A Follow-Up Study of Ovarian Cancer (OOPS): A Study Protocol.

The ovarian cancer (OC) follow-up study (OOPS) is an on-going hospital-based large prospective longitudinal cohort study aimed to explore the relationship between pre/post-diagnostic biological, clinical, environmental, and lifestyle factors with focus on the diet and OC prognosis (including drug resistance, relapse, and mortality). Patients recruited during the baseline survey were between 18 and 79 years old, with histologically confirmed OC diagnosis. Their follow-up and medical treatment were conducted at the gynecological oncology ward at Shengjing Hospital of China Medical University, Shenyang, China after 2015. A total of 703 OC patients made up the final OOPS study population. The follow-up stage was conducted in both passive and active modes. In the passive mode, the follow-up was performed by linkage to the Liaoning Providence Center for Disease Control and Prevention every 6 months to obtain health outcome results. The status of lifestyle factors was re-estimated using the same measurements as those in the baseline survey. OC participants in the OOPS study completed a questionnaire and anthropometric examinations. In addition, biological specimens were collected during the baseline survey, which included blood, urine, and stool samples that were stored for further use. This article is intended to serve as an introduction to this project and to provide details for investigators who may be carry out related analysis.

Shift work and health outcomes: an umbrella review of systematic reviews and meta-analyses of epidemiological studies.

STUDY OBJECTIVES: Shift work is commonly increasing, and some physiological changes occur as workers sleep less and their circadian rhythms are disrupted. This umbrella review not only summarizes the evidence but also evaluates the validity of the associations of shift work with different health outcomes. METHODS: We searched the MEDLINE, Web of Science, and Embase databases from their inception to April 25, 2020. For each systematic review and/or meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. RESULTS: Eight eligible systematic reviews and meta-analyses were identified, providing data on 16 associations. We observed highly suggestive evidence for associations between shift work and myocardial infarction (having ever vs having never done shift work) and diabetes mellitus incidence (per 5-year increment in shift work). Furthermore, we observed suggestive evidence for an association between shift work and diabetes mellitus incidence (having ever vs having never done shift work). Two health outcomes, including prostate cancer incidence (having ever vs having never done shift work and rotating night shift work vs daytime work) and colorectal cancer incidence (longest vs shortest shift work time), were only supported by weak evidence. CONCLUSIONS: This umbrella review found that shift work was associated with several health outcomes with different levels of evidence. Associations for myocardial infarction and diabetes mellitus incidence were supported by highly suggestive evidence. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; Identifier: CRD42020188537. CITATION: Wu Q-J, Sun H, Wen Z-Y, et al. Shift work and health outcomes: an umbrella review of systematic reviews and meta-analyses of epidemiological studies. J Clin Sleep Med. 2022;18(2):653-662.

Isothiocyanate Iberin inhibits cell proliferation and induces cell apoptosis in the progression of ovarian cancer by mediating ROS accumulation and GPX1 expression.

Ovarian cancer (OC) is one of the most common gynecologic malignancies with poor survival rate, and Iberin is a member of isothiocyanate family with anti-tumor activity. However, the role of Iberin in OC development has not been reported yet. In this study, A2780 and OVCAR-3 cells were treated with gradient concentrations of Iberin to investigate the effect of Iberin on OC in vitro. Meanwhile, the in vivo tumorgenesis experiment was performed using female BALB/c nude mice treated with Iberin. Iberin inhibited cell proliferation, induced G2 cell cycle arrest and promoted cell apoptosis in OC cells. Besides, Iberin reduced GSH/GSSG level, enhanced ROS accumulation, and activated MAPK signaling in OC cells. More interestingly, ROS scavenger (NAC) compensated the anti-proliferative and pro-apoptotic effects of Iberin on OC cells, suggesting the involvement of ROS in the regulation of Iberin on OC cell growth. Notably, Iberin induced down-regulation of glutathione peroxidase-1 (GPX1), and over-expression of GPX1 reversed Iberin-mediated alterations in the proliferation, apoptosis and ROS accumulation of OC cells. The in vivo tumorgenesis study further evidenced the protection of Iberin against OC development. Besides, Iberin displayed a synergistic effect on the enhancement of chemo-sensitivity in OC cells. In summary, our study demonstrates the anti-tumor effect of Iberin on OC and its potential as a therapeutic agent against OC in the future.

