[Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen].

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

Outcomes of intracytoplasmic sperm injection in oligozoospermic men with Y chromosome AZFb or AZFc microdeletions.

We investigated whether the presence of Y chromosome azoospermia factor (AZF) microdeletions impacts upon the outcomes of intracytoplasmic sperm injection (ICSI) using fresh ejaculated spermatozoa. Sixteen oligozoospermia patients with Y chromosome AZFb or AZFc microdeletions and undergoing ICSI cycles between March 2013 and November 2014 were studied. Twenty-six infertile men with normal Y chromosomes and also undergoing IVF/ICSI in the same time period were used as controls. A retrospective case-control study approach was used. Among the 16 cases, 12 (75%, 12/16) had deletions of AZFc markers (sY152, sY254 and sY255), one (6.25%, 1/16) had a deletion of sY152, and two (12.5%, 2/16) had deletions of sY152, sY254, sY255 and sY157. AZFb microdeletions were found in one patient (6.25%, 1/16). There were no significant differences between groups for cleaved embryo rate, high-grade embryo rate, blastocyst formation rate, embryo implantation rate, clinical pregnancy rate and delivery rate. The clinical outcomes of ICSI for oligozoospermic patients with Y chromosome AZF microdeletion are comparable to those of infertile patients with normal Y chromosomes. Our findings indicate that ICSI should be offered to patients with an AZFc deletion and that oligozoospermia patients with AZFb microdeletions are likely to father children.

Cognitive impairment in Chinese neuromyelitis optica.

BACKGROUND: Cognitive dysfunction is frequently seen in neuromyelitis optica (NMO). However, the features and influencing factors of cognitive impairment of Chinese NMO patients are unclear. OBJECTIVE: To investigate the patterns of cognitive impairment in Chinese NMO patients, and correlate the neuropsychiatric scores with clinical and MRI parameters. METHODS: Thirty-six Chinese NMO patients, and 30 sex and age-matched healthy controls were recruited with extensive neuropsychological assessments, using the modified Minimal Assessment of Cognitive Function in MS (MACFIMS). The demographic and clinical characteristics as well as MRI parameters were compared between cognitively impaired (CI) and cognitively preserved (CP) patients. RESULTS: NMO patients were significantly impaired in the Paced Auditory Serial Addition Task (P<0.05), the Symbol Digit Modalities Test (P<0.001), the California Verbal Learning Test-Second Edition (P<0.05), the Brief Visuospatial Memory Test-Revised (P<0.05) and semantic fluency (P<0.001). Only lower education level was associated with cognitive dysfunction in NMO (odds ratio: 0.57, P<0.05). There were no significant differences of MRI parameters regarding white matter (WM) lesions, grey matter and WM brain volume between CI and CP patients. CONCLUSIONS: Chinese NMO patients particularly demonstrated cognitive impairment in information processing speed, executive function and memory. Lower education level was the main factor contributing to cognitive impairment in NMO.

Inheritance of balanced translocation t(17; 22) from a Down syndrome mother to a phenotypically normal daughter.

We report that a 30-year-old woman with mental retardation was referred for prenatal diagnoses during pregnancy. An ultrasound scan showed that the heart structure and function of the fetus were normal. Cytogenetic analysis showed that the female karyotype was 47,XX, t(17; 22) (q21; q11), +21. The woman's husband had a normal male karyotype and was phenotypically normal. During this first pregnancy, an amniocentesis, which was done at 19 weeks, revealed that the fetal karyotype was 46,XX, t(17; 22) (q21; q11). Fluorescence in situ hybridization testing of amniotic fluid gave a normal result for chromosome 21. The child was a phenotypically normal female baby.

[The relationship between genetic polymorphism of CYP2C19 and the efficacy of Helicobacter pylori eradication therapy in children].

