[Research progress on the application of specially lense related to myopia prevention and control].

In order to decelerate the growth of myopia in children and adolescents and reduce the risks of associated eye complications, extensive research has been conducted on preventive measures, including optical, behavioral, and pharmaceutical interventions. Spectacle lenses, due to their safety, convenience, and high patient compliance, stand out as the most common method for correcting refractive errors compared to other interventions. As far as we know, various forms of spectacle lenses are currently used in clinical practice, including bifocal lenses, progressive multifocal lenses, peripheral defocus lenses, defocus incorporated multiple segments (DIMS) lenses, highly aspherical lenslets, diffusion optics technology lenses, and violet light transmission (VL) glasses. However, a systematic and comprehensive overview of myopia-controlling spectacle lenses is still lacking. Therefore, this article summarizes the latest research progress on the myopia prevention and control technology of spectacle lenses at home and abroad, providing theoretical support for the myopia prevention and control effect of different spectacle lens technologies, promoting the application of related technologies in clinical work, and offering new ideas for myopia prevention and control.

[The comparison between endoscopic and surgical treatment of delayed iatrogenic bile duct injury by propensity score matching].

Objective: To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2. Methods: The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged (M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test,χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results: There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675,P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group(P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%,P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups(P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups(P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5,P=0.037). Conclusions: For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.

Comparation of quality of life in Chinese patients undergoing leadless versus conventional pacemaker implantation.

BACKGROUND: Leadless pacemakers are widely used, but the quality of life assessment of patients with leadless pacemakers is still unclear. HYPOTHESIS: Assume that leadless pacemakers can improve the patients' quality of life. METHODS: Total of 119 patients who received pacemaker implantation at Beijing Anzhen Hospital from January 2020 to March 2022 were selected, including 35 leadless pacemakers and 84 conventional pacemakers. The SF-36 questionnaire was used to evaluate quality of life at baseline, 1 month and 3 months after surgery. We also used a questionnaire consisted of 4 specific questions related to the implant procedure to assess the surgery. RESULTS: There were no differences in baseline characteristics between the two groups, except for age and oral anticoagulant treatment. There was no difference in baseline SF-36 scores. At the 3-month follow-up, patients in leadless pacemakers group were significantly better at physical function (63.63 vs 47.50, p = .000), role physical (60.20 vs 40.23, p = .000), bodily pain (65.57 vs. 61.69, p = .042), physical component summary (61.25 vs. 50.57, p = .000), vitality (56.26 vs 49.57, p = .001), social function (80.14 vs 74.70, p = .004), role emotional (76.14 vs. 71.42, p = .015), mental health (75.46 vs. 68.18, p = .000), mental component summary (72.00 vs. 65.97, p = .000), even after adjusting for clinical baseline and SF-36 baseline. Pacemaker-related discomfort and mobility limitations were significantly reduced in leadless pacemakers group. CONCLUSIONS: Leadless pacemakers is associated with better quality of life with less activity limitations due to surgical discomfort and less emotional distress. However, current use of leadless pacemakers in China is limited due to the high cost.

A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.

BACKGROUND: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely. AIM: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures. METHODS: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS). FINDINGS: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (CT) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed. CONCLUSION: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak.

[Clinical observation of surgical resection combined radiofrequency in patients with CNLC â ¡a~â ¢a stage multiple hepatocellular carcinoma].

