Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.

BACKGROUND: Targeting DNA damage response (DDR) pathway is a cutting-edge strategy. It has been reported that Schlafen-11 (SLFN11) contributes to increase chemosensitivity by participating in DDR. However, the detailed mechanism is unclear. AIM: To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects. METHODS: To reach the purpose, eight esophageal squamous carcinoma cell lines, 142 esophageal dysplasia (ED) and 1007 primary esophageal squamous cell carcinoma (ESCC) samples and various techniques were utilized, including methylation-specific polymerase chain reaction, CRISPR/Cas9 technique, Western blot, colony formation assay, and xenograft mouse model. RESULTS: Methylation of SLFN11 was exhibited in 9.15% of (13/142) ED and 25.62% of primary (258/1007) ESCC cases, and its expression was regulated by promoter region methylation. SLFN11 methylation was significantly associated with tumor differentiation and tumor size (both P < 0.05). However, no significant associations were observed between promoter region methylation and age, gender, smoking, alcohol consumption, TNM stage, or lymph node metastasis. Utilizing DNA damaged model induced by low dose cisplatin, SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways, while inhibiting the ATM/CHK2 signaling pathway. Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor (AZD0156), both in vitro and in vivo. CONCLUSION: SLFN11 is frequently methylated in human ESCC. Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

Iodine status and its association with prevalence of thyroid diseases in adults from Jiangxi Province, China.

BACKGROUND: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). METHODS: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. RESULTS: The median UIC was 176.4 µg/L, and a significant difference was found in median UIC between men (182.45 µg/L) and women (169.25 µg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40-2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32-8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19-2.60; OR = 1.52, 95%CI: 1.04-2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = -0.44, P < 0.01) and TAI (r = -0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = -0.24, P > 0.05). CONCLUSION: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI.

Efficacy of different antibiotics in treatment of children with respiratory mycoplasma infection.

BACKGROUND: Respiratory infections in children are common pediatric diseases caused by pathogens that invade the respiratory system. Children are considerably susceptible to Mycoplasma pneumoniae infection. There has been widespread clinical attention on treatment strategies for this disease. AIM: To analyze the clinical efficacy of different antibiotics in treating pediatric respiratory mycoplasma infections. METHODS: We included 106 children with a confirmed diagnosis of respiratory mycoplasma infection who were admitted to our hospital from April 2017 to July 2019 and grouped them using a random number table. Among them, 53 children each received clarithromycin or erythromycin. The clinical efficacy of both drugs was evaluated and compared. We performed the multiplex polymerase chain reaction (MP-PCR) test and determined the MP-PCR negative rate in children after the end of the treatment course. We compared the incidence of toxic and side effects, including nausea, diarrhea, and abdominal pain; further, we recorded the length of hospitalization, antipyretic time, and drug costs. Additionally, we evaluated and compared the compliance of the children during treatment. RESULTS: The erythromycin group showed a significantly higher total effective rate of clinical treatment than the clarithromycin group. MP-PCR test results showed that the clarithromycin group had a significantly higher MP-PCR negative rate than the erythromycin group. Moreover, children in the clarithromycin group had shorter fever time, shorter hospital stays, and lower drug costs than those in the erythromycin group. The clarithromycin group had a significantly higher overall drug adherence rate than the erythromycin group. The incidence of toxic and side effects was significantly lower in the clarithromycin group than in the erythromycin group (P < 0.05). CONCLUSION: Our findings indicate that clarithromycin has various advantages over erythromycin, including higher application safety, stronger mycoplasma clearance, and higher medication compliance in children; therefore, it can be actively promoted.

The Effects of Acarbose on Non-Diabetic Overweight and Obese Patients: A Meta-Analysis.

