Risk of Esophageal Adenocarcinoma After Bariatric Surgery: A Meta-Analysis of Retrospective Studies.

PURPOSE: This study aims to systematically review and meta-analyze the evidence on the risk of esophageal adenocarcinoma (EAC) following metabolic and bariatric surgery (MBS). MATERIALS AND METHODS: A systematic literature search was conducted on the China National Knowledge Infrastructure (CNKI), Wanfang, EMBASE, MEDLINE, Web of Science, The Cochrane Library, and PubMed databases. Meta-analysis utilized odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the correlation between MBS and the risk of EAC. Meta-analysis was performed using STATA software (version 12.0). RESULTS: Fourteen studies involving patients with obesity undergoing bariatric surgery and control groups receiving conventional treatment were included. The meta-analysis indicated a reduction in the overall incidence of esophageal cancer after bariatric surgery (OR = 0.69, 95% CI: 0.51-0.95, P = 0.022). Subgroup analysis results demonstrated a decreased risk of EAC in European patients with obesity undergoing MBS treatment (OR: 0.60, 95% CI: 0.38-0.95, P = 0.028). In studies with a sample size greater than or equal to 100,000 patients, the risk of EAC in patients with obesity undergoing MBS was significantly lower than the non-surgery group (OR: 0.59, 95% CI: 0.42-0.83, P = 0.003). Articles published before 2020 and those published in 2020 or earlier showed a significant difference in the incidence of EAC between the surgery and non-surgery groups (OR: 0.57, 95% CI: 0.43-0.75, P < 0.001). The risk of EAC in patients with obesity with a follow-up time of less than 5 years was statistically significant (OR: 0.46, 95% CI: 0.25-0.82, P = 0.009). CONCLUSION: Our meta-analysis results suggest a reduced risk of esophageal cancer in patients with obesity after bariatric surgery. PROSPERO REGISTRATION: CRD 42024505177.

Liver-Derived Ketogenesis via Overexpressing HMGCS2 Promotes the Recovery of Spinal Cord Injury.

The liver is the major ketogenic organ of the body, and ketones are reported to possess favorable neuroprotective effects. This study aims to elucidate whether ketone bodies generated from the liver play a critical role in bridging the liver and spinal cord. Mice model with a contusive spinal cord injury (SCI) surgery is established, and SCI induces significant histological changes in mice liver. mRNA-seq of liver tissue shows the temporal changes of ketone bodies-related genes, ß-hydroxybutyrate dehydrogenase (BDH1) and solute carrier family 16 (monocarboxylic acid transporters), member 6 (SLC16A6). Then, an activated ketogenesis model is created with adult C57BL/6 mice receiving the tail intravenous injection of GPAAV8-TBG-Mouse-Hmgcs2-CMV- mCherry -WPRE (HMGCS2liver ) and mice receiving equal AAV8-Null being the control group (Vectorliver ). Then, the mice undergo either a contusive SCI or sham surgery. The results show that overexpression of HMG-CoA synthase (Hmgcs2) in mice liver dramatically alleviates SCI-mediated pathological changes and promotes ketogenesis in the liver. Amazingly, liver-derived ketogenesis evidently alleviates neuron apoptosis and inflammatory microglia activation and improves the recovery of motor function of SCI mice. In conclusion, a liver-spinal cord axis can be bridged via ketone bodies, and enhancing the production of the ketone body within the liver has neuroprotective effects on traumatic SCI.

Pathologic outcomes of transanal versus laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of 26 studies.

PURPOSE: Transanal total mesorectal excision (TaTME) has the potential advantages for patients with low rectal cancer. The objective of this meta-analysis was to identify the pathologic outcomes between the TaTME and laparoscopic total mesorectal excision (LaTME) in rectal cancer. METHODS: The literature searches were conducted in PubMed, Cochrane Library, and EMBASE with English language restriction. The primary endpoint was circumferential margin (CRM), and the secondary endpoints were distal resection margin (DRM), mesorectal excision quality, and harvested lymph nodes. RESULTS: Our research identified 1090 articles, and 26 studies met the inclusion criteria for the meta-analysis. The positive CRM was lower in the TaTME than the LaTME (OR = 0.72; 95% CI = 0.53, 0.98; P = 0.04). There was no significant difference in the positive CRM between the TaTME and LaTME published after 2016 (OR = 0.80; 95% CI = 0.57, 1.12; P = 0.19), prospective study (OR = 2.70; 95% CI = 0.51, 14.24; P = 0.24), respective study (OR = 0.76; 95% CI = 0.55, 1.04; P = 0.09), BMI > 26 (OR = 1.00; 95% CI = 0.63, 1.58; P = 0.98), or sample size > 100 (OR = 0.84; 95% CI = 0.57, 1.23; P = 0.38). In addition, there was no significant difference observed between the TaTME and LaTME in terms of DRM, mesorectum incompleteness, and harvested lymph nodes. CONCLUSIONS: The TaTME is associated with lower positive CRM compared to the LaTME and similar pathologic outcomes including DRM, harvested lymph node, and mesorectal excision quality.

