Association of PM2.5 Components with Acceleration of Aging: Moderating Role of Sex Hormones.

Fine particulate matter (PM2.5) has been linked to aging risk, and a lack of knowledge about the relationships between PM2.5 components and aging risk impeded the development of healthy aging. Participants were recruited through a multicenter cross-sectional study in the Beijing-Tianjin-Hebei region in China. Middle-age and older males and menopausal women completed the collection of basic information, blood samples, and clinical examinations. The biological age was estimated by Klemera-Doubal method (KDM) algorithms based on clinical biomarkers. Multiple linear regression models were applied to quantify the associations and interactions while controlling for confounders, and a restricted cubic spline function estimated the corresponding dose-response curves of the relationships. Overall, KDM-biological age acceleration was associated with PM2.5 component exposure over the preceding year in both males and females, with calcium [females: 0.795 (95% CI: 0.451, 1.138); males: 0.712 (95% CI: 0.389, 1.034)], arsenic [females: 0.770 (95% CI: 0.641, 0.899); males: 0.661 (95% CI: 0.532, 0.791)], and copper [females: 0.401 (95% CI: 0.158, 0.644); males: 0.379 (95% CI: 0.122, 0.636)] having greater estimates of the effect than total PM2.5 mass. Additionally, we observed that the associations of specific PM2.5 components with aging were lower in the higher sex hormone scenario. Maintaining high levels of sex hormones may be a crucial barrier against PM2.5 component-related aging in the middle and older age groups.

Association between the MCP-1 -2518 A > G (rs1024611) polymorphism and susceptibility to type 2 diabetes mellitus and diabetic nephropathy: a meta-analysis.

BACKGROUND: Studies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk. METHODS: Eligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger's test. RESULTS: In total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66-0.93, P = 0.006; PQ = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11-1.71, P = 0.004, PQ = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041). CONCLUSION: The MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

Effectiveness of seminar-case learning for use in practice teaching of statistics for undergraduates majoring in preventive medicine: a prospective cluster-randomized controlled trial.

BACKGROUND: The seminar-case learning (SCL) method is a case-oriented teaching model, with teachers and students as the main body of teaching, characterized by communication, interaction, and mutual inspiration. This study explored the effects of the SCL method versus traditional lecture-based learning (LBL) in the statistics curriculum for undergraduate students majoring in preventive medicine. Research questions were: 1) whether the scores of students in the experimental group (the SCL model) were higher than those in the control group (the LBL model); 2) whether the students' satisfaction in the experimental group was better than that in the control group; and 3) whether the self-report benefit of students in the experimental group was better than that in the control group. METHODS: We conducted a two-armed cluster-randomized education intervention trial in practice teaching of health statistics among undergraduates majoring in preventive medicine. Two administrative classes (classes 1-4 and classes 5-8) were divided into the experimental group and the control group according to the principle of drawing lots. The students in two groups received the same statistical theory course. For the arrangement of statistical practice course, the experimental group adopted the SCL model, and the control group used the LBL model. The teaching effect was evaluated via an examination and an anonymous questionnaire survey. RESULTS: Scores for noun explanation questions in the experimental group showed no statistical significance with that of the control group(U = 2911.0, P = 0.964). The scores of single choice, calculation, and case analysis questions, and the total scores were significantly higher than that of the control group (P < 0.05). Students' satisfaction with arrangements of the practice course in the experimental group (92.41%) was significantly higher than that of in the control group (77.03%), the difference was statistically significant (χ2 = 7.074, P = 0.008). The self-report benefit of students in the experimental group was better than that in the control group (P < 0.05). CONCLUSION: As an effective method of high-quality education, the SCL model is worthy of further promotion in the practice teaching of preventive medicine.

Association between TNF-α G-308A (rs1800629) polymorphism and susceptibility to chronic periodontitis and type 2 diabetes mellitus: A meta-analysis.

