Objective:To summarize the clinical characteristics of patients with acute pancreatitis (AP) in plateau areas, and screen potential biomarkers for the pathogenesis of AP at high altitudes by metabolomics.Methods:A total of 42 patients with AP admitted to the Department of Gastroenterology in Lhasa People's Hospital from December 2023 to May 2024 were prospectively enrolled (AP group), and 33 healthy controls (Control group) were included during the same period. Demographic and clinical data were collected, and serum non-targeted metabolomics was performed based on ultra-performance liquid chromatography-mass spectrometry techniques. The serum metabolites map was evaluated by using principal component analysis, and a regression model with orthogonal partial least squares-discriminant analysis (OPLS-DA) was constructed to evaluate the explanatory power ( R2) and predictive power ( Q2) of these metabolites. The OPLS-DA-based dimensionality reduction was applied to compute variable importance in projection (VIP), while fold change (FC) values were used to assess the difference of metabolites between groups. A bidirectional clustering heat map was generated for samples and differential metabolites to evaluate sample similarity within groups. Additionally, a volcano plot was created to visualize differential metabolites, and the top five up-regulated and down-regulated metabolites distinguishing AP from healthy controls were selected. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC), sensitivity and specificity based on ROC analysis were calculated to evaluate the differential power of differential metabolites. Results:The majority of participants were Tibetans in both the AP group (37 cases, 88.1%) and the control group (27 cases, 81.8%). The average age of AP patients was (50.45±17.85) years old, and the male to female ratio was 1.1∶1.0. The leading etiology was biliary disease (33 cases, 78.6%), and most patients encountered moderately severe disease (26 cases, 61.9%). The incidence of local complications was 83.3%, mainly thoracoabdominal effusion and peripancreatic effusion (30 cases, 71.4%). The incidence of systemic complications was 59.5%, mainly systemic inflammatory response syndrome (22 cases, 52.4%) and respiratory failure (15 cases, 35.7%). Principal component analysis showed significant differences in serum metabolites between groups. OPLS-DA showed that these metabolites effectively distinguished AP patients from healthy controls: R2=0.992 and Q2=0.913 in the positive ion mode, R2=0.983 and Q2=0.914 in the negative ion mode. There were 450 up-regulated and 366 down-regulated differential metabolites in AP group, respectively. Among them, gamma-glutamylleucine, cortisone, 4(15)-Copaen-11-ol, mytiloxanthin, and indole-3-glycol aldehyde were the top five up-regulated metabolites, while N-Acetyltryptophan, kynurenic acid, deoxyuridine monophosphate, pseudouridine, and farnesyl acetate were the top five down-regulated metabolites. ROC analysis of these markers showed that all AUC values were >0.8, with all P values <0.001, with both sensitivity and specificity exceeding 80%. Among them, N-Acetyltryptophan and farnesyl acetate possessed the best differential performance. Conclusions:Biliary causes are most frequent among AP patients in plateau area. The disease severity is mainly moderately severe, accompanied by high incidences of local and systemic complications. Some amino acids and prenol lipids could significantly distinguish AP patients from healthy controls, and might be involved in the pathogenesis of AP at high altitudes.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

Objective:Currently, there is a lack of targeted training programs for resident physicians in cardiopulmonary resuscitation (CPR) in China. This study aims to establish a stratified training indicator system for resident physicians in CPR that is in line with the medical realities in China.Methods:Expert consultation questionnaires were designed through literature review, group discussions, and surveys. Two rounds of expert consultation were conducted using the modified Delphi method to develop the stratified training indicator system for resident physicians in CPR. Statistical analysis was performed using SPSS 26.0 software and Kendall's coefficient of concordance was used to assess the consistency of expert opinions.Results:A total of 15 experts participated in two rounds of questionnaire consultation, with a positive coefficient of 100.00% and an authority coefficient of 0.91, indicating high expert engagement and authority, thus ensuring the credibility of the results. The coefficient of variation for expert ratings in the first round of questionnaire consultation ranged from 0 to 0.40, with a concordance coefficient of 0.22 ( P<0.001). In the second round of questionnaire consultation, the coefficient of variation for expert ratings ranged from 0 to 0.24, with a concordance coefficient of 0.25 ( P<0.001). The Kendall's coefficient of concordance for expert opinions showed statistically significant differences in both rounds of questionnaire consultation, indicating consensus among experts and reliable results. This system consisted of 6 primary indicators and 32 secondary indicators. Conclusions:Based on the modified Delphi method, this study established a stratified training indicator system for resident physicians in CPR. In the future, based on the research findings, CPR training programs adapted to the medical realities in China will be developed and promoted to validate their scientific and practical value.

