PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

This study aims to explore the role and mechanism of CXC chemokine receptor 3 (CXCR3) in cisplatin-induced skeletal muscle atrophy. Wild-type mice were divided into two groups: cisplatin group and control group (treated by normal saline). The results showed that, compared to the control group, the expression levels of CXCR3 mRNA and protein were significantly up-regulated in the skeletal muscle of the cisplatin group, suggesting that CXCR3 may play an important role in the model of cisplatin-induced skeletal muscle atrophy. To further investigate its role and potential mechanisms, CXCR3 knockout mice and wild-type mice were treated with cisplatin to induce skeletal muscle atrophy. The results revealed that CXCR3 knockout not only failed to alleviate cisplatin-induced skeletal muscle atrophy, but also further reduced body weight, skeletal muscle mass, and muscle fiber cross-sectional area. Further analysis showed that, in the cisplatin-induced muscle atrophy model, CXCR3 knockout significantly up-regulated the expression levels of E3 ubiquitin ligases in skeletal muscle and down-regulated the expression levels of myogenic regulatory factors. To explore the molecular mechanism by which CXCR3 gene deletion exacerbated cisplatin-induced skeletal muscle atrophy, transcriptomic sequencing was performed on the atrophied skeletal muscles of wild-type and CXCR3 knockout mice. The results showed that, compared to wild-type mice, 14 genes were significantly up-regulated and 12 genes were significantly down-regulated in the skeletal muscle of CXCR3 knockout mice. Gene set enrichment analysis (GSEA) revealed a significant enrichment of genes related to fatty acid β-oxidation. Quantitative real-time PCR validation results were consistent with the transcriptomic sequencing results. These findings suggest that CXCR3 may counteract cisplatin-induced skeletal muscle atrophy by up-regulating E3 ubiquitin ligases, down-regulating myogenic regulatory factors, and enhancing the recruitment of fatty acid β-oxidation-related genes.
Animals ; Cisplatin/adverse effects* ; Muscular Atrophy/physiopathology* ; Mice ; Receptors, CXCR3/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; Mice, Knockout ; Oxidation-Reduction ; Fatty Acids/metabolism* ; Muscle, Skeletal/metabolism* ; Mice, Inbred C57BL ; Male

Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopaminergic neurons in the midbrain substantia nigra. This study aimed to investigate the effects of exercise preconditioning on motor deficits and mitochondrial function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sedentary + saline (SS), sedentary + MPTP (SM), exercise + saline (ES), and exercise + MPTP (EM) groups. Mice in the ES and EM groups received 4 weeks of treadmill training, and then SM and EM groups were treated with MPTP for 5 days. Motor function was assessed by behavioral tests, and morphological and functional changes in dopaminergic neurons and mitochondria in the substantia nigra of the midbrain were evaluated using immunohistochemistry, Western blot, and transmission electron microscopy technology. The results showed that, compared with the SM group, the EM group exhibited significantly improved motor ability, up-regulated protein expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the midbrain, and down-regulated protein expression of α-synuclein (α-Syn) in the mitochondria of substantia nigra. Compared with the SM group, the EM group showed up-regulated protein expression levels of mitochondrial fusion proteins, including optical atrophy protein 1 (OPA1) and mitofusin 2 (MFN2), and biogenesis-related proteins, including peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), while the protein expression levels of dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1) were significantly down-regulated. Compared with the SM group, the EM group showed significantly reduced damage to substantia nigra mitochondria, restored mitochondrial membrane potential and ATP production, and decreased levels of reactive oxygen species (ROS). These results suggest that 4-week treadmill pre-training can alleviate MPTP-induced motor impairments in PD mice by improving mitochondrial function, providing a theoretical basis for early exercise-based prevention of PD.
Animals ; Male ; Physical Conditioning, Animal/physiology* ; Mice ; Mice, Inbred C57BL ; Mitochondria/physiology* ; Dopaminergic Neurons ; MPTP Poisoning/physiopathology* ; Substantia Nigra ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Based on the regulation of mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway, this study investigated the effect of Jianpi Qinghua Formula on the mitochondrial fatty acid β-oxidation pathway in the livers of mice with metabolic-associated fatty liver disease(MAFLD) induced by a high-fat diet. MAFLD mice were fed a high-fat diet to establish the model, and after successful modeling, the mice were divided into the model group, the Jianpi Qinghua Formula group, and the metformin group, with an additional control group. Each group was treated with the corresponding drug or an equivalent volume of saline via gavage. Body mass and food intake were measured regularly during the experiment. At the end of the experiment, blood lipid levels and liver function-related indices were measured, liver pathological changes were observed, and protein expression levels of PGC1α, PPARα, PPARγ, and CPT1A were detected by Western blot. The results showed that, with no difference in food intake, compared to the model group, the body mass of the Jianpi Qinghua Formula group and the metformin group was reduced, liver weight and liver index decreased, and levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol(LDL-C) were lowered. Additionally, a decrease in alanine aminotransferase(ALT) and aspartate aminotransferase(AST) was observed. Hematoxylin and eosin(HE) staining revealed reduced pathological damage to hepatocytes, while oil red O staining showed improvement in fatty infiltration. The liver disease activity score decreased, and transmission electron microscopy revealed improvement in mitochondrial swelling and restoration of internal cristae. Western blot analysis indicated that Jianpi Qinghua Formula significantly increased the expression of PGC1α, PPARα, and CPT1A proteins in the liver and reduced the expression of PPARγ. These results suggest that the Jianpi Qinghua Formula improves mitochondrial function, promotes fatty acid oxidation, and alleviates the pathological changes of MAFLD. In conclusion, Jianpi Qinghua Formula can improve MAFLD by mediating mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway.
Animals ; PPAR alpha/genetics* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Carnitine O-Palmitoyltransferase/genetics* ; Male ; Liver/metabolism* ; Fatty Liver/genetics* ; Humans ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects*

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*

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Objective To analyze the metabolic changes of myocardial tissue in rats under acute exposure to macleaya cordata by gas chromatography mass spectrometry(GC-MS),explore forensic identifications of its characteristic metabolites,and verify its toxicological mechanism in poisoning cases.Methods The rats in the exposure group were given 382 mg/kg macleaya extract solution by gavage,and the rats in the control group were given the same dose of solvent.The myocardial samples were analyzed by GC-MS,and pattern recognition was conducted through partial least squares discriminant analysis(PLSDA).The differential metabolites with characteristic changes were identified by variable importance projection(VIP value＞1)and Student's t test(P＜0.01).Results Compared with the control group,21 potential characteristic metabolites were identified.Through KEGG pathway enrichment analysis,it was found that these metabolites were mainly involved in the pathways of glycine,serine and threonine metabolism;pyruvate metabolism and glycerolipid metabolism.Conclusion Through the study of myocardial metabolism in rats exposed to macleaya cordata,we found the information on metabolites closely related to poisoning,which provides new insight and reference for studies on the mechanisms of macleaya cordata poisoning in the field of forensic medicine.