Objective: To investigate the relationship between genetic polymorphisms of cytochrome P450 2C19 (CYP2C19) and the efficacy of Helicobacter pylori (Hp) eradication therapy in children. Methods: The retrospective cohort study was conducted on 125 children with gastroscopy and positive rapid urease test (RUT) from September 2016 to December 2018 who presented to the Children's Hospital of Zhejiang University School of Medicine due to gastrointestinal symptoms including nausea, vomiting, abdominal pain, bloating, acid reflux, heartburn, chest pain, vomiting blood and melena. Hp culture and drug susceptibility test were carried out with gastric antrum mucosa before treatment. All the patients completed 2 weeks of standardized Hp eradication therapy and had 13C urea breath test 1 month after that, which was used to evaluate the curative effect. The DNA of gastric mucosa after RUT was analyzed and CYP2C19 gene polymorphism was detected. Children were grouped according to metabolic type. Combined with the results of Hp culture and drug susceptibility, the relationship between CYP2C19 gene polymorphism and the efficacy of Hp eradicative treatment was analyzed in children. Chi square test was used for row and column variables, and Fisher exact test was used for comparison between groups. Results: One hundred and twenty five children were enrolled in the study, of whom 76 were males and 49 females. The genetic polymorphism of CYP2C19 in these children found poor metabolizer (PM) of 30.4% (38/125), intermediate metabolizer (IM) of 20.8% (26/125), normal metabolizer (NM) of 47.2% (59/125), rapid metabolizer (RM) of 1.6% (2/125), and ultrarapid metabolizer (UM) of 0. There were statistically significant in positive rate of Hp culture among these groups (χ2=124.00, P<0.001). In addition, the successful rates of Hp eradication in PM, IM, NM and RM genotypes were 84.2% (32/38), 53.8% (14/26), 67.8% (40/59), and 0, respectively, with significant differences (χ2=11.35, P=0.010); those in IM genotype was significantly lower than that in PM genotype (P=0.011). With the same standard triple Hp eradicative regimen, the successful rate of Hp eradication for IM type was 8/19, which was lower than that of PM (80.0%, 24/30) and NM type (77.3%, 34/44) (P=0.007 and 0.007, respectively). There was a significant difference in the efficacy of Hp eradication treatment among different genotypes (χ2=9.72, P=0.008). According to the clarithromycin susceptibility result, the successful rate of Hp eradication treatment for IM genotype was 4/15 in the sensitive group and 4/4 in the drug-resistant group (χ2=6.97, P=0.018). Conclusions: The genetic polymorphism of CYP2C19 in children is closely related to the efficacy of Hp eradication treatment. PM has a higher successful rate of eradication treatment than the other genotypes.

Resveratrol, an effective regulator of ovarian development and oocyte apoptosis.

Resveratrol, a phytopolyphenol compound found chiefly in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. However, little is known about the effects of resveratrol on ovarian development and oocyte apoptosis. We investigated the effects of resveratrol on ovarian development in rats with different ages [from post-natal day (PD) 1 to 15 months], as well as on oocyte apoptosis in PD1 and PD2 rat ovaries. We show that: a) ip injection of resveratrol (20 mg/kg/day) increased the percentage of unassembled follicles and the total number of oocytes in PD1 and PD2 rat ovaries. Similar results were obtained when mothers were treated with resveratrol (20 mg/kg/day) by intragastric administration from day 11, after the detection of vaginal plug, until delivery. In PD4 rat ovaries, the total number of oocytes was significantly increased in the groups treated with resveratrol. Moreover, more unassembled follicles and fewer primary follicles were present in the groups treated with resveratrol than in the controls; b) in 15-month-old rat ovaries, resveratrol increased the number of resting follicles and total oocytes, and decreased the number of developing follicles and atretic follicles; 3) the percentage of TUNEL-positive oocytes decreased in PD1 and PD2 rat ovaries after resveratrol treatment, and the number of oocytes positive for Foxo3a, Bim, and p27KIP1 in PD2 rat ovaries was lower in the resveratrol treatment group than in controls. These results suggest that resveratrol may delay oocyte nest breakdown and inhibit both the primordial-to-developing-follicle transition and apoptosis by decreasing the activation of Foxo3a, Bim, and p27KIP1, thus augmenting the resting follicle reserves, maintaining regular estrous cycles of early aged rats and delaying climacterium.

Ultrasonic atomization and subsequent desolvation for monoclonal antibody (mAb) to the glycoprotein (GP) IIIa receptor into drug eluting stent.

An eluting-stent system with mAb dispersed in the PLLA (poly (L-lactic acid)) was validated in vitro. Specifically designed spray equipment based on the principle of ultrasonic atomization was used to produce a thin continuous PLLA (poly (L-lactic acid)) polymer coating incorporating monoclonal antibody (mAb). This PLLA coating was observed in light microscopy (LM) and scanning electron microscopy (SEM). The concentration of the monoclonal antibody (mAb) to the platelet glycoprotein (GP) IIIa receptor and the eluting rate were then measured by a radioisotope technique with (125)I-labelled GP IIIa mAb. An in vitro perfusion circuit was designed to evaluate the release rates at different velocities (10 or 20 ml min(-1)). The PLLA coating was thin and transparent, uniformly distributed on the surface of the stent. Three factors influenced its thickness: PLLA concentration, duration and gas pressure. The concentration of mAb was influenced by the duration of absorption and the concentration of the mAb solution; the maximum was 1662.23 + or - 38.83 ng. The eluting rate was fast for the first 2 h, then decreased slowly and attained 80% after 2 weeks. This ultrasonic atomization spray equipment and technological process to prepare protein eluting-stents were proved to be effective and reliable.

