BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

OBJECTIVE: To explore the integrated traditional Chinese and Western medicine treatment plan for ankylosing spondylitis complicated with lower cervical spine fracture and dislocation, adopt the treatment plan of preoperative continuous traction, intraoperative prizing reduction combined with anterior long-segment plate-screw and posterior short-segment pedicle screw-rod system internal fixation, and evaluate its surgical efficacy and clinical application value. METHODS: From June 2018 to September 2022, 7 male patients with ankylosing spondylitis complicated with lower cervical spine fractures were admitted, aged 43 to 65 years old. Among them, there was 1 case of C_3,4 fracture, 1 case of C_4,5 fracture, 1 case of C_6,7 fracture, and 4 cases of C_5,6 fracture, all of which were fracture and dislocation. All patients received preoperative continuous skull traction, and intraoperative prizing reduction combined with anterior long-segment plate-screw and posterior short-segment pedicle screw-rod system internal fixation. The Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) score, and Frankel scale were used to evaluate the neurological function and quality of life before and after surgery. The visual analogue scale (VAS) was used to evaluate neck and limb pain. The operation time, blood loss, hospital stay, and surgery-related complications were recorded. RESULTS: All 7 patients were followed up for 6 to 24 months after surgery. The operation time of the 7 patients ranged from 300 to 480 minutes, the blood loss ranged from 300 to 1000 ml, and the hospital stay ranged from 8 to 25 days. The preoperative NDI of the 7 patients ranged from 25% to 42%, which decreased to 12% to 30% at 1 week after surgery and 5% to 25% at the last follow-up. The preoperative JOA score ranged from 8 to 13 points, which increased to 12 to 15 points at 1 week after surgery and 13 to 16 points at the last follow-up. The preoperative VAS ranged from 6 to 8 points, which decreased to 2 to 4 points at 1 week after surgery and 0 to 3 points at the last follow-up. Regarding the Frankel grade of neurological function, 2 patients were grade C before surgery and recovered to grade D at the last follow-up after surgery, and the remaining patients recovered to grade E at the last follow-up after surgery. There were 3 cases of pressure ulcers, including 1 case of intraoperative pressure ulcer, 1 case of cervical cerebrospinal fluid leakage, 1 case of screw loosening, and 1 case of aggravated fracture dislocation due to preoperative traction. CONCLUSION Preoperative cervical traction combined with intraoperative prizing reduction and anterior long-segment plate combined with posterior short-segment pedicle screw internal fixation provides a safe and effective surgical option for ankylosing spondylitis complicated with lower cervical spine fracture and dislocation, which can minimize surgical trauma and improve clinical efficacy. However, this study has a small sample size and a short follow-up time for some patients, so further verification with large-sample and long-term follow-up data is still needed.
Humans ; Male ; Adult ; Middle Aged ; Fracture Fixation, Internal/methods* ; Spondylitis, Ankylosing/surgery* ; Cervical Vertebrae/surgery* ; Spinal Fractures/surgery* ; Traction ; Aged ; Joint Dislocations/surgery*

Early screening, diagnosis, and intervention for congenital muscular torticollis (CMT) in infants are crucial for improving clinical outcomes. However, in China, limited awareness of CMT among child healthcare institutions and caregivers, as well as inconsistent professional standards among rehabilitation personnel, pose significant challenges to the effective diagnosis and management of CMT. The "Physical therapy management of congenital muscular torticollis: a 2024 evidence-based clinical practice guideline from the American Physical Therapy Association Academy of Pediatric Physical Therapy" includes 17 action statements, primarily addressing the prevention, identification, assessment, and intervention of CMT. This guideline is expected to facilitate early detection of CMT in infants, enhance the treatment capabilities of physical therapists, and improve clinical outcomes. This article provides an interpretation of the guideline in the context of the current status of CMT diagnosis and management in China, aiming to offer a reference for improving the ability of primary child healthcare providers and physical therapists to recognize and manage CMTropriately.
Humans ; Torticollis/diagnosis* ; Physical Therapy Modalities ; Practice Guidelines as Topic ; Infant ; United States

OBJECTIVE: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis. METHODS: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively. RESULTS: The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis. CONCLUSIONS SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals ; Myocytes, Cardiac/metabolism* ; Apoptosis/drug effects* ; MicroRNAs/genetics* ; Rats, Sprague-Dawley ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Doxorubicin/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Drug Combinations ; Injections ; Rats

