Background: Targeting the gut microbiota may become a new therapeutic to prevent and delay the progression of chronic kidney disease (CKD). Nonetheless, the causal relationship between specific intestinal flora and CKD is still unclear. Materials and Method: To identify genetically predicted microbiota, we used summary data from genome-wide association studies on gut microbiota in 18340 participants from 24 cohorts. Furthermore, we genetically predicted the causal relationship between 211 gut microbiotas and six phenotypes (outcomes) (CKD, estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), dialysis, rapid progress to CKD, and rapid decline of eGFR). Four Mendelian randomization (MR) methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the casual relationship between gut microbiotas and various outcomes. The result of IVW was deemed as the primary result. Then, Cochrane’s Q test, MR-Egger, and MR-PRESSO Global test were used to detect heterogeneity and pleiotropy. The leave-one method was used for testing the stability of MR results and Bonferroni-corrected was used to test the strength of the causal relationship between exposure and outcome. Results: Through the MR analysis of 211 microbiotas and six clinical phenotypes, a total of 36 intestinal microflora were found to be associated with various outcomes. Among them, Class Bacteroidia (=−0.005, 95% CI: −0.001 to −0.008, p = 0.002) has a strong causality with lower eGFR after the Bonferroni-corrected test, whereas phylum Actinobacteria (OR = 1.0009, 95%CI: 1.0003–1.0015, p = 0.0024) has a strong causal relationship with dialysis. The Cochrane’s Q test reveals that there is no significant heterogeneity between various single nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to MR-Egger and MR-PRESSO Global tests. Conclusions: Through the two-sample MR analysis, we identified the specific intestinal flora that has a causal relationship with the incidence and progression of CKD at the level of gene prediction, which may provide helpful biomarkers for early disease diagnosis and potential therapeutic targets for CKD.

Background: Limited studies have explored the joint effect of physical activity (PA) and dietary quality (DQ) on the mortality outcomes of the cancer population. The authors aim to investigate the separate and joint prognostic effect of PA and DQ on the survival of US cancer survivors. Methods: Data of cancer survivors (n=3007, representing 22 million cancer survivors) were from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. PA was assessed using the self-reported Global Physical Activity Questionnaire (GPAQ) and DQ was evaluated through the Health Eating Index-2015 (HEI-2015). Kaplan–Meier (KM) curves and the Cox proportional hazard model were used to evaluate the associations between separate and joint prognostic effects of PA and DQ with mortality outcomes among cancer survivors. Results: In the joint analyses, cancer survivors with sufficiently active PA (≥600 MET-min/week) and qualified DQ (≥60) presented reduced risks of all-cause mortality (HR 0.45, 95% CI: 0.35–0.59) as compared with each lifestyle intervention separately. Meanwhile, the joint effects of either insufficiently or sufficiently active PA (>0 MET-min/week) and qualified DQ (≥60) were associated with lower risks for cancer (HR 0.60, 95% CI: 0.40–0.90) and noncancer mortality (HR 0.43, 95% CI: 0.32–0.59). Conclusions: Our study highlights the combination of active PA and qualified DQ was strongly associated with reduced mortality risk of cancer survivors. Our findings might help to refine the lifestyle intervention recommendations for this population.

Background: Young women with breast cancer are determined to present poorer survival compare with elderly patients. Therefore, identifying the clinical prognostic factors in young women with early-stage (T_1-2N_0-1M₀) breast cancer is pivotal for surgeons to make better postoperative management.Methods: The clinicopathological characteristics of female patients with early-stage breast cancer from the Surveillance, Epidemiology, and End Results program between Jan 2010 and Dec 2015 were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analyses were used to determine the potential risk factors of cancer-specific survival in young women with early-stage breast cancer. The nomogram was constructed and further evaluated by an internal validation cohort. The Kaplan-Meier survival curves were used to estimate cancer-specific survival probability and the cumulative incidence.Results: Six variables including race, tumor location, grade, regional lymph node status, tumor subtype, and size were identified to be significantly associated with the prognosis of young women with early-stage breast cancer during the postoperative follow-up. A nomogram for predicting the 3-, 5- year cancer-specific survival probability in this subpopulation group was established with a favorable concordance index of 0.783, supported by an internal validation cohort with the AUC of 0.722 and 0.696 in 3-, 5- year cancer-specific survival probability, respectively.Conclusions: The first predictive nomogram containing favorable discrimination is successfully established and validated for predicting the 3-, 5- year cancer-specific survival probability in young women with early-stage breast cancer during the postoperative follow-up. This model would help clinicians to make accurate treatment decisions in different clinical risk population.

3050Background: We performed the first phase I clinical trial (NCT02793856) to assess safety of CRISPR/Cas9-mediated knockout of PD-1 gene in autologous T lymphocytes (PD-1-/- T) therapy in patients with metastatic non-small cell lung cancer (NSCLC). Methods: We assigned patients with advanced NSCLC with positive PD-L1 expression who had progressed after 3rd line standard therapeutic regimens. Two patients were enrolled in Pre-A cohort who received PD-1-/- T therapy with 2 x 107 cells/kg for one cycle and were observed for another cycle. Then 3 cohorts (A, B, C) enrolled 3 patients in each group receiving PD-1-/- T cells therapy with 1×107/kg, 2×107/kg, 4×107/kg in each cycle, respectively. Patients received PD-1-/- T therapy until disease progression or study withdrawal. Primary outcome was safety. Secondary end points were 8 weeks disease control rate (DCR) and progression-free survival (PFS). In exploratory analyses, next-generation sequencing was performed on PD-1 editing region of T cells and CDR3 re...

Background: Recent evidence suggests that the Ki-67 labeling index is associated with lymph node metastasis and the prognosis of papillary thyroid carcinoma (PTC). Methods: We retrospectively evaluated the clinicopathological features of consecutive PTC patients between Jan 2019 and Oct 2020 in our medical center. The molecular analysis was also conducted by using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) program. The Chi-square test was performed for the comparison of variables between patients with central lymph node metastasis (CLNM) and not. Besides, univariate and stepwise multivariate logistic regression analyses were further used to determine the risk factors for CLNM in PTC. Results: Our results showed that male gender (odd ratio (OR) = 3.02; 95% CI: 1.81-5.04), tumor size >1 cm (OR = 2.81; 95% CI: 1.84-4.29), multifocality (OR = 2.08; 95% CI: 1.31-3.30, and Ki-67 labeling index (>3% and ≤5%: OR = 1.20; 95% CI: .73-1.97; >5%: OR = 3.85; 95% CI: 1.62-9.14) were independent risk factors for CLNM. After excluding the patients with harvested central lymph nodes 5%) is significantly associated with the CLNM in PTC patients, like other indicators of the male gender, larger tumor size, and multifocality. Besides, the Ki-67 was also determined to be associated with CLNM and DFS in PTC patients, which may act as an important molecular marker in PTC.