Effects of feeding diets with processed Moringa oleifera stem meal on growth and laying performance, and immunological and antioxidant activities in laying ducks.

This study was conducted to determine the effect of Moringa oleifera stem (MOS) meal in ducks. A total of 225 ducklings at 1 D of age were randomly assigned to 3 dietary treatment groups with 3 replicates of 25 each. The growth experiment lasted 63 D . The egg experiment started from 23 to 27 wk of age. Ducks were randomly divided into 3 treatment groups with 3 replications of 15 each. The following dietary treatments were applied: 1) Control (CON), basal diet + 0% MOS meal; 2) basal diet + 2% MOS meal; 3) basal diet + 4% MOS meal. During 0 to 4 wk of age, ducks fed 2% MOS diet showed significantly increase in average daily feed intake (ADFI) and average daily gain (ADG; P < 0.05) and ducks fed 4% MOS diet had a significant improvement in feed conversion rate (FCR; P < 0.05). However, ADFI, ADG, and FCR were not affected significantly during 5 to 9 wk of age (P > 0.05). In egg production experiment, ADFI, average egg weight, laying rate, and FCR showed significant increase in 4% MOS diets (P < 0.05). Laying ducks fed 4% MOS diet had a higher egg shape index, whereas a lower yolk color compared with CON (P < 0.05). The proportion of broken shell eggs were zero in experimental diets, whereas 3% of which occurred in CON (P < 0.05). However, no significant effects in proportion of soft shell eggs, proportion of abnormal-shape eggs, albumen height, haugh unit, and eggshell thickness were observed among all treatments (P > 0.05). For serum biochemical parameters, total protein and albumin were increased in MOS diets during 0 to 4 wk of age, but decreased during 5 to 9 wk of age. For serum antioxidant index, superoxide dismutase and glutathione peroxidase values were increased whereas malondialdehyde values were decreased in MOS diets from 0 to 9 wk of age. The results suggest that MOS positively affects early growth performance and laying performane of duckling but partially affects egg quality. The antioxidative activity and immunological index may be improved.

Presence of pldA and exoU in mucoid Pseudomonas aeruginosa is associated with high risk of exacerbations in non-cystic fibrosis bronchiectasis patients.

OBJECTIVES: To explore the association between the virulence genes exoU and pldA in isolated mucoid Pseudomonas aeruginosa and the clinical outcomes of patients with non-cystic fibrosis (CF) bronchiectasis. METHODS: A prospective observational cohort study was performed in the Shanghai Pulmonary Hospital from October 2012 to January 2015. We consecutively enrolled all non-CF bronchiectasis patients with mucoid P. aeruginosa isolates obtained from bronchoalveolar lavage fluid or sputum. The exposure variable was the presence of virulence gene, exoU or pldA, in the strains. The primary outcome was exacerbation of bronchiectasis. Logistic regression analysis was performed to evaluate the association between virulence genes and exacerbation. RESULTS: The final analysis included 147 patients (mean (SD) age, 57.86 (11.43) years, 101 female subjects) with median (interquartile range) follow-up of 18 (13-26) months. The following factors were relative to exacerbations: body mass index ≤18.5 kg/m2 (odds ratio (OR) = 5.05; 95% confidence interval (CI), 1.37-18.57), length of stay ≥8 days (OR = 2.65; 95% CI, 1.14-6.19) and positive for either virulence gene (OR = 6.80; 95% CI, 1.47-31.37). The gene-positive group had more exacerbations per year (mean 2.37, SD 2.10, n = 33 vs. mean 0.79, SD 0.83, n = 114) and a higher proportion of patients with exacerbation (31/33, 93.94% vs. 74/114, 64.91%). The proportion of patients being exoU or pldA positive increased as the exacerbation frequency of bronchiectasis increased. CONCLUSIONS: The virulence genes exoU and pldA in mucoid P. aeruginosa are significant risk factors for exacerbations in patients with non-CF bronchiectasis.

