Exploration and thinking on promoting the innovational and transformational ability of an outstanding discipline in a grade A tertiary hospital / 中华医学科研管理杂志

Objective:The paper aims to take the Department of Nephrology of Peking University First Hospital as an example to explore the practice of promoting innovation and transformation of an outstanding discipline.Methods:A descriptive analysis was carried out on the research basis, research output, and the status quo of disciplinary innovation and transformation of the nephrology department.Results:The main result showed that through the strategic layout of research direction from the characteristics of the discipline, transformation of traditional consciousness, enhancement of the capacity of innovation subject, policy guidance and incentive, promotion of collaborative innovation of medical enterprises and research institutes, the effect of enhancement of innovation and transformation had been shown.Conclusions:In order to do a good job in the innovation and transformation of an outstanding discipline, clinical hospitals need to support clinical medical research based on clinical problems and resource coordination, strengthen the whole process management and service of intellectual property protection, implement performance evaluation related to innovation and transformation, and introduce and cultivate complex talents for innovation and transformation.

CiteSpace-based visualization analysis of domestic and foreign researches on post-traumatic stress disorder in recent five years / 四川精神卫生

ObjectiveTo understand the research status of post-traumatic stress disorder （PTSD） at home and abroad in recent five years， and to grasp the research frontiers and hot spots in this field. MethodsTwo electronic databases， Web of Science and China National Knowledge Infrastructure （CNKI）， were retrieved for the literature published from January 1， 2017 to December 31， 2021. A total of 8 505 literatures were included， then the visualization analysis of the number of publications， authors， countries， institutions and keywords was conducted based on Microsoft Excel and CiteSpace software. Results① The number of publications in domestic and foreign showed an increasing trend in recent five years. ② In foreign literature， the top five countries in terms of the number of publications were the United States， the United Kingdom， China， Australia and Canada， with Canada having the highest centrality （0.18）. ③ Both domestic and foreign research institutions were dominated by universities. ④ In terms of the number of articles published， the top three foreign scholars were Bryant RA， Ressler KJ and Greenberg N， and the top three Chinese scholars were Wu Xinchun， Li Yuefeng， Yan Xingke and Zhang Guiqing （tied for the third place）. Compared with foreign authors， the number of articles published by Chinese scholars was relatively small. ⑤ In terms of research keywords， PTSD and depression were of more concern in both domestic and foreign. ConclusionIn recent five years， PTSD has been a hot topic at home and abroad， with both domestic and international studies focusing on PTSD and depression， and strengthening international exchanges may help promote progress in the field of PTSD research.

Analysis of the clinical features and the risk factors of severe human metapneu movirus-associated community acquired pneumonia in children / 中华儿科杂志

Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ2=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.

Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years / 中国中药杂志

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, β-amyloid(Aβ), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Pharmacotherapies for Central Post-Stroke Pain: A Systematic Review and Network Meta-Analysis.

Background: Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown. Aim: The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs. Results: Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31; P - score = 0.93), prednisone (SMD -2.38, 95% CI -3.09 to -1.67; P - score = 0.92), levetiracetam (SMD -2.11, 95% CI -2.97 to -1.26; P - score = 0.87), lamotrigine (SMD -1.39, 95% CI -2.21 to -0.58; P - score = 0.73), etanercept (SMD -0.92, 95% CI -1.8 to -0.03; P - score = 0.59), and pregabalin (SMD -0.46, 95% CI -0.71 to -0.22; P - score = 0.41) had significantly better treatment effect. Pamidronate, prednisone, and levetiracetam ranked as the first three most effective treatments. In subgroup analyses, prednisone, levetiracetam, lamotrigine, and pregabalin were more effective than placebo as oral pharmacotherapies, while etanercept was more effective than placebo as injectable pharmacotherapy. Conclusions: Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.

