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Chemotherapeutic drug of paclitaxel (PTX) has been shown to cause reproductive toxicity thus affecting male fertility, but its underlying molecular basis is unclear. Melatonin (MLT) can mitigate the reproductive damage caused by certain chemotherapy drugs. In this study, we aimed to identify impact of PTX on the main biological processes and protective effect of MLT on reproductive damage caused by PTX. Mice exposed to PTX mainly impaired spermatogenesis, such as decreased sperm counts, reduced sperm motility and increased abnormal sperm. Decreased expressions of germ cell proliferation-associated protein PCNA and meiosis-related protein SYCP3 induced by PTX were determined by Western blot, while MLT ameliorated this effect and increased the expressions of PCNA, SYCP3, DMC1, STRA8 and fertility-related protein of HSPA2, resulting in significantly improved spermatogenesis and sperm quality levels. In vitro fertilization experiment showed that PTX significantly decreased blastocyst formation rates, which can be improved by MLT administration, but not two-cell development rates. Taken together, this work demonstrated PTX can adversely affect germ cell proliferation and meiosis, which ultimately influence sperm quality and male fertility, and highlighted the protective ability of MLT on ameliorating the side effects of PTX, especially on sperm quality. The results provide information to further the study on the molecular mechanism of PTX's effects on male reproduction and the protective mechanism of MLT.
Research on the relationship between creatinine to body weight ratios (Cre/BW ratios) and the prevalence of diabetes is still lacking. The intention of this research was to explore the potential relationship between Cre/BW ratio and diabetes prevalence in Chinese adults.
This retrospective study was conducted on 199 526 patients in the Chinese Rich Healthcare Group from 2010 to 2016. The participants were divided into four groups on the basis of the quartiles of the Cre/BW ratios. Multivariate multiple imputation and dummy variables were used to handle missing values. Multivariate regression analysis was applied to detect the relationship between Cre/BW and diabetes. A smoothing plot was also used to identify whether there were nonlinear relationships.
After handling missing values and adjusting for potential confounders, the multivariate Cox regression analysis results showed that Cre/BW was inversely correlated with diabetes risk (hazard ratio [HR] 0.268; 95% confidence interval [CI] 0.229-0.314, p < 0.00001). For men, the HR of incident diabetes was 0.255 (95% CI 0.212-0.307) and for women it was 0.297 (95% CI 0.218-0.406). Moreover, sensitivity analysis confirmed the stability of the results. Furthermore, the smoothing plot revealed that there was a saturation effect between Cre/BW and the incidence of diabetes.
This study demonstrated that increased Cre/BW is negatively correlated with diabetes in Chinese adults. It also found that Cre/BW has a nonlinear relationship with the incidence of diabetes.
This study demonstrated that increased Cre/BW is negatively correlated with diabetes in Chinese adults. It also found that Cre/BW has a nonlinear relationship with the incidence of diabetes.
The HPTN 071 (PopART) trial demonstrated that universal HIV testing-and-treatment reduced community-level HIV incidence. Door-to-door delivery of HIV testing services (HTS) was one of the main components of the intervention. From an early stage, men were less likely to know their HIV status than women, primarily because they were not home during service delivery. To reach more men, different strategies were implemented during the trial. We present the relative contribution of these strategies to coverage of HTS and the impact of community hubs implemented after completion of the trial among men.
Between 2013 and 2017, three intervention rounds (IRs) of door-to-door HTS delivery were conducted in eight PopART communities in Zambia. Additional strategies implemented in parallel, included community-wide "Man-up" campaigns (IR1), smaller HTS campaigns at work/social places (IR2) and revisits to households with the option of HIV self-testing (HIVST) (IR3). In 2018, community "hubs" offering HTS were implementeivery combined with an option of HIVST and delivery of HTS through community-based hubs. When men are reached, they are willing to test for HIV. Reaching men thus requires implementers to adapt their HTS delivery strategies to meet men's needs.
NCT01900977.
