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

This study investigated the functions and regulatory mechanism of Portulacae Herba and its chemical components on the Toll-like receptor 4(TLR4)/myeloid differentiation primary response 88(MyD88)/nuclear factor kappa B(NF-κB) inflammatory signaling pathway in the colon tissue of mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC). A total of 35 mice were randomly divided into groups, including a blank group, a model group, a mesalazine group(0. 5 g·kg~(-1)), and low, medium,and high dose alkaloids from Portulacae Herba groups(9, 18, 36 mg·kg~(-1)), and a combination treatment group, with 5 mice in each group. The blank group was given purified water, while the other groups were continuously given a 3% DSS solution for 7 days to induce the UC model. From day 8 onwards, the treatment group received oral gavage according to the prescribed doses for 14 days. The overall condition, body weight, stool characteristics, and presence of blood in the stool were recorded daily. After the experiment, the disease activity index(DAI) was assessed for each group, and colon length was measured. Histopathological changes in colon tissue were examined using hematoxylin-eosin(HE) staining. The levels of pro-inflammatory cytokines, tumor necrosis factor-α(TNF-α),and interleukin-1β( IL-1β) in serum were measured by enzyme-linked immunosorbent assay( ELISA). The protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were measured using Western blot and quantitative real-time PCR(qPCR).Compared to the blank group, the model group showed a significant decrease in body weight, a notable increase in DAI scores, a significant shortening of colon length, and evident histopathological damage. The levels of inflammatory cytokines TNF-α and IL-1β in the serum were significantly elevated, and the protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were significantly up-regulated. In contrast, the alkaloids from Portulacae Herba treatment groups significantly improved symptoms and reduced body weight loss in mice, decreased DAI scores, alleviated colon shortening, lowered serum levels of TNF-α and IL-1β,significantly down-regulated the expression levels of TLR4, MyD88, and NF-κB proteins and genes in colon tissue, as well as reduced histopathological damage. Therefore, the study suggests that alkaloids from Portulacae Herba can alleviate intestinal inflammation damage in DSS-induced UC mice, with its mechanism involving the TLR4/MyD88/NF-κB signaling pathway.
Animals ; Colitis, Ulcerative/immunology* ; Toll-Like Receptor 4/immunology* ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Male ; Alkaloids/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Female ; Colon/metabolism* ; Disease Models, Animal

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

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: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 Exploring the clinical diagnosis and treatment status of epilepsy patients at the epilepsy specialty clinic in a single-center comprehensive hospital in the Lhasa area of the Tibetan Plateau.Methods Epilepsy patients who visited the epilepsy specialty clinic of the Department of Neurology at the Tibet Autonomous Region People's Hospital from September 2021 to June 2023 were continuously enrolled.Data such as clinical characteristics and diagnosis and treatment conditions of the enrolled patients was analyzed.Results A total of 121 patients were enrolled in this study,with 33.9%(41/121 cases)being new patients at our hospital and 6.6%(8/121 cases)being referred to our hospital.Non-adherence to treatment,with patients self-reducing or stopping medication without medical advice,accounted for 8.3%(10/121 cases)of the cases.The majority of epilepsy patients were in the young and middle-aged group,with 51.2%(62/121 cases)being between 18 and 44 years old.There were significant differences in the distribution of epilepsy patients across different age groups(P<0.001),while there was no significant difference in gender distribution(49.6%male vs.50.4%female,P>0.05).Generalized seizures were the predominant type of seizure(75.2%,91/121 cases),and 73.6%(89/121 cases)of the patients had an unknown etiology for their epilepsy,with symptomatic epilepsy accounting for 26.4%(32/121 cases)and structural causes being the most common at 24.8%(30/121 cases).Monotherapy was the main treatment for epilepsy(55.4%,67/121 cases),with sodium valproate being the most frequently prescribed drug for monotherapy at 22.3%(27/121 cases).Conclusion In the epilepsy specialty clinic in the plateau region,newly diagnosed patients account for about one-third,and over one-tenth of revisiting patients have not been receiving standardized treatment.The majority of our epilepsy patients are young to middle-aged adults.Generalized seizures are the predominant type.The etiology is unknown in the majority of cases,with structural causes being a common etiology in symptomatic epilepsy.Sodium valproate is the most frequently used antiseizure medication(ASM)in monotherapy in the plateau area.