ULK1 polymorphisms confer susceptibility to pulmonary tuberculosis in a Chinese population.

OBJECTIVE: The autophagy pathway is a critical process in Mycobacterium tuberculosis infection, and can be regulated by uncoordinated 51-like kinase 1 (ULK1). We investigated the associations between single-nucleotide polymorphisms (SNPs) in ULK1 and risk of tuberculosis (TB) in a Chinese Han population. DESIGN: We recruited 380 pulmonary tuberculosis (PTB) cases, 242 extra-pulmonary tuberculosis (EPTB) cases and 606 healthy controls from a Chinese Han population and sequenced ULK1. Five SNPs in ULK1 were selected to investigate the correlations between ULK1 polymorphisms and TB susceptibility. RESULTS: The rs7138581 C allele was associated with a reduced risk of PTB (P = 0.001), whereas the rs9481 A allele was associated with an increased risk (P = 0.025). The rs7138581 CG genotype was significantly associated with a low risk of PTB, with a higher PTB disease severity in clinical parameters. Estimation of haplotype frequencies in ULK1 revealed a protective haplotype CCGAA (P = 0.007) and a potential risk haplotype TGAAA (P = 0.010) for PTB. CONCLUSION: These results demonstrated that ULK1 polymorphisms have significant associations with susceptibility to PTB.

Effects of tea polyphenols on ovarian development in rats.

Tea is the most consumed beverage in the world. Tea polyphenols are the major constituents of tea leaves and have shown many potential healthy benefits. However, whether tea polyphenols influence ovarian follicle assembly and development and ovarian life span is unknown. To study the effect of tea polyphenols on ovarian follicle development and oocyte apoptosis, we investigated rat ovarian development of different ages [from postnatal day (PD)1 after birth to 10 months] after treatment with tea polyphenols. Our data showed that the percentage of unassembled follicles increased in the ovaries of 1- and 2-day-old rats which were ip injected with tea polyphenols (50 mg/kg/d) or whose mothers were treated with tea polyphenols (100 mg/kg/d) by intragastric administration from the day 11 after the detection of vaginal plug till delivery. The percentage of primordial follicles increased, while that of developing follicles decreased in the ovaries of 4- and 8-day-old rats following peritoneal injection with tea polyphenols compared with controls. The ratio of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL)-positive oocytes decreased in the ovaries of neonatal rats following tea polyphenol treatment. In the 3- and 10-month-old rat ovaries, the number of primordial follicles augmented, whereas that of atretic follicles decreased after the treatment for 4 weeks. These data suggest that tea polyphenols may inhibit the transition from primordial to developing follicles, extend the entire growth phase of a follicle, and reduce dominant follicle numbers per cycle to increase the reserve of germ cells, inhibit oocyte apoptosis and follicle atresia during ovarian development from birth to early aged, and retard climacterium in rats. Drinking even a small cup of tea per day may benefit to extent the productive life of ovary.

Effect of immune RNA on NK activity of infants born to mothers with cytomegalovirus infection.

The effect of specific immune RNA (i-RNA) on the activity of natural killer (NK) cells in the peripheral blood of 27 newborn infants was studied by lactic dehydrogenase (LDH) release assay. Peripheral blood mononuclear cells (PBMC) were used as effector cells with K-562 tumour cells as target cells. The results showed that in the therapeutic group (n = 17) the average activity of NK cells after therapy (24.13 +/- 4.62%) was 13.67 +/- 5.79% higher than before therapy (10.47 +/- 3.57%). In the control group (n = 10) these were only 10.78 +/- 3.94% and 11.58 +/- 3.37%, the difference was not statistically significant (P > 0.05). However, NK activity in the therapeutic group and control group was markedly different (P < 0.01). The data indicate that specific i-RNA can enhance the activity of NK cells in the peripheral blood of newborn infants. Therefore, we believe that specific i-RNA may play an important role in defence against CMV infection. The mechanism of i-RNA augmenting NK cellular activity is also discussed.

[Diagnosis and treatment of cornual obstruction by transcervical fallopian tube cannulation under hysteroscopy].

Transcervical cannulation of the proximal oviduct was performed with a tube catheter and flexible guidewire under hysteroscopic guidance to evaluate and treat intramural fallopian tube obstruction in 37 patients. Hysteroscopic cannulation with direct visualization by laparoscopy was successful in 69.2% of the obstructed tubes, 77.4% of the cases. 74% of the obstructed tubes diagnosed by HSG and/or laparoscopy was patent after hydrotubation and cannulation by hysteroscopy. Transcervical cannulation of the proximal oviduct is an effective method for evaluation and treatment of cornual obstruction.

