Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

The transgender children and adolescents(TCAs)face serious social dilemmas in the process of gender identity and expression,which hinders this group from seeking reasonable and equal rights to survival and development.From the perspective of equal rights and the theoretical framework of social dilemma,by interviewing TCAs who seek help from medical social workers in a hospital's multi-disciplinary transgender clinic,this paper revealed that under the traditional system of"binary gender",TCAs lacked social inclusiveness and infrastructure,which led to the two major social dilemmas of"social traps"and"social barriers"encountered by this group in the process of gender expression and gender identity.Specifically,the social gender selection of TCAs often leads to collective irrational reactions and gender punishment,preventing their legal and effective medical services.To this end,the research team used critical methodology to construct a joint disciplinary diagnosis and treatment path for TCAs with the participation of medical social workers,as well as verified that the path has significant intervention effects in rationalizing the needs of TCAs and their families,alleviating their psychological pressure and social adaptation problems in the process of gender identity,fostering a diverse dialogue environment in their families,as well as enhancing their self-efficacy and social participation,to provide assistahce to the TCAs groups in social difficulties,assisting their rights and interests be included in the child-friendly indicator system,and improving the whole society's tolerance and understanding for TCAs group.

In recent years，the prevalence of childhood obesity has increased rapidly，and obesity can seriously affect physical and mental health of children and adolescents，and is likely to extend into adulthood. The onset and development of childhood obesity is related to multiple factors such as genetic predisposition and environment. So far，more and more studies have found that the gut microbiota，as an important part of the internal environment，is closely related to childhood obesity. Perturbed gut microbiota and its derived metabolites such as short-chain fatty acids，bile acids，indole and their derivatives are widely involved in the onset and development of childhood obesity. At present，regulating the compositions and function of gut microbiota through probiotics and prebiotics，fecal microbiota transplantation，dietary intervention，and bariatric surgery is a new direction for the prevention and treatment of obesity. This paper reviews the research progress on the association between gut microbiota and childhood obesity，in order to provide novel insights for prevention and intervention of childhood obesity based on gut microbiota.

Objective:To study the clinical characteristics of neonatal onset of diabetes mellitus.Methods:Neonatal onset diabetes mellitus infants admitted to Children's Hospital of Fudan University from January 2003 to December 2020 were selected for retrospective analysis. All clinical characteristics including the basic conditions, family history, clinical manifestations, laboratory examination, diagnosis and treatment were recorded and analyzed.Results:There were 21 cases of diabetes mellitus diagnosed during neonatal period, including 13 males and 8 females. There were 16 term infants and 5 premature infants with gestational age between 34 weeks and 40 weeks. The birth weight ranged from 1 420 g to 3 450 g, including 14 low birth weight infants, 2 very low birth weight infants and 13 small for gestational age infants. Four infants had family history of diabetes. All diabetic infants with onset time within 28 days after birth included 10 cases within 10 days, 4 cases between 11 days and 20 days, 7 cases between 21 days and 28 days. Hyperglycemia was the main feature of 21 infants, and their blood glucose was ≥11.1 mmol/L for many times, with a maximum of 41.98 mmol/L. Only 2 cases had ketoacidosis and 8 cases were complicated with infections. Genetic testing was performed in 6 neonates,2 cases of ABCC8 gene pathogenic variant, 1 case of KCNJ11 and 1 case of INS pathogenic variant, and 2 cases of negative results. Insulin was mainly used in the initial stage of treatment, and then orally glibenclamide was taken in 9 infants. After treatment, 15 patients had stable blood glucose and were discharged with medication. 5 infants were withdrawn the treatment and discharged, and 1 infant combined with other serious illness died after giving up the treatment by the parents.Conclusions:When diabetes is diagnosed during the neonatal period, it is helpful to choose the appropriate treatment and get good results.

Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

Objective:To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight.Methods:A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P 50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results:The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P 50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P 50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P 50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion:The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.

Objective To summarize the clinical feature,gene mutations,diagnosis,treatment,and follow-up data of protein-sensitive hypoglycemia,so as to improve the clinical understanding of the disease.Methods Five patients were diagnosed with protein-sensitive hypoglycemia during June in 2015 and December in 2017 from the Department of Pediatric Endocrinology and Inherited Metabolic Diseases,Children's Hospital of Fudan University.Clinical data of 5 cases were summarized,including clinical manifestations,findings of protein sensitivity test,therapy effect and prognosis.The endocrine and metabolic panel was used to investigate the genetic cause of four patients.Related literatures of protein-sensitive hypoglycemia were reviewed,and the phenotypes,genotypes,and therapy effects were summarized.Results Among the 5 patients diagnosed with positive results of protein-sensitive hypoglycemia,three were found to harbor glutamate dehydrogenase 1 (GLUD 1) mutations (c.965G ＞ A,p.R322H:2 cases;c.943C ＞T,p.H315Y:1 case),and another one had complex heterozygous mutations in L-3-hydroxyacyl-CoA dehydrogenase (HADH,c.29G ＞ C,p.R10P;c.89T＞ A,p.V30E).5 patients were euglycemia without any medical support after low protein diet.In 18 literatures retrieved and this study,there were totally 161 cases of protein-sensitive hypoglycemia (149 cases with GLUD1 mutations and 10 cases with HADH mutations).Conclusions When a child was admitted because of hypoglycemia,the diagnosis of protein-sensitive hypoglycemia should be suspected if he or she also had postprandial hypoglycemia,with or without hyperammonemia.Protein sensitivity test is helpful for us to make the diagnosis of protein-sensitive hypoglycemia.

