Search

Simple Summary: Ovarian cancer is commonly associated with poor survival; patients with a diagnosis of high-grade serous ovarian carcinoma (HGSC) have an overall survival of 39% at 5 years. For reasons not well known, about 32% of ovarian cancer patients survive 10 years or more. In this study, our goal was to determine the molecular differences that drive long-term survival (LTS) in patients with HGSC. Indeed, this study shows that patients with LTS have a distinct pattern of gene expression, with TMEM62 being related to LTS. Increased TMEM62 expression led to decreased proliferation of ovarian cancer cells in vitro and decreased tumor burden in vivo. Despite having similar histologic features, patients with high-grade serous ovarian carcinoma (HGSC) often experience highly variable outcomes. The underlying determinants for long-term survival (LTS, ≥10 years) versus short-term survival (STS, <3 years) are largely unknown. The present study sought to identify molecular predictors of LTS for women with HGSC. A cohort of 24 frozen HGSC samples was collected (12 LTS and 12 STS) and analyzed at DNA, RNA, and protein levels. OVCAR5 and OVCAR8 cell lines were used for in vitro validation studies. For in vivo studies, we injected OVCAR8 cells into the peritoneal cavity of female athymic nude mice. From RNAseq analysis, 11 genes were found to be differentially expressed between the STS and LTS groups (fold change > 2; false discovery rate < 0.01). In the subsequent validation cohort, transmembrane protein 62 (TMEM62) was found to be related to LTS. CIBERSORT analysis showed that T cells (follicular helper) were found at higher levels in tumors from LTS than STS groups. In vitro data using OVCAR5 and OVCAR8 cells showed decreased proliferation with TMEM62 overexpression and positive correlation with a longevity-regulating pathway (KEGG HSA04213) at the RNA level. In vivo analysis using the OVCAR8-TMEM62-TetON model showed decreased tumor burden in mice with high- vs. low-expressing TMEM62 tumors. Our results demonstrate that restoring TMEM62 may be a novel approach for treatment of HGSC. These findings may have implications for biomarker and intervention strategies to help improve patient outcomes [ABSTRACT FROM AUTHOR]

Background: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. Methods: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). Results: Five hundred and ten patients were included and grouped based on dosage as A (0.10–0.14 mg/kg/week), B (0.15–0.16 mg/kg/week), C (0.17–0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). Conclusions: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15–0.20 mg/kg/week might be preferred. Trial registration: ClinicalTrials.gov: NCT03249480, retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The human immunodeficiency virus (HIV) continues to be one of the major public health challenges in the world. Despite the advancement in medication and changes in views towards HIV in Chinese society, little is known about the changes in the psychosocial and mental health of HIV‐positive women in recent years. Objectives: The present study examined the change in depression, anxiety, stigma, relationship with the child, intimacy with a partner, and social support from family, friends, and health professionals, for HIV‐positive women in China from 2015 to 2020. Methods: Two cross‐sectional surveys were conducted in 2015 and 2020, and 429 and 382 HIV‐positive women were recruited from the Women's Health Department in Yunnan and Guangxi, China between November 2015 to May 2016, and November 2019 to January 2020, respectively. Results: After controlling for significant sociodemographic variables, participants recruited in 2019–2020 had significantly lower levels of depression and anxiety and higher scores on emotional and tangible support from friends. On the other hand, they had lower scores in intimacy with partners and emotional and tangible support from family. No significant changes were found in stigma, relationship with the child, and support from health professionals. Conclusion: Results provide important information on the changes in psychosocial and mental health, which offer insights into the design of interventions to promote psychosocial and mental health among HIV‐positive women in China. Patient or Public Contribution: HIV‐positive women contributed to the data of this study. Health care professionals were involved in the discussion of the methods and results. [ABSTRACT FROM AUTHOR]

Objective Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. Methods A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. Results After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048–0.715, P  = 0.014; HR = 0.435, CI: 0.234–0.812, P  = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P  = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers. Conclusions Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation. [ABSTRACT FROM AUTHOR]

