Objective To investigate the clinical characteristics of the hepatolenticular degeneration in children,and to clarify the significance of gene diagnosis in children with hepatolenticular degeneration.Methods A total of 75 patients with hepatolenticular degeneration were enrolled in the Department of Pediatrics,Peking Union Medical College Hospital from 2011 to 2018.All of them carried out a generation of gene sequencing for ATPase Cu2+trans-porting beta polypeptide(ATP7B)gene and multiplex ligation-dependent probe amplification(MLPA)analysis.Results Among the 75 pediatric patients,55 patients were asymptomatic and had elevated aminotransferases as the incidental findings.All the pediatric patients had decreased ceruloplasmin.Seventy-two of pediatric patients had 24-hour urinary copper＞40 μg/d.There were 16 cases that had Kayser-Fleischer(K-F)rings.Sixteen six out of 75(21.33%)cases were diagnosed clinically and 15 cases were＞7 years old.All the remaining patients needed genetic diagnosis.Sixty-six patients had two mutations and 9 patients had only one mutation,1 had no mutation.Forty eight different mutations were found to be localized in ATP7B gene.These mutations included 32 missense mutations,6 splice mutations,5 deletion mutations,2 repeated mutations,2 insert mutations and 1 nonsense muta-tions.The most frequently three mutations were c.2333G＞T,p.R778L,c.2621C＞T,p.A874V,c.2975C＞T,p.P992L,whose allele frequencies were 30.49%,14.89%,9.92%.Conclusions The research showed that in young aged patients,the nervous system symptoms are not obvious and the positive rate of laboratory tests are lower than adults so is a challenge to clinical diagnosis.So Genetic testing is of great significance for the early diagnosis and early treatment of disease in pediatric patients.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Objective:To investigate the safety, efficacy and effective dose of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb).Method:This was a cross sectional study. A total of 28 children with GSDⅠb who started oral empagliflozin treatment from January 2021 to June 2023 in the WeChat group of patients with glycogen storage disease were selected as the study objects. Clinical data such as general situation, current situation of medication and adverse reactions of the children were collected through questionnaires from June 18 to 30, 2023. The differences of symptoms and laboratory tests before and after empagliflozin treatment were compared by using paired chi-square test and Wilcoxon signed rank sum test.Results:Totally 28 children with GSD Ⅰb were from 12 different provinces, autonomous regions and municipalities in China. There were 14 males and 14 females. Empagliflozin treatment was started at the age of 4.8 (2.4, 10.8) years, the time of treatment was 14.5 (11.3, 21.5) months, the initial dosage was (0.23±0.11) mg/(kg·d), and the maintenance dosage was (0.28±0.12) mg/(kg·d). Empagliflozin showed positive effects on neutropenia, severity of inflammatory bowel disease like symptoms( Z=-3.70 , -2.65, both P<0.05), The proportion of recurrent oral ulcers, recurrent bacterial infections and anemia was significantly lower than that before medication (18% (5/28) vs. 46% (13/28), 14% (4/28) vs. 46% (13/28), 21% (6/28) vs. 46% (13/28), χ2=4.05, 5.26, 3.05 , all P<0.05). Granulocyte colony-stimulating factor (GCSF) was once used in 5 children with GSD Ⅰb, all of them had completely stopped GCSF after empagliflozin treatment. The most common adverse events during empagliflozin treatment were hypoglycemia (5 children) and urinary infection (3 children). All 28 patients had no serious adverse reactions. Conclusions:Empagliflozin can increase the neutrophil count of children with GSD Ⅰb, and had a favorable effect on symptoms such as recurrent oral ulcers, and recurrent infection. The common adverse events during empagliflozin treatment were hypoglycemia and urinary infection.

Objective:To analyze the current situation of low copper diet management in children with hepatolenticular degeneration, so as to provide reference and help for individualized low copper diet guidance.Methods:Questionnaire survey and semi-structured interview were used. In the questionnaire survey, a total of 113 parents of children with hepatolenticular degeneration who were treated in the Pediatric Outpatient Department and ward of Chinese Academy of Medical Sciences, Peking Union Medical College Hospital from August 2021 to October 2022 were selected as the research objects. And a self-designed Low Copper Diet Status Questionnaire for Children with Hepatolenticular Degeneration was used for investigation. In the semi-structured interview, the purposive sampling method was used to recruit research objects that met the inclusion criteria. When the information reached saturation, they were no longer included, and finally 16 interviewees were included. Results:The results of the questionnaire showed that the items with the lowest accuracy in the part of the low-copper diet knowledge questionnaire for parents of children with hepatolenticular degeneration were "whether the food was edible according to the amount of copper in the food, for example, if the copper content in 100 g food exceeded 0.5 mg, it was forbidden to eat" and "in the following bean food (tofu, yuba, dried bean curd, oily bean curd), which one had the highest copper content". Among the 113 children, 55 were completely managed by their parents on a low copper diet, 53 children were jointly managed with their parents on a low copper diet, and 4 children were self-managed on a low copper diet. A total of 64 children currently followed the principle of a low copper diet, only consuming a few major categories of foods with low copper content. A total of 32 children ensured a diversified diet while ensuring that the total copper content in their daily food did not exceed the standard. The themes extracted from semi-structured interviews included insufficient awareness of low copper diet among parents of affected children, concerns about their children dining outside, doubts about how to balance low copper diet and nutritional balance among parents, and hopes that medical staff could provide some assistance in low copper diet guidance.Conclusions:The management of low-copper diet in children with hepatolenticular degeneration is poor. The parents of the affected children lack knowledge about low copper diet and have many confusions, and there is an urgent need for medical personnel to provide more specific, rich and practical guidance on low copper diet.

