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  • BMJ  (11)
  • Zhang, Xin  (11)
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  • 1
    Online Resource
    Online Resource
    Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis
    BMJ ; 2021
    In:  Journal of Medical Genetics Vol. 58, No. 1 ( 2021-01), p. 56-65
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 58, No. 1 ( 2021-01), p. 56-65
    Abstract: Infertility affects approximately 15% of couples worldwide with male infertility being responsible for approximately 50% of cases. Although accumulating evidence demonstrates the critical role of the X chromosome in spermatogenesis during the last few decades, the expression patterns and potential impact of the X chromosome, together with X linked genes, on male infertility are less well understood. Methods We performed X chromosome exome sequencing followed by a two-stage independent population validation in 1333 non-obstructive azoospermia cases and 1141 healthy controls to identify variant classes with high likelihood of pathogenicity. To explore the functions of these candidate genes in spermatogenesis, we first knocked down these candidate genes individually in mouse spermatogonial stem cells (SSCs) using short interfering RNA oligonucleotides and then generated candidate genes knockout mice by CRISPR-Cas9 system. Results Four low-frequency variants were identified in four genes ( BCORL1 , MAP7D3 , ARMCX4 and H2BFWT ) associated with male infertility. Functional studies of the mouse SSCs revealed that knocking down Bcorl1 or Mtap7d3 could inhibit SSCs self-renewal and knocking down Armcx4 could repress SSCs differentiation in vitro. Using CRISPR-Cas9 system, Bcorl1 and Mtap7d3 knockout mice were generated. Excitingly, Bcorl1 knockout mice were infertile with impaired spermatogenesis. Moreover, Bcorl1 knockout mice exhibited impaired sperm motility and sperm cells displayed abnormal mitochondrial structure. Conclusion Our data indicate that the X-linked genes are associated with male infertility and involved in regulating SSCs, which provides a new insight into the role of X-linked genes in spermatogenesis.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2019-106598
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2009590-9
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    RNA Interference of Human Papillomavirus Type 16 E7 Increases HLA Class I Antigen Expression in HaCaT-E7 Cells
    BMJ ; 2011
    In:  International Journal of Gynecologic Cancer Vol. 21, No. 1 ( 2011), p. 28-34
    Details
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 21, No. 1 ( 2011), p. 28-34
    Abstract: High-risk human papillomaviruses (HPVs) are the major causative agents of cervical cancer. The E7 protein of high-risk HPV disturbs cell cycle control and down-regulates components of the antigen presentation pathway, suggesting an ideal target for development of the immunotherapy in HPV-positive cervical cancers. We previously reported that HPV16 E7 could down-regulate cell-surface HLA class I antigen accompanying decreased expression of transporter associated with antigen processing 1 (TAP-1). The purpose of this study was to determine whether knockdown of HPV16 E7 could up-regulate surface HLA class I antigen expression in HPV16 E7 expressing HaCaT cells (HaCaT-E7). Methods: An E7-specific small interfering RNA (siRNA) was transfected into the HaCaT-E7 cells, and the expression of HPV16 E7 was measured by real-time reverse transcriptase polymerase chain reaction and Western blot. With the use of flow cytometry analysis, the levels of cell surface HLA class I antigen and intracellular TAP-1 expression were detected. Results: It was found that transfection of HPV16 E7-siRNA reduced HPV16 E7 expression as measured on messenger RNA and protein levels. The flow cytometry analysis showed that, compared with mock transfection, a statistically significant increase of approximately 75% in surface HLA class I levels was observed in HaCaT-E7 cells at 72 hours after transfection of E7 siRNA. Moreover, he knockdown of E7 in HaCaT-E7 cells could result in an increase of intracellular TAP-1 expression, which is essential for the expression of HLA class I at cell surface. Conclusions: Our study showed that the knockdown of HPV16 E7 could increase cell surface HLA class I antigen expression in HaCaT-E7 cells. In addition, for HPV-positive human cervical cancer, our observations indicate that the HPV E7 gene is a target of choice.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    URL: Article
    DOI: 10.1097/IGC.0b013e3181ffcca1
    Language: English
    Publisher: BMJ
    Publication Date: 2011
    detail.hit.zdb_id: 2009072-9
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  • 3
