Objective: To prepare an inactivated hepatitis A vaccine using a attenuated strain of hepatitis A virus (HAV) H2 and to analyze its immunizing dose, so as to provide the reference for development and production of inactivated hepatitis A vaccines. Methods: Human embryonic lung diploid cells (KMB17) were infected with attenuated HAV H2 strain to proliferate the virus, then the cells containing viruses were harvested, extracted and purified. The obtained virus concentrate was prepared into vaccine bulk and test vaccines with 1 280 EU/mL antigen content. Vaccine testing was carried out according to the inactivated hepatitis A vaccine standards specified in the Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). A total of 110 mice were randomly divided into 11 groups, including 5 dose groups (80, 160, 320, 640 and 1 280 EU/dose) of the test vaccine and the reference vaccine, as well as the adjuvant control group. Mice were immunized twice by intraperitoneal injection, their serum HAV antibodies were detected, and the geometric mean titer (GMT) and positive conversion rate of antibodies were analyzed to evaluate the immunising dose of the vaccine. Results: The antigen content and viral titer of the virus harvest solution were 5 120 EU/mL and 8.33 lgCCID50/mL, respectively. The removal rate of foreign protein reached 98.05% and the recovery rate of antigen was 66.25%. The test vaccine met the requirements of Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). The GMTs of HAV antibodies in the test vaccine and the reference vaccine dose groups after the second immunization were more than twice higher than those after the first immunization. Regardless of primary immunization or secondary immunization, the GMTs (log2) of HAV antibodies in the test vaccine groups with doses of 160 EU/dose and above were higher than those in the 80 EU/dose group (all P<0.05), while there was no statistically significant differences between the dose groups of 160 EU/dose and above (all P>0.05). The antibody positive conversion rate of 160 EU/dose and above of the test vaccine was 100.00% after the secondary immunization. Conclusions The inactivated hepatitis A vaccine of attenuated H2 strain tested in this study demonstrates strong immunogenicity in mice, suggesting its potential as a candidate vaccine. The preliminary analysis indicates an immunizing dose of 320 EU/dose for children and 640 EU/dose for adults.

Objective:To investigate the clinical effect of autologous fat transplantation combined with hair transplantation in the treatment of hard and/or thin scalp flat scar after burn.Methods:The clinical data of patients with hard and thin scalp scar after burn admitted to the Department of Plastic Surgery of Peking University Third Hospital from January 2017 to December 2022 were retrospectively analyzed. Fat was extracted from the lower abdomen or outer thigh during the operation, and then injected into the scalp scar after standing for 15 minutes, about 0.8 ml/cm 2 under the hard and/or thin scar area, and 0.2-0.4 ml/cm 2 under the thick and soft scar area. Three months after fat transplantation, hair transplantation was performed in the scar bald area, and the transplant density was 25-35 follicular units (FUs)/cm 2 in the hard and thin scar area, and 30-40 FUs /cm 2 in the thick and soft scar area. The Vancouver scar scale (VSS) was used by two third party plastic surgeons to score the hard and/or thin scar areas of the scalp before and 3 months after scalp fat transplantation. The VSS score was expressed as M ( Q1, Q3), and the preoperative and postoperative data were compared by paired sample Wilcoxon signed rank test. During hair transplantation, the density of implanted hair in the hard and/or thin scar area were recorded. The density of living hair at these sites was measured at the last follow-up, and then the survival rate of hair (living hair density/implant hair density ×100%) was calculated. A third party plastic surgeon evaluated the extent to which scalp scars in the hair transplant area were covered, including completely covered, basically covered, partially covered. Patients’ evaluation with the surgical result was divided into very satisfied, satisfied and dissatisfied. Results:A total of 57 patients with scalp scar after burn were included in this group, including 31 males and 26 females, aged 13-47 years old. The time from scalp scarring to treatment was 8-41 years. The area of scalp scar was 17-120 cm 2, with an average of 63.3 cm 2. The fat injection volume of 57 patients was 13-75 ml. The hair transplantation was performed 3-8 months after a single fat filling procedure. The total amount of hair transplantation was 510-3 120 FUs. The total score of postoperative scar VSS was 4(3, 4), significantly lower than the preoperative score of 7(6, 7) ( W=6.70, P < 0.001). The color, thickness, blood vessel distribution and softness were significantly reduced compared with those before surgery ( P< 0.01). All patients were followed up for 12-18 months (mean, 14 months) after hair transplantation. The survival rate of hair in hard and thin scar area was 68.2% (22.7 FUs/cm 2/33.3 FUs/cm 2) to 89.7% (26.1 FUs/cm 2/29.1 FUs/cm 2), with an average of 81.3%. In 32 patients, scalp scars were completely covered. The scalp scar of 25 patients was basically covered. Twenty-nine patients were very satisfied with the result of the operation, and 28 patients were satisfied. Conclusion:The high survival rate of hair transplantation can be obtained by injecting fat under the hard and/or thin scalp scars before hair transplantation, which is an effective method to repair scalp scars.

