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.

Effect of Modified Gegen Qinlian Tang on Inflammatory Factors in Hippocampus for Diabetic Rats / 中国实验方剂学杂志

Objective: To investigate the effect of modified Gegen Qinlian Tang on learning and memory ability and interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), nuclear factor-κB(NF-κB) protein expression in hippocampus of type 2 diabetic (T2DM) rats. Method: A total of 62 rats were randomly divided into normal group (n=12),and the remaining 50 rats were established by feeding high sugar and high fat diet and injecting with low dosage of streptozocin(STZ) to T2DM. The successful modeling rats were selected and randomly divided into model group, Saxagliptin and modified Gegen Qinlian Tang group. The normal group and the model group received 10 mL·kg-1·d-1 nomal saline by intragastric administration. 0.005 g·kg-1·d-1 Saxagliptin crude drug and 0.435 g·kg-1·d-1 modified Gegen Qinlian Tang crude drug were given in Saxagliptin group and modified Gegen Qinlian Tang group, and all the treatment lasted for 8 weeks. Learning and memory ability of rats was observed by using Morris water maze. Histopathological changes of hippocampus was observed by hematoxylin-eosin staining.Western blot was used to test the NF-κB p65 in the cytoplasmic and nucleus in rat hippocampus. Enzyme-linked immunosorbent assay(ELISA) was used to test the levels of IL-1β and TNF-α. Result: Compared with normal group, the mean incubation period of model group was significantly prolonged on the 4th day(PPκB p65 in the nucleus was significantly increased (Pβ, TNF-α in the hippocampus were significantly increased (PPPPPβ, TNF-α and NF-κB p65 in hippocampus were significantly improved. Conclusion: Modified Gegen Qinlian Tang could obviously improve the learning and memory ability of the T2DM rat model which was induced by the high-sugar, high-lipid diet and low-dose STZ, and the mechanism may be achieved by suppressing the inflammation of the rat' s hippocampus.

Euthyroid sick syndrome in children with diabetic ketoacidosis

To investigate characteristics of euthyroid sick syndrome [ESS] in children with diabetic ketoacidosis [DKA]. This retrospective study was carried out between May 2010 and April 2013 at the Pediatric Department of Shandong Provincial Hospital, Shandong University, Shandong, China. Diabetic ketoacidosis children were divided into 2 groups: euthyroidism [group one, n=30] and ESS [group 2, n=40]. C-peptide, glycosylated hemoglobin [HbA1c], bicarbonate, anion gap [AG], free triiodothyronine [FT3], free thyroxine [FT4], and thyrotropin [TSH] levels were measured before and after 7 days of insulin treatment. Daily blood glucose [BG] profiles were recorded. Glycosylated hemoglobin, AG, the mean daily BG, and fasting blood glucose levels were higher, and bicarbonate, FT3, FT4, and TSH levels were lower in group 2 than in group one [all p<0.05]. Free triiodothyronine [r=-0.593, p<0.001] and FT4 [r=-0.402, p=0.001] were negatively correlated with HbA1c. Free triiodothyronine [r=-0.438, p<0.001] and FT4 [r=-0.505, p<0.001] were negatively correlated with AG, and FT3 [r=0.503, p<0.001] and FT4 [r=0.448, p<0.001] were positively correlated with bicarbonate. Diabetic ketoacidosis children with ESS have poor diabetic control. Free thyroid hormones are associated with the severity of DKA

Ultrastructural changes of hepatocyte fibrogenesis in cholelithiasis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the ultrastructural changes of hepatocyte fibrogenesis in cholelithiasis in biliary tract.</p><p><b>METHODS</b>l0 liver biopsies were taken from the patients suffered from gallstone and choledocholithiasis during surgical treatment and the ultrastructural changes were observed under electromicroscope.</p><p><b>RESULTS</b>There were plentiful collagenous microfibrils (CMFs) grown within some hepatocytes. These CMFs distributed locally or diffusely in cytoplasm even extended into nucleus. In 7 cases numerous megamitochondrias appeared in several hepatocytes, the inclusions mimicking fibrils could be frequently seen and grew beyond the envelope. Furthermore, typical CMFs could be seen in the large microbodies, and several vesicular or cystic structures similar as fibroblast were presented in marginal areas of the hepatocytes.</p><p><b>CONCLUSIONS</b>We deduce that the fibrosed hepatocytes may be remained and take part in the hyperplasia of hepatic fibrous tissue.</p>

Postoperative pituitary hormonal disturbances and hormone replacement therapy time and dosage in children with craniopharyngiomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas (CP) often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency (MPHD). This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy (HRT) time and dosage in children with CP.</p><p><b>METHODS</b>Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of (10.63 +/- 3.18) years (Group A) and 10 male patients of group A aged > 10 years (Group B) were entolled. Thirty age-, sex- and Tanner stage-matched normal children (control Group A), and 44 male older children > 10 years (control Group B) served as controls. The serum concentrations of insulin-like growth factor-1 (IGF-1), growth hormone (GH), free thyroxine (FT4), thyroid-stimulating hormone (TSH), adrenocorticortropic hormone (ACTH), cortisol (COR), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine (L-T4) dosage and primary FT4 in CP patients after resection.</p><p><b>RESULTS</b>All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased (P < 0.001); however, E2 and PRL were significantly increased (P < 0.001) in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus (DI) by water deprivation test and MRI. There was a significant negative linear regression (r = -0.8, P < 0.001) between L-T4 and primary FT4 in Group A patients with CP after resection, giving a regression equation of L-T4 dosage (microg.kg(-1).d(-1)) = 3.5-0.2 x FT4 (microg.kg(-1).d(-1)). The time and corresponding dosage of HRT for CP after resection were: rhGH started 1 year after resection and no recurrence of CP on MRI, when IGF-1 reached the normal range, the rhGH dosage was (0.13 +/- 0.04) U.kg(-1).d(-1); hydrocortisone (H-C) was started as soon as possible, and was kept in the lower normal range, at a dosage of (12.6 +/- 4.8) mg/m2; levothyroxine started after H-C or at the same time to maintain FT4 in the higher normal range, at a dosage of (1.65 +/- 0.70) microg.kg(-1).d(-1); Minirin (DDAVP) was started as soon as possible, elicited no symptoms, and maintained normal electrolyte levels; the dosage was (0.16 +/- 0.04) mg/m2.</p><p><b>CONCLUSION</b>Patients with CP after resection often displayed MPHD, and needed total HRT at appropriate time and dosage to improve the quality of life and normal growth.</p>

