PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Hexafluoropropylene oxide trimer acid, a perfluorooctanoic acid alternative, induces cardiovascular toxicity in zebrafish embryos.

As an increasingly used alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been widely detected in global water environments. However, little is known regarding its toxic effects on cardiovascular development. Here, zebrafish embryos were treated with egg water containing 0, 60, 120, or 240 mg/L HFPO-TA. Results showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart rate. Furthermore, HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance (SV-BA) in Tg (myl7: GFP) transgenic larvae, disrupting the expression of genes involved in heart development and thus causing abnormal heart looping. Obvious sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg (fli: GFP) transgenic larvae. HFPO-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor (VEGF) pathway and embryonic vascular development. HFPO-TA exposure significantly decreased erythrocyte number in Tg (gata1: DsRed) transgenic embryos and influenced gene expression associated with the heme metabolism pathway. HFPO-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis, inhibiting cell proliferation while promoting apoptosis. Therefore, HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos, suggesting it may not be a suitable or safe alternative for PFOA.

Is Pathologic Complete Response a Good Predictor for the Long-Term, Clinical Outcome in Patients with Gastric Cancer After Neoadjuvant Chemotherapy? A Retrospective, Multi-institution Study in China.

BACKGROUND: Many studies have used pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) as the primary endpoint for the short-term efficacy in gastric cancer, but whether it is a good indicator for overall survival is poorly understood. METHODS: This study reviewed a multi-institution database of patients who underwent radical gastrectomy and achieved pCR after NAC. Cox regression models were used to identify clinicopathologic predictors of overall survival (OS) and disease-free survival (DFS). Survival curves were calculated by using the Kaplan-Meier method and compared by means of the log-rank test. RESULTS: OS and DFS in patients with pCR were significantly higher than in those with non-pCR (both P < 0.001). Multivariable analysis confirmed pCR was an independent prognostic factor for OS and DFS (P = 0.009 and P = 0.002 for OS and DFS, respectively). However, the survival benefit for pCR was present only for ypN0 tumors (P = 0.004 and P = 0.001 for OS and DFS, respectively), and OS (P = 0.292) and DFS (P = 0.285) among patients with ypN+ gastric cancer could not be stratified by pCR. CONCLUSIONS: In our study, pCR is an independent prognostic factor for OS and DFS, but the survival benefit for pCR is present only for ypN0 tumors but not ypN+ tumors.

Exploring the role of pyroptosis in shaping the tumor microenvironment of colorectal cancer by bulk and single-cell RNA sequencing.

BACKGROUND: Emerging studies have shown that pyroptosis plays a non-negligible role in the development and treatment of tumors. However, the mechanism of pyroptosis in colorectal cancer (CRC) remains still unclear. Therefore, this study investigated the role of pyroptosis in CRC. METHODS: A pyroptosis-related risk model was developed using univariate Cox regression and LASSO Cox regression analyses. Based on this model, pyroptosis-related risk scores (PRS) of CRC samples with OS time > 0 from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database were calculated. The abundance of immune cells in CRC tumor microenvironment (TME) was predicted by single-sample gene-set enrichment analysis (ssGSEA). Then, the responses to chemotherapy and immunotherapy were predicted by pRRophetic algorithm, the tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms, respectively. Moreover, the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset (PRISM) were used to explore novel drug treatment strategies of CRC. Finally, we investigated pyroptosis-related genes in the level of single-cell and validated the expression levels of these genes between normal and CRC cell lines by RT-qPCR. RESULTS: Survival analysis showed that CRC samples with low PRS had better overall survival (OS) and progression-free survival (PFS). CRC samples with low PRS had higher immune-related gene expression and immune cell infiltration than those with high PRS. Besides, CRC samples with low PRS were more likely to benefit from 5-fluorouracil based chemotherapy and anti-PD-1 immunotherapy. In novel drug prediction, some compounds such as C6-ceramide and noretynodrel, were inferred as potential drugs for CRC with different PRS. Single-cell analysis revealed pyroptosis-related genes were highly expressed in tumor cells. RT-qPCR also demonstrated different expression levels of these genes between normal and CRC cell lines. CONCLUSIONS: Taken together, this study provides a comprehensive investigation of the role of pyroptosis in CRC at the bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) levels, advances our understanding of CRC characteristics, and guides more effective treatment regimens.

