Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

OBJECTIVE: To explore the relationship between plasma sST2/Reg3α levels and acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children's Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay. RESULTS: Among 29 patients there were 15 males and 14 females with a median age of 53 (29-117) months. After allo-HSCT, 18 patients developed grade 0-I aGVHD; while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD (GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in 5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81 (73.94-150.77) ng/ml vs 48.97 (28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74 (87.00-243.36) ng/ml vs 48.97 (23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥65.34 ng/ml at 28 days after allo-HSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of < 65.34 ng/ml after allo-HSCT (P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones. CONCLUSION The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.
Child ; Child, Preschool ; Female ; Gastrointestinal Tract ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Male ; Plasma

Objective:To control the quality of the reference sample of Wenjingtang by establishing the specific chromatograms. Method:On the basis of analyzing 15 batches of Wenjingtang freeze-dried powder samples， a high performance liquid chromatography （HPLC） specific chromatogram analysis method of Wenjingtang was established. The system adaptability was investigated and the retention time， relative retention value and deviation caused by different chromatographic columns and instruments were calculated by using the same brand of chromatographic columns， four different brands of chromatographic columns and instruments from three different manufacturers. The precision， repeatability and stability of this method was further completed. The possible chemical components of the freeze-dried powders were speculated and identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MSⁿ）. Chromatographic separation was performed on ACQUITY UPLC BEH C₁₈ column （2.1 mm×100 mm， 1.7 μm） with acetonitrile （A）-0.1% formic acid aqueous solution （B） as mobile phase for gradient elution （0-2.8 min， 10%A； 2.8-8.0 min， 10%-18%A； 8.0-12.2 min， 18%-25%A； 12.2-15.3 min， 25%-40%A； 15.3-17.4 min， 40%A； 17.4-20.5 min， 40%-90%A）， and column temperature was set at 30 ℃ with flow rate of 0.4 mL·min^-1. Mass spectrometry was performed on electrospray ionization， data were collected under positive and negative ion modes， and the detection range was m/z 50-1 600. Result:Ten characteristic peaks were selected as the distinguishing features in this specific chromatograms， and eight of them were identified by comparing with the reference standards， including paeoniflorin （peak 1）， liquiritin apioside （peak 2）， liquiritin （peak 3）， ferulic acid （peak 4）， iquiritigenin （peak 6）， cinnamaldehyde （peak 8）， paeonol （peak 9）and glycyrrhizic acid （peak 10）. By mass spectrometry analysis， 30 compounds were identified， and the source of medicinal materials were assigned. It mainly contained triterpenoid saponins and flavonoids from Glycyrrhizae Radix et Rhizoma， ginsenosides from Ginseng Radix et Rhizoma， monoterpenoid glycosides and tannins from Paeoniae Radix Alba， steroids in Achyranthis Bidentatae Radix， phenolic acids in Angelicae Sinensis Radix. Conclusion:The established characteristic chromatographic analysis method of Wenjingtang is simple， stable and repeatable. The chemical composition of the freeze-dried powder of Wenjingtang is basically defined by mass spectrometry identification and source attribution， which can provide reference for the development and quality control of Wenjingtang in the future.

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome

Gastrodia elata is a kind of precious traditional Chinese medicine. In the process of cultivation of G. elata, due to the influence of continuous cropping obstacles and other factors, the fungus materials and land that have been planted with G. elata are often abandoned, resulting in a great waste of resources. Based on the planting characteristics of G. elata and Phallus impudicus and the previous research experience in ecological agriculture, this paper analyzed the ecological adaptability characteristics of G. elata and P. impudicus, and summarized the key techniques of the G. elata-P. impudicus sequential planting pattern. Keeping track of the planting area, fungus-growing materials consumption and market sales of G. elata-P. impudicus sequential planting pattern, the ecological benefits of G. elata-P. impudicus sequential planting pattern from the aspects of utilization rate of fungus-growing materials were analyzed, the value of land resources per unit area, ecological environmental protection, labor cost and economic benefits were consi-dered. The technical principle of G. elata-P. impudicus sequential planting pattern was expounded according to their ecological habit, the season of harvest and planting, the difference of composition of fungus-growing materials, and the microbial ecology. The sequential planting pattern of G. elata-P. impudicus not only realized the double production of medicinal materials and edible fungi, reduced the waste of old fungus-growing materials, but also transformed the energy from nutrition-supplied fungi to edible and medicinal fungi, which guaranteed the ecological recycling and utilization of G. elata in the process of cultivation.
Agaricales/growth & development* ; Agriculture/methods* ; Gastrodia/growth & development* ; Medicine, Chinese Traditional ; Plants, Medicinal/growth & development*