BACKGROUND AND OBJECTIVE: Although the association between tumor necrosis factor-α (TNF-α) G-308A (rs1800629) polymorphism and chronic periodontitis (CP), chronic periodontitis with type 2 diabetes mellitus (DP) is assumed, results of this association have been contradictory. The aim of this study was to assess the relationship between rs1800629 polymorphism and CP/DP susceptibility. METHODS: We searched for studies on PubMed, Web of Science, MEDLINE, Chinese National Infrastructure, and WanFang databases. Study selection was performed using specific inclusion and exclusion criteria and fulfilled the PECO (participant, exposure, comparison, and outcome) format. The relationship between rs1800629 polymorphism and CP/DP susceptibility was evaluated by the effect summary odds ratio (OR) and 95% confidence intervals (CIs). Allele, dominant, and recessive genetic models were computed to assess the strength of the association. RESULTS: A total of 25 case-control studies were included in the analysis. In the Asian population, TNF-α rs1800629 polymorphism was found to be significantly associated with CP in the overall analyses and for all genetic contrasts, while no significant risks were found among Caucasian populations for all genetic contrasts. The TNF-α rs1800629 polymorphism was also associated with increased DP risk in Asians under the fixed-effects model, but not in the recessive comparison. CONCLUSION: The meta-analysis suggested that TNF-α rs1800629 polymorphism might affect the risk of CP and DP, particularly in individuals of Asian descent.

Upregulation of long non-coding RNA MEG3 in type 2 diabetes mellitus complicated with vascular disease: a case-control study.

Previous studies have indicated that long non-coding RNAs (lncRNAs) were closely related to diabetes. In this study, we aimed to explore the possible role and mechanism of lncRNA MEG3 in the occurrence and development of type 2 diabetes mellitus (T2DM) and its vascular complications. A case-control study involving 115 subjects was conducted, including 53 T2DM patients (37 patients with vascular complication and 16 patients without vascular complications) and 62 healthy subjects. We performed real-time polymerase chain reaction (RT-PCR) analysis of the lncRNA MEG3 and miR-146a levels in peripheral blood mononuclear cells (PBMCs) in the 115 samples. We found that the expression of lncRNA MEG3 was upregulated in the T2DM patients with vascular complication (DC group) compared with T2DM patients without vascular complication (D group) (P < 0.05) and the control group (P < 0.01). miR-146a levels in DC group were significantly lower compared with control group. There was a significant positive correlation between the expression of lncRNA MEG3 and glucose (GLU) (r = 0.301, P = 0.0011) and hemoglobin A1C (HbA1c) (r = 0.477, P = 0.0006). Our study suggests MEG3 may play as an important role in progression of diabetes-related vascular complications, contributing to a novel understanding of pathogenesis and prognosis for diabetes and its complications.

Leucine-Rich Repeat Neuronal Protein 1 Regulates Differentiation of Embryonic Stem Cells by Post-Translational Modifications of Pluripotency Factors.

Stem cell surface markers may facilitate a better understanding of stem cell biology through molecular function studies or serve as tools to monitor the differentiation status and behavior of stem cells in culture or tissue. Thus, it is important to identify additional novel stem cell markers. We used glycoproteomics to discover surface glycoproteins on human embryonic stem cells (hESCs) that may be useful stem cell markers. We found that a surface glycoprotein, leucine-rich repeat neuronal protein 1 (LRRN1), is expressed abundantly on the surface of hESCs before differentiation into embryoid bodies (EBs). Silencing of LRRN1 with short hairpin RNA (shLRRN1) in hESCs resulted in decreased capacity of self-renewal, and skewed differentiation toward endoderm/mesoderm lineages in vitro and in vivo. Meanwhile, the protein expression levels of the pluripotency factors OCT4, NANOG, and SOX2 were reduced. Interestingly, the mRNA levels of these pluripotency factors were not affected in LRRN1 silenced cells, but protein half-lives were substantially shortened. Furthermore, we found LRRN1 silencing led to nuclear export and proteasomal degradation of all three pluripotency factors. In addition, the effects on nuclear export were mediated by AKT phosphorylation. These results suggest that LRRN1 plays an important role in maintaining the protein stability of pluripotency factors through AKT phosphorylation, thus maintaining hESC self-renewal capacity and pluripotency. Overall, we found that LRRN1 contributes to pluripotency of hESC by preventing translocation of OCT4, NANOG, and SOX2 from nucleus to cytoplasm, thereby lessening their post-translational modification and degradation. Stem Cells 2018;36:1514-1524.

