Global, regional, and national time trends in myocarditis-related mortality, 1990-2019: An age-period-cohort analysis.

OBJECTIVE: The aim of this study was to analyze the tendency of myocarditis mortality in 204 countries and areas during the last three decades and its connection with age, epoch, and birth cohort. MATERIALS AND METHODS: The Global Burden of Disease 2019 Study acquired a cause-specific myocarditis mortality estimate. The net drift, as well as the influence caused by age, period, and birth cohort, were evaluated by the age-period-cohort model. Additionally, we analyzed the tendency in research intensity and international collaboration across countries using 3,983 myocarditis-related publications from four periods during 1990-2019. RESULTS: During the last three decades, 101 of 204 countries and areas experienced an increase (net drifts ≥0.0%) or stagnant declines (≥-0.5%) in the death rate. In particular, increasing death rate was generally discovered in most countries whose Socio-demographic indexes (SDIs) are high and middle-high, such as the United States [net drift=2.11% (95% CI 1.71-2.51)] and Italy [2.65% (1.24-4.08)]. Countries with a higher number of deaths were more active in this field of study, such as the United States (237 publications), China (120), and Italy (73). The United States and Italy, whose total link strengths were 209 and 135, respectively, were more active in international collaborative studies. CONCLUSIONS: Despite the global decrease in myocarditis death rate during the last three decades, negative period and cohort effects and elevated mortality were discovered in numerous countries, especially in those whose SDIs were high, and the age distribution of deaths shifted from adolescent to middle-aged and older populations. We also observed a decline in myocarditis research in some countries with increased mortality.

[Sinogram interpolation combined with unsupervised image-to-image translation network for CT metal artifact correction].

OBJECTIVE: To propose a framework that combines sinogram interpolation with unsupervised image-to-image translation (UNIT) network to correct metal artifacts in CT images. METHODS: The initially corrected CT image and the prior image without artifacts, which were considered as different elements in two different domains, were input into the image transformation network to obtain the corrected image. Verification experiments were carried out to assess the effectiveness of the proposed method using the simulation data, and PSNR and SSIM were calculated for quantitative evaluation of the performance of the method. RESULTS: The experiment using the simulation data showed that the proposed method achieved better results for improving image quality as compared with other methods, and the corrected images preserved more details and structures. Compared with ADN algorithm, the proposed algorithm improved the PSNR and SSIM by 2.4449 and 0.0023 when the metal was small, by 5.9942 and 8.8388 for images with large metals, and by 8.8388 and 0.0130 when both small and large metals were present, respectively. CONCLUSION: The proposed method for metal artifact correction can effectively remove metal artifacts, improve image quality, and preserve more details and structures on CT images.

[Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness].

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

Directional atherectomy combined with drug-coated balloon angioplasty for superficial femoral arteriosclerosis obliterans.

INTRODUCTION: This study is an analysis of the therapeutic effects of directional atherectomy combined with drug-coated balloon angioplasty (DA+DCB) in treating superficial femoral arteriosclerosis obliterans. METHODS: Patients in our hospital with superficial femoral arteriosclerosis obliterans who received DA+DCB during the period June 2016 to February 2019 were identified retrospectively. Preoperative demographics, operative details and postoperative follow-up outcomes were analysed statistically. RESULTS: Between June 2016 and February 2019, 48 patients were enrolled in this retrospective study. The average age of the patients was 66.85 ± 11.28 years; 83.3% of the patients were male. During the procedure, flow-limiting dissection occurred frequently (9/48 patients) and there were six bailout stent implantations owing to flow-limiting dissections. The incidence rate of target artery thrombosis was 4.2% (2/48). There was no vessel perforation, embolism or operation-related death. The technical success rate was estimated at 100%. The mean ankle-brachial index of the patients was 0.54 ± 0.28 before the operation and 0.93 ± 0.13 before discharge (p < 0.0001). The mean follow-up time was 19.6 ± 9.0 months. The primary patency rate was 89.4%, 82.4% and 76.5% at 12, 24 and 36 months. The freedom from target lesion revascularisation (TLR) was 97.9%, 93.8% and 84.4% at 12, 24 and 36 months. CONCLUSION: The use of DA+DCB showed good clinical benefit for superficial femoral arteriosclerosis obliterans, which had good primary patency and freedom from TLR. Multicentre randomised controlled trials with long-term follow-up are needed.

