[Clinical features and Y chromosome abnormalities in children with 45, X/46, XY mosaicism].

Objective: To investigate the clinical and genetic characteristics of children with 45, X/46, XY mosaicism. Methods: The retrospective study included 20 children diagnosed with 45, X/46, XY and 45, X/46, X,+mar mosaicism in the First Affiliated Hospital of Zhengzhou University from 2018 to 2022. The clinical features, gonadal pathology, treatment and follow-up were summarized. Genetic tests were performed by SRY gene test, azoospermia factor region (AZF) deletion test, copy number variation-sequencing (CNV-seq). Age at first diagnosis was compared between boys and girls using independent sample t-test. Results: The 20 patients included 3 boys and 17 girls, and the age at first diagnosis were (7.6±5.5) years, it is (2.1±1.9) years in boys, (8.7±5.4) years in girls, significantly younger for boys (t=-3.86, P=0.004). The chief complaint was external genitalia malformation for boys, and short stature (13 cases) and dysplastic external genital for girls (4 cases). Five girls presented with features of Turner syndrome. The gonadal phenotypes included mixed gonadal dysplasia (MGD, 6 cases), complete gonadal dysplasia (CGD, 10 cases), unilateral ovotestis (2 cases), possible ovaries (1 case) and undetermined gonad (1 case). One female with dysplastic genital was reassigned to male, and the gender of the remaining cases remained unchanged. Seven females were treated with recombinant human growth hormone. The height increased by (17±7) cm during the (2.9±1.2) years follow-up. No gonadal malignancy was observed. The karyotype was 45, X/46, XY in 16 cases, and 45, X/46, X,+mar in 4 cases. All of the 4 marker chromosomes were derived from Y chromosome confirmed by CNV-seq. SRY gene was detected in all 20 patients genome, and AZF deletion was found in 7 girls. Conclusions: 45, X/46, XY mosaicism presented with dysplastic external genital or female with remarkable short stature. Gonadal phenotypes included MGD, CGD and ovotestis. AZF microdeletions were found in the majority of female cases.

[Budd-Chiari syndrome with hepatopulmonary syndrome: a case report and literature review].

Objective: To summarize the clinical features and prognosis of Budd-Chiari syndrome with hepatopulmonary syndrome (HPS) in children. Methods: The clinical data of a child who had Budd-Chiari syndrome with HPS treated at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in December 2016 was analyzed retrospectively. Taking "Budd-Chiari syndrome" and "hepatopulmonary syndrome" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2023. Combined with this case, the clinical characteristics, diagnosis, treatment and prognosis of Budd-Chiari syndrome with HPS in children under the age of 18 were summarized. Results: A 13-year-old boy, presented with cyanosis and chest tightness after activities for 6 months, and yellow staining of the skin for 1 week. Physical examination at admission not only found mild yellow staining of the skin and sclera, but also found cyanosis of the lips, periocular skin, and extremities. Laboratory examination showed abnormal liver function with total bilirubin 53 µmol/L, direct bilirubin 14 µmol/L, and indirect bilirubin 39 µmol/L, and abnormal blood gas analysis with the partial pressure of oxygen of 54 mmHg (1 mmHg=0.133 kPa), the partial pressure of carbon dioxide of 31 mmHg, and the alveolar-arterial oxygen gradient of 57 mmHg. Hepatic vein-type Budd-Chiari syndrome, cirrhosis, and portal hypertension were indicated by abdominal CT venography. Contrast-enhanced transthoracic echocardiography (CE-TTE) was positive. After symptomatic and supportive treatment, this patient was discharged and received oxygen therapy outside the hospital. At follow-up until March 2023, there was no significant improvement in hypoxemia, accompanied by limited daily activities. Based on the literature, there were 3 reports in English while none in Chinese, 3 cases were reported. Among a total of 4 children, the chief complaints were dyspnea, cyanosis, or hypoxemia in 3 cases, and unknown in 1 case. There were 2 cases diagnosed with Budd-Chiari syndrome with HPS at the same time due to respiratory symptoms, and 2 cases developed HPS 1.5 years and 8.0 years after the diagnosis of Budd-Chiari syndrome respectively. CE-TTE was positive in 2 cases and pulmonary perfusion imaging was positive in 2 cases. Liver transplantation was performed in 2 cases and their respiratory function recovered well; 1 case received oxygen therapy, with no improvement in hypoxemia; 1 case was waiting for liver transplantation. Conclusions: The onset of Budd-Chiari syndrome with HPS is insidious. The most common clinical manifestations are dyspnea and cyanosis. It can reduce misdiagnosis to confirm intrapulmonary vascular dilatations with CE-TTE at an early stage. Liver transplantation is helpful in improving the prognosis.