Electronic vs steric effects on the stability of anionic species: a case study on the ortho and para regioisomers of organofullerenes.

The stability of the anionic species of the ortho and para regioisomers of (MeO)BnC(2n) (Me = methyl, Bn = benzyl, n = 30 or 35) has been examined. The results show that the ortho adducts (electronically favored regioisomers) are stable upon receiving one or two electrons, while the para ones (sterically favored adducts) decompose by removing the methoxy group under similar conditions. Computational calculations indicate that the stability of the anionic species is significantly affected by the electronic structure, where the [5,6]-double bond is responsible for the instability of the reduced species of the para adducts. Further study with 1,15-(MeO)2-2,4-Bn2C60, an adduct with both the ortho and para positioned methoxy, shows that the reduced species is stable, indicating that the 1,2,4,15-configuration is an electronically preferential structure even though it has a [5,6]-double bond.

An updated meta-analysis of transforming growth factor-ß1 gene: three polymorphisms with gastric cancer.

To derive a more precise estimation of the relationship between TGF-ß1 polymorphisms and gastric cancer (GC) risk, we conducted a meta-analysis of all available case-control studies relating the C-509 T, T869C, and G 915C polymorphisms of the TGF-ß1 gene to the risk of developing GC. The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Funnel plots and Egger's test were used to estimate publication bias. Finally, 11 studies were included in the final meta-analysis. With respect to C-509 T polymorphism, it was found that significantly increased GC risk was associated with the TT genotype in the recessive genetic model in overall analysis (TT vs. CC + CT: OR = 1.23, 95% CI 1.09-1.38, P(heterogeneity) = 0.13) and in Asian population (TT vs. CC + CT: OR = 1.24, 95% CI 1.10-1.39, P(heterogeneity) = 0.18). With respect to T869C and G915C polymorphisms, no significant association with GC risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that the T allele of TGF-ß1 509C/T polymorphism is probably the susceptibility factor for GC.

Meta-analysis of the transforming growth factor-ß1 polymorphisms and susceptibility to Alzheimer's disease.

The association between transforming growth factor-ß1 (TGF-ß1) gene polymorphisms and Alzheimer's disease (AD) risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-ß1 polymorphisms and AD risk, we conducted a meta-analysis of all available case-control studies relating the T869C and/or C-509T polymorphisms of the TGF-ß1 gene to the risk of developing AD. Eligible articles were identified by search of databases including Pub Med, Web of Science, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and the Wan Fang (Chinese) for the period up to March 2012. Finally, a total of 14 articles were identified, 10 with 1,657 cases and 6,971 controls for T869C polymorphism and 8 with 2,618 cases and 7,473 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity. With respect to T869C and C-509T polymorphism, the combined results showed that there were no significant differences in genotype distribution between AD and control based on all studies. When stratifying for the race, there were also no statistically significant differences in genotype distribution between AD and controls. This meta-analysis did not provide an evidence of confirming association between the T869C and/or C-509T polymorphisms of the TGF-ß1 gene and AD.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to diabetic nephropathy in Chinese type 2 diabetic patients: a meta-analysis.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and diabetic nephropathy (DN) or diabetes mellitus (DM) risk has been widely reported, but the results are still debatable. To investigate the role of MTHFR C677T polymorphism on DM or DN, 13 separate studies in the Chinese population on the relation between MTHFR C677T polymorphism and DM or DN were analyzed by a meta-analysis. Five genetic models were used to estimate the association between MTHFR C677T polymorphism and the risk of DM or DN. Overall, our meta-analysis for DN versus healthy controls produced significant results for all genetic contrasts except for the co-dominant model (allele contrast: OR = 2.24, 95%CI: 1.88-2.65, p < 0.00001, Pheterogeneity = 0.49). However, the meta-analysis for DM versus healthy controls produced non-significant results for all contrasts (allele contrast: OR = 1.12, 95%CI: 0.92-1.35, p = 0.25, Pheterogeneity = 0.07). In addition, the meta-analysis for DM versus DN produced significant results for all contrasts (allele contrast: OR = 1.88, 95%CI: 1.65-2.15, p < 0.00001, Pheterogeneity = 0.83). The current meta-analysis suggested that MTHFR C677T polymorphism might influence DN risk, but not for DM in the Chinese population.

