This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective:To explore the clinical characteristics of patients with brucellosis complicated with epididymo-orchitis (Brucellar epididymo-orchitis, BEO), so as to provide reference for clinical diagnosis and treatment of BEO.Methods:General and clinical data of 293 male patients with acute brucellosis admitted to the Beidahuang Industry Group General Hospital from January 2023 to December 2024 were retrospectively collected. They were divided into a BEO group (30 cases) and a non-BEO group (263 cases) based on the presence or absence of epididymo-orchitis. Epidemic characteristics, clinical manifestations and laboratory examination results were compared and analyzed.Results:Among 293 male patients with acute brucellosis, the incidence of BEO was 10.24% (30/293). Their age was mainly concentrated in 45 - < 60 years old (53.33%, 16/30), and occupation was mostly farmers (63.33%, 19/30). There were no statistically significant differences in the distribution of age, occupation, exposure history and onset season between the BEO group and the non-BEO group ( P > 0.05). The distribution of abdominal pain and urinary frequency/urgency/pain symptoms was compared, and the differences were statistically significant ( P < 0.05). White blood cell count (WBC), neutrophil count (NEUT), and C-reactive protein (CRP) levels in the BEO group were higher than those in the non-BEO group ( P < 0.05), while the levels of cytokines interleukin (IL)-6 and interferon-γ (IFN-γ) were lower than those in the non-BEO group ( P < 0.05). After 6 - 8 weeks of hospitalization, the levels of WBC, NEUT, CRP, albumin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, α-hydroxybutyrate dehydrogenase, lactate dehydrogenase, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, and IFN-γ in patients of the BEO group were significantly different from before treatment ( P < 0.05). Twenty-eight patients were cured, 1 patient underwent orchiectomy, and 1 patient experienced recurrence. Conclusions:Middle-aged male patients with brucellosis are more prone to BEO. Clinical manifestations and laboratory tests have certain diagnostic value for BEO. Suspected BEO patients should be diagnosed and treated as early as possible to reduce the occurrence of adverse prognosis.

Objective To develop a graded early mobility implementation pathway for critically ill adult patients in tertiary hospitals in Beijing and to preliminarily validate its feasibility and effectiveness.Methods Based on the"goal-directed"early mobility concept,a graded early mobility implementation pathway for critically ill patients was developed through evidence synthesis and the Delphi method,consisting of 3 components:patient inclusion,mobility implementation,and mobility evaluation.Using convenience sampling,patients meeting inclusion criteria in the general ICU of a tertiary hospital in Beijing from October 2024 to January 2025 were selected as participants.Among them,25 patients admitted from December 2024 to January 2025 were assigned to an experimental group and received early mobility interventions following the developed pathway.25 patients admitted from October to November 2024 served as a control group and received routine ICU mobility care.Outcomes including diaphragm excursion,muscle strength,ICU length of stay,and adverse events were compared between the 2 groups.Results The graded early mobility pathway achieved an implementation rate of 70.05％in the experimental group,significantly higher than it in the control group(P＜0.001),without increasing adverse events.Post-intervention diaphragm excursion in the experimental group was significantly greater than that in the control group(P=0.018).Conclusion The developed graded early mobility implementation pathway for ICU patients demonstrates scientific rigor and clinical practicality.It provides a reference for the widespread and effective implementation of early mobility in ICUs,standardizing its clinical application.