Polymyxin serves as the"last line of defense"for treating infection with multidrug-resistant Gram-ne-gative bacteria.However,the emergence and spread of polymyxin-resistant genes such as mcr-1 severely weakens its clinical efficacy.This paper systematically summarizes the antimicrobial and resistance mechanisms of polymy-xin,comprehensively summarizes the current research progresses in polymyxin sensitizers particular focusing on three aspects:natural compounds,synthetic small molecules,and drug repurposing.Furthermore,this paper explores the innovative strategies of gene intervention,new targets,and nanotechnology-based formulations in the develop-ment of sensitizer,aiming to provide systematic theoretical support and research ideas against polymyxin resistance.

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

Under the background of carbon peaking and carbon neutrality goals, the Ministry of Ecology and Environment, together with 15 national ministries and commissions, has formulated the Implementation Plan on Establishing a Carbon Footprint Management System, and it is urgent for traditional Chinese medicine(TCM) pharmaceutical enterprises to carry out research on carbon footprint accounting methods of related products. Based on the life cycle assessment(LCA) theory, taking mulberry leaf extract produced by a certain enterprise as an example, this study analyzed the carbon footprint of TCM extracts during the life cycle. The results show that for every 1 kg of product produced, the carbon emissions from the stages of raw material acquisition, transportation, and extract production are-20.569, 1.205, and 173.577 kgCO_2eq(CO_2 equivalent), respectively. The carbon footprint of the product is 154.213 kgCO_2eq·kg~(-1). In addition, the carbon emission is the highest in the production stage, in which the consumption of ethanol solvents makes the greatest contribution to the carbon footprint, accounting for 25.71%, more than one-fourth of the total carbon footprint. The second contribution was from the treatment process of TCM residues, accounting for 19.67%, closely followed by wastewater treatment(17.71%), the consumption of hot steam(17.43%), and drinking water(16.90%). The consumption of electric power and packaging materials has a smaller carbon emission of 2.58%. In particular, the carbon emission caused by the consumption of packaging materials is only 0.04%, which is negligible. The results of the study are expected to provide a reference for TCM enterprises to carry out research on the carbon footprint of products, offer ideas for collaborative innovation in reducing pollution and carbon emissions throughout the entire industry chain of TCM, and develop new quality productivity of modern TCM industry based on green and low-carbon manufacturing.
Morus/chemistry* ; Plant Leaves/chemistry* ; Carbon Footprint ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/analysis* ; Medicine, Chinese Traditional

This study explored the active ingredients for anti-angiogenesis in Wenyujin Rhizoma Concisum. Ten sesquiterpenoids were isolated from Wenyujin Rhizoma Concisum by silica gel column chromatography, thin layer chromatography, and high performance liquid chromatography. According to the results of multiple spectroscopic methods and circular dichroism, they were identified as wenyujinlactam A(1),(4S,7S)11-hydroxycurdione(2), 8,9-seco-4β-hydroxy-1α,5βH-7(11)-guaen-8,10-olide(3), curcumadione(4), phaeocaulisin E(5), procurcumadiol(6), zedouronediol(7), epiprocurcumenol(8), gajutsulactone A(9), and(7Z)-1β,4α-dihydroxy-5α,8β(H)-eudesm-7(11)-en-8,12-olide(10). Compounds 1 and 2 were new sesquiterpenoids. Compounds 1, 6, 8, and 10 can inhibit human umbilical vein endothelial cells(HUVEC) proliferation with IC_(50) values of 38.83, 45.19, 32.12, and 37.80 μmol·L~(-1), respectively. Compounds 1 and 10 can inhibit HUVEC migration with IC_(50) values of 29.70 and 36.48 μmol·L~(-1), respectively.
Sesquiterpenes/isolation & purification* ; Humans ; Drugs, Chinese Herbal/isolation & purification* ; Rhizome/chemistry* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Molecular Structure ; Cell Proliferation/drug effects*