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    Online Resource
    miR-541 potentiates the response of human hepatocellular carcinoma to sorafenib treatment by inhibiting autophagy
    BMJ ; 2020
    In:  Gut Vol. 69, No. 7 ( 2020-07), p. 1309-1321
    Details
    In: Gut, BMJ, Vol. 69, No. 7 ( 2020-07), p. 1309-1321
    Abstract: Autophagy participates in the progression of hepatocellular carcinoma (HCC) and the resistance of HCC cells to sorafenib. We investigated the feasibility of sensitising HCC cells to sorafenib by modulating miR-541-initiated microRNA-autophagy axis. Design Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the malignant properties and autophagy of human HCC cells. Autophagy was quantified by western blotting of LC3, transmission electron microscopy analyses and confocal microscopy scanning of mRFP-GFP-LC3 reporter construct. Luciferase reporter assays were conducted to confirm the targets of miR-541. HCC xenograft tumours were established to analyse the role of miR-541 in sorafenib-induced lethality. Results The expression of miR-541 was downregulated in human HCC tissues and was associated with malignant clinicopathologic phenotypes, recurrence and survival of patients with HCC. miR-541 inhibited the growth, metastasis and autophagy of HCC cells both in vitro and in vivo. Prediction software and luciferase reporter assays identified autophagy-related gene 2A (ATG2A) and Ras-related protein Rab-1B (RAB1B) as the direct targets of miR-541. Consistent with the effects of the miR-541 mimic, inhibition of ATG2A or RAB1B suppressed the malignant phenotypes and autophagy of HCC cells. Furthermore, siATG2A and siRAB1B partially reversed the enhancement of the malignant properties and autophagy in HCC cells mediated by the miR-541 inhibitor. More interestingly, higher miR-541 expression predicted a better response to sorafenib treatment, and the combination of miR-541 and sorafenib further suppressed the growth of HCC cells in vivo compared with the single treatment. Conclusions Dysregulation of miR-541-ATG2A/RAB1B axis plays a critical role in patients’ responses to sorafenib treatment. Manipulation of this axis might benefit survival of patients with HCC, especially in the context of the highly pursued strategies to eliminate drug resistance.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2019-318830
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1492637-4
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  • 4
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    Online Resource
    Association of socioeconomic status with glycated haemoglobin level and risk factors for diabetic retinopathy: a cross-sectional study in Sichuan, western China
    BMJ ; 2023
    In:  BMJ Open Vol. 13, No. 2 ( 2023-02), p. e067475-
    Details
    In: BMJ Open, BMJ, Vol. 13, No. 2 ( 2023-02), p. e067475-
    Abstract: Diabetes affects 1 in 10 adults in China. Diabetic retinopathy (DR) is a diabetes-related complication that, if untreated, impairs vision and causes blindness. Evidence on DR diagnosis and risk factors is limited. This study aimed to add evidence from socioeconomic factors. Design A cross-sectional survey of people with diabetes conducted in 2019 was analysed by using logistic regression to evaluate the association of socioeconomic factors with the glycated haemoglobin (HbA1c) level and DR. Setting Five counties/districts of western China (Sichuan) were included. Participants Registered participants with diabetes aged from 18 to 75 years were selected, and at last 2179 participants were included in the analysis. Results In this cohort, 37.13% (adjusted value 36.52%), 19.78% (adjusted value 19.59%) and 17.37% of participants had HbA1c 〈 7.0%, DR (24.96% of those in the high-HbA1c group) and non-proliferative DR, respectively. Participants with higher social health insurance coverage (urban employee insurance (UEI)), higher income and urban residents tended to have glycaemic control (HbA1c) compared with their counterparts (OR: 1.48, 1.08 and 1.39, respectively). Participants with UEI or higher income had a lower risk of DR (OR: 0.71 and 0.88, respectively); higher education was associated with a 53%–69% decreased risk of DR. Conclusion This study shows disparities in the effect of socioeconomic factors on glycaemic (HbA1c) management and DR diagnosis among people with diabetes in Sichuan. Lower socioeconomic (especially non-UEI) status conferred a higher risk of high HbA1c and DR. The insights from this study indicate the need for national programmes to implement community-level measures to facilitate access to better HbA1c management and early detection of DR in patients with lower socioeconomic status and diabetes. Trial registration number Chinese Clinical Trial Registry (ChiCTR1800014432).