Objective: To investigate the effects of four therapeutic methods in the comprehensive treatment of China liver cancer staging (CNLC)Ⅱa~Ⅲa stage multiple hepatocellular carcinoma. Method: A retrospective study was conducted to collect clinical data of patients with multiple hepatocellular carcinoma (CNLC stage Ⅱa-Ⅲa), who received transhepatic arterial chemoembolization (TACE group, 73 cases), radiofrequency ablation (RFA group, 70 cases), TACE combined RFA (TACE combined RFA group, 69 cases) and surgical resection combined RFA (surgical resection combined RFA group, 57 cases) in the First Hospital of Lanzhou University from January 11, 2010 to January 31, 2017. The general data of age, gender, primary tumor, and laboratory examination were collected. The differences in overall survival rates and the survival rates among stratified subgrouping with different clinical factors between the four groups of patients were compared by the Kaplan-Meier method. Cox proportional hazards regression model analyzed the prognostic factors. Result: A total of 269 patients were enrolled and there were 194 males and 59 females with a median age of 58 years ranging from 23 to 84. The TACE group's 1, 3, and 5-year survival rates were 43.5%, 10.2%, and 0, respectively. The RFA group were 46.3%, 17.7%, and 0, respectively. The TACE combined RFA group were 56.8%, 21.5%, and 2.3%, respectively. The surgical resection combined RFA group was 76.5%, 38.7%, and 3.8%, respectively. The surgical resection combined RFA group has the best outcome(P<0.05). Univariate analysis showed that surgery combined RFA, tumor diameter<5 cm, no vascular invasion, preoperative AFP≤400 µg/L and TB<34 µmol/L are protective factors to improve the survival prognosis of patients with CNLCⅡa~Ⅲa stage multiple hepatocellular carcinoma(HR=0.784,0.718,0.633,0.846,0.617;all P<0.05). Multivariate Cox analysis showed that surgery combined RFA, tumor diameter<5 cm, preoperative AFP≤400 µg/L were independent risk prognostic factors for CNLCⅡa-Ⅲa stage multiple hepatocellular carcinoma (HR=0.702,0.743,0.647;all P<0.05). Conclusions: Surgical resection combined RFA is an effective method for the treatment of stage Ⅱa-Ⅲa hepatocellular carcinoma. Surgical resection combined RFA has more advantages in treatment patients with complicated hepatocellular carcinoma whose diameter<5 cm, tumor number<3, and preoperative AFP≤400 µg/L. Surgical resection combined RFA, tumor diameter<5 cm, preoperative AFP≤400 µg/L are independent influencing factors for the survival prognosis of patients with complicated hepatocellular carcinoma.

[Mutation of RAS gene in follicular-differentiated thyroid tumors and its significance].

Objective: To investigate the frequency and clinical significance of RAS mutation in thyroid tumors with follicular differentiation. Methods: The samples and clinical data of 207 patients with thyroid follicular-differentiated tumors were collected at Shunyi Region Hospital of Beijing from January 2000 to December 2017, including 60 cases of follicular variant of papillary thyroid carcinoma (FVPTC), 42 cases of classical papillary thyroid carcinoma (CPTC), 26 cases of follicular thyroid carcinoma (FTC), 40 cases of follicular adenoma (FTA) and 39 cases of adenomatoid hyperplasia. BRAF V600E mutations were detected using immunohistochemical staining. FVPTC was divided into BRAF-like (BRAF V600E mutant) and RAS-like (without BRAF V600E mutant). Real-time fluorescence quantitative polymerase chain reaction was used to detect the RAS mutation in RAS-like FVPTC, CPTC, FTC, FTA and adenomatoid hyperplasia. The genetic differences in RAS mutation and their correlation with clinicopathological features were analyzed. Results: The average age of patients with benign and malignant tumors in thyroid with follicular differentiation was 53.2 years and 47.7 years, respectively. In these patients, 42 were male and165 were female. Most of the tumors had a maximum diameter of less than 4 cm, and rarely spread to the surrounding tissues of thyroid and were at early stage (stages Ⅰ and Ⅱ). The diameter of tumors in FTC was significantly larger than that in RAS-like FVPTC and CPTC groups (P<0.01). Peripheral thyroid invasion was rare in the RAS-like FVPTC, CPTC and FTC groups, but the clinical stage of FTC was more advanced than that of RAS-like FVPTC group (P<0.01) or CPTC group (P<0.01). The real-time fluorescence quantitative PCR showed that the RAS mutation rate in FTC was the highest (61.5%), significantly higher than that in others (P<0.01). The RAS mutation rate in CPTC was the lowest (4.8%), while those in RAS-like FVPTC, FTA and adenomatous hyperplasia were similar (about 15%). The Spearman rank correlation analysis showed that the RAS mutation was not correlated with age, sex or tumor size in benign lesions (FTA and adenomatous hyperplasia), nor was it associated with age, sex, tumor size, lymph node metastasis, spreading of tumors to thyroid and clinical stage in malignant tumors (RAS-like FVPTC, CPTC and FTC). Conclusions: RAS mutation can occur in both benign and malignant thyroid tumors with follicular differentiation, in which the incidence is the highest in FTC. Both morphologic and immunohistochemical changes should be taken into account. The molecular genetics of RAS-like FVPTC is similar to FTA and adenomatous hyperplasia. RAS gene mutation appears not to be a prognostic factor for thyroid diseases.

[Traditional nasal therapy in Uighur medicine].

Nasal therapy, extensively documented in the ancient Uighur medical literature, is one of the external therapies of Uighur medicine. Based on the relevant records of 14 Uighur medical works, the application, classification, clinical features, and medications characteristics of nasal therapy were preliminarily sorted out. The results show that the nasal therapy can be divided into 7 categories, covering more than 200 kinds of common medicinal herbs, 8 kinds of processing methods and 10 kinds of preparations. Clinically, there is a large number of nasal therapy prescriptions, with flexible administration of prescriptions and medications, significant features of comprehensive therapy, with significance of application for further development.

