[Analysis of the epidemiological traits of occupational pneumoconiosis in Qinhuangdao between 1961 and 2020].

Objective: To study the prevalence of occupational pneumoconiosis in Qinhuangdao from 1961 to 2020 and offer a foundation for developing occupational pneumoconiosis prevention and control methods. Methods: In December 2020, the data of occupational pneumoconiosis cases diagnosed by medical institutions with occupational disease diagnosis qualifications in Qinhuangdao City from 1961 to 2020 were collected Anova or kruskal-Walls tests and chi-square tests were used for inter-group comparisons of continuous and categorical variables, and LSD tests or Tamhane T2 tests were used for multiple comparisons. Results: Between 1961 and 2020, 384 cases of pneumoconiosis were documented in Qinhuangdao, of which 382 (99.5%) patients were men and 2 (0.5%) were women. The average dust service duration is 15 (9, 25) years, with a minimum duration of 0.5 years and a maximum duration of 49 years; Cases were primarily distributed in Qinglong Manchu Autonomous County (187 cases, 48.7%) and the Haigang district (160 cases, 41.7%) ; Type of pneumoconiosis was silicosis (340 cases, 88.5%), mainly 273 cases (71.1%) of stage I, 88 cases (22.9%) of stage II, and 23 cases (6.0% of stage III) ; Cases of Phase II and III and with short lengths of service are mainly concentrated in medium-sized, small, private limited liability companies and collective enterprises. Rrock work (166 cases, 43.2%), and loading kiln workers (42 cases, 10.9%) were the main types. Conclusion: Because the distribution of pneumoconiosis cases in Qinhuangdao city is concentrated and the length of service is decreasing, it is important to enhance the oversight of important area, businesses, industries, and job categories in line with the growth of the region's mineral resources.

[Clinical observation of orthokeratology with increased compression factor in the treatment of myopia].

Objective: To discuss the efficacy and safety of orthokeratology with increased compression factor (ICF) in myopia correction in children. Methods: It was a prospective cohort study. Data of the right eyes of myopic children who visited the First Affiliated Hospital of Chengdu Medical College for orthokeratology were collected continuously from May 2016 to Dec 2018. All children had low myopia (<3.00 D) or moderate myopia (≥3.00 D), and were grouped using random numbers in Excel to receive orthokeratology with ICF or conventional compression factor (CCF). The axial length (AL), spherical equivalent (SE), best corrected visual acuity (BCVA), near visual acuity (NVA), Efron grade, corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), tear film break-up time (BUT), higher-order aberrations (HOAs), accommodative amplitude (AA) and accommodative facility (AF) were compared between groups during the 1-year treatment period. The Chi-squared test was used to compare the categorical data, while the independent-sample t-test was performed to assess the measurement data. Results: After 1 year of treatment, there were no statistical differences in AL, SE, BCVA, NVA, Efron grade, CH, CRF, IOPcc, BUT, HOAs, AA and AF between the low myopia ICF group and the low myopia CCF group (all P>0.05). After 6 months of treatment, the AL increased by (0.05±0.03) mm in the moderate myopia ICF group and by (0.08±0.04) mm in the moderate myopia CCF group (t=-3.416, P=0.001). After 1 year of treatment, the AL increased by (0.12±0.04) mm in the moderate myopia ICF group and by, (0.16±0.05) mm in the moderate myopia CCF group (t=-4.017, P<0.001). The SE was (-0.16±0.40) D in the moderate myopia ICF group, significantly different from that in the moderate myopia CCF group [(-0.58±0.60) D; t=3.529, P=0.001]. There were also statistical differences in HOAs, spherical aberrations and AF (all P<0.05), but no statistical differences in BCVA, NVA, Efron grade, CH, CRF, IOPcc, BUT and AA between the two groups (all P>0.05). Conclusions: Orthokeratology with ICF safely and effectively corrected myopia in children during the observation period. It could control the progression of moderate myopia more effectively than that of low myopia.

Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

[Comparative study on metagenomics of esophageal flora in elderly and middle-aged esophageal squamous cell carcinoma patients].

Objective: To explore the flora characteristics and differences of esophageal tissues between elderly esophageal squamous cell carcinoma (ESCC) patients and young and middle-aged ESCC patients, so as to assist in studying the potential biomarkers of elderly ESCC patients. Methods: In this study, a retrospective study was adopted. 72 ESCC patients diagnosed in Taihe Hospital, Shiyan City, Hubei Province from July 2018 to July 2019 were selected, including 49 patients in the elderly group (≥ 60 years old, 40 males and 9 females), 23 patients in the young and middle-aged group (<60 years old, 21 males and 2 females). In the same period, 20 healthy persons without abnormal gastroscopy in endoscopy center were selected as the control group (aged 35-78 years old, median age 57 years old, 16 males and 4 females). The genomic DNA was extracted from the affected esophageal tissues of patients with ESCC and the middle esophageal samples of the control group. The V4 hypervariable region of bacterial 16SrRNA gene sequence was amplified. Illumina HiSeq sequencing technology was adopted. The flora characteristics of elderly, young and middle-aged ESCC patients was compared and analyzed. QIIME and Rstudio software were used to analyze the sequence data, and nonparametric Kruskal-Wallis test or Wilcoxon rank sum test were used for statistical methods. Results: Shannon index [5.17 (4.53, 5.95) vs. 4.79 (3.74, 5.97)], Simpson index [0.94 (0.91, 0.96) vs. 0.92 (0.83, 0.96)] and Chao1 index [343.55 (259.76, 570.59) vs. 329.16 (268.88, 648.00)] were similar in flora of two groups, and there was no significant difference (Z=-0.791, -1.057, -0.380, all P>0.05). There was no significant difference in ß-diversity between the elderly group and the young and middle-aged group (PC1=19.14%, PC2=6.95%, PPC1=0.67, PPC2=0.42). At the phyla level, the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria in the young and middle-aged group, while the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria in the elderly group; the significant difference between the two groups was Fusobacteria (Q=0.596, P<0.05). At the genus level, the top 5 genera in the young and middle-aged group in abundance were as follows: Prevotella, Bacteroides, Streptococcus, Selenomonas and Veillonella. In the elderly group, Prevotella, Bacteroides, Streptococcus, Selenomonas and Haemophilus were the top 5 in abundance, and there were significant difference in Fusobacterium between the two groups (Q=0.938, P<0.05). PICRUSt function prediction showed that the abundance of Aminoacyl.tRNA.biosynthesis, Nucleotide.excision.repair, RNA.polymerase, Ribosome, Clavulanic.acid.biosynthesis, Photosynthesis and Photosynthesis. proteins in the elderly group were lower than those in the young and middle-aged group (all Q=0.734, P<0.05). Conclusion: There is no significant difference in α-diversity and ß-diversity between elderly ESCC patients and young and middle-aged patients, but the abundance of Fusobacterium flora increased.

[Effect of miR-23b on the malignant phenotype and the sensitivity of lenvatinib in human hepatocellular carcinoma cells].

Objective: To investigate the effect of miR-23b on the malignant phenotype and the sensitivity of lenvatinib in human hepatocellular carcinoma cells. Methods: Human hepatocellular carcinoma cell line HepG2, SMMC-7721 and QGY-7703 were transfected with miR-23b mimic and its control, respectively. CCK-8 and EdU assay were used to detect cell proliferation. Transwell assay were used to detect changes in cell migration and invasion. Tube formation assay were used to detect vasculogenic mimicry formation. The comparison of the mean between groups was analyzed by t-test. Results: CCK-8 results showed that the A values ​​of human hepatocellular carcinoma cell line HepG2 and SMMC-7721 in the miR-23b mimic group were 0.325 ± 0.011 and 0.537 ± 0.026, respectively, which were significantly lower than the control group 0.430±0.017 and 0.752 ± 0.051 (P < 0.05). Transwell assay result showed that the number of cell migration of human hepatocellular carcinoma cell line HepG2 and SMMC-7721 in the miR-23b mimic group was (517.220 ± 32.873) and (242.327 ± 20.793), respectively, which were significantly lower than that of the control group (724.130 ± 15.142) and (424.432 ± 27.212) (P < 0.01). Simultaneously, the number of cell invasions in the miR-23b mimic group were (55.671 ± 7.514) and (64.670 ± 6.011), respectively, which were significantly lower than those in the control group (124.320 ± 11.782) and (156.204 ± 12.501) (P < 0.01). Tube formation assay showed that the number of tube forming branches of hepatocellular carcinoma cell line QGY-7703 and SMMC-7721 in the miR-23b mimic group was (489.824 ± 42.035) and (435.201 ± 44.143), respectively, which were significantly lower than that of the control group (878.620 ± 31.618) and (785.430 ± 38.723) (P ​​< 0.01). In addition, EdU results showed that after miR-23b combined with lenvatinib, the positive rates of EdU staining of hepatocellular carcinoma cell line HepG2 and SMMC-7721 in the miR-23b mimic group were (32.905 ± 1.342)% and (24.811 ± 0.820)%, respectively, which were significantly lower than the control group (52.623 ± 2.441)% and (38.702 ± 1.312)% (P < 0.05). Conclusion: miR-23b can inhibit the proliferation, migration, invasion and vasculogenic mimicry formation, and enhance the sensitivity of lenvatinib drug in human hepatocellular carcinoma cells.