Background: This population-based cross-sectional study aimed to evaluate the prevalence of oral mucosal lesions (OMLs) in children in a rural area in China as epidemiological data on these conditions from such areas are insufficient. Methods: A total of 3145 children in Xiangyun of Yunnan were enrolled. A socio-economic questionnaire and a field survey of OMLs were administered. We gathered information on factors (sex, age, caregiver, parental education, and last-month household income) that might be associated with OMLs in these children. Results: OMLs in children in Xiangyun of Yunnan had a prevalence of 1.8% (95% CI; 1.3–2.3%). The most prevalent OML was oral ulcer (n = 11; 18.3%), followed by linea alba (n = 10; 16.7%), whereas the least prevalent OMLs were frenal tag (n = 1; 1.7%) and herpes labialis (n = 1; 1.7%). On unadjusted or adjusted regression, school-aged children had about 50% lower risk of OMLs than preschoolers. Conclusions: These findings indicate that the prevalence of OMLs in Xiangyun of Yunnan is lower than previously reported. Additionally, the age might be associated with the occurrence of OMLs in children in Xiangyun of Yunnan, China. [ABSTRACT FROM AUTHOR]

Objective. To study the correlation between Traditional Chinese Medicine (TCM) constitution and dyslipidemia. Methods. CNKI, VIP, Wanfang database, CBMdisc, PubMed, and Embase were searched, and meta-analysis was performed by Review Manager 5.2 software. Results. Altogether 11 studies were included with 12890 individuals. The results showed that balanced constitution was a protective factor of dyslipidemia (OR = 0.62, 95% CI 0.47~0.82) while phlegm-dampness constitution was a risk factor of it (OR = 2.50, 95% CI 2.22~2.80), and the effect of phlegm-dampness constitution in South China (OR = 3.31, 95% CI 1.71~6.43) was more obvious than that in East (OR = 2.40, 95% CI 2.06~2.80) and North China (OR = 2.24, 95% CI 1.81~2.78). Conclusion. This study provides evidence for the prevention and treatment of dyslipidemia in TCM. However, most of the studies included are of moderate quality; more high quality, multicenter, large-sample studies are expected to provide higher level evidence. [ABSTRACT FROM AUTHOR]

In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α. [ABSTRACT FROM AUTHOR]

The medicinal plant Ferula has been widely used in Asian medicine, especially in Uyghur medicine in Xinjiang, China. Given that various substitutes and closely related species have similar morphological characteristics, Ferula is difficult to distinguish based on morphology alone, thereby causing confusion and threatening the safe use of Ferula. In this study, internal transcribed spacer 2 (ITS2) sequences were analyzed and assessed for the accurate identification of two salable Ferula species (Ferula sinkiangensis and Ferula fukangensis) and eight substitutes or closely related species. Results showed that the sequence length of ITS2 ranged from 451 bp to 45 bp, whereas guanine and cytosine contents (GC) were from 53.6% to 56.2%. A total of 77 variation sites were detected, including 63 base mutations and 14 insertion/deletion mutations. The ITS2 sequence correctly identified 100% of the samples at the species level using the basic local alignment search tool 1 and nearest-distance method. Furthermore, neighbor-joining tree successfully identified the genuine plants F. sinkiangensis and F. fukangensis from their succedaneum and closely related species. These results indicated that ITS2 sequence could be used as a valuable barcode to distinguish Uyghur medicine Ferula from counterfeits and closely related species. This study may broaden DNA barcoding application in the Uyghur medicinal plant field. [ABSTRACT FROM AUTHOR]

Objective Rheumatoid arthritis (RA) is an inflammatory and angiogenic disease. However, the molecular mechanisms that promote angiogenesis in RA have not been clearly identified. Our objective was to study the role of CD147 in angiogenesis and determine whether the strategy in which CD147 is suppressed might be useful in reducing angiogenesis in RA. Methods Correlations among expression levels of CD147, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were determined by immunohistochemistry staining. RA fibroblast-like synoviocytes (FLS) cells were cultured under various conditions, and the production of VEGF and HIF-1α was examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The SCID mouse coimplantation model of RA (SCID-HuRAg) was established, mice were treated with CD147 monoclonal antibody, infliximab, or both CD147 and infliximab, and the volume of the grafts and the average vascular density were measured and analyzed. Western blot analyses were performed to examine the potential signaling pathways. Results The expression levels of CD147 showed significantly positive correlations with VEGF and HIF-1α levels, as well as with vascular density, in RA synovium. After small interfering RNA transfection or after addition of specific antibodies for CD147, the production of VEGF and HIF-1α were significantly reduced. The expression of VEGF and HIF-1α decreased more after CD147 inhibition than after infliximab treatment in the engrafted tissues in SCID-HuRAg mice. The phosphatidylinositol 3-kinase/Akt pathway may be involved in this process. Conclusion CD147 induces up-regulation of VEGF and HIF-1α in RA FLS, further promotes angiogenesis, and leads to the persistence of synovitis. Inhibition of CD147 may be a promising target for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]