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As an increasing number of noncoding RNAs (ncRNAs) have been suggested to encode short bioactive peptides in cancer, the exploration of ncRNA-encoded small peptides (ncPEPs) is emerging as a fascinating field in cancer research. To assist in studies on the regulatory mechanisms of ncPEPs, we describe here a database called SPENCER (http://spencer.renlab.org). Currently, SPENCER has collected a total of 2806 mass spectrometry (MS) data points from 55 studies, covering 1007 tumor samples and 719 normal samples. Using an MS-based proteomics analysis pipeline, SPENCER identified 29 526 ncPEPs across 15 different cancer types. Specifically, 22 060 of these ncPEPs were experimentally validated in other studies. By comparing tumor and normal samples, the identified ncPEPs were divided into four expression groups: tumor-specific, upregulated in cancer, downregulated in cancer, and others. Additionally, since ncPEPs are potential targets for neoantigen-based cancer immunotherapy, SPENCER also predicted the immunogenicity of all the identified ncPEPs by assessing their MHC-I binding affinity, stability, and TCR recognition probability. As a result, 4497 ncPEPs curated in SPENCER were predicted to be immunogenic. Overall, SPENCER will be a useful resource for investigating cancer-associated ncPEPs and may boost further research in cancer., Graphical Abstract Graphical AbstractSPENCER: a comprehensive database for small peptides encoded by non-coding RNAs in cancer patients.

Objective To investigate the effects of Flash Glucose Monitoring (FGM) on glucose profile in people with Type 2 Diabetes Mellitus (T2DM) receiving anti-diabetic drug medication. Methods This is a prospective non-randomized uncontrolled study. 111 people with T2DM were enrolled and received FGM for 14 days. There was no change of anti-diabetic medication during the 14 days. The plasma glucose concentration on day 2 was used as baseline and the day 13 was considered as study end point. The parameters to compare were mean plasma glucose (MPG), glucose variations, and incidence of hypoglycemia during the FGM period. The multivariate linear stepwise regression analysis was applied to determine the independent factors that affect MPG difference. Results This study analyzed the data of a total of 111 people with T2DM (male 60 and female 51). The general clinical data of these patients were as follows: age: 65.0±6.7 years old; duration of diabetes: 11.6±6.8 years; HbA1c: 61.2±13.3 mmol/mol; body mass index (BMI): 25.2±3.2 kg/m². Using FGM, people with T2DM were able to change daily diet and exercise through which significant reductions in MPG on days 12 or 13 were achieved as compared with that of day 2 (P=0.04 or P=0.003, respectively). The glucose variations, such as standard deviation (SD) of plasma glucose, coefficient of variation (CV), and mean amplitude of glycemic excursion (MAGE), progressively declined starting from day 6 as compared with baseline (P=0.016, P=0.003, or P=0.012, respectively). The incremental area over the curve (AOC) of the hypoglycemia (66.1 mmol/mol).

To analyze the relationship between brain MRI, clinical symptoms, and cerebrospinal fluid (CSF) and to provide a reference for early diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. A total of 62 patients with anti-NMDAR encephalitis in Zhengzhou, China (2016–2018) were observed and registered prospectively. First, we analyzed the characteristics of clinical symptoms. Second, according to the disease duration, patients were divided into two groups, and then we analyzed the CSF features. In addition, they were divided into two groups according to the brain MRI, and then the CSF features were analyzed. Finally, the characteristics of cerebrospinal fluid in patients with seizure as the initial symptom were analyzed. Seizure presents as the initial symptom in 14 patients (22.5%), including 11 males (78.57%). The proportion and concentration of CSF total protein abnormalities in the early stage group were significantly higher than those in the middle and late group (P < 0.05). The total protein concentration in the abnormal brain MRI group was significantly higher than that in the normal MRI group (P < 0.05). Anti-NMDAR encephalitis should be suspected, when male patients complain of seizure as an initial symptom and have simultaneously had headaches or fever prior to onset. The sensitivity of anti-NMDAR antibody is higher in CSF than in serum. Total CSF protein is more prone to elevation in the middle and late stages of anti-NMDAR encephalitis. Brain MRI abnormalities with anti-NMDAR encephalitis are related to the total protein concentration of CSF, which may be related to the disease duration.

Aims: To compare the efficacy of ginkgolide in the treatment of Chinese patients with ischemic stroke between pre-marketing and post-marketing studies. Methods: This is a re-analysis of a pre-marketing (phase II/III, multicenter, double-blind, parallel-controlled; February 2005 to September 2005) and post-marketing (phase IV, multicenter, open, single-arm registration; April 2013 to June 2014) studies. The intervention groups received intravenous ginkgolide (10 mL daily, 14 days). Primary outcome was an improvement of National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores after 14 days. Results: In pre- and post-marketing studies, NIHSS and mRS scores all improved, compared to that of baseline (P < 0.001) in acute phase. Those factors significantly associated with △NIHSS after 14 days of therapy with ginkgolide were grouping (pre-marketing vs. post-marketing; OR 2.169, 95%CI = 1.462–3.216, P < 0.001), male (OR = 1.532, 95%CI = 1.152–2.037, P = 0.003), enrollment within 30 days after onset (OR = 1.915, 95%CI = 1.452–2.526, P < 0.001) and NIHSS score more than 8 points at baseline (OR = 15.140, 95%CI = 11.436–20.045, P < 0.001) after adjustment. Ginkgolide had a greater effect on patients in a relatively acute phase (time of onset to enrollment ≤30 days) and moderate-severe stroke (baseline NIHSS>8 points). Incidences of adverse reactions in the pre-marketing and post-marketing studies were 0.46% and 5.28%, respectively (P < 0.001). Conclusion: Intravenous ginkgolide may improve the outcome of acute ischemic stroke. Differences in effect between pre-marketing and post-marketing studies may be associated with gender, time of onset to enrollment and severity of stroke.

Background. The purpose of this study was to investigate the accuracy of the continuously stored data from the Abbott FreeStyle Libre flash glucose monitoring (FGM) system in Chinese diabetes patients during standard meal tests when glucose concentrations were rapidly changing. Subjects and Methods. Interstitial glucose levels were monitored for 14 days in 26 insulin-treated patients with type 2 diabetes using the FGM system. Standard meal tests were conducted to induce large glucose swings. Venous blood glucose (VBG) was tested at 0, 30, 60, and 120 min after standard meal tests in one middle day of the first and second weeks, respectively. The corresponding sensor glucose values were obtained from interpolating continuously stored data points. Assessment of accuracy was according to recent consensus recommendations with median absolute relative difference (MARD) and Clarke and Parkes error grid analysis (CEG and PEG). Results. Among 208 paired sensor-reference values, 100% were falling within zones A and B of the Clarke and Parkes error grid analysis. The overall MARD was 10.7% (SD, 7.8%). Weighted least squares regression analysis resulted in high agreement between the FGM sensor glucose and VBG readings. The overall MTT results showed that FGM was lower than actual VBG, with MAD of 22.1 mg/dL (1.2 mmol/L). At VBG rates of change of -1 to 0, 0 to 1, 1 to 2, and 2 to 3 mg/dl/min, MARD results were 11.4% (SD, 8.7%), 9.4% (SD, 6.5%), 9.9% (SD, 7.5%), and 9.5% (SD, 7.7%). At rapidly changing VBG concentrations (>3 mg/dl/min), MARD increased to 19.0%, which was significantly higher than slow changing BG groups. Conclusions. Continuously stored interstitial glucose measurements with the FGM system were found to be acceptable to evaluate VBG in terms of clinical decision during standard meal tests. The continuously stored data from the FGM system appeared to underestimate venous glucose and performed less well during rapid glucose changes.

