MiR-5195-3p functions as a tumor suppressor by targeting RHBDD1 in ovarian cancer.

BACKGROUND: Recent studies have reported the tumor suppressive role of miR-5195-3p in the progression of several cancers, but the potential roles of miR-5195-3p in ovarian cancer (OC) remain largely unknown. METHODS: We first analyzed the expression levels of miR-5195-3p in 83 pairs of human OC tissues and adjacent specimens by reverse transcription-quantitative PCR. The correlation of miR-5195-3p/rhomboid domain containing 1 (RHBDD1) and clinicopathological parameters was analyzed by chi-square test. The prognostic value of miR-5195-3p was evaluated by Kaplan-Meier method Cox proportional hazards models. The effects of miR-5195-3p on cell proliferation, cell cycle distribution, migration and invasion were examined by CCK-8 assay, colony formation assay, flow cytometry and transwell assay. Tumor forming was evaluated by nude mice model in vivo. The association between miR-5195-3p and RHBDD1 was verified by luciferase reporter assay. RESULTS: We observed that miR-5195-3p level was remarkably reduced in OC tissues as compared to adjacent tissues. The expression of miR-5195-3p was associated with FIGO stage, depth of invasion and poor survival prognosis in OC patients. Overexpression of miR-5195-3p significantly suppressed cell proliferation, cell cycle G1/S transition, migration and invasion in OC cell lines (SKOV-3 and OVCAR3), while knockdown of miR-5195-3p obtained the opposite results. We further confirmed miR-5195-3p as a negative post-transcriptional modulator of RHBDD1. RHBDD1 expression was upregulated in OC tissues compared with adjacent tissues, which was inversely correlated with miR-5195-3p expression. The expression of RHBDD1 was associated with FIGO stage and distant metastasis. RHBDD1 overexpression reversed the suppressive role of miR-5195-3p on OC cell proliferation, migration and invasion. Consistent with the in vitro results, miR-5195-3p overexpression decreased the growth of subcutaneously inoculated tumors in nude mice. CONCLUSIONS: Taken together, the present results indicated that miR-5195-3p acts a tumor suppressor by targeting RHBDD1 in OC.

KIAA0101 promotes cisplatin resistance through regulating cell apoptosis in lung cancer cells.

Lung cancer is one of the most server mortality in the world and remains a huge threat to human health. Recently, cisplatin-based chemotherapy represented a common therapeutic strategy, however, cisplatin resistance greatly limits the therapy efficacy. We investigated whether KIAA0101 plays a role in cisplatin resistance of lung cancer cells and its mechanisms of action. The expression of KIAA0101 was evaluated based on comprehensive bioinformatic analysis. KIAA0101 knockdown and overexpression A549 cells were constructed to investigate its effects on cell proliferation and apoptosis induced by cisplatin treatment. Western blot analysis was performed to measure the levels of p53-related apoptosis proteins. We found that KIAA0101 was greatly increased in lung cancer tissues and cells. Knockdown of KIAA0101 suppressed cell proliferation and increased cisplatin-induced apoptosis. Knockdown of KIAA0101 also augmented the cisplatin-induced cell apoptosis signaling pathway. Then p53 was found to account for the role of KIAA0101 in cisplatin resistance. In conclusion, our findings provide a novel factor of KIAA0101 in lung cancer resistance, which suggests as a novel target for lung cancer therapy.

Lentinan Attenuates Damage of the Small Intestinal Mucosa, Liver, and Lung in Mice with Gut-Origin Sepsis.

