To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Aim To explore the correlation between carotid atherosclerosis(CAS)and neutrophil/lymphocyte ratio(NLR)in patients with early morning hypertension,and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning.Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected,and their basic data,blood routine and blood biochemical indexes were collected.All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection.According to the presence or absence of CAS,all selected patients were divided into morning hypertension with CAS group(n=197)and morning hypertension without CAS group(n=58).Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS,and to construct and verify an individual line chart model to predict the risk of early morning hypertension pa-tients with CAS.Results The age,NLR,neutrophils(NE),monocytes(MO),white blood cell(WBC),total cho-lesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDLC)increased in the early morning hyperten-sion with CAS group compared with those in the morning hypertension group without CAS,while the HDLC decreased(P＜0.05).The results of multivariate Logistic regression analysis showed that the age,NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group,while HDLC was lower;Age,NLR and TC were independent risk factors of early morning hypertension with CAS,while HDLC was inde-pendent protective factors of morning hypertension with CAS.Based on the results of multivariate Logistic regression anal-ysis,an individualized line chart model for predicting early morning hypertension with CAS was constructed.The area un-der the ROC curve of the line chart model was 0.853(95％CI:0.802-0.904,P＜0.01).The result of Hosmer Leme-show fit test was x2=1.665(P＞0.05).Conclusions There was a positive correlation between NLR and morning hy-pertension with CAS,and NLR was an independent risk factor for morning hypertension with CAS.The individualized line chart model based on age,NLR,TC and HDLC can effectively predict the risk of hypertension with CAS in the early morn-ing,which provides a theoretical basis for early detection and prevention of atherosclerosis.

OBJECTIVE: To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression. METHODS: A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment. RESULTS: After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05). CONCLUSION Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.
Humans ; Female ; Electroacupuncture ; Adult ; Acupuncture Points ; Meridians ; Ovarian Reserve ; Young Adult ; Liver Diseases/physiopathology* ; Liver/metabolism* ; Ovary/physiopathology* ; Treatment Outcome ; Depression/therapy*

Objective To investigate the independent influences on the occurrence of ICU Acquired Weakness(ICU-AW)in elderly patients undergoing third-and fourth-level surgeries,to construct a prediction model and draw a column-line diagram,and to internally validate the model.Methods A convenience sampling method was used to select 186 elderly patients undergoing tertiary and quaternary surgeries who were hospitalized in 3 tertiary A hospitals in Beijing from May to December 2022 as the study subjects.Single-factor and multifactor logistic regression were used to analyze the risk factors for ICU-AW in elderly patients undergoing third-and fourth-degree surgeries.A risk prediction model was established and the model was visualized by drawing a column-line diagram,and the receiver operator characteristic curve(ROC)and the Hosmer-Lemeshow tests were applied to verify the predictive effect of the model.Results ICU-AW occurred in 40 of 186 cases in the modeling group,with an incidence rate of 21.5％.The results of univariate analysis showed that the 2 groups of preoperative physiology score and surgical severity score included in the physiology and surgical severity scoring system,age,presence of cardiac disease,hemoglobin(within 24 h of admission to the ICU),blood urea nitrogen(within 24 h of admission to the ICU),blood creatinine(within 24 h of admission to the ICU),presence of braking,mode of establishment of mechanical ventilation,presence of nutritional therapy,number of sedative or analgesic drugs used,whether vasoactive drugs were used,whether diuretics were used,and the level of hemoglobin,blood urea nitrogen and blood creatinine within 24 h after admission to ICU the difference is statistically significant(P＜0.05).The results of multifactorial logistic regression analysis showed that preoperative physiology scores included in the physiology and surgical severity scoring system,the presence of cardiac disease,the presence of braking,the presence of nutritional therapy,and the number of sedative or analgesic medications used were the predictors of the occurrence of ICU-AW in elderly patients undergoing third-and fourth-degree surgeries(OR were 1.364,2.344,5.568,5.823,1.109,all P＜0.05).The above 5 factors were plotted as independent variables in a column-line graph,and the area under the ROC curve of the model was 0.859(95％CI 0.793～0.924),with an optimal critical value of 0.156,a sensitivity of 0.875,a specificity of 0.705,and a Hosmer-Lemeshow goodness-of-fit test of x2=3.906,P=0.865,Brier score of 0.109,and a decision analysis curve indicating that patients could benefit.Conclusion The predictive effect of the constructed model is good,and it can be used as a reference for early and rapid identification of the risk of ICU-AW in elderly patients undergoing third-and fourth-degree surgeries by clinical staff,and timely provision of preventive intervention programs.

