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

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Objective To compare the technical indicators and clinical effect of catheter-directed thrombolysis(CDT)via two types of non-popliteal venous access in the treatment of acute mixed-type lower extremity deep vein thrombosis(DVT).Methods The clinical data of 119 patients with acute mixed-type lower extremity DVT,who were admitted to the Affiliated Jiangning Hospital of Nanjing Medical University and the Affiliated Nanjing Hospital of Nanjing Medical University of China to receive CDT treatment from January 2016 to June 2022,were retrospectively analyzed.Of the 119 patients,CDT via deep calf vein access was carries out in 45(calf vein group)and CDT via healthy-side femoral venous access was performed in 74(femoral vein group).The success rate of vascular puncture,success rate of catheterization technique,number of successful CDT venous puncturing,time spent for sheath placement,time spent for catheterization,thrombolysis time,used amount of thrombolytic agent and associated complications(including vein puncturing and anticoagulant thrombolysis-related complications),the thrombolytic effect of different anatomical segments,and the clinical efficacy during the follow-up period for at least 12 months were compared between the two groups.Results Successful catheterization via deep calf vein access and via healthy-side femoral vein access was obtained in 31 and 58 CDT patients respectively,with a technical success rate of 68.89％(31/45)and 78.38％(58/74)respectively,the difference between the two groups was not statistically significant(P=0.248).In 26 patients(67.74％)of the calf vein group,more than two times of puncturing were needed before the sheath placement could be successfully achieved.The time spent for sheath placement in the femoral vein group was(1.84±0.87)min,which was remarkably shorter than(10.52+6.13)min in the calf vein group(P＜0.001),but the time spent for catheterization in the femoral vein group was(41.60±13.31)min,which was obviously longer than(20.06+4.46)min in the calf vein group(P＜0.001).The thrombolysis time in the femoral vein group and the calf vein group was(5.34+1.43)days and(5.06±1.18)days respectively(P=0.354),and the used amount of thrombolytic agent in the femoral vein group was(352.16±71.98)×104 U,which was prominently larger than(284.68±77.64)× 104 U in the calf vein group(P＜0.001).The last follow-up check showed that the patency rate of the popliteal vein in the calf vein group was significantly higher than that in the femoral vein group(P=0.037).No statistically significant differences in the incidence of post-thrombotic syndrome(PTS)and the mean VEINES-QOL/Sym scores existed between the two groups(all P＞0.05).Conclusion Compared with CDT via healthy-side femoral vein access,CDT via deep calf vein access can better remove the thrombus in the popliteal vein and superficial femoral vein,and improve the femoropopliteal vein patency rate,although it has no obvious advantages in reducing the occurrence of PTS and in improving the VEINES-QOL/Sym score,moreover,the deep calf vein puncture and sheath placement require a high-level technique.

Objective To observe the role of the renin-angiotensin system in myocardial injury induced by experi-mental vascular dementia.Methods Eighteen adult male rats were categorized into a normal group,sham group,and modified 2-vessel occlusion group(model).To assess the myocardial injury caused by experimental vascular dementia,immunostaining was conducted to evaluate the interstitial collagen fraction and myocyte cross-sectional ar-ea.The concentrations of angiotensin Ⅱ(Ang Ⅱ)and angiotensin 1-7(Ang1-7)in the serum,as well as the ex-pression levels of angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2),Ang Ⅱ,Ang1-7,angiotensin type 1(AT1)receptor,and Mas receptor in the myocardium,were assessed.Results Modified 2-vessel occlusion led to pronounced cognitive dysfunction(P＜0.01)and myocardial injury(P＜0.000 1)when compared to the sham and normal groups.Additionally,modified 2-vessel occlusion induced significant upregulation of the ACE/Ang Ⅱ/AT1 receptor axis(P＜0.01)and downregulation of the ACE2/Ang1-7/Mas axis(P＜0.05)of the renin-angiotensin system in the myocardium.Conclusion Myocardial injury in rats with experimental vascu-lar dementia may be related to dysregulation of the renin-angiotensin system.