Human babesiosis, a worldwide emerging tick-borne disease, is caused by the intraerythrocytic apicomplexan parasite, babesia. In recent years, the number of infected patients globally has continued to rise, and thus human babesiosis poses a significant public health threat. Therefore, stronger initiatives should be undertaken to prevent further spread and development of this disease. In the present review, we summarize the epidemiology of reported human babesiosis cases in China from 1993 until now. The data show that Babesia microti is the dominant species causing human babesiosis in China and has led to more than 100 human infections thus far, where Babesia crassa-like is the second-most common. Moreover, Guangxi province is the second-most infected area after the Heilongjiang province. We also review the babesia life cycle, manifestation, diagnosis, and treatment. Additionally, we discuss babesiosis prevention strategies to raise public awareness, and also provide suggestions for improved babesiosis control.

Previous studies have suggested that even in euthyroid subjects, thyroid function may affect the risk factors of diabetic nephropathy (DN). Thus, we investigated the association between thyroid parameters and DN in euthyroid subjects with type 2 diabetes mellitus (T2DM). This was a cross-sectional study of 1,071 euthyroid subjects with T2DM (mean age of 61.90 ± 12.74 years; 622 men). Clinical factors, including levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid autoantibodies, albumin excretion rate were measured. DN was present in 400 (37.35%) individuals. Patients with DN exhibited higher serum TSH and lower serum FT3 and FT4 levels than those without DN (P

High-throughput sequencing technologies have identified millions of genetic mutations in multiple human diseases. However, the interpretation of the pathogenesis of these mutations and the discovery of driver genes that dominate disease progression is still a major challenge. Combining functional features such as protein post-translational modification (PTM) with genetic mutations is an effective way to predict such alterations. Here, we present PTMsnp, a web server that implements a Bayesian hierarchical model to identify driver genetic mutations targeting PTM sites. PTMsnp accepts genetic mutations in a standard variant call format or tabular format as input and outputs several interactive charts of PTM-related mutations that potentially affect PTMs. Additional functional annotations are performed to evaluate the impact of PTM-related mutations on protein structure and function, as well as to classify variants relevant to Mendelian disease. A total of 4,11,574 modification sites from 33 different types of PTMs and 1,776,848 somatic mutations from TCGA across 33 different cancer types are integrated into the web server, enabling identification of candidate cancer driver genes based on PTM. Applications of PTMsnp to the cancer cohorts and a GWAS dataset of type 2 diabetes identified a set of potential drivers together with several known disease-related genes, indicating its reliability in distinguishing disease-related mutations and providing potential molecular targets for new therapeutic strategies. PTMsnp is freely available at: http://ptmsnp.renlab.org.

Vitamin A (VA), which is stored in several forms in most tissues, is required to maintain metabolite homeostasis and other processes, including the visual cycle, energy balance, epithelial cell integrity, and infection resistance. In recent years, VA molecules, also known as retinoids, have been extensively explored and used in the treatment of skin disorders and immune-related tumors. To date, several observational and interventional studies have explored the relationship between VA status and the pathogenesis of diabetes. In particular, VA micronutrients have been shown to regulate pancreatic development, β-cell function, pancreatic innate immune responses, and pancreatic stellate cells phenotypes through multiple mechanisms. However, there are still many problems to be proven or resolved. In this review, we summarize and discuss recent and available evidence on VA biological metabolism in the pancreas. Analysis of the effects of VA on metabolism in the pancreas will contribute to our understanding of the supportive physiological roles of VA in pancreas protection.

Local tumor failure remains a major problem after radiation‐based nonsurgical treatment for unresectable locally advanced nonsmall cell lung cancer (NSCLC）and inoperable stage II NSCLC. The aim of this study was to evaluate the feasibility of simultaneous integrated boost of intensity‐modulated radiation therapy (SIB‐IMRT) to stage II‐III NSCLC with metastatic lymph nodes (ChiCTR 2000029304). Patients were diagnosed by pathology or PET‐CT. PTV was divided into two parts as follows, the PTV of primary tumor (PTVp) and the PTV of metastatic lymph nodes (PTVn). The radiotherapy doses were simultaneously prescripted 78 Gy (BED = 101.48 Gy) for PTVp and 60‐65 Gy (BED = 73.6‐81.25 Gy) for PTVn, 26f/5.2 weeks. Response was scored according to WHO criteria. Radiotherapy toxicity was scored according to RTOG criteria. Hematology and gastrointestinal toxicity were scored according to CTCAE1.0 criteria. A total of 20 patients were enrolled. Seventeen patients were diagnosed by pathology and three patients were diagnosed by PET‐CT. All patients were treated with SIB‐IMRT. The objective response rate (ORR) was 90%, with CR 25%, PR 65%, NC 10%, and PD 0%. Although radiotherapy toxicity was common, there were no grade ≥3, with radiation pneumonitis (10 cases), esophagitis (17 cases), and dermatitis (12 cases). The local control rates at 1, 3, and 5 years were 85%, 75%, and 70%, respectively. The overall survival（OS）and local progression‐free survival (LPFS) rates at 1, 3, and 5 years were 90%, 42.6%, and 35.5% and 84.4%, 35.5%, and 28.4%, respectively. SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety, and satisfactory efficacy. However, due to the limitation of small sample, these findings are needed to confirm by future trials with a larger sample size., The different radiation doses were simultaneously prescripted 78 Gy (PTVp）and 60‐65 Gy (PTVn). SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety and satisfactory efficacy.

The effects of insulin delivered by needle-free jet injector on glycemic variations (GV) in patients with type 2 diabetes (T2D) which remains largely unknown.We aimed to compare the glucose variabi...