INTRODUCTION: This systematic review aims to verify the efficacy of acarbose monotherapy in treating obese or overweight patients without diabetes. METHODS: In the study, we conducted a systematic search of the Pub-Med, EMBASE, Cochrane and Science Citation Index Expanded databases in search of clinical trials on acarbose treatment, overweight and obesity. The crucial inclusion criteria were as follows: (1) patients were diagnosed as overweight or obese (BMI ≥ 25 kg/m2); (2) randomized controlled trials (RCTs); (3) patients had undergone acarbose monotherapy or placebo control; (4) acarbose treatment had been carried out for at least 3 months. Exclusion criteria were as follows: (1) patients diagnosed with diabetes mellitus (DM); (2) patients had received a weight loss medication or surgery in the past 3 months; (3) papers not published in English; (4) repeated research results of the same experiment or repeated published documents. RESULTS: A total of 7 studies involving 132 in the acarbose group and 137 in placebo group, 269 subjects in total, were included in this meta-analysis. From the selected seven papers, we extracted the following clinical parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), body mass index (BMI), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density cholesterol (HDL) and fasting plasma glucose (FPG). An important finding of our research is that TG was the only significantly reduced parameter in the acarbose group. Weight mean difference (WMD) was - 0.21 (95% CI - 0.33, - 0.09) mmol/l between acarbose (P = 0.0006) and placebo patients. Reduction of BMI was also greater for acarbose than placebo subjects, although the discrepancy was not statistically significant (P = 0.56). Moreover, no hypoglycemia occurred in either the acarbose group or placebo group. A few subjects experienced gastrointestinal reactions, but these were mild and improved over time. Acarbose has no obvious influence on other metabolic indexes. CONCLUSION: Acarbose monotherapy is beneficial in reducing TG levels in obese or overweight patients and will not result in hypoglycemia during medication. The side effects of acarbose are mild.

Prevalence and associated factors of metabolic syndrome in adults: a population-based epidemiological survey in Jiangxi province, China.

BACKGROUND: Metabolic syndrome (MS) has abruptly increased in China in the past two decades, gradually representing an important public health threat over the years. Here, we firstly reported the prevalence and associated factors of metabolic syndrome in Jiangxi province, China. METHODS: A population-based cross-sectional survey was performed in Jiangxi province, China, from April to August 2015. MS was diagnosed by International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) criteria, respectively. Factors associated with MS were investigated by multivariate logistic regression. RESULTS: A total of 2665 residents aged over 18 years were enrolled, and 2580 effectively participated. According to IDF and CDS criteria, age-standardized prevalence of MS were 21.1 and 15.2% in all participants, respectively; prevalence were 19.6% or 17.1% in men, and 22.7% or 13.0% in women, based on these respective criteria. Rural participants had a significantly higher prevalence than urban individuals, so did rural females. Prevalence in males did not differ between rural and urban participants. Factors independently associated with MS were low education level and menopausal state. CONCLUSIONS: To the best of our knowledge, this was the latest study on MS prevalence in Jiangxi province. In conclusion, MS prevalence is high in Jiangxi province. Considering the unhealthy lifestyle, education is urgently needed to prevent the rapid increase of MS prevalence.

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS: Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Acute liver failure and infarction complicating TIPS placement.

Here in we report a case of acute liver failure with hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS). An upper gastrointestinal hemorrhage patient with a medical history of alcoholic cirrhosis underwent a TIPS procedure. One day after TIPS, his alanine aminotransferase and aspartate aminotransferase levels increased to 1214 U/L and 1511 U/L, respectively. Two days after TIPS, they peaked at alanine aminotransferase 8389 U/L and aspartate aminotransferase >7500 U/L, respectively. An emergent stent occlusion was performed on the second day. Portography showed that there were no portal vein branches or parenchymal stains on the edge of the right liver lobe. A CT scan demonstrated diffuse hepatic parenchyma, homogeneous hypodense lesion, and bilateral pleural effusion. The patient died of liver failure and multiple organ dysfunction syndrome 6 hours after the stent occlusion.

Effects of Beclin 1 overexpression on aggressive phenotypes of colon cancer cells.

