Background Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, the causal association between gut microbiota and cancer remains to be determined. Methods We first identified two sets of gut microbiota based on phylum, class, order, family, and genus level information, and cancer data were obtained from the IEU Open GWAS project. We then performed two-sample Mendelian randomisation (MR) to determine whether the gut microbiota is causally associated with eight cancer types. Furthermore, we performed a bi-directional MR analysis to examine the direction of the causal relations. Results We identified 11 causal relationships between genetic liability in the gut microbiome and cancer, including those involving the genus Bifidobacterium. We found 17 strong associations between genetic liability in the gut microbiome and cancer. Moreover, we found 24 associations between genetic liability in the gut microbiome and cancer using multiple datasets. Conclusions Our MR analysis revealed that the gut microbiota was causally associated with cancers and may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer.
Hepatocyte nuclear factors 4 alpha (HNF4alpha) and 3 beta (HNF3beta) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV). Using cell culture and animal models, we showed that HNF4alpha supports HBV replication in nonhepatic cells and HNF3beta inhibits HBV replication. However, the expression of HNF4alpha and HNF3beta in the liver tissue of chronic HBV-infected patients and the relationship between the levels of HNF4alpha and HNF3beta and HBV replication are unclear. In this study, liver biopsy specimens from 86 chronic HBV-infected patients were collected. The expression levels of HNF4alpha, HNF3beta, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were detected by an immunohistochemical technique and the level of HBV DNA was checked by in situ hybridization with serial sections from liver biopsy tissue samples. We show here that samples with higher levels of HNF4alpha expression also have higher levels of HBsAg, HBcAg and HBV DNA. In contrast, in samples with higher levels of HNF3beta expression, levels of HBsAg, HBcAg and HBV DNA were lower. There was a positive correlation between HNF4alpha expression and HBV replication, and a negative correlation between HNF3beta expression and HBV replication, in the liver of chronic HBV-infected patients. This suggests that HNF4alpha and HNF3beta likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4alpha and HNF3beta in the liver.
Background The purpose of this study was to compare short-course radiotherapy (SC) or neoadjuvant long-course chemoradiotherapy (LC) treatment for locally advanced rectal cancer patients. Methods Patients with a diagnosis of locally advanced rectal cancer (LARC) who had undergone neoadjuvant radiotherapy before surgery between 2013 and 2018 at the medical center in China were included in this study. All patients’ MRI confirmed T2N+M0 or T3-4N0-3M0 clinical stages. Patients in the SC group received pelvic radiotherapy with a dose of 5 × 5 Gy (with or without chemotherapy at any time), followed by immediate or delayed surgery. Patients in the LC group received a dose of 50–50.4 Gy in 25–28 fractions, concomitantly with FOLFOX or capecitabine-based chemotherapy, followed by surgery 4–6 weeks later. All clinical data were retrospectively collected, and long-term follow-up was completed and recorded at the same time. Results A total of 170 were eligible to participate in this study, 32 patients in the SC group, and 138 in the LC group. The median follow-up time of living patients was 39 months. The disease-free survival (DFS) and overall survival (OS) rates in the SC group and LC group at 3 years, were, 84.9% versus 72.4% (P = 0.273) and 96.2% versus 87.2% (P = 0.510), respectively. The complete pathological response (pCR) rates in the SC group and LC group were, 25% versus 18.1% (the difference was not statistically significant, P = 0.375), respectively. However, the SC group had better node(N) downstaging compared to the LC group (P = 0.011). Conclusions There were no differences observed in DFS and OS between short-course radiotherapy and long-course chemoradiation, and both can be used as treatment options for patients with locally advanced rectal cancer.
AIMTo investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B.METHODSA total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response.RESULTSThe rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk.CONCLUSIONHepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.
Neoadjuvant therapy and adjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC) with ALK fusion mutation have not been thoroughly studied. Here, a stage IIIB NSCLC patient with EML4-ALK fusion mutation receiving immunotherapy plus chemotherapy as neoadjuvant treatment followed by lobectomy plus lymph node dissection is reported. The patient achieved a pathological complete response according to pathological evaluation. The patient received adjuvant crizotinib for 3 months and achieved a disease-free survival time of 36 months.