[Annual review of interventional pulmonology in 2022].

Interventional pulmonology is an essential part of the treatment of respiratory diseases and an important component of modern respiratory medicine. In recent years, interventional respiratory medicine has kept up with the trend of the times, constantly developing and integrating various techniques, expanding the scope of application of interventional respiratory medicine, and developing in the direction of personalized and precision medicine as well. Here, we reviewed the new progress and up-to-date research achievements of interventional pulmonology from December 2021 to September 2022.

The incidence, prevalence, and survival analysis of pancreatic neuroendocrine tumors in the United States.

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) was increasing. The main purpose of this study was to statistically analyze the incidence and prevalence of pNETs and the main risk factors for the prognosis. METHODS: Based on the Surveillance, Epidemiology, and End Results (SEER) database, with three registries integrated, this study comprehensively displayed the annual age adjust incidence of pNETs from 1975 to 2018, the estimated 20-year limited-duration prevalence, and conducted the univariate and multivariate survival analysis. RESULTS: The incidence of pNETs has increased to about 1.5 per 100,000 population, and the prevalence has reached about 0.008% with the aged, Grade 1 and nonfunctional tumors accounting for the majority. The average median overall survival (OS), 5-year survival rate, and median disease-free survival (DFS) of pNETs patients from 1975 to 2018 were 85 months, 57.55%, and 220 months, respectively. From 2000 to 2018, the median OS was 94 months, and the 5-year survival rate was 59.94%. In multivariate survival analysis, the greatest risk factor was Grade 3&4 with HR = 3.62 (3.10-4.28), followed by distant stage with HR = 2.77 (2.28-3.36), and aged over 80 years old with HR = 2.26 (1.33-3.83). Surgery was a protective prognostic factor with HR = 0.34 (0.29-0.40). CONCLUSION: The incidence and prevalence of pNETs were still increasing, but the trend was gradual and aging in recent years. The survival time of pNETs was longer but has not changed much in recent years. The degrees of malignancy, stage, and operation were the most important prognosis factors.

It was the best of times, it was the worst of times: a tale of two cities-Beijing and Shanghai-why the divergent COVID-19 control outcomes?

Coronavirus disease 2019 (COVID-19) both creates and complicates public health challenges. Yet, the pandemic also provides a unique lens for dissecting complex issues in global health that could benefit society in the long run. In this article, we discuss the underlying reasons that can help explain the divergent COVID-19 control outcomes between Beijing and Shanghai-two advanced metropolises that are similar in their municipal capacity, administrative capability and pandemic strategy. We hope insights from this investigation contribute to the development of disease prevention systems, such as context-specific and data-driven public health strategies that could yield optimal pandemic control outcomes with minimal unintended consequences, both amid and beyond COVID-19.

[Phenotype and genotype analyses of two pedigrees with inherited fibrinogen deficiency].

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BßAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BßSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BßAla98Asp and p.BßSer473* were pathogenic. Protein models demonstrated that the p.BßAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BßSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BßAla98Asp heterozygous missense mutation and the p.BßSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.

[Evaluation of diagnostic efficacy of digital liquid chip method for detection of specific antineutrophil cytoplasmic antibodies].

To explore the clinical diagnostic efficacy of antineutrophil cytoplasmic antibody associated vasculitis (AAV) by comparing the consistency and coincidence rate of serum anti-myeloperoxidase (MPO) antibody and anti-protease 3 (PR3) antibody detected by digital liquid chip method (DLCM) and enzyme-linked immunosorbent assay (ELISA). To provide reference for the selection of detection methods of anti-MPO antibody and anti-PR3 antibody in clinical laboratory. This study is a cross-sectional study, a total of 307 cases of antineutrophil cytoplasmic antibodies were detected in the Department of Clinical Immunology, West China Hospital of Sichuan University from January to March 2021. The serum samples and related clinical information were collected. At the same time, the levels of anti-MPO antibody and anti-PR3 antibody in serum samples were detected by ELISA and DLCM, indirect immunofluorescence (IIF) was used to re-test the differential samples between the two methods. SPSS 26.0 was used to analyze the test results, Cohen's kappa coefficient analysis was used to compare the consistency of the two methods, and paired chi-square test was used to compare the sensitivity and specificity of the two methods to AAV. The results showed that the positive cases of anti-MPO antibody detected by ELISA and DLCM were 63 and 44, and the negative cases were 244 and 263; the positive cases of anti-PR3 antibody detected by ELISA and DLCM were 34 and 28, and the negative cases were 273 and 279. The results of anti-MPO antibody and anti-PR3 antibody detected by the two methods had good consistency and coincidence rate, in which the total coincidence rate of anti-MPO antibody was 92.51%, the positive coincidence rate was 66.67%, and the negative coincidence rate was 99.18%. The results of consistency analysis showed that kappa=0.741 had well consistency. The total coincidence rate of anti-PR3 antibody is 96.74%, the positive coincidence rate is 76.47%, and the negative coincidence rate is 99.27%. The consistency analysis results show that kappa=0.821 had strong consistency. The results of IIF re-test of differential samples showed that the coincidence rate between DLCM and IIF was higher. The results of comparative analysis of anti-MPO antibody and anti-PR3 antibody showed that the specificity of DLCM was better than that of ELISA, and its sensitivity was lower than that of ELISA. In conclusion, the results of anti-MPO antibody and anti-PR3 antibody detected by DLCM were consistent with those of ELISA. In the combined detection of anti-MPO antibody and anti-PR3 antibody, the specificity of DLCM is better than that of ELISA.

