Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

Objective: To analyze the safety, effectiveness, economics, innovation, suitability and accessibility of tetrandrine in the treatment of pneumoconiosis, and provide evidence-based basis for health policy decision-making and clinical practice. Methods: In July 2022, the system searched PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed databases (the retrieval time was from the establishment of the database to June 30, 2022), screened the documents that meet the standards, extracted and evaluated the data, and used the "HTA checklist" developed by the International Network of Agencies for Health Technology Assessment (INAHTA) to evaluate the HTA report. AMSTAR-2 Scale was used to evaluate the quality of systematic evaluation/Meta analysis. CHEERS Scale was used to evaluate the quality of pharmacoeconomics research. The included cohort study or case-control study was evaluated with the Newcastle-Ottawa Scale. The included randomized controlled trial (RCT) studies were evaluated using the Cochrane Risk Bias Assessment Tool (Cochrane RCT) quality evaluation criteria. Comprehensive comparison and analysis based on the characteristics of the data included in the study. Results: A total of 882 related literatures were detected from the initial screening. According to relevant standards, 8 RCT studies were finally selected for analysis. Statistical results showed that basic treatment with tetrandrine could better improve FEV(1) (MD=0.13, 95%CI: 0.06-0.20, P<0.001), FEV(1)/FVC (MD=4.48, 95%CI: 0.61-8.35, P=0.02) and clinical treatment efficiency. Tetrandrine had a low incidence of adverse reactions. The affordability coefficient of tetrandrine tablets was 0.295-0.492. Conclusion: Tetrandrine can improve the clinical symptoms and pulmonary ventilation function of pneumoconiosis patients, most of the adverse reactions are mild, and the clinical application is safe.
Humans ; Pneumoconiosis/drug therapy* ; Benzylisoquinolines/therapeutic use* ; Drugs, Chinese Herbal ; Case-Control Studies

In the 1960s, sperm cryopreservation was developed as a method to preserve fertility. Currently, techniques for the cryopreservation of human spermatozoa have been widely used in assisted reproduction. However, although sperm cryobiology has made notable achievements, the optimal method for the recovery of viable spermatozoa after cryopreservation remains elusive. Postthawing sperm quality can be affected by cryoprotectants, ice formation, storage conditions, and osmotic stress during the freezing process. This review discusses recent advances in different cryopreservation techniques, cryoprotectants, and freezing and thawing methods during cryopreservation and new indications for the use of cryopreserved spermatozoa.
Humans ; Male ; Semen Preservation/methods* ; Sperm Motility ; Semen ; Cryopreservation/methods* ; Spermatozoa ; Cryoprotective Agents/pharmacology*

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

Objective:To evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of post stroke cognitive impairment (PSCI). Method:Seven databases, including CNKI, WanFang, VIP, CBM, PubMed, The Cochrane library and ClinicalTrials.gov, were electronically searched for relevant randomized controlled trials (RCTs) of TCM in the treatment of PSCI. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of the included studies, descriptive analysis was carried out on the included studies, and the Meta quantitative analysis was carried out with RevMan 5.3 software. Result:A total of 16 RCTs were included with 1 296 participants, and they were assigned to the intervention group (n=649) and the control group (n=647). The results showed that TCM combined with western medicine group and TCM group were better than western medicine group in improving the scores of Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Barthel Index (BI), Activity of Daily Living (ADL), Chinese stroke scale (CSS) and National Institutes of Health stroke scale (NIHSS) of PSCI patients, and no serious adverse events were observed. Conclusion:TCM has potential advantages in improving the cognitive function of patients with PSCI, and it also has certain efficacy in improving the daily living ability and neurological impairment symptoms, and no serious adverse events have been observed. Due to the low quality of methodology included in the studies, in order to provide reliable basis for clinical decision-making, high-quality of RCTs are still needed to study the efficacy and safety of TCM for PSCI.