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2022-067475
    DOI: 10.1136/bmjopen-2022-067475.supp1
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2599832-8
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  • 5
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    Online Resource
    Prevalence of metabolic syndrome among the adult population in western China and the association with socioeconomic and individual factors: four cross-sectional studies
    BMJ ; 2022
    In:  BMJ Open Vol. 12, No. 4 ( 2022-04), p. e052457-
    Details
    In: BMJ Open, BMJ, Vol. 12, No. 4 ( 2022-04), p. e052457-
    Abstract: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation. Design Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015. Setting From 2010 to 2018, 8–15 counties/districts of West China were included. Participants A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors. Results The overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (p 〈 0.05). The ORs of people who smoked at least 20 cigarettes/day, ate more than 100 g of red meat/day, consumed fruit or vegetable juice and drank carbonated soft drinks less than weekly were 1.10, 1.16, 1.19–1.27 and 0.81–0.84, respectively. The ORs rose with increasing sedentary time and decreased with higher physical activity. Conclusion The high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2021-052457
    DOI: 10.1136/bmjopen-2021-052457.supp1
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2599832-8
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  • 6
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    Associations between anthropometric indicators and both refraction and ocular biometrics in a cross-sectional study of Chinese schoolchildren
    BMJ ; 2019
    In:  BMJ Open Vol. 9, No. 5 ( 2019-05), p. e027212-
    Details
    In: BMJ Open, BMJ, Vol. 9, No. 5 ( 2019-05), p. e027212-
    Abstract: To identify associations between anthropometric indicators (height, weight and body mass index (BMI)) and both refraction and ocular biometrics in Chinese schoolchildren in Tianjin, China. Design Cross-sectional study. Participants A total of 482 (86.07%) students (6–15 years old) with no history of ocular or systemic pathologies were enrolled in this study. Methodology Height and weight were measured using standardised protocols. Ocular biometrics (axial length (AL), vitreous chamber depth (VCD) and corneal curvature (CC)) were measured by a low-coherence optical reflectometry device. Cycloplegic refraction was measured using autorefraction. The AL/CC ratio and spherical equivalent refraction (SER) were calculated. Myopia was defined as SER ≤−0.50 dioptres (D). Multiple linear regression analysis was performed to explore the associations between anthropometric indicators (height, weight and BMI) and both refraction and ocular biometrics. Results The overall prevalence of myopia was 71.16%. Overall, only height was associated with ALs, VCDs, AL/CC ratios and refractions after controlling for age, gender, parental myopia, family income, reading and writing distance and time spent outdoors. Furthermore, age-specific results demonstrated that height and weight were independently associated with refraction in participants aged 6–8 years and 9–11 years participants. Higher heights in schoolchildren were associated with longer ALs (regression coefficient b =+0.25 for each 10 cm difference in height, p 〈 0.01), deeper VCDs ( b =+0.23, p 〈 0.01), higher AL/CC ratios ( b =+0.04, p 〈 0.01) and more negative refractions ( b =−0.48, p 〈 0.01). Heavier weights were also associated with longer ALs (+0.29 mm, p 〈 0.01), deeper VCDs (+0.29 mm, p 〈 0.01), higher AL/CC ratios (+0.04, p 〈 0.01) and more negative refractions (−0.48 D, p 〈 0.01). Conclusions Height and weight remained independently related to refraction and various ocular biometrics during the early adolescent growth period after adequately controlling for covariates, which could support the idea that a shared mechanism may regulate the coordinated growth of body and eye size in children.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2018-027212
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2599832-8
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  • 7
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    Online Resource
    Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma
    BMJ ; 2012
    In:  Journal of Medical Genetics Vol. 49, No. 9 ( 2012-09), p. 563-568
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 49, No. 9 ( 2012-09), p. 563-568
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2012-100868
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2012
    detail.hit.zdb_id: 2009590-9
    SSG: 12
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  • 8
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    Role of the IL-33/ST2 axis in cigarette smoke-induced airways remodelling in chronic obstructive pulmonary disease
    BMJ ; 2021
    In:  Thorax Vol. 76, No. 8 ( 2021-08), p. 750-762
    Details
    In: Thorax, BMJ, Vol. 76, No. 8 ( 2021-08), p. 750-762
    Abstract: Efficient therapy and potential prophylaxis are confounded by current ignorance of the pathogenesis of airway remodelling and blockade in COPD. Objective To explore the role of the IL-33/ST2 axis in cigarette smoke (CS) exposure-induced airways remodelling. Methods C57BL/6, BALB/c and IL-1RL1 -/- mice exposed to CS were used to establish an animal surrogate of COPD (air-exposed=5~8, CS-exposed=6~12). Hallmarks of remodelling were measured in mice. Cigarette smoke extract (CSE)-induced proliferation and protein production in vitro by fibroblasts in the presence of anti-interleukin-33 (anti-IL-33) or hST2 antibodies were measured. Expression of IL-33 and ST2 and other remodelling hallmarks were measured, respectively, in bronchoalveolar lavage fluid (BALF) (controls=20, COPD=20), serum (controls=59, COPD=90) and lung tissue sections (controls=11, COPD=7) from patients with COPD and controls. Results Wild-type mice exposed to CS elevated expression of hallmarks of tissue remodelling in the lungs and also in the heart, spleen and kidneys, which were significantly abrogated in the IL-1RL1 -/- mice. Fibroblasts exposed to CSE, compared with control, exhibited early cellular translocation of IL-33, accompanied by proliferation and elevated protein synthesis, all inhabitable by blockade of IL-33/ST2 signalling. Expression of IL-33 and ST2 and hallmarks of tissue remodelling were significantly and proportionally elevated in BALF, serum and tissue samples from patients with COPD. Conclusions Exposure to CS induces remodelling changes in multiple organs. The data support the hypothesis that CS-induced lung collagen deposition is at least partly a result of CS-induced IL-33 translocation and release from local fibroblasts.