[Seroepidemiological investigation of hepatitis C virus in Zhejiang Province: a hospital-based study].

Objective: To study serum HCV antibody (anti-HCV) with geographic distribution characteristics in Zhejiang Province. Methods: A stratified random cluster sampling method was used. Serum samples of the surveyed population were collected from selected hospitals, anti-HCV antibodies were examined, then hepatitis C infection rates among different genders, regions and age groups were analyzed. The anti-HCV rate was compared using the χ (2) test. Results: The average anti-HCV positive rate in Zhejiang Province was 0.24% [95% confidence interval (CI): 0.16% ~ 0.32%]. The antibody positive rate in the plain area was 0.32% (95% CI: 0.19% ~ 0.45%), which was significantly higher than the coastal islands 0.05%(95% CI: 0.00% ~ 0.12%, χ (2) = 7.638, P < 0.05). There was no significant difference between plain area and hilly area 0.22% (95% CI: 0.03% - 0.41%). There was no statistically significant difference in anti-HCV positive rates between males and females (χ (2) = 2.238, P = 0.135). The highest positive rate of anti-HCV (0.93%) was in the population aged 56-60 years and the lowest in the population aged less than 20 years. Anti-HCV positive rate of all age groups in 2017 was lower than that of 2006 seroepidemiological study of hepatitis C. Conclusion: Zhejiang Province is a region with low anti-HCV positive rate and the disease prevalence further reduced than 10 years ago. The positive rate of anti-HCV in plain areas is higher than islands. Middle-aged and elderly people are the age group with high prevalence, and the anti-HCV positive rate in people under 20 years old is exceptionally low. Gender differences in anti-HCV positive rate have little effect.

Association between dopamine D2 receptor gene polymorphisms and the risk of heroin dependence.

Heroin dependence is a chronic relapsing brain disease. Researchers have reported that the dopamine D2 receptor (DRD2) is involved in the development of opiate dependence. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin dependence and six polymorphisms of the DRD2 gene using the MassARRAY system. Three hundred and thirty-four patients with heroin dependence and 299 healthy controls participated in the research. Compared with the healthy controls, heroin-dependent patients had a significantly lower frequency of the AA genotype of rs6275 (P = 0.038), and a significantly higher frequency of the C allele of rs1125394 (P = 0.030). Statistically significant differences were observed in the genotypic and allelic frequencies of rs17115583 (P = 0.005 and P = 0.001, respectively) and rs1079597 (P = 0.03 and P = 0.02, respectively). Haplotype analysis revealed that the T-G-A (block 1) haplotype of the DRD2 gene conferred a protective effect (P = 0.020). These findings point to a role for DRD2 polymorphism in heroin dependence in the Chinese Han population, and may be informative for future genetic or neurobiological studies on heroin dependence.

A novel variant of the ß-lactamase ADC-61 gene in multi-drug resistant Acinetobacter baumannii.

