Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

Objective:To analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Objective:Exploring gene-age interactions associated with breast cancer prognosis based on epigenomic data.Methods:Differential expression analysis of DNA methylation was conducted using multiple independent epigenomic datasets of breast cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The false discovery rate (FDR) method was used for multiple corrections, retaining differentially methylated sites with q-FDR≤0.05. A three-stage analytic strategy was implemented, using a multivariable Cox proportional hazards regression model to examine gene-age interactions. In the discovery phase, signals with q-FDR ≤ 0.05 were screened out using TCGA-BRCA database. In validation phaseⅠ, the interaction was validated using GSE72245 data, with criteria of P≤0.05 and consistent effect direction. In validation phaseⅡ, the signals were further validated using GSE37754 and GSE75067 data. A prognostic prediction model was constructed by incorporating clinical indicators and interaction signals. Results:The three-stage analytic strategy identified a methylation site (cg16126280 EBF1), which interacted with age to jointly affect the overall survival time of patients (interaction HR= 1.001 1,95% CI:1.000 7-1.001 5, P<0.001). Stratified analysis by age showed that the effect of hypermethylation of cg16126280 EBF1 was completely opposite in younger patients ( HR=0.550 5, 95% CI: 0.383 8-0.789 6, P=0.001) and older patients ( HR=2.166 5, 95% CI: 1.285 2-3.652 2, P=0.004). Conclusions:The DNA methylation site cg16126280 EBF1 exhibits an interaction with age, jointly influencing the prognosis of breast cancer in a complex association pattern. This finding contributes new population-based evidence for the development of age-specific targeted drugs.

Objective By comparison with the surgical resection,to evaluate the relapse-free survival(RFS),overall survival(OS),and clinical safety of transcatheter hepatic arterial chemoembolization(TACE)combined with microwave ablation(MWA)in the treatment of early primary hepatocellular carcinoma(HCC).Methods From January 2013 to January 2018 at authors'hospital,51 HCC patients received TACE combined with MWA(TACE+MWA group)and 58 HCC patients received surgical resection(RES group).The HCC lesions were single tumor with diameter ≤7 cm or multiple tumors with stage Ⅰ a-Ⅱ a meeting the"up-to-7"criteria.The postoperative RFS,OS,and clinical safety were compared between the two groups.Results The one-,3-and 5-year RFS in the TACE+MWA group were 84.3％,37.3％and 13.7％respectively,which in the RES group were 67.2％,27.6％and 13.8％respectively.The difference in the one-year RFS between the two groups was statistically significant(P=0.039),and the differences in the 3-and 5-year RFS between the two groups were not statistically significant(P=0.281 and P=0.992,respectively).The one-,3-and 5-year survival rates in the TACE+MWA group were 98％,62.7％and 45.1％respectively,which in the RES group were 94.8％,75.9％and 44.8％respectively,and the differences between the two groups were not statistically significant(P=0.704,P=0.137 and P=0.977 respectively).No treatment-related death occurred in both groups.In the TACE+MWA group,the main complications included transient embolism syndrome,abdominal pain during ablation procedure,and mild to moderate transient elevation of transaminase after treatment.In the RES group,the main postoperative complications included fever,pleural effusion,abdominal effusion,and intraoperative bleeding;and in one patient the postoperative liver function impairment worsened to Child grade C.The average cost of hospitalization in the TACE+MWA group was(39 834.98±6 717.38)Chinese yuan,which in the RES group was(49 042.59±11 810.69)Chinese yuan,the difference between the two groups was statistically significant(P=0.017).The hospitalization length in the TACE+MWA group was 23 days(19-28 days),which in the RES group was 21 days(17-25 days),and the difference between the two groups was not statistically significant(P=0.196).Conclusion For the treatment of early HCC,TACE combined with MWA has reliable curative effect,and also has the advantages of being safe and economical.Therefore,this therapy can be used as a preferred option of non-surgical treatment for single tumor with ≤7 cm diameter or multiple tumors with stage Ⅰ a-Ⅱa meeting"up-to-7"criteria.(J Intervent Radiol,2024,33:488-494)