Preferential formation of stereocomplex crystals in poly(L-lactic acid)/poly(D-lactic acid) blends by a fullerene nucleator.

Selective formation of stereocomplex (sc) crystallization in enantiomeric poly(L-lactic acid)/poly(D-lactic acid) (PLLA/PDLA) blends is considered as one of the most effective and promising way to improve the mechanical and thermal properties of polylactide (PLA) materials. However, homocrystallization (hc) prevails over sc crystallization in high-molecular-weight (HMW) PLLA/PDLA blends. Herein, we propose a simple and straightforward approach for fabricating sc crystallization and suppress hc crystallization for HMW PLLA/PDLA blends through the addition of C70 as a nucleator. Non-isothermal crystallization and wide-angel X-ray diffraction studies demonstrate that, the incorporation of 1 wt% C70 overwhelmingly leads to the formation of sc crystallites, while preventing the formation of hc crystallites. Isothermal crystallization experiments at 140 °C reveal a significant reduction in the half-crystallization period of the PLLA/PDLA blend upon the addition of C70. Fourier-transformed infrared spectroscopy suggests that, the improved intermolecular interactions between PLLA and PDLA chains, as well as the inhibition of molecular chain diffusion and mobility, contribute to the accelerated formation of sc facilitated by C70. The enhanced sc crystallization results in a 15.5 °C higher thermal stability in the as-prepared PLLA/PDLA blend with 1 wt% C70 compared to the neat counterpart.

Association of tag single nucleotide polymorphisms (SNPs) at lncRNA MALAT1 with type 2 diabetes mellitus susceptibility in the Chinese Han population: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic, lifelong disease. The molecular mechanisms and pathophysiology of T2DM have not yet been fully elucidated. Dysregulation of the long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) is considered one of the main contributing factors of the dysfunction found in many diseases, including those of the endocrine system. The aim of this study was to investigate the association between lncRNA MALAT1 single nucleotide polymorphisms (SNPs) and T2DM in the Chinese Han population. METHODS: We genotyped three SNPs (rs3200401 C > T, rs619586 A > G, rs11227209 C > G) of the MALAT1 gene, including 571 T2DM patients and 526 controls. The association between different genotypes and the risk of T2DM was analyzed using logistic regression, and the results were expressed by odds ratio (OR) and its 95% confidence interval (95%CI), and then stratified by age, sex, and BMI. P < 0.05 on both sides was considered as statistically significant. RESULTS: We found that the CT + TT genotypes of the rs3200401 polymorphism were significantly associated with an increased risk of T2DM in Chinese Han population (OR = 1.77; 95% CI:1.35-2.33; Padjusted < 0.001), whereas MALAT1 rs619586 AG + GG genotypes were associated with a reduced risk of T2DM (OR = 0.67; 95% CI:0.48-0.94; Padjusted = 0.021). Subsequent stratified analysis showed that compared with the rs3200401 CC genotype, CT + TT genotypes were associated with an increased risk of T2DM in the male, female, age ≥ 65 years, and BMI ≥ 24 subgroups (OR = 1.68, 95% CI:1.10-2.56, Padjusted = 0.016; OR = 1.83, 95% CI:1.27-2.62, Padjusted = 0.001; OR = 1.86, 95% CI:1.38-2.52, Padjusted < 0.001; OR = 2.13, 95% CI:1.45-3.15, Padjusted < 0.001; respectively). Haplotype analysis showed that T-A-C haplotype had a 1.533-fold increased risk of T2DM (95% CI, 1.208-1.945, P < 0.001) and C-G-G was associated with a decreased risk of T2DM. No significant association was found between rs11227209 and T2DM risk (P > 0.05). CONCLUSION: The results suggest that MALAT1 rs619586 and rs3200401 confer susceptibility for T2DM in the Chinese Han population and provide new genetic targets for the treatment of diabetes and its complications in the future.

Protective effects of metformin on pancreatic ß-cell ferroptosis in type 2 diabetes in vivo.

