OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi- components by single-marker method （QAMS） to determine the contents of 7 components， so as to provide a scientific basis for their quality control. METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules （No. S1- S10）， and similarity evaluation， cluster analysis （CA） and partial least squares-discriminant analysis （PLS-DA） were performed. At the same time， the contents of seven components， including puerarin， daidzin， calycosin-7-O- β -D-glucoside， stilbene glycoside， naringin， icariin and tanshinone ⅡA， were determined by QAMS method， and were compared with the results of external standard method. RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules， namely puerarin （peak 4）， daidzin （peak 7）， calycosin-7-O-β-D-glucoside （peak 9）， stilbene glycoside （peak 10）， naringin （peak 12）， icariin （peak 17）， and tanshinone ⅡA （peak 18）； the similarities among them were more than 0.990， and CA and PLS-DA results showed that S4-S5，S8-S10，S1-S3 and S6-S7 were clustered into three categories， respectively. Using naringin as the internal standard， the contents of puerarin， daidzin， calycosin-7-O-β-D-glucoside， stilbene glycoside， icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2， 1.709 2-2.374 1， 0.285 2-0.326 3， 1.024 1- 1.523 9， 0.140 2-0.290 4， and 0.077 1-0.219 4 mg/g， respectively， by the QAMS. These results showed no significant differences compared to those obtained by the external standard method. CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient， stable and accurate， which can provide a basis for the quality evaluation of Xintong granules.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: To investigate the efficacy and safety of chidamide combined with DICE regimen (cisplatin+ ifosfamide + etoposide + dexamethasone) for relapsed/refractory diffuse large B-cell lymphome(R/R DLBCL). METHODS: The clinical data of 31 R/R DLBCL patients treated by chidamide combined with DICE regimen in the Hematology Department of the Fourth Hospital of Hebei Medical University from October 2016 to October 2020 were retrospectively analyzed. The clinical efficacy and adverse events were observed. RESULTS: Among the 31 patients, 20 were male and 11 were female. The median age of the patients was 55 (range: 27-71) years old, 21 cases were < 60 years old, 10 cases were ≥60 years old. 26 cases were refractory and 5 cases were relapsed. There were 13 cases of germinal center B-cell like (GCB), 17 cases of non-GCB, and 1 case had missing Hans type. There were 17 cases of double-expression lymphoma (DEL) and 14 cases of non-DEL. The complete response rate of patients was 38.7%(12/31), the overall response rate was 67.7%(21/31). The median progression-free survival time and the median overall survival time were 9.8(95%CI : 4.048-15.552) months, 13.9(95%CI : 9.294-18.506) months, respectively. Multipvariate analysis showed that GCB and DEL reduced the risk of disease recurrence in R/R DLBCL patients. The main grade 3/4 hematological adverse events in this study were thrombocytopenia, agranulocytosis, anemia and leukopenia. CONCLUSION The chidamide combined with DICE regimen is effective in the treatment of R/R DLBCL, and hematological adverse events should be closely monitored.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Female ; Male ; Adult ; Aged ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Benzamides/administration & dosage* ; Aminopyridines/administration & dosage* ; Etoposide/therapeutic use* ; Cisplatin/administration & dosage* ; Ifosfamide/administration & dosage* ; Dexamethasone/therapeutic use*