Traditional Chinese medicine(TCM) processing is a specialized pharmaceutical technique with the primary objective of reducing the toxicity of medicinal substances. Euphorbia pekinensis, E. ebracteolata, and E. fischeriana, all belonging to Euphorbiaceae, are classified as drastic purgative herbs, traditionally used for eliminating retained water, reducing swelling, resolving toxicity, and dispersing masses. However, these herbs are also associated with adverse effects such as abdominal pain and diarrhea. Accordingly, they are commonly processed with vinegar, milk, or Terminalia chebula decoction to reduce the toxicity. This review summarizes the chemical constituents, pharmacological activities, historical evolution of processing methods, and detoxification mechanisms of the three toxic Euphorbia species. The primary toxic constituents are terpenoids. Specifically, E. ebracteolata and E. fischeriana are rich in diterpenoids, while E. pekinensis contains diterpenoids, triterpenoids, and sesquiterpenoids. Studies have shown that vinegar processing promotes structural transformations of diterpenoids, including ether bond hydrolysis, lactone ring opening, esterification, oxidation, and epoxide ring cleavage, thereby reducing the content and toxicity of these compounds. Milk processing facilitates the dissolution of toxic components into the residual liquid of excipients, leading to decreases in their concentrations in the final decoction pieces. Processing with T. chebula decoction raises the levels of tannin-derived phenolic acids, which antagonize the adverse effects of the intestine. These findings reveal a shared detoxification pattern among the three toxic herbs. Accordingly, this review proposes the concept of a shared detoxification mechanism for toxic herbs belonging to the same family or genus. That is, toxic herbs belonging to the same taxon often exhibit similar toxicological profiles and can undergo detoxification through the same processing methods, reflecting common underlying mechanisms. Investigating such shared mechanisms across multiple species of the same genus offers a promising research strategy. Ultimately, the research into processing-induced detoxification mechanisms provides both theoretical and practical support for ensuring the safety of toxic TCM.
Euphorbia/classification* ; Drugs, Chinese Herbal/metabolism* ; Humans ; Animals ; Inactivation, Metabolic ; Medicine, Chinese Traditional