Metformin (Met) is the recommended first-line therapeutic drug for type 2 diabetes mellitus (T2DM) and exerts protective effects on ß-cell damage. Ferroptosis, a new form of cell death, is associated with pancreatic islet injury in patients with T2DM. However, the protective effects of Met treatment against ß-cell damage through ferroptosis modulation remain under-reported. This study investigated the in vivo effects of Met treatment on pancreatic ß-cell ferroptosis using two different diabetic mouse models, namely, low-dose streptozotocin (STZ) and high-fat diet (HFD)-induced diabetic mice and db/db mice. Met treatment significantly restored insulin release, reduced cell mortality, and decreased the overproduction of lipid-related reactive oxygen species in the islets of both STZ/HFD-induced diabetic mice and db/db mice. Administration of the Ras-selective lethal 3 injection significantly attenuated the antiferroptosis effects of Met. Mechanistically, Met treatment alleviated ß-cell ferroptosis in T2DM, which was associated with the regulation of the GPX4/ACSL4 axis in the islets. In conclusion, our findings highlight the significance of ferroptosis in T2DM ß-cell damage and provide novel insights into the protective effects of Met against islet ß cells.

Chronotypes and their association with sleep quality among Chinese college students of Anhui Province: a cross-sectional study.

OBJECTIVES: To describe the prevalence of chronotype and sleep quality among Chinese college students and explore the relationship between chronotype and sleep quality. DESIGN: A cross-sectional study. SETTING: Four colleges and universities in Anhui, China, between November and December 2020. PARTICIPANTS: A total of 4768 college students were recruited using a stratified, multistage, cluster sampling survey. OUTCOME MEASURES: Morningness-Eveningness Questionnaire 19 was used to determine the chronotype of the students and the Pittsburgh Sleep Quality Index (PSQI) was used to measure their sleep quality. The multiple logistic regression model was used to explore the potential association between chronotype and sleep quality. RESULTS: The self-reported proportions of evening-type (E-type), neutral-type and morning-type among college students were 51.17%, 45.14% and 3.69%, respectively. The mean PSQI score was 4.97±2.82 and the prevalence of poor sleep quality was 18.2%. After adjusting the covariates by multiple logistic regression analysis, E-type was positively associated with subjective sleep quality (OR=1.671, 95% CI 1.414 to 1.975), sleep latency (OR=1.436, 95% CI 1.252 to 1.647), sleep duration (OR=2.149, 95% CI 1.506 to 3.067), habitual sleep efficiency (OR=1.702, 95% CI 1.329 to 2.180), daytime dysfunction (OR=1.602, 95% CI 1.412 to 1.818) and overall poor sleep quality (OR=1.866, 95% CI 1.586 to 2.196). CONCLUSIONS: College students mainly exhibited E-type, and an elevated prevalence of poor sleep quality existed among these students. The E-type was positively associated with poor sleep quality.

Metformin alleviates glucolipotoxicity-induced pancreatic ß cell ferroptosis through regulation of the GPX4/ACSL4 axis.

Ferroptosis, a new type of cell death, is associated with pancreatic ß cell damage. However, the role of glucolipotoxicity in inducing ß cell ferroptosis remains unclear. Metformin (Met), exenatide (Exe), and saxagliptin (Sax) are frequently used anti-hyperglycaemic drugs. However, their protective effects on ß cells through ferroptosis modulation are not well-established. In this study, we observed significant ferroptosis in NIT-1 cells and primary mouse islets after exposure to high glucose and palmitate (HG/PA). Compared to Exe and Sax, Met significantly alleviated glucolipotoxicity-induced pancreatic ß cell ferroptosis. Blocking the activity of glutathione peroxidase 4 (GPX4) with Ras-selective lethal 3 or inhibiting its expression by small interfering RNA transfection significantly attenuated the anti-ferroptosis effects of Met. Mechanistically, Met alleviates HG/PA-induced ß cell ferroptosis by regulating the GPX4/ACSL4 axis. Collectively, our findings highlight the significance of ferroptosis in pancreatic ß cell glucolipotoxicity-induced injury and provide novel insights into the protective effects of Met on islet ß cells.

Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis.

