenbunao liquid could revise the general state and behavioral changes of insomnia model rats,increase the content of AChE,5-HT and GABA in serum(P<0.01).Conclusion This study comprehensively reflects the chemical components of Sugmule-4 decoction,and preliminarily summarizes the mass spectrum decomposition characteristics of various chemical components.The network pharmacology and pharmacodynamics experiments show that Sugmule-4 decoction has significant anti-insomnia effect,which provides a reference basis for the quality control and mechanism study of Sugmule-4 decoction.

Objective:Considering the large amount and poor quality of clinical data, this study aims to explore the establishment of high-quality research database and its role in real-world research by taking the establishment of lymphoma research database as an example.Methods:The expert opinions in the field of lymphoma were collected, and the relevant guidelines and standards were referenced to establish a standard medical knowledge dataset. The electronic diagnosis and treatment data of lymphoma patients treated in Peking University Cancer Hospital from February 2005 to December 2020 were retrospectively extracted, the deep Learning, natural language processing were adopted to build a dynamic intelligent information integration and processing system of " lymphoma database based on electronic medical record system - biological sample information database - extended genetic information database" .Results:The research database not only meets the research needs of clinical researchers, but also realizes the management of traces in the whole process of application, approval, traceability and analysis of hospital medical record data and biological sample data. The total number of research variables in the database was 668, and the structured variables accounted for 46.0%. On December 25, 2021, there were 68 687 lymphoma patients in the database, the ratio of male to female patients was 8/9, and the proportion of patients with ≥3 visits accounted for 23.0%. In addition, researchers can superimpose searches in the database according to the target conditions, display the targeted medical records according to research hypothesis, and then establish a research cohort, conducting statistical modeling, and mining data information.Conclusions:By integrating management processes and using new natural language artificial intelligence technology to establish a high-level evidence-based database, it is helpful for the interconnection and resource sharing of hospital information systems, so as to achieve the purpose of providing reliable and detailed data for real-world research.

The three-day-old female infant was admitted to the hospital due to respiratory distress after birth. She was born premature at 36⁺² weeks gestational age. Prenatal ultrasound suggested abnormal development of the fetal liver vessels, and she had dyspnea that required respiratory support after birth. Chest X-ray indicated an enlarged cardiac silhouette, and cardiac ultrasound revealed enlargement of the right atrium and right ventricle. Diagnosis of hepatic hemangioma with arteriovenous fistula was confirmed through liver ultrasound and abdominal enhanced CT. At 19 days old, she underwent ligation of the hepatic artery under general anesthesia, which led to an improvement in cardiac function and she was subsequently discharged. Genetic testing revealed a mutation in the ACVRL1 gene, which was inherited from the mother. The article primarily introduces a case of neonatal heart failure caused by hepatic hemangioma with arteriovenous fistula, and multi-disciplinary diagnosis and treatment of this disease.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Activin Receptors, Type II ; Arteriovenous Fistula/complications* ; Dyspnea ; Heart Failure/etiology* ; Hemangioma/complications* ; Liver

Background/Aims:  Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods:  From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.
Mice ; Animals ; Depression/etiology* ; Antidepressive Agents/pharmacology* ; Brain-Derived Neurotrophic Factor ; Serotonin