The efficacy and safety of PD-1/PD-L1 inhibitors versus chemotherapy in patients with previously treated advanced non-small-cell lung cancer: A meta-analysis.

BACKGROUND: Immune checkpoint inhibitor therapy for non-small cell lung cancer is widely used in clinical practice. However, there has not been a systematic statistical proof of the efficacy of PD-1 inhibitors in patients with advanced cancer. This meta-analysis aims to evaluate its efficacy and related influencing factors, so as to provide a basis for clinical diagnosis and treatment. OBJECTIVE: To assess the effectiveness and safety of programmed death-1 (PD-1)/PD ligand 1 (PD-L1) inhibitors versus chemotherapy as second-line or late-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) via a systematic review of published randomized controlled trials (RCTs). METHODS: Studies were identified through PubMed, EMBASE, and Cochrane Library electronic databases. RevMan 5.3.5 was used to analyze the data extracted from all eligible studies. RESULTS: All 4122 eligible patients from 8 RCTs were included in this study. The meta-analysis showed that PD-1/PD-L1 inhibitors could significantly improve overall survival (hazards ratio [HR] 0.71, 95% confidence interval [CI] 0.66-0.77, P < .001), progression-free survival (HR 0.88, 95%CI 0.81-0.94, P = .01), and objective response rate (HR 2.03, 95%CI 1.66-2.49, P < .001) compared with chemotherapy drugs. The incidence of side effects of any grade (HR 0.34, 95%CI 0.29-0.39, P < .001) or grades 3 to 5 (HR 0.15, 95%CI 0.10-0.23, P < .001) consistently showed that PD-1/PD-L1 inhibitors were safer than chemotherapy. Furthermore, subgroup analysis based on tumor proportion score or pathology classification revealed that PD-1/PD-L1 inhibitors significantly improved overall survival compared with chemotherapy. CONCLUSION: As a second-line or late-line treatment, PD-1/PD-L1 inhibitors are safer and more effective than chemotherapy in patients with advanced NSCLC.

Chromosomal polymorphisms associated with reproductive outcomes after IVF-ET.

PURPOSE: This study aimed to investigate the effect of the detail type of chromosomal polymorphisms (1/9/16qh+/-, D/G group polymorphisms, and inv(9)) on the IVF-ET outcomes. METHODS: A total of 1335 infertile couples undergoing IVF/ICSI were enrolled and comprehensively analyzed the correlation between three detail types of chromosomal polymorphisms (1/9/16qh+/-, D/G group polymorphisms, and inv(9)) and the outcome of IVF/ICSI embryo transfer. The fertilized rate, cleaved embryo rate, good-quality embryo rate, clinical pregnancy rate, implantation rate, and early stage miscarriage rate were compared between the chromosomal polymorphisms groups and the control group. RESULTS: Both the inv(9) and D/G group chromosomal polymorphisms related to female infertility significantly lead to a lower 2PN cleavage rate (86.44% vs. 97.58% and 90.67% vs. 97.58%, respectively, P < 0.05) undergoing IVF insemination, the inv(9) adversely increasing the early miscarriage rate, either undergoing IVF (21.4% vs. 3.0%, P < 0.05) or ICSI (50.0% vs. 2.0%, P < 0.05) insemination, female carriers (23.08% vs. 2.87%, P < 0.05) or male carriers (44.44% vs. 2.87%, P < 0.05). For D/G groups, ICSI insemination may increase the implantation rate (44.8% vs. 23.69%, P < 0.05) and clinical pregnancy rate (78.6% vs. 40.65%, P < 0.05). 1/9/16qh+/- had no apparent adverse effect on the patient's clinical outcomes. CONCLUSIONS: Our study suggests that chromosome karyotype analysis is necessary for IVF patients in clinical practice; we should afford individual genetic counseling suggestion according to the polymorphism types.

Changes in vessel density of the patients with narrow antenior chamber after an acute intraocular pressure elevation observed by OCT angiography.

BACKGROUND: Although the pathogenesis of glaucoma is not fully understood,an elevated intraocular pressure (IOP) is a major factor contributing to its development and progression. The aim of this study was to investigate the changes in the vessel densities of the macula and optic nerve head (ONH) after an acute elevation in the intraocular pressure (IOP) observed using optical coherence tomography angiography (OCTA). METHODS: This was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and one hour after the LPI. The retinal vessel densities of the macula and ONH were measured using OCTA at the baseline and one hour after the LPI. RESULTS: A total of 64 eyes of 51 individuals were enrolled in this study, and 58 eyes of 43 individuals finally completed the study with a mean IOP rise of 10.5 ± 7.6 mmHg after the LPI. Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤10 mmHg, group B = 10 mmHg < IOP rise ≤20 mmHg, and group C = IOP rise > 20 mmHg. The vessel density did not differ after the acute IOP elevation in either the macular region or papillary region in group A or group B (p > 0.05), but there was a significant difference in group C (p < 0.05). However, when the subjects were not separated into groups, the vessel densities of the ONH and macular region did not differ between the measurements obtained at the baseline and one hour after the LPI (p > 0.05). The correlation existed in peripapillary and macular vessel density (p < 0.05). CONCLUSION: In these subjects with narrow antenior chamber, an acute mild or moderate IOP elevation for one hour after the LPI did not affect the vessel density in the macula or ONH, as examined using OCTA. However, when the IOP rise was greater than 20 mmHg, the macular and papillary vessel density decreased significantly.