This study is aimed at exploring the effects of lentinan on small intestinal mucosa as well as lung and liver injury in mice with gut-origin sepsis. Cecal ligation and perforation (CLP) were used to construct a mouse model of gut-origin sepsis. The mice were randomly divided into six groups: sham operation group (sham), gut-origin sepsis model group (CLP), ulinastatin-positive drug control group (UTI), lentinan low concentration group (LTN-L, 5 mg/kg), lentinan medium concentration group (LTN-M, 10 mg/kg), and lentinan high concentration group (LTN-H, 20 mg/kg). H&E staining was used to detect the pathological damage of the small intestine, liver, and lung. The serum of mice in each group was collected to detect the expression changes of inflammatory cytokines, oxidative stress biomarkers, and liver function indexes. In vitro assessment of bacterial translocation was achieved through inoculated culture media. Western blot and RT-qPCR were used to detect the expression of molecules related to the NF-κB signaling pathway in the small intestine tissues of mice. The results showed that compared with the CLP group, the injury degree of the small intestine, liver, and lung in mice with gut-origin sepsis was improved with the increase of lentinan concentration. In addition, TNF-α, IL-1ß, IL-6, and HMGB1 were decreased with the increase of lentinan concentration, but the expression of IL-10 was increased. Lentinan could also reduce the expression of oxidative stress injury indexes and liver function indexes and inhibit bacterial translocation to liver and lung tissues. Further mechanism investigation revealed that lentinan downregulated the expression of the NF-κB signaling pathway molecules (NF-κB, TLR4, and Bax) and upregulated the expression of occludin and Bcl-2. In conclusion, lentinan inhibits the activity of the NF-κB signaling pathway, thus attenuating injuries of small intestinal mucosa and liver and lung in mice with gut-origin sepsis and reducing the inflammatory response in the process of sepsis.

The mid-domain effect and habitat complexity applied to elevational gradients: Moss species richness in a temperate semihumid monsoon climate mountain of China.

The utility of elevational gradients as tools to test either ecological hypotheses and delineate elevation-associated environmental factors that explain the species diversity patterns is critical for moss species conservation. We examined the elevational patterns of species richness and evaluated the effects of spatial and environmental factors on moss species predicted a priori by alternative hypotheses, including mid-domain effect (MDE), habitat complexity, energy, and environment proposed to explain the variation of diversity. Last, we assessed the contribution of elevation toward explaining the heterogeneity among sampling sites. We observed the hump-shaped distribution pattern of species richness along elevational gradient. The MDE and the habitat complexity hypothesis were supported with MDE being the primary driver for richness patterns, whereas little support was found for the energy and the environmental factors.

Polymorphisms in the Uncoupling Protein 2 Gene Are Associated with Diabetic Retinopathy in Han Chinese Patients with Type 2 Diabetes.

BACKGROUND: The uncoupling protein 2 (UCP2) gene plays an important role in the complications of type 2 diabetes (T2D). However, the association between variants in the UCP2 gene and diabetic retinopathy (DR) in Han Chinese T2D patients remains unclear. METHODS: Two single-nucleotide polymorphisms (SNPs) [rs659366 (-866G/A) and a 45-bp insertion/deletion (I/D) in the 3'-UTR] in the UCP2 gene were genotyped in a study cohort of 209 T2D patients with DR and 199 T2D patients without DR by direct DNA sequencing. RESULTS: Logistic regression analysis showed that the AA and GA genotypes of rs659366 were significantly associated with an increased risk for nonproliferative DR (NPDR) in the codominant model (corrected p-value <0.01) and the dominant model (corrected p-value = 0.006). Patients harboring the II and DI genotypes had a higher risk for PDR in the codominant model (corrected p-value = 0.011) and the dominant model (corrected p-value = 0.006), and the DI genotype showed a higher risk for NPDR in the dominant model (corrected p-value = 0.007) or codominant model (corrected p-value = 0.006). Further, haplotype analyses verified that the A-I haplotype is a risk haplotype for NPDR and PDR. CONCLUSION: This study suggests that the UCP2 gene may be involved in the pathogenesis of NPDR and PDR in Han Chinese patients with T2D.

Suppression of atom motion and metal deposition in mixed ionic electronic conductors.

Many superionic mixed ionic-electronic conductors with a liquid-like sublattice have been identified as high efficiency thermoelectric materials, but their applications are limited due to the possibility of decomposition when subjected to high electronic currents and large temperature gradients. Here, through systematically investigating electromigration in copper sulfide/selenide thermoelectric materials, we reveal the mechanism for atom migration and deposition based on a critical chemical potential difference. Then, a strategy for stable use is proposed: constructing a series of electronically conducting, but ion-blocking barriers to reset the chemical potential of such conductors to keep it below the threshold for decomposition, even if it is used with high electric currents and/or large temperature differences. This strategy not only opens the possibility of using such conductors in thermoelectric applications, but may also provide approaches to engineer perovskite photovoltaic materials and the experimental methods may be applicable to understanding dendrite growth in lithium ion batteries.

