ImmRNA: a database of RNAs associated with tumor immunity.

The relationship between different ribonucleic acids (RNAs) and tumor immunity has been widely investigated. However, a systematic description of tumor immune-related RNAs in different tumors is still lacking. We collected the relationship of tumor immune-related RNAs from the published literature and presented them in a user-friendly interface, "ImmRNA" (http://www.immrna.cn/), to provide a resource to study immune-RNA-cancer regulatory relations. The ImmRNA contains 49 996 curated entries. Each entry includes gene symbols, gene types, target genes, downstream effects, functions, immune cells, and other information. By rearranging and reanalyzing the data, our dataset contains the following key points: (i) providing the links between RNAs and the immune in cancers, (ii) displaying the downstream effects and functions of RNAs, (iii) listing immune cells and immune pathways related to RNA function, (iv) showing the relationship between RNAs and prognostic outcomes, and (v) exhibiting the experimental methods described in the article. ImmRNA provides a valuable resource for understanding the functions of tumor immune-related RNAs. Database URL:  http://www.immrna.cn/.

The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells.

BACKGROUND: Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3'-phospoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC). RESULTS: Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin. CONCLUSIONS: These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target.

Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis.

BACKGROUND: Emerging evidence suggests that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors and may contribute to the etiology of diabetes. OBJECTIVES: This study aimed to systematically review the epidemiological evidence on the associations of PFAS with mortality and morbidity of diabetes and to quantitatively evaluate the summary effect estimates of the existing literature. METHODS: We searched three electronic databases for epidemiological studies concerning PFAS and diabetes published before April 1, 2022. Summary odds ratio (OR), hazard ratio (HR), or ß and their 95% confidence intervals (CIs) were respectively calculated to evaluate the association between PFAS and diabetes using random-effects model by the exposure type, and dose-response meta-analyses were also performed when possible. We also assessed the risk of bias of the studies included and the confidence in the body of evidence. RESULTS: An initial literature search identified 1969 studies, of which 22 studies were eventually included. The meta-analyses indicated that the observed statistically significant PFAS-T2DM associations were consistent in cohort studies, while the associations were almost non-significant in case-control and cross-sectional studies. Dose-response meta-analysis showed a "parabolic-shaped" association between perfluorooctanoate acid (PFOA) exposure and T2DM risk. Available evidence was rated with "low" risk of bias, and the level of evidence for PFAS and incident T2DM was considered "moderate". CONCLUSIONS: Our findings suggest that PFAS exposure may increase the risk of incident T2DM, and that PFOA may exert non-monotonic dose-response effect on T2DM risk. Considering the widespread exposure, persistence, and potential for adverse health effects of PFAS, further cohort studies with improvements in expanding the sample size, adjusting the covariates, and considering different types of PFAS exposure at various doses, are needed to elucidate the putative causal associations and potential mode of action of different PFAS on diabetes. IMPACT STATEMENT: A growing body of evidence suggests that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors and may contribute to the development of diabetes. However, epidemiological evidence on the associations of PFAS and diabetes is inconsistent. We performed this comprehensive systematic review and meta-analysis to quantitatively synthesize the evidence. The findings of this study suggest that exposure to PFAS may increase diabetes risk among the general population. Reduced exposure to these "forever and everywhere chemicals" may be an important preventative approach to reducing the risk of diabetes across the population.

Better or worse? The prognostic role of the mesenchymal subtype in patients with high-grade serous ovarian carcinoma: A systematic review and meta-analysis.