Objective To report a case of immunodeficiency 41 with lymphoproliferation and autoimmunity (IMD41) and type 10 insulin-dependent diabetes mellitus(IDDM10), caused by mutations of the interleukin 2 receptor α(IL2RA)gene.Methods Clinical symptoms were colleted,while IL2RA gene was sequenced.Results Here we reported a girl of 7 years and 6 months old who came to our hospital presented with lymphadenovarix for 5 years,debilitation for 2 months and alternation of hyperglycemia and hypoglycemia for 20 days. She was subsequently diagnosed with fungal pneumonia and ANCA-associated vasculitis. All exons of IL2RA gene were sequenced. c.340C>T(p.Q114X,paternal,novel mutation),c.64G>A(p.E22X,maternal) were detected. After treatments of dihydrocortisone,voriconazole combined with diabetic diet plus raw cornstarch, the pulmonary lesions reduced, autoantibodies disappeared and the blood glucose returned to normal. Literature review suggested that totally 5 IL2RA gene mutation patients were reported, the major clinical features were recurrent infection(infection of lung, skin, gastrointestinal tract) and immune abnormalities ( such as lymph node disease, autoimmune disease, hepatosplenomegaly,and diabetes mellitus). Conclusion In cases of atypical clinical symptoms, whole exon sequencing helps early diagnosis.

Objective To explore the layers of the facial and angular arteries between the orbital notch and the antegonial notch.Methods Anatomical studies were performed on 5 cases of adult cadavers (10 sides).Parallel lines were drawn on each cadaver through the position of the orbital incise,inner canthus,above of wing nose,nasal wing point,mouth angle,anterior incise.When the region of the arterial level changes,the parallel lines could be temporarily divided.The levels of the arteries that appeared on every horizontal line were recorded.Results The surface artery between the orbital notch (including the supraorbital notch) and the inner canthus (including the inner cantholes) was mainly in the orbicularis muscle layer.In the middle of the inner canthus and the highest point of the nasal wing,1/3 of the arteries were mainly walking in the orbicularis orbicularis muscular layer,and the next 1/3 were mainly located in the superficial layer or subcutaneous fat layer of the orbicularis oculi muscle.The highest point of the nose wing was found in the middle of the subcutaneous fat.The main line between the top of the nose and the lower part of the nose was deep in the subcutaneous fat.At the bottom of the nose,the main line was located in the fat layer of the zygomaticus,the zygomaticus maximus.In the middle and upper part of the nose and the middle of the mouth,a third of the main lines were walking in the lower fat layer (from shallow to deep) under the zygomaticus,and the next 1/3 segment was found in the subcutaneous fat deep.On the outside of the corner of the mouth,the main line was walking the subcutaneous fat layer or the lower fat layer of the platysma.Conclusions This study preliminarily clarifies the walking level of the facial artery from the upper orbital notch and the anterior notch of the angle.Bearing in mind the depth and the location of the vasculature within each zone,clinical practitioners can tailor their injection techniques to prevent vessel injury and avoid cannulation.

Objective: To observe the clinical effects of the Joint Active System on the treatment of joint dysfunction after deep burn. Methods: Twenty-two patients with joint dysfunction after deep burn were hospitalized in Institute of Burns of Tongren Hospital of Wuhan University & Wuhan Third Hospital from January 2015 to October 2016, involving 18 elbow joints with flexion disorder, 10 wrist joints with dorsal extension disorder, and 12 ankle joints with dorsal extension disorder. They were treated with the elbow joint activity training device, the wrist joint activity training device, and the ankle joint activity training device of the Joint Active System, respectively. The treatment was carried out 3 times each day with interval of 6 h, 30 minutes each time, and it lasted for four to seven months, with one month as a course of treatment. Before treatment and 1, 2, 3, 4 month (s) after, active motion range of each joint was measured by joint goniometer. Function improvement of each joint was evaluated, and the total effective ratio was calculated 4 months after treatment. Satisfaction degree of patients was assessed by the modified Likert Scale 1, 2, 3, 4 month (s) after treatment. Data were processed with one-way analysis of variance for repeated measurement and LSD test. Results: Before treatment and 1, 2, 3, 4 month (s) after, flexion active motion range of elbow joints were (61±23), (78±22), (89±20), (96±20), and (103±19)°; dorsal extension active motion range of wrist joints were (23±7), (31±6), (38±9), (44±5), and (49±8)°; dorsal extension active motion range of ankle joints were (-31±12), (-23±10), (-16±7), (-12±6), and (-8±4)°, respectively. The active motion range of each joint was obviously higher 1, 2, 3, 4 month (s) after treatment than the previous time point of the same joint (with P values below 0.01). Four months after treatment, the total effective ratios of function improvement of elbow joints, wrist joints, and ankle joints were 5/6, 9/10, and 2/3, respectively. Scores of satisfaction degree of the patients 1, 2, 3, 4 month (s) after treatment were (1.3±0.7), (2.2±1.0), (2.8±0.8), and (3.3±0.6) points, respectively. Scores of satisfaction degree of the patients were obviously higher 2, 3, 4 months after treatment than the previous time point (with P values below 0.05). Conclusions Joint Active System can improve the active range of motion of each joint obviously in treating joint dysfunction after deep burn, with total effective ratio of function improvement of each joint surpassing 0.66, and the majority of patients are quite satisfied with the curative effects.