Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Objective: To investigate the distribution characteristics of LymphGen genotyping in a diffuse large B-cell lymphoma (DLBCL) population and verify its prognostic value. Methods: We collected the clinical data and paraffin-embedded tumor tissue samples of 155 patients with newly diagnosed DLBCL in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. DNA was extracted from tumor tissue and 475 gene mutations were detected by next-generation sequencing technology. We investigated the distribution of LymphGen genotyping in the DLBCL population, patients with different COO genotypes in the Xinjiang region, and their effects on PFS and OS. Results: ①Among 155 patients, 105 patients (67.7%) could be genotyped, including 14 (9.0%) for MCD, 26 (16.8%) for BN2, 10 (6.5%) for N1, 8 (5.2%) for EZB, 27 (17.4%) for A53, and 20 (12.9%) for ST2. ②The distribution of each gene subtype was different in different cell origin (COO) types (P=0.021) . ST2 was dominant in the germinal center type (GCB) group (28.8%) , and A53 and MCD were dominant in the non-GCB group (35.8%, 17.0%) . The BN2 type was the most common in both groups (23.1%, 26.4%) . ③There were statistically significant differences in progression-free survival (PFS) and overall survival (OS) among different gene subtypes (P=0.031 and 0.005, respectively) . N1 and A53 had poor prognosis. The 2-year PFS and OS rates of N1 were both (21.3±18.4) %, and the 3-year PFS and OS rates of A53 were (60.9±11.3) %, (46.8±10.9) %, respectively. ④ The 3-year PFS and OS rates of MCD were the best, but the 5-year PFS and OS rates were worse. ⑤In the ROC curve of LymphGen genotyping for OS prediction, the AUC was 0.66, showing a certain degree of differentiation. Conclusion: LymphGen genotyping in the DLBCL population was different from previous reports and was of great significance for the prognosis of patients with DLBCL.
Antineoplastic Combined Chemotherapy Protocols ; Disease-Free Survival ; Genotype ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prognosis ; Retrospective Studies

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

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.

PURPOSE: The International Study Group on Pancreatic Fistula's definition of postoperative pancreatic fistula (POPF) has recently been updated. This study aimed to identify risk factors for POPF in patients having pancreaticoduodenectomy (PD) and to generate a nomogram to predict POPF. METHODS: Data on 298 patients who underwent PD from March 2012 to October 2017 was retrospectively reviewed and POPF statuses were redefined. A nomogram was constructed using data from 220 patients and validated using the remaining 78 patients. Independent risk factors for POPF were identified using univariate and multivariate analyses. A predictive nomogram was established based on the independent risk factors and was compared with existing models. RESULTS: Texture of the pancreas, size of the main pancreatic duct, portal vein invasion, and definitive pathology were the identified risk factors. The nomogram had a C-index of 0.793 and was internally validated. The nomogram performed better (C-index of 0.816) than the other most cited models (C-indexes of 0.728 and 0.735) in the validation cohort. In addition, the nomogram can assign patients into low- (less than 10%), intermediate- (10% to 30%), and high-risk (equal or higher than 30%) groups to facilitate personalized management. CONCLUSION The nomogram accurately predicted POPF in patients having PD.

Background: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios⁺ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Based on the electric field shielding and insulation technology, the single electrode dielectric barrier discharge ion source ( DBDI ) has the characteristics of uniform discharging, stability, and high ionization energy, and thus can be used to detect various samples with a large range of polarity. However, the ionization energy is too high to reduce the background signal noise, and thus affects the detection effectiveness to low polarity and low boiling point samples. To enhance the detection effectiveness to these samples, a method of eliminating electrons of single electrode DBDI by using external metal electrodes was developed in this study. Then, the single electrode DBDI was improved by an external needle electrode and an external metal net, respectively. The mechanism of those external metal electrodes was discussed, and the experimental studies were carried out. The results showed that the external metal net technology had an advantage in improving signal to noise ratio ( SNR ) , and the enhancement of SNR for the detection of isoprocarb, perfluorooctanoic acid and SudanⅢwas about 5-6 times. Based on the technology, a method for determination of Sudan Ⅲ in chili powder was developed. The recoveries, RSD and LOD were 83. 7%-94. 6% , 5. 6%-9. 0% and 23 mg/kg, respectively. The external metal electrode technique has broadened the detection range of single electrode DBDI to the field of low polarity, low boiling point and complex samples.

This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus.From April 2010 to January 2015,we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests,electrophysiological examinations,and clinical confirmation.Muscular branches of the radial nerve,which innervate the supinator in the forearm,were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function.Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis,as well as the distance between the thumb tip and index finger tip,were monitored.All patients were followed up for 24 to 30 months,with an average of 27.5 months.Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months,while MUP of the extensor pollicis longus appeared at an average of 7 months.Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis,and 12 months in the extensor pollicis longus.Furthermore,the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade Ⅲ at 21 months.Lastly,the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months.In conclusion,for patients with middle and lower trunk injuries of the brachial plexus,transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.

BACKGROUNDPrevious studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific.

METHODSResting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and "small-world" property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz, and 0.11-0.25 Hz).

RESULTSAt lower-frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz), the global efficiency, the CC and the "small-world" properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11-0.25 Hz), the CpL was much longer, and the "small-world" property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD.

CONCLUSIONSThis study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.

Aged ; Aged, 80 and over ; Alzheimer Disease ; diagnosis ; Brain ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged