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*

Objective To investigate the correlation of vascular senescence indicators,brachial-ankle pulse wave velocity(baPWV),cardio-ankle vascular index(CAVI),ankle-brachial index(ABI)with total burden of MRI in patients with cerebral small vessel disease(CSVD).Methods A total of 200 CSVD patients admitted to our hospital from November 2023 to October 2024 were retrospectively recruited,and based on their total MRI burden,they were divided into a low-burden group(score:0-1,103 cases)and a high-burden group(score:2-4,97 cases).A athero-sclerosis monitoring device(VS-1500A)was used to detect baPWV,CAVI,and ABI values.The relationships of the three indicators with total MRI burden score and their predictive values for the burden score were analyzed.Results The high-burden group had significantly higher BMI,el-evated homocysteine and uric acid levels,and increased baPWV and CAVI,but lower ABI than the low-burden group(P＜0.01).Multivariate logistic analysis showed that baPWV,CAVI and ABI were independent influencing factors for high MRI burden of CSVD patients.Spearman correlation analysis showed that baPWV and CAVI values were positively correlated(r=0.589,P=0.000;r=0.458,P=0.000),and ABI was negatively correlated with the total MRI burden score of CSVD patients(r=-0.352,P=0.000).ROC curve analysis showed that baPWV(AUC=0.816,P=0.000),CAVI(AUC=0.725,P=0.000)and ABI(AUC=0.676,P=0.000)were all predic-tors for high MRI burden score in CSVD patients.Conclusion baPWV and CAVI are positively,and ABI is negatively correlated with the total MRI burden score of CSVD patients.baPWV,CAVI and ABI show higher predictive value for the high burden score,with baPWV most significant.

Objective:To investigate the diagnostic features of eosinophilic gastroenteritis (EGE) of the stomach and duodenum.Methods:A case-control study was conducted to retrospectively analyze 238 biopsy specimens of gastric and duodenal EGE (75 cases) and 133 biopsy specimens of chronic active gastroenteritis (97 cases) in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China from 2012 to 2023. The eosinophil count, infiltration site and other pathological features (e.g., infiltration of neutrophils into the epithelium, edema, and increase of background lymphocytes and plasma cells) were examined under a microscope. Chi-square test, chi-square multiple comparison ( Bonferroni method) and modified Poisson regression were used to analyze the data. Results:The results showed that there were significant differences in eosinophil count ( χ2=43.926, P<0.01), location ( χ2=31.391, P<0.01), neutrophilic infiltration of the epithelium ( χ2=5.199, P=0.023), edema ( χ2=3.934, P=0.047), and lymphoplasmacytosis ( χ2=36.813, P<0.01) between the EGE and control cases. The results of Chi-square multiple comparisons showed that eosinophils distributed in clusters or sheets (versus other grades of eosinophil presence) were statistically associated with EGE. When eosinophils infiltrated the epithelium (versus eosinophils in other locations of the mucosa), there was a statistically significant association with EGE. Modified Poisson regression also showed that EGE was more likely to have eosinophilic infiltration of epithelium [ RR=1.661, P=0.001,95% CI (1.397,1.973)] and that of muscularis mucosa [ RR=1.818, P<0.01,95% CI (1.491,2.216)]. Conclusions:The important pathological features for diagnosing EGE of the stomach and duodenum are that eosinophils are clustered or distributed in sheets with epithelial infiltration. However, epithelial infiltration by neutrophils, edema and background lymphoplasmacytosis are relatively rare.

Objective:To observe the characteristics of gastrointestinal tract symptoms in patients with Parkinson′s disease (PD) and analyze the characteristics of these symptoms in patients with different PD subtypes.Methods:A total of 297 PD patients who were admitted to the Neurology Department of the Second Affiliated Hospital of Soochow University from November 2022 to March 2024 were enrolled. The gastrointestinal symptoms of PD patients were evaluated using Drooling Severity and Frequency Scale (DSFS), Sialorrhea Clinical Scale for Parkinson′s disease (SCS-PD), Drooling Rating Scale (DRS), Eating Assessment Tool 10 (EAT-10), Gastroparesis Cardinal Symptom Index (GCSI), and Rome Ⅳ diagnostic criteria. The patients were grouped based on the presence or absence of gastrointestinal symptoms. Additionally, they were stratified according to disease duration (≤2 years, 2-5 years, 5-10 years, and>10 years) and motor symptom subtype [tremor-dominant (TD) vs. postural instability and gait difficulty (PIGD)]. One-way ANOVA and logistic regression analysis were applied to examine between-group differences while Spearman correlation analysis was employed to assess correlations between clinical symptoms.Results:The average age of the patients with PD was 67.0 (60.0, 72.0) years, and 161 (54.2%) were male. The incidence of PD combined with gastrointestinal symptoms was, in descending order: constipation (191, 64.3%), salivation (155, 52.2%), gastroparesis (93, 31.3%), and dysphagia (68, 22.9%). Compared with PD patients without gastrointestinal symptoms, those with symptoms had higher scores in the RBD-HK [12.0 (5.0, 21.5) vs. 5.0 (0.0, 9.0), Z=-3.74, P=0.017], ESS [6.0 (2.0, 12.0) vs. 3.0 (0.0, 6.0), Z=-3.20, P=0.023], and MDS-UPDRS Part Ⅰ [9.0 (5.0, 14.0) vs. 5.0 (2.3, 9.0), Z=-3.61, P=0.014]. The severity of sialorrhea and deglutition disorders, along with the incidence of constipation, all increased with longer disease duration. Patients with the PIGD subtype had higher GCSI scores than those with the TD subtype [0.0 (0.0, 1.9) vs. 0.0 (0.0, 0.0), Z=-3.57, P=0.007]. Across the cohort, sialorrhea, deglutition disorders, gastroparesis, and constipation were positively associated with the H-Y stage, MDS-UPDRS Ⅰ, HAMD, NMSQ, and SCOPA-AUT; EAT-10 scores were negatively correlated with MoCA ( r=-0.171, P<0.05); and GCSI scores were negatively correlated with MMSE and MoCA ( r=-0.154, r=-0.169, both P<0.05). Conclusions:Overall, 84.5% of the patients with PD had one or more gastrointestinal symptoms, and the incidence and severity of gastrointestinal symptoms increased with disease duration. The severity of gastroparesis was higher in the PIGD group than in the TD group. The scores of all gastrointestinal symptoms were positively correlated with the H-Y stage and MDS-UPDRS Ⅰ, while the GCSI scores were negatively correlated with the cognitive scores.

