ObjectiveTo identify immunogenic cell death （ICD）-related genes in hepatocellular carcinoma （HCC）， and to establish a scoring model based on these genes for predicting the prognosis and tumor microenvironment characteristics of HCC. MethodsThe Cancer Genome Atlas database was used to obtain HCC datasets， and heatmaps were used to display the expression of 57 ICD-related genes in HCC. A cluster analysis was conducted based on the expression of ICD-related genes， and two ICD subtypes （low and high ICD expression groups） were analyzed in terms of gene ontology enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis， somatic mutation， and immune cell infiltration. The LASSO Cox regression risk model was constructed to evaluate its clinical application value， and a nomogram model was established to predict the 1-， 3-， and 5-year survival rates of patients. In addition， qRT-PCR was used to validate the expression levels of key genes in the model. The independent-samples t test was used for comparison between two groups， and the univariate and multivariate Cox regression analyses were used to determine prognostic factors among clinicopathological features. The Kaplan-Meier survival curve was used for prognostic analysis， and the Spearman rank correlation test was used for correlation analysis. ResultsThe low ICD expression group had a poorer prognosis， while the high ICD expression group had relatively favorable clinical outcomes （P=0.004）. Further analysis showed that the high ICD expression group was associated with an immune-active microenvironment， and the genes were mainly enriched in immune-related pathways such as immunoglobulin receptor binding， hematopoietic cell lineage， and B cell receptor. The results of somatic mutation analysis showed that the high ICD expression group had higher expression levels of CD274， CTLA4， HAVCR2， TIGIT， PDCD1， and PDCD1LG2 （all P<0.05）. A risk prediction model was established using 8 ICD-related genes， i.e.， HSP90AA1， ATG5， BAX， PPIA， HSPA4， TLR2， TREM1， and LY96， and this model showed a good predictive value across different clinical characteristics. The univariate and multivariate Cox regression analyses showed that age and risk score were independent prognostic factors for overall survival in the training set （both P<0.05）. The results of qRT-PCR showed that the relative expression levels of HSPA4 and REM1 in HCC tumor samples were significantly higher than those in adjacent tissue samples （both P<0.001）. For the patients with an increase in ICD risk score， the ICD risk score was negatively correlated with γδT cells （r=-0.29， P<0.05）， plasma cells （r=-0.3， P<0.05）， and CD8⁺T lymphocytes （r=-0.37， P<0.05） and was positively correlated with memory B cells （r=0.38， P<0.05）， resting dendritic cells （r=0.47， P<0.05）， and M0 macrophages （r=0.49， P<0.05）. ConclusionThis study identifies the ICD-related genes that are associated with the prognosis of HCC， which provides insights into the immune characteristics of different ICD expression profiles. The risk model and the nomogram model established in this study have a significant value for predicting the prognosis of HCC patients and guiding immunotherapy for HCC patients.

OBJECTIVE To mine the cardiovascular safety signal of relugolix， and provide a reference for the listing of this drug in China and future clinical safety drug evaluation. METHODS The adverse event （AE） report data of relugolix， as the primary or secondary suspected drug， was collected from the FDA Adverse Event Reporting System （FAERS） from the first quarter of 2021 to the third quarter of 2023. The reporting odds ratio （ROR） method was used for data mining. The AEs in the FAERS database were identified and coded using preferred terms （PT） stated in version 24.0 of the Medical Dictionary for Drug Regulatory Activities （MedDRA）. The AEs of the target drug were identified by the narrow standardized MedDRA query （SMQ） terms and high-level term （HLT）. Sensitivity analysis was conducted using AEs suspected to be primarily or secondarily related to relugolix or related to drug interaction and concomitant drug， and broad SMQ terms. RESULTS A total of 4 354 relugolix-related AE reports were extracted. In the primary analysis， nine SMQ terms were analyzed， involving 2 positive signals such as dyslipidemia and hyperglycemia/new onset diabetes mellitus. Eleven HLTs were analyzed， and three positive signals were detected for three terms including cholesterol analyses， triglyceride analyses and hyperglycemia conditions （non-alternative analysis）. Sensitivity analysis results indicated the reliability of the study findings. CONCLUSIONS Relugolix may induce risk signals related to high blood lipids and high blood glucose， but no moderate risk signals such as hypertension， heart disease， and stroke are found. During relugolix treatment in clinical practice， attention must be paid to hyperlipidemia and hyperglycemia-related AE.