NCT01900977.Colorectal large cell neuroendocrine carcinoma (LCNEC) is rare and multiple LCNECs have not been previously reported. We encountered a case of multiple LCNECs in the rectum and the descending colon. A 66-year-old man presented with anal pain. Colonoscopy showed an ulcerated infiltrating tumor in the rectum, and 0.5 cm of erosion in the descending colon. A biopsy revealed LCNEC in both regions. Abdominal computed tomography revealed irregularly enhanced wall thickening at the rectum and hepatic metastases. Due to the diagnosis of LCNEC, laparoscopic abdominoperineal resection of the rectum was performed. Histopathological examination showed a poorly differentiated, LCNEC in both regions. Immunohistochemical examination demonstrated that the tumor cells were positive for chromogranin and synaptophysin. LCNEC was confirmed, and systemic chemotherapy with cisplatin/irinotecan was initiated. To our knowledge, this is the first case report that describes multiple LCNECs in the rectum and descending colon.The purpose of this study was to analyze the structure of a polysaccharide (HMP-1) from Hippocampus mohnikei, and to explore its anti-inflammatory effect. HMP-1 was obtained from Hippocampus mohnikei by ethanol sedimentation and secondary column chromatography purification. Its structural characteristics were analyzed by gel permeation chromatography (GPC), Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and scanning electron micrograph (SEM). Tyrphostin B42 supplier Results showed its molecular weight (Mw) was 7296 Da, and it mainly consisted of six residues 1,3-β-Glcp, 1,4-α-Manp, 1,4-α-GalpA, 1,4-β-GlcpA2S, 1,4-α-Galp3S, and 1,4-β-GlcNAc. HMP-1 could protect RAW246.7 cells from the cytotoxic effect induced by LPS. HMP-1 also could reduce the levels of nitric oxide and reactive oxygen species produced by LPS stimulation, suggesting that HMP-1 has anti-inflammatory activities within a certain concentration range.We report the synthesis of 16 new compounds obtained from kokusaginine and flindersiamine, the main alkaloids isolated from the bark of Balfourodendron riedelianum. The activity of the compounds against axenic cultures of Trypanosoma cruzi epimastigtotes and trypomastigotes, as well as intracellular amastigotes, is described, together with their cytotoxic activity against three different human cell lines. The synthetic strategy for the preparation of the new compounds was based on the reactivity at the C4 position of the furoquinoline core towards nucleophiles. The new derivatives were synthesized by a Buchwald-Hartwig reaction, in most cases under green, solvent-free conditions. Compounds 1 c and 1 e displayed better in-vitro activity against trypomastigotes than benznidazole and nifurtimox (positive controls) with IC50 less then 4 μM. In addition, both compounds were not cytotoxic against the three human cell lines K562 (erytroleukimia), LM2 (breast cancer), and HaCat (keratinocyte). Interestingly, when evaluated against intracellular amastigotes, compound 1 c was able to significantly reduce the number of this parasite form, compared to the negative control.Strømme syndrome (MIM #243605) is a rare autosomal recessive ciliopathy resulting from compound heterozygous or homozygous pathogenic alterations in the CENPF gene (# 600236). Although there are a number of case reports featuring individuals with clinically compatible Strømme syndrome, only 13 affected individuals had molecular confirmation worldwide. Herein, we report a 24 years old Chinese gentleman with molecularly confirmed Strømme syndrome with compound heterozygous pathogenic nonsense variants in NM_016343.3(CENPF)c.436C > T, p.(Gln146*) and c.9280C > T, p.(Arg3094*). He presented with microcephaly, unilateral microphthalmia, single central upper incisor and bilateral preaxial polydactyly. To our knowledge, this is the first reported Chinese individual with molecularly confirmed Strømme syndrome.
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma and architecture is destroyed, compliance is lost, and gas exchange is compromised in this debilitating condition that leads inexorably to respiratory failure and death within 3-5 years of diagnosis. This review discusses treatment approaches to IPF in current use and those that appear promising for future development.
The data were obtained from the Randomized Controlled Trials and scientific studies published in English literature. We used search terms related to IPF, antifibrotic treatment, lung transplant, and management.
Etiopathogenesis of IPF is not fully understood, and treatment options are limited. Pathological features of IPF include extracellular matrix remodeling, fibroblast activation and proliferation, immune dysregulation, cell senescence, and presence of aberrant basaloid cells. The mainstay therapies are the oral antifibrotic drugs pirfenidone and nintedanib, which can improve quality of life, attenuate symptoms, and slow disease progression. Unilateral or bilateral lung transplantation is the only treatment for IPF shown to increase life expectancy.
Clearly, there is an unmet need for accelerated research into IPF mechanisms so that progress can be made in therapeutics toward the goals of increasing life expectancy, alleviating symptoms, and improving well-being.
Clearly, there is an unmet need for accelerated research into IPF mechanisms so that progress can be made in therapeutics toward the goals of increasing life expectancy, alleviating symptoms, and improving well-being.Conventional embryo assessment is performed by removing embryos from incubators at least once a day. However, it is static and limited to specific time points, reducing the amount of information that could potentially be obtained. Fortunately, the time-lapse system is a powerful technology that enables to observe embryo development progression by image acquisition at recurrent time intervals, without interfering in the culture conditions. There are numerous studies that used time-lapse incubators, focusing on embryo kinetics, patient characteristics and clinical outcomes. This review aims to find agreements in the literature concerning embryo kinetics and patient characteristics age, body mass index, smoking habit, polycystic ovary syndrome and endometriosis; as well as culture conditions that involved culture media and oxygen concentration. Furthermore, they showed differences according to ploidy status, direct/reverse cleavage, gender and the potential association between embryo collapse and clinical outcomes.In vitro fertilization (IVF) success involves ovarian stimulation with conventional or mild stimulation protocols aimed to yield an adequate number of mature oocytes. These oocytes can be further fertilized and generate good quality embryos to be transferred, ideally in the same cycle. Since 2013, following the results of a meta-analysis including more than 60,000 IVF cycles, the negative effects of premature progesterone elevation on reproductive outcomes have been demonstrated. Nowadays, evidence is emerging on the limited regulation on serum progesterone values, demonstrating significantly lower live birth rates in patients with either low ( less then 0.5ng/ml) late follicular phase progesterone or higher levels decreasing sharply. This review discusses and summarizes the different mechanisms of progesterone elevation and its impact on IVF treatments. Different approaches to diminish the impact of progesterone on fertility outcomes are also addressed.
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