Chronotype and cognitive function: Observational study and bidirectional Mendelian randomization.

Background: Association has been found between chronotype and cognitive function in conventional observational studies but whether this association is causal and if so, its direction, is uncertain. There are also concerns among people with later chronotype that their habits may be detrimental to cognitive function. Methods: We analyzed the association between chronotype (measured as sleep midpoint) and cognitive function (measured by Mini-Mental Status Examination (MMSE) and Delayed Word Recall Test (DWRT)) using multivariable linear regression on 14,582 participants in the Guangzhou biobank cohort study (GBCS) from 2008 to 2012. Using bidirectional Mendelian randomization, we used 207 single nucleotide polymorphisms (SNPs) associated with chronotype from the combination of UK Biobank and 23andMe (n = 697,828), and 127 SNPs associated with cognitive function from the combination of UK Biobank and COGENT consortium (n = 257,841). Findings: Observationally in GBCS, later chronotype was associated with better cognitive function (MMSE scores: ß = 0.14 per hour; 95% confidence interval (CI), 0.09-0.19; DWRT scores: ß = 0.07 per hour; 95% CI, 0.04-0.11). Bidirectional MR showed genetic predisposition to early, versus later, chronotype was not associated with cognitive function using inverse-variance weighted (ß = -0.02; 95% CI, -0.05 to 0.01). However, better cognitive function was associated with decreased odds of early chronotype (UK Biobank: odds ratio = 0.88 per standardized score; 95% CI, 0.83-0.93; 23andMe: 0.87 per standardized score; 95% CI, 0.80-0.95). Interpretation: It is a reassuring finding for adults with later chronotype who may be concerned if such a habit has a negative impact on cognitive function. Funding: The National Natural Science Foundation of China; Natural Science Foundation of Guangdong; The University of Hong Kong Foundation for Educational Development and Research; The Health Medical Research Fund in Hong Kong; The University of Birmingham, UK.

Cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma.

BACKGROUND: Cuproptosis has recently been considered a novel form of programmed cell death. To date, long-chain non-coding RNAs (lncRNAs) crucial to the regulation of this process remain unelucidated. AIM: To identify lncRNAs linked to cuproptosis in order to estimate patients' prognoses for hepatocellular carcinoma (HCC). METHODS: Using RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma (TCGA-LIHC), a co-expression network of cuproptosis-related genes and lncRNAs was constructed. For HCC prognosis, we developed a cuproptosis-related lncRNA signature (CupRLSig) using univariate Cox, lasso, and multivariate Cox regression analyses. Kaplan-Meier analysis was used to compare overall survival among high- and low-risk groups stratified by median CupRLSig risk score. Furthermore, comparisons of functional annotation, immune infiltration, somatic mutation, tumor mutation burden (TMB), and pharmacologic options were made between high- and low-risk groups. RESULTS: Three hundred and forty-three patients with complete follow-up data were recruited in the analysis. Pearson correlation analysis identified 157 cuproptosis-related lncRNAs related to 14 cuproptosis genes. Next, we divided the TCGA-LIHC sample into a training set and a validation set. In univariate Cox regression analysis, 27 LncRNAs with prognostic value were identified in the training set. After lasso regression, the multivariate Cox regression model determined the identified risk equation as follows: Risk score = (0.2659 × PICSAR expression) + (0.4374 × FOXD2-AS1 expression) + (-0.3467 × AP001065.1 expression). The CupRLSig high-risk group was associated with poor overall survival (hazard ratio = 1.162, 95%CI = 1.063-1.270; P < 0.001) after the patients were divided into two groups depending upon their median risk score. Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as the validation set. The area under the curve of 0.741 was found to be a better predictor of HCC prognosis as compared to other clinicopathological variables. Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses (median survival of 30 mo vs 102 mo of low-risk combinations with low TMB group). The low-risk group had more activated natural killer cells (NK cells, P = 0.032 by Wilcoxon rank sum test) and fewer regulatory T cells (Tregs, P = 0.021) infiltration than the high-risk group. This finding could explain why the low-risk group has a better prognosis. Interestingly, when checkpoint gene expression (CD276, CTLA-4, and PDCD-1) and tumor immune dysfunction and rejection (TIDE) scores are considered, high-risk patients may respond better to immunotherapy. Finally, most drugs commonly used in preclinical and clinical systemic therapy for HCC, such as 5-fluorouracil, gemcitabine, paclitaxel, imatinib, sunitinib, rapamycin, and XL-184 (cabozantinib), were found to be more efficacious in the low-risk group; erlotinib, an exception, was more efficacious in the high-risk group. CONCLUSION: The lncRNA signature, CupRLSig, constructed in this study is valuable in prognostic estimation of HCC. Importantly, CupRLSig also predicts the level of immune infiltration and potential efficacy of tumor immunotherapy.