Background:The clinical outcome of transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH) remains controversial,and the promising clinical results of several Japanese studies could not be reproduced in American and European studies.Trying to solve controversies on TRO for ONFH rising from apparently conflicting studies,a meta-analysis was conducted to assess the 5-and 10-year hip survival rates (with conversion to artificial joint replacement and radiographic failure as endpoints) after TRO.Methods:All eligible studies were searched in seven comprehensive databases including PubMed,Web of Science,Embase,Cochrane Library,VIP Database,China Knowledge Resource Integrated Database,and Wan Fang Database prior to June 2019.The outcomes evaluated were 5-and 10-year hip survival rates after TRO.The odds ratio and risk difference for the non-comparative binary data with the 95％ confidence intervals (CIs) were calculated for each outcome.The included studies were assessed for methodologic bias and potential reasons for heterogeneity were explored.Results:Nineteen studies of TRO for ONFH were eligible for this meta-analysis according to inclusion criteria.Based on the previous report,two calculation methods (Methods 1 and 2) were adopted in this meta-analysis.Furthermore,we performed a subgroup analysis of the 5-and 10-year hip survival rates (Method 1) after TRO for ONFH:Asian sub-population and non-Asian subpopulation.Taking conversion to artificial joint replacement as the endpoint,5-and 10-year hip survival rates (Method 1) after TRO for ONFH in the Asian population were 0.86 (95％ CI =0.82-0.89) and 0.72 (95％ CI =0.65-0.78),respectively,and 5-and 10-year hip survival rates after TRO for ONFH in the non-Asian population were 0.55 (95％ CI =0.43-0.67) and 0.42 (95％ CI =0.28-0.55),respectively.The 5-and 10-year hip survival rates (Method 2) after TRO for ONFH were 0.90 (95％ CI =0.79-0.95) and 0.89 (95％ CI =0.81-0.94),respectively.Taking radiographic failure as the endpoint,5-and 10-year hip survival rates after TRO for ONFH were 0.70 (95％ CI =0.64-0.76) and 0.53 (95％ CI =0.46-0.61),respectively.Conclusions:The 5-and 10-year hip survival rates after TRO for ONFH were satisfactory in the Asian population,and were acceptable in the non-Asian population despite high early failure rates.

Objective: To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia. METHODS: From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups. RESULTS: Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (［2.50 ± 0.71］ vs ［3.37 ± 0.70］ ml, P <0.05), sperm concentration (［12.00 ± 1.65］ vs ［19.34 ± 2.04］ ×10⁶/ml, P <0.05), percentage of progressively motile sperm (PMS) (［18.01 ± 3.01］% vs ［35.41 ± 6.49］%, P<0.05), MDA level (［14.96 ± 2.76］ vs ［10.04 ± 1.04］ nmol/ml, P <0.05), and TAC in the seminal plasma (［9.83 ± 1.02］ vs ［12.25 ± 1.11］ U/ml, P <0.05), and so did the controls in the semen volume (［2.76 ± 0.67］ vs ［3.36 ± 0.93］ ml, P <0.05), sperm concentration (［11.47 ± 1.10］ vs ［17.77 ± 3.56］ ×10⁶/ml, P <0.05), percentage of PMS (［19.22 ± 1.41］ vs ［36.01 ± 5.22］ %, P <0.05), MDA level (［14.66 ± 2.75］ vs ［10.14 ± 1.01］ nmol/ml, P <0.05), and TAC in the seminal plasma (［9.84 ± 0.90］ vs ［11.14 ± 0.84］ U/ml, P <0.05). There were no statistically significant differences in the above post-medication parameters between the trial and control groups (P >0.05) except in TAC, which was markedly more improved in the former than in the latter (P <0.05), nor in the percentage of morphologically normal sperm before and after treatment in either of the two groups (P >0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment. CONCLUSIONS Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.
Antioxidants ; Asthenozoospermia ; drug therapy ; Biomarkers ; analysis ; Carnitine ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Oligospermia ; drug therapy ; Oxidative Stress ; Pregnancy ; Pregnancy Rate ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; Tamoxifen ; therapeutic use ; Thioctic Acid ; therapeutic use

OBJECTIVETo explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer.

METHODSPCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined.

RESULTSHPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins.

CONCLUSIONHPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.

Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Breast Neoplasms ; genetics ; therapy ; Female ; Genetic Therapy ; methods ; Humans ; Middle Aged ; Oncogene Proteins, Viral ; genetics ; metabolism ; Papillomaviridae ; physiology ; Papillomavirus Infections ; genetics ; therapy ; Sequence Alignment