BACKGROUND Postprandial hyperglycemia and glycemic fluctuations are significant cardiovascular disease risk factors for patients with type 2 diabetes. We investigated the effects of a single session of post-dinner moderate-intensity exercise on the postprandial glycemic response compared with a non-exercise condition in a study population of Chinese patients with type 2 diabetes. MATERIAL AND METHODS This randomized crossover self-controlled pilot study involved 29 patients with type 2 diabetes who participated in post-dinner exercise days using non-exercise days as a control. The interstitial glucose level was monitored using a continuous glucose monitoring system, with a standardized diet and medication. For the non-exercise control days, patients pursued normal daily activities but refrained from unusual strenuous physical activity. On the exercise days, participants walked on a treadmill for 20 minutes after dinner, with a heart rate reserve of 40%. RESULTS Post-dinner moderate-intensity exercise reduced the 2-hour postprandial glucose spike, mean glucose level, and peak glucose level compared to the control condition. The cumulative glucose total area under the curve during 1-hour post-exercise was lower with exercise than under the control condition. The 12-hour standard deviation of blood glucose and the coefficient variation of glucose were significantly lower in the with exercise day compared to the control day, although the 12-hour mean amplitude of glycemic fluctuations did not reach statistical significance. No nocturnal hypoglycemia subsequently occurred on the exercise day. CONCLUSIONS A short session of moderate-intensity post-dinner exercise can improve postprandial hyperglycemia and glycemic excursions in Chinese patients with type 2 diabetes, with no potential hypoglycemia risk at a later period.

Drug-loaded phase-transformation lipid nanoparticles (NPs) combined with low-intensity focused ultrasound (LIFU) for ultrasound molecular imaging and therapy, which is a very promising drug carrier and can provide both physical and chemical therapeutics, simultaneously. We successfully prepared the paclitaxel (PTX) loaded anti-LHRHR targeted phase-transformation lipid nanoparticles (PTX-anti-LHRHR-PTNPs) for ovarian cancer in this study combined with LIFU has the following characteristics: On the one hand, it showed smaller size and greater stability than blood cells, which significantly prolonged its half-life in the body, and can actively target ovarian cancer OVCAR-3 cells, and smoothly penetrate the endothelial gap into the tumor site for specifically killing the ovarian cancer cells. Thereby, the special drug carrier improved the therapeutic effect and reduced toxic and side effects, maximized the protection of normal tissues and minimized adverse reactions. On the other hand, PTX-anti-LHRHR-PTNPs can be targeted to focus after being injected intravenously and remain in the tumor target tissue for a long time. At the same time, liquid-gas phase-transformation can occur under LIFU triggering, resulting in more ideal and sustained ultrasound imaging effects. Then acoustic contrast agent is used to develop the molecular level of ultrasound scattering, so as to evaluate the diseased tissue from the molecular level.

Background: This study evaluated the efficacy and safety of docetaxel combined with lobaplatin, relative to docetaxel combined with gemcitabine, for treating patients with recurrent metastatic breast cancer (rMBC). Methods: Patients with rMBC received ≥2 cycles (21 days each) of either docetaxel and lobaplatin (DL; n = 21), or docetaxel and gemcitabine (DG; n = 22). On day 1 of each cycle, all patients were given 75 mg/m2 intravenous docetaxel. Patients in DL and DG were also given, respectively, 35 mg/m2 intravenous lobaplatin (day 2) or 1000 mg/m2 intravenous gemcitabine (days 1, 8). Results: Five (11.6%) and 16 (37.2%) patients achieved complete remission and partial response, respectively; rates of response and disease control were 48.8%. The response rates of the groups were comparable (47.6%, 50.0%). The median survival times after relapse and metastasis of the DL group (18 months) were significantly less than that of the DG group (25 months). Median progression-free survivals after relapse and metastasis were similar (12 cf. 14 months). The main toxic side reaction was grade 2, with no treatment-related deaths. Rates of the following were comparable between DG and DL: grade 3 or 4 white blood cells (23.8%, 31.8%) and digestive tract toxicity (4.8%, 4.5%); neutropenia (28.6%, 22.7%); anemia (4.8%, nil); and thrombocytopenia (19.0%, 13.6%). Other toxicities included hepatic toxicity, myalgia, infection, and fatigue. Conclusions: Both the DL and DG regimens were associated with encouraging benefits, while treatment-related toxicity was manageable. Therefore, these regimens are effective options for treatment of rMBC. Trial registration: This clinical trial study was approved by the Ethics Committee of Guizhou Cancer Hospital, and has been registered in the China Clinical Trial Center (December 8, 2014, No. ChiCTR-IPR-14005633).

Purpose/Objective(s) To evaluate the efficiency and safety of Nab-paclitaxel plus cisplatin and concomitant thoracic radiotherapy in locally advanced non-small-cell lung cancer. Materials/Methods A total of 68 cases locally advanced NSCLC patients were enrolled in this study, and 38 cases were enrolled so far (1:1 in the experimental group and the control group, 19 cases in each group, 1 case in each group did not complete the treatment, a total of 36 cases were available for statistical analysis). The control group received paclitaxel combined with cisplatin regimen chemotherapy (paclitaxel 175mg/m2 on day 1, cisplatin 75mg/m2 on day 2; every 3-4 weeks for 2 consecutive cycles. Experimental group: nab-paclitaxel weekly at a dose of 40mg/m2, Cisplatin 75mg/m2 and repeated every 3-4 weeks for 2 consecutive cycles. Both groups received concomitant aggressive radical three-dimensional thoracic radiotherapy with continuously accelerated hyperfractionation. The primary endpoint was ORR and safety (including treatment-induced bone marrow suppression, the toxicity of liver and kidney function, cardiotoxicity, radiation pneumonia, and other toxic side effects). Secondary endpoints were local progression-free survival rate, the local recurrence rate of the primary tumor, and the local control rate of the primary tumor. Results 38 patients completed concomitant chemoradiotherapy. The effective rates ORR of experimental group and control group were 89.6% and 68.5%, respectively. The short-term efficacy was CR (0 cases 0%, 1 case 5.2%), PR (17 cases 89.6%, 12 cases 63.3%), SD (1 case 5.2%, 5 cases 26.3%), PD (1 case 5.2%, 1 case 5.2%) P = 0.001. Grade 3/4 leukopenia 2 (10.5%), 14 (73.7%), P = 0.001; grade 3/4 neutropenia 2 (10.5%), 14 (73.7%), P = 0.001; grade 3/4 anemia 1 (5.3%) and 2 (10.5%), P = 0.547; grade 3/4 thrombocytopenia 0(0%) and 2 (10.5%) of, P = 0.146. There were 11 (57.9%) and 6 (31.6%) of grade I radiation esophagitis, and 8 (42.1%) and 13 (68.4%) of grade II esophagitis respectively. No grade III-IV esophagitis was found. Conclusion The ORR and short-term efficiency of nab-paclitaxel plus cisplatin concomitant radiotherapy are better than the control group, and the hematological toxicity is lower than the control group.