The aim of this study was to investigate the existence of a ß-lactamase gene in a group of multi-drug resistant Acinetobacter baumannii. Twenty strains of multi-drug resistant A. baumannii were isolated. Thirty-four ß-lactamase genes and the ISaba1-OXA-23 linkage were analyzed in these strains by polymerase chain reaction (PCR) and verified by DNA sequencing. Three kinds of ß-lactamase genes (TEM, ADC, and OXA-23) were identified, among which the sequence of strain No. 20, ADC, was different from ADC subtypes recorded by GenBank, and was identified as a new variant of ß-lactamase genes (named ADC-61 and registered in GenBank: accession No. JQ753702); all the other 19 strains were ADC-30. Eighteen strains of the OXA-23 group were all positive as indicated by detection of ISaba1-OXA-23 linkage. Gene sequencing indicated that the TEM gene was TEM-1. These results suggest that the three kinds of ß-lactamase genes identified in this study, TEM, ADC, and OXA-23, play a key role in drug resistance in this group of A. baumannii. To our knowledge, this is the first report of an emergent new mutation of the ß-lactamase gene, ADC-61, in China or abroad.

Association of the VRK2 gene rs3732136 polymorphism with schizophrenia in a Northwest Chinese Han population.

Previous studies have found that the vaccinia related kinase 2 gene (VRK2) polymorphism was associated with schizophrenia (SCZ) in the worldwide population. This association was further supported by VRK2 mRNA expression patterns and brain structure variations. Here, we analyzed four single nucleotide polymorphisms (SNPs) of the VRK2 gene in a total population of 893 samples, consisting of 360 patients with SCZ and 533 healthy controls of Han Chinese descent using the SNPscan method. Single SNP, haplotype, and gender-specific association analyses were performed. We found that rs3732136 was significantly associated with SCZ (P = 0.042; odds ratio = 1.25; 95% confidence interval = 1.01-1.55). Further genotype and haplotype association analyses suggested a similar pattern. Our data provide preliminary evidence that the VRK2 gene might play a major role in the development of SCZ in the Northwest Chinese Han population.

Expression of aquaporins 1 and 3 in degenerative tissue of the lumbar intervertebral disc.

Lumbar intervertebral disc degeneration is induced by multiple factors, but few studies have examined the effects of aquaporins on this process. We compared the expression levels of aquaporins 1 and 3 in normal and degenerative lumbar intervertebral discs. Fifteen normal and 15 degenerative lumbar intervertebral disc tissues were excised from lumbar burst fracture patients during orthopedic operations at the Dali College subsidiary hospital. Tissues were stained with hematoxylin-eosin and the expression levels of aquaporins 1 and 3 were measured by immunohistochemistry. Hematoxylin-eosin-staining results illustrated that the structures of the intervertebral disc tissues from the control group were clear, with distinct collagen fiber shapes and slight edema but without mucoid degeneration. Structures of the intervertebral disc tissues from the disease group were obscure and disordered with hyperplastic collagen fibers and tissues of severe inflammatory edemas with necrosis mucoid degeneration. Immunohistochemistry results demonstrated that the average absorbances of aquaporins 1 and 3 in the disease group were significantly lower than those in the control group (P < 0.01), suggesting that the reduction of aquaporins 1 and 3 may be a factor resulting in lumbar intervertebral disc degeneration.

[Effect of zirconia personalized gingival penetration on peri-implant soft and hard tissue of thin gingival biotypes in the anterior region: a retrospective study].

Objective: To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline. Methods: This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2±10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index. Results: The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration (0) (Z=-1.03, P=0.394; Z=-2.05, P=0.065). Conclusions: Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.

Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage.

Endothelial nitric oxide synthase (eNOS) is an enzyme that influences placental human chorionic gonadotropin production during gestation. Previous studies have indicated an association between eNOS activity, implantation, and maintenance of pregnancy, but proposed associations between polymorphisms of the eNOS gene and recurrent miscarriage (RM) are controversial. To identify markers contributing to the genetic susceptibility to RM, we examined the potential association between RM and 8 single nucleotide polymorphisms (SNPs; rs1799983, rs2070744, rs11771443, rs3918188, rs2853796, rs7830, rs1541861, and rs2853792) of the eNOS gene using the MassARRAY system (Sequenom, USA). The enrolled participants included 192 RM patients and 201 women with normal fertility as controls. The results showed that rs1799983 at exon 7 of the eNOS gene was significantly associated with RM (genotype: chi-square = 15.071, P = 0.001; allele: chi-square = 6.250, P = 0.016). Another significant association was observed for rs11771443 in the promoter (genotype: chi-square = 6.259, P = 0.044; allele: chi-square = 7.076, P = 0.008). Furthermore, strong linkage disequilibrium was observed in 3 blocks (D' > 0.9), and significantly fewer T-T-G haplotypes (chi-square = 5.981, P = 0.015) residing in block 1 were found in RM patients. These findings point to a role for eNOS gene polymorphisms in RM in the Chinese Han population and may be informative for future genetic or neurobiological studies of RM.