    Type of Medium: Online Resource
    ISSN: 0040-6376 , 1468-3296
    URL: Article
    DOI: 10.1136/thoraxjnl-2020-214712
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1481491-2
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  • 9
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    Role of the intelligent exercise rehabilitation management system on adherence of cardiac rehabilitation in patients with coronary heart disease: a randomised controlled crossover study protocol
    BMJ ; 2020
    In:  BMJ Open Vol. 10, No. 6 ( 2020-06), p. e036720-
    Details
    In: BMJ Open, BMJ, Vol. 10, No. 6 ( 2020-06), p. e036720-
    Abstract: The benefits of cardiac rehabilitation (CR) on the reduction of cardiac and all-cause mortality are well documented. However, adherence remains suboptimal in China. It is clear that traditional CR does not meet the needs of many eligible patients and innovation is required to improve its application. Home-based CR (HBCR) is a cost-effective method that may be a valuable alternative for many individuals in China. In HBCR, it is often difficult to maintain an exercise intensity that is both effective and within safe limits, factors that are essential for patient safety. Mobile health interventions have the potential to overcome these obstacles and may be efficacious in improving adherence. The purpose of this study is to evaluate whether an Intelligent Exercise Rehabilitation Management System (IERMS)-based HBCR could improve adherence to CR and to assess the effects on exercise capacity, mental health, self-efficacy, quality of life and lifestyle-related risk factors. Methods and analysis We propose a single-blinded, two-arm, randomised controlled crossover study of 70 patients with coronary heart disease (CHD). Participants will be randomly assigned in a 1:1 ratio to one of the two groups. Patients in group 1 will receive the IERMS intervention together with usual care for the first 6 weeks and usual care for the last 6 weeks, while patients assigned to group 2 will receive usual care for the first 6 weeks and will use IERMS in the last 6 weeks. The primary outcome is adherence to the programme and secondary outcomes include exercise capacity, psychological well-being, quality of life, self-efficacy and lifestyle-related risk factors. All secondary outcomes will be measured at baseline, 6 weeks and 12 weeks. Ethics and dissemination This study has been approved by the Human Research Ethics Committee of the School of Nursing, Jilin University (HREC 2019120901). The results will be published in peer-reviewed journals and at conferences. Trial registration number ChiCTR1900028182; Pre-results.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2019-036720
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 10
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    Morphology parameters for rupture in middle cerebral artery mirror aneurysms
    BMJ ; 2020
    In:  Journal of NeuroInterventional Surgery Vol. 12, No. 9 ( 2020-09), p. 858-861
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 12, No. 9 ( 2020-09), p. 858-861
    Abstract: To identify the morphological parameters correlated with the rupture of middle cerebral artery (MCA) aneurysms. Methods We retrospectively analyzed the digital subtraction angiography (DSA) data of 48 patients with ruptured mirror MCA aneurysms. Morphological parameters included aneurysm with wall protrusion, maximum diameter (Dmax), height, neck width, aneurysm width, dome projection, parent artery average diameter (Dp), aspect ratio (AR), bottleneck factor (BNF), size ratio (SR), M1/M2 ratio, and height/width (H/W) ratio. These paired parameters were analyzed by conditional univariate and multivariate logistic regressions to screen out the independent risk factors. We established a score based on the independent risk factors. Receiver operating characteristics (ROC) were generated to estimate the prediction performance of the score in our large database of 763 aneurysms. Results In the univariate regressions, Dmax, height, aneurysm width, neck width, AR, BNF, H/W ratio, SR, anterior dome projection and aneurysm with wall protrusion were significant risk factors. Aneurysm width (OR 3.296, p=0.015), AR (OR 11.594, p=0.014) and anterior dome projection (OR 9.385, p=0.016) were independent risk factors in multivariate regression. The area under the curve (AUC) value of the score based on the three independent risk factors was 0.829. Conclusion Aneurysm width, AR and anterior dome projection were independent risks factors of rupture.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/neurintsurg-2019-015620
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2506028-4
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