Background Ovarian cancer is a common gynecological malignant tumor that greatly threatens women's health, so we screened potential biomarkers of ovarian cancer and analyzed their prognostic value. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the ovarian cancer-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of ovarian cancer-related genes. The survival-related genes were screened out through the least absolute shrinkage and selection operator (LASSO) method. Multivariate Cox regression model and stepwise regression analysis were performed to construct the risk model. The receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to evaluate the prediction accuracy of risk score model. Finally, gene set enrichment analysis (GSEA) and immune cell infiltration analysis were performed to investigate the biological function and immune cell infiltration. Results A total of 111 genes were found to have common effects on survival. These genes were mainly involved in metabolism, protein phosphorylation and immune-related signaling pathways. Seven risk genes (AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1, ZNF426) were screened out. Among these genes, AP3D1 and LRFN4 are risk genes and DCAF10, FBXO16, PTPN2, SAYSD1, and ZNF426 are protective genes. These findings suggest that risk status may be an independent prognostic factor. The risk score had a high predictive value for the prognosis of ovarian cancer. In addition, GSEA revealed that the biological function of genes expressed in patients at a high risk was mostly related to immune-related function. The contents of CD4+ T cells, macrophages, myeloid dendritic cells (mDC) and neutrophils were high in samples at a high risk for ovarian cancer. Conclusions The abnormal expression of AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1 and ZNF426 is highly related to the progression of ovarian cancer. These seven genes can be used as independent prognostic markers of ovarian cancer. This study not only adds evidence to the pathogenesis of ovarian cancer but also provides scientific basis for judging the prognosis of ovarian cancer.

The aim of this study was to determine the relationship between glucose fluctuation and global registry of acute coronary events (GRACE) risk score in patients with acute coronary syndrome (ACS) and abnormal glucose metabolism using continuous glucose monitoring system (CGMS). A total of 76 patients with ACS admitted into coronary care unit (CCU) were divided into two groups based on their blood glucose level and were further divided into subgroups based on GRACE risk score. A CGMS was used to real-time monitor blood glucose for 72 h in all patients after admitted into CCU. Twenty-four-hour mean blood glucose (24-h MBG) and 24-h mean amplitude of glycemic excursion (24-h MAGE) were calculated. Among the 76 patients, 52 patients had abnormal glucose metabolism. Among the 52 patients, there were 8 patients in low-risk group, 19 patients in moderate-risk group, and 25 in high-risk group. Among the 24 patients with normal glucose metabolism, there were 6 patients in the low-risk group, 6 patients in the moderate-risk group, and 12 in the high-risk group based on GRACE score. For patients with abnormal glucose metabolism, the 24-h MBG and 24-h MAGE of moderate- and high-risk groups were significantly higher than that of the low-risk group, which were not found in patients with ACS and normal glucose metabolism. High prevalence of abnormal glucose metabolism was found in ACS patients admitted into CCU and larger blood glucose fluctuation is associated with moderate and high GRACE risk scores in patients with ACS and abnormal glucose metabolism.

To determine the clinical non-inferiority of recombinant glargine-Basalin vs glargine-Lantus, in treatment of type 2 diabetes mellitus (T2DM) using continuous glucose monitoring system (CGMS). One hundred patients with T2DM were recruited. They were either regularly taking Basalin (Basalin group) or Lantus (Lantus group) (n = 50 each). CGMS was employed to real-time monitor blood glucose profile for 4 days (from day 1 to day 5). To exclude the effect of patient background, the study design was to have a blinded crossover from glargine-Basalin to glargine-Lantus on day 3, and vice versa. 24-hour mean blood glucose (24hMBG), 24-hour standard deviation of blood glucose (24hSDBG), 24-hour mean amplitude of glycemic excursion (24hMAGE), and number of glycemic excursion (NGE) every 24 h (24hNGE) were calculated for each glargine from 100 patients. No significant difference of 24hMBG, 24hSDBG, 24hMAGE, and 24hNGE (p > 0.05 for all) was found between Basalin and Lantus treatments. The glucose area under the curve and time when blood glucose was below 3.9 mmol/L, between 3.9 and 10.0 mmol/L, or above 10.0 mmol/L were similar between Basalin and Lantus treatment. The frequency of hypoglycemic episodes was also similar. However, the mean cost of Basalin was only 72% of Lantus’s in one treatment course. Glargine-Basalin is non-inferior in clinical efficacy compared to glargine-Lantus. In view of the large difference in the cost of glargine-Basalin, it would be much more cost-effective for our patients.

Background The aim of our work is to identify the functional mechanism of microRNA-138 (miR-138) in human cervical cancer. Methods MiR-138 expression was investigated by qRT-PCR in cervical cancer cell lines and human tumors. Correlations of patients' clinicopathological factors and overall survival with miR-138 expression were analyzed. In SiHa and HeLa cells, miR-138 was either upregulated or downregulated to evaluate its regulations on cervical cancer in vitro proliferation, invasion and in vivo xenograft growth. Downstream target gene of miR-138, TCF3, was analyzed by dual-luciferase reporter assay, and by qRT-PCR to evaluate its expression in cervical tumors and cervical cancer cell lines. TCF3 was either upregulated or downregulated in SiHa and HeLa cells to further evaluate its role in regulating cervical cancer proliferation and invasion. Results MiR-138 is downregulated in both cervical tumors and cervical cancer cell lines. Low expression of miR-138 in cervical tumors is closely correlated with patients' clinicopathological factors and poor survival. In SiHa and HeLa cells, lentivirus-induced miR-138 upregulation inhibited cancer proliferation and invasion in vitro , and xenograft growth in vivo , whereas miR-138 downregulation had little effect. TCF3 was confirmed to be regulated by miR-138, and upregulated in cervical cancer tumors and cell lines. In vitro cervical cancer proliferation and invasion were significantly inhibited by SiRNA-mediated TCF3 downregulation, but unaffected by TCF3 overexpression. Conclusion MiR-138 may be a tumor suppressor and potential prognostic biomarker in cervical cancer. Its downstream target, TCF3, may also regulate cancer development in a reverse manner as miR-138.

To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P 1c values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

Background: This study aimed to evaluate the association between thyroid parameters and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Materials and Methods: I...

Objective: To analyse the impact of survival with three-dimensional radiotherapy for stage IV squamous non-small cell lung cancer (NSCLC). Methods: Data for 629 eligible patients who received three-dimensional radiotherapy between 2002 and 2016 were retrospectively analyzed.161 of 183 cases were included pre-protocol. Patients received platinum-doublet chemotherapy with concurrent irradiation of the primary tumour. Primary endpoints were overall survival (OS) and progress-free survival (PFS). Results: Of 161 patients, the 1-, 2-, 3- and 5-year OS rates and median survival time (MST) were 45.7%, 14.1%, 11.2%, 2.2% and 11months, respectively. Using contrastive analysis PTV dose ≥63 Gy and

