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.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

BackgroundNanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.

MethodsWe synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.

ResultsWe demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.

ConclusionThe use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

BACKGROUNDLuminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure.

METHODSAdult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice.

RESULTSTwo different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain.

CONCLUSIONSThis study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

Objective To evaluate the protective efficacy of influenza vaccine in the elderly in China. Methods The Chinese databases (CNKI, Wan Fang, VIP) and English databases (Pubmed, Embase) were searched, then studies related to the protective efficacy of influenza vaccine in the elderly according to pre-designed criteria were included and the vaccine efficacy(VE) was selected as an evaluation index. Rev Man 5.3 and Stata 12.0 were used in this meta analysis. Results A total of 26 studies (2000-2016) including 6 kinds of outcomes were eligible, of which, 22 articles related to influenza like illness (ILI) , 5 articles related to common cold (CC) , 11 articles related to the attendance rate due to ILI and CC, 7 articles about chronic diseases (including Hypertension, Diabetes, Coronary Heart Disease (CHD) , Stroke, Cancer, Chronic bronchitis and others) , 6 articles about chronic disease treatment and 3 articles about all-cause mortality. The VE of influenza vaccine was 58.00% (95%CI: 48.00%-66.00%), 40.00%(95% CI: 30.00%-50.00%), 42.00% (95% CI: 34.00%-49.00%), 17.00% (95% CI: 11.00%-23.00%), 28.00%(95% CI: 14 .00 % -40.00 %) and 28 .00 % (95% CI: 15 .00 % -39 .00 %) , respectively. Conclusion Influenza vaccination can effectively prevent the occurrence of influenza like disease and other symptoms in the elderly in China.

OBJECTIVETo study the effects of using Compound Danshen Injection (CDI) and low molecular weight heparin (LMWH) on early severe preeclampsia women.

METHODSRetrospective analysis was carried out in 95 patients with early severe preeclampsia from October 2008 to January 2011. They were assigned to 3 groups based on anticoagulant drugs. The routine therapy of magnesium sulfate (MgSO4) was given to the MgSO4 group (40 cases); the MgSO4 + CDI was given to those in the CDI group (23 cases), the MgSO4 + LMWH group was given to those in the LMWH group (32 cases). The general data of all patients were collected to analyze their effects on labor, postpartum hemorrhage, reasons for terminating the pregnancy, and maternal complications.

RESULTS(1) The average gestational week (weeks) of terminating the pregnancy was 31.7 +/- 1.9 in the MgSO4 group, 33.0 +/- 1.8 in the CDI group, and 32.8 +/- 1.7 in the LMWH group. The average weight of newborn babies (g) was 1 450.5 +/- 402.3 in the MgSO4 group, 1 582.2 +/- 332.5 in the CDI group, and 1 590.0 +/- 340.1 in the LMWH group. There was no obviously difference in the average gestational weeks or the average weight of newborn babies among the three groups. (2) The way of terminating the pregnancy was uterine-incision delivery. The main reasons for operation were sequenced as maternal complications, unsatisfied control of the blood pressure, and fetal distress. (3) The maternal complications in the three groups were sequenced as renal failure (12 cases), placental abruption (9 cases), hemolysis, increased liver enzymes and low platelet (HELLP) syndrome (8 cases). Sixteen (40.0%) had complications in the MgSO4 group, 12 (52.2%) in the CDI group, and 15 (46.9%) in the LMWH group. No statistic difference existed among the 3 groups.

CONCLUSIONSLMWH and CDI were helpful to improving the therapeutic effects of severe preeclampsia patients. They did not increase adverse drug reactions. They seemingly had effects on prolonging the gestational week.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Magnesium Sulfate ; therapeutic use ; Phenanthrolines ; therapeutic use ; Pre-Eclampsia ; drug therapy ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies

Objective To assess the prevalence,demographic characteristics,risk factors and protective factors on major depression disorder(MDD)among the affected people in the epicenter,7 months after the 2008-earthquake in Wenchuan,China.Methods Stratified multistage cluster randomization was conducted to choose 14 503 subjects aged 15 years or over in the city of Dujiangyan,Beichuan county and Qingchuan county,Sichuan province.We used the general health questionnaire(GHQ-12)as the screening instrument,and the structured clinical interview for DSM-Ⅳ-TR axis Ⅰ disorder-patient edition(SCID-Ⅰ/P)as the tool for diagnosis.Results There were 180 persons diagnosed as MDD with other 13 asymptomatic ones.The point prevalence of MDD was 1.27% and the lifetime prevalence was 1.36%.Risk factors were including:being female(OR=1.56,95%CI:1.136～ 2.143,P＜0.05),co-morbidity with somatic diseases(OR=4.02,95%CI:2.75-5.90,P＜0.05),wounded in the earthquake(OR=3.29,95%CI:1.92-5.65,P＜0.05),property loss up to 10 000-20 000 Yuan(OR=2.09,95%CI:1.18-3.69,P＜0.05),property loss up to＞20 000 Yuan(OR=2.54,95%CI:1.38-4.68,P＜0.05),death or missing of family members(OR=3.79,95%CI:2.08-6.89,P＜0.05)and in middle-age(OR=2.31,95%CI:1.38-3.86,P＜0.05)etc.Having had a job seemed to be a protective factor(OR=0.60,95%CI:0.43-0.83,P＜0.05).Conclusion Major depressive disorder appeared to be a common psychiatric disease in these quake-stricken areas,that causing serious problems.Sustained follow-up and care provided to the affected people in these areas were of extreme importance.

OBJECTIVEShen Yan Ling Tablet is an innovative compound of traditional Chinese medicine, scientifically prepared with Tripterygium wilfordii, Radix Astragali, and others, with precise efficacy on renal diseases and reduced adverse effects of Tripterygium wilfordii. Based on the Guiding Principles for New Drug Toxicity Research Before Clinical Application, we investigated the long-term toxicity of Shen Yan Ling Tablet and its effect on the reproductive function in rats.

METHODSAccording to the clinical therapeutic dose and the results of the acute toxicity test of Shen Yan Ling Tablet, we equally divided 80 rats (males and females half-and-half) into a low-dose (1.25 g/kg body wt), a medium-dose (2.50 g/kg body wt), a high-dose (5.00 g/kg body wt) and a control group. After a 3-month medication, we conducted standardized long-term toxicity tests and observed the effects of Shen Yan Ling on the serum sexual hormones and epididymal sperm count.

RESULTSAfter 3 months of treatment with Shen Yan Ling, no death occurred, the general status remained unchanged, and the parameters of blood cytology and biochemistry fluctuated within the normal range, without any significant changes (P > 0.05). Some blood parameters, RBC, WBC, HGB, AST and TBIL, showed statistic changes (P < 0.05), but with no clinical significance. There were no significant differences in the mass coefficients of the main organs between the medication and control groups. The high-dose group exhibited slight hepatic and pulmonary pathological changes and significantly reduced sperm counts in the epididymis, but no significant changes in serum sexual hormones (P < 0.05).

CONCLUSIONThree-month medication of Shen Yan Ling at 1.25 - 5.00 g/kg produced no significant accumulated toxicity on rats, but it had a negative effect on their reproductive function at a higher dose of > or = 5.00 g/kg.

Animals ; Drugs, Chinese Herbal ; toxicity ; Epididymis ; drug effects ; Female ; Male ; Nephritis ; drug therapy ; Organ Size ; Phytotherapy ; Plant Extracts ; toxicity ; Rats ; Rats, Sprague-Dawley ; Spermatozoa ; drug effects ; Tablets ; Toxicity Tests, Acute ; Tripterygium

OBJECTIVETo provide reliable evidence of "J in three-needle therapy" for treatment of stroke.

METHODSMulti-central randomized controlled trials were adopted, 180 hemiplegia patients of ischemic stroke were randomly divided into a fin three-needle group (90 cases) and a routine acupuncture group (90 cases). Two groups were both treated with basic neurology therapies, and J in three-needle group was treated with J in three-needle therapy, three acupoints of tempora, hand and foot etc. were selected; the routine acupuncture group was treated with traditional acupuncture, Quchi (LI 11), Huantiao (GB 30), Futu (ST 32) etc. were selected. Both groups were treated with acupuncture for 5 weeks. The cognitive function score of functional comprehensive assessment scale (FCA), the scores of mini-mental state examination scale (MMSE) and modified Barthel index (BI) were compared before and after treatment between two groups. Results After treatment, the scores of FCA, MMSE and BI in both groups were significantly improved compared to those before treatment (P < 0.01, P < 0.05); the improvement of FCA score, MMSE score and BI score in the J in three-needle group were superior to those of the routine acupuncture group after treatment (P < 0.01, P < 0.05). The total effective rate of 85.4% in the J in three-needle group was superior to tohat of 70.0% in the routine acupuncture group (P < 0.05).