Objective : To investigate the prevalence of negative emotions in hospitalized youth patients with type 2 diabetes(T2DM) and its correlation with coping strategies and psychological resilience. Methods : 141 youth T2DM patients who met the research standards were selected. Blood glucose related indicators, blood pressure, body mass index(BMI), diabetes chronic complications screening results and other data were collected. The basic information and disease related information questionnaire, self-rating depression scale(SDS), self-rating anxiety scale(SAS), diabetes distress scale(DDS), medical coping modes questionnaire(MCMQ) and Connor-Davidson resilience scale(CD-RISC) were completed. Results: Among 141 hospitalized youth T2DM patients, 37.6% were combined with depression, 32.6% were combined with anxiety, and 35.5% were combined with diabetic distress(DD). Univariate analysis showed that systolic blood pressure(P<0.01), educational level, and the form of hospitalization expenses(P<0.05) were significantly correlated with depression. Marital status(P<0.01), family residence, blood glucose monitoring methods, and the last fasting blood glucose(P<0.05) were significantly correlated with anxiety. BMI, whether it was first diagnosed or treated(P<0.01), gender, occupation, disease course, weekly blood glucose monitoring frequency, and the presence of chronic complications(P<0.05) were significantly correlated with DD. In multivariate analysis, systolic blood pressure(P<0.01), educational level, and the form of hospitalization expenses were significantly correlated with depression, marital status(P<0.05) was significantly correlated with anxiety; BMI and weekly blood glucose monitoring frequency(P<0.01) were significantly correlated with DD. SDS, SAS, total scores and dimensions of DDS were negatively correlated with the total score and dimensions of CD-RISC(rs=-0.182--0.467, P<0.05 or 0.01), and positively correlated with the yielding coping strategies(rs=0.177-0.271,P<0.05 or 0.01). SAS,total scores and dimensions of DDS were positively correlated with avoiding coping strategies(rs=0.237-0.419,P<0.05 or 0.01). The total and dimensions of CD-RISC were positively correlated with facing coping strategies(rs=0.215-0.349,P<0.05 or 0.01),and negatively correlated with yielding coping strategies(rs=-0.234--0.325,P<0.01). Conclusion More than 30% of hospitalized youth T2DM may experience negative emotions such as depression,anxiety,and DD. The occurrence of negative emotions in such patients may be related to disease management or socio-economic issues such as systolic blood pressure,educational level,hospitalization expenses,marital status,BMI,and frequency of blood glucose monitoring,as well as decreased psychological resilience and negative coping strategies.

Objective:To analyze the incidence of co-infection of HIV and HBV and death in HIV/AIDS cases who newly received antiretroviral therapy (ART) from 2005-2020 in Jiangsu Province.Methods:According to the baseline and follow-up data of HIV/AIDS cases on ART enrolled between January 2005 and December 2020, the last follow-up clinical visit was up until December 31, 2022, the national information system was retrospectively collected for HIV/AIDS cases from Chinese System Disease for Control and Prevention. Excel database was established, and statistical analysis was performed using the SPSS 16.0 software. Kaplan-Meier method was used to draw the survival curves, the log rank test was used to compare the survival curves, and Cox proportional hazards modeling was used to assess the mortality and potential risk factors.Results:There were 33 322 HIV/AIDS cases that newly received ART during 2005-2020.The rate of HBsAg test was 57.3%(19 098/33 322). Among HIV/AIDS cases tested HBsAg, the ratio of male to female was 7.1∶1 (16 745∶2 353), the average age was (39.4±14.0) years old, 49.5% (9 446/19 098) of the HIV/AIDS cases were married, 57.8% (11 048/19 098) were infected with HIV through homosexual contact and 36.6% (6 990/19 098) were through heterosexual contact. The M ( Q1, Q3) of CD4 +T lymphocytes (CD4) counts at ART initiation was 297 (166, 445) cells/μl. A total of 8.2% (1 566/19 098, 95% CI:7.8%-8.6%) were HBsAg positive. There were 1 062 HIV/AIDS died by December 31, 2022. The log rank test showed that there were differences in survival curves between HIV/AIDS co-infected with HBV or not ( χ2=28.07, P<0.001). Multivariate analysis of the Cox proportional risk regression model showed that enrollment year, age, marital status, route of HIV infection, baseline CD4 counts before ART, and co-HBV infection were the influencing factors for HIV/AIDS death (all P<0.05), compared with those enrolled in 2015 and before, age ≥45 years, and those who were unmarried. Those enrolled in treatment from 2016 to 2020, those younger than 45 years, and married/cohabitation had a lower risk of death. Compared with baseline CD4 counts ≥201 cells/μl, other routes of infection, and HIV infection alone, baseline CD4 counts ≤200 cells/μl, injecting drug use, and co-HBV infection were associated with a higher risk of death. Conclusion:Effective treatment for coinfection with HBV and HBV vaccination for HBV-negative people with HIV should be integrated into HIV treatment programs to reduce HIV-related mortality in Jiangsu Province, 2005-2020.

Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

Objective To investigate the incidence of anemia and evaluate the immune status among newly reported HIV/AIDS patients in Jiangsu Province in 2021, and to identify the risk factors of anemia among patients living with HIV infections. Methods Newly reported HIV/AIDS patients in Jiangsu Province from January 1 to December 31, 2021 that were registered in China’s National AIDS Comprehensive Control Information Management System were enrolled. Subjects’ fresh whole blood samples were collected, and hemoglobin levels, CD4 and CD8 cell counts and HIV viral loads were measured. Anemia was defined according to hemoglobin levels, and the immunological parameters and HIV viral loads were compared between HIV-infected patients with and without anemia. The risk factors of anemia were identified among individuals living with HIV infections using univariate analysis and multivariate logistic regression analysis. In addition, subjects’ CD4 cell counts one year following antiretroviral therapy (ART) were retrieved from China’s National AIDS Comprehensive Control Information Management System, and compared between subjects with and without anemia. Results A total of 635 newly diagnosed HIV/AIDS patients were reported in Jiangsu Province in 2021, including 544 males (85.67%) and 91 females (14.33%), and with ages of 15 to 83 years, and the overall incidence of anemia was 5.51% (35/635) among the study subjects. Men, individuals at ages of 45 years and lower and workers had relatively higher hemoglobin levels, with median hemoglobin levels of 156 (interquartile range, 22), 154 (interquartile range, 23) g/L and 162 (interquartile range, 19) g/L, respectively. The median baseline HIV viral load was 40 500.00 (interquartile range, 119 735.00) copies/mL among HIV-infected individuals with anemia and 29 754.00 (69 183.00) copies/mL among those without anemia (Z = -0.91, P = 0.31), and the median baseline CD4 and CD8 cell counts were significantly lower among HIV-infected individuals with anemia [166 (interquartile range, 143) cells/μL and 755 (653) cells/μL] than those without anemia [308 (253) cells/μL and 892 (638) cells/μL] (Z = -4.36 and -2.37, both P values < 0.05). The median CD4 cell counts remained lower among HIV-infected individuals with anemia than those without anemia [296 (interquartile range, 229) cells/μL vs. 457 (interquartile range, 313) cells/μL; Z = -3.71, P < 0.05] one year following ART, and the proportions of moderate and severe immunosuppression were significantly higher among HIV-infected individuals with anemia (40.00% and 17.14%) than those without anemia (21.00% and 9.33%) (χ² = 10.37 and 8.79, both P values < 0.01). Univariate analysis showed a higher detection rate of anemia among female HIV-infected individuals than among males [odds ratio (OR) = 4.528, 95% confidence interval (CI): (3.811, 5.245), P < 0.001], a higher rate among HIV-infected individuals at ages of 45 to < 60 years [OR = 3.415, 95% CI: (1.191, 9.788), P = 0.022] and 60 years and older [OR = 5.820, 95% CI: (2.013, 16.826), P < 0.001] than among those at ages of 15 to < 30 years, a higher rate among HIV-infected individuals through heterosexual transmission than among those through homogeneous transmission [OR = 3.015, 95% CI: (1.423, 6.387), P = 0.004], a lower rate among HIV-infected individuals with an educational level of college and above than among those with an educational level of primary school [OR = 0.103, 95% CI: (0.028, 0.386), P < 0.001], a higher rate among HIV-infected individuals with baseline CD4 cell counts of < 200 cells/μL than among those with baseline CD4 cell counts of 200 cells/μL and higher [OR = 4.340, 95% CI: (2.165, 8.702), P < 0.001], and lower detection rates among HIV-infected individuals with CD4/CD8 cell ratios of 0.208 to < 0.326 [OR = 0.232, 95% CI: (0.076, 0.711), P = 0.011] and 0.516 and higher [OR = 0.292, 95% CI: (0.104, 0.818), P = 0.019] than among those with CD4/CD8 cell ratios of < 0.208. Multivariate logistic regression analysis identified woman [OR = 4.945, 95% CI: (3.944, 5.946), P = 0.002], and CD4 cell counts of < 200 cells/μL [OR = 3.597, 95% CI: (1.448, 8.937), P = 0.006] as risk factors of anemia among newly reported HIV/AIDS patients. Conclusions The incidence of anemia was low among newly reported HIV/AIDS patients in Jiangsu Province in 2021, and the immune status was poorer among HIV-infected individuals with anemia than those without anemia at baseline and one year following ART. Female and CD4 cell counts of < 200 cells/μL are risk factors of anemia among individuals living with HIV infections, and intensified surveillance, follow-up and precision interventions are recommended targeting female HIV-infected individuals and HIV-infected individuals with low CD4 cell counts.