Aim. To compare the effects of once-weekly Dulaglutide with once-daily glargine in poorly oral-antidiabetic controlled patients with type 2 diabetes mellitus (T2DM). Method. A total of 25 patients with T2DM admitted into Department of Endocrinology from December 2012 to August 2013 were randomly assigned into two groups: Dulaglutide group (n=16) and glargine group (n=9). All patients received either Dulaglutide or glargine treatments for 52 weeks. Continuous glucose monitoring systems (CGMS) were applied to them for two 72 h periods at before and after the treatment each. Patient general clinical data were collected and analyzed. Result. Fast blood glucose (FBG) of the glargine group declined more significantly than the Dulaglutide group after treatment (p<0.05). The mean blood glucose (MBG), standard deviation of blood glucose (SDBG), mean amplitude of glycemic excursion (MAGE) within a day, the largest amplitude of glycemic excursion (LAGE), M-value, absolute means of daily difference (MODD) of glycemic excursion, the percentage of time (≤2.8 mmol/L, ≤3.9 mmol/L, ≥10.0 mmol/L, ≥13.9 mmol/L, 3.9–7.8 mmol/L, and 9–10.0 mmol/L), maximum glycemic value, and minimum glycemic value were similar between the two groups (p>0.05). The incidence of hypoglycemia was also similar between the two groups (p>0.05). Though serum levels of TNF-α, IL-6, and 8-PGF2α all decreased, significant reduction was found in TNF-α and 8-PGF2α. TNF-α was only significantly reduced in the Dulaglutide group, while 8-PGF2α was seen in both groups. Conclusion. For T2DM patients with poorly controlled oral antidiabetic drugs, once-weekly Dulaglutide not only has the same effect on glucose fluctuation as once-daily glargine but also significantly reduced TNF-α and 8-PGF2α after a 52 week treatment protocol. This trial is registered with ClinicalTrials.gov NCT01648582.

Objective. To evaluate the effects of once-weekly dulaglutide injection and once-daily glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) using the Continuous Glucose Monitoring System (CGMS). Methods. A total of 23 patients with T2DM were randomly assigned into two groups for 26 weeks: the dulaglutide group (n=13) and the glimepiride group (n=10). 72-hour CGMS was applied to all patients: before and after the treatment. General clinical data were collected and measured, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), tumor necrosis factor-α (TNF-α), 8-iso-prostaglandin F2α (8-iso-PGF2α), and interleukin-6 (IL-6). Results. HbA1c of the dulaglutide group was reduced from 8.38±0.93% to 6.68±0.73% after the treatment (P<0.05); similarly, it was reduced from 7.91±0.98% to 6.67±0.74% (P<0.05) in the glimepiride group. The levels of serum 8-iso-PGF2α, TNF-α, and IL-6 all decreased significantly in both groups after treatment, and there was no significant difference found between the two groups (P>0.05). The Mean Blood Glucose (MBG) of the two groups declined significantly after therapy (P<0.05). However, the Standard Deviation of Blood Glucose (SDBG) decreased significantly only in the dulaglutide group (from 2.57±0.74 mmol/L to 1.98±0.74 mmol/L, P<0.05). There were no significant changes of Mean Amplitude of Glycemic Excursion (MAGE) and Absolute Means of Daily Difference (MODD) after treatment in both groups. Furthermore, no statistically significant difference was found between the two groups in MBG, SDBG, MAGE, and MODD (P>0.05). The percentage time (PT) (>10 mmol/L and 3.9-10 mmol/L) of the two groups was significantly changed after the treatment (P<0.05). However, this was not seen in the PT<3.9 mmol/L after the treatment (P>0.05). Conclusion. Once-weekly dulaglutide injection has the same effectiveness as daily glimepiride on lowering blood glucose and decreasing oxidation stress and inflammation and is more effective in controlling glucose fluctuation as compared with glimepiride. This trial is registered with ClinicalTrials.gov NCT01644500.

Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.

Recombination contributes substantially to the genetic diversity of HIV-1. Recently, many kinds of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified in China, especially in areas with multiple subtypes of HIV-1 circulating. Yunnan, which borders the "Golden triangle" region of South China, is an epicenter of HIV-1 infections in China. Multiple subtypes, including subtypes B, CRF01_AE, CRF07_BC, and CRF08_BC, were found epidemic in the area. Many URFs composed of subtypes B and C genomes were identified in Yunnan; however, CRF01_AE/B recombinant form is relatively rare. In this study, we identified a novel recombinant form of CRF01_AE/B, which was isolated from a heterosexual transmitted individual. The genomic structure of the strain is distinctly different from any previously reported URFs. Three CRF01_AE segments were inserted into the subtype B backbone genome. In the past few years, many kinds of URFs and CRFs have emerged and spread quickly in China, which implies that coinfection or super infection of more than one HIV-1 subtype might be common in China, especially in Yunnan. Therefore, more work is needed to monitor the appearance of URFs and survey the epidemiologic significance of the new recombination.

Aims Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). Methods A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC0-60 min). Results The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC0-60 min (standardized β = −0.386, P Conclusions PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. Clinical trials registration: ChiCTR-ONC-17010400 , www.chictr.org.cn

Purpose The aim of this prospective multi-institutional phase 2 study was to investigate disease control, survival outcomes, and toxicity after thoracic three-dimensional radiation therapy (3D-RT) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer (NSCLC). Methods and Materials Eligible patients were 18 to 80 years of age, had a Karnofsky performance status (KPS) score ≥70%, and newly diagnosed stage IV NSCLC with limited metastatic disease (defined as involving ≤3 organs). Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor. Primary endpoints were overall survival (OS) and acute toxicity. Results From May 2008 to May 2012, 198 eligible patients were enrolled from 7 cancer centers. Most patients died with distant metastasis; only 10% died with isolated primary recurrence. Median OS time was 13.0 months (95% confidence interval [CI]: 11.7-14.3); OS rates were 53.5% at 1 year, 15.8% at 2 years, and 9.2% at 3 years. Median progression-free survival (PFS) time was 9.0 months (95% CI: 7.7-10.3); corresponding PFS rates were 30.8%, 8.2%, and 6.1%. The 1-year, 2-year, and 3-year local (primary tumor) control rates were 78.8%, 57.7%, and 55.4%. Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor ( P =.014), having a primary tumor volume 3 ( P =.008), and having a stable or higher KPS score after treatment ( P =.01) were independent predictors of better OS. The most common severe (grades 3-4) acute toxicities were hematologic: leukopenia (37.9%), thrombocytopenia (10.1%), and anemia (6.9%). No patients experienced grade 4 or 5 radiation-related toxicity; 2.5% had acute grade 3 pneumonitis, and 6.6% had acute grade 3 radiation esophagitis. Conclusions Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity. Radiation dose, primary tumor volume, and PFS after treatment all predicted survival in these patients with limited-metastasis NSCLC.

Lung cancer is the leading cause of cancer mortality worldwide. Despite increases in the survival rate for various types of cancer over the past several decades, lung cancer remains an overwhelmingly lethal disease and the majority of patients succumb to the disease in a short period of time. A number of treatment options are available depending on the stage of lung cancer. The present review focused on palliative care and is associated with stage IIIB and IV of non-small cell lung cancer (NSCLC). Stage IIIB disease is not amenable to curative treatment and for stage IV disease, treatment is palliative in nature, with a focus on increasing survival time, controlling symptoms and improving or maintaining quality of life. Palliative treatment options include chemotherapy, radiotherapy and supportive care. The present review examines the important aspects of palliative therapy with regard to NSCLC.