[Clinical and genetic characteristic in patients with disorders of sex development caused by Y chromosome copy number variant].

Objective: To investigate the clinical phenotype and genetic characteristics of disorders of sex development (DSD) caused by Y chromosome copy number variant (CNV). Methods: A retrospective analysis was performed on 3 patients diagnosed with DSD caused by Y chromosome CNV admitted to the First Affiliated Hospital of Zhengzhou University from January, 2018 to September, 2022. Clinical data were collected. Clinical study and genetic test were performed by karyotyping, whole exome sequencing (WES), low coverage whole genome copy number variant sequencing (CNV-seq), fluorescence in situ hybridization (FISH) and gonadal biopsy. Results: The 3 children, aged 12, 9, 9 years, the social gender were all female, presented with short stature, gonadal dysplasia and normal female external genital. No other phenotypic abnormality was found except for case 1 with scoliosis. The karyotype of all cases were identified as 46, XY. No pathogenic vraiants were found by WES. CNV-seq determined that case 1 was 47, XYY,+Y(2.12) and case 2 was 46, XY,+Y(1.6). FISH concluded that the long arm of Y chromosome was broken and recombined near Yq11.2, and then produced a pseudodicentric chromosome idic(Y). The karyotype was reinterpreted as mos 47, X, idic(Y)(q11.23)×2(10)/46, X, idic(Y)(q11.23)(50) in case 1. The karyotype was redefined as 45, XO(6)/46, X, idic(Y)(q11.22)(23)/46, X, del(Y)(q11.22)(1) in case 2. 46, XY, -Y(mos) was found by CNV-seq in case 3, and the karyotype of 45, XO/46, XY was speculated. Conclusions: The clinical manifestations of children with DSD caused by Y chromosome CNV are short stature and gonadal dysgenesis. If there is an increase of Y chromosome CNV detected by CNV-seq, FISH is recommended to classify the structural variation of Y chromosome.

Intermittent fasting in type 2 diabetes: from fundamental science to clinical applications.

Type 2 diabetes mellitus (T2DM) is a huge challenge for global public health systems. Currently, healthcare policies advocate the prevention of the onset and progression of T2DM by improving individual lifestyles. The increasing benefits of intermittent fasting (IF) as a dietary intervention have been elucidated. However, the beneficial effects of IF in T2DM remain inconclusive. We demonstrated the physiological mechanisms underlying the positive effects of IF in T2DM. IF could trigger metabolic transformation to improve systemic metabolism and induce tissue-specific metabolic adaptations through alterations in the gut microbiota, adipose tissue remodeling, correction of circadian rhythm disturbances, and increased autophagy in peripheral tissues. The efficacy and safety of IF regimens in clinical applications carry a risk of hypoglycemia and require monitoring of blood glucose and timely adjustment of medications. However, there is limited evidence of a positive effect of IF in weight loss and improvement of glycemic variables. Overall, IF serves as a promising therapeutic target for T2DM and needs to be established by a large randomized controlled trial.

[Evaluation of the diagnostic efficiency of three anti-Echinococcus antibody-based assays for the serodiagnosis of echinococcosis].