Preoperative Progressive Pneumoperitoneum Enables Defect Closure and Laparoscopic Repair of Large Parastomal Hernias.

PURPOSE: Preoperative progressive pneumoperitoneum (PPP) has not been reported in the management of parastomal hernias; therefore, the present study evaluated its effectiveness in the surgical management of large parastomal hernias. PATIENTS AND METHODS: This prospective, observational study included 23 consecutive patients with large parastomal hernias who underwent PPP between January 2016 and September 2018. The volume of parastomal hernia (VPH), volume of the abdominal cavity (VAC), and the VPH/VAC ratio were measured before and after PPP using abdominal computed tomography scan data. All the hernias were repaired by a laparoscopic or laparoscopic-open-laparoscopic approach using the intraperitoneal Sugarbaker technique. RESULTS: Before and after PPP, the mean VPH was 1442 and 1581 mL (P<0.01), and the mean VAC was 5667 and 9194 mL (P<0.01). The VAC increased by 3527 mL (P<0.01) and was greater than the mean VPH before PPP. The VPH/VAC ratio after PPP was reduced at an average of 8.1% (P<0.01). Fascial closure was achieved in all patients, with no clinical evidence of elevated intra-abdominal pressures. The mean follow-up was 24 months (13 to 40 mo), and, to date, no hernia recurrences have been reported in these patients. CONCLUSIONS: PPP is a feasible and useful tool in the surgical management of large parastomal hernias. It passively expands the abdominal volumes, thereby resulting in respiratory adaptation to elevated intra-abdominal pressures.

MicroRNA-520c enhances cell proliferation, migration, and invasion by suppressing IRF2 in gastric cancer.

Dysregulation of microRNA (miRNA) is actively involved in the development and progression of gastric cancer (GC). MiR-520c was previously found to be overexpressed in GC specimens and cells. However, the clinical significance of miR-520c and its biological function in GC remain largely unknown. Here, we found that miR-520c expression in GC tissues was significantly increased compared to normal adjacent gastric tissues. Its increased level was prominently correlated with poor clinical parameters and prognosis of GC patients. Accordingly, the expression of miR-520c was obviously elevated in GC cell lines as compared with gastric epithelial cells. Overexpression of miR-520c in N-87 cells significantly increased the proliferative ability, migration, and invasion of cancer cells, while miR-520c silencing suppressed MKN-45 cell proliferation, migration, and invasion in vitro. Mechanically, miR-520c inversely regulated interferon regulatory factor 2 (IRF2) abundance in GC cells. Herein, IRF2 was found to be a downstream target of miR-520c in GC. Furthermore, IRF2 was down-regulated in GC tissues compared to nontumor tissues. An inverse correlation between IRF2 and miR-520c expression was observed in GC cases. Taken together, miR-520c may serve as a prognostic predictor and a therapeutic target for GC patients.

Long-term outcome for open preperitoneal mesh repair of recurrent inguinal hernia.

AIM: Recurrent inguinal hernia represents a major challenge for surgeons with high risks of re-recurrence and complications, especially when an anterior approach is adopted. The aim of this study was to evaluate the long-term results of the open preperitoneal mesh repair for recurrent inguinal hernia. METHODS: We performed a prospective clinical study of 107 consecutive patients having recurrent inguinal hernias between April 2006 and November 2010. All patients were operated on using open preperitoneal mesh repair. The demographics, perioperative variables, complications and recurrences were evaluated with all patients. RESULTS: There were no major intraoperative complications. The average operative time was 42.1 min (range 28-83 min) for unilateral and 62.7 min (range 38-106 min) for bilateral hernias. The mean postoperative hospital stay was 1.6 days (range 1-9 days). The overall complication rate was 8.4%. There were two superficial wound infections, two groin seroma and three urinary retention. The mean follow-up time was 42.3 months (range 28-73 months), three patients developed hernia recurrence. No testicular, chronic pain or mesh-related complications were noted in these series. CONCLUSION: Open posterior preperitoneal mesh repair offers a viable option for recurrent inguinal hernias and achieves equally effective results to laparoscopic approaches with acceptable complication and recurrence rates. It is safer and easier to learn than laparoscopic repair and has become the preferred approach for treatment of the majority of recurrent inguinal hernias at our institution, especially useful for complex multirecurrent hernias and patients with cardiopulmonary insufficiency.

A label-free fluorescent molecular beacon based on DNA-templated silver nanoclusters for detection of adenosine and adenosine deaminase.

A simple and reliable fluorescent molecular beacon is developed utilizing DNA-templated silver nanoclusters as a signal indicator and adenosine triphosphate (ATP) and adenosine deaminase as mechanical activators.