The chief concerns for antiretroviral therapy (ART) programs considering removal of CD4+ cell count thresholds for treatment are the increased incidence of ART-related adverse events. A nationwide observational cohort study was conducted among patients who initiated ART in 2012. We divided the eligible patients into three groups: an early ART group with a baseline CD4+ cell count of 500 cells/μL or greater, a standard ART group with a baseline CD4+ cell count between 350 and 499 cells/μL, and a late ART group with a baseline CD4+ cell count between 200 and 349 cells/μL. These patients were followed up to December 31, 2014 and observed for three outcomes: virological failure, treatment nonretention, or time to death. Patients who met the eligibility criteria numbered at 26,752. Out of all study participants, 20,827 participants were in late ART group, 4336 were in standard ART group, and 1589 were in early ART group. Patients in late ART group were more likely to become virally suppressed 12 and 24 months after treatment initiation than patients in early ART group [adjusted odds ratio (aOR) 0.81; 95% CI, 0.69–0.95 and aOR, 0.78; 95% CI, 0.65–0.94]. Treatment nonretention was also less likely to occur among patients in late ART group than early ART group 12 months after treatment initiation (aOR, 0.85; 95% CI, 0.75–0.96). Compared with early ART group, neither standard ART group nor late ART group had a statistically significant difference in the time-to-death analysis. Late ART initiates were more likely to be virally suppressed and retained on treatment than early ART initiates. The importance of treatment retention and adherence should be emphasized for high CD4+ patients newly initiated to ART therapy through education and counseling programs.

Background and purpose Patients with unresectable stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy often develop esophagitis that may lead to unplanned treatment interruptions, which may severely reduce rates of locoregional tumor control and survival. No effectivetreatment that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of normal tissue protection using epigallocatechin-3-gallate (EGCG) has been reported, its actual clinical practicability remains obscure. Methods and materials This is a phase I study of EGCG in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with radiation. EGCG solution was swallowed three times a day after the occurrence of grade 2 esophagitis at six concentration levels and dose escalation followed a standard phase I design. Esophageal toxicity and patient-reported pain was recorded weekly. Results Twenty-four patients with AJCC stage IIIA (six) and IIIB (eighteen) completed the course of therapy. Twelve had squamous histology, ten adenocarcinoma, and two not specified. Patients were treated in six cohorts at six dose levels of EGCG. RT was not interrupted with a median dose of 64Gy. There were no dose-limiting toxicities reported in all EGCG dosing tiers. Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24 patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of radiotherapy. The pain score was also reduced from a mean of 4.58 ( N =24), 1.29 ( N =24), 1.42 ( N =24), 0.96 ( N =23) to 1.13 ( N =16) every week in turn. Conclusion We conclude that the oral administration of EGCG is feasible, safe and effective. The phase II recommended concentration is 440μmol/L.

// Jian Wang 1,* , Rengna Yan 1,* , Juan Wen 2,* , Xiaocen Kong 1 , Huiqin Li 1 , Peihua Zhou 1 , Honghong Zhu 1 , Xiaofei Su 1 and Jianhua Ma 1 1 Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 2 Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China * These authors have contributed equally to this study Correspondence to: Jianhua Ma, email: // Keywords : body mass index, glycemic variability, continuous glucose monitoring, obesity, postprandial glucose excursion Received : December 14, 2016 Accepted :April 03, 2017 Published : April 14, 2017 Abstract Previous studies have indicated that the pathogenesis of diabetes differs between obese and lean patients. We investigated whether newly diagnosed Chinese diabetic patients with different body mass indices (BMIs) have different glycemic variability, and we assessed the relationship between BMI and glycemic variability. This was a cross-sectional study that included 169 newly diagnosed and drug-naive type 2 diabetic patients (mean age, 51.33 ± 9.83 years; 110 men). The clinical factors and results of the 75-g oral glucose tolerance test were all recorded. Glycemic variability was assessed using continuous glucose monitoring. Compared with overweight or obese patients (BMI ≥ 24 kg/m 2 ), underweight or normal-weight patients (BMI < 24 kg/m 2 ) had higher levels of blood glucose fluctuation parameters, particularly in terms of mean amplitude of glycemic excursion (MAGE 6.64 ± 2.38 vs . 5.67 ± 2.05; P = 0.007) and postprandial glucose excursions (PPGEs) (PPGE at breakfast, 7.72 ± 2.79 vs . 6.79 ± 2.40, P = 0.028; PPGE at lunch, 5.53 ± 2.70 vs . 5.07 ± 2.40, P = 0.285; PPGE at dinner, 5.96 ± 2.24 vs . 4.87 ± 2.50, P = 0.008). BMI was negatively correlated with glycemic variability ( r = −0.243, P = 0.002). On multiple linear regression analyses, BMI ( β = −0.231, P = 0.013) and Insulin Secretion Sensitivity Index-2 ( β = −0.204, P = 0.048) were two independent predictors of glycemic variability. In conclusion, lower BMI was associated with increased glycemic variability, characterized by elevated PPGEs, in newly diagnosed Chinese type 2 diabetic patients.

This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44–4.00; P

Aim: Patients with cardiac diseases, especially ischemic heart disease, are known to have a high prevalence of diabetes mellitus (DM). They are at risk of having inadequate glucose control. An intensive diabetes screening and treatment program was developed to identify and treat DM in patients admitted with cardiac diseases. Methods: Adult inpatients of 2 cardiac wards, namely Ward-A and Ward-B, at Nanjing Hospital, Nanjing, China, were studied. Patients were randomly assigned into either ward. In addition to routine examination and treatment, an intensive screening and treatment program to identify and treat patients with DM or impaired glucose regulation (IGR) was only applied in Ward-A patients. The glycated serum protein concentration, the length of hospitalization, and medical and total hospital cost were compared between the 2 wards. Results: The prevalence of DM was 17.85% in Ward-B. With implementation of this program, DM was higher in Ward-A (29.7%) and the prevalence of IRG was 7.8%. The overall prevalence of abnormal glucose metabolism was 37.5% in Ward-A. This program is associated with significantly reduced medical cost and length of inhospital days in patients requiring percutaneous coronary intervention (PCI) and reduced both the medical and total hospital costs in patients without PCI of Ward-A as compared with those of Ward-B who received standard treatment. Conclusion: The intensive screening and treatment program increases diagnosis rate of DM and IRG in inpatient with cardiac diseases, more effectively controls hyperglycemia, and is associated with shorter length of inhospital days and lower medical and total hospital costs. The trial registry number: ChiCTR-IPR-15007487

Background: To determine the therapeutic efficacy and cost-effective of pancreatic kininogenase (PKase) on treatment of diabetic peripheral neuropathy (DPN) compared with Prostaglandin E1 (PGE1) in patients with type 2 diabetes. Methods: 104 patients with DPN receiving standard glucose control therapy were randomly assigned into 3 groups: Group-A received PKase treatment, Group-B received PGE1 treatment, and Group-C received only standard glucose control therapy. Michigan neuropathy screening instrument (MNSI) score, neurophysiology examination, and nerve conduction velocity were measured. Results: Standard glucose control therapy significantly reduced hyperglycemia to a similar level in all groups. Questionnaire grading and neurophysiology examination both indicated that no significant difference was found at the end of treatment between Groups -A and -B. Except for the ulnar nerve sensory conduction velocity that was significantly improved in Group-B, the remaining nerve conduction velocity (regardless of sensory or motor nerve conduction velocities) was improved to a similar level in Groups -A and -B. Group-A had significantly reduced questionnaire grading and better improvement in motor nerve conduction velocity of the common peroneal nerve, ulnar nerve, and sensory nerve conduction velocity of the sural nerve as compared with Group-C. However, the medical cost of PKase was only 18.9% of that of PGE1 during one course of treatment. Conclusions: PKase has the similar therapeutic efficacy as PGE1 on treatment of DPN in patients with type 2 diabetes. However, the medical cost of PKase is one fifth of that of PGE1. Thus, PKase is a cost-effective drug for treatment of DPN.

