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Background: N6-methyladenosine (m6A) RNA methylation plays a critical role in key genetic events for various cancers; yet, how m6A functions within the tumor microenvironment (TME) remains to be elucidated.Methods: A total of 65,362 single cells from single-cell RNA-seq data derived from 33 CRC tumor samples were analyzed by nonnegative matrix factorization (NMF) for 23 m6A RNA methylation regulators. CRC and Immunotherapy cohorts from public repository were used to determine the prognosis and immune response of TME clusters.Results: The fibroblasts, macrophages, T and B cells were respectively grouped into 4 to 5 subclusters and then classified according to various biological processes and different marker genes. Furthermore, it revealed that the m6A RNA methylation regulators might be significantly related to the clinical and biological features of CRC, as well as the pseudotime trajectories of main TME cell types. Bulk-seq analysis suggested that these m6A-mediated TME cell subclusters had significant prognostic value for CRC patients and distinguished immune response for patients who underwent ICB therapy, especially for the CAFs and macrophages. Notably, CellChat analysis revealed that RNA m6A methylation-associated cell subtypes of TME cells manifested diverse and extensive interaction with tumor epithelial cells. Further analysis showed that ligand-receptor pairs, including MIF -  (CD74 + CXCR4), MIF -  (CD74 + CD44), MDK-NCL and LGALS9 - CD45, etc. mediated the communication between m6A associated subtypes of TME cells and tumor epithelial cells.Conclusions: Taken together, our study firstly revealed the m6A methylation mediated intercellular communication of the tumor microenvironment in the regulation of tumor growth and antitumor immunomodulatory processes. [ABSTRACT FROM AUTHOR]

Background: The incidence of the para-aortic lymph node metastasis (PALM) in patients with advanced gastric cancer is 6 to 33 %. The prognosis is poor and the 5-year survival rate is only 12 to 23 % after gastrectomy with super-extended lymph node dissection. We applied an individualized comprehensive treatment for affected patients including neoadjuvant chemotherapy via intra-arterial and intravenous administration, surgery and radiotherapy, to investigate the safety and prognostic value.Methods: Between January 2005 and December 2010, 47 advanced gastric cancer patients with PALM received 5-Fu (370 mg/m(2)) and leucovorin (200 mg/m(2)) intravenously on days 1-5, and intra-arterial infusion of etoposide (80 mg/m(2)) and oxaliplatin (80 mg/m(2)) on days 6 and 20, repeated 2 cycles. Patients achieved PR or CR of the para-aortic lymph node (PAL) were performed D2 dissection, followed by 6 cycles chemotherapy with XELOX regimen, oxaliplatin (130 mg/m(2)) on day 1 and xeloda (1000 mg/m(2)) on days 1 to 14 of a 28-day cycle, and radiotherapy to the region of PALM.Results: Forty-six patients completed 2 cycles of neoadjuvant chemotherapy. The overall response rate of the primary tumor was 80.4 % (37/46). The response rate of PAL was 76.1 % (35/46). Thirty-two patients underwent D2 dissection and six cases achieved pathological complete response (pCR). The toxicity profile was well tolerable and there was no treatment-related death. The median survival time for all patients was 23 months, and for nonsurgical and surgical patients were 12 and 29 months (p < 0.001), respectively. The 1-year, 2-year and 3-year survival rate was 70.96, 43.27 and 35.48 % for all patients, and for surgical patients was 96.875, 68.75, and 40.63 %.Conclusion: Advanced gastric cancer patients with PALM can obtain a survival benefit from neoadjuvant chemotherapy, subsequent surgery and radiotherapy.Trial Registration: Current Controlled Trials ChiCTR-TRC-12002046 . [ABSTRACT FROM AUTHOR]

Background: Drug-resistant tuberculosis (TB) has emerged as a major challenge toward TB control and prevention. In Lianyungang city, the extent and trend of drug resistant TB is not well known. The objective of the survey was to assess drug resistance pattern of MTB and risk factors for drug resistant TB, including multidrug resistance tuberculosis (MDR-TB) in this area.Methods: We performed drug susceptibility testing on Mycobacterium tuberculosis (MTB) isolates with first- and second-line anti-tuberculosis drugs of 1012 culture positive TB cases by using the proportion method, who were consecutively enrolled from January 2011 to December 2012 in Lianyungang city, China. The patterns of drug resistance in MTB were investigated and multiple logistic regression analysis was performed to assess the risk factors for drug resistant TB.Results: Among the 1012 strains tested, 308 (30.4%) strains were resistant to at least one first-line drug; the prevalence of MDR-TB was 88 (8.7%), 5 (0.5%) strains were found to be extensively drug-resistant tuberculosis (XDR-TB). Female gender was a risk factor for MDR-TB (adjusted odds ratio (aOR) 1.763, 95% CI (1.060-2.934). The aged 28-54 years was significantly associated with the risk of MDR-TB with an aOR: 2.224, 95% CI (1.158-4.273) when compared with those 65 years or older. Patients with previous treatment history had a more than 7-fold increased risk of MDR-TB, compared with those never previously treated.Conclusions: The burden of drug resistant TB cases is sizeable, which highlights an urgent need to reinforce control, detection and treatment strategies for drug resistant TB. [ABSTRACT FROM AUTHOR]