The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to systemic lupus erythematosus are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and SLE, a meta-analysis of 18 published case-control studies was performed. 18 studies meeting our inclusion criteria comprising 1806 SLE cases and 2,490 controls were included. The effect summary odds ratio (OR) and 95 % confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between SLE cases and control on the basis of all studies, GG versus AA (OR = 1.53, 95 % CI: 1.12-2.10), GG versus GA/AA (OR = 1.30, 95 % CI: 1.04-1.64), GG versus GA (OR = 1.27, 95 % CI: 1.03-1.55). When stratifying for the race, the phenomenon was found that SLE cases had a significantly higher frequency of GG/GA versus AA (OR = 1.58, 95 % CI: 1.23-2.03), GG versus AA (OR = 1.89, 95 % CI: 1.23-2.91), GG versus GA/AA(OR = 1.39, 95 % CI: 1.03-1.89), GA versus AA(OR = 1.38, 95 % CI: 1.06-1.80) and G versus A(OR = 1.34, 95 % CI: 1.07-1.67) than control in Asians. Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for SLE susceptibility, at least in Asians. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of CTLA-4 exon-1 +49A/G polymorphism with SLE susceptibility.

Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis.

The results of studies on association between the C677T polymorphism of the 5,10-methylene-tetrahydrofolate reductase (MTHFR) gene and osteonecrosis of the femoral head (ONFH) are controversial. To derive a more precise estimation of the relationship between the MTHFR C677T polymorphism and ONFH, a meta-analysis was performed. Eight studies on MTHFR C677T association with ONFH were searched up to April 2011, and the genotype frequencies in control group were consistent with Hardy-Weinberg equilibrium. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's regression test, and heterogeneity was assessed. Eight studies containing 778 cases and 1,162 controls were included. Heterogeneity was observed (χ(2) = 18.58, P = 0.01). Under the random effects model, the common OR was 1.38 (95% CI: 0.92-2.08; P = 0.12). In the subgroup meta-analysis, there was an association between MTHFR C677T polymorphism and ONFH in non-Asian population for CT + TT vs. CC (OR = 1.72; 95% CI: 1.21-2.43; P = 0.002; I(2) = 37.9%, P = 0.17), but not for Asian population (OR = 0.88; 95% CI: 0.66-1.66; P = 0.35; I(2) = 45.4%, P = 0.16). There was heterogeneity between studies and no clear evidence of an association on a worldwide population. When stratifying for the race, this meta-analysis did not provide an evidence of confirming association between MTHFR C677T polymorphism and ONFH. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of MTHFR C677T polymorphism with ONFH susceptibility.

Immune checkpoint inhibitors in advanced and recurrent/metastatic cervical cancer.

Cervical cancer (CC) poses a serious threat to women's health. Although many early-stage patients have a good prognosis, there are still a lack of effective therapies for advanced and recurrent/metastatic CC. In this context, immunotherapy and immune checkpoint inhibitors (ICIs) are particularly likely to play a role in the treatment of cervical tumors in a variety of disease settings. Some promising immune checkpoints include programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), which exert immunomodulatory effects as negative regulators of T-cell activation and suppress immune responses in cervical cancer through cancer cell immune evasion. Initial trials of ICIs for CC have shown encouraging results in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both monotherapy and combination strategies. Meanwhile, human papillomavirus, vaginal microecology and intestinal microenvironment play an important role in CC, which provides new treatment directions. This review analyzed a number of completed or ongoing clinical trials of ICIs in the treatment of advanced and recurrent/metastatic CC. And we also analyzed the important relationship between vaginal microecology and intestinal microecology with CC and their related immunotherapy prospects.

Correction: Reactions of [60]fullerene with alkynes promoted by OH.

[This corrects the article DOI: 10.1039/D2RA01300B.].

Reactions of [60]fullerene with alkynes promoted by OH.

In the current work, the reactions of [60]fullerene with alkynes promoted by OH- (base) are addressed. The treatment of C60 with alkynes in the presence of TBAOH produces alkynylation products (R-C60-H) with high selectivity in o-DCB at 100 °C. Plausible reaction mechanisms were proposed. This work provides a convenient and environmental friendly method for the functionalization of fullerenes.