[Application of fat clearance technique in pathologic staging for colon cancer].

OBJECTIVE: To evaluate whether the use of fat clearance technique improves the accuracy of staging for colon cancer. METHODS: Between June 2007 and December 2008, surgical specimens of 91 patients with colon cancer were procured. Between June 2007 and January 2008, routine technique for lymph node harvest including visualization and tactile sensation was used in 45 patients (conventional group), while lymph nodes of 46 patients between February 2008 and December 2008 were examined using fat clearance technique(fat clearance group). RESULTS: The mean of lymph nodes harvested was 32.7 using fat clearance technique, significantly higher than that(15.3) of the conventional group(P<0.01). The mean positive lymph nodes was 2.7 and 1.8 in the two groups, respectively, with a statistically significant difference(P<0.05). There were more stage III( colon cancer in the postoperative staging than that in the preoperative staging using fat clearance technique (31 vs.19, P<0.05), while there was no difference in stage III( colon cancer between postoperative staging and preoperative staging using conventional method (21 vs.19, P>0.05). CONCLUSIONS: Fat clearance technique significantly increases number of lymph node retrieval and positive nodes, therefore the accuracy of postoperative staging is improved.

[The influence of lymph nodes detection on pathological staging in rectal cancer].

OBJECTIVE: To investigate the influence of lymph nodes detection on the pathological staging in rectal cancer specimens. METHODS: From January 2007 to June 2008, 75 patients with rectal cancer who underwent total mesorectal excision were randomly divided into two groups: conventional group (n = 39), in which lymph nodes were detected by sight and palpation; fat clearance group (n = 36), in which lymph nodes were harvested after the specimens immersed in a fat clearance solution for 24 hours. The lymph node number harvested was compared between the two groups, and metastasis of the lymph nodes and its impact on the pathologic staging was analyzed in the two groups. RESULTS: A total of 75 patients (42 male and 33 female, the average age was 53.2 years) were enrolled in this study. In the conventional group, a mean of 14.4 lymph nodes (range, 8 - 27) was detected, and was significantly less than that in fat clearance group (mean 36.2, range, 18 - 62) (t = 5.800, P < 0.05). The tumor invasion was classified as T1 in 4 cases and 5 cases, T2 in 9 cases and 6 cases, T3 in 24 cases and 22 cases and T4 in 2 cases and 3 cases in conventional group and fat clearance group, respectively. No significant difference was found in T classification between the two groups (Z = 0.160, P = 0.850). The mean number of metastatic lymph nodes harvested in conventional group was 1.5, and it was 3.2 in the fat clearance group (Z = 3.500, P < 0.05). According to the regional lymph nodes, patients classified as N0, N1 and N2 were 20, 12, 7 cases in conventional group, and were 9, 14, 13 cases in the fat clearance group, respectively; and there was significant difference between the two groups (Z = 2.410, P = 0.016). CONCLUSIONS: The variation of the number of harvested lymph nodes in surgical specimens from rectal cancer after total mesorectal excision is great. The metastasis of mesorectal lymph nodes is not only associated with the tumor staging, but also related to the number of harvested lymph nodes. It is questionable that 12 lymph nodes is currently seen as enough to evaluate the pathologic staging for rectal cancer.

[Comparison of fat clearance and fat lucidification in examining rectal cancer specimen].

OBJECTIVE: To compare fat clearance and fat lucidification in the examination of rectal cancer specimen, and to study the distribution pattern of lymph nodes in rectal cancer specimen. METHOD: Between January 2007 and December 2007, sixty-four cases undergone total mesorectal excision were divided into two groups. The fat clearance technique was used to examine the specimens in one group, while fat lucidification was used in the other. The total number and the number of metastatic lymph nodes between two groups were compared, as well as the time for processing specimens and that for dissecting the lymph nodes. RESULTS: An average of 37.4 lymph nodes were detected with fat clearance, in which 3.3 lymph nodes were metastatic; while an average of 36.2 nodes were detected with fat lucidification, in which 3.2 were metastatic. There were no significant differences in either the total number or the number of metastatic lymph nodes. The time for processing specimens in the fat lucidification group was 28 hours, while in the fat clearance group was 72 hours. The time for specimen processing was significantly shorter in the fat lucidification group (P<0.05). The mean time for dissecting lymph nodes in the fat clearance group was 2.1 hours, while in the fat lucidification group was 2.0 hours, the difference was not statistically significant. CONCLUSION: When processing rectal cancer specimens with the fat lucidification technique can result in the similar number of lymph nodes compared to the fat clearance technique, with significantly shorter specimen processing time. The spatial position of the lymph nodes is better preserved using the fat lucidification technique, which may help study the distribution pattern of the normal and metastatic lymph nodes.