BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective:To compare and explore the diagnostic performance of adding value of transabdominal and transvaginal contrast-enhanced ultrasound (CEUS) to Ovarian-Adnexal Reporting and Data System (O-RADS US) risk stratification and management system in differential diagnosis of adnexal masses.Methods:A total of 180 adnexal masses with solid components in 175 women were enrolled retrospectively between September 2021 and November 2022. All patients underwent routine Doppler ultrasound examinations and CEUS examinations. Among these masses, 107 masses underwent with transabdominal CEUS, 58 masses underwent with transvaginal CEUS, and 15 masses underwent both transvaginal and transabdominal CEUS. All patients were scheduled for surgery and pathological results served as the reference standard. Routine Doppler ultrasound and CEUS images and video were reviewed by a subspecialty radiologist using Vuebox software. The O-RADS US was downgraded or upgraded according to the CEUS characteristics of the masses. The diagnostic accuracy was assessed using ROC curve analysis. The area under the ROC curve (AUC) was calculated to compare the diagnostic performance of adding value of transabdominal and transvaginal CEUS to O-RADS US.Results:The diagnostic performance of adding transabdominal and transvaginal CEUS to O-RADS US were both significantly higher than of O-RADS US alone (transabdominal CEUS: AUC 0.83 vs 0.76, P=0.018; transvaginal CEUS: AUC 0.92 vs 0.81, P=0.013). Combination of transvaginal CEUS and O-RADS US was superior to that of combination of transabdominal and O-RADS US in the differential diagnosis of adnexal masses ( P=0.047). When the maximal diameter of adnexal masses ≤40 mm, transabdominal combined with O-RADS US presented the lowest diagnostic performance, with an AUC of 0.73. Conclusions:Combination of transvaginal CEUS and O-RADS US was superior to that of combination of transabdominal and O-RADS US in assessing adnexal masses with solid components. When the maximal diameter of adnexal masses ≤40 mm, transvaginal CEUS examination was recommended.

Neuregulin 4 (NRG4) is a newly discovered adipokine,which plays crucial roles in many physiological processes such as energy balance,and glucose and lipid metabolism.The transcriptional regulation of NRG4 gene remains largely unknown.Our previous 5'RACE analysis showed that the tran-scription start sites (TSS) of chicken NRG4 gene were dispersed over a region of 200 bp,suggesting that chicken NRG4 gene possesses a dispersed promoter.In the present study,the promoter activity of the proximal exon and intron of chicken NRG4 gene was analyzed.Dual-luciferase reporter assay demonstra-ted that the genomic fragment (-122/+452) containing exon 1,intron 1,and exon 2 of chicken NRG4 gene had strong bidirectional promoter activity.Bioinformatics analysis showed that there was a putative binding site of the transcription factor CCAAT enhancer-binding proteinα(C/EBPα) in exon 2 of chick-en NRG4 gene.Reporter gene assay showed that both deletion and site-directed mutagenesis of the C/EBPα binding site abrogated the regulatory effect of C/EBPα on the promoter activity of the-122/+452 fragment of chicken NRG4 gene.Gene expression correlation analysis showed that C/EBPα and NRG4 gene expression were positively correlated in chicken adipose tissues.ChIP-PCR revealed that C/EBPα directly binds to the exon 2 of NRG4 gene in chicken adipose.In conclusion,the proximal exon and intron of chicken NRG4 gene has bidirectional promoter activity,and C/EBPα directly regulates NRG4 gene expression in chicken adipose via binding to its exon 2.

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.
Humans ; Male ; Carcinoma, Transitional Cell/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Urinary Bladder Neoplasms/pathology* ; Urinary Bladder/pathology* ; Retrospective Studies ; Prostatic Neoplasms ; Biomarkers, Tumor

Aim To investigate the effects of menthol, a transient receptor potential melastatin-8 channel activator, on treating pulmonary arterial hypertension (PAH) in PAH model rats caused by monocrotaline (MCT). Methods Male Sprague-Dawley rats were divided into six groups randomly (control group, MCT group, MCT + menthol 1 mg • kg

Aim To explore the important role of HDAC5 in P-gp expression in rats in high-altitude low oxygen environment and its effect on phenytoin sodium pharmacokinetics. Methods Wistar rats were transported to Batang, Yushu, Qinghai, at an altitude of 4010 m, with 6 rats in each group, divided into 1 d and 3 d groups. Different groups were given phenytoin, phenytoin combined with hypericin, and phenytoin combined with verapamil. Plasma and liver tissues were collected at different time after taking the drug in the plateau area. The concentration of phenytoin sodium in plasma was determined by UFLC-MS method. Changes in protein expression were detected by Western blot. Results The results of UFLC-MS showed that the AUC

OBJECTIVE: This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer. METHODS: A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors. RESULTS: Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia. CONCLUSION Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.
Humans ; Female ; Caregivers ; Activities of Daily Living ; Cross-Sectional Studies ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Lung Neoplasms/epidemiology*

OBJECTIVE: To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province. METHODS: Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression. RESULTS: The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66). CONCLUSION The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.
Female ; Humans ; Aged ; Menarche ; Menopause ; Regression Analysis ; Fertility ; China/epidemiology* ; Age Factors