The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans ; Dopamine/metabolism* ; Nervous System Diseases/physiopathology* ; Parkinson Disease/physiopathology* ; Receptors, Dopamine/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Alzheimer Disease/physiopathology* ; Schizophrenia/physiopathology* ; Animals

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Pancreatic cancer patients often have complaints such as upper abdominal pain and obstructive jaundice when seeking diagnosis and treatment. However, acute pancreatitis as a rare initial clinical manifestation of pancreatic cancer is often overlooked in clinical practice. This oversight often leads to a delayed diagnosis of pancreatic cancer, uncertainty in treatment strategies, and significantly affects patients′ quality of life and prognosis. Therefore, early diagnosis and treatment, and active follow-up are crucial for patients with acute pancreatitis as an initial symptom of pancreatic cancer. Upon admission to such patients, common causes such as gallstones, alcohol abuse, and hyperlipidemia should be initially ruled out. Evaluation with tumor markers, CT and MRI, and endoscopic ultrasound are essential to confirm the diagnosis of pancreatic cancer. For patients with mild pancreatitis, managing peripancreatic inflammation first before radical resection of pancreatic cancer could reduce postoperative complications. Moreover, pancreatitis serves as a high-risk factor for pancreatic cancer, so it is crucial to closely follow up patients with pancreatitis to detect pancreatic cancer early.

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective:To explore the changes of serum levels of angiopoictin-1(Angpt1)and endothelin-1(ET-1)in patients with newly-onset atrial fibrillation(AF)after heart valve replacement,and analyze their clinical sig-nificance.Methods:A total of 130 patients who underwent heart valve replacement in our hospital from January 2020 to March 2022 were divided into no AF group(n=72)and AF group(n=58)according to presence of AF within 7d after surgery.Serum levels of Angpt1 and ET-1 were detected by ELISA in two groups;the correlation between serum Angptl and ET-1 was analyzed by Pearson method in AF patients;ROC curve analysis was used to analyze the predictive value of serum Angpt1 and ET-1 levels for postoperative AF in these patients;Logistic re-gression was used to analyze the influencing factors of postoperative AF in these patients.Results:The left atrial diameter(LAD),proportion of NYHA class Ⅳ and cardiopulmonary bypass time in AF group were significantly higher than those of no AF group(P＜0.05 or＜0.01).One day after surgery,compared with no AF group,serum Angpt1 level significantly reduced and ET-1 level significantly increased in AF group(P＜0.001 both).Pearson correlation analysis indicated that serum Angpt1 level was significant inversely correlated with ET-1 level in AF pa-tients(r=-0.366,P=0.005).ROC analysis indicated that area under the curve(AUC)of combined detection of serum Angpt1 and ET-1 in predicting AF after heart valve replacement was significantly higher than those of each single detection(Z=2.761,1.998,P=0.006,0.046).Multivariate Logistic regression analysis indicated that LAD,NYHA class Ⅳ,cardiopulmonary bypass time and postoperative ET-1 were independent risk factors for postoperative AF in these patients(OR=1.471～1.739,P＜0.05 or＜0.01),while postoperative Angpt1 was its independent protective factor(OR=0.634,P=0.004).Conclusion:Serum Angpt1 level significantly reduces and ET-1 level significantly increases in patients with newly-onset AF after heart valve replacement.Combined detec-tion of Angpt1 and ET-1 levels possesses high predictive value for postoperative AF.

Objective To investigate the relationship between serum levels of E-cadherin and β-catenin and calcium phosphorus metabolism and carotid artery calcification in patients with diabetic nephropathy.Methods A total of 112 patients with diabetic nephropathy admitted to the hospital from May 2019 to No-vember 2022 were selected as the study group,and were divided into a carotid artery calcification group(n=44)and a non-carotid artery calcification group(n=68)according to the results of bilateral carotid artery col-or Doppler ultrasound.In addition,90 healthy people who underwent physical examination in the hospital dur-ing the same period were selected as the control group.Serum E-cadherin,β-catenin,calcium phosphorus me-tabolism levels were detected and compared.Pearson correlation analysis was used to explore the relationship between serum E-cadherin,β-catenin and calcium phosphorus metabolism in patients with diabetic nephropa-thy.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum E-cad-herin and β-catenin for carotid artery calcification in patients with diabetic nephropathy.Multivariate Logistic regression analysis was used to explore the influencing factors of carotid artery calcification in patients with di-abetic nephropathy.Results The levels of glycosylated hemoglobin,serum phosphorus,calcium-phosphorus product,parathyroid hormone(iPTH),creatinine,alkaline phosphatase and β-catenin in the study group were higher than those in the control group,and the level of E-cadherin was lower than that in the control group(P＜0.05).The levels of serum phosphorus,serum calcium,calcium phosphorus product,iPTH,creatinine,al-kaline phosphatase and β-catenin in the carotid artery calcification group were higher than those in the non-ca-rotid artery calcification group,and the level of E-cadherin was lower than that in the non-carotid artery calci-fication group(P＜0.05).Pearson correlation analysis showed that serum E-cadherin level in patients with di-abetic nephropathy was negatively correlated with serum phosphorus,serum calcium,calcium phosphorus product,iPTH,creatinine and alkaline phosphatase(r=-0.453,-0.654,-0.365,-0.490,-0.411,-0.377,all P＜0.001).The level of serum β-catenin was positively correlated with serum phosphorus,serum calcium,calcium phosphorus product,iPTH,creatinine,and alkaline phosphatase(r=0.444,0.345,0.421,0.398,0.651,0.622,all P＜0.001).ROC curve analysis showed that the area under the curve of serum E-cad-herin,β-catenin and their combination for predicting carotid artery calcification in diabetic nephropathy were 0.844(95％CI 0.795-0.894),0.853(95％CI 0.801-0.901)and 0.901(95％CI 0.801-0.901),respec-tively.Multivariate Logistic regression analysis showed that serum E-cadherin(OR=3.789,95％CI 2.055-6.983),β-catenin(OR=4.104,95％CI 1.795-9.385),calcium phosphorus product(OR=2.998,95％CI 1.895-4.743)and iPTH(OR=2.713,95％CI 1.787-4.118)were the influencing factors of carotid artery calcification in patients with diabetic nephropathy(P＜0.05).Conclusion The level of β-catenin is increased and the level of E-cadherin is decreased in patients with diabetic nephropathy.β-catenin and E-cadherin are closely related to calcium phosphorus metabolism and carotid artery calcification,which could be used as effec-tive indicators to evaluate carotid artery calcification in patients with diabetic nephropathy.The combination ofβ-catenin and E-cadherin has a higher predictive value for carotid artery calcification.