How to avoid future "Covid-19 origins" questions?

Origins debates regarding Covid-19 are gaining momentum again. In light of the continued infections and deaths of Covid-19 seen in countries rich and poor, rather than focusing the approach with "whodunit", developing solutions that can help societies become better prepared for future pandemics might be a more meaningful way to move forward. In this paper, we propose a solution that could help society better predict and prevent future pandemics. A system could allow humans to anonymously report potential infectious disease outbreaks without fearing backlash or prejudice and could automatically surveil for potential disease transfers or virus leaks. The proposed autonomous and anonymous pandemic reporting and surveillance system has the potential to help health officials locate infectious disease outbreaks before they form into pandemics. And in turn, it better prevents future pandemics and avoids Covid-19 origins debates.

Symptom burden, psychological distress, and symptom management status in hospitalized patients with advanced cancer: a multicenter study in China.

BACKGROUND: The management of physical symptoms and psychological distress of cancer patients is an important component of cancer care. The purpose of this study was to evaluate the symptom burden, psychological distress, and management status of hospitalized patients with advanced cancer in China and explore the potential influencing factors of undertreatment and non-treatment of symptoms. PATIENTS AND METHODS: A total of 2930 hospitalized patients with advanced cancer (top six types of cancer in China) were recruited from 10 centers all over China. Patient-reported MD Anderson Symptom Inventory, Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9) scales and symptom management-related information were collected and linked with the patient's clinical data. The proportion of patients reporting moderate-to-severe (MS) symptoms and whether they were currently well managed were examined. Multivariable logistic regression models were applied to explore the factors correlated to undertreatment and non-treatment of symptoms. RESULTS: About 27% of patients reported over three MS symptoms, 16% reported over five, and 9% reported over seven. Regarding psychological distress, the prevalence of HADS-anxiety was 29% and that of PHQ-9 depression was 11%. Sixty-one percent of patients have at least one MS symptom without any treatment. Sex [odds ratio (OR) = 2.238, 95% confidence interval (95% CI) 1.502-3.336], Eastern Cooperative Oncology Group (ECOG; OR = 0.404, 95% CI 0.241-0.676), and whether currently undergoing anticancer treatment (OR = 0.667, 95% CI 0.503-0.886) are the main factors correlated with the undertreatment of symptoms. Age (OR = 1.972, 95% CI 1.263-3.336), sex (OR = 0.626, 95% CI 0.414-0.948), ECOG (OR = 0.266, 95% CI 0.175-0.403), whether currently undergoing anticancer treatment (OR = 0.356, 95% CI 0.249-0.509), and comorbidity (OR = 0.713, 95% CI 0.526-0.966) are the main factors correlated with the non-treatment of symptoms. CONCLUSIONS: This study shows that hospitalized patients with advanced cancer had a variety of physical and psychological symptoms but lacked adequate management and suggests that a complete symptom screening and management system is needed to deal with this complex problem.

LINC00265 Promotes Metastasis and Progression of Hepatocellular Carcinoma by Interacting with E2F1 at The Promoter of CDK2.