Objective To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia(AVNRT)and atrioventricular re-entrant tachycardia(AVRT)using 12-lead wearable electrocardiogram devices.Methods A total of 356 samples of 12-lead supraventricular tachycardia(SVT)electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model,and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October,2021 to March,2023 were selected as the testing set.The changes in electrocardiogram parameters before and during induced tachycardia were compared.Based on multiscale deep neural network,an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated.The 3-lead electrocardiogram signals from Ⅱ,Ⅲ,and V1 were extracted to build new classification models,whose diagnostic efficacy was compared with that of the 12-lead model.Results Of the 101 patients with SVT in the testing set,68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study.The pre-trained model achieved a high area under the precision-recall curve(0.9492)and F1 score(0.8195)for identifying AVNRT in the validation set.The total F1 scores of the lead Ⅱ,Ⅲ,V1,3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597,0.6061,0.3419,0.6003 and 0.6136,respectively.Compared with the 12-lead classification model,the lead-Ⅲ model had a net reclassification index improvement of-0.029(P=0.878)and an integrated discrimination index improvement of-0.005(P=0.965).Conclusion The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Objective To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia(AVNRT)and atrioventricular re-entrant tachycardia(AVRT)using 12-lead wearable electrocardiogram devices.Methods A total of 356 samples of 12-lead supraventricular tachycardia(SVT)electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model,and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October,2021 to March,2023 were selected as the testing set.The changes in electrocardiogram parameters before and during induced tachycardia were compared.Based on multiscale deep neural network,an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated.The 3-lead electrocardiogram signals from Ⅱ,Ⅲ,and V1 were extracted to build new classification models,whose diagnostic efficacy was compared with that of the 12-lead model.Results Of the 101 patients with SVT in the testing set,68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study.The pre-trained model achieved a high area under the precision-recall curve(0.9492)and F1 score(0.8195)for identifying AVNRT in the validation set.The total F1 scores of the lead Ⅱ,Ⅲ,V1,3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597,0.6061,0.3419,0.6003 and 0.6136,respectively.Compared with the 12-lead classification model,the lead-Ⅲ model had a net reclassification index improvement of-0.029(P=0.878)and an integrated discrimination index improvement of-0.005(P=0.965).Conclusion The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Objective:To investigate the clinical effect of autologous fat transplantation combined with hair transplantation in the treatment of hard and/or thin scalp flat scar after burn.Methods:The clinical data of patients with hard and thin scalp scar after burn admitted to the Department of Plastic Surgery of Peking University Third Hospital from January 2017 to December 2022 were retrospectively analyzed. Fat was extracted from the lower abdomen or outer thigh during the operation, and then injected into the scalp scar after standing for 15 minutes, about 0.8 ml/cm 2 under the hard and/or thin scar area, and 0.2-0.4 ml/cm 2 under the thick and soft scar area. Three months after fat transplantation, hair transplantation was performed in the scar bald area, and the transplant density was 25-35 follicular units (FUs)/cm 2 in the hard and thin scar area, and 30-40 FUs /cm 2 in the thick and soft scar area. The Vancouver scar scale (VSS) was used by two third party plastic surgeons to score the hard and/or thin scar areas of the scalp before and 3 months after scalp fat transplantation. The VSS score was expressed as M ( Q1, Q3), and the preoperative and postoperative data were compared by paired sample Wilcoxon signed rank test. During hair transplantation, the density of implanted hair in the hard and/or thin scar area were recorded. The density of living hair at these sites was measured at the last follow-up, and then the survival rate of hair (living hair density/implant hair density ×100%) was calculated. A third party plastic surgeon evaluated the extent to which scalp scars in the hair transplant area were covered, including completely covered, basically covered, partially covered. Patients’ evaluation with the surgical result was divided into very satisfied, satisfied and dissatisfied. Results:A total of 57 patients with scalp scar after burn were included in this group, including 31 males and 26 females, aged 13-47 years old. The time from scalp scarring to treatment was 8-41 years. The area of scalp scar was 17-120 cm 2, with an average of 63.3 cm 2. The fat injection volume of 57 patients was 13-75 ml. The hair transplantation was performed 3-8 months after a single fat filling procedure. The total amount of hair transplantation was 510-3 120 FUs. The total score of postoperative scar VSS was 4(3, 4), significantly lower than the preoperative score of 7(6, 7) ( W=6.70, P < 0.001). The color, thickness, blood vessel distribution and softness were significantly reduced compared with those before surgery ( P< 0.01). All patients were followed up for 12-18 months (mean, 14 months) after hair transplantation. The survival rate of hair in hard and thin scar area was 68.2% (22.7 FUs/cm 2/33.3 FUs/cm 2) to 89.7% (26.1 FUs/cm 2/29.1 FUs/cm 2), with an average of 81.3%. In 32 patients, scalp scars were completely covered. The scalp scar of 25 patients was basically covered. Twenty-nine patients were very satisfied with the result of the operation, and 28 patients were satisfied. Conclusion:The high survival rate of hair transplantation can be obtained by injecting fat under the hard and/or thin scalp scars before hair transplantation, which is an effective method to repair scalp scars.