Beclin 1 is involved in autophagy, differentiation, apoptosis and cancer progression, and functions as a haploinsufficient tumor suppressor gene. The aim of the present study was to elucidate the function of Beclin 1 in colon cancer. A Beclin 1-expressing plasmid was transfected into HCT-15 and HCT-116 cells, and the phenotypes and associated molecules were determined. Beclin 1 transfectants were subcutaneously injected into nude mice to determine tumor growth, and proliferation and apoptosis levels using Ki-67 immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. Beclin 1 overexpression inhibited viability as determined using a Cell Counting Kit-8 assay, inhibited migration and invasion as determined using a wound healing assay or Transwell assay, and lamellipodia formation by filamentous actin staining, induced autophagy as determined using electron microscopy, and light chain 3B (LC-3B) expression, and apoptosis as determined using Annexin V staining in the two cell lines (P<0.05). Beclin 1 induced G2 arrest of HCT-15 transfectants as determined using propidium iodide staining (P<0.05), whereas HCT-116 transfectants were arrested in G1 phase (P<0.05). The two transfectants exhibited increased expression of c-Myc, cyclin D1, ß-catenin, insulin-response element 1 and 78 kDa glucose-regulated protein compared with the control and mock cells as determined using the reverse transcription-quantitative polymerase chain reaction (P<0.05). Beclin 1 overexpression upregulated LC-3B and cyclin-dependent kinase 4 expression, but downregulated cyclin E expression of the cancer cell lines as determined using western blot analysis (P<0.05). Beclin 1 expression in vivo significantly suppressed the proliferation of colon cancer cells in xenograft models via inducing apoptosis by TUNEL, and inhibiting proliferation by Ki-67 expression (P<0.05). Beclin 1 overexpression may reverse aggressive phenotypes and suppress colon cancer tumor growth, and be employed as a target molecule for gene therapy of patients with colon cancer.

[Analysis on prescription rules of Chen Baogui's prescriptions for treating epigastric fullness based on data mining].

To summary and analyze the prescription rules of Professor Chen Baogui, a famous traditional Chinese medicine (TCM) doctor, for treating epigastric fullness. Professor Chen Baogui's prescriptions for treating epigastric fullness were collected and the treatment data were input into traditional Chinese medicine inheritance support system (TCMISS) to analyze the rules of the prescriptions by using data mining methods. Based on the screened 214 cases, the treatment experience of Professor Chen Baogui for treating epigastric fullness was summarized and analyzed. It was found that Professor Chen gave priority to recuperation of Qi activity. The results of four properties and five tastes showed Professor Chen's medication compatibility rules: one was simultaneous use of cold and warm drugs, and the other was simultaneous use of pungent drugs for dispersion and bitter drugs for purgation. In drug use, the basic prescriptions had the efficacy of promoting Qi circulation and regulating viscera function, additionally with the drugs with functions of eliminating digestion and inducing stagnation, activating blood circulation to dissipate blood stasis, replenishing Qi and nourishing Yin, tranquilizing mind, strengthening muscles and bones according to the TCM syndrome type. The clinical experience of Professor Chen for treating epigastric fullness was objectively summarized with the help of TCMISS, which was significant for analyzing and inheriting academic thinking and medication experience from famous TCM doctors.

Genome-wide identification of transcription factors that are critical to non-small cell lung cancer.

To systematically unveil transcription factors (TFs) that are critical to lung carcinogenesis, here we conducted a genome-wide lethality screening in non-small cell lung cancer (NSCLC) cells and reported that among the 1530 TFs tested, 21 genes were required for NSCLC cell proliferation and were negatively or positively associated with overall survival (OS) of patients with NSCLC. These included 11 potential tumor suppressing genes (AFF3, AhR, AR, CBFA2T3, CHD4, KANK2, NR3C2, PTEN, PRDM16, RB1, and STK11) and 10 potential oncogenic TFs (BARX1, DLX6, ELF3, EN1, ETV1, FOXE1, HOXB7, IRX4, IRX5, and SALL1). The expression levels of IRX5 were positively associated with OS of smoker and inversely associated with OS of non-smoker patients with lung adenocarcinoma. We showed that tobacco carcinogen benzo(a)pyrene (BaP) induced upregulation of IRX5 in lung epithelial cells, and Cyclin D1 was a downstream target of IRX5. Furthermore, silencing of IRX5 by lentivirus mediated transfection of short hairpin RNA significantly inhibited tumor growth in nude mice. These results indicate that tobacco smoke can modulate TFs to facilitate lung carcinogenesis, and inhibition of IRX5 may have therapeutic potentials in NSCLCs.