Traditional Chinese medicine integrated with chemotherapy for stage IV non-surgical gastric cancer: a retrospective clinical analysis.

OBJECTIVE: Traditional Chinese medicine (TCM) is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS: In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status (KPS) score were measured as the main outcome. RESULTS: The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups (χ2 = 42.244, P > 0.001). After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively (P > 0.001). The Cox regression analysis showed that TCM treatment is a protective factor for patients' overall survival. CONCLUSION: This study demonstrated that TCM integrated with chemotherapy may prolong overall survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer.

Clinical features and surgical procedures of congenital vaginal atresia-A retrospective study of 67 patients.

OBJECTIVE: To explore the characteristics of congenital vaginal atresia, further improve its classification, and therefore help the clinical diagnosis and treatment of congenital vaginal atresia. METHODS: This was a retrospective study of 67 patients with congenital vaginal atresia (from March 1984 to March 2015). Clinical and surgical characteristics were analyzed. RESULTS: For lower vaginal atresia, 25 patients successfully underwent vaginoplasty at the lower portion of the vagina. For complete vagina atresia, 25 patients with type i cervical atresia were treated with artificial vaginoplasty+tracheloplasty, and all showed no dysmenorrhea within six months after surgery. Four patients with type ii cervical atresia and two patients with type iii cervical atresia successfully underwent hysterectomy+artificialvaginoplasty. Two patients with type iv cervical atresia underwent combined abdominoperineal artificial vaginoplasty+tracheloplasty. One patient with upper vaginal atresia successfully underwent hysterectomy via the narrow segment of the cervix. Three patients with top vaginal atresia had no dysmenorrhea after transvaginaltracheloplasty. CONCLUSION: This study suggests two new categories of vaginal atresia (upper vaginal atresia and top vaginal atresia), which could be used as a reference for treatment of this condition. Appropriate treatments were performed using a personalized approach and satisfactory results were achieved.

Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes.

Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1ß, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

Complete mtDNA genomes reveal similar penetrances of maternally inherited type 2 diabetes in two Chinese families.

Previous work suggests that mitochondrial DNA (mtDNA) derived from the maternal genome has a close affinity with type 2 diabetes. This would support a familial pattern for type 2 diabetes. Thereby, we analyzed complete mtDNA genomes from two families, A and B, from Southwest China that demonstrated maternally inherited type 2 diabetes. Our data support that mtDNA lineages from families A and B belong to haplogroups A4 and D4h1, respectively. This suggests that maternally inherited type 2 diabetes with similar penetrances can arise in Chinese individuals with strikingly different maternal genetic backgrounds. Two private coding region mutations (G13759A in MT-ND5 and G15930A in tRNA-Thr) were identified in family B. Further evolutionary and phylogenetic analyses suggest that both these mutations have multiple origins and are unlikely to be disease causing.

Clinical characteristics of congenital cervical atresia based on anatomy and ultrasound: a retrospective study of 32 cases.

BACKGROUND: To explore the clinical characteristics of congenital cervical atresia. METHODS: This retrospective analysis included 32 cases of congenital cervical atresia treated from March 1984 to September 2010. The anatomic location, ultrasonic features, surgical treatments, and outcomes were recorded. RESULTS: Based on clinical characteristics observed during preoperative ultrasound and intraoperative exploration, congenital cervical atresia was divided into four types. Type I (n?=?22/32, 68.8%) is incomplete cervical atresia. Type II (n?=?5/32, 15.6%) defines a short and solid cervix with a round end; the structure lacked uterosacral and cardinal ligament attachments to the lower uterine body. Type III (n?=?2/32, 6.3%) is complete cervical atresia, in which the lowest region of the uterus exhibited a long and solid cervix. Type IV (n?=?3/32, 9.4%) defines the absence of a uterine isthmus, in which no internal os was detected, and a blind lumen was found under the uterus. CONCLUSIONS: Observations of clinical characteristics of congenital cervical atresia based on the anatomy and ultrasound may inform diagnosis and treatment strategy.

