[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.

Correlation between peripheral skeletal muscle functions and the stable phase of COPD in older patients.

OBJECTIVE: To establish normal values for detection indexes of peripheral skeletal muscle dysfunction (quadriceps femoris) of healthy older subjects, and investigate the functional status of the peripheral skeletal muscle of patients with stable phase COPD. PATIENTS AND METHODS: Patients with stable phase COPD and healthy subjects of similar age were included. The assessments of strength and myoelectricity of the quadriceps femoris were recorded. The twitch tension of the quadriceps femoris (TwQ), quadriceps maximum voluntary contraction (QMVC), and endurance time (Tf) were measured. The multiple-parameter malnutrition index (MNI) was used for overall evaluation of the nutritional status of patients. The femoral muscle volume was estimated. All subjects were subjected to a routine pulmonary function test including indexes such as FEV1, FVC, FEV1/FVC (%), and PEF. Enzyme-linked immunoassay (ELISA) was used to measure the levels of myostatin, tumor necrosis factor-α, TNF-like apoptosis-inducing factor (TWEAK), surface active protein D (SPD), C-reactive protein (CRP), interleukin (IL)-1ß, and IL-6. The cell immunohistochemical method was used to detect the expression of nuclear factor Kappa B (NF-κB). RESULTS: There were significant differences in body weight, BMI, femoral muscle volume, and physical activity scores between the two groups (p<0.01). The MNI of patients in the COPD group was significantly higher than that in the control group (p<0.01). The QMVC of 51 male and 16 female patients decreased. All eight tested cytokines increased in the COPD group but there were only significant differences in four cytokines (p<0.05). CONCLUSIONS: Chronic systemic inflammation is a major risk factor of skeletal muscle dysfunction (SMD) in COPD patients. The levels of SPD, myostatin, TWEAK, and TNF-α decreased significantly in COPD patients.

Experiments on the effects of several factors on the 1-hydroxypyrene level in human urine as an indicator of exposure to polycyclic aromatic hydrocarbons.

The concentration of 1-hydroxypyrene in human urine was determined in six volunteers who lived under the same conditions. Samples were collected four times per day for three consecutive days; the maximum concentration of 1-hydroxypyrene was found in the samples collected late in the evening (21:00-23:00 h) which is the time recommended as suitable for determination of urinary 1-hydroxypyrene for the purpose of evaluating human exposure to polycyclic aromatic hydrocarbons (PAHs). Statistical tests show that the influence of sex, age, and smoking on urinary 1-hydroxypyrene is statistically insignificant.

Urinary 1-hydroxypyrene as an indicator of human exposure to ambient polycyclic aromatic hydrocarbons in a coal-burning environment.

Urinary 1-hydroxypyrene of residents of Beijing, Shenyang and Taiyuan, and workers at two coke plants, a steel plant and control groups was determined using high pressure liquid chromatography. Polycyclic aromatic hydrocarbons (PAHs) of airborne particulates from these cities and coke plants were analyzed using GC-MS; chromatogram profiles, from which 15 chemical compounds were quantified, were similar. The percentage of pyrene and benzo[a]pyrene in PAHs was fairly constant. Statistical analysis showed significant correlation of urinary 1-hydroxypyrene with the concentration of pyrene and benzo[a]pyrene in the ambient PAHs; the correlation coefficient was 0.978 and 0.959, respectively. It is suggested that urinary 1-hydroxypyrene can be used as a biological monitoring index for human exposure to genotoxic PAHs from the burning of coal.