Comprehensive treatment with Chinese medicine in patients with advanced non-small cell lung cancer: A multicenter, prospective, cohort study.

OBJECTIVE: To determine whether additional Chinese medicine (CM) could prolong survival and improve the quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC) compared with Western medicine (WM) alone. METHODS: This was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage III-IV NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network (NCCN) guidelines. In the integrative medicine (IM) group, individualized CM (Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months. RESULTS: The median survival was 16.60 months in the IM group and 13.13 months in the WM group (P<0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group (P<0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course (P<0.05). CONCLUSIONS: Additional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio- and chemotherapy may be attenuated as CM is used in combination with conventional treatments.

Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH) were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05). According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM) than adenoma and carcinoma (p < 0.05). Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05). Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05), but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM) staging, differentiation or serum carcinoembryonic antigen (CEA) concentration (p > 0.05). Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05). Cox's model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05). It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

Testis-specific Fank1 gene in knockdown mice produces oligospermia via apoptosis.

Fank1 is exclusively expressed in the testis from the meiosis phase to the haploid phase of spermatogenesis. In this study, we examined the function of Fank1 by establishing a Fank1-knockdown transgenic mouse model. The apoptotic statuses of the testes of the transgenic mice were tested using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. The FANK1 consensus DNA-binding sequence was identified using cyclic amplification of sequence target (CAST) analysis. Differentially expressed genes were examined using microarray analysis. A reduction in sperm number and an increase in apoptotic spermatocytes were observed in Fank1-knockdown mice, and the apoptotic cells were found to be primarily spermatogonia and spermatocytes. The CAST results demonstrated that the consensus DNA-binding sequence was AAAAAG, in which the percentage occurrence of each base at each position ranged from 55 to 86%. This sequence was present in the promoter regions of 10 differentially expressed genes that were examined using microarray analysis. In total, 17 genes were differentially expressed with changes in their expression levels greater than twofold. The abnormal expression of Fank1 target genes that were regulated directly or indirectly by Fank1 reduced the number of sperm in the knockdown mice. Thus, FANK1 may play a pivotal role in spermatogenesis as a transcription factor.

High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time.

Mucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells. Previous in vitro studies have indicated that MUC2 promotes cancer growth and metastasis through a tumor-associated macrophage (TAM)-dependent mechanism. However, this mechanism has never been linked to clinical oncology, and its prognostic significance needed to be clarified. Here, we collected 102 consecutive ovarian cancer specimens and used the multiple immuno-histo-chemical/-fluorescent technique to determine the correlations between the MUC2 expression status, the ratio of M1/M2 TAMs and the densities of cyclooxygenase-2 (COX-2)(+) TAMs and COX-2(+) cancer cells. The Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to evaluate the prognostic influences of these parameters. As a result, we found that the MUC2 overexpression (immunostaining ++/+++) was significantly correlated with a reduced ratio of M1/M2 TAMs (p<0.001), an increased density of COX-2(+) TAMs (p<0.001) and an increased density of COX-2(+) cancer cells (p=0.017). Moreover, most of the M2 TAMs (93%-100%) and COX-2(+) TAMs (63%-89%) overlapped; and the COX-2(+) cancer cells were frequently observed near the COX-2(+) TAMs. In the Cox regression analysis, MUC2 overexpression was found to be an independent prognostic factor for ovarian cancer patients, of which the hazard ratio (HR) was 2.354 (95% confidence interval (CI): 1.031-10.707, p=0.005). Also, the reduced ratio of M1/M2 TAMs and the increased densities of COX-2(+) TAMs and COX-2(+) cancer cells were demonstrated to be the predictors of poor prognosis, among which the reduced M1/M2 ratio possessed the highest HR (1.767, 95% CI: 1.061-6.957, p=0.019). All these findings revealed that MUC2 can concurrently exert M2-polarizing and COX-2-inducing effects on TAMs, by which it causes an imbalanced TAM M1-/M2-polarization pattern and induces local PGE2 synthesis (in both TAMs and cancer cells). The positive feedback between local PGE2 synthesis and TAM M2-polarization accelerates ovarian cancer progression.