LncRNA LENGA acts as a tumor suppressor in gastric cancer through BRD7/TP53 signaling.

It has been established that long noncoding RNAs (lncRNAs) play a crucial role in various cancer types, and there are vast numbers of long noncoding RNA transcripts that have been identified by high-throughput methods. However, the biological function of many novel aberrantly expressed lncRNAs remains poorly elucidated, especially in gastric cancer (GC). Here, we first identified a novel lncRNA termed LENGA (Low Expression Noncoding RNA in Gastric Adenocarcinoma), which was significantly downregulated in GC tissues compared to adjacent normal tissues. Next, we found that reduced expression of LENGA in GC was also associated with a shorter life expectancy. The proliferation, migration, and invasion of GC cells were increased after LENGA knockdown but restrained after LENGA overexpression in vitro and in vivo. It was further demonstrated that LENGA physically binds to BRD7 (bromodomain-containing 7) in the bromodomain domain and acts as a scaffold that enhances the interaction between BRD7 and TP53 (tumor protein p53), regulating the expression of a subset of genes in the p53 pathway, including CDKN1A (cyclin-dependent kinase inhibitor 1A) and PCDH7 (protocadherin 7), at the transcriptional level. Consistently, the expression of CDKN1A has a positive correlation with LENGA in GC patients. Taken together, this study uncovers a novel tumor suppressor lncRNA, LENGA, and describes its biological function, molecular mechanism, and clinical significance. This highlights the potential importance of targeting the LENGA/BRD7/TP53 axis in GC treatment.

Preference matters: Knowledge of beneficiary's preference influences children's evaluations of the act of leaving a choice for others.

People value indirect prosocial actions that benefit others as byproducts of self-oriented actions. One example of such an action is the act of leaving a choice for others when selecting an item for oneself. In this study, we investigated how knowledge of the beneficiary's preference may influence children's evaluations of such actions. Children (n = 91, 4- to 10-year-olds) and adults (n = 43) were asked to evaluate characters taking a snack for themselves from a set of three items-two identical items and one unique item-in a way that either leaves a choice (two different items) or leaves no choice (two identical items) for the next person (the beneficiary). The beneficiary's preference was systematically manipulated as unknown, preferring the unique item, or preferring the item of which there are two. We found notable developmental changes: Children as young as 4 years of age understand that it is nicer not to take away the only thing others prefer; with age, children increasingly appreciate the value of leaving a diverse choice when the beneficiary's preference is unknown; however, when the beneficiary clearly prefers the item of which there are two, children increasingly think that it is nicer to leave two identical but preferred items than to leave a diverse choice. These findings reveal increasing flexibility and subtlety in children's social evaluation of indirect prosocial actions; their evaluation develops from a mere understanding of the value of preference to a flexible appreciation of both preference and choice.

Benchmark for establishment of organoids from gastrointestinal epithelium and cancer based on available consumables and reagents.

Gastrointestinal cancers are a public health problem that threatens the lives of human being. A good experimental model is a powerful tool to promote the uncovering pathogenesis and establish novel treatment methods. High-quality biomedical research requires experimental models to recapitulate the physiological and pathological states of their parental tissues as much as possible. Organoids are such experimental models. Organoids refer to small organ-like cellular clusters formed by the expansion and passaging of living tissues in 3D culture medium in vitro. Organoids are highly similar to the original tissues in terms of cellular composition, cell functions, and genomic profiling. Organoids have many advantages, such as short preparation cycles, long-term storage based on cryopreservation, and reusability. In recent years, researchers carried out the establishment of organoids from gastrointestinal mucosa and cancer tissues, and accumulated valuable experiences. In order to promote effective usage and further development of organoid-related technologies in the research of gastrointestinal diseases, this study proposes a benchmark based on utilization of available experimental consumables and reagents, which are involved in the key steps such as collection and pretreatment of biospecimen, organoid construction, organoid cryopreservation and recovery, growth status evaluation, and organoid quality control. We believe that the standard for the construction and preservation of organoids derived from human gastrointestinal epithelium and cancer tissues can provide an important reference for the majority of scientific researchers.