Difference in risk behaviors and STD prevalence between street-based and establishment-based FSWs in Guangdong Province, China.

The major mode of HIV/AIDS transmission in China is now heterosexual activities, but risk for HIV and sexually transmitted diseases (STDs) may differ among different strata of female sex workers (FSWs). Respondent-driven sampling was used to recruit 320 FSWs in Guangdong Province, China. The respondents were interviewed using a structured questionnaire, and tested for HIV, syphilis, gonorrhea, and Chlamydia. The street-based FSWs had lower education levels, a higher proportion supporting their families, charged less for their services, and had engaged in commercial sex for a longer period of time than establishment-based FSWs. The proportion consistently using condoms with clients and with regular non-paying partners was also lower. The prevalence of syphilis, gonorrhea, and Chlamydia was higher among street-based sex workers. Being a street-based sex worker, having regular non-paying sex partners, and having non-regular non-paying partners were independent risk factors for inconsistent condom. Street-based FSWs had more risk behaviors than establishment-based FSWs, and should therefore be specifically targeted for HIV as well as STD intervention programs.

Prevalence of HIV and STIs and associated risk factors among female sex workers in Guangdong Province, China.

OBJECTIVES: To assess the prevalence of HIV and sexually transmitted infections (STIs) and associated factors among female sex workers (FSWs) in Guangdong, China. METHODS: Respondent-driven sampling was used to recruit 320 FSWs. The recruited participants were interviewed face-to-face using a structured questionnaire and tested for HIV, syphilis, gonorrhea, and Chlamydia. RESULTS: The prevalence of syphilis, gonorrhea, and Chlamydia were 8.0% (4.6%-12.2%), 9.5% (5.6%-14.3%), and 3.9% (1.7%-6.2%), respectively, and of any STIs was 19.7% (13.9%-26.2%). None of the participants were HIV positive. The median number of clients during the previous week was 5. The proportion of consistent condom use with the clients during the previous week was 58.0% (50.4%-65.5%), use with regular nonpaying partners and nonregular nonpaying partners were much lower than that with clients. Multivariate analysis indicated that years of education and perception of HIV risk were protective factors. Awareness of HIV/AIDS; regular sex partners deciding about condom use when having sex; recruiting clients at hotels, hair/beauty salons, or streets instead of massage parlors; and higher charge for last sexual service were associated with STI infection. CONCLUSIONS: Future intervention programs should not only address personal risk factors but also empower FSWs to require condom use by both clients and nonpaying partners.

Increasing HIV prevalence among drug users in western Guangdong province, China, 1995-2005.

Sentinel surveillance data from 1995 to 2005 for drug users in Guangdong province, China, showed an increasing prevalence of HIV in the West region while stabilizing in the East and Center. Several factors were significantly associated with HIV infection including gender, age, sharing needles, years injecting, engaging in commercial sex, and being part of the migrant population of Guangdong. Data help effectively prioritize and target HIV prevention efforts for drug users.

Potential bridges for HIV infection to men who have sex with men in Guangzhou, China.