Combined effects of land reclamation, channel dredging upon the bioavailable concentration of polycyclic aromatic hydrocarbons (PAHs) in Victoria Harbour sediment, Hong Kong.

The up-to-date concentration of polycyclic aromatic hydrocarbons (PAHs) in sediment materials of Victoria Harbour was investigated so as to evaluate the pollution potential associated with the reclamation projects in Hong Kong. A total of 100 sediment samples were collected at 20 locations. Except the control point in reservoir, the PAHs concentrations were detectable levels all sites (131-628.3ng/g, dw) and such values were higher than Dutch Target and Intervention Values (the New Dutch standard in 2016). The PAHs concentration indicating that construction waste and wastewater discharges were the main pollutant sources. Results of correlation in single cell gel electrophoresis assay (comet assay) studies also revealed that the PAHs concentration was highly correlated (<0.01) with DNA migration (i.e. the length of tail moment of fish cells) in 5mg/ml of PAHs. The above observation indicates that the PAHs present in the sediment may substantially effect the marine ecosystem. Although the dredged sediment can be a useful sea-filling material for land reclamation; however, the continuing leaching of PAHs and its impact on the aquatic environment need to be studied further.

[Abnormality of TOP2A expression and its gene copy number variations in neuroblastic tumors].

Objective: To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors (NT). Methods: Immunohistochemistry was used to detect TOP2A protein expression. Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A. Results: TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation (P=0.006), Ki-67 index (P<0.01) and MKI (P=0.001). Twenty-eight cases (35.0%, 28/88) showed TOP2A gene amplification, which was correlated with the age (P<0.01), clinical stage (P=0.028), high risk group (P=0.001), Ki-67 index (P=0.040) and differentiation (P=0.014). Survival analysis showed that TOP2A expression was related to survival rate. Multivariate analyses showed that TOP2A expression was an independent predictor for poor prognosis (P=0.010). Conclusions: More than half of the cases show TOP2A expression, which is more likely associated with NB, high Ki-67 index and high MKI. Cases with TOP2A expression have shorter survivals and poorer prognosis. TOP2A amplification is seen in 35% and likely occurs in patients older than 18 months and at advanced INSS stages (Ⅲ and Ⅳ). As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.

Inhibition of mTOR complex 2 induces GSK3/FBXW7-dependent degradation of sterol regulatory element-binding protein 1 (SREBP1) and suppresses lipogenesis in cancer cells.

Cancer cells feature increased de novo lipogenesis. Sterol regulatory element-binding protein 1 (SREBP1), when presented in its mature form (mSREBP1), enhances lipogenesis by increasing transcription of several of its target genes. Mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, are master regulators of cellular survival, growth and metabolism. A role for mTORC1 in the regulation of SREBP1 activity has been suggested; however, the connection between mTORC2 and SREBP1 has not been clearly established and hence is the focus of this study. mTOR kinase inhibitors (for example, INK128), which inhibit both mTORC1 and mTORC2, decreased mSREBP1 levels in various cancer cell lines. Knockdown of rictor, but not raptor, also decreased mSREBP1. Consistently, reduced mSREBP1 levels were detected in cells deficient in rictor or Sin1 compared with parent or rictor-deficient cells with re-expression of ectopic rictor. Hence it is mTORC2 inhibition that causes mSREBP1 reduction. As a result, expression of the mSREBP1 target genes acetyl-CoA carboxylase and fatty-acid synthase was suppressed, along with suppressed lipogenesis in cells exposed to INK128. Moreover, mSREBP1 stability was reduced in cells treated with INK128 or rictor knockdown. Inhibition of proteasome, GSK3 or the E3 ubiquitin ligase, FBXW7, prevented mSREBP1 reduction induced by mTORC2 inhibition. Thus mTORC2 inhibition clearly facilitates GSK3-dependent, FBXW7-mediated mSREBP1 degradation, leading to mSREBP1 reduction. Accordingly, we conclude that mTORC2 positively regulates mSREBP1 stability and lipogenesis. Our findings reveal a novel biological function of mTORC2 in the regulation of lipogenesis and warrant further study in this direction.

Inhibition of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs response of cancer cells to DR5-mediated apoptosis and T cell-induced killing.

