Causal association of immune cells and polycystic ovarian syndrome: a Mendelian randomization study.

Background: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that affects a considerable number of women worldwide. It is accompanied by irregular menstruation, hyperandrogenism, metabolic abnormalities, reproductive disorders and other clinical symptoms, which seriously endangers women's physical and mental health. The etiology and pathogenesis of PCOS are not completely clear, but it is hypothesized that immune system may play a key role in it. However, previous studies investigating the connection between immune cells and PCOS have produced conflicting results. Methods: Mendelian randomization (MR) is a powerful study design that uses genetic variants as instrumental variables to enable examination of the causal effect of an exposure on an outcome in observational data. In this study, we utilized a comprehensive two-sample MR analysis to examine the causal link between 731 immune cells and PCOS. We employed complementary MR methods, such as the inverse-variance weighted (IVW) method, and conducted sensitivity analyses to evaluate the reliability of the outcomes. Results: Four immunophenotypes were identified to be significantly associated with PCOS risk: Memory B cell AC (IVW: OR [95%]: 1.123[1.040 to 1.213], p = 0.003), CD39+ CD4+ %CD4+ (IVW: OR [95%]: 0.869[0.784 to 0.963], p = 0.008), CD20 on CD20- CD38-(IVW: OR [95%]:1.297[1.088 to 1.546], p = 0.004), and HLA DR on CD14- CD16+ monocyte (IVW: OR [95%]:1.225[1.074 to 1.397], p = 0.003). The results of the sensitivity analyses were consistent with the main findings. Conclusions: Our MR analysis provides strong evidence supporting a causal association between immune cells and the susceptibility of PCOS. This discovery can assist in clinical decision-making regarding disease prognosis and treatment options, and also provides a new direction for drug development.

[Mongolian medicine three acupoints balance needling improves depressive behavior by regulating p11/tPA/BDNF pathway and miRNA-16 of hippocampus and middle raphe nucleus in depression model rats].

OBJECTIVE: To observe the effect of Mongolian medicine three-acupoints balance needling on the expression of p11/tPA/BDNF pathway and miRNA-16 in the hippocampus and middle raphe nucleus (MRN) in chronic stress depression model rats, so as to explore its mechanisms underlying improvement of depression. METHODS: Male SD rats were randomly divided into blank control, model, medication and Mongolian medicine acupuncture (acupuncture) groups, with 12 rats in each group. The depression model was established by using chronic unpredictable mild stress method. The rats in the medication group received gavage of prozac (2 mg/kg, diluted with normal saline, 1 mg/mL) 1 h after stress stimulation, once per day for 28 days, and those in the acupuncture group received three-acupoints (Heyi, Badagan and Xin) needling, once a day for 28 days. The behavioral changes were detected by using open field test and sugar consumption test before modeling and after the intervention. The immunoactivity of p11 and tPA proteins in the MRN, and their expression levels in both the MRN and hippocampus were detected by using immunofluorescence histochemistry and Western blot, separately, and the expression levels of miRNA-16 and BDNF mRNA in the hippocampus and MRN detected by using real-time quantitative PCR. RESULTS: After modeling, the crossing and rearing scores of open field tests and the relative consumption of sucrose in the model group were apparently lower than those of the blank control group (P<0.05), the expression levels of p11 and tPA in the MRN, and those of p11 and tPA proteins and BDNF mRNA in the MRN and hippocampus were significantly down-regulated (P<0.05), while those of miRNA-16 in the hippocampus and MRN were significantly up-regulated (P<0.05). Compared with the model group, the crossing and rearing scores of open field tests and glucose consumption, as well as the expression levels of p11 and tPA proteins and BDNF mRNA in the hippocampus and MRN were obviously increased in both the medication and acupuncture groups (P<0.05), while the expression of miRNA-16 in hippocampus was markedly down-regulated in both the medication and acupuncture groups (P<0.05). No significant differences were found between the acupuncture and medication groups in all the indexes mentioned above (P>0.05). CONCLUSION: Mongolian medicine three-acupoints balance needling can improve the depressive state in depression rats, which may be associated with its effects in up-regulating the expression of p11 and tPA proteins and BDNF mRNA in the hippocampus and MRN and in down-regulating miRNA-16 in the hippocampus, suggesting an involvement of miRNA-16 controlled p11/tPA/BDNF signaling pathway in the antidepressant effect of acupuncture.

Prognosis of patients with newly diagnosed glioblastoma treated with molecularly targeted drugs combined with radiotherapy vs temozolomide monotherapy: A meta-analysis.

BACKGROUND: Glioblastoma (GB) is one of the most common malignancies with limited standard therapies such as surgery, radiotherapy (RT) plus temozolomide (TMZ). Molecularly targeted drugs have been investigated among various clinical trials and are expected to develop in the field of tumor therapy, while the efficacy remains uncertain due to limited previous results. Thus, we focus on the evaluation of molecularly targeted drugs to clarify its overall effectiveness in terms of treating newly diagnosed GB. METHODS: Electronic databases were searched for eligible literatures updated to April 2018. Randomized-controlled trials were included to assess the efficacy and safety of molecularly targeted drugs in patients with newly diagnosed GB. The main outcomes were further calculated including the following parameters: PFS (progression-free survival), OS (overall survival) as well as AEs (adverse events). All data were pooled along with their 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were evaluated quantitatively. RESULTS: The combination of molecularly targeted drugs with TMZ + RT had no significant effects on OS (OR = 0.96, 95%CI = 0.89-1.04, P = .36). Meanwhile, the combination regimen significantly improved the PFS of patients with newly diagnosed GB (OR = 0.86 ,95% CI 0.75-0.98, P = .02). The rate of AEs (OR = 1.68,95%CI = 1.44-1.97, P < .00001) was higher in patients receiving molecularly targeted drugs, which was comparable to the contemporary group. CONCLUSION: Longer PFS and a higher rate of AEs were observed with the addition of molecularly targeted drugs to standard chemoradiation in patients harboring newly diagnosed GB. Nevertheless, compared with the control arm, the regimen did not significantly prolong OS.