Nickel isotopes link Siberian Traps aerosol particles to the end-Permian mass extinction.

The end-Permian mass extinction (EPME) was the most severe extinction event in the past 540 million years, and the Siberian Traps large igneous province (STLIP) is widely hypothesized to have been the primary trigger for the environmental catastrophe. The killing mechanisms depend critically on the nature of volatiles ejected during STLIP eruptions, initiating about 300 kyr before the extinction event, because the atmosphere is the primary interface between magmatism and extinction. Here we report Ni isotopes for Permian-Triassic sedimentary rocks from Arctic Canada. The δ60Ni data range from -1.09‰ to 0.35‰, and exhibit the lightest δ60Ni compositions ever reported for sedimentary rocks. Our results provide strong evidence for global dispersion and loading of Ni-rich aerosol particles into the Panthalassic Ocean. Our data demonstrate that environmental degradation had begun well before the extinction event and provide a link between global dispersion of Ni-rich aerosols, ocean chemistry changes, and the EPME.

Robotic-assisted versus conventional laparoscopic surgery for colorectal cancer: Short-term outcomes at a single center.

BACKGROUND: The robotic technique has been established as an alternative approach to laparoscopy for colorectal surgery. The aim of this study was to compare the short-term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer. METHODS: The cases of robot-assisted or laparoscopic colorectal resection were collected retrospectively between July 2015 and September 2018. We evaluated patient demographics, perioperative characteristics, and pathologic examinations. Short-term outcomes included time to passage of flatus and length of postoperative hospital stay. RESULTS: A total of 580 patients were included in the study. There were 271 patients in the robotic colorectal surgery (RCS) group and 309 in the laparoscopic colorectal surgery (LCS) group. The time to passage of flatus in the RCS group was 3.62 days shorter than the LCS group. The total costs were increased by 2,258.8 USD in the RCS group compared to the LCS group (P < 0.001). CONCLUSION: The present study suggests that colorectal cancer robotic surgery was more beneficial to patients because of a shorter postoperative recovery time of bowel function and shorter hospital stays.

Short-Term Outcomes of Robotic versus Laparoscopic Total Mesorectal Excision for Rectal Cancer: A Cohort Study.

The aim of this study was to evaluate and compare the intestinal function recovery time and other short-term outcomes between robotic-assisted total mesorectal excision (R-TME) and laparoscopic total mesorectal excision (L-TME) for rectal cancer. This is a retrospective study using a prospectively collected database. Patients' records were obtained from Gansu Provincial Hospital between July 2015 and October 2017. Eighty patients underwent R-TME, and 116 with the same histopathological stage of the tumor underwent an L-TME. Both operations were performed by the same surgeon, comparing intra- and postoperative outcomes intergroups. The time to the first passage of flatus (P < 0.001), the time to the first postoperative oral fluid intake (P < 0.001), and the length of hospital stay (P < 0.01) of the R-TME group were about three days faster than those in the L-TME group. The rate of conversion to open laparotomy (P = 0.038) and postoperative urinary retention (P = 0.016) were significantly lower in the R-TME group than in the L-TME group. Intraoperative blood loss of the R-TME group was more than that of the L-TME group (P < 0.01).The operation time, number of lymph nodes harvested, and rate of positive circumferential resection margin were similar intergroup. The total cost of the R-TME group was higher than that of the L-TME group, but with a lack of statistical significance (85,623.91 ± 13,310.50 vs 67,356.79 ± 17,107.68 CNY, P = 0.084). The R-TME is safe and effective and has better postoperative short-term outcomes and faster intestinal function recovery time, contrasting with the L-TME. The large, multicenter, prospective studies were needed to validate the advantages of robotic surgery system used in rectal cancer.