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective To investigate the impact of phase Ⅱ cardiac rehabilitation on the rehabilitation needs and physical activity status of patients after coronary heart disease intervention.Methods A total of 90 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI)in the Coronary Heart Disease Center of the hospital from August 2023 to August 2024 were selected as the research subjects.They were subjected to a 12-week standardized phase Ⅱ cardiac rehabilitation training.General data survey forms,cardiac rehabilitation scales,and the International Physical Activity Questionnaire were used for scale surveys to understand the patients' needs before and after rehabilitation and their weekly physical activity en-ergy expenditure.The cardiopulmonary exercise test gold standard,which reflects exercise capacity through three indicators-maximum oxygen uptake(VO2 max),anaerobic threshold(AT),and metabolic equivalents(MET),were used to compare the physical activity status before and after cardiac rehabilitation.Results Compared with before the implementation,after the implementation of cardiac rehabilitation,the autonomy score in-creased(21.36±1.85 vs.16.73±3.28),the process anxiety(12.60±3.87 vs.14.27±2.12)and outcome anxiety scores(2.31±1.76 vs.4.56±3.56)decreased,the level of low-intensity physical activity decreased[(2 711.62±1 487.09)min/week vs.(3 845.97±2 083.71)min/week],the levels of moderate-intensity[(1 314.67±783.54)min/week vs.(686.22±126.79)min/week],high-intensity[(1 861.33±798.27)min/week vs.(112.00±40.77)min/week],and total physical activity increased[(5 887.62±2 843.54)min/week vs.(4 644.19±2 287.16)min/week].The levels of VO2 max[(28.11±14.28)mL·min-1·kg-1 vs.(23.82±12.34)mL·min-1·kg-1],AT[(16.06±5.41)mL·min-1·kg-1 vs.(13.53±4.56)mL·min-1·kg-1],and MET[(6.89±1.59)mL·min-1·kg-1 vs.(5.78±1.21)mL·min-1·kg-1]all in-creased,with statistically significant differences(P＜0.05).Conclusion Phase Ⅱ rehabilitation after PCI can effectively improve patients' physical activity levels.

Objective To design a novel bromodomain-containing protein 4(BRD4)and histone deacetylase(HDAC)dual-target inhibitor(11b),and to elucidate its therapeutic efficacy and mechanisms in suppressing prostate cancer through epigenetic regulation.Methods BRD4 and HDAC expression levels were assessed via immunohistochemistry(IHC)using prostate cancer tissue microarrays.The inhibitory activity of 11b was screened across three prostate cancer cell lines,with the half-maximal inhibitory concentration(IC50)determined by CCK-8 assay.Western blot was employed to analyze changes in the expression of target proteins,including BRD4,c-Myc proto-oncogene protein(c-Myc),and Ac-H3K27,with parallel comparisons to single-target agents,including suberoylanilide hydroxamic acid(SAHA),a HDAC inhibitor,and JQ-1,a BRD4 inhibitor.Cell invasion and proliferation were evaluated using Transwell and colony formation assays,and the autophagy mechanism was validated using 3-methyladenine(3-MA),an autophagy inhibitor.A PC-3 xenograft model was established in nude mice.Then,11b(7.5 mg/kg or 15 mg/kg),normal saline,SAHA,and JQ-1 were administered via intraperitoneal injection,and their tumor growth inhibition effects were observed.The percentage of target protein-positive cells and the expression levels of target genes were quantified via IHC and RT-PCR,respectively.Results BRD4 and HDAC expression levels were both higher in tumor tissues than those in normal tissues(P<0.01).11b exhibited the strongest inhibitory activity against PC-3 cells(IC50=8.28 μmol/L),outperforming SAHA(22.61 μmol/L)and JQ-1(22.09 μmol/L).Treatment with 11b reduced BRD4 and c-Myc expression by(41.58±3.28)%and(63.21±6.91)%,respectively(P<0.01),and increased the Ac-H3K27 level to 6.52-fold that of the negative control(NC)group(P<0.01),demonstrating greater modulation than either SAHA or JQ-1 did.The in vitro experiment showed that 8 μmol/L 11b treatment reduced PC-3 colony formation and migration by 97.5%and 96.3%,respectively(P<0.001),and co-treatment with 3-MA reversed its cytotoxic effects.The in vivo experiment showed that 11b at both 7.5 mg/kg and 15 mg/kg significantly reduced tumor volume and weight compared with the control,SAHA,and JQ-1 groups(all P<0.01),with the proportion of percentage of target protein-positive cells and the expression of target genes showing trends consistent with in vitro findings.Conclusion The dual-target inhibitor 11b exerts potent antitumor effects in prostate cancer by synergistically modulating the BRD4/HDAC pathways.11b demonstrates therapeutic efficacy superior to that of the single-target agents SAHA and JQ-1 in suppressing prostate cancer progression,highlighting its potential for clinical translation.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.