ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

AIM:To investigate the effect of fenofibrate(FF)on the heart of rats with high-altitude heart dis-ease-induced right ventricular hypertrophy(H-RVH),and to explore the mechanisms and associated signaling pathways.METHODS:A total of 36 six-week-old male SD rats were randomly divided into control,model(H-RVH),and FF inter-vention(H-RVH+FF)groups with 12 rats each.A rat model of H-RVH was established by single subcutaneous injection of Sugen 5416(20 mg/kg)and exposure to a hypoxic condition(5 000 m above sea level)for 21 d in all groups except the control group.The rats in H-RVH+FF group were given FF(60 mg·kg-1·d-1)through gavage,while those in control and model groups received equal volume of saline once daily for 21 d.Rat heart gross morphology was observed,and the heart volume and weight,right ventricular weight and other hypertrophy indexes were measured in each group at the end of the experiment.A right heart floating catheter was used for measuring pulmonary artery and right ventricular pressure.Cardi-ac function was checked through cardiac ultrasonography.The serum levels of atrial natriuretic peptide(ANP),N-termi-nal pro-brain natriuretic peptide(NT-proBNP),free fatty acids(FFA),and myocardial tissue glucose(Glu)in all groups of rats were detected.The protein expression of peroxisome proliferator-activated receptor α(PPARα),fatty acid binding protein 1(FABP1),carnitine palmitoyl transferase 1a(CPT1a),pyruvate dehydrogenase kinase(PDK),and pyruvate dehydrogenase(PDH)were detected through Western blot.RESULTS:(1)Compared with the control group,the H-RVH group showed a significant increase in heart morphology and weight and increases in heart weight/body weight(HW/BW),heart volume,right ventricular weight/heart weight(RVW/HW),and Fulton index(FI)(P<0.05).Cardiac mor-phology,volume,heart weight,and HW/BW significantly decreased in the fenofibrate intervention group compared with the H-RVH group(P<0.05).RVW/HW and FI also decreased.(2)The right heart float catheter test showed that the mean right ventricular pressure(mRVP)and mean pulmonary artery pressure(mPAP)significantly increased in the H-RVH group compared with the control group(P<0.01).The increases in mRVP and mPAP were reversed in rats in the fe-nofibrate intervention group compared with the H-RVH group.(3)Cardiac ultrasonography showed that compared with the control group,the H-RVH group had significantly increased right ventricular anterior wall(RVAW)and right ventricular posterior wall(RVPW)thickness(P<0.01),significantly decreased right ventricular end-diastolic diameter(RVEDD),and right ventricular end-diastolic length(RVEDL)(P<0.01).In addition,pulmonary artery acceleration time(PAAT)was reduced,ejection time(PAET)was prolonged,and PAAT/PAET ratio decreased(P<0.01).Compared with the H-RVH group,the fenofibrate intervention group showed significant decreases in RVAW and RVPW(P<0.05),increases in RVEDD and RVEDL,and an increase in PAAT/PAET ratio.(4)The kit assay showed that the levels of ANP and NT-Pro BNP in serum were significantly higher in the H-RVH group than in the control group(P<0.05),while the levels of both were lower in the fenofibrate intervention group.The levels of serum FFA and myocardial tissue Glu levels(P<0.05)were significantly higher in the H-RVH group than in the control group.The levels of serum FFA and myocardial tissue Glu level were significantly lower in the fenofibrate intervention group than in the H-RVH group(P<0.05).(5)Western blot results showed that the expression levels of PPARα,FABP1,CPT1a,and PDH in the myocardial tissues of rats in the H-RVH group were significantly reduced(P<0.01),whereas the expression level of PDK significantly increased relative to those of the control group(P<0.01).All the effects on the above indices in the H-RVH group can be significantly re-versed by fenofibrate intervention(P<0.05).CONCLUSION:Fenofibrate exerts a protective effect on the hearts of rats with right ventricular hypertrophy associated with high-altitude heart disease by activating PPARα/FABP1/CPT1a,en-hancing fatty acid oxidation,inhibiting PDK,and activating PDH to promote the aerobic oxidation of glucose.Hence,the medication can ameliorate glucose-lipid metabolism disorders.