Fusarium solani and Fusarium oxysporum Associated with Root Rot of Glycyrrhiza uralensis in China.

Liquorice (root of Glycyrrhiza uralensis Fisch.) is an important Chinese traditional medicine for many ailments (4). From 2002, severe outbreaks of root rot occurring on cultivated G. uralensis plants in Ningxia, China, have affected the yield and quality of liquorice and been considered as a major threat to commercial production of liquorice. Approximately 30% of the plants die from this disease in Ningxia every year. The disease, mainly affecting 2- to 4-year-old G. uralensis seedlings, begins with brown rot of root tips or lateral roots followed by internal decay of taproots during June to August every year. The infected plants are wilted with chlorotic foliage and easily pulled up from the soil. Root rot is clearly visible as a severe brown discoloration of vascular tissue along taproots. In severe cases, white mycelia are clearly visible on the surface of diseased roots and roots are decomposed. Isolations from diseased roots were made on potato dextrose agar (PDA) amended with streptomycin sulfate. Isolates (n = 78) were recovered from symptomatic roots (n = 105) and pure cultures were established by the single spore method. The two most frequently isolated fungi were transferred to potato sucrose agar and identified as Fusarium solani (61.5%) and F. oxysporum (30.8%) (1). The monophialides bearing microconidia of F. solani are long when compared to those of F. oxysporum. Genomic DNA of strains F. solani G013 and F. oxysporum FLR were extracted from mycelia with the cetyltrimethylammonium bromide (CTAB) method. Primers EF1-728F and EF1-986R were used to amplify the translation elongation factor-1α (TEF-1α) gene (2). The TEF-1α sequences of F. solani G013 (GenBank Accession No. AB777258) and F. oxysporum FLR (AB777257) shared 99 and 100% similarity with F. solani isolate NRRL52790 and F. oxysporum isolate NRRL 38328, respectively. Pathogenicity tests with one representative isolate of each species were conducted in the greenhouse on 1-month-old potted G. uralensis seedlings (12 plants per treatment). Isolates of the tested fungi were transferred to PDA and incubated in darkness at 24 ± 1°C for 7 days. Plant taproots about 5 cm below the soil surface were wounded with a sterile needle and five 5-mm-diameter fungal disks on the margin of colony were taken and firmly placed on the wounded location of each taproot with tinfoil; wounded taproots of seedlings inoculated with sterile PDA disks were used as controls (3). Root rot was assessed 2 months after inoculation. F. solani G013 and F. oxysporum FLR produced root rot symptoms on inoculated plants that were the same as those observed in field plants, and the fungi were reisolated from roots with typical symptoms. Control plants inoculated with sterile PDA disks remained asymptomatic, and no pathogen was isolated from them. To our knowledge, this is the first report of root rot caused by F. solani and F. oxysporum on G. uralensis in China. Effective control strategies are needed to minimize losses. References: (1) C. Booth. The Genus Fusarium. Commonwealth Mycological Institute, Farnham Royal, 1971. (2) I. Carbone and L. M. Kohn. Mycologia 91:553, 1999. (3) M. Guo et al. Plant Dis. 96:909, 2012. (4) T. Wu et al. Am. Assoc. Pharm. Sci. J. 13:1, 2011.

Polymorphisms in the glutamate decarboxylase 1 gene associated with heroin dependence.