A Modified Billroth-II with Braun Anastomosis in Totally Laparoscopic Distal Gastrectomy: Initial Experience Compared with Roux-en-Y Anastomosis.

BACKGROUND: This retrospective study aimed to compare the feasibility and effectiveness of a modified Billroth-II with Braun (B-II Braun) reconstruction and those of a Roux-en-Y (R-Y) reconstruction after laparoscopic distal gastrectomy. METHODS: From January 2016 to December 2019, 247 patients underwent total laparoscopic distal gastrectomy (TLDG), with B-II Braun reconstruction for 145 patients and R-Y reconstruction for 102 patients. The patients' data were collected prospectively and reviewed retrospectively. RESULTS: In this study, the median times of the operation were statistically shorter for B-II Braun than for R-Y (167 min [range, 110-331 min] vs 191 min [range, 123-384 min]; p = 0.001), including anastomotic times (33 min [range, 30-42 min] vs 42 min [range, 40-48 min]; p = 0.001). After a short-term follow-up period, endoscopy showed 31 cases of bile reflux (21.4%), 15 cases of grade 2 gastritis (10.3%), and 6 cases of grade 2 food residue (4.1%) in the B-II Braun group after 6 months. After 1 year, 10 patients (6.9%) had grade 2 gastritis and 2 patients (1.4%) had grade 3 gastritis. However, the remnant stomach of the two groups did not differ significantly in the rate of gastric residue (p = 0.112 after 6 months; p = 0.579 after 1 year, respectively), gastritis (p = 0.726 after 6 months; p = 0.261 after 1 year, respectively), or bile reflux (p = 0.262 after 6 months; p = 0.349 after 1 year, respectively). CONCLUSIONS: For gastric cancer patients, TLDG with modified B-II Braun reconstruction could be technically feasible. It has an acceptable range of postoperative complications and is effective in preventing bile reflux into the gastric remnant.

ACACB is a novel metabolism-related biomarker in the prediction of response to cetuximab therapy inmetastatic colorectal cancer.

Cetuximab is one of the most valuable targeted therapy monoclonal antibodies in the treatment of metastatic colorectal cancer (CRC). However, the mechanisms affecting cetuximab resistance in CRC treatment remain unclear. Metabolism, especially fatty acid metabolism, has been reported to play an important role in tumor treatment. The correlation between cetuximab resistance and metabolism and whether it can be a new biomarker to evaluate the sensitivity of cetuximab in CRC treatment still need to be further explored. In this study, we perform a comprehensive analysis to confirm the relationship between fatty acid metabolism and cetuximab resistance, and the differentially expressed genes (DEGs) related to cetuximab drug resistance in CRC are screened by bioinformatics technology. We find that acetyl-CoA carboxylase beta (ACACB), ADH1C, CES1, MGLL, FMO5, and GPT are the hub DEGs, and ACACB is the most important biomarker among them. In addition, we systematically analyze the role of ACACB in the tumorigenesis of CRC, including tissue expression, CRC cell growth, cetuximab sensitivity, and potential downstream pathways, by using bioinformatics techniques, in vitro experiments and clinical cohort validation. Our results confirm that cetuximab resistance is correlated with metabolism. ACACB can lead to decreased sensitivity to cetuximab in CRC, and its mechanism may be related to EGFR phosphorylation, which could affect the activation of the mTOR/Akt signaling pathway and regulation of CDT1-, cyclin D1-, and p21-related cell cycle modulation.

Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes the Osteoblast Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting the microRNA-96/Osterix Axis.