To assess the potential for HIV acquisition among men who have sex with men (MSM) in Guangzhou, China, we conducted a cross-sectional, anonymous, face-to-face survey of MSM in the metropolitan area of Guangzhou, China. As a pilot recruitment for a cohort study, participants were recruited by convenience sampling through newspaper and television advertising, website information, and respondent referral. Blood samples were tested for HIV, hepatitis B (HBV), hepatitis C (HCV), and syphilis. Client-centered HIV and STD counseling was provided.A total of 201 MSM were interviewed and 200 blood samples were tested. The prevalence of HIV antibody was 0% (97.5% CI 0-1.8%); 17.5% of MSM were HBV surface antigen positive; 1.0% had HCV antibodies; 10.5% had antibodies to syphilis. Syphilis seropositivity was associated with sex with a foreign MSM in the last six months and 10.4% reported sex with a foreign MSM overall. The majority (54.7%) reported unprotected anal sex with other men. Nearly one-third (31.8%) had regular female partners; 25.9% were currently married to a woman; 6% had casual female partners; 4.5% had sex with a female sex worker; 4.5% had sex with a male sex worker; and 12.9% had unprotected vaginal sex and unprotected anal sex with a man in the past six months. Only one MSM reported injection drug use (0.5%). The currently low prevalence of HIV but high level of unprotected anal sex, high prevalence of syphilis infection, and sexual networks that include foreign MSM point to a transient window for HIV prevention among MSM in Guangzhou. We recognize challenges to recruiting a representative sample of MSM and retaining them in longitudinal cohort studies.

[Evaluation of a pilot study on needle and syringe exchange program among injecting drug users in a community in Guangdong, China].

OBJECTIVE: To evaluate the feasibility and effectiveness of needle and syringe exchange program among a community of injecting drug users (IDUs) on AIDS prevention. METHODS: A quasi-experiment design was used in a controlled community intervention study. Needle and syringe exchange program was implemented for 10 months in IDUs of an intervention community, including peer education and health education, provision of free needles and syringes, and collecting back of used needles and syringes by trained peer educators and local health workers, whereas no intervention measure in a control community was instituted. Interviews with IDUs were conducted before and after intervention with a snowballing strategy to evaluate its effectiveness. RESULTS: A total of 428 and 429 IDUs were interviewed with structured questionnaire before and after intervention in intervention and control communities, respectively. Results revealed that awareness of HIV-related knowledge increased from 29.4% to 58.7% in the intervention community. Multivariate logistic regression analysis showed that awareness of HIV-related knowledge was higher in those who had read health education materials (OR = 2.93, 95% CI 2.12 - 4.04). As compared with the baseline data, frequency of sharing needles and syringes in past 30 days in the intervention community decreased from 48.9% to 20.4% in before intervention community (chi(2) = 41.02, P = 0.001), whereas there was no significant change in the control community. The causes of sharing needles and syringes in the intervention community included 'disable to get needle and syringe during the night', 'lack of needle and syringe when injecting at friend's home', 'not daring to buy needle and syringe for fear of being arrested' and 'no money to buy needle and syringe', declined markedly. CONCLUSIONS: Needle and syringe exchange program was feasible and effective in reducing their risky drug injecting behavior among IDUs in communities. Such strategy should be adopted in the country to reduce rapid spread of HIV.

[Severe acute respiratory syndrome in Guangdong Province of China: epidemiology and control measures].

OBJECTIVE: To explore epidemiological features and risk factors of severe acute respiratory syndrome (SARS) in Guangdong Province of China, so as to work out effective strategies for its better control. METHODS: A total of 1 511 clinically confirmed SARS cases in Guangdong Province of China from November 16, 2002 to Jun 15, 2003 were retrospectively analyzed. RESULTS: The first SARS case was identified in Foshan municipality on November 16, 2002, followed by 1 511 clinically confirmed cases (including 58 deaths) up to May 15, 2003. Of all cases, health care workers and community family cluster cases accounted for 19.38% and 12.04%. 65.86% SARS patients aged 20 - 49 years, and increased incidence was positively related to their ages. 95.97% cases lived in the following five cities around Pearl Delta Area: Foshan, Guangzhou, Shenzhen, Zhongshan, and Jiangmen. Eleven early reported cases in the communities took animal-related positions. Face-to-face contacts with infected droplets were the main transmission route. An epidemic peak occurred during January 28 to February 26, and those cases accounted for 50.69% of total. Incidence, mortality, and case fatality of SARS were 1.77/100,000, 0.07/100,000, and 3.84% respectively. The mean incubation period was 4.5 days. CONCLUSION: The most effective way to control SARS is to break the chain of transmission from infected to healthy persons-early identification, prompt and effective isolation, and vigorous close contact tracing. Hospital infections among health care workers is critical. Several observations support the hypothesis of an animal origin for the disease.