The GAD1 gene encodes the 67-kDa glutamic acid decarboxylase isoform (GAD67), the rate-limiting enzyme responsible for γ-aminobutyric acid (GABA) biosynthesis from glutamic acid, and may be involved in the development of drug dependence. To identify markers contributing to the genetic susceptibility to heroin dependence, this study examined the potential association between heroin dependence and 15 single nucleotide polymorphisms (SNPs, rs1978340, rs3762556, rs3791878, rs3749034, rs11542313, rs2241165, rs2241164, rs769407, rs3749033, rs16858977, rs701492, rs16858988, rs4668331, rs7578661, rs769395) of GAD1 gene using the MassARRAY system. Participants included 370 heroin-dependent subjects and 389 healthy controls. The allelic or genotypic frequencies of the rs1978340 (promoter region), rs3791878 (promoter region), and rs11542313 (exon 3) polymorphisms in heroin addicts were significantly different from those in healthy controls. Strong linkage disequilibrium was observed in two blocks (D'>0.9). Significantly more C-C-C-C-A haplotypes (p=0.0053 after Bonferroni correction) and significantly fewer T-C-A-C-A haplotypes (p=0.0003 after Bonferroni correction) were found in heroin dependent subjects. These findings point to a role for GAD1 polymorphism in heroin dependence among Han Chinese, and may be informative for future genetic or neurobiological studies on heroin dependence.

Correlation of Y-chromosome multiple segmental deletions and chromosomal anomalies in non-obstructive azoospermic males from northeastern China.

We investigated the frequency and types of Y-chromosome microdeletions and chromosomal anomalies in non-obstructive azoospermic and severely oligozoospermic infertile males in northeastern China. The sample consisted of 519 infertile males (456 azoospermic, 63 severely oligozoospermic). PCR assays for Y-chromosome microdeletions and chromosome analysis were performed on all patients and controls. Array-comparative genomic hybridization was performed for three patients with chromosomal anomalies. Fifty-nine of 519 patients (11.37%) had Y-chromosome microdeletions. Microdeletions were found in 11.18% (51/456) of the non-obstructive azoospermic patients and in 12.7% (8/63) of the severely oligozoospermic patients. Eleven of 51 non-obstructive azoospermic patients with Y-chromosome microdeletions had multiple segmental deletions in the AZFb+c regions; four of these patients had chromosomal anomalies. Our sample from northeastern China had a higher frequency of microdeletions among severely oligozoospermic than among non-obstructive azoospermic males.

WT1 Inhibits Human Renal Carcinoma Cell Proliferation and Induces G2/M Arrest by Upregulating IL-24 Expression.

The transcription factor Wilms' tumor 1 (WT1) is involved in development, tissue homeostasis, and disease. However, the exact roles and the mechanisms of WT1 in renal carcinoma are not well understood. Therefore, in this study, we evaluated the ability of WT1 to block proliferation in renal carcinoma cells in vitro. Experimental analysis showed that WT1 overexpression inhibited the proliferation of renal carcinoma A498 cells and promoted arrest at the G2/M checkpoint. RNA-Seq identified differentially expressed genes, including IL-24, related to both the cell proliferation and the cell cycle. WT1 overexpression upregulated IL-24 expression, and IL-24 overexpression induced G2/M arrest. ChIP-Seq identified JUN as a direct target of WT1 in A498 cells, in which positive regulation was shown by RT-qPCR. It has been shown that the transcription factor JUN can regulate IL-24 expression, and therefore, we hypothesize that WT1 might regulate the IL-24 through JUN. Furthermore, analysis based on TCGA datasets showed that the expression of WT1-regulated genes, including TXNIP and GADD45A, was significantly correlated with the stage and histological grade of tumors, with high levels linked to favorable prognoses. Our results demonstrated that the overexpression of WT1 upregulates IL-24, leading to G2/M checkpoint arrest to reduce proliferation. These results indicate that regulation of IL-24 by WT1 inhibits proliferation and may represent a potential target for treating renal carcinoma.

Polymorphism G861C of 5-HT receptor subtype 1B is associated with heroin dependence in Han Chinese.