Delivery of Circular mRNA via Degradable Lipid Nanoparticles against SARS-COV-2 Delta Variant

mRNA vaccines have emerged as a most promising and potent platform in the fight against various diseases including the COVID-19 pandemic. However, the intrinsic instability, varying side effects associated with the delivery systems, and continuous emergence of virus variants highlight the urgent need for the development of stable, safe and efficacious mRNA vaccines. In this study, by screening a panel of proprietary biodegradable ionizable lipidoids, we reported on a novel mRNA vaccine (cmRNA-1130) formed from a biodegradable lipidoid with eight ester bonds in the branched tail (AX4) and synthetic circular mRNA (cmRNA) encoding the trimeric Delta receptor binding domain (RBD) of SARS-CoV-2 spike protein for the induction of robust immune activation. The AX4-based lipid nanoparticles (AX4-LNP) revealed much faster elimination rate from liver and spleen in comparison with commercialized MC3-based LNP (MC3-LNP) and afforded normal level of alanine transferase (ALT), aspartate aminotransferase (AST), and creatinine (CRE) in BALB/c mice. Following intramuscular (IM) administration in BALB/c mice, cmRNA-1130 elicited potent and sustained neutralizing antibodies, RBD-specific CD4+ and CD8+ T effector memory cells (Tem), and Th1-biased T cell activations. cmRNA-1130 vaccine showed excellent stability against 6-month storage at 4 {degrees}C and freezing-thawing cycles. In brief, our study highlights mRNA vaccines based on cmRNA and biodegradable AX4 lipids hold great potential as superb therapeutic platforms for the treatment of varying diseases.

Analysis of RECQL4 gene variant in a child with Rothmund-Thomson syndrome / 中华医学遗传学杂志

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.

Knowledge levels of chronic obstructive pulmonary disease among physicians in primary care and related factors: a survey in Zhumadian City of Henan Province / 中华全科医师杂志

Objective:To survey the knowledge levels of chronic obstructive pulmonary disease(COPD) among physicians in primary care and related factors.Methods:A questionnaire survey was conducted during December 2020 to December 2021 among 1 232 primary care doctors in Zhumadian City of Henan Province. The questionnaire included basic information, knowledge of COPD and its management, and the training received. The COPD-related knowledge levels and the influencing factors were analyzed using logistic regression model.Results:A total of 1 232 questionnaires were collected, and 1 221(99.1%) were valid, which were included in the analysis. The survey showed that the COPD-related knowledge level was significantly associated with the educational level of primary care physicians(χ2=9.91, P<0.05); and the Pearson correlation analysis showed that the knowledge level was positively correlated with educational level( r=0.09, P<0.05). In terms of risk factors, causes of acute exacerbations, and treatment and management of COPD, there was a linear relationship between the education level and knowledge level(χ2=13.86, P<0.001;χ2=20.93, P<0.001); the Pearson correlation analysis showed that the knowledge level was correlated with higher educational level( r=0.11, P<0.001; r=0.13, P<0.001). In terms of symptoms and diagnosis, there was no correlation between educational level and awareness level(χ2=1.90, P=0.168). Logistic regression model showed that compared to doctors aged 20-30, those aged 31-40 had a higher COPD-related knowledge level( OR=2.24, 95% CI: 1.16-4.30, P=0.016); compare to the doctors with associate degree, doctors with bachelor degree or above had a higher COPD-related knowledge( OR=1.71, 95% CI:1.24-2.37, P=0.001); compared to doctors without professional title, those with primary or middle-rank professional title had a higher knowledge level( OR=1.65, 95% CI: 1.28-2.13, P<0.001; OR=2.15, 95% CI: 1.46-3.16, P<0.001); compared to doctors with training time<3, those with training time ≥3 had a higher knowledge level( OR=1.15, 95% CI: 1.21-2.61, P=0.021). Conclusion:The COPD-related knowledge levels(especially in knowledge of risk factors and causes of acute exacerbations, and treatment and management of COPD) among doctors in primary care are affected by age, educational background, professional title, and the number of training sessions.