Objective:To evaluate the clinical efficacy of endoclip papillaplasty (ECPP) for preventing recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP).Methods:A retrospective analysis was conducted on 1 941 patients who underwent ERCP for choledocholithiasis in Henan Provincial People's Hospital from January 2019 to December 2023. A total of 250 patients who received ECPP were assigned to the ECPP group, while 251 matched controls were selected via 1∶1 year-stratified sampling into the control group. After follow-up, 209 ECPP cases and 190 controls were ultimately included in the analysis. Stone removal success rate, incidence of perioperative complications, and postoperative choledocholithiasis recurrence were compared between the two groups. Univariate and multivariate logistic regression were used to determine the risk factors for choledocholithiasis recurrence after ERCP.Results:Both groups achieved 100.0% stone removal success rate. There was no significant difference in the incidence of intraoperative perforation [0.5% (1/209) VS 1.1% (2/190), χ2=0.01, P=0.934], postoperative hyperamylasemia [21.5% (45/209) VS 17.4% (33/190), χ2=1.10, P=0.295] or post-ERCP pancreatitis [3.8% (8/209) VS 8.1% (9/190), χ2=0.20, P=0.653] between the ECPP group and the control group. The ECPP group showed significantly lower bleeding rate [5.1% (11/209) VS 12.3% (23/190), χ2=5.98, P=0.014] and choledocholithiasis recurrence rate [10.5% (22/209) VS 18.9% (36/190), χ2=5.68, P=0.017] compared with the control group. The multivariate logistic regression identified dilated common bile duct diameter ( OR=1.881, 95% CI: 1.101-3.213, P=0.021) as an independent risk factor for choledocholithiasis recurrence, while being female ( OR=0.482, 95% CI: 0.266-0.875, P=0.016) and ECPP ( OR=0.497, 95% CI:0.278-0.887, P=0.018) were protective factors. Conclusion:ECPP effectively reduces choledocholithiasis recurrence rate and bleeding risk after ERCP. ECPP and being female serve as protective factors for choledocholithiasis recurrence, while dilated bile duct diameter is an independent risk factor.

Objective To assess the intervention effect of nicotinamide mononucleotide (NMN) on the mouse model of hematotoxicity induced by subacute benzene exposure. Methods Benzene exposure and NMN intervention were adopted in a 2×2 factorial design, as benzene exposure and non-exposure, and NMN intervention and non-intervention. Male specific pathogen-free C57BL/6J mice were randomly assigned to negative control group, NMN control group, simple benzene exposure group and NMN intervention group, with 12 mice in each group. Benzene exposure of mice in simple benzene exposure group and NMN intervention group was conducted by dynamic inhalation of benzene at a concentration of 325 mg/m³ for six hours per day, five days per week for four weeks (28 days). Mice in the negative control and NMN control group inhaled clean air. During benzene exposure, mice in the NMN control group and NMN intervention group received NMN in drinking water at a dose of 300 mg/kg body weight. Peripheral blood samples of mice were collected for complete blood count analysis and calculation of composite inflammatory indices after 28 days. Results Interaction analysis showed that the counts of peripheral white blood cell, neutrophil, lymphocyte, and platelet of mice in the simple benzene exposure group were lower than those in the negative control group (all P<0.05). Neutrophil and platelet counts in the NMN intervention group were higher than those in the simple benzene exposure group (all P<0.05). The results of main effect analysis showed that the monocyte count of peripheral blood, systemic inflammatory index, systemic inflammatory response index, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio of mice in the benzene exposure group increased (all P<0.05), and the basophil count and lymphocyte/monocyte ratio decreased (all P<0.05), compared with the control group. Conclusion Oral NMN alleviates subacute benzene-induced decreases in peripheral neutrophil and platelet counts in mice. This protective effect may be related to the targeted intervention of NMN on mitochondrial energy metabolism disorder and oxidative damage induced by benzene exposure in male mice.

This paper reviews the current situation of massive open online course (MOOC) construction both domestically and internationally, highlighting the similarities, differences, and limitations of MOOC construction across nations. Based on the full-cycle MOOC construction of the "clinical epidemiology" course at Southern Medical University, including course design, resource integration, online deployment, and teaching evaluation, this study explored the significance, implementation path, and challenges of MOOC construction. This paper also reflects on the activation of teaching content, teacher-student interaction, and teaching mode, aiming to provide a reference for the construction and continuous enhancement of MOOC in China.

This paper reviews the current situation of massive open online course (MOOC) construction both domestically and internationally, highlighting the similarities, differences, and limitations of MOOC construction across nations. Based on the full-cycle MOOC construction of the "clinical epidemiology" course at Southern Medical University, including course design, resource integration, online deployment, and teaching evaluation, this study explored the significance, implementation path, and challenges of MOOC construction. This paper also reflects on the activation of teaching content, teacher-student interaction, and teaching mode, aiming to provide a reference for the construction and continuous enhancement of MOOC in China.