This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (mim-1), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand (complex F) ismore stable than that inthereverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen-bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA‍-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.
Molecular Dynamics Simulation ; Consensus ; DNA ; Hydrogen

Hepatocellular carcinoma (HCC) is a kind of primary liver cancer with a high mortality rate. In China, the incidence ratio in males to females with HCC is 2:1–5:1. The difference in sex hormone pathways between males and females and the interaction between androgen/androgen receptors and HBV can lead to an incidence difference between males and females with HCC. Hence, the androgen/androgen receptor oncogenic pathway in hepatocellular carcinoma has received considerable attention. This review mainly summarizes the recent research progress on the androgen/androgen receptor oncogenic pathway in hepatocellular carcinoma.

Statistics plays an important role in medical research， and the selection of appropriate statistical methods is crucial for drawing reliable and valuable conclusions. This paper provides a brief introduction to commonly used statistical analysis methods for medical data， covering descriptive analysis， parametric test， nonparametric test， correlation analysis， regression analysis， and analysis of survival data. It focuses on discussing the assumptions of multiple linear regression， logistic regression and Cox proportional risk regression， as well as how to choose the appropriate statistical methods for analyzing and interpreting medical data based on different research objectives and data types.

Clinical research reports serve as the presentation of scientific research findings and directly reflect the quality of the research. This article describes the writing of different types of clinical research reports， such as observational studies and randomized controlled trial studies， with a particular focus on randomized controlled trials. Each scientific research design has its reporting focus， and the writing of scientific research papers has uniform requirements and a specific writing format. Mastering the proper format of drafting research reports is of practical value and significant importance for conduction high-quality clinical research.

Objective:To compare the geographical differences and time trends of liver cancer incidence and mortality in different regions around the world so as to predict the future burden of liver cancer.Methods:The incidence and mortality data of liver cancer in different Human Development Index (HDI) countries from 2000 to 2020 were collected from the GLOBOCAN 2020 database. The joinpoint model and annual percent change (APC) were used to analyze the liver cancer global incidence and mortality as well as future epidemic trends from 2000 to 2020.Results:ASMR for male liver cancer was increased from 8.0/100, 000 in 2000 to 7.1/100,000 in 2015 (APC = -0.7, 95% CI: -1.2 ~ -0.3, P = 0.002), while ASMR for female liver cancer was increased from 3.0/100, 000 in 2000 to 2.8/100, 000 in 2015 (APC = -0.5, 95% CI: -0.8 ~ -0.2, P < 0.001). The ratio of male to female ASMR was 2.67:1 in 2000 and 2.51:1 in 2015, indicating a slight narrowing of the difference in mortality between men and women. In 2020, the global ASIR and ASMR for liver cancer were 9.5/100 000 and 8.7/100 000, respectively. Male ASIR and ASMR (14.1/100, 000 and 12.9/100, 000, respectively) were 2 ~ 3 times higher than females (5.2/100, 000 and 4.8/100, 000, respectively). There were significant differences between ASIR and ASMR in different HDI countries and regions ( PASIR = 0.008, PASMR < 0.001), and the distributions of ASMR and ASIR were very similar. New cases and deaths were expected to increase by 58.6% (143,6744) and 60.9% (133, 5 375) in 2040, with the number of cases and deaths increasing by 39,7003 and 37,4208 in Asia, respectively. Conclusion:ASMR due to liver cancer worldwide has had a downward trend between 2000 and 2015. However, the latest epidemiological status and predictions of liver cancer in 2020 indicate that prevention and control will still be a major challenge globally in the next 20 years.