The study aims to explore the prevalence and clinical features of fulminant type 1 diabetes mellitus (F1DM).We analyzed 11,202 patients who were diagnosed having diabetes and admitted to the Department of Endocrinology, Nanjin First Hospital, Nanjin, China, from September 2005 to April 2011. Among 198 patients classified having type 1 diabetes mellitus (T1DM), nine patients were diagnosed having F1DM. Clinical features of F1DM were analyzed and compared with typical T1DM.The prevalence of F1DM was 4.5% (nine of 198 T1DM patients) in this study. F1DM patients had significantly high levels of random blood glucose (40±9 mmol/L). However, glycated hemoglobin (7.1±1.0%) and C-reactive peptide (0.21±0.15 μg/L) at 2 h postprandial were significantly lower in F1DM patients compared with typical T1DM patients. Six of them had flu-like symptoms. Five of them showed gastrointestinal symptoms. Three patients experienced disturbance of consciousness. However, none of these symptoms was found in patients with typical T1DM. A continuous intravenous insulin infusion therapy using a portable pump was given during the acute phase to control hyperglycemia and ketoacidosis. All F1DM patients survived after treatment.In this single hospital-based study, nine Chinese patients met the criteria for diagnosis of F1DM. Although F1DM may be fatal, prompt treatment is required and useful to rescue these patients.

Breast cancer is a highly heterogeneous disease, with several different subtypes being characterized by distinct histology, gene expression patterns, and genetic alterations. The tumor suppressor gene retinoblastoma 1 (RB1) is frequently lost in both luminal-B and triple-negative tumor (TNT; i.e., estrogen receptor–, progesterone receptor–, and human epidermal growth factor receptor 2–negative) breast cancer subtypes. However, a causal role for RB1 loss in different subtypes remains undefined. Here we report that deletion of Rb alone or together with its relative p107 in mouse mammary stem/bipotent progenitor cells induced focal acinar hyperplasia with squamous metaplasia. These lesions progressed into histologically diverse, transplantable mammary tumors with features of either luminal-B or TNT subtypes. The TNTs included basal-like tumors as well as tumors that exhibited epithelial-to-mesenchymal transition (EMT). The EMT-type tumors and a subset of the basal-like tumors, but not luminal-B–like tumors, expressed mutant forms of the tumor suppressor p53. Accordingly, targeted deletion of both Rb and p53 in stem/bipotent progenitors led to histologically uniform, aggressive, EMT-type tumors. Reintroduction of Rb into these tumor cells suppressed growth in vitro and tumor formation in vivo. These results establish a causal role for Rb loss in breast cancer in mice and demonstrate that cooperating oncogenic events, such as mutations in p53, dictate tumor subtype after Rb inactivation.

Objective To identify factors associated with mother-to-child-transmission and late access to prevention of maternal to child transmission (PMTCT) services among HIV-infected women; and risk factors for infant mortality among HIV-exposed infants in order to assess the feasibility of virtual elimination of vertical transmission and pediatric HIV in this setting. Design Observational study evaluating the impact of a provincial PMTCT program. Methods The intervention was implemented in 26 counties of Yunnan Province, China at municipal and tertiary health care settings. Log linear regression models with generalized estimating equations were used to identify unadjusted and adjusted correlates for late ARV intervention and MTCT. Cox proportional hazard models with robust sandwich estimation were applied to examine correlates of infant mortality. Results Mother-to-child- transmission rate of HIV was controlled to 2%, with late initiation of maternal ARV showing a strong association with vertical transmission and infant mortality. Risk factors for late initiation of maternal ARV were age, ethnicity, education, and having a husband not tested for HIV. Mortality rate among HIV-exposed infants was 2.9/100 person-years. In addition to late initiation of maternal ARV, ethnicity, low birth weight and preterm birth were associated with infant mortality. Conclusions This PMTCT program in Yunnan achieved low rates of MTCT. However the infant mortality rate in this cohort of HIV-exposed children was almost three times the provincial rate. Virtual elimination of MTCT of HIV is an achievable goal in China, but more attention needs to be paid to HIV-free survival.

Background The impact of thoracic three-dimensional radiotherapy on the prognosis for stage IV non-small-cell lung cancer is unclear. This study is to investigate survival outcomes and prognosis in patients with stage IV non-small cell lung cancer (NSCLC) treated with thoracic three-dimensional radiotherapy and systemic chemotherapy. Methods Ninety three patients with stage IV NSCLC had received at least four cycles of chemotherapy and thoracic three-dimensional radiotherapy of ≥40 Gy on primary tumors. The data from these patients were retrospectively analyzed. Results Of the 93 patients, the median survival time (MST) was 14.0 months, and the 1, 2, and 3-year survival rates were 54.8%, 20.4%, and 12.9%, respectively. The MST of patients received radiation dose to primary tumor ≥63Gy and

Aim To identify the prevalence and predictors of abnormal renal function among HIV-positive Chinese patients prior to antiretroviral therapy (ART) initiation and to evaluate subsequent changes in renal function after ART exposure. Methods We conducted a nationwide cohort study of subjects who enrolled in the national Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the glomerular filtration rate (eGFR) of subjects prior to and after initiating ART. Risk factors for abnormal renal function, as defined by eGFR 6.1 mmol/L (AOR = 1.46, 95% CI: 1.25–1.72), and hepatitis C co-infection (AOR = 1.36, 95% CI: 1.06–1.73). Among subjects with baseline eGFR >90 ml/min/1.73m2, the incidence of the eGFR falling to

Background To evaluate the efficacy of three-dimensional radiotherapy for non-small cell lung cancer (NSCLC) patients with bone metastases. Methods Clinical data for 95 NSCLC patients with bone metastases were collected and prognostic factors were analyzed. All patients received radiation to their thoracic primary tumor and ≥2 cycles of chemotherapy. Results Of these 95 patients, 47 patients had only bone metastases and 48 had both bone metastases and other organ metastases. Univariate analysis showed that factors that statistically significantly contributed to patients having longer overall survival (OS) included receiving a radiation dose to the primary tumor ≥63 Gy, responding to treatment and receiving ≥4 cycles of chemotherapy (p = 0.001, p = 0.037 and p = 0.009, respectively). A radiation dose to the primary tumor ≥63 Gy remained significant for patients with bone metastases only as well as those with bone and other organ metastases when they were analyzed separately (p = 0.045 and p = 0.012, respectively). For patients with bone metastases only, those with T1-2 tumors had longer OS than those with T3-4 (p = 0.048); and patients who received ≥4 cycles chemotherapy compared with those who received