Objective:To carry out high-risk foot examination and grading combined with two examination methods for inpatients with type 2 diabetes, and explore the influencing factors of the occurrence and development of high-risk foot, and investigate their foot care behavior status.Methods:From July 2021 to January 2022, 409 patients with diabetes who were admitted to the Department of Endocrinology, Department of Geriatrics, Department of Cardiology, Urology Surgery and Department of Ophthalmology of Xuanwu Hospital of Capital Medical University were selected as research subjects by convenience sampling. The General Information Questionnaire, Standardized Process of At-risk Foot Screening and Stratification for Diabetic Patients, InIow's Screening for the High-Risk Diabetic Foot: A 60-Second Tool, and Foot Care Behavior Questionnaire for Diabetic Patients. Single factor analysis and Logistic regression analysis were used to explore the factors influencing the occurrence and development of high-risk foot in type 2 diabetes patients. A total of 409 questionnaires were distributed, and 392 valid questionnaires were collected, with an effective response rate of 95.8% (392/409) .Results:Among 392 patients, the detection rate of high-risk diabetic foot (HRDF) was 76.3% (299/392), and the proportion of high-risk foot grade 2 was the largest (193). Age ( OR=1.042, P<0.01) and years of hypertension ( OR=1.030, P<0.05) were independent influencing factors for the occurrence of HRDF, with statistically significant differences. Taking the high risk foot grade 3 as a reference, cerebrovascular disease [ OR=16.408, 95% CI (1.323, 203.417) ], diabetes course [ OR=1.066, 95% CI (1.008, 1.128) ], education level in middle school [ OR=0.180, 95% CI (0.056, 0.581) ], education level in primary school and below [ OR=0.126, 95% CI (0.019, 0.841) ] were independent influencing factors for the progress of high risk foot. The foot care behavior of high-risk foot patients with high risk levels was not superior to that of patients with low risk levels. Conclusions:The combination of the two screening methods can meet the examination needs of clinical and nursing medical staff for inpatients with type 2 diabetes. Emphasizing the influencing factors of HRDF occurrence and development can provide reference for early identification of high-risk foot.

Objective:To explore the correlation between frailty and foot care behavior in elderly patients with high-risk diabetic foot.Methods:From January to June 2022, 220 patients with high-risk diabetic foot who were admitted to the Department of Endocrinology and Department of Geriatrics of Xuanwu Hospital of Capital Medical University were selected by convenience sampling as the research object. The patients were investigated with the General Information Questionnaire, Gavin's Weighted Scale for Diabetic Foot Risk Factors for Progression to Ulceration, the Chinese version of the Frail Scale and the Foot Care Behavior Questionnaire for Diabetic Patients. Spearman correlation analysis was used to explore the correlation between frailty and foot care behavior in elderly patients with high-risk diabetic foot. Multiple linear regression was used to analyze the influencing factors of foot care behavior in elderly patients with high-risk diabetic foot. A total of 220 questionnaires were distributed, and 210 valid questionnaires were collected, with an effective response rate of 95.45% (210/220) .Results:The standardized score of the Foot Care Behavior Questionnaire for Diabetic Patients among 210 elderly patients with high-risk diabetic foot was (56.65±11.27), which was in the middle to low level. Among them, 126 patients (60.00%) were at a low level, and 80 patients (38.10%) were at a middle level. The incidence of frailty in 210 elderly patients with high-risk diabetic foot was 27.14% (57/210). The results of correlation analysis showed that the frailty score of elderly patients with high-risk diabetic foot were negatively correlated with the scores of the foot and footwear examination, foot cleaning and maintenance, footwear selection, and the total score of Foot Care Behavior Questionnaire for Diabetic Patients ( P<0.05). The results of multiple linear regression analysis showed that gender, frailty, foot risk classification and living conditions were the influencing factors of foot care behavior in elderly patients with high-risk diabetic foot ( P<0.05) . Conclusions:The foot care behavior of elderly patients with high-risk diabetic foot needs to be improved. The higher the degree of frailty, the lower the level of foot care behavior. Medical and nursing staff should formulate targeted intervention measures according to the characteristics of patients to improve or delay the progression of patients' frailty, thereby improving their foot care behavior and preventing the occurrence of diabetic foot.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