Protective effects and mechanism of shenmai injection on cardiomyocytes / 实用儿科临床杂志

Objective To investigate the protective effects and mechanism of shenmai injection(SMI) on cardiomyocytes injured by hydrogen peroxide(H 2O 2) or angiotension Ⅱ(AngⅡ). Methods According to the different concentrations of H 2O 2, AngⅡ,SMI,Vitamin C(VitC) added into the cardiomyocytes culture media(CCM), the cultures were divided into 15 groups. Lactate dehydrogenase(LDH ),malondialdehyde(MDA),superoxide dismutase (SOD) of CCM and cardiomyocytes viability(CMV), Na +-K +-ATPase,Ca 2+-ATPase?cardiomyocytes apoptosis rate(CMAR) ,nitrogen oxide(NO), nitrogen oxide synthesis enzyme(NOS),eNOS expression of cardiomyocytes were detected respectively .Results H 2O 2 or AngⅡ could decrease CMV, SOD, Na +-K +-ATPase,Ca 2+-ATPase,NOS,NO,eNOS expression and increase CMAR,LDH and MDA.SMI could lessen the changes of the items mentioned above ,which were caused by H 2O 2 or AngⅡ.The effects of SMI 10 ml/L were stronger than those of SMI 5 ml/L or VitC 50 mg/L.Conclusion SMI has a significant protective effect on cardiomyocyte injured by H 2O 2 or AngⅡ.

Reversal of multidrug resistance in leukemic cell line K562/AO2 by chlordelazine in vitro / 中华儿科杂志

<p><b>OBJECTIVE</b>Some recent studies revealed that phenthiazine might be able to reverse tumor cell drug-resistance. Chlorderazin belongs to the phenthiazine compounds. The study aimed to investigate the reversing effect and mechanism of chlorderazin on multidrug resistance of leukemic cell line K562/AO2.</p><p><b>METHODS</b>(1) The cytotoxicities of chlorderazin were assayed with the tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. (2) The reverse effect of chlorderazin on K562/AO2 cells was analyzed with MTT method. The multidrug resistance reversal index (RI) was equal to the ratio of control group IC(50)/test group half inhibition concentration IC(50). (3) The intracellular daunorubicin (DNR) concentrations were measured by the flow cytometry. (4) Mdr1 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). The ratio of mdr-1/beta-actin density was calculated.</p><p><b>RESULTS</b>(1) Chlorderazin 3 micro g/ml showed little toxicity to K562/AO2 cells and the suppression rate was less than 5%, so the concentration of 3 micro g/ml chlorderazin was selected as the experiment concentration. (2) The cytotoxicities of DNR to K562/AO2 were enhanced by 3 micro g/ml of chlorderazin (P < 0.05) and RI was 1.901. (3) Chlorderazin of 3 micro g/ml could increase the intracellular DNR accumulation significantly (P < 0.05), and the fluorescence staining by the flow cytometry was higher (250.95 +/- 18.96) than the control group (112.75 +/- 15.78) and shift right in K562/AO2 cells treated with chlorderazin, and the difference was significant (P < 0.05). (4) Chlorderazin has no significant influence to the expression level of mdr-1 mRNA. Both test group and control group showed a clear mdr-1 mRNA band located at the position of 157 kb. The ratios of mdr-1/beta-actin density were 0.414 +/- 0.012 in the test group and 0.447 +/- 0.027 in the control group, respectively, and the difference was not significant (P > 0.05).</p><p><b>CONCLUSION</b>Chlorderazin could reverse the multidrug resistance by increasing the intracellular DNR accumulation in K562/AO2 cells. The effects had no correlation to the mdr-1 gene. Further study is needed.</p>

Detection of Borna disease virus-p24 specific antibody in the sera of schizophrenic patients of China by means of Western-blot / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate whether Borna disease virus (BDV) infection is related to the schizophrenic patients from China.</p><p><b>METHODS</b>A reliable Western-blot method for detection of BDV-p24 antibody was established by adjusting the reaction conditions of BDV-p24 recombinant protein and specific antibodies. The sera of schizophrenic patients and normal controls from Heilongjiang Province were screened for specific BDV-p24 antibody by this method, and the BDV-p24 antibody positive sera were confirmed by the Western-blot method with sera-GST protein absorption.</p><p><b>RESULTS</b>Ten of 116 (8.6%) schizophrenic patients were found to be positive for BDV-p24 specific antibody, while no BDV-p24 specific antibody was found in sera of normal controls.</p><p><b>CONCLUSIONS</b>The results demonstrate that the Borna disease virus infection also exists in China, and the infection is possibly associated with schizophrenia in some way.</p>