[Ultrasonic study with hydrotubation of tubal patency].

Ultrasonic study of tubal patency using 1.5% hydrogen peroxide as the contrast medium during hydrotubation was performed in 147 sterile women. Hysterosalpingography was also done for the same patients. In 42 cases, laparoscopic examination of the tubes was carried out to assess the accuracy of the above two diagnostic procedures. The correspondence rate between laparoscopic findings and ultrasonography was 88.0% and 60.0% with hysterosalpingography. The difference was statistically significant (P less than 0.05). Animal experiment did not reveal any untoward effect of 1.5% hydrogen peroxide on the local tissues exposed to the solution except a transient increase of lymphocyte infiltration and exudate. Regardless of its numerous advantages, neither hysterosalpingography nor ultrasonic examination can demonstrate minute pathologic changes in the lumen of the tube. The authors pointed out that ultrasonic study combined with laparoscopic examination is the best choice diagnosis for tubal abnormalities.

[Intrauterine device-induced menorrhagia and endometrial content of prostacyclins].

The endometrial concentration of 6-keto-PGF1 alpha and TXB2 were measured by RIA in women with Tcu-IUD induced menorrhagia (MBL greater than 80 ml) and in levonorgestrel-IUD users with oligomenorrhea or amenorrhea. Non-IUD users with normal menses (MBL less than 80 ml) were chosen as control. It was found that the Tcu-IUD group showed a significantly higher 6-keto-PGF1 alpha concentration than the other two groups (P less than 0.01). Conversely, the TXB2 concentration of levonorgestrel-IUD group was significantly higher than that of the other groups (P less than 0.05). As a result, the 6-keto-PGF1 alpha/TXB2 ratio was much higher in Tcu-IUD group (P less than 0.01). Our results indicated that the unbalance of PGI2/TXA2 ratio may be the direct cause of the IUD-induced menorrhagia.

[Transcervical salpingography and tubal recanalization].

The results of transcervical salpingography and tubal recanalization by means of modified Thurmond and Rösch's technique were reported. Proximal tubal obstruction was diagnosed in 20 infertile women by X-ray hysterosalpingography and/or laparoscopy. Our results showed that tubal recanalization was achieved in 19(95%) of 20 patients, four patients became pregnanCy following the procedure. Distal tubal diseases were seen in 8 of 20 patients. Follow up studies revealed tubal patency was maintained in 7(54%) of 13 patients. The mean radiation dosage received by the patient was 6.35mGy. Compared with Thurmond and Rösch technique the modified technique has the advantage of decreasing the time of fluoroscopy and is a safe, effective and simple method for the diagnosis and treatment of infertile women with proximal tubal obstruction.

Layer-by-layer assembly of chitosan and platelet monoclonal antibody to improve biocompatibility and release character of PLLA coated stent.

The aim of this study is to construct a biocompatible coating of a drug-eluting stent through the incorporation of chitosan with monoclonal antibody (mAb) to a platelet glycoprotein (GP) IIIa receptor, by electrostatic layer-by-layer (LBL) adsorption of oppositely charged polyelectrolytes and proteins. The platelet maximum aggregation rate and aggregation inhibition rate tests confirm the bioactivity of mAb in different pH assembly environments. The fluorescence spectra test and confocal laser scanning microscopy observation were used to monitor the LBL assembly process of the mAb/chitosan multilayer on the surface of the aminolyzed Poly-L-lactic acid (PLLA) membrane, when using Rhodamine B isothiocyanate-labeled mAb and Fluorescein isothiocyanate-labeled chitosan. The in vitro platelet adhesion experiment demonstrated the amicable blood compatibility of the mAb/chitosan multilayer. The endothelial cell adhesion and migration test revealed that the multilayer could improve the cytocompatibility of the PLLA matrix in terms of cell attachment, proliferation, and migration. An in vitro perfusion circuit was designed to evaluate the release rates measured by a radioisotope technique with ¹²5I-labeled GP IIIa mAb. The different eluting curves of the mAb/chitosan-assembled stent and mAb physically absorbed stent showed the improvement of mAb's release character when using LBL self-assembly technology. Our method to prepare a biocompatible stent surface with mAb/chitosan multilayers has proved to be favorable and effective in vitro, thus justifying further evaluation to improve the biocompatibility in an animal model test.