BACKGROUND: Tumor characteristics can be prognostically relevant in patients with high-grade serous ovarian carcinoma (HGSOC). This study aimed to determine whether different subtypes of HGSOC, especially the mesenchymal subtype, are associated with overall survival (OS) or progression-free survival (PFS) in patients with HGSOC. METHODS: PubMed, Embase, and the Cochrane Library were searched for studies published up to September 2020. The eligibility criteria were (1) population: patients with HGSOG with molecular subtyping of their tumor, (2) exposure: mesenchymal subtype, (3) non-exposure: differentiated, immunoreactive, proliferative, and other non-mesenchymal subtypes, (4) outcome: survival, with hazard ratios (HRs), and (5) English language. RESULTS: The mesenchymal subtype showed no statistically significant difference in OS compared with the immunoreactive subtype (HR = 1.47, 95% CI: 0.78-2.78, p = 0.238; I2  = 81.2%, pheterogeneity  = 0.005) or all non-mesenchymal subtypes (HR = 1.65, 95% CI: 0.97-2.80, p = 0.063; I2  = 79.4%, pheterogeneity  = 0.008). The mesenchymal subtype showed no statistically significant difference in PFS compared with the immunoreactive subtype (HR = 1.19, 95% CI: 0.71-2.00, p = 0.514; I2  = 71.6%, pheterogeneity  = 0.030) but a significant differences was observed when using all non-mesenchymal subtypes as reference (HR = 1.51, 95% CI: 1.00-2.28, p = 0.049). The results were robust according to the sensitivity analyses. CONCLUSIONS: There are no statistically significant differences in OS between the mesenchymal subtype of HGSOC and other subtypes of HGSOC. Because of statistical power, this meta-analysis cannot conclude about non-inferiority, and the relationship between the molecular subtypes and HGSOC prognosis remains controversial. Based on one study, the mesenchymal subtype could have a poorer PFS than the non-mesenchymal subtypes of HGSOC, but this conclusion requires further evidence.

Association Between Exposure to Per- and Polyfluoroalkyl Substances and Birth Outcomes: A Systematic Review and Meta-Analysis.

Background: A large body of emerging evidence suggests that per- and polyfluoroalkyl substances (PFAS) affect birth outcomes in various pathways, but the evidence is inconsistent. Therefore, this study aimed to systematically review the epidemiological evidence on PFAS exposure and birth outcomes. Methods: Three electronic databases were searched for epidemiological studies through February 13, 2021. We used random-effects meta-analysis for eight birth outcome indicators to calculate summary effect estimates for various exposure types. The risk of bias and the overall quality and level of evidence for each exposure-outcome pair were assessed. Results: The initial search identified 58 potentially eligible studies, of which 46 were ultimately included. Many PFAS were found to have previously unrecognized statistically significant associations with birth outcomes. Specifically, birth weight (BW) was associated with PFAS, with effect sizes ranging from -181.209 g (95% confidence interval (CI) = -360.620 to -1.798) per 1 ng/ml increase in perfluoroheptanesulfonate (PFHpS) to -24.252 g (95% CI = -38.574 to -9.930) per 1 ln (ng/ml) increase in perfluorodecaoic acid (PFDA). Similar patterns were observed between other PFAS and birth outcomes: perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with birth length (BL) and ponderal index (PI), PFOS and perfluorododecanoic acid (PFDoDA) with head circumference (HC), PFHpS with gestational age (GA), and perfluorononanoic acid (PFNA) and PFHpS with preterm birth (PTB). Additionally, PFDA showed a statistically significant association with small for gestational age (SGA). The level of the combined evidence for each exposure-outcome pair was considered to be "moderate". Conclusion: This study showed that PFAS exposure was significantly associated with increased risks of various adverse birth outcomes and that different birth outcome indicators had different degrees of sensitivity to PFAS. Further studies are needed to confirm our results by expanding the sample size, clarifying the effects of different types or doses of PFAS and the time of blood collection on birth outcomes, and fully considering the possible confounders.

Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer.

