BACKGROUND: Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. METHODS: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. RESULTS: GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. CONCLUSIONS The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans ; Parkinson Disease/mortality* ; China/epidemiology* ; Global Burden of Disease ; Male ; Incidence ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Quality-Adjusted Life Years ; Aged, 80 and over ; Cost of Illness ; Adolescent ; Pattern Analysis, Machine

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Background In the Global Burden of Disease research, it has been found that atmospheric fine particulate matter (PM_2.5) pollution significantly harms human health. Currently, there is limited research on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) that exhibit high toxicity effects in PM_2.5 . Objective By studying the spatiotemporal distribution and variation characteristics of PCDD/Fs in PM_2.5 in Pudong area of Shanghai, to assess the associated population health risk. Methods This study set up 28 sampling points in Pudong area. One sample of PM_2.5 was collected during winter (February 2022) and summer (July 2022) at each site, with a sampling period lasting 24 h. The concentration of PM_2.5 was measured by membrane filter method, and the content of 17 kinds of 2,3,7,8-substituted chlorinated PCDD/Fs in the samples was analyzed using isotope dilution. Seasonal variations (winter and summer) in the concentrations of PM_2.5 and PCDD/Fs were evaluated, sources of PCDD/Fs pollution were tracing by principal component analysis, and health risks to the population from respiratory exposure to PCDD/Fs were estimated by VLIER-HUMAAN model. Results The PM_2.5 concentrations in the 28 samples ranged from 10 to 126 μg·m⁻³, while the concentrations of PCDD/Fs in PM_2.5 ranged from 58 to 2625 fg·m⁻³. The concentration of PM_2.5 during winter (11-126 μg·m⁻³) was higher than that during summer (10-60 μg·m⁻³). The concentration range of PCDD/Fs in winter was from 58 to 2625 fg·m⁻³, which corresponded to a range of toxic equivalent quantity (WHO-TEQ) concentration from 2.99 to 40.97 fg·m⁻³ when taking World Health Organization's toxic equivalency factor (WHO-TEQ); the concentration range of PCDD/Fs in summer was from 72 to 446 fg·m⁻³, which corresponded to a range of WHO-TEQ concentration from 2.66 to 16.61 fg·m⁻³. This range in summer was significantly lower than that observed in winter. The results of principal component analysis revealed that waste incineration was the primary source of PCDD/Fs in winter PM_2.5 in the area, whereas traffic emissions emerged as the main source in summer. The assessment of Pudong residents' respiratory exposure to PCDD/Fs in PM_2.5 showed significantly higher exposure of children in summer and winter than that of adults, indicating higher susceptibility of children to air pollutants. Both the hazard ratios (HR) for children and adults were below 1, while the cancer risks (CR) ranged from 8.41×10⁻⁸ to 2.35×10⁻⁶. Notably, during winter, the CR at 4 locations slightly exceeds 1×10⁻⁶, indicating a potential carcinogenic risk. Conclusion The overall pollution level of PCDD/Fs in PM_2.5 in Pudong area is relatively low, but it shows clear seasonal patterns. Waste incineration and traffic are the main sources of PCDD/Fs in PM_2.5 in the area. Although the cancer risk of exposure to PCDD/Fs in PM_2.5 for children or adults is relatively low, there is a certain risk at some locations in winter, necessitating additional monitoring and control.