Inhibition of B-Raf/MEK/ERK signaling is an effective therapeutic strategy against certain types of cancers such as melanoma and thyroid cancer. While demonstrated to be effective anticancer agents, B-Raf or MEK inhibitors have also been associated with early tumor progression and development of secondary neoplasms. The ligation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with its receptor, death receptor 5 (DR5), leading to induction of apoptosis, offers a promising anticancer strategy. Importantly, this is also a natural immunosurveillance mechanism against cancer development. We previously demonstrated that activated B-Raf/MEK/ERK signaling positively regulates DR5 expression. Hence, our current work sought to address whether B-Raf/MEK/ERK inhibition and the consequent suppression of DR5 expression impede cancer cell response to DR5 activation-induced apoptosis and activated immune cell-induced killing. We found that both B-Raf (for example, PLX4032) and MEK inhibitors (for example, AZD6244 and PD0325901) effectively inhibited ERK1/2 phosphorylation and reduced DR5 levels in both human thyroid cancer and melanoma cells. Similar to the observed effect of genetic knockdown of the B-Raf gene, pre-treatment of cancer cell lines with either B-Raf or MEK inhibitors attenuated or abolished cellular apoptotic response induced by TRAIL or the DR5 agonistic antibody AMG655 or cell killing by activated T cells. Our findings clearly show that inhibition of B-Raf/MEK/ERK signaling suppresses DR5 expression and impairs DR5 activation-induced apoptosis and T cell-mediated killing of cancer cells. These findings suggest a potential negative impact of B-Raf or MEK inhibition on TRAIL- or DR5-mediated anticancer therapy and on TRAIL/DR5-mediated immune-clearance of cancer cells.

Epidemiology, diagnosis, surgical treatment and prognosis of the pancreatic neuroendocrine tumors: Report of 125 patients from one single center.

OBJECTIVE: The objective of the following study is to summarize the epidemiology of pancreatic neuroendocrine tumors (p-NETs) in our single institution, analyze the diagnostic characteristics, share the experience of surgical treatments and discuss the prognostic factors. METHODS: A retrospective collection and analysis of clinical data of 125 patients with p-NETs which were pathologically confirmed in our hospital from January 2002 to December 2012. RESULTS: A total of 125 patients of which 52 were males and 73 were females. Totally 92 patients had functional p-NETs, while non-functional p-NETs were diagnosed in 33 patients. The most common operative procedures performed were local resection of pancreatic tumor (47.2%), followed by distal pancreatectomy (29.6%). Thirty patients (28%) had post-operative complications, the most common of which was pancreatic fistula (22.4%). The overall survival rate at 5 years was 68.4%. The 5-year survival rate for patients with functional tumors was 75.1%, compared with 50.0% for those with non-functional tumors (P = 0.021). The survival time of patients with R0 resection was statistically longer than that of patients with Not R0 resection (P < 0.005). In univariate analysis, the most powerful predictors of poor outcome were gender, age, tumor size, functional status, surgical margins, lymph node invasion and distant metastasis. However only surgical margin and distant metastasis were significant predictors in multivariate analysis (P = 0.001, 0.047, respectively). CONCLUSION: p-NETs are an uncommon and heterogeneous group of tumors, with a rising incidence. Surgery is the most effective treatment. Surgical margin and distant metastasis were the most significant prognostic factors. Radical resection should be taken more into considerations.

Cushing Syndrome Caused by a Pancreatic Neuroendocrine Tumour and Its Pelvic Metastases.

Cushing's syndrome caused by an ectopic tumour secreting adrenocorticotropic hormone (ACTH) is not common. Furthermore, an ACTH-secreting panreatic neoplasm is extremely rare. We present a 27-year old female patient suffering from a pancreatic neuroendocrine tumour (p-NET) with extensive pelvic metastases, which could secrete ACTH and cause Cushing's syndrome. The postoperative pathologic examinations of this patient prompted pancreatic poorly differentiated neuroendocrine tumour with extensive metastases of bilateral ovarian, uterus and pelvic peritoneum. The immunohistochemical staining of her tumour tissues was positive for Chromogranin A, Synaptophysin and ACTH. The main aim of this article is to share the experience of her diagnosis and treatment and to review the relevant literature, with an emphasis on discussing the possible transfer modes. Moreover, we strongly suggest that a careful examination of pelvic cavity during the follow-up of patients diagnosed as ACTH-secreting p-NET should also be carried out.

Prevalence of musculoskeletal symptoms in relation to psychosocial factors.