The application of transanal total mesorectal excision for patients with middle and low rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Recently, in order to overcome the shortcomings of laparoscopic surgery in the treatment of low rectal cancer, a new kind of surgical procedure, transanal total mesorectal excision (TaTME), has rapidly become a research hotspot in the field of rectal cancer surgery study. Our study aimed to evaluate the efficacy and safety of transanal total mesorectal excision (TaTME) for the patients with rectal cancer. METHODS: Relevant studies were searched from the databases of the Cochrane Library, PubMed, Embase, Web of science. All relevant studies were collected to evaluate the efficacy and safety of TaTME for patients with rectal cancer. The quality of the included studies was assessed by the Newcastle-Ottawa Quality Assessment Scale (NOS) and Cochrane Library Handbook 5.1.0. Data analysis was conducted using the Review Manager 5.3 software. RESULTS: Thirteen studies including 859 patients were included in our analysis. In terms of efficacy, compared with laparoscopic total mesorectal excision (LaTME), meta-analysis showed that the rate of complete tumor resection increased and the risk of positive circumferential margins decreased in the TaTME group. For complete tumor resection and positive circumferential margins in the TaTME group, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.93 and 1.09 to 3.42 (P = .02) and 0.43 and 0.22 to 0.82 (P = .01), respectively. Concerning safety, results showed that the rates of postoperative complications were similar in the 2 groups, and differences in the risk of ileus and anastomotic leakage were not statistically significant (OR = 0.75, 95%CI = 0.51-1.09, P = .13; OR = 0.91, 95%CI = 0.46-1.78, P = .78; OR = 0.79, 95%CI = 0.45-1.38, P = .40). CONCLUSIONS: The results of this meta-analysis show that TaTME is associated with a reduced positive circumferential resection margin (CRM) rate, and could achieve complete tumor resection and improved the long-term survival in patients with mid- and low-rectal cancer.

New pyridinium-based fluorescent dyes: A comparison of symmetry and side-group effects on G-Quadruplex DNA binding selectivity and application in live cell imaging.

A series of C1-, C2-and C3-symmetric pyridinium conjugates with different styrene-like side groups were synthesized and were utilized as G-quadruplex selective fluorescent probes. The new compounds were well-characterized. Their selectivity, sensitivity, and stability towards G-quadruplex were studied by fluorescence titration, native PAGE experiments, FRET and circular dichroism (CD) analyses. These new compounds investigated in the fluorescence assays were preferentially bound with G-quadruplex DNA compared with other type of nucleic acids and it is fascinating to realize the effects of molecular symmetry and associated side groups showing unexpectedly great influence on the fluorescent signal enhancement for the discrimination of G-quadruplexes DNA from other nucleic acids. This may correlate with the pocket symmetry and shape of the G-quadruplex DNA inherently. Among the compounds, a C2-symmetric dye (2,6-bis-((E)-2-(1H-indol-3-yl)-vinyl)-1-methylpyridin-1-ium iodide) with indolyl-groups substituted was screened out from the series giving the best selectivity and sensitivity towards G-quadruplexes DNA, particularly telo21, due to its high equilibrium binding constant (K=2.17×10(5)M(-1)). In addition, the limit of detection (LOD) of the dye to determine telo21 DNA in bioassays was found as low as 33nM. The results of the study give insight and certain crucial factors, such as molecular symmetry and the associated side groups, on developing of effective fluorescent dyes for G-quadruplex DNA applications including G-quadruplex structure stabilization, biosensing and clinical applications. The compound was also demonstrated as a very selective G-quadruplex fluorescent agent for living cell staining and imaging.

A molecular fluorescent dye for specific staining and imaging of RNA in live cells: a novel ligand integration from classical thiazole orange and styryl compounds.

A new RNA-selective fluorescent dye integrated with a thiazole orange and a p-(methylthio)styryl moiety shows better nucleolus RNA staining and imaging performance in live cells than the commercial stains. It also exhibits excellent photostability, cell tolerance, and counterstain compatibility with 4',6-diamidino-2-phenylindole for specific RNA-DNA colocalization in bioassays.

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines.

PURPOSE: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-alpha, and lymphotoxin-beta) or fibrogenic cytokines (transforming growth factor [TGF]-beta) during the same acute and chronic phases. METHODS AND MATERIALS: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. RESULTS: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-alpha, and lymphotoxin-beta) and the fibrogenic cytokine, TGF-beta, in cutaneous tissues at 21 days postradiation. CONCLUSION: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

Interleukin 1beta (IL1B) signaling is a critical component of radiation-induced skin fibrosis.