CONCLUSIONJ in three-needle acupuncture treatment can obviously improve the cognitive function and activity ability of daily life of hemiplegia patients after stroke, and the therapeutic effect of J in three-needle therapy is superior to that of traditional acupuncture treatment.

Activities of Daily Living ; Acupuncture Therapy ; Adult ; Aged ; Cognition ; Female ; Hemiplegia ; etiology ; psychology ; rehabilitation ; therapy ; Humans ; Male ; Middle Aged ; Stroke ; complications

OBJECTIVETo investigate how smoking was affecting the prevalence of sleep apnea/ hypopnea syndrome (SAHS) among adults aged over 30 years in Chengde city of Hebei province.

METHODS1168 subjects, over 30 years of age were derived from a random sample from a community-based population in Shuangqiao district of Chengde city. All subjects responded to a questionnaire at their own houses regarding their habits of snoring and smoking. 1168 subjects (95.2%) answered the questions satisfactorily.

RESULTS(1) Among the smoking groups, the prevalence of snoring was 69.09%, higher than that in the nonsmoking groups 45.07% (P = 0.000). (2) In males, the smoking group had a higher prevalence (69.72%) of snoring than in the nonsmoking group (60.80%, P = 0.033). (3) Females in the smoking group had a higher prevalence of snoring (61.80%) than in the nonsmoking group (39.70%, P = 0.011). (4) The prevalence of snoring in males (60.80%) was significantly higher than that in females (39.70%, P = 0.000). (5) The prevalence (69.72%) of snoring in smoking males was similar to that in smoking females (61.80%, P = 0.336). (6) Data from logistic regression analysis indicated that smoking was one of the factors affecting snoring. (7) According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated. According to the AHI > or = 5 and the ESS > or = 9 cutoff-points, the prevalence rates of SAHS in smoking groups were both significantly higher than that in nonsmoking groups (P < 0.001).

CONCLUSIONSmoking and snoring among adults aged over 30 years had correlation in our city.

Adult ; Aged ; Aged, 80 and over ; Epidemiologic Studies ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Polysomnography ; Prevalence ; Sleep Apnea Syndromes ; epidemiology ; Smoking ; adverse effects ; Snoring ; epidemiology ; Surveys and Questionnaires

OBJECTIVETo investigate whether 5alpha-reductase inhibitor and dihydrotestosterone (DHT) play a role in spermatogenesis in male rats.

METHODSThirty-two male rats were divided into 4 groups (Groups C, T, F and FT). Group C received plant oil injection and oral starch perfusion, Group T testosterone undecanoate (TU, 20 mg/kg) injection and oral starch perfusion, Group F plant oil injection and oral Finasteride perfusion, and Group FT TU (20 mg/kg) injection and oral Finasteride perfusion. Data on serum T and DHT, sperm count, sperm mobility and reproductive function were collected and analysed.

RESULTS(1) 5alpha-reductase inhibitor, Finasteride and TU reduced the weight of the testis and epididymis in the experiment groups compared with the negative control (Group C), but TU increased the weight of the prostate while Finasteride decreased it compared with the positive control (Group T). TU combined with Finasteride could counteract the effect of the weight increase of the prostate, but not that of the testis. (2) Finasteride, or Finasteride combined with TU, reduced the DHT but increased the testosterone level in comparison with the control group. (3) Both Finasteride and TU could inhibit epididymal sperm count and reproductive function compared with the control, but the effect was less significant in Group FT than in Group F.

CONCLUSIONHigh dosages of 5alpha-reductase inhibitor, Finasteride, can suppress male reproductive function, but the inhibiting effect could be counteracted by administration of 5alpha-reductase inhibitor along with TU.

Animals ; Cholestenone 5 alpha-Reductase ; antagonists & inhibitors ; Dihydrotestosterone ; pharmacology ; Dose-Response Relationship, Drug ; Finasteride ; pharmacology ; Male ; Organ Size ; Prostate ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; drug effects ; Testis ; drug effects ; pathology ; Testosterone ; analogs & derivatives ; pharmacology