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) represent a common occupational problem for healthcare workers throughout the world. However, few epidemiological studies have investigated the effect of psychosocial factors on WMSDs among different Chinese occupational groups. AIMS: To assess the prevalence of WMSDs and psychosocial risk factors contributing to them among miners and teachers in China. METHODS: WMSDs were assessed in 500 teachers and 500 miners using the modified Chinese version of the Standardized Nordic Questionnaire and the Copenhagen Psychosocial Questionnaire. Logistic regression analyses were conducted to estimate the associations between psychosocial factors and WMSDs. RESULTS: There was a 73% participation rate. During a 12-month period, the prevalence of WMSDs among teachers and miners was comparable (72% and 78%, respectively), but miners had a higher prevalence of WMSD-related absence. Multivariate analyses indicated stronger associations between high job demands and upper limbs (odds ratio [OR] 3.05, 95% confidence interval [CI]: 1.67-5.58), neck and shoulder (OR 1.82, 95% CI: 1.05-3.16) and lower limbs (OR 1.97, 95% CI: 1.12-3.49) symptoms among miners. Low job satisfaction was related to low back (OR 2.40, 95% CI: 1.42-4.07), neck and shoulder (OR 2.18, 95% CI: 1.26-3.78) and lower limb (OR 1.69, 95% CI: 1.01-2.89) symptoms among teachers. CONCLUSIONS: We found that WMSDs in the two populations presented different characteristics associated with their occupational features. This study provides further evidence that WMSDs occur commonly in both miners and school teachers in China.

Ginsenoside-Rb1 promotes adipogenesis through regulation of PPARγ and microRNA-27b.

Ginsenoside-Rb1 (Rb1), one of the bioactive components in ginseng extract, is recently reported to be able to promote adipogenesis and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Meanwhile, microRNA-27b (miR-27b) is also identified to regulate adipogenesis by targeting PPARγ2. In the present study, we attempted to link up the Rb1-promoted adipogenesis with PPARγ binding and miR-27b regulation. First, we demonstrated that GW9662, an antagonist of PPARγ, could block Rb1-induced 3T3-L1 differentiation with little toxicity towards cell proliferation. Then, expression levels for both of miR-27b and its primary transcript, pri-mir-27b, were found to decrease upon Rb1 treatment. Again, GW9662 could attenuate the inhibitory effect of Rb1 on both miR-27 and pri-mir-27b expression. Since Rb1 was demonstrated to have binding activity towards PPARγ, we thus speculate that Rb1 may act though PPARγ to downregulate mir-27b gene transcription and mature miR-27b activity, which in turn promotes PPARγ expression and adipogenesis. Enhancement on adipogenesis of adipose tissues is expected to prevent lipotoxicty in nonadipose tissues. Our data may give a better illustration to explain the antidiabetic effect of Rb1 and provide a hint on treatment of lipid related metabolic diseases in the future.

Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells.

We present evidence that the cisplatin-resistant human ovarian cancer lines, A2780S/CP1 (S/CP1), A2780S/CP3 (S/CP3) and A2780S/CP5 (S/CP5), derived by subjecting the sensitive A2780S ovarian cancer line to multiple rounds of cisplatin treatments followed by recovery and are resistant to 1, 3 and 5 µM cisplatin, respectively, have increased colony-forming ability and altered morphology that is consistent with enhanced motility, migration and invasiveness in vitro. The malignant phenotype progresses with increasing resistance and is associated with hyperactive epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (Erk)1/2 and janus kinases (Jaks), aberrant signal transducer and activator of transcription (Stat) 3 activation promoted by EGFR and Jaks, and epithelial-mesenchymal transition (EMT) in vitro. Survivin and FLIP anti-apoptotic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase activities are also elevated in the resistant cells. Accordingly, the ectopic expression of constitutively-active Stat3C in the sensitive A2780S cells diminished cisplatin sensitivity. The inhibition of EGFR or Stat3 activity repressed Survivin, VEGF and Vimentin expression and the colony-forming potential, viability, motility and migration of the resistant cells, and sensitized them to cisplatin. Analysis of human ovarian cancer patients' tumor tissues shows aberrantly-active EGFR and Stat3 that in certain cases correlate with Vimentin over-expression. Intra-peritoneal mouse xenograft studies revealed, compared with the sensitive A2780S line that had low tumor incidence restricted to the ovary, a high tumor incidence for the resistant S/CP3 and S/CP5 lines that formed tumor nodules at several locations on the small intestine and colon, and which responded poorly to cisplatin, but were sensitive to concurrent treatment with cisplatin and EGFR or Stat3 inhibitor. Hyperactive EGFR signaling through Stat3 and the Jak-Stat3 activity together promote ovarian cancer progression to cisplatin resistance and therefore represent targets for preventing the development of cisplatin resistance and the recurrent disease during cisplatin therapy in ovarian cancer.