[Risk of cervical cancer and precancerous diseases in the oral HPV carriers].

OBJECTIVE: To evaluate the risk of the occurrence of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer in the oral HPV carriers through a population-based investigation in Shanghai. METHODS: A total of 1200 cases of outpatients who attended the annual cervical examination and 50 preoperational cases of inpatients with CINIII or invasive cervical cancer were enrolled from three clinical centers in Shanghai. The oral HPV infection was determined by real-time PCR. In 1200-case cross-sectional study, the incidence rate of CIN was compared between the oral HPV positive and negative cohort. In 1250-case case-control study, the positive rate of oral HPV DNA test was compared among normal control group, CINI-III, and invasive cancer case groups, and all odds ratio (OR) values were calculated, respectively. The HPV transmission-related demographic and behavioral characters of the oral HPV carriers were also analyzed. RESULTS: The oral HPV carriers accounted for 5.9% (71/1200) of the investigated outpatients. The oral HPV DNA positive rates were gradually increased with the cervical disease grades, which were 5.8% (68/1182, normal), 2/13 (CIN I), 1/5 (CINII), 31.4% (11/35, CINIII) and 5/15 (invasive cancer). In cross-sectional cohort studies, the relative risks (RR) of CINI,II were 2.9 and 4.0 for oral HPV carriers, respectively. In case-control study, the OR values for CINI-III and invasive cervical cancer were 3.1(95%CI: 1.6-10.1), 4.2(95%CI: 1.7-28.4), 7.1(95%CI: 4.8-19.8) and 10.1(95%CI: 3.2-32.1), respectively. The oral sex and multi-sexual partner were two major risk factors for the oral and cervical HPV co-infection, HPV-related cervical cancer and precancerous diseases according to behavioral analysis. CONCLUSIONS: There are complicated transmission pathways between oral and cervical HPV. Oral HPV carriers should be intensively followed up and their oral HPV infection and HPV-related cervical diseases should be treated together.

Overexpression of RPS6KB1 predicts worse prognosis in primary HCC patients.

RPS6KB1 (ribosomal protein S6 kinase, 70 kDa, polypeptide 1) plays a key role in regulating protein translation. The role of RPS6KB1 in HCC (hepatocellular carcinoma) has not been fully investigated. This study was undertaken to determine the clinicopathological features and prognostic value of RPS6KB1 in HCC. We examined RPS6KB1 expression in 30 paired liver cancer tissues and adjacent noncancerous tissues by reverse transcription real-time PCR and Western blotting. In addition, we analyzed RPS6KB1 expression in 87 HCC samples by immunohistochemistry. The expression of RPS6KB1 was significantly increased in cancer tissues. Clinicopathological analysis showed that the expression of RPS6KB1 was significantly correlated with tumor size, histopathologic classifications, and serum alpha-fetoprotein (AFP). Kaplan-Meier survival curves revealed that increased expression of RPS6KB1 correlated with poor prognosis of HCC patients. RPS6KB1 expression was an independent prognostic marker for overall survival of HCC patients by multivariate analysis. Our data suggest that RPS6KB1 may play an important role in the progression of HCC and could serve as a potential molecular target for HCC therapy.

Identification of a gene-expression signature for predicting lymph node metastasis in patients with early stage cervical carcinoma.