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Objective:To explore the diagnostic value of clinical, multi-parameter magnetic resonance imaging (MP-MRI) combined with transrectal ultrasound elasticity data for prostate cancer.Methods:A retrospective analysis was conducted on patient data from November 2021 to March 2023 when transrectal prostate two-dimensional ultrasound, real-time strain elastography of the prostate, MP-MRI examination of the prostate, and prostate biopsy were performed simultaneously at the Meizhou People′s Hospital. We collected patient age, height, weight, free serum prostate specific antigen (fPSA), total prostate specific antigen (tPSA), fPSA/tPSA, MRI prostate imaging report and data system (PI-RADS) scores, and ultrasound elasticity values. Four predictive models for prostate cancer diagnosis were constructed using multivariate logistic regression for comparison, and the optimal model was selected to construct a column chart. The diagnostic performance of different models was evaluated using receiver operating characteristic (ROC) curves, and the diagnostic performance of column charts was evaluated using calibration curves.Results:This study included a total of 117 patients with 117 prostate lesions, 47 benign prostate lesions, and 70 prostate cancer lesions. There were statistically significant differences in age, fPSA, tPSA, fPSA/tPSA, PI-RADS scores, and ultrasound elasticity values between benign and malignant lesions patients (all P<0.01). The area under the curve (AUC) of the clinical model (age+ tPSA+ fPSA+ fPSA/tPSA), MRI model (PI-RADS score), ultrasound elastic model, and clinical+ MRI+ ultrasound elastic combined model for diagnosing prostate cancer were 0.86, 0.86, 0.92, and 0.98, respectively. Conclusions:Compared with a single diagnostic model, the combination of age, tPSA, fPSA/tPSA, PI-RADS scores, and ultrasound elasticity value model can improve the diagnostic rate of prostate cancer.

Objective:To investigate the application effect of a sequential clinical skill curriculum system in standardized residency training.Methods:A total of 300 residents who participated in the residency training of a clinical medical school from 2020 to 2022 were selected as the research subjects, among whom 46 residents in the experimental group had received the clinical skill training course of the clinical medical school in the undergraduate stage, and 254 in the control group had not received such training in the undergraduate stage. The teaching effect of the two groups was observed from the first year to the third year after they entered the residency training base and were trained together based on the curriculum system. SPSS 24.0 statistical software was used for data analysis, and the main statistical methods included descriptive analysis, the Kolmogorov-Smirnov test, the Mann-Whitney U test, and the chi-square test. Results:Before the residents entered the residency base, class 2020 [60.0(52.0,60.0) vs. 51.0(48.0,53.0)], class 2021 [54.0(52.0,56.0) vs. 51.0(48.0,53.0)] and class 2022 [53.0(51.0,55.0) vs. 50.0(47.0,51.0)] The difference between the entry base grades of the residents in the experimental group compared to the control group was statistically significant ( P<0.05). After 36 months of residency training, the difference between the residents in the trial group and the control group in the 2020 class was not statistically significant when it came to the passing rate of the final exam ( χ2=1.20, P=0.273). At the end of 12 months of residency training, there was a statistically significant difference ( P<0.05) between the scores of residents in the experimental group compared with the control group in the theoretical examination [124.0 (123.8,125.0) vs. 115.0 (101.0,125.0)] and medical history taking [92.0 (91.0,95.0) vs. 85.1 (79.3,94.5)]. The differences were not statistically significant ( P>0.05) at the end of 6, 18, and 24 months of residency training. At the end of 6 months [93.0(90.0,97.0) vs. 89.0(86.3,95.0)], 12 months [94.0(92.0,95.0) vs. 89.0(87.0,92.0)] and 18 months [90.0(86.5,93.5) vs. 81.0(69.0,91.0)] of residency training, residents in the experimental group Physical examination scores were statistically significant compared to the control group ( P<0.05). At the end of 24 months of residency training, there was no statistically significant difference ( P>0.05) between the physical examination scores of residents in the experimental group compared with the control group in the classes of 2020 [92.0(87.5,95.3) vs. 85.0(79.0,92.0)] and 2021 [94.0(87.0,96.0) vs. 90.0(84.0,95.0)]. Conclusions:The clinical skill curriculum system can help to improve the comprehensive clinical ability of residents, and the teaching contents and methods of physical examination should be further optimized, with a focus on the training of doctor-patient communication skills and humanistic literacy among residents in the future.