Objective:To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 ( CYP19A1) gene with risk of breast cancer. Methods:Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No.2021-182). Results:No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups ( P>0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group ( P<0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages Ⅲ-Ⅳ were significantly higher than those at stage Ⅰ-Ⅱ ( P<0.05). Conclusion:Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.

OBJECTIVE: To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 (CYP19A1) gene with risk of Breast cancer. METHODS: Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No. 2021-182). RESULTS: No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups (P > 0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group (P < 0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages III-IV were significantly higher than those at stage I-II (P < 0.05). CONCLUSION Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.
Humans ; Female ; Breast Neoplasms/genetics* ; Aromatase/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Middle Aged ; Genetic Predisposition to Disease ; Adult ; Genotype ; Case-Control Studies ; Alleles ; Gene Frequency ; Risk Factors ; Aged

Objective:To investigate the changes in and correlations between melanin-concentrating hormone (MCH) and androgen levels in the serum of patients with polycystic ovary syndrome (PCOS), aiming to provide a novel research perspective for its diagnosis.Methods:A cross-sectional study. A total of 307 subjects were enrolled from the physical examination center and endocrinology clinic of the Affiliated Hospital of Zunyi Medical University from June 2023 to June 2024. The cohort comprised 114 healthy controls and 193 patients with PCOS, diagnosed according to the Rotterdam criteria. The patients were grouped into four phenotypes: Phenotype A (hyperandrogenemia [HA]+ovulatory dysfunction [OA]+polycystic ovarian morphology [PCOM], n=44), Phenotype B (HA+OA, n=50), Phenotype C (HA+PCOM, n=46), and Phenotype D (OA+PCOM, n=53). Clinical data were collected for all subjects. Serum MCH levels were determined by enzyme-linked immunosorbent assay. The relationship between MCH and androgen-related risk factors for PCOS was analyzed using Spearman partial correlation analysis and stepwise multiple linear hierarchical regression. Binary logistic regression was used to analyze factors influencing PCOS onset. The diagnostic value of MCH for PCOS was evaluated using a receiver operating characteristic (ROC) curve. Results:There were no significant differences in age and height between the healthy control group and the PCOS phenotypic groups (both P>0.05). MCH levels [17.63 (12.69, 22.00), 17.31 (11.05, 20.09), 17.82 (11.47, 19.40), 16.50 (11.14, 19.41) μg/L vs. 12.14 (9.78, 15.05) μg/L], homeostatic model assessment of insulin resistance, fasting plasma glucose, fasting serum lisulin, body mass index, and weight were significantly higher across all four PCOS phenotypes (A, B, C, and D) than in healthy controls (all P<0.05), whereas sex hormone-binding globulin (SHBG) contents were significantly lower ( P<0.05). Free androgen index (FAI), total testosterone (TES) and dehydroepiandrosterone (DHEA) levels were significantly higher in PCOS phenotypes A, B, and C than in the control group and PCOS phenotype D (all P<0.05). Spearman partial correlation analysis revealed no significant correlation between MCH and TES, DHEA, or FAI in healthy controls and patients with non-HA PCOS (all P>0.05). However, in PCOS patients with HA, MCH showed a significant positive correlation with TES and DHEA ( r=0.227 and 0.196, respectively; both P<0.05), but not FAI ( P>0.05). Stepwise multiple linear hierarchical regression analysis showed that MCH was positively correlated with TES, DHEA and luteinizing hormone and negatively correlated with SHBG (all P<0.05). Binary logistic regression indicated that an increase in MCH may be a potential risk factor for PCOS occurrence ( OR=1.113, 95% CI 1.012-1.224, P=0.028). ROC analysis showed that MCH has diagnostic value for PCOS ( P<0.05), with an area under the curve of 0.713. Conclusion:Serum MCH is closely related to FAI, TES, and DHEA levels in PCOS patients and may play an important role in the etiology and progression of the syndrome.