Background: The incidence of the para-aortic lymph node metastasis (PALM) in patients with advanced gastric cancer is 6 to 33 %. The prognosis is poor and the 5-year survival rate is only 12 to 23 % after gastrectomy with super-extended lymph node dissection. We applied an individualized comprehensive treatment for affected patients including neoadjuvant chemotherapy via intra-arterial and intravenous administration, surgery and radiotherapy, to investigate the safety and prognostic value., Methods: Between January 2005 and December 2010, 47 advanced gastric cancer patients with PALM received 5-Fu (370 mg/m(2)) and leucovorin (200 mg/m(2)) intravenously on days 1-5, and intra-arterial infusion of etoposide (80 mg/m(2)) and oxaliplatin (80 mg/m(2)) on days 6 and 20, repeated 2 cycles. Patients achieved PR or CR of the para-aortic lymph node (PAL) were performed D2 dissection, followed by 6 cycles chemotherapy with XELOX regimen, oxaliplatin (130 mg/m(2)) on day 1 and xeloda (1000 mg/m(2)) on days 1 to 14 of a 28-day cycle, and radiotherapy to the region of PALM., Results: Forty-six patients completed 2 cycles of neoadjuvant chemotherapy. The overall response rate of the primary tumor was 80.4 % (37/46). The response rate of PAL was 76.1 % (35/46). Thirty-two patients underwent D2 dissection and six cases achieved pathological complete response (pCR). The toxicity profile was well tolerable and there was no treatment-related death. The median survival time for all patients was 23 months, and for nonsurgical and surgical patients were 12 and 29 months (p < 0.001), respectively. The 1-year, 2-year and 3-year survival rate was 70.96, 43.27 and 35.48 % for all patients, and for surgical patients was 96.875, 68.75, and 40.63 %., Conclusion: Advanced gastric cancer patients with PALM can obtain a survival benefit from neoadjuvant chemotherapy, subsequent surgery and radiotherapy., Trial Registration: Current Controlled Trials ChiCTR-TRC-12002046 .

Background: The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX) with different routes of administration for unresectable gastric cancer., Methods: A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients) received the FLEEOX regimen(fluorouracil, leucovorin, http://epirubicin, epotoside, and oxaliplatin), which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients) received XELOX (capecitabine plus oxaliplatin) via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared., Results: In the FLEEOX group, the clinical response rate (RR) of chemotherapy was 85.4% (41 of 48 patients) and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS) rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P < 0.05) in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups., Conclusions: For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.

Background: Globally, China is the second place with high burden of tuberculosis (TB). To explore the characteristics of the pathogens of Mycobacterium tuberculosis (MTB) circulating in this area is helpful for understanding and controlling the spread of the strains. Recent developments in molecular biology have allowed prompt identification and tracking specific strains of MTB spreading through the population., Methods: Spacer-oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) were performed in combination to yield specific genetic profiles of 260 MTB strains isolated from 30 counties of Jiangsu province in China between June and July 2010. The spoligotyping results were in comparison to the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4). Drug susceptibility test (DST) was performed on all strains by proportion method on Lowenstein-Jensen (LJ) culture media., Results: Based on the spoligotyping method, 246 strains displayed known patterns and 14 were absent in the database. Predominant spoligotypes belonged to the Beijing family (80.4%). By using the 24-loci VNTR typing scheme, 224 different patterns were identified, including 20 clusters and 204 unique patterns. The largest clade comprised 195 strains belonging to the Beijing family. The combination of spoligotyping and 24-loci MIRU-VNTR demonstrated maximal discriminatory power. Furthermore, we observed a significant association between Beijing family strains and drug-resistant phenotypes. The Beijing family strains presented increased risks for developing multi-drug resistant TB, with the OR (95% CI) of 11.07(1.45-84.50)., Conclusions: The present study demonstrated that Beijing family isolates were the most prevalent strains circulating in Jiangsu province of China. The utility of spoligotyping in combination with 24-loci MIRU-VNTR might be a useful tool for epidemiological analysis of MTB transmission.

Background: Statins are first-line pharmacotherapeutic agents for hypercholesterolemia treatment in humans. However the effects of statins on atherosclerosis in mouse models are very paradoxical. In this work, we wanted to evaluate the effects of simvastatin on serum cholesterol, atherogenesis, and the expression of several factors playing important roles in reverse cholesterol transport (RCT) in apoE-/- mice fed a high-fat diet., Results: The atherosclerotic lesion formation displayed by oil red O staining positive area was reduced significantly by 35% or 47% in either aortic root section or aortic arch en face in simvastatin administrated apoE-/- mice compared to the control. Plasma analysis by enzymatic method or ELISA showed that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) contents were remarkably increased by treatment with simvastatin. And plasma lecithin-cholesterol acyltransferase (LCAT) activity was markedly increased by simvastatin treatment. Real-time PCR detection disclosed that the expression of several transporters involved in reverse cholesterol transport, including macrophage scavenger receptor class B type I, hepatic ATP-binding cassette (ABC) transporters ABCG5, and ABCB4 were induced by simvastatin treatment, the expression of hepatic ABCA1 and apoA-I, which play roles in the maturation of HDL-C, were also elevated in simvastatin treated groups., Conclusions: We demonstrated the anti-atherogenesis effects of simvastatin in apoE-/- mice fed a high-fat diet. We confirmed here for the first time simvastatin increased the expression of hepatic ABCB4 and ABCG5, which involved in secretion of cholesterol and bile acids into the bile, besides upregulated ABCA1 and apoA-I. The elevated HDL-C level, increased LCAT activity and the stimulation of several transporters involved in RCT may all contribute to the anti-atherosclerotic effect of simvastatin.