Objective:To explore the risk factors for in-hospital death after complete recanalization by mechanical thrombectomy and establish a risk prediction model in patients with acute large vessel occlusion stroke of the anterior circulation.Methods:A total of 468 patients with anterior circulation acute large vessel occlusion stroke who underwent mechanical thrombectomy in Stroke Center (Second Affiliated Hospital of Dalian Medical University), Department of Interventional Therapy (First Affiliated Hospital of Dalian Medical University), and Department of Neurointervention and Neurocritical Care (Central Hospital Affiliated to Dalian University of Technology) from January 2016 to November 2023 were selected. All patients achieved complete recanalization (modified thrombolysis in cerebral infarction: grading 3) immediately after thrombectomy. The clinical data, laboratory and imaging results of the patients were collected, and these patients were divided into in-hospital death group ( n=52) and in-hospital survival group ( n=416) according to occurrence of in-hospital death (all-cause death). Univariate analysis and multivariate Logistic regression analysis were used to screen the risk factors for in-hospital death, and a risk prediction model was constructed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the model, calibration curve and Hosmer-Lemeshow test were used to evaluate the accuracy of the model, and decision curve was used to evaluate the clinical utility of the model. Results:Univariate analysis showed that the in-hospital death group had significantly higher proportions of female patients, patients with atrial fibrillation, and patients with symptomatic intracranial hemorrhage compared with the in-hospital survival group (50.0% vs. 31.3%; 57.7% vs. 41.6%; 38.5% vs.11.8%), and significantly higher baseline blood glucose, and National Institutes of Health Stroke Scale score, neutrophil count, and neutrophil/lymphocyte ratio within 24 hours of thrombectomy (8.10 [7.05, 11.79] vs. 7.31[6.46, 9.25], 20 [16, 32] vs. 15 [10, 22], 10.09 [7.87, 13.19] vs. 8.47 [6.73, 10.32], 10.63 [5.87, 15.69] vs. 7.13 [5.16, 10.91], P<0.05). Multivariate Logistic regression analysis showed that female ( OR=2.533, 95% CI: 1.306-4.910, P=0.006), atrial fibrillation history ( OR=1.999, 95% CI: 1.044-3.827, P=0.037), neutrophil count within 24 hours of thrombectomy ( OR=1.162, 95% CI: 1.055-1.279, P=0.002), and symptomatic intracranial hemorrhage ( OR=4.066, 95% CI: 1.897-8.718, P<0.001) were independent risk factors for in-hospital death after complete recanalization; risk prediction model, accordingly, was 0.929×female+0.692×atrial fibrillation history+0.150×neutrophil count+1.403×symptomatic intracranial hemorrhage-5.349 ( P: probability of event occurrence). Area under ROC curve of the model was 0.765 (95% CI: 0.689-0.842, P<0.001); calibration curve and Hosmer-Lemeshow test of the model showed good accuracy ( χ2=7.656, P=0.468); decision curve of the model showed good clinical utility at threshold probability of 0.05-0.90. Conclusion:For patients with acute large vessel occlusion stroke at the anterior circulation complicated with atrial fibrillation, symptomatic intracranial hemorrhage or elevated neutrophil count within 24 hours of thrombectomy, or female patients with acute large vessel occlusion stroke at the anterior circulation, in-hospital death still needs to be highly alert after complete recanalization by mechanical thrombectomy.

Objective To explore the role of the protein kinase R-like endoplasmic reticulum kinase(PERK)-mediated endoplasmic reticulum stress pathway in a model of lipopolysaccharide(LPS)-induced microglia inflammation.Methods To investigate its effects on endoplasmic reticulum(ER)stress,an inflammation model of microglia was established by stimulating with LPS at gradient concentrations for 24 hours and with 1 mg/L LPS for different durations.Cell viability was assessed by the CCK-8 assay;The mRNA and protein expression levels of related inflammatory factors were measured by Real-time PCR and ELISA kits.Cellular oxidative stress was evaluated by detecting reactive oxygen species(ROS),and Real-time PCR and Western blotting were used to examine the mRNA and protein expression levels of ER stress pathway markers associated with inflammation.Results 1.The effects of different concentrations of LPS on cell viability and morphology were not statistically significant after acting on BV-2 cells for 24 hours(P＞0.05);2.1 mg/L LPS incubated with BV-2 cells for different times and the cell viability decreased with the increase of time;3.Compared with the 0 hour group,the levels of pro-inflammatory cytokine interleukin(IL)-1β,tumor necrosis factor-α(TNF-α)mRNA and protein expression increased significantly(P＜0.05)in the LPS-stimulated 9 hours,12 hours,and 24 hours groups,and the inflammation model was successfully established;4.Compared with the 0 hour group,the protein and mRNA expression levels of the endoplasmic reticulum stress pathway-related indexes in the LPS-stimulated 9 hours,12 hours,and 24 hours groups increased significantly(P＜0.01),which showed the time-dependence;5.After adding the PERK inhibitor GSK2606414,the mRNA and protein expression levels of endoplasmic reticulum stress-related indicators in the PERK inhibitor group were significantly reduced compared with those in the LPS group(P＜0.05);6.The mRNA and protein expression levels of pro-inflammatory cytokines and the fluorescence intensity of ROS in the PERK inhibitor group were significantly reduced compared with those in the LPS group(P＜0.01).Conclusion Targeting PERK-mediated endoplasmic reticulum stress inhibits LPS-induced inflammatory responses in microglia.