Objective:To compare the safety and efficacy of 3D-printed porous bioceramic artificial bone and artificial bone substitutes in the treatment of limb bone defects.Methods:A total of 220 patients with post-traumatic limb bone defects admitted to Xijing Hospital Affiliated to Air Force Medical University of the Chinese People's Liberation Army (34 cases), the Third Hospital of Hebei Medical University (60 cases), Xi'an Honghui Hospital (28 cases), the Third Hospital of Southern Medical University (18 cases), Changsha Third Hospital (28 cases), Foshan Traditional Chinese Medicine Hospital (16 cases), Foshan Fuxing Chancheng Hospital (12 cases), and Henan Provincial Orthopaedic Hospital (24 cases) from May 2022 to October 2023 were included as research subjects. According to the manufacturing method of the bone graft material, the subjects were randomly divided into the 3D printed porous bioceramic artificial bone group (3D printing group) and the artificial bone substitute group (non-3D printing group) at a ratio of 1:1 by the envelope method. Adverse events that might be related to the surgery were selected through correlation evaluation and classified as abnormal laboratory indicators, systemic or other site symptoms and abnormalities, and local symptoms and abnormalities of the affected limb. The safety of the two groups was compared. The bone graft fusion rate, bone defect repair and healing rate, and short form 12 (SF-12) score of the two groups were calculated to evaluate the postoperative recovery.Results:Thirty-two cases were excluded (4 cases refused to use their data after reconsideration, 7 cases were not used after preoperative assessment, and 21 cases exceeded the standard for body mass index and laboratory indicators upon re-examination). A total of 188 cases were randomly divided into the 3D printing group and the non-3D printing group according to the random method, with 94 cases in each group. Among them, 11 cases in the 3D printing group and 9 cases in the non-3D printing group dropped out due to loss to follow-up. Finally, 168 cases completed the follow-up, including 83 cases in the 3D printing group and 85 cases in the non-3D printing group. In the 3D printing group, there were 53 males and 30 females, with an average age of 47.9±12.7 years; in the non-3D printing group, there were 53 males and 32 females, with an average age of 48.6±12.9 years. A total of 51 cases in the two groups experienced adverse events related to the surgery, including 13 cases of abnormal laboratory indicators (5 cases in the 3D printing group and 8 cases in the non-3D printing group), 15 cases of systemic or other site symptoms and abnormalities (9 cases in the 3D printing group and 6 cases in the non-3D printing group), and 23 cases of local symptoms and abnormalities of the affected limb (13 cases in the 3D printing group and 10 cases in the non-3D printing group). There was no statistically significant difference in the incidence of adverse events between the two groups ( P>0.05). The bone graft fusion rates of the 3D printing group and the non-3D printing group at 6 months after surgery were 99%(82/83) and 99%(84/85), respectively, and the bone defect repair and healing rates were 89%(74/83) and 89%(76/85), respectively. At the time of 12 months after surgery, the bone graft fusion rates were 99%(82/83) and 99%(84/85), respectively, and the bone defect repair and healing rates were 94%(78/83) and 92%(78/85), respectively. There was no statistically significant difference in the bone graft fusion rate and bone defect repair and healing rate between the two groups ( P>0.05). The SF-12 scores during the screening period were 27.82±2.96 points and 27.22±4.23 points in the 3D printing group and the non-3D printing group, respectively, and at 3 months after surgery were 28.08±3.13 points and 27.64±3.16 points, at 6 months after surgery were 29.42±3.10 points and 28.55±3.45 points, and at 12 months after surgery were 29.78±2.80 points and 29.58±2.94 points, respectively. There was no statistically significant difference between the groups ( P>0.05). Both groups of surgeries were successfully completed without any serious surgical or bone graft-related complications. Conclusion:The safety and efficacy of 3D-printed porous bioceramic artificial bone in the treatment of limb bone defects are not significantly different from those of currently clinically applied artificial bone substitutes.

Objective:To explore the latent categories of hospice care attitudes among nurses in a geriatric hospital and to analyze the characteristic differences among these categories.Methods:A total of 434 in-service nurses from Beijing Geriatric Hospital were selected by convenience sampling from April to May 2024. Data were collected using the general information questionnaire, the Chinese version of the Frommelt Attitude Toward Care of the Dying Scale Form B, the Self-Efficacy in Coping with Death Scale, and the General Well Being Schedule. Latent profile analysis was used to identify potential categories of hospice care attitudes, and Logistic regression analysis was conducted to examine influencing factors.Results:A total of 434 questionnaires were distributed, and 431 valid responses were received, with a valid response rate of 99.31% (431/434). The hospice care attitudes of the 431 nurses were categorized into two latent profiles: "negative attitude-low communication willingness type" (55.45%, 239/431) and "positive attitude-high caring type" (44.55%, 192/431). Logistic regression analysis showed that participating in palliative care continuing education within the past year, having discussed death with patients, perceiving difficulties in caring for dying patients, self-efficacy in coping with death, and subjective well-being were statistically significant influencing factors of the latent categories of hospice care attitudes ( P<0.05) . Conclusions:Hospice care attitudes among nurses in geriatric hospitals can be classified into two latent categories: "negative attitude-low communication willingness type" and "positive attitude-high caring type". These are influenced by many factors. Nursing administrators should develop targeted interventions to support nurses in coping with stressors effectively and improving the quality of life of terminally ill patients.

The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

BACKGROUND: Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment. METHODS: Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models. RESULTS: Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin ( OMD ), apolipoprotein A4 ( APOA4 ), and insulin like growth factor binding protein 6 ( IGFBP6 ) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells. CONCLUSIONS Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD , APOA4 , and IGFBP6  may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.
Machine Learning ; Humans ; Computational Biology/methods* ; Biomarkers/metabolism* ; Diabetes Mellitus, Type 2/genetics* ; Animals ; Mice ; Gluconeogenesis/physiology* ; Gene Expression Profiling ; Transcriptome/genetics* ; Gene Regulatory Networks/genetics* ; Clinical Relevance

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Animals ; Lung Neoplasms/metabolism* ; Chemokines, CC/antagonists & inhibitors* ; Mice ; Mice, Nude ; Drugs, Chinese Herbal/administration & dosage* ; Cell Line, Tumor ; Neoplasm Metastasis ; Tumor-Associated Macrophages/drug effects* ; Mice, Inbred BALB C ; Signal Transduction/drug effects*