Aim To investigate the protective effects and potential mechanisms of Radix Angelica sinensis and Radix Hedysari ultrafiltrate(RAS-RH)on X-ray-induced cellular damage in Raw264.7 macrophages.Methods An integrated approach combining network pharmacology,molecular docking,and bioinformatics a-nalysis was employed to predict therapeutic targets and signaling pathways of RAS-RH in coronary heart dis-ease(CHD).Subsequent in vitro validation was per-formed using an X-ray(6 Gy)-induced macrophage in-jury model with four experimental groups:control,radi-ation-only model,and three RAS-RH-treated groups at varying concentrations.Cell viability was assessed by CCK-8 assay,apoptosis by flow cytometry with Annexin V-FITC/PI staining,mitochondrial membrane potential by JC-1 fluorescence,and inflammatory cytokine levels(IL-1 β,IL-6,IL-18,TNF-α)by ELISA.Molecular mechanisms were investigated through Western blot and qRT-PCR analyses of TLR4/NLRP3/Caspase-1 sig-naling pathway components and Bcl-2 family proteins.Results Network pharmacology revealed RAS-RH's multi-target action on apoptosis and inflammation-relat-ed pathways,particularly NF-κB and Bcl-2 signaling.Molecular docking identified strong binding affinities between RAS-RH components and TLR4/NLRP3 pro-teins.In vitro studies demonstrated that RAS-RH treat-ment significantly improved cell viability(P＜0.01),reduced apoptosis(P＜0.01),restored mitochondrial membrane potential(P＜0.05),and attenuated radia-tion-induced ultrastructural damage including mem-brane disruption and cytoplasmic vacuolization.ELISA showed marked suppression of pro-inflammatory cyto-kines(P＜0.01).Transmission electron microscopy(TEM)analysis revealed that RSA-RH ameliorated pyroptosis-associated ultrastructural alterations,inclu-ding plasma membrane disruption and cytoplasmic vac-uolization.Protein and gene expression analyses con-firmed downregulation of TLR4/NLRP3/Caspase-1 pathway and modulation of Bcl-2/Bax ratio.Conclu-sion RAS-RH exerts radioprotective effects through dual regulation of pyroptosis and apoptosis pathways,suggesting its potential as an adjuvant therapy for radia-tion-induced cardiovascular complications in CHD pa-tients.

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.

Objective:To explore the correlation between ASXL1 gene mutation characteristics and clinical manifestations and prognosis in patients with myelodysplastic syndrome(MDS).Methods:The clinical date of 264 patients with MDS in Xuzhou Central Hospital,Southeast University from August 2010 to April 2024 was retrospectively analyzed.The patients were divided into ASXL1wt group and ASXL1mut group according to the presence of ASXL1 gene mutation,and the correlation between gene mutation characteristics and clinical manifestations and prognosis was analyzed.Results:Compared with ASXL1wt group,the ASXL1mut group had a higher age of onset(P＜0.05),a higher proportion of males(P＜0.05),while the incidence of del(5q)was lower(P＜0.01).The mutation frequency of ASXL1 in MDS patients was 21.97％,and most of them were frameshift mutations.The p.Gly646fs was the most common amino acid variant,with a mutation frequency of 20.69％.The median overall survival(OS)and leukemia-free survival of patients with this sequence variant was 18.1 and 23.8 months,respectively,while in those without this sequence variant was 30 months and not reached,and the differences were statistically significant(P＜0.05).The results of multivariate analysis showed that the mutation of NRAS,WT1,KIT gene and the p.Gly646fs sequence mutation of ASXL1 gene were independent prognostic factors for OS in ASXL1mut patients.The median OS of ASXL1wt and ASXL1mut patients was 27.9(21.3-40.4)and 23.7(18.6-NA)months,respectively(P＞0.05).Among 58 ASXL1mut patients,5 cases(8.6％)transformed to acute leukemia,including 3 cases with RUNX1 mutation and 3 cases with TET2 mutation.Among 206 ASXL1wt patients,28 cases(13.6％)transformed to acute leukemia.The difference in leukemia transformation rate between the two groups was not statistically significant(P＞0.05).The efficacy of different treatment regimens was similar in the ASXL1mut group,while in the ASXL1wt group,patients receiving allogeneic hematopoietic stem cell transplantation had a significantly better prognosis than those receiving other treatment regimens(P＜0.001).The overall response rate to demethylation therapy was 68.7％and 67.6％in ASXL1mut and ASXL1wt group,respectively,and the difference between the two groups was not significant(P＞0.05).Conclusion:The overall survival of MDS patients with ASXL1mut is poor.The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis.There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group.ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.