Objective A diagnostic model was established to discriminate infectious diseases from non-infectious diseases. Methods The clinical data of patients with fever of unknown origin (FUO) hospitalized in Xiangya Hospital Central South University, from January, 2006 to April, 2011 were retrospectively analyzed. Patients enrolled were divided into two groups. The first group was used to develop a diagnostic model: independent variables were recorded and considered in a logistic regression analysis to identify infectious and non-infectious diseases (αin = 0.05, αout = 0.10). The second group was used to evaluate the diagnostic model and make ROC analysis. Results The diagnostic rate of 143 patients in the first group was 87.4%, the diagnosis included infectious disease (52.4%), connective tissue diseases (16.8%), neoplastic disease (16.1%) and miscellaneous (2.1%). The diagnostic rate of 168 patients in the second group was 88.4%, and the diagnosis was similar to the first group. Logistic regression analysis showed that decreased white blood cell count (WBC < 4.0×109/L), higher lactate dehydrogenase level (LDH > 320 U/L) and lymphadenectasis were independent risk factors associated with non-infectious diseases. The odds ratios were 14.74, 5.84 and 5.11 (P ≤ 0.01) , respectively. In ROC analysis, the sensitivity and specificity of the positive predictive values was 62.1% and 89.1%, respectively, while that of negative predicting values were 75% and 81.7%, respectively (AUC = 0.76, P = 0.00). Conclusions The combination of WBC < 4.0×109/L, LDH > 320 U/L and lymphadenectasis may be useful in discriminating infectious diseases from non-infectious diseases in patients hospitalized as FUO.
BackgroundThe purpose of this study was to compare short-course radiotherapy (SC) or neoadjuvant long-course chemoradiotherapy (LC) treatment for locally advanced rectal cancer patients.MethodsPatients with a diagnosis of locally advanced rectal cancer (LARC) who had undergone neoadjuvant radiotherapy before surgery between 2013 and 2018 at the medical center in China were included in this study. All patients’ MRI confirmed T2N+M0 or T3-4N0-3M0 clinical stages. Patients in the SC group received pelvic radiotherapy with a dose of 5×5 Gy (with or without chemotherapy at any time), followed by immediate or delayed surgery. Patients in the LC group received a dose of 50-50.4 Gy in 25-28 fractions, concomitantly with FOLFOX or capecitabine-based chemotherapy, followed by surgery 4-6 weeks later. All clinical data were retrospectively collected, and long-term follow-up was completed and recorded at the same time.ResultsA total of 170 were eligible to participate in this study, 32 patients in the SC group, and 138 in the LC group. The median follow-up time of living patients was 39 months. The disease-free survival (DFS) and overall survival (OS) rates in the SC group and LC group at 3 years, were, 84.9% versus 72.4% (P= 0.273) and 96.2% versus 87.2% (P= 0.510), respectively. The complete pathological response (pCR) rates in the SC group and LC group were, 25% versus 18.1% (the difference was not statistically significant, P=0.375), respectively. However, the SC group had better node(N) downstaging compared to the LC group (P=0.011).ConclusionsThere were no differences observed in DFS and OS between short-course radiotherapy and long-course chemoradiation, and both can be used as treatment options for patients with locally advanced rectal cancer.
Background:The purpose of this study was to compare short-course radiotherapy (SC) or neoadjuvant long-course chemoradiotherapy (LC) treatment for locally advanced rectal cancer patients.Methods:Patients with a diagnosis of locally advanced rectal cancer (LARC) who had undergone neoadjuvant radiotherapy before surgery between 2013 and 2018 at the medical center in China were included in this study. All patients’ MRI confirmed T2N+M0 or T3-4N0-3M0 clinical stages. Patients in the SC group received pelvic radiotherapy with a dose of 5×5 Gy (with or without chemotherapy at any time), followed by immediate or delayed surgery. Patients in the LC group received a dose of 50-50.4 Gy in 25-28 fractions, concomitantly with FOLFOX or capecitabine-based chemotherapy, followed by surgery 4-6 weeks later. All clinical data were retrospectively collected, and long-term follow-up was completed and recorded at the same time.Results:A total of 170 were eligible to participate in this study, 32 patients in the SC group, and 138 in the LC group. The median follow-up time of living patients was 39 months. The disease-free survival (DFS) and overall survival (OS) rates in the SC group and LC group at 3 years, were, 84.9% versus 72.4% (P= 0.273) and 96.2% versus 87.2% (P= 0.510), respectively. The complete pathological response (pCR) rates in the SC group and LC group were, 25% versus 18.1% (the difference was not statistically significant, P=0.375), respectively. However, the SC group had better node(N) downstaging compared to the LC group (P=0.011).Conclusions:There were no differences observed in DFS and OS between short-course radiotherapy and long-course chemoradiation, and both can be used as treatment options for patients with locally advanced rectal cancer.
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