Objective: To investigate the prospective effects of intake of each food group on the development of lung function of pupils,so as to provide theoretical basis for promoting the healthy development of lung function and preventing chronic respiratory diseases in Chinese children. Methods: A cluster stratified sampling method was used to select a total of 893 pupils in grades 2-5 from Chengdu in November 2021. Dietary data of respondents were collected using a food frequency questionnaire within the past year,then the food group intake was categorized into T1, T2 and T3 from low to high by the trichotomous method, and anthropometric measurements including lung capacity were obtained in 2022. Logistic regression models and test for trend were used to analyze the prospective effects of intake of each food group on lung function development of pupils. Results: Among male students, consumption of vegetables [118.6(50.5, 188.2)g/d] and milk and dairy products [200.0(73.3, 250.0)g/d] were higher in the excellent lung capacity group than in the non excellent lung capacity group [90.0(37.1, 192.9), and 178.6(35.7, 250.0)g/d],with statistically significant differences ( Z =-1.98, -2.24); among girls, the group with excellent lung capacity consumed less staple food [391.1(273.6, 511.4)g/d] than the group with non excellent lung capacity [407.4(309.5, 594.3)g/d], and the group with excellent lung capacity consumed more aquatic products [31.2(14.6, 69.8)g/d] and milk and dairy products [215.0(107.1, 250.1) g/d ] than that of the non excellent lung capacity [19.4(10.7, 58.3), 114.3(35.7, 250.0)g/d] ( Z =-2.01, -3.33, -5.10)( P < 0.05 ). After adjusting for energy, body mass index Z score(BMI Z ), mother s education level, averge family income monthly, whether presence of smokers in the living environment, and whether participation in physical activities during the past week, among male students, T3 group of vegetable intake ( OR =0.48, 95% CI = 0.27-0.86), T2 group of bean and soy product intake ( OR = 0.52 , 95% CI =0.27-0.96)，T2 and T3 groups of milk and dairy products intake (T2： OR =0.54, 95% CI =0.31-0.93; T3： OR = 0.52 , 95% CI =0.30-0.90) were negatively associated with non excellent lung capacity ( P <0.05). Among girls, T3 group of aquatic product intake( OR =0.52, 95% CI =0.28-0.97), T2 and T3 groups of milk and dairy product (T2: OR =0.44, 95% CI =0.25- 0.76 ;T3: OR =0.33, 95% CI =0.19-0.59) were negatively associated with nonexcellent lung capacity, whereas the T2 group of red meat intake ( OR =2.51, 95% CI =1.37-4.67) was positively associated with non excellent lung capacity. Non excellent lung capacity was found to be negatively associated with vegetable and milk and dairy product intake in boys by test for trend; in girls, milk and dairy products intake was negatively associated with non excellent lung capacity, whereas red meat intake was positively associated with non excellent lung capacity ( t =-1.13，-0.44；-3.03，1.95, P trend <0.05). Conclusions Milk and dariy products intakes reduce the risk of non excellent lung capacity in pupils, vegetables intakes reduce the risk of non excellent lung capacity in boys, and the intake of red meat increases the risk of non excellent lung capacity in girls. Promoting rational food choices is necessary for children to improve healthy lung development.