AIM:To investigate the effect of fenofibrate(FF)on the heart of rats with high-altitude heart dis-ease-induced right ventricular hypertrophy(H-RVH),and to explore the mechanisms and associated signaling pathways.METHODS:A total of 36 six-week-old male SD rats were randomly divided into control,model(H-RVH),and FF inter-vention(H-RVH+FF)groups with 12 rats each.A rat model of H-RVH was established by single subcutaneous injection of Sugen 5416(20 mg/kg)and exposure to a hypoxic condition(5 000 m above sea level)for 21 d in all groups except the control group.The rats in H-RVH+FF group were given FF(60 mg·kg-1·d-1)through gavage,while those in control and model groups received equal volume of saline once daily for 21 d.Rat heart gross morphology was observed,and the heart volume and weight,right ventricular weight and other hypertrophy indexes were measured in each group at the end of the experiment.A right heart floating catheter was used for measuring pulmonary artery and right ventricular pressure.Cardi-ac function was checked through cardiac ultrasonography.The serum levels of atrial natriuretic peptide(ANP),N-termi-nal pro-brain natriuretic peptide(NT-proBNP),free fatty acids(FFA),and myocardial tissue glucose(Glu)in all groups of rats were detected.The protein expression of peroxisome proliferator-activated receptor α(PPARα),fatty acid binding protein 1(FABP1),carnitine palmitoyl transferase 1a(CPT1a),pyruvate dehydrogenase kinase(PDK),and pyruvate dehydrogenase(PDH)were detected through Western blot.RESULTS:(1)Compared with the control group,the H-RVH group showed a significant increase in heart morphology and weight and increases in heart weight/body weight(HW/BW),heart volume,right ventricular weight/heart weight(RVW/HW),and Fulton index(FI)(P<0.05).Cardiac mor-phology,volume,heart weight,and HW/BW significantly decreased in the fenofibrate intervention group compared with the H-RVH group(P<0.05).RVW/HW and FI also decreased.(2)The right heart float catheter test showed that the mean right ventricular pressure(mRVP)and mean pulmonary artery pressure(mPAP)significantly increased in the H-RVH group compared with the control group(P<0.01).The increases in mRVP and mPAP were reversed in rats in the fe-nofibrate intervention group compared with the H-RVH group.(3)Cardiac ultrasonography showed that compared with the control group,the H-RVH group had significantly increased right ventricular anterior wall(RVAW)and right ventricular posterior wall(RVPW)thickness(P<0.01),significantly decreased right ventricular end-diastolic diameter(RVEDD),and right ventricular end-diastolic length(RVEDL)(P<0.01).In addition,pulmonary artery acceleration time(PAAT)was reduced,ejection time(PAET)was prolonged,and PAAT/PAET ratio decreased(P<0.01).Compared with the H-RVH group,the fenofibrate intervention group showed significant decreases in RVAW and RVPW(P<0.05),increases in RVEDD and RVEDL,and an increase in PAAT/PAET ratio.(4)The kit assay showed that the levels of ANP and NT-Pro BNP in serum were significantly higher in the H-RVH group than in the control group(P<0.05),while the levels of both were lower in the fenofibrate intervention group.The levels of serum FFA and myocardial tissue Glu levels(P<0.05)were significantly higher in the H-RVH group than in the control group.The levels of serum FFA and myocardial tissue Glu level were significantly lower in the fenofibrate intervention group than in the H-RVH group(P<0.05).(5)Western blot results showed that the expression levels of PPARα,FABP1,CPT1a,and PDH in the myocardial tissues of rats in the H-RVH group were significantly reduced(P<0.01),whereas the expression level of PDK significantly increased relative to those of the control group(P<0.01).All the effects on the above indices in the H-RVH group can be significantly re-versed by fenofibrate intervention(P<0.05).CONCLUSION:Fenofibrate exerts a protective effect on the hearts of rats with right ventricular hypertrophy associated with high-altitude heart disease by activating PPARα/FABP1/CPT1a,en-hancing fatty acid oxidation,inhibiting PDK,and activating PDH to promote the aerobic oxidation of glucose.Hence,the medication can ameliorate glucose-lipid metabolism disorders.

Objective:To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 ( CYP19A1) gene with risk of breast cancer. Methods:Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No.2021-182). Results:No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups ( P>0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group ( P<0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages Ⅲ-Ⅳ were significantly higher than those at stage Ⅰ-Ⅱ ( P<0.05). Conclusion:Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.