OBJECTIVE: To evaluate the efficiency of three Chinese commercial anti-Echinococcus antibody-based assays for the serodiagnosis of echinococcosis. METHODS: A total of 142 sera from cystic echinococcosis patients, 89 sera from alveolar echinococcosis and 39 sera from healthy controls were sampled, and detected by kits A (ELISA), B (ELISA) and C (colloidal gold immunoassay). The routine blood testing results and biochemical parameters were compared between the cystic and alveolar echinococcosis patients, and the associations of the absorbance (A value) of the serum specific antibody detected by A and B kits with the routine blood testing results and biochemical parameters were examined in echinococcosis patients. In addition, the performance of these three assays for the serodiagnosis of echinococcosis was evaluated. RESULTS: There were no significant differences between the cystic and alveolar echinococcosis patients in terms of the median white blood cell count (WBC), neutrophil count (NEU), monocyte count (MONO), basophil count (BASO), alanine aminotransferase concentration (ALT), aspirate aminotransferase concentration (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) (all P values > 0.05), and higher median lymphocyte count (LYM) and albumin levels (ALB) were detected in cystic echinococcosis patients than in alveolar echinococcosis patients (both P values < 0.05), while the median eosinophil count (EOS) was greater in the alveolar echinococcosis patients than in the cystic echinococcosis patients (P < 0.01). The A value of the serum specific antibody detected by kit A showed a linear positive correlation with WBC (rs = 0.153, P < 0.05) and EOS (rs = 0.174, P < 0.05), and a linear negative correlation with TBIL (rs = -0.134, P < 0.05) and IBIL (rs = -0.146, P < 0.05), while the A value of the serum specific antibody detected by kit B showed a linear positive correlation with WBC (rs = 0.257, P < 0.01), NEU (rs = 0.203, P < 0.01), MONO (rs = 0.159, P < 0.05), EOS (rs = 0.330, P < 0.01), ALT (rs = 0.171, P < 0.01) and AST (rs = 0.160, P < 0.05), and a linear negative correlation with ALB (rs = -0.168, P < 0.05). The overall coincidence rate, sensitivity, specificity, Youden's index and Kappa value of A, B and C kits were 86.30%, 69.63% and 91.48%; 84.42%, 64.94% and 92.21%; 97.44%, 97.44% and 87.18%; 0.82, 0.62 and 0.79; and 0.600, 0.337 and 0.750 for the diagnosis of echinococcosis, respectively. The overall coincidence rate, sensitivity, specificity and Youden's index of A, B and C kits were 84.54%, 64.64% and 71.82%; 80.99%, 55.63% and 68.31%; 97.44%, 97.44% and 87.18%; and 0.78, 0.53 and 0.56 for the diagnosis of cystic echinococcosis, respectively, while the overall coincidence rate, sensitivity, specificity and Youden's index of A, B and C kits were 92.19%, 85.16% and 85.16%; 89.89%, 79.78% and 84.27%; 97.44%, 97.44% and 87.18%; and 0.87, 0.77 and 0.72 for the diagnosis of alveolar echinococcosis, respectively. The C kit showed cross-reactions in the serodiagnosis of cystic echinococcosis and alveolar echinococcosis. There were no significant difference in the area under the receiver operating characteristic curve (ROC) between A and B kits for the diagnosis of echinococcosis (0.970 vs. 0.948, Z = 1.618, P > 0.05), and there was a high agreement between A and B kits in the diagnosis of echinococcosis (Kappa = 0.585, P < 0.01). CONCLUSIONS: The three commercial anti-Echinococcus antibody-based kits exhibit a higher serodiagnostic efficiency for alveolar echinococcosis than for cystic echinococcosis. The A kit shows a high sensitivity and specificity for the diagnosis of echinococcosis, and has a relatively stable diagnostic performance and fewer influencing factors, which is suitable for the pre-surgical preliminary diagnosis and post-surgical follow-up monitoring of serum anti-Echinococcus antibody, while the C kit shows a high sensitivity and specificity for the diagnosis of echinococcosis, and is easy to perform and high in reporting rate, which is feasible for initial screening of echinococcosis.