BACKGROUND: Pelvic lymph node metastasis (PLNM) is an important prognostic factor for patients with cervical carcinoma. The objective of this study was to identify a gene-expression signature that could predict PLNM in cervical carcinoma. METHODS: Eighty-eight women with cervical carcinoma with PLNM (n = 23) and without PLNM (n = 65) were divided randomly into a training group and a test group. An oligonucleotide microarray that contained probes for 1440 human cancer-related genes was fabricated in-house and was used to detect the gene expression profile of cervical carcinoma. The gene expression levels detected in the microarray were verified by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). RESULTS: A gene-expression signature for predicting PLNM was developed in patients from the training group, including 11 genes: ribosomal protein L35 (RPL35); thymosin ß 10 (TMSB10); tyrosine 3-mono-oxytenase/tryptophan 5-mono-oxygenase activation protein, ζ polypeptide (YWHAZ); biotinidase (BTD); lactate dehydrogenase A (LDHA); glucuronidase ß (GUSB); superoxide dismutase 2 (SOD2); nuclear receptor subfamily 3, group C, member 2 (NR3C2); fructosamine 3 kinase (FN3K); x-ray repair cross-complementing 4 (XRCC4); and wingless-type mouse mammary tumor virus integration site family member 2 (WNT2). In the test group, the signature's accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 91%, 90.9%, 93.9%, 83.3%, and 96.9%, respectively, for predicting PLNM. The expression levels of 5 genes in the signature were confirmed by qRT-PCR. A multivariate analysis demonstrated that patients with 11-gene high-risk scores were had a 33-fold increased risk for PLNM compared with patients who had low-risk scores. The 5-year overall and disease-free survival rates for patients who had 11-gene high-risk scores were marginally significantly lower than the rates for patients who had 11-gene low-risk scores (P = .087 and P = .174, respectively). CONCLUSIONS: In this study, 11-gene signature for predicting PLNM in cervical carcinoma was identified that may help clinicians in planning therapy for patients with cervical carcinoma.

[Effect of berberine on the differentiation and apoptosis of K562 cell line].

OBJECTIVE: To study the effect of Berberine on proliferation, differentiation and apoptosis of K562 cells for supplying the theoretical evidence on the clinical application of Coptis chinensis to cure chronic myeloid leukemia. METHODS: The proliferation-inhibiting capability of K562 cells was investigated by MTT assay and colony conform test. The apoptosis effect of Berberine on K562 cells were analyzed by Wright's-Giemsa staining; DNA fragmentation was performed by agarose gel electrophoresis. The cell cycle distribution and the cell surface marker-cluster of differentiation were determined by flow cytometry. RESULTS: Berberine effectively inhibited the proliferation of K562 cells in a dose and time-dependent manner. In addition, when combined with different concentrations of Ara-C, the cells' viability percentage was prominently higher than only Berberine used. Treated with Berberine for 48 hours, the cells could be induced differentiation towards erythrocyte, granulocyte and megakaryocyte and with the treated time extending, the percentage of apoptosis cells gradually increased. CONCLUSIONS: Berberine can efficiently inhibit the proliferation of K562 cells, maybe by the way of blocking cells at the stage of G0/G1 and (or) G2, then leading to its apoptosis and differentiation.

Anti-coxsackie virus B3 norsesquiterpenoids from the roots of Phyllanthus emblica.

Three new norsesquiterpenoid glycosides, 4'-hydroxyphyllaemblicin B (1) and phyllaemblicins E (2) and F (3), were isolated from the roots of Phyllanthus emblica, together with three known compounds, phyllaemblic acid (4), phyllaemblicin B (5), and phyllaemblicin C (6). Of these, 3 is a new norsesquiterpenoid dimer. The structures of 1-3 were established by spectroscopic data information and by acidic hydrolysis. The isolated compounds, together with two other known analogues, phyllaemblic acid methyl ester (7) and phyllaemblicin A (8), were evaluated for their antiviral activity toward coxsackie virus B3 (CVB3) by an in vitro cytopathic effect inhibitory assay. Compounds 5-7 exhibited strong anti-CVB3 activity.