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 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*

BACKGROUND:It has been confirmed that the mixing of decellularized matrix and polymer electrospinning can not only improve the structural properties of fibers,but also preserve the biological decellularized of decellularized matrix.However,there is no relevant report on the preparation of skin tissue engineering scaffolds by electrospinning polyurethane and decellularized skin matrix. OBJECTIVE:To investigate the reparative effect of a decellularized skin matrix/polyurethane blended fibrous scaffold on rat skin defects. METHODS:Polyurethane electrospun fibrous scaffold and decellularized skin matrix/polyurethane blended fibrous scaffold were fabricated using the electrospinning technique.The fiber structure was observed under scanning electron microscope.Rat adipose mesenchymal stem cells were inoculated on two kinds of scaffolds respectively.The morphology of the scaffolds was observed under scanning electron microscope.Three full-thickness skin defects of 1 cm×1 cm were fabricated on the back of 10 SD rats.Polyurethane electrospun fibrous scaffolds(control group)and decellularized skin matrix/polyurethane blended fibrous scaffolds(experimental group)were implanted in two of the defects,and no material was implanted in the remaining defects(blank control group).The skin wound healing was observed at 1,2,and 3 weeks after operation.At 3 weeks after implantation,the wound was stained with hematoxylin and eosin and the scar area was calculated. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two kinds of electrospun fibers were reticulated,and the rat adipose mesenchymal stem cells attached to the fibers on the two kinds of scaffolds,and the adhesion was good.(2)With the extension of the postoperative time,the skin wounds of each group gradually healed.By week 3 after the operation,the skin wounds of the experimental group and the control group were basically healed,and small ulcers could be seen on the wounds of the blank control group.Hematoxylin-eosin staining of skin wounds showed that the epidermal coverage of the wound was basically complete in the control group and the experimental group,and fibroblast growth and inflammatory cell infiltration could be seen in the dermis.In addition,the collagen fibers of the wound in the experimental group were abundant and arranged in a regular order,basically parallel to the epidermal surface.The wound epidermis of blank control group was still defective.The scar area of the experimental group was smaller than that of the other two groups(P<0.05,P<0.01).(3)These results indicate that the decellularized skin matrix/polyurethane blended fibrous scaffold can effectively repair full-thickness skin defects and improve scar formation in rats.

Objective To investigate the function and mechanism of miR-29 family in trauma induced coagulopathy(TIC).Methods Bioinformatics was used to analyze the targeting relationship between miR-29 family members and hepatocyte nuclear factor-4α(HNF-4α).HE staining results,TEG parameters and coagu-lation parameters were used to verify the TIC rat model construction.Real-time quantitative fluorescent PCR(RT-qPCR)and Western blot were used to detect the expression of miR-29 family,HNF-4α and coagulation factor Ⅹ(FⅩ)in rat liver tissues.Overexpression of miR-29b-3p(miR-29b-3p mimics)or silence of miR-29b-3p(miR-29b-3p inhibitor)was transfected into hepatocytes,and the levels of miR-29b-3p,HNF-4α and FⅩ in hepatocytes were detected by RT-qPCR and Western blot.Double lucifase reporter gene assay verified the targeted regulation of miR-29b-3p on HNF-4α.The miR-29b-3p mimics and/or HNF-4α overexpression vector were transfected into hepatocytes,and the levels of miR-29b-3p,HNF-4α and FⅩ in hepatocytes were detected by RT-qPCR and Western blot.Results Bioinformatic prediction results from the miRDIP database identified that multiple members of the miR-29 family(miR-29a-3p,miR-29b-3p,miR-29b-5p,and miR-29c-3p)contain potential binding sites with HNF-4α.Histopathological evaluation through HE staining,combined with TEG parameters and coagulation profiles,confirmed successful establishment of the TIC rat model.Quantitative analyses using RT-qPCR and Western blot revealed that compared to controls,both HNF-4α and coagulation FⅩ expression levels were markedly suppressed in the model group,while miR-29b-3p expression showed significant elevation in TIC rats(P＜0.01).In vitro functional studies demonstrated that neither overexpression nor silencing of miR-29b-3p significantly influenced hepatocyte proliferation(P＞0.05).How-ever,forced expression of miR-29b-3p effectively downregulated HNF-4α and its downstream target FⅩ,whereas miR-29b-3p knockdown substantially upregulated these molecules(P＜0.05).This regulatory rela-tionship was further validated by dual luciferase reporter assays confirming direct targeting between HNF-4α and miR-29b-3p.Notably,exogenous HNF-4α overexpression significantly rescued FⅩ suppression induced by miR-29b-3p overexpression(P＜0.05).Conclusion miR-29b-3p is up-regulated in TIC,which can promote the progression of TIC by targeting HNF-4α to regulate FⅩ expression.

Objective To construct nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)knockout mice in order to investigate the effects of NLRP3 knockout on radiation-induced acute pneumonitis and pulmonary fibrosis.Methods Nlrp3+/+and Nlrp3-/-mice were randomly divided into the control group and irradiation group.To induce radiation-caused acute pneumonitis,the control group was exposed to sham irradiation while the irradiation group was exposed to 60Co γ-rays at a dose of 22 Gy at a dose rate of 184.30 R/min.At 14 days post-irradiation,the body weight of each mouse and the wet weight of its lung tissue were measured separately using an analytical balance to calculate the lung coefficient.Quantitative real-time PCR(qPCR)and cytometric bead array(CBA)were used to detect inflammatory responses in lung tissues and serum.Hematoxylin-eosin(HE)staining and F4/80 immunohistochemical staining were used to assess pathological changes and inflammatory cell infiltration in lung tissues.Cysteinyl aspartate specific proteinase-1(caspase-1)activation was analyzed by Western blotting.To establish a model of radiation-induced pulmonary fibrosis,mice were irradiated with 60Co γ-rays at a dose of 18 Gy at a dose rate of 174.67 R/min.At 24 weeks post-irradiation,HE staining and Masson staining were performed to evaluate pulmonary fibrosis.Results NLRP3 knockout inhibited caspase-1 activation,reduced inflammatory responses in lung tissues and serum,suppressed macrophage infiltration,alleviated pulmonary edema,and thereby protected against acute radiation-induced lung injury.Additionally,NLRP3 knockout significantly ameliorated late-stage radiation-induced pulmonary fibrosis.Conclusion NLRP3 knockout can mitigate both early radiation-induced pneumonia and lateradiation-induced pulmonary fibrosis.

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.

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 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.

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 analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.