OBJECTIVE: The population density and diversity of Sinomenium acutum (Menispermaceae) have been greatly reduced recently by overharvesting for medicinal purposes in China. Therefore, it is urgent that the remaining populations are investigated, and that strategies for the utilization and conservation of this species are developed. This study aimed to find the possible glacial refugia and define the genetic diversity of S. acutum for its proper utilization and conservation. METHODS: A total of 77 S. acutum samples were collected from four locations, Qinling Mountains, Daba Mountains, Dalou Mountains, and Xuefeng Mountains, in subtropical China. Genetic diversity among and between these populations were phylogenetically analyzed using four chloroplast DNA molecular markers (atpI-atpH, trnQ-5'rps16, trnH-psbA and trnL-trnF). RESULTS: A total of 14 haplotypes (C1 to C14) were found in collected samples. Haplotypes C1 and C3 were shared among all populations, with C3 as the ancestral haplotype. Haplotypes C11 and C12 diverged the most from C3 and other haplotypes. No obvious phylogeographic structure was found in four locations using the GST/NST test. There is no evidence of rapid demographic expansion in S. acutum based on the mismatch distribution, and the results of Tajima's D test, and Fu's FS test. Our analyses of molecular variance revealed a high level of genetic variation within populations. In contrast, the genetic differentiation among S. acutum populations was low, indicating frequent gene flow. CONCLUSION Xuefeng, Dalou, and Daba Mountains were possible glacial refugia for the populations of S. acutum. C1, C3, C11 and C12 haplotypes of S. acutum should be carefully preserved and managed for their genetic value.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Gaucher′s disease (GD) is a lysosomal storage disease, and the etiology of GD is the decreased activity of glucocerebrosidase, which leads to the accumulation of glucocerebroside in the lysosomes of macrophages. Because GD is rare and lacks specific clinical manifestations, it is easy to be misdiagnosed, which delays the best time for treatment. Early diagnosis, clinical evaluation, and regular monitoring of the disease have important clinical significance for enzyme replacement therapy in patients with GD. Recent studies have found that radionuclide imaging is playing an increasingly important role in the diagnosis and treatment of GD. This article introduces the application of radionuclide imaging in the diagnosis and management of GD.

Objective:To investigate the percutaneous permeability of sinomenine hydrochloride （SNH） and optimize the parameters of electroporation to achieve the best permeation enhancing effect on SNH. Method:The percutaneous permeability of SNH and the enhancement effect of electroporation were studied by in vitro diffusion cell method， and the enhancement effect of electroporation was further evaluated by in vivo study in mice. Result:Under steady-state condition， the permeation rates of SNH in stripped skin and intact skin of hairless mice were （385.81±12.88）， （0.88±0.20） μg·cm^-2·h^-1， respectively. The permeation rate in stripped skin was 438 times higher than that in intact skin. The results of percutaneous permeation kinetics analysis showed that the solubility and diffusion coefficient of SNH in stratum corneum were relatively low， which were （70.82±9.63）×10³ g·m^-3 and （3.07±1.52）×10^-14 cm²·s^-1， respectively. Under the optimized electroporation conditions （voltage of 72 V， time of 60 min）， the 24 h cumulative permeation amount of SNH through skin of mice was （10 008.39±1 961.57） μg·cm^-2， and the steady-state permeation rate was （456.01±51.26） μg·cm^-2·h^-1， which were 5.4 times and 5.1 times higher than those of blank group， respectively. In vivo studies in mice showed that the contents of SNH in skin and muscle of electroporation group were 2.0 times and 1.5 times higher than those of blank group. Conclusion:The low solubility and low diffusion coefficient of SNH in the stratum corneum are the main factors hindering the percutaneous permeation of SNH. Electroporation can significantly increase the percutaneous permeation of SNH and its retention in skin and muscle of mice.

Objective:To summarizes the diet management of one child with GSD I and severe hyperlipidemia.Methods:Key points of diet management include: making an individual diet plan, correcting parents' dietary misunderstanding, adjusting dietary and keeping following up regularly and keeping a food diary.Results:Following up for 11 months, the children basically formed a stable diet pattern, the blood glucose level was basically maintained between 4~6 mmol/L, the indicators of hyperlipidemia, hyperlactic acid and liver function were significantly improved compared with the previous period, and the height increase was guaranteed, while the weight gain was effectively controlled.Conclusions:It shows that individualized dietary guidance has a significant effect on the maintenance of blood glucose level, improvement of growth and development status and metabolic control in children with GSD I.