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Objective To analysis the effectiveness and cost of Internet-based anticoagulation clinic versus traditional anticoagulation clinic treatment at Nanjing Drum Tower Hospital during the COVID-19 pandemic.Methods We reviewed and analyzed the clinical data of patients receiving anticoagulation management through Internet-based outpatient care and traditional outpatient care in Nanjing Drum Tower Hospital,from June 1,2020 to June 30,2021.Variability in time in therapeutic range(TTR)and international normalized ratio(INR)were calculated for enrolled patients.Patients meeting TTR≥60%and INR variability<0.65 were considered optimal anticoagulation quality.Cost-effectiveness analysis was conducted from the patients'perspective,with results expressed using the incremental cost-effectiveness ratio(ICER).Results In the"Internet-based anticoagulation outpatient care"and"traditional face-to-face anticoagulation outpatient care"groups,19 individuals(67.86%)and 67 individuals(76.14%)met the criteria for optimal anticoagulation quality,respectively.The mean TTR was(71.83±19.17)%in the Internet-based group and(71.74±23.41)%in the traditional face-to-face group,indicating similar levels of warfarin anticoagulation quality between the two groups.The ICER was calculated as 327.17 yuan,less than the per capita gross domestic product(GDP)of 2021.Conclusion During the COVID-19 pandemic,Nanjing Drum Tower Hospital's Internet-based anticoagulation outpatient care effectively complemented the government's epidemic control policies.It ensured equivalent anticoagulation outcomes and significantly reduced patients'financial burdens.This approach offers new insights and guidance for optimizing healthcare services in the post-pandemic era.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To determine the impact of progressive rehabilitation intervention based on the FITT principle on the recovery of elderly patients with acute ST-segment elevation myocardi-al infarction(STEMI)after percutaneous coronary intervention(PCI).Methods A total of 184 STEMI patients admitted to our hospital between December 2021 and June 2023 were enrolled and randomly divided into a study group(n=92)and a control group(n=92).Routine rehabilita-tion intervention was given to the control group,and progressive rehabilitation intervention based on the FITT principle was given to the study group.Both groups were intervened for 12 weeks.Metabolite equivalents(MET)of the two groups were evaluated before and at 4,8 and 12 weeks after intervention.Their cardiopulmonary reserve function and quality of life were evaluated with cardiopulmonary exercise testing and myocardial infarction multidimensional assessment scale(MIDAS)before and at 12 weeks after intervention.The incidence of adverse cardiovascular events such as ventricular arrhythmia and heart failure(HF)during 6 months of follow-up was recorded.Results There were significant differences in two sets of MET value groups,time points,and group time point interactions(P＜0.01).No statistical difference was found in MET values be-tween the two groups before intervention(P＞0.05).The MET values were increased in both groups at 4,8 and 12 weeks after intervention than before intervention,and those in the study group were higher than those in the control group at above three time points(P＜0.05).Com-pared with before intervention,the peak oxygen uptake and anaerobic threshold oxygen uptake in 2 groups increased after intervention(P＜0.05).The peak oxygen uptake and anaerobic threshold oxygen uptake in the study group were higher than those in the control group[(23.52±1.86)ml/(min·kg)vs(21.36±2.60)ml/(min·kg),P＜0.01;(14.33±2.02)ml/(min·kg)vs(12.08±1.76)ml/(min·kg),P＜0.01];Compared with before intervention,the carbon dioxide ventilation equivalent slope of 2 groups decreased after intervention(P＜0.05).The carbon dioxide equivalent slope of the study group was lower than that of the control group(26.12±2.34 vs 28.10±2.52,P＜0.01).Compared with before intervention,the MIDAS score was decreased in both groups af-ter intervention(65.30±5.20 vs 96.64±7.33,P＜0.01;70.46±5.87 vs 95.80±7.26,P＜0.01),and the score of the study group was lower than that of the control group(65.30±5.20 vs 70.46±5.87,P＜0.01).After a 6-month follow-up,there was no significant difference in the incidence of adverse cardiovascular events between the two groups(P＞0.05).Conclusion Progressive reha-bilitation interventions based on the FITT principle can promote exercise tolerance,improve car-diopulmonary reserve function,and enhance the quality of life of elderly STEMI patients after PCI.