Diagnosis, treatment and management status of COPD in county-level hospitals of China / 中华健康管理学杂志

Objective:To understand the current management status of chronic obstructive pulmonary disease (COPD) in county-level hospitals in China from 2020 to 2021.Methods:This survey was led by the China Association of County Hospital President. In 2021, a questionnaire survey was conducted on 633 secondary and tertiary hospitals from 24 provinces, and the questionnaire was filled out according to the actual situation of the hospital in 2020, including diagnosis, treatment, rehabilitation and comprehensive management of COPD. The nature of the hospital was divided into public or private. The type of hospital was divided into general or specialist. The economic zones was divided into eastern, central or western. Through the content of the questionnaire, the influencing factors of the diagnosis, treatment and management capabilities of COPD in county-level hospitals were explored.Results:A total of 633 questionnaires were collected in this survey, and 26 were removed due to the incorrect information or information loss. Thus, a total of 607 questionnaires were finally included in this survey, including 425 secondary hospitals and 182 tertiary hospitals; 591 public hospitals and 16 private hospitals. For the capabilities of diagnosis and treatment, the tertiary hospital was significantly better than the secondary hospital on the availability of respiratory outpatient clinics, COPD outpatient clinics, outpatient comprehensive clinics, respiratory ward and intensive care unit (ICU) (94.5% and 78.4%, 51.1% and 32.7%, 79.7% and 67.3 %, 84.6% and 59.8%, 78.6% and 61.9%, respectively) (all P<0.01). In terms of lung function test and bronchodilation test, tertiary hospitals performed significantly better than secondary hospitals ( P<0.05). There was no difference in availability of inhaled bronchodilators and expectorant drugs among different hospital levels, nature, type, and economic zones ( P>0.05). However, the proportion of hospitals with available triple inhalation drugs was lower in secondary hospitals than tertiary hospitals. For the non-drug treatment, the proportion of general hospitals carrying out vaccination was significantly higher than that of specialized hospitals (52.7% and 28.1%, P=0.010). The tertiary hospitals performed significantly better than secondary hospitals in smoking cessation guidance (98.4% and 94.4%, P=0.031). In terms of rehabilitation, tertiary hospitals also performed significantly better than secondary hospitals (79.7% and 61.9%, P<0.001). The proportion of hospitals carrying out long-term management of COPD in tertiary hospitals was significantly higher than secondary hospitals, and the proportion in public hospitals was significantly higher than private hospitals (80.2% and 61.2%, 68.2% and 18.8%, both P<0.001). Conclusions:County hospitals in China have a good overall performance in the diagnosis and drug treatment of COPD, but need to be further improved in non-drug treatment, rehabilitation, and comprehensive management. The hospital level is the main factor affecting the management ability of COPD. The nature and type of hospital mainly affect the construction of departments and comprehensive management of COPD.

Screening status of high-risk population of chronic obstructive pulmonary disease in areas where “Happy Breathing” is running / 中华健康管理学杂志

Objective:To analyze the screening status of high-risk population of chronic obstructive pulmonary disease (COPD) in areas where “Happy Breathing” project was carried out.Method:There were 1 008 518 COPD screening questionnaires (COPD-SQ) filled out in 18 pilot areas of “Happy Breathing” program from November 2017 to October 2019. Within subjects who scored 16 points or more with COPD-SQ, 63 523 of them underwent pulmonary function tests before bronchodilator inhalation. Stratified analysis, chi-square test and other statistical methods were performed to analyze the distribution of COPD high-risk groups, the prevalence of COPD among high-risk groups and risk factors of COPD.Results:Results in this study suggested that the high-risk population of COPD accounted for 18.99% (191 498/1 008 518) of the population who received the questionnaire screening. Among the high-risk population who received lung function test, 31.59% (20 070/63 523) were screened and diagnosed as COPD patients. As for risk factors of COPD, the proportion of high-risk population was higher in people with a smoking index ≥600 compared with never-smokers (54.20% vs 12.60%), and the prevalence of COPD was also higher in people with a smoking index ≥600 (35.62% vs 25.22%); people who were exposed to second-hand smoke almost every day also showed an increased proportion of high-risk groups (27.39% vs 10.97%) and a high prevalence of COPD (31.36% vs 27.93%) than those without second-hand smoke exposure; the presence or absence of biofuel exposure also caused the difference in the proportion of high-risk groups (33.92% vs 13.11%); compared with people without a family history of respiratory diseases, the proportion of high-risk groups (56.38% vs 16.42%) and the prevalence of COPD in high-risk groups (32.40% vs 29.19%) were both higher in those with family history of respiratory diseases.Conclusion:The high-risk group of COPD accounts for a high proportion of the screened population, suggesting that the “Happy Breathing” project is feasible and necessary in COPD screening, which is helpful for the development of COPD diagnosis and treatment.