The serotoninergic (5-HT) system regulates neuronal activity in broad brain regions, and appears to be particularly important for modulating behavioral and physiological functions such as mood, emotion, sleep and appetite. Central 5-HT deregulation may be involved in many neuropsychological disorders, which include substance abuse and addiction. Previous studies suggest that genetic polymorphisms in some 5-HT receptor genes may relate to heroin dependency. Here we examined potential association between heroin dependence and four single nucleotide polymorphisms (SNPs) of 5-HT receptors (A-1438G and T102C of HTR(2A), and G861C and A1180G of HTR(1B)) in a cohort of Han Chinese. Participants included 303 heroin-dependent subjects who were recruited into the Methadone Maintenance Treatment (MMT) Program in the Xi'an Mental Health Center, and 300 healthy controls. The resulting data yielded a significantly higher frequency of the HTR(1B) G allele with G861C among the heroin-dependent subjects relative to controls (p=0.001 after Bonferroni correction). Further genotype and clinical phenotype correlation study of the G861C carriers showed that the amount of heroin self-injection was higher in patients with the GG genotype relative to CC and CG genotypes (p<0.01). These findings point to a role for HTR(1B) polymorphism in heroin dependence among Han Chinese, and may be informative for future genetic or neurobiological studies on heroin dependence.

A new single-nucleotide mutation (rs362719) of the reelin (RELN) gene associated with schizophrenia in female Chinese Han.

Reelin is an extracellular signaling protein that plays an important role in the development of the central nervous system. Post-mortem studies have shown lower reelin protein levels in the brains of patients with schizophrenia and bipolar disorder compared with controls. Genetic studies have also shown that mutations in the reelin gene (RELN) increase the risk for schizophrenia and bipolar disorder. We evaluated whether an RELN gene variant, rs362719, which has been associated with increased susceptibility to bipolar disorder, is also associated with susceptibility to schizophrenia. We included 405 Chinese Han schizophrenia patients and 390 controls in our study. The polymorphism was genotyped by PCR and RFLP methods. We found a significant difference in allele frequency distribution (P< 0.05) between schizophrenia patients and controls. The frequency of the A allele was significantly higher in schizophrenia patients than in healthy controls. The effect of SNP rs362719 on allele distribution was significant in female (P < 0.05) but not in male participants (P = 0.473). Besides the gender factor, demographic and clinical characteristics of the rs362719 genotype groups were also analyzed using the chi-square test, but no significant differences were found. We conclude that rs362719 of the RELN gene is associated with susceptibility to schizophrenia in Chinese Han, possibly through a gender-specific mechanism. Further studies will be needed to confirm this genetic risk factor for schizophrenia.

Polymorphisms of three new microsatellite sites of the dystrophin gene.

To look for novel microsatellites in the dystrophin gene for the diagnosis of Duchenne muscular dystrophy, candidate microsatellite sites in the dystrophin gene were analyzed with the SSRHunter software and were also genotyped. Among the 15 candidate microsatellite sites, three novel microsatellite sites in the 60th, 30th, and 2nd intron were found to have a high degree of polymorphism. We submitted these three new loci to the European Molecular Biology Laboratory, under accession Nos. FN547040, FN547041 and FN557526, which were called DXSDMD-in60, DXSDMD-in30 and DXSDMD-in2, respectively. In these three loci, we found 9, 6 and 11 alleles, respectively, in the 205 individuals. In addition, we also detected 20, 19 and 20 genotypes for the three loci in female samples, with a polymorphism information content of more than 0.600. In conclusion, the three microsatellite sites in the intron region of the dystrophin gene have a high degree of polymorphism, and they can be used in population genetics, as well as to provide a theoretical basis for genetic diagnosis and elucidation of molecular mechanisms in Duchenne muscular dystrophy.

A study on the relationship between TCTA tetranucleotide polymorphism of the HPRT gene and primary hyperuricemia.

We examined polymorphism of the TCTA tetranucleotide sequence in the 3rd intron of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in the Han population of Ningxia Province in China. We also looked for a possible relationship between STR polymorphism in the 3rd intron of the HPRT gene and primary hyperuricemia. We used Chelex-100 to extract DNA, then PCR, PAGE and silver staining for allele genotyping and DNA sequencing to obtain the distribution of the alleles. We found, for the first time, that there is high STR polymorphism in the 3rd intron of the HPRT gene. We detected 5 STR alleles in this intron in the Han population of Ningxia Province, with 15 genotypes in females; significant differences were observed in the distribution of alleles and genotypes between control and patient groups for both males and females. Alleles of the TCTA repeat in the 3rd intron of the HPRT gene were found to be associated with primary hyperuricemia; consequently, these alleles may be considered risk factors for primary hyperuricemia.