Upregulation of ADAMTS­7 and downregulation of COMP are associated with spontaneous abortion.

A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS­7) has been revealed to serve an important role in inflammation­associated diseases. However, the role of ADAMTS­7 in spontaneous abortion (SA) remains unclear. In the present study, human and mouse decidual tissues were used to detect the expression of ADAMTS­7 and cartilage oligomeric matrix protein (COMP) in mice with lipopolysaccharide (LPS)­induced abortion (10 mice/group), and in SA humans and the corresponding control group (21 participants in the SA group and 15 participants in the control group). The results revealed that ADAMTS­7 expression was upregulated and that COMP expression was downregulated in the mouse decidual tissue of the LPS­induced abortion group, when compared with that of the normal control group. The results were further confirmed by western blot analysis and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis, which revealed increased ADAMTS­7 and decreased COMP expression at the protein and mRNA levels in mice treated with LPS. Additionally, the expression of ADAMTS­7 was negatively correlated with the expression of COMP in mice, with a correlation coefficient of ­0.936 (P<0.001). In addition, the expression of ADAMTS­7 and COMP exhibited was similar in the decidual tissue of SA patients when compared with the levels observed in the tissues of the normal control participants, as demonstrated by increased ADAMTS­7 expression and decreased COMP expression. Western blotting and RT­qPCR analysis revealed that ADAMTS­7 was increased and COMP was decreased in the decidual tissue of SA subjects. The correlation analysis of ADAMTS­7 and COMP in human decidual tissue also revealed a similar result, with a correlation coefficient of ­0.836 (P<0.001). The results of the present study demonstrated that ADAMTS­7 was upregulated and COMP was downregulated in the decidual tissues of humans and mice with SA, and a negative correlation was identified between the expression levels of ADAMTS­7 and COMP, thereby providing novel evidence for a better understanding of the pathogenesis of SA, which may lead to improvements in the clinical pregnancy outcomes of these individuals.

MIF May Participate in Pathogenesis of Polycystic Ovary Syndrome in Rats through MAPK Signalling Pathway.

The polycystic ovary syndrome (PCOS) model was established in rats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA). Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups: control group, PCOS group, and PCOS with high-fat diet (HFD) group. Serum hormones were assayed by radioimmunoassay (RIA). The ovaries were immunohistochemically stained with MIF, and the expression of MIF, p-JNK and p-p38 was detected by Western blotting in ovaries. The serum testosterone level, LH concentration, LH/FSH ratio, fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478, 13.809±1.701, 1.820±0.404, 10.83±1.123 and 1.8692±0.1096) and PCOS with HFD group (6.075±0.439, 14.075±1.927, 1.779±0.277, 10.20±1.377 and 1.7736±0.6851) were significantly higher than those in the control group (4.949±0.337, 2.458±0.509, 1.239±0.038, 9.53±0.548 and 1.5329±0.7363), but there was no significant difference between the PCOS group and PCOS with HFD group. The expression levels of MIF, p-JNK, and p-p38 in the PCOS group (0.4048±0.013, 0.6233±0.093 and 0.7987±0.061) and PCOS with HFD group (0.1929±0.012, 0.3346±0.103 and 0.3468±0.031) were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061), but no significant difference was observed between PCOS group and PCOS with HFD group. It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.

Mental health status assessment in polycystic ovarian syndrome infertility patients: A pilot study.

Polycystic ovary syndrome (PCOS) is a major endocrine disorder afflicting women of reproductive age. Women with PCOS are more likely to suffer from mental health disturbances than healthy women. The "infertility" suffered by PCOS patients would also lead to mental health disturbances. Symptom Checklist 90 (SCL-90) and questionnaire which includes patients' socio-economic and demographic data were used to assess the mental health status of PCOS (n=103) and non-PCOS (n=110) infertile patients. Logistic regression analysis and t-tests were used for comparative analysis. The data demonstrated that scores of depression, interpersonal sensitivity, obsessive-compulsive, and hostility symptoms in PCOS infertile patients were significantly higher than those in the non-PCOS infertile patients (P<0.05). Logistic regression analysis revealed that acne had negative effect on mental health status (P<0.05). Secondary infertile PCOS patients were more easily to suffer from somatization, interpersonal sensitivity, obsessive-compulsive, anxiety, hostility and paranoid ideation symptoms than the primary infertile PCOS patients (P<0.05). The results suggested that the PCOS patients especially the secondary infertile PCOS patients had obvious mental health disturbances. The acne might play an importance role in the occurrence of mental health disturbances in PCOS patients. PCOS related symptoms may be risk factors of mental health status in PCOS patients with infertility. More attention should be paid to the PCOS infertile patients, and mental health therapy should be considered if necessary.