BACKGROUND: Several reports indicated that the expression of Yes-associated protein (YAP) was associated with multi-drug resistance. Acidic microenvironment increased by the overexpression of vacuolar-ATPase (V-ATPase) was also observed in tumor growth and drug resistance. We hypothesize that proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. Thus, our objective is to explore the reversal of drug resistance by the inhibition of YAP through specific PPIs in the epithelial ovarian carcinoma (EOC) cells. . RESULTS: We found that V-ATPase D1 was a positive regulator of YAP. Sub-lethal doses of the proton pump inhibitor esomeprazole (EMSO) in combination with paclitaxel (PTX) increased the PTX sensitivity in PTX-resistant EOC cells, as compared to PTX single treatments by inhibiting YAP and reserving pH gradient created by the V-ATPase D1. Moreover, sub-lethal doses of EMSO combined with PTX decreased autophagy and improved caspases independent apoptosis of PTX-resistant EOC cells. CONCLUSIONS: These results suggested that sub-lethal doses of esomeprazole reverse YAP-mediated PTX resistance through the inhibiting of both YAP expression and acidic tumor microenvironment created by the V-ATPase D1. Therefore, we think the use of PPIs represents a promising strategy to improve the effectiveness of anti-EOC.

A case report for severe hand-foot skin reaction caused by chemotherapy with actinomycin D in a patient with oculocutaneous albinism.

Gestational trophoblastic neoplasms (GTN) are highly curable tumors, with an overall patient survival of 90%, due to the individualized chemotherapy. However, chemotherapy regimens vary between different treatment centers and the comparable benefits and risks of these different regimens are unclear. Here, we reported a case of GTN with oculocutaneous albinism (OCA) is resistant to fluorouracil (5-FU), extremely sensitive to actinomycin D (Act-D) with severe hand-foot skin reaction (HFSR). We hypothesized that the known, or unknown, gene mutations might be correlated with drug resistance, supersensitivity and severe drug side effects in OCA patients. Thus, we considered that OCA related genes influence some drug sensitivity and that the absence of melanin likely contributes to some drug resistance. It is important to assess the OCA related gene mutations locus of drug sensitivity, and resistance in OCA patients in future research.

A single nucleotide polymorphism in the MTOR gene is associated with recurrent spontaneous abortion in the Chinese female population.

Recurrent spontaneous abortion (RSA) is a multi-factor disease. The mammalian target of the the rapamycin (MTOR) gene has been reported to be involved in mouse embryo development and regulates the proliferation of embryonic stem cells. Our study explored the relationship between the single nucleotide polymorphism (SNP) rs17027478 in the promoter region of MTOR gene and the development of RSA. A total of 306 patients with RSA and 127 healthy females as the controls were recruited in the case-control study. The predesigned TaqMan SNP Genotyping Assay was adopted to analyze the association between rs17027478 and the development of RSA. Quantitative real-time reverse transcription polymerase chain reaction and luciferase reporter assays were conducted to analyze the function of the variant. It was found that a significant association exists between the variant and the risk of RSA among the patients who experienced no less than three spontaneous abortions (p = 0.043). However, the significant difference disappeared among the total samples (p = 0.524). Furthermore, we observed lower MTOR mRNA levels in the blood of RSA patients compared with healthy females (p = 0.020). The luciferase reporter assay showed that the rs17027478A allele significantly reduced the luciferase activity (p = 0.029). The results demonstrated that the variant rs17027478 in the promoter region of MTOR might be a good candidate responsible for the pathogenesis of RSA. Abbreviations RSA recurrent spontaneous abortion MTOR mammalian target of rapamycin SNP single nucleotide polymorphism qRT-PCR quantitative real-time polymerase chain reaction URSA unexplained recurrent spontaneous abortion mTORC1 mTOR complex 1 ESC embryonic stem cells HKE-293 human embryonic kidney 293 cells HWE Hardy-Weinberg equilibrium ANOVA one-way analysis of variance.

Association of polymorphisms in the estrogen receptor ß (ESR2) with unexplained recurrent spontaneous abortion (URSA) in Chinese population.

OBJECTIVES: To investigate the association of 1082G > A(RsaI) (rs1256049) and 1730A > G(AluI) (rs4986938) single nucleotide polymorphisms(SNPs), respectively - located on estrogen receptor ß (ESR2) gene with recurrent spontaneous abortion (RSA) in Chinese population. METHODS: The study group consisted of 196 patients with RSA and 182 fertile women as control. Two functional polymorphisms 1082G > A (a silent mutation in exon 5) and 1730A > G (3' nontranslated region of the exon 8) of ESR2 were studied by association analysis. RESULTS: There were no significant differences between ESR2 gene polymorphisms and RSA (χ(2) =1.793, P=0.408; χ(2) =.432, P=0.489, respectively). CONCLUSION: The present data indicate that the studied SNPs on ESR2 gene may not be associated with RSA in Chinese population.