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

Objective·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea(OSA)published worldwide.Methods·The guidelines of OSA were retrieved in PubMed,Embase,China National Knowledge Infrastructure(CNKI),Wanfang Data,SinoMed,MedSci,The Cochrane Library,and the websites such as Medlive,U.S.Preventive Services Task Force(USPSTF),National Institute for Health and Care Excellence(NICE),New Zealand Guidelines Group(NZGG),Scottish Intercollegiate Guidelines Network(SIGN),and Guidelines International Network(GIN)from establishment to December 2022.Two reviewers screened the literature and extracted the main information independently,using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ)and Reporting Items for Practice Guidelines in Healthcare(RIGHT)to evaluate the quality of the included OSA guidelines.Subgroup analysis was performed according to the publication regions of guidelines.The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient(ICC).All the included guidelines were read entirely and the clinical questions they raised were summarized.Results·A total of 35 OSA guidelines were included.The ICC value of 0.975 showed a good inter-evaluator agreement.The results of AGREE Ⅱ showed that the average score of all guidelines was(63.60±16.45)%,with a minimum of 23.40%and a maximum of 91.67%.In the six domains,the scores of"Rigor of development"[(56.07±25.89)%]and"Applicability"[(53.57±15.52)%]were relative low.The average reporting rate of RIGHT of all the included guidelines was(67.84±20.03)%,with a minimum of 14.29%and a maximum of 94.29%,and the three domains with the lowest reporting rates were"Review and quality assurance"[(31.40±45.51)%],"Funding and conflict of interest declaration and management"[(56.43±33.95)%]and"Other aspects"[(56.19±36.85)%].Subgroup analysis showed that guidelines in Asian had a lower score in"Rigor of development"and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe(both P<0.05),and the reporting rates in the domains of"Evidence"and"Other information"of RIGHT of the Asian guidelines were also lower than those in the guidelines in America and Europe(P<0.05).These guidelines focused on 42 clinical questions which were classified to 3 aspects,i.e.screening and diagnosis,treatment and long-term management of OSA.Conclusion·The quality of current global OSA guidelines varies a lot,and they need to be strengthened in terms of rigor of development,applicability,review and quality assurance,funding and conflict of interest declaration and management,especially those in Asia.

BACKGROUND:The landing error scoring system test is a standard for assessing the risk of non-contact injuries and has not yet been developed for Chinese college soccer programs. OBJECTIVE:To establish a test evaluation standard for the landing error scoring system to provide a basis for evaluating the risk of non-contact injuries in college soccer students. METHODS:A prospective cohort study was designed in which 219 athletes from 10 college soccer teams were tested with the standard landing error scoring system,and the subjects were followed up by questionnaires and medical examinations for non-contact injuries of the lower extremities and trunk for 1 year after testing to determine sex differences and assessment criteria for the landing error scoring system test indicators. RESULTS AND CONCLUSION:The total score of the landing error scoring system was(8.22±1.65)points for 219 subjects,(8.29±1.74)for males and(8.07±1.44)for females,with no significant difference between males and females(P>0.05).Within 1 year after the test,the overall injury rate of 219 subjects was 10.05%and the morbidity rate was 15.98%;the injury rate of male subjects with non-contact injury of the lower limbs and trunk was 12.75%and the morbidity rate was 20.13%;the injury rate of female subjects with non-contact injury of the lower limbs and trunk was 4.29%and the morbidity rate was 7.14%.There were no significant differences in the injury rate between men and women(P<0.05).The total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.50±1.14)vs.(8.08±1.64),P<0.01];for male subjects,the total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.63±1.12)vs.(8.09±1.73),P<0.01].The area under the curve for the total score of the landing error scoring system was 0.773(P=0.000),which had a diagnostic value for the risk of non-contact injury of the lower extremities and trunk in male subjects,with a best cut-off point of 8.5,sensitivity of 0.842,specificity of 0.623,positive likelihood ratio of 2.233,negative likelihood ratio of 0.254,relative risk factor of 8.400,and odds ratio of 8.816;the total score of the landing error scoring system was not applicable for assessing the risk of non-contact injury of the lower extremities and trunk in female subjects.To conclude,the landing error scoring system test can be used as a criterion to assess the risk of non-contact injury to the lower extremity and trunk in Chinese college male soccer players,with an optimal cut-off point of 8.5.The risk of non-contact injury to the lower extremity and trunk is 8.40 times higher in male athletes with a landing error scoring system test score of≥8.5 than in male athletes with a score of<8.5.