Interleukin 1 beta (IL1B), a potent pro-inflammatory cytokine, is directly up-regulated by radiation and is known to regulate other inflammation-related molecules, such as the matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs). However, the nature of the interaction of IL1B with MMPs and TIMPs in radiation-induced skin fibrosis is unknown. We examined the response of primary dermal keratinocytes, fibroblasts and endothelial cells to single-fraction radiation (10 Gy) and compared the results to a temporal sequence of histology from irradiated C57BL/6 and IL1R1 knockout mice. These studies showed that keratinocytes are the major IL1-producing cells in vitro and that radiation induces an immediate and chronic elevation in the expression of IL1B mRNA in the skin of C57BL/6 mice. This elevation was principally early and was less pronounced in the IL1R1 knockout strain, which also demonstrated reduced late radiation fibrosis. Radiation also increased expression of MMP mRNA in C57BL/6 mice. Finally, exogenous IL1B protein induced robust endogenous IL1B mRNA expression, along with a brisk increase in MMPs and collagen III, but only in the C57BL/6 mice. In conclusion, these data suggest that IL1B plays a critical role in radiation-induced fibrosis and that the increased MMPs fail to block the IL1-related collagen accumulation.

Combination of radiation and celebrex (celecoxib) reduce mammary and lung tumor growth.

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, alone and in combination with radiation was investigated in vitro and in vivo. Murine mammary tumor line (MCa-35) and human lung carcinoma line (A549) have high and low basal levels of COX-2 protein, respectively. Treatment of both tumor cells with celecoxib alone resulted in a dose- and time-dependent reduction of cell number (clonogenic cell death) and tumor cell growth rate in vitro; however, inhibition of tumor cell growth by celecoxib was not correlated with the reduction of COX-2 protein in tumor cells. Although both tumor cell types had similar DNA damage after celecoxib treatment, significant induction of tumor cell apoptosis was only observed in MCa-35. Celecoxib-mediated radiation sensitization also occurred in MCa-35 cells determined by clonogenic assay, in part due to a G2/M arrest at 8 to 24 hours after treatment. The tumor growth inhibitory effects of celecoxib were also studied in vivo. It was found that celecoxib inhibited both tumor growth after intragastric administration of celecoxib (5 daily doses of 50 mg/kg). Combined with a single 30-Gy dose of radiation, celecoxib resulted in additive effects on A549 tumors. Celecoxib-treated A549 tumors had marginal reduction of total and perfused blood vessels compared with untreated controls. Reduction of tumor angiogenic cytokine and growth factor mRNA was associated with decreased perfused vessels. Finally, reduction of vascular endothelial growth factor protein after celecoxib was also observed in both tumor lines by Western blot. Our results indicate that the selective inhibition of COX-2 combined with radiation has potential application in radiotherapy, and celecoxib-mediated antitumor effects may act through different mechanisms including direct inhibition of tumor cell proliferation, alteration of tumor cell cycle, and antiangiogenesis.

Celecoxib reduces skin damage after radiation: selective reduction of chemokine and receptor mRNA expression in irradiated skin but not in irradiated mammary tumor.

Inflammatory cytokine and chemokine production is mediated, at least in part, by prostaglandin E (PGE2). Cyclooxygenases, COX-1 and COX-2, are two key enzymes in the conversion of arachidonic acid to PGE2. Radiation induces the overproduction of cytokines and chemokines, and it also increases PGE2 production, both locally and systemically. In this study, we tested the effects of a COX-2 inhibitor (celecoxib) after 50 Gy radiation of MCa-35 tumor and cutaneous tissues of C3H/He mice. Preclinical toxicity endpoints and associated alterations in chemokine production and cellular infiltrates were measured. Celecoxib was given by daily gavage (50 mg/kg for 15 days), with the first dose delivered either 2 hours before, 2 days after, or 7 days after a single dose of radiation. Celecoxib-treated animals had less inflammation of the dermis compared with saline-treated controls. Severe skin dermatitis occurred in 23.8% (5/21) of mice treated with 50 Gy, whereas only 17.6%, 5.3%, and 11.1% of mice in the 2-hour pre-, or the 2-day post-, and 7-day postirradiation groups, respectively, had severe dermatitis on day 20. The decreased skin toxicity scores were associated with a reduction of both blood vessels and focal necrosis in MCa-35 tumors. Celecoxib also significantly decreased C-C family chemokine (Rantes and MCP-1) mRNA expression in irradiated skin tissues, but not in tumor tissues, which was accompanied by a decrease in skin mRNA expression of both C-C (CCR2 and CCR5) and C-X-C (CXCR2 and CXCR4) chemokine receptors. A significant positive correlation was also found between skin damage (skin scores) and chemokine and its receptor mRNA expression in radiation-treated mice. Finally, celecoxib also decreased the infiltration of monocytes and neutrophils in locally irradiated tumor and surrounding normal tissue. The differential effects of celecoxib on inflammation help to explain the selective protection by celecoxib of irradiated cutaneous tissues without a concurrent protection of MCa-35 tumors.