Objective:To explore the safety and efficacy of Propafenone in terminating paroxysmal supraventricular tachycardia (PSVT) in children and analyze the factors influencing the effectiveness.Methods:A retrospective study was conducted on 169 PSVT children treated with Propafenone in the Department of Pediatric Cardiology, Heart Center, the First Hospital of Tsinghua University from September 2014 to October 2021.There were 118 boys and 51 girls with an average age of (2.84±2.91) years (age range: 14 days-13 years). According to age, they were divided into ≤ 1-year-old group, >1-3-year-old group, >3-7-year-old group, and >7-year-old group.Mea-surement data were compared between groups using t-test and Mann- Whitney U test.Counting data were analyzed by χ2 test. Results:Among the 169 children with PSVT, 65 cases (38.5%) were below 1 year old, 47 cases (27.8%) were >1-3 years old, 40 cases (23.7%) were >3-7 years old, 17 cases (10.1%) were above 7 years old.About 24 cases (14.2%) were combined with congenital heart disease.A total of 153 cases (90.5%) had nonspecific symptoms at the first visit.A total of 4.1% (7/169 cases) were complicated with tachycardia-induced cardiomyopathy, and their left ventricular ejection fraction increased from (44.0±4.0)% to (53.7±6.9)% after successful control of PSVT ( t=-4.700, P=0.003). The complete termination of PSVT by intravenous Propafenone was achieved in 125 of 169 cases (74.0%, 125/169 cases). The complete termination rate after multiple times of administration (74.0%) was significantly higher than that after the first intravenous injection (53.3%, 90/169 cases) ( χ2=15.657, P<0.001). There was a significant difference regarding the complete termination rate between children ≤1 year old (60.0%, 39/65 cases) and those >1 year old (82.7%, 86/104 cases) ( χ2=10.696, P=0.001). For children ≤1 year old, 1.5 mg/kg Propafenone (51.1%, 23/45 cases) showed better efficacy for PSVT termination than 1.0 mg/kg Propafenone (20.0%, 4/20 cases) ( χ2=5.519, P=0.019). For children >1 year old, there was no significant diffe-rence between 1.5 mg/kg and 1.0 mg/kg Propafenone groups (57.9% vs.62.1%) ( χ2=0.180, P=0.671). The adverse reaction rate of intravenous Propafenone was 9.5% (16/169 cases). One case presented with severe hypotension, which occurred in a child with right cardiac insufficiency with tricuspid valve depression; 15 cases showed abnormal cardiac conduction and recovered spontaneously in a short time.There was no deterioration of cardiac function in children with mildly to moderately reduced cardiac function. Conclusions:It is relatively safe and effective to terminate PSVT in children with intravenous Propafenone.The complete termination rate is 74.0%, which is related to age, dose and times of administration.Despite of low incidence of side effects, Propafenone should not be used to treat PSVT with cardiac function which is significantly impaired or unclear secondary to persistent tachycardia.Special attention should be paid to cardiac function deterioration in these patients.

Clinical data of 43 patients who underwent endoscopic resection for gastrointestinal stromal tumors (GIST) of length ≤1.2 cm at the Digestive Endoscopy Center of the 909th Hospital from January 2016 to December 2018 were retrospectively analyzed. The patients were divided into the endoscopic ligation resection (ELR) group ( n=27) and the endoscopic submucosal excavation (ESE) group ( n=16). The general, perioperative and follow-up data of the two groups were compared. The results showed that there was no significant difference in the general data between the two groups. The operation time was 20.0 (18.0,25.0) min in the ELR group and 27.5 (23.0,37.5) min in the ESE group, showing significant difference ( U=92.5, P=0.001). The en bloc resection rates were 100.0% (27/27) in the ELR group and 81.3% (13/16) in the ESE group, showing significant difference ( P=0.045). The postoperative hospital stays were 3 (2,4) days in the ELR group and 5 (4,6) days in the ESE group, showing significant difference ( U=125.5, P=0.020). There was no significant difference in the intraoperative bleeding rate, intraoperative hemorrhage volume, intraoperative perforation rate, number of hemostatic clips or postoperative complications including hemorrhage, fever and peritonitis between the two groups ( P>0.05). During the follow-up, there was no recurrence or metastasis of GIST in both groups. ELR and ESE can be safe and effective for small GIST ≤1.2 cm in diameter. Compared with the ESE group, the operation time and postoperative hospital stay are shorter with higher en bloc resection rate in the ELR group.