Application of machine learning in prediction of Chemotherapy resistant of Ovarian Cancer based on Gut Microbiota.

Background: Ovarian cancer (OC) has the highest mortality among gynecological malignancies, and resistance to chemotherapy drugs is common. We aim to develop a machine learning approach based on gut microbiota to predict the chemotherapy resistance of OC. Methods: The study included patients diagnosed with OC by pathology and treated with platinum and paclitaxel in Shengjing Hospital of China Medical University between 2017 and 2018. Fecal samples were collected from patients, and 16S rRNA sequencing was used to analyze the differences in gut microbiota between OC patients with and without chemotherapy resistance. Nine machine learning classifiers were used to derive the chemotherapy resistance of OC from gut microbiota. Results: A total of 77 chemoresistant OC patients and 97 chemosensitive OC patients were enrolled. The gut microbiota diversity was higher in OC patients with chemotherapy resistance. There were statistically significant differences between the two groups in Shannon indexes (P <0.05) and Simpson indexes (P <0.05). Machine learning techniques can predict the chemoresistance of OC, and the random forest showed the best performance among all models. The area under the ROC curve for RF model was 0.909. Conclusions: The diversity of gut microbiota was higher in OC patients with chemotherapy resistance. Further studies are warranted to validate our findings based on machine learning techniques.

Chinese herbal medicine Shenzhuo Formula treatment in patients with macroalbuminuria secondary to diabetic kidney disease: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is a serious complication associated with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) is widely used in China to treat DKD, and in particular microalbuminuria and macroalbuminuria. This study will address the efficacy and safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients with macroalbuminuria. METHODS/DESIGN: This study is a 24-week, randomized, multi-center, double-blinded, double-dummy, controlled, clinical trial that will include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24-h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) ≤ 133 µmol/L (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to week 24 will represent the primary endpoint with secondary endpoints including SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin excretion rate (UAER), etc. Safety assessments will also be evaluated. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of SZF relative to irbesartan in the treatment of DKD patients with macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311 . Registered on 15 April 2015.

[PCR products with heterozygous mutations containing two types of heteroduplexes].

OBJECTIVE: To confirm that PCR products with heterozygous mutations contain not only wide-type and mutant homoduplexes, but also two types of heteroduplexes. METHODS: An insertion-deletion mutation in the exon 1 of KRT9 gene (497delAinsGGCT), which caused Chinese epidermolytic palmoplantar keratoderma (EPPK) was investigated by polymerase chain reaction (PCR), polyacrylamide gel electrophoresis (PAGE) and denaturing high-performance liquid chromatography(DHPLC). RESULTS: Two heteroduplexes and two homoduplexes in the PCR product from the heterozygous mutation of the exon 1 of KRT9 (497delAinsGGCT) were detected. CONCLUSION: PCR products from KRT9 gene with heterozygous mutations contain two types of heteroduplexes. It is without the need to perform heating and cooling PCR products obtained from heterozygous mutations in advance before the mutation screening steps such as denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE), conformation-sensitive gel electrophoresis (CSGE), DHPLC and heteroduplex analysis (HA), etc.

[Present status of the molecular genetics in epidermolytic palmoplantar keratoderma].

In this article we reviewed the current researches on the molecular basis of epidermolytic palmoplantar keratoderma (EPPK) and the structure and function of the keratins with mutations that can cause inherited keratin disorders. Also summarized are seventeen mutations of keratin 9 in EPPK in different ethnic populations.

102T/C SNP in the 5-hydroxytryptamine receptor 2A (HTR2A) gene and schizophrenia in two southern Han Chinese populations: lack of association.

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter that occupies a uniquely important place in neurobiology because of its role in many physiologic processes such as sleep, appetite, thermoregulation, pain perception, hormone secretion, and sexual behavior. Serotonin dysfunction has been implicated in the pathogenesis of schizophrenia. Previous studies have shown an association between the T102C polymorphism of the 5-hydroxytryptamine receptor 2A (HTR2A) gene and schizophrenia. However, many negative findings have also been reported. We analyzed the T102C polymorphism of HTR2A of schizophrenic patients in two southern Chinese populations (n = 291) and matched controls (n = 307). No significant positive association was observed between either of the polymorphisms and all schizophrenics, nor was the polymorphisms and any population of schizophrenia. These data did not provide evidence for a contribution of the 102T/C SNP of HTR2A gene to susceptibility to the southern Han Chinese schizophrenia.