Objective To explore the predictive value of serum homo sapiens microRNA(hsa-miR)-30c-5p expression in patients with type 2 diabetes mellitus(T2DM)for microvascular complications.Methods A total of 205 T2DM patients admitted to Bazhong Central Hospital from May 2021 to September 2022 were selected as the diabetes group,and the diabetes group was further divided into diabetes with combined group(n=124)and non combined group(n=81)according to the microvascular complications of the patients.In addition,205 healthy people who underwent physical examination during the same period were selected as the control group.The expression of hsa-miR-30c-5p in serum was detected by reverse transcription-polymerase chain reaction(RT-PCR)and compared.The factors affecting microvascular complications were analyzed using multivariate logistic regression analysis,and receiver operating characteristic(ROC)curves were plotted to predict the value of serum hsa-miR-30c-5p expression in predicting microvascular complications in T2DM patients.Results The expression of serum hsa-miR-30c-5p in the combined group(0.58±0.06)and the non-combined group(0.72±0.08)were lower than that in the control group(0.89±0.21),and the differences were significant(t=16.038,7.079,all P=0.001).The combined group was lower than the non-combined group,and the difference was significant(t=14.289,P=0.001).The course of diabetes[(OR(95％CI):3.873(2.976～4.770)],uric acid[(OR(95％CI):2.125(1.211～3.040)]and glycosylated hemoglobin[(OR(95％CI):2.680(1.745～3.616)]were independent risk factors for microvascular complications in T2DM patients(all P＜0.05),while the time within the target range of glucose[(OR(95％CI):0.491(0.135～0.846)]and serum hsa-miR-30c-5p[(OR(95％CI):0.532(2.976～4.770)]were protective factors for microvascular complications in T2DM patients(all P＜0.05).The sensitivity,specificity and area under the curve(95％CI)of serum hsa-mir-30c-5p expression in predicting microvascular complications in T2DM patients were 81.45％,85.19％and 0.802(0.741～0.854),respectively.Conclusion The expression of serum hsa-miR-30c-5p in patients with T2DM is abnormally reduced,and serum hsa-miR-30c-5p is a protective factor for microvascular complications in patients with T2DM.It may have a certain predictive value for microvascular complications in patients with T2DM.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the correlation of MPV,NLR,PT,APTT and FIB with early pro-gression of ACI in patients with BAD.Methods A total of 303 ACI patients with BAD admitted in our department of neurology from October 2021 to September 2023 were consecutively recrui-ted,and according to their progression within 7 d of onset,they were divided into progression group(89 cases)and un-progression group(214 cases).The general clinical data,blood routine re-lated indicators(MPV,NLR)and coagulation related indicators(PT,APTT,FIB)were compared between the two groups.Multivariate logistic regression analysis was applied to identify the rela-tionship of above indicators with early progression of ACI in BAD patients.ROC curve was plot-ted to analyze the predictive value of the indictors for disease progression in these patients.Results The progression group had significantly advanced age,larger proportions of diabetes,hyperlipi-demia and stroke history,and increased levels of uric acid,LDL-C,homocysteine,MPV,platelet distribution width,NLR,D-dimer and FIB,and shorter TT,PT and APTT when compared with the un-progressed group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that MPV,NLR,PT,APTT,and FIB were all independent influencing factors for early disease pro-gression of ACI in patients with BAD(P＜0.05,P＜0.01).ROC curve indicated that the AUC value of combined MPV,NLR,PT,APTT and FIB in detecting early disease progression was 0.859(95％CI:0.813-0.905).Conclusion Blood routine(MPV,NLR)and coagulation related indicators(PT,APTT,FIB)are closely associated with the early disease progression of ACI in BAD patients,and these indicators are of high value in predicting the early disease progression.

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

Objective To explore the possible role of thrombospondin-1(THBS1)in the excessive fibrosis of vaginal wall induced by estrogen deficiency in rats,the morphological structure of collagen fibers and the expression of THBS1 in the vaginal wall were detected in the estrogen deficiency model of rats.Methods Twenty-four SD rats aged 3 months without delivery were randomly divided into sham operation group and experimental group,with 12 rats in each group.After 12 weeks of modeling,the rats were killed and the vaginal walls were taken for analysis.Masson staining was used to observe the morphological and structural changes of collagen fibers in vaginal wall of rats.Immunohistochemical staining and Western blotting were used to detect the expression level of THBS1 protein.Results After 12 weeks of modeling,the uterine atrophy of experimental group was obvious,the increase of body mass was significantly higher than that of sham operation group,and the level of estradiol was significantly lower than that of sham operation group(P<0.01).Compared with the sham operation group,the upper cortex of vaginal wall of experimental group was significantly atrophy,the smooth muscle bundles were thinner,the muscle gap was wider,the collagen fiber deposition in lamina propria and muscle layer was increased,and the arrangement and distribution were disordered and fragmented.THBS1 expression in vaginal wall of experimental group was significantly higher than that of sham operation group(P<0.05).Conclusion Estrogen deficiency may mediate excessive fibrosis of vaginal wall by upregulating THBS1 expression,thereby damaging the biomechanical properties of vaginal wall and leading to an increased susceptibility to pelvic organ prolapse development.