OBJECTIVE: To explore the genetic basis for a child with Rothmund-Thomson syndrome (RTS). METHODS: The child has featured poikeloderma, short stature, cataract, sparse hair and skeletal malformation. Peripheral blood samples of the child and her family members were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The child was found to harbor compound heterozygous variants of the RECQL4 gene, namely c.1048_1049delAG and c.2886-1G>A, among which c.2886-1G>A was unreported previously. According to the ACMG guidelines, the c.1048_1049delAG was predicted to be pathogenic (PVS1+PM3_Strong+PM2), while the c.2886-1G>A was predicted to be likely pathogenic (PVS1+PM2). CONCLUSION The compound heterozygous variants of the RECQL4 gene probably underlay the pathogenesis of RTS in this patient. Above finding has enriched the mutational spectrum of the RECQL4 gene.
Child ; Family ; Female ; Humans ; Mutation ; RecQ Helicases/genetics* ; Rothmund-Thomson Syndrome/genetics* ; Whole Exome Sequencing

Objective:To evaluate the performance of the Cepheid Xpert Xpress Flu/RSV assay (Xpert) in the detection of children infected with influenza virus (Flu) or respiratory syncytial virus (RSV).Methods:Nasopharyngeal specimens were collected from children who showed symptoms of respiratory infection and tested FluA, FluB and RSV by Xpert and sequencing assay respectively side by side. Discordant result were tested with a laboratory-developed real-time PCR for resolution.Results:A total of 388 nasopharyngeal swabs (NAPs) from children with acute respiratory tract infection were analyzed and the result showed 91.75-94.85% agreement between two tests. The sensitivity of FluA, FluB and RSV detected by Xpert and sequencing assay were 99.21% (125/126) vs. 92.86% (117/126), 100.00% (109/109) vs. 84.40% (92/109) and 100.00% (52/52) vs. 40.38% (21/52), respectively. The specificity of FluA, FluB and RSV detected by Xpert were all lower than that of the sequencing assay: 95.42% (250/262) vs 99.24% (260/262), 99.28% (277/279) vs 99.64% (278/279) and 99.70% (335/336) vs 100.00% (336/336). The positive predictive values (PPV) of FluA, FluB and RSV detected by Xpert were lower than those of the sequencing assay: 91.30% (126/138) vs. 98.33% (118/120), 98.18% (108/110) vs. 98.92% (92/93) and 98.11% (52/53) vs. 100.00% (21/21), respectively. The negative predictive values (NPV) of FluA, FluB and RSV detected by Xpert were higher than those of the sequencing assay: 99.60% (251/252) vs. 96.67% (261/270), 99.64% (279/280) vs. 94.27% (280/297) and 100.00% (337/337) vs. 91.60% (338/369).Conclusions:The Cepheid Xpert Xpress Flu/RSV assay is a sensitive, reliable and rapid assay for the detection of FluA, FluB and RSV in pediatrics.