[Systematic evaluation on effectiveness and safety of recombinant human growth hormone in treating adult patients with severe burn].

Objective: To systcmatically evaluate the effectiveness and safety of recombinant human growth hormone (rhGH) in treating adults with severe burn. Methods: Databases including PubMed, Cochrane Library, and Embase were searched using key words " burns, thermal, human growth hormone, growth hormone, hGH, and somatropin (human)" , and China Biology Medicine disc, Chinese Journals Full-text Database, VIP Database, and Wanfang Database were searched using key words in Chinese version "," to obtain the randomized controlled trials about rhGH in the treatment of adults with severe burn from the establishment of each database to December 2016. The measurement indexes included hemoglobin (Hb) and plasma total protein, inflammatory factors [including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)], incidence rate of sepsis, incidence rate of hyperglycemia, wound healing time, length of stay, and mortality rate. Meta-analysis was conducted by RevMan 5.3 statistical software. Results: A total of 8 trials involving 534 patients were included; 276 patients in rhGH group were treated with rhGH and 258 patients in placebo control group were treated with placebo. One trial had low risk of bias, while the other 7 trials had unclear risk of bias. The levels of Hb and plasma total protein of patients in rhGH group were higher than those in placebo control group, with standardized mean differences (SMDs) respectively 2.00 and 2.23 [with 95% confidence intervals (CIs) respectively 0.19-3.82 and 1.21-3.26, P<0.05 or P<0.01]. The levels of IL-6 and TNF-α of patients in rhGH group were lower than those in placebo control group, with SMDs respectively -1.46 and -1.13 (with 95% CIs respectively -2.40--0.53 and -1.75--0.51, P values below 0.05). Incidence rate of sepsis and mortality rate of patients in rhGH group were lower than those in placebo control group, with relative risks (RRs) respectively 0.60 and 0.35 (with 95% CIs respectively 0.42-0.85 and 0.15-0.83, P values below 0.05). Incidence rate of hyperglycemia of patients in rhGH group was higher than that in placebo control group, with RR of 2.39 (with 95% CI 1.79-3.18, P<0.001). The wound healing time and length of stay of patients in rhGH group were lower than those in control group, with SMDs respectively -1.54 and -2.00 (with 95% CIs respectively -2.22--0.86 and -3.51--0.49, P<0.05 or P<0.01). Hb, plasma total protein, inflammatory factors, incidence rate of sepsis, wound healing time, length of stay, and mortality rate showed no significant publication bias (P values above 0.05), while there may be publication bias in incidence rate of hyperglycemia (P=0.026). Conclusions: rhGH can inhibit the breakdown of Hb and plasma total protein, reduce the level of inflammatory factors and incidence rate of sepsis, thus shorten the wound healing time and length of stay, thereby reduce mortality rate of adult patients with severe burn. However rhGH may cause hyperglycemia.

Model simulation of inflow water to the Baltic Sea based on ¹²9I.

The semi-enclosed Baltic Sea represents a vital economic and recreational resource for more than 90 million people inhabiting its coasts. Extensive contamination of this sea by a variety of anthropogenic pollutants has raised the concern of the people in the region. Quantifying seawater inflow is crucial for estimating potential environmental risks as well as to find the best remedial strategy. We present here a model to estimate water inflow from the North Sea to the Baltic Sea by utilizing ¹²9I as a tracer. The results predicted inflow range of 230-450 km³/y with best fit value around 330 km³/y from the North Sea to the Baltic Sea during 1980-1999. Despite limited time series data on ¹²9I, the model presented here demonstrates a new management tool for the Baltic Sea to calculate inflow water compared to conventional methods (such as salinity, temperature and hydrographic models).