[Clinical application of in vitro maturation of human immature oocytes for infertile women with polycystic ovary syndrome].

OBJECTIVE: To investigate clinical effect and safety of in vitro maturation (IVM) of human immature oocytes in infertile women with polycystic ovary syndrome by comparing with conventional in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI). METHODS: From Jan. 2003 to Dec. 2009, 157 infertile women with PCOS underwent 162 cycles IVM in Center for Reproductive Medicine, the First Affiliated Hospital of Anhui Medical University. In the mean time, 109 patients with PCOS underwent 114 IVF/ICSI cycles as control group 1 and 106 patients with other factors underwent 106 IVF/ICSI cycles as control group 2. Treatment and outcome of pregnancy and infant were compared among those 3 groups. RESULTS: No statistically significant difference were found in terms of the positive rate of hCG in urine [35.7% (56/157), 42.2% (46/109), 44.3% (47/106)], the rate of clinical pregnancy [29.3% (46/157), 37.6% (41/109), 41.5% (44/106)], the rate of entopic pregnancy [1.9% (3/157), 1.8% (2/109), 0.9% (1/106)], the rate of miscarriage [18.6% (8/43), 12.8% (5/39), 20.9% (9/43)] and the rate of live-birth [22.3% (35/157), 31.2% (34/109), 32.1% (34/106)] among three groups (IVM group, control group 1, control group 2, P > 0.05). The rate of preterm labor, low weight newborn, mean birth weight, ratio of male to female did not show significantly difference among 3 groups (P > 0.05). The average control ovarian stimulation was 6 days, the median dose of gonadotropin (Gn) was 675 IU, and the total hospital cost was (8392 ± 1328) RMB in IVM group, which were statistically lower than those in the other two control groups (P < 0.01). The rate of multiple pregnancy was 4.7% (2/43) and ovarian hyperstimulation syndrome (OHSS) 0 in IVM group, which were significantly lower than those in the other control group (P < 0.01). CONCLUSION: In vitro maturation is an effective treatment in infertile women with PCOS, it could obtain the similar pregnancy outcome and reduce total cost, the dosage of gonadotropin-releasing hormone and rate of OHSS compared with conventional IVF/ICSI.

[Association between recurrent miscarriages and insulin resistance: a meta analysis].

OBJECTIVE: To evaluate the association between recurrent miscarriages and insulin resistance. METHODS: The case-control studies on the association between recurrent spontaneous abortion and insulin resistance from June 1996 to April 2012 were collected from Medline, Elsevier, Chinese Journal Full-text Database, Chinese Biological Medicine Database, data base of Wanfang, Springer link and EMBASE. RevMan 5.1 software was used for Meta analysis. RESULTS: According to the included criteria, 7 clinical trials were finally selected. Total 467 cases with recurrent pregnancy loss were enrolled in study group, while 413 women with no history of abnormal pregnancies were enrolled in control group. No significant difference was found in average age and body mass index between the two groups (P > 0.05). Meta analysis results showed that the level of fasting glucose was no statistical difference between study group and control group (WMD = 2.27, 95%CI: -1.11 to 5.65, P > 0.05); fasting insulin level was higher 2.05 mU/L in study group than that of in control group, the difference was statistically significant (WMD = 2.05, 95%CI: 1.03 to 3.08, P < 0.01). Case number of study group on Homa-insulin resistance > 4.5 was more than that of control group (OR = 3.36, 95%CI: 1.72 to 6.57, P < 0.01). Case number of study group on glucose/insulin ratio < 4.5 was more than that of the control group, statistical difference was found (OR = 3.37, 95%CI: 1.90 to 5.99, P < 0.01). CONCLUSION: Insulin resistance is associated with the susceptibility to recurrent miscarriages, and it may contribute to the occurrence of recurrent miscarriages.