Objective: This study aimed to explore biological function of long intergenic non-protein coding RNA 265 (LINC00265) in hepatocellular carcinoma (HCC) cells, and evaluate its potential function as a biomarker. Materials and Methods: In this experimental study, GEPIA database and Kaplan-Meier Plotter database were employed to analyze LINC00265 expression in HCC tissue samples and its predicting value for prognosis. LINC00265 expression in HCC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After overexpressing and knocking-down of LINC00265 in HCC cells, cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays were adopted to detect proliferation of HCC cells. Transwell assay was used to detect migration and invasion of HCC cells. Interaction of LINC00265 with E2F transcription factor 1 (E2F1) was verified by the catRAPID online analysis tool, RNA pull-down experiment and RNA binding protein immunoprecipitation (RIP) assay. Binding of E2F1 to the promoter region of cyclin-dependent kinases 2 (CDK2) was detected by dual-luciferase reporter assay and chromatin immunoprecipitation. Regulatory effects of LINC00265 and E2F1 on CDK2 expression were probed by Western blot. Results: LINC00265 expression was increased in HCC tissues and cells. LINC00265 overexpression promoted proliferation, migration and invasion of HCC cells, and knocking-down LINC00265 worked oppositely. LINC00265 could bind to E2F1 and it could enhance combination of E2F1 and CDK2 promoter regions, thus promoting CDK2 transcription. LINC00265 overexpression promoted expression of CDK2 in HCC cells. Conclusion: Our data suggested that LINC00265 can promote malignant behaviors of HCC cells by recruiting E2F1 to the promoter region of CDK2.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

Norepinephrine potentiates and serotonin depresses visual cortical responses by transforming eligibility traces.

Reinforcement allows organisms to learn which stimuli predict subsequent biological relevance. Hebbian mechanisms of synaptic plasticity are insufficient to account for reinforced learning because neuromodulators signaling biological relevance are delayed with respect to the neural activity associated with the stimulus. A theoretical solution is the concept of eligibility traces (eTraces), silent synaptic processes elicited by activity which upon arrival of a neuromodulator are converted into a lasting change in synaptic strength. Previously we demonstrated in visual cortical slices the Hebbian induction of eTraces and their conversion into LTP and LTD by the retroactive action of norepinephrine and serotonin Here we show in vivo in mouse V1 that the induction of eTraces and their conversion to LTP/D by norepinephrine and serotonin respectively potentiates and depresses visual responses. We also show that the integrity of this process is crucial for ocular dominance plasticity, a canonical model of experience-dependent plasticity.

Excimer laser atherectomy combined with drug-coated balloon angioplasty for the treatment of femoropopliteal arteriosclerosis obliterans.

INTRODUCTION: It has been reported that excimer laser atherectomy combined with a drug-coated balloon (ELA+DCB) can achieve better results than simple balloon angioplasty, especially for the treatment of femoropopliteal in-stent restenosis. However, reports on the application of ELA+DCB in China for femoropopliteal arteriosclerosis obliterans are lacking. This study focuses on analysing the effectiveness and safety of ELA+DCB. METHODS: This was a single-centre retrospective study that enrolled patients from November 2016 to January 2019 who had femoropopliteal arteriosclerosis obliterans treated by ELA+DCB. Preoperative demographics, operative details and postoperative follow-up outcomes were analysed statistically. RESULTS: There were 43 patients with an average patient age of 68.0±8.6 years; 79.1% were male. In 30 cases, the lesions were de novo and the others were in-stent restenosis (ISR). During the procedure, flow-limiting dissection (48.8%) was the main adverse event and there were 17 bailout stent implantations due to dissection. Mean (±sd) ankle-brachial index (ABI) in the patients was 0.42±0.31 before the operation and 0.83±0.13 before discharge. The mean (±sd) follow-up time was 29.35±9.71 months. The primary patency rate was 66.8%, 64.3% and 60.9% at 12, 24 and 36 months. Freedom from target lesion revascularisation (TLR) was 85.7%, 80.7% and 75.3% at 12, 24 and 36 months. Rutherford categories also greatly improved during follow-up. Overall mortality was 6.9% (3/48), and no deaths were related to the intervention. CONCLUSION: The use of ELA+DCB had good clinical benefit for femoropopliteal arteriosclerosis obliterans, which had good primary patency and freedom from TLR, although intraoperative complications still required attention. Multicentre randomised controlled trials with long-term follow-up are needed.

[Relationship between body mass index and sexual development in Chinese children].

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.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

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.