Methodological quality assessment of systematic reviews or Meta-analyses of intervention randomized controlled trials published in the Sichuan Mental Health / 四川精神卫生

ObjectiveTo evaluate the methodological quality of systematic review / Meta analysis （SR/MA） of intervention randomized controlled trial （RCT） published in the Sichuan Mental Health. MethodsThe literature databases such as Wanfang Data， China National Knowledge Infrastructure （CNKI）， VIP Database for Chinese Technical Periodical （VIP） and Chinese Biomedical Literature Database （CBM） were searched for the SRs/MAs of intervention RCTs published in the Sichuan Mental Health from the initial issue to the issue published on 31 June 2021. Then the methodological quality of eligible SRs/MAs were assessed using A Measurement Tool to Assess systematic Reviews 2 （AMSTAR 2）. ResultsThe literature search yielded 24 full-text articles， and the mean AMSTAR 2 score of the included SRs/MAs was （5.21±3.63） with a range from 1 to 11. The total AMSTAR 2 score for SRs/MAs showed difference in terms of the publication date prior to or later than the publication of AMSTAR-2 tool （t=-5.499）， number of authors ≤ 2 or ≥ 3 （t=-6.736）， with or without funding support （t=3.329） and author unit nature （F=7.827）， with statistical significance （P<0.01）. All selected studies had deficiencies on explicit statement of a priori design and registrations， list of excluded studies and reasons for exclusion， sources of funding for the research in systematic review， potential conflicts of interest statement， and funding information of the systematic review. ConclusionThe methodological quality of SRs/MAs of intervention RCTs published in the Sichuan Mental Health varies widely， After the release of AMSTAR 2， the methodological quality has improved， but the report still needs to be further standardized to provide high-quality evidence-based evidence.

A deep-learning model for the assessment of coronary heart disease and related risk factors via the evaluation of retinal fundus photographs / 中华心血管病杂志

Objective: To develop and validate a deep learning model based on fundus photos for the identification of coronary heart disease (CHD) and associated risk factors. Methods: Subjects aged>18 years with complete clinical examination data from 149 hospitals and medical examination centers in China were included in this retrospective study. Two radiologists, who were not aware of the study design, independently evaluated the coronary angiography images of each subject to make CHD diagnosis. A deep learning model using convolutional neural networks (CNN) was used to label the fundus images according to the presence or absence of CHD, and the model was proportionally divided into training and test sets for model training. The prediction performance of the model was evaluated in the test set using monocular and binocular fundus images respectively. Prediction efficacy of the algorithm for cardiovascular risk factors (e.g., age, systolic blood pressure, gender) and coronary events were evaluated by regression analysis using the area under the receiver operating characteristic curve (AUC) and R2 correlation coefficient. Results: The study retrospectively collected 51 765 fundus images from 25 222 subjects, including 10 255 patients with CHD, and there were 14 419 male subjects in this cohort. Of these, 46 603 fundus images from 22 701 subjects were included in the training set and 5 162 fundus images from 2 521 subjects were included in the test set. In the test set, the deep learning model could accurately predict patients' age with an R2 value of 0.931 (95%CI 0.929-0.933) for monocular photos and 0.938 (95%CI 0.936-0.940) for binocular photos. The AUC values for sex identification from single eye and binocular retinal fundus images were 0.983 (95%CI 0.982-0.984) and 0.988 (95%CI 0.987-0.989), respectively. The AUC value of the model was 0.876 (95%CI 0.874-0.877) with either monocular fundus photographs and AUC value was 0.885 (95%CI 0.884-0.888) with binocular fundus photographs to predict CHD, the sensitivity of the model was 0.894 and specificity was 0.755 with accuracy of 0.714 using binocular fundus photographs for the prediction of CHD. Conclusion: The deep learning model based on fundus photographs performs well in identifying coronary heart disease and assessing related risk factors such as age and sex.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Relationship between body mass index and sexual development in Chinese children / 中华儿科杂志

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

Immune Microenvironment in Langerhans Cell Histiocytosis: Potential Prognostic Indicators.