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To evaluate the effect of preventive application of PEG-rhG-CSF on the prevention of neutropenia during concurrent chemoradiotherapy in patients with lung cancer.Methods:A total of 149 patients with lung cancer who received concurrent chemoradiotherapy at Peking University Cancer Hospital from April 2020 to April 2021 were retrospectively analyzed. There were 79 cases in the prevention group, including 48 cases of primary prevention group (preventive application of PEG-rhG-CSF in all concurrent chemoradiotherapy cycles) and 31 cases of secondary prevention group (preventive application of PEG-rhG-CSF in the concurrent chemoradiotherapy cycles after neutropenia occurred). There were 70 cases in non-prevention group. The incidence of grade 3-4 neutropenia, the completion rate of concurrent chemoradiotherapy, the rate of chemoradiotherapy dose reduction and treatment delay, and the rate of hematological toxicities related hospitalization were compared between the prevention group and the non-prevention group.Results:The incidence of grade 3-4 neutropenia in the whole group was 32.2% (48/149), including 6.3% (3/48) in the primary prevention group, 9.7% (3/31) in the secondary prevention group, and 35.7% (25/70) in the non-prevention group. The difference was statistically significant ( χ2=17.81, P<0.001) in the incidence of grade 3-4 neutropenia. The incidence of febrile neutropenia was 3.4% (5/149) in the whole group, but none of them occurred in the primary prevention group. The full completion rate of concurrent chemotherapy was 96.2% (76/79) in the prevention group, which was significantly higher than 82.9% (58/70) in the non-prevention group ( χ2=7.30, P=0.007). The incidence of treatment delayed and dose reduction of chemoradiotherapy was 19.0% (15/79) in the prevention group and 40.0% (28/70) in the non-prevention group, and the difference was statistically significant ( χ2=7.98, P=0.005). Conclusions:The preventive application of PEG-rhG-CSF can effectively reduce the incidence of neutropenia and better ensure the concurrent chemoradiotherapy in lung cancer patients on schedule.

Objective:To investigate clinical electrophysiological characteristics of idiopathic ventricular arrhythmias (VAs) and outcomes of radiofrequency catheter ablation (RFCA) in pediatric patients.Methods:A total of 328 consecutive pediatric patients with VAs and treated with RFCA in the First Hospital of Tsinghua University from January 2014 to December 2019 were recruited, involving 205 males and 123 females with the mean age of (7.8±3.9) years and the mean body weight of (32.8±17.7) kg.Their clinical electrophysiological characteristics, RFCA outcomes of different origins of VAs and complications were analyzed.Results:Among the 328 patients with the mean onset age of (5.4±4.1) years, 57.6% had frequent premature ventricular complex (PVC), 28.7% had paroxysmal ventricular tachycardia (VT) and 13.7% had incessant VT.A total of 38/328 cases (11.6%) VAs children were complicated with tachycardia-induced cardiomyopathy.Except for 13 cases of non-induced VAs, among 315 cases there were 152/328 cases (46.4%) originated from the ventricular outflow tract (including 46.1% of the origination of the right ventricular outflow tract septum, 27.6% of the origination of the left coronary cusp, 18.4% of the origination of the right coronary cusp, and 7.9% of the origination of the right ventricular outflow tract free wall), 55/328 cases (16.5%) originated from the tricuspid valve, 54/328 cases (17.4%) originated from the left posterior fascicle, 39/328 cases (11.9%) originated from the left posterior papillary muscle, 5/328 cases (1.5%) originated from multi-origin VAs, 3/328 cases (0.9%) originated from the left anterior fascicle, and 7/328 cases (2.1%) originated from other origins.Among 307/328 cases (93.6%) VAs patients receiving RFCA, 271/307 cases (88.3%) were instantly successful, 14/307 cases (4.6%) were effectively treated and 22/307 cases (7.2%) were invalid.During the follow-up time of 3 to 36 months, there were 42/271 cases (15.5%) recurrent cases.The mean radiation time and dose were (3.2±5.8) min, and (1.4±2.6) mGy, respectively.The mean dose-area product (DAP) was (384.2±42.6) mGy·cm 2.A total of 4/328 cases (1.2%) reported perioperative vascular complication.In 20 infant patients younger than 3 years, only 1 case was not induced during procedure of RFCA, and the remaining 19 cases were performed with RFCA, including 18/19 cases (94.7%) with an instant success and 4/18 (22.2%) recurrent cases during follow-up.There were 1/20 case (5.0%) had perioperative vascular complication caused by vascular puncture.No serious complications, such as myocardial perforation, cardiac tamponade and atrioventricular block were reported. Conclusions:The right ventricular outflow tract septum is the most common origin of the idiopathic VAs in pediatric patients.VAs originated from the ventricular outflow tract and tricuspid valve usually have an acceptable outcome following ablation.The recurrent rate is high following ablation in VAs cases originated from the left ventricular fascicle and posterior papillary muscle.RFCA is safe and effective for drug resistant or intolerant VAs in infants, but the surgical indications should be strictly mastered and operated by experienced pediatric electrophysiologists.The radiation dose of RFCA can be limited in a safe range under the guidance of the 3-dimensional mapping system.