Approximately two thirds of breast cancer patients have estrogen-dependent carcinomas. The biosynthesis of estrogens is catalyzed by the microsomal enzyme aromatase. Mechanisms controlling human aromatase gene expression are complicated by the existence of multiple tissue specific promoters. The most proximally located Pll promoter is mainly active in ovarian granulosa cells. PlI can be switched on in human breast cancer cells. Since there are strong silencer elements located within the 3' portion of the PlI promoter, we propose that the function of these silencer elements could be reversed by breast cancer cell specific signals/factors, resulting in aberrant expression of aromatase. We have identified and characterized a novel silencer element, S2, which is upstream of S1, a silencer element recently identified by another group. S2, a 54-bp fragment 100% conserved between humans and rodents, functions in both orientation- and promoter-independent manners. The core region of S2 contains two consensus binding sites for members of the GATA transcription factors. GATA-4 was found to be expressed in three out of four human breast cancer cell lines examined by RT-PCR, and transfection with GATA-4 partially reversed the repressive function of S2. However, we were unable to demonstrate that DNA-protein complexes formed between nuclear extracts of human breast and ovarian cancer cells and S2 contain GATA-4 using a supershifting approach. We suggest that the expression of GATA-4, and more importantly, other yet to be identified GATA or GATA-related factor(s), are implicated in provoking aberrant expression of aromatase, and therefore, the biosynthesis of estrogens, in human breast cancer cells.

The ibeB gene in neonatal meningitis Escherichia coli (NMEC) contribute to the penetration of human brain microvascular endothelial cells (HBMECs). However, whether IbeB plays a role in avian pathogenic E. coli (APEC) infection remains unclear. Thus, this study was conducted to investigate the distribution of the ibeB gene in Chinese APEC strains and examine whether IbeB is involved in APEC pathogenicity. The ibeB gene was found in all 100 detected E. coli isolates with over 97% sequence homology. These results indicated that ibeB is a conserved E. coli gene irrelevant of pathotypes. To determine the role of ibeB in APEC pathogenicity, an ibeB mutant of strain DE205B was constructed and characterized. The inactivation of ibeB resulted in reduced invasion capacity towards DF-1 cells and defective virulence in animal models as compared to the wild-type strain. Animal infection experiments revealed that loss of ibeB decreased APEC colonization and invasion capacity in brains and lungs. These virulence-related phenotypes were partially recoverable by genetic complementation. Reduced expression levels of invasion- and adhesion-associated genes in ibeB mutant could be major reasons as evidenced by reduced ibeA and ompA expression. These results indicate that IbeB is involved in APEC invasion and pathogenicity.

In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system.

BACKGROUND Coinfection of hepatitis B virus (HBV) or hepatitis C virus (HCV) may compromise pediatric antiretroviral therapy (ART) in China. In this study, we evaluated the seroprevalence of HBV and HCV in children receiving ART and associated factors. METHODS Patients were selected from HIV-1-infected children under age 16 enrolled in China National Pediatric ART Cohort since July 2005. Medical assessments, hepatitis B surface antigen (HBsAg), and anti-HCV antibody serologies, and transaminase levels were obtained for analysis. RESULTS A total of 53 of 1082 children tested were HBsAg seropositive [4.9%; 95% confidence interval (CI): 3.6% to 6.2%], and 90 of 938 children tested were anti-HCV antibody positive (9.6%; 95% CI: 7.7% to 11.5%). No other serologic assays were performed for HBV detection. Age was associated with HBV coinfection in univariate analysis; older children were more likely to be HBsAg positive. Multivariate analysis revealed that children infected with HIV through transfusion of contaminated blood or blood products were more likely to be anti-HCV antibody positive than those infected with HIV through other routes (adjusted odds ratio = 6.2; 95% CI: 3.3% to 11.7%). CONCLUSIONS The high prevalence of HBV and HCV coinfection in HIV-infected children in China receiving ART demands routine screening for viral hepatitis coinfection, intensive prevention of childhood HBV and HCV transmission, and modification of the management of pediatric HIV infection.

Background The objective of this study was to evaluate the radiation dose and response in terms of local-regional progression-free survival (LRPFS) and overall survival (OS) of patients with stage IV non-small cell lung cancer (NSCLC) undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy. Methods In all, we enrolled 201 patients with stage IV NSCLC in this study and analyzed OS in 159 patients and LRPFS in 120. Results The 1-, 2-, 3-, and 5-year OS rates were 46.2%, 19.5%, 11.7%, and 5.8%, respectively, the median survival time being 12 months. The median survival times in differential treatment response of primary tumors were 19 of complete response, 13 of partial response, 8 of stable disease, and 6 months of progressive disease, respectively (P = 0.000). The 1-, 2-, 3-, and 5-year LRPFS rates of patients undergoing four to five cycles with doses ≥63 Gy and

Background The role of chemotherapy given concurrently with thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC) is not well defined. We performed this study to investigate overall survival and toxicity in patients with stage IV NSCLC treated with this modality. Methods From 2003 to 2010, 201 patients were enrolled in this study. All patients received chemotherapy with concurrent thoracic three-dimensional radiotherapy. The study endpoints were the assessment of overall survival (OS) and acute toxicity. Results For all patients, the median survival time (MST) was 10.0 months, and the 1-, 2- and 3-year OS rates were 40.2%, 16.4%, and 9.6%, respectively. The MST was 14.0 months for patients who received a total radiation dose ≥63 Gy to the primary tumor, whereas it was 8.0 months for patients who received a total dose P = 0.000). On multivariate analysis, a total dose ≥63 Gy, a single site of metastatic disease, and undergoing ≥4 cycles of chemotherapy were independent prognostic factors for better OS (P = 0.007, P = 0.014, and P = 0.038, respectively); radiotherapy involving metastatic sites was a marginally significant prognostic factor (P = 0.063). When the whole group was subdivided into patients with metastasis at a single site and multiple sites, a higher radiation dose to the primary tumor remained a significant prognostic factor for improved OS. For patients who received ≥4 cycles of chemotherapy, high radiation dose remained of benefit for OS (P = 0.001). Moreover, for the subgroup that received P = 0.063). Treatment-related toxicity was found to be acceptable. Conclusions Radiation dose to primary tumor, the number of metastatic sites, and the number of chemotherapy cycles were independent prognostic factors for OS in stage IV NSCLC patients treated with concurrent chemoradiotherapy. In addition to systemic chemotherapy, aggressive thoracic radiotherapy was shown to play an important role in improving OS. Trial registration Registered on (ChiCTR-TNC-10001026)