In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum samples from 54 treatment-naïve patients were analyzed quantitatively for inflammatory cytokines and immunoglobulins before and after the induction of chemotherapy. The initial serum sIL-2R, TNF-α, and IL-10 of untreated LCH patients with risk organ involvement (RO+) were significantly higher than those with single-system (SS) involvement. LCH patients with hematologic involvement exhibited a significantly higher sIL-2R, TNF-α, IL-10, and IL-1ß expression, as compared to the group without involvement. sIL-2R, TNF-α, and IL-10 were increased in patients with liver or spleen involvement. Th cells have decreased in the liver+ and spleen+ group, and Ts cells were significantly decreased in non-response group after induction chemotherapy. The serum level of immune indices represents, to some extent, the severity of the disease. Pertinent laboratory inspections can be used to improve risk stratification and guide immunotherapy.

Central precocious puberty with primary pigmented nodular adrenocortical disease: One case report / 中华内分泌代谢杂志

To report the clinical, imaging, and pathological feature of a rare case of central precocious puberty with primary pigmented nodular adrenocortical disease(PPNAD), and to conduct a retrospective analysis of PPNAD with relevant literatures. The pubic hair was found in the child for more than one year. Physical examination showed Cushing′s syndrome. ACTH in blood decreased, cortisol rhythm was disordered, 24-hour urine free cortisol increased and the paradoxical increase of urine free cortisol after high dose dexamethasone suppression test. Adrenal enhancement computed tomography(CT)showed multiple small nodular shadows in bilateral adrenal glands. Gonadotropin releasing hormone(GnRH)stimulation test supported central precocious puberty and GnRH analogue was used to control the sexual development. PPNAD was supported by pathology result. The symptoms of Cushing′s syndrome were relieved partially after left adrenalectomy.

Analysis of Clinical Characteristics and Prognosis in Children with Acute Megakaryoblastic Leukemia without Down Syndrome / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL).@*METHODS@#The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment.@*RESULTS@#The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10@*CONCLUSION@#Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.

Congenital lipoid adrenal hyperplasia with 46, XY karyotype and male external genitalia: Two cases and literature review / 中华内分泌代谢杂志

Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder, which is characterized by adrenal insufficiency and 46, XY sex reversal. Two cases of CLAH with 46, XY karyotype exhibited male external genitalia were reported to explore the clinical and genetic features. A retrospective analysis of CLAH with relevant literatures was performed.

Molecular evolution of SARS-CoV-2 structural genes: evidence of positive selection in spike glycoprotein

SARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed roughly 3090 SARS-CoV-2 isolates from GenBank database. The distribution of the four gene alleles is determined:16 for E, 40 for M, 131 for N and 173 for S genes. Phylogenetic analysis shows that global SARS-CoV-2 isolates can be clustered into three to four major clades based on the protein sequences of these genes. Intragenic recombination event isnt detected among different alleles. However, purifying selection has conducted on the evolution of these genes. By analyzing full genomic sequences of these alleles using codon-substitution models (M8, M3 and M2a) and likelihood ratio tests (LRTs) of codeML package, it reveals that codon 614 of S glycoprotein has subjected to strong positive selection pressure and a persistent D614G mutation is identified. The definitive positive selection of D614G mutation is further confirmed by internal fixed effects likelihood (IFEL) and Evolutionary Fingerprinting methods implemented in Hyphy package. In addition, another potential positive selection site at codon 5 in the signal sequence of the S protein is also identified. The allele containing D614G mutation has undergone significant expansion during SARS-CoV-2 global pandemic, implying a better adaptability of isolates with the mutation. However, L5F allele expansion is relatively restricted. The D614G mutation is located at the subdomain 2 (SD2) of C-terminal portion (CTP) of the S1 subunit. Protein structural modeling shows that the D614G mutation may cause the disruption of salt bridge among S protein monomers increase their flexibility, and in turn promote receptor binding domain (RBD) opening, virus attachment and entry into host cells. Located at the signal sequence of S protein as it is, L5F mutation may facilitate the protein folding, assembly, and secretion of the virus. This is the first evidence of positive Darwinian selection in the spike gene of SARS-CoV-2, which contributes to a better understanding of the adaptive mechanism of this virus and help to provide insights for developing novel therapeutic approaches as well as effective vaccines by targeting on mutation sites.