OBJECTIVES: To investigate whether and how the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) sponges microRNA-96 (miR-96) to achieve the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). METHODS: Protein levels were detected by Western blot. Mineralized bone matrix formation was studied by alizarin red staining. Metastasis-associated lung adenocarcinoma transcript 1, miR-96, and osteogenesis-related Messenger RNA expression was assessed by Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The interactions between miR-96 and osterix (Osx), MALAT1, and miR-96 were determined by luciferase reporter assay. RESULTS: The expression of MALAT1 was upregulated whereas that of miR-96 was downregulated in osteogenic hBMSCs. In addition, the expression of MALAT1 significantly decreased whereas that of miR-96 increased in the hBMSCs of osteoporosis (OP) patients. qRT-PCR and alizarin red staining assays showed that MALAT1 silencing or miR-96 overexpression inhibits hBMSC osteogenic differentiation and vice versa. overexpression of miR-96 reversed the promotive effect of MALAT1 on the osteogenic differentiation of hBMSCs. Dual luciferase report assay verified that miR-96 is a regulatory target of MALAT1 and that Osx is a gene target of miR-96. CONCLUSIONS: Taken together, the results demonstrate that MALAT1 promotes the osteogenic differentiation of hBMSCs by regulating the miR-96/Osx axis. Our study provides novel mechanistic insights into the critical role of lncRNA MALAT1 as a microRNA sponge in OP patients and sheds new light on lncRNA-directed diagnostics and therapeutics in OP.

A greater lymph node yield is required during pathological examination in microsatellite instability-high gastric cancer.

BACKGROUND: The impact of microsatellite status on lymph node (LN) yield during lymphadenectomy and pathological examination has never been assessed in gastric cancer (GC). In this study, we aimed to appraise the association between microsatellite instability-high (MSI-H) and LN yield after curative gastrectomy. METHODS: We retrospectively analyzed 1757 patients with GC undergoing curative gastrectomy and divided them into two groups: MSI-H (n = 185(10.5%)) and microsatellite stability (MSS) (n = 1572(89.5%)), using a five-Bethesda-marker (NR-24, BAT-25, BAT-26, CAT-25, MONO-27) panel. The median LN count and the percentage of specimens with a minimum of 16 LNs (adequate LN ratio) were compared between the two groups. The log odds (LODDS) of positive LN count (PLNC) to negative LN count (NLNC) and the target LN examined threshold (TLNT(x%)) were calculated in both groups. RESULTS: Statistically significant differences were found in the median LN count between MSI-H and MSS groups for the complete cohort (30 vs. 28, p = 0.031), for patients undergoing distal gastrectomy (DG) (30 vs. 27, p = 0.002), for stage II patients undergoing DG (34 vs. 28, p = 0.005), and for LN-negative patients undergoing DG (28 vs. 24, p = 0.002). MSI-H was an independent factor for higher total LN count in patients undergoing DG (p = 0.011), but it was not statistically correlated to the adequate LN ratio. Statistically significant differences in PLNC, NLNC and LODDS were found between MSI-H GC and MSS GC (all p < 0.001). The TLNT(90%) for MSI-H and MSS groups were 31 and 25, respectively. TLNT(X%) of MSI-H GC was always higher than that of MSS GC regardless of the given value of X%. CONCLUSIONS: MSI-H was associated with higher LN yield in patients undergoing gastrectomy for GC. Although MSI-H did not affect the adequacy of LN harvest, we speculate that a greater lymph node yield is required during pathological examination in MSI-H GC.

Prognostic value of apical lymph node metastasis at the inferior mesenteric artery in sigmoid and rectal cancer patients who undergo laparoscopic surgery.

BACKGROUND AND OBJECTIVES: Evidence supporting the importance of apical lymph nodes (LNs) and the potential long-term impact of LN metastases at the inferior mesenteric artery (IMA) lymphectomy remains limited. This study aimed to evaluate the prognostic value of LNs at the IMA (IMA-LN) in sigmoid and rectal cancer patients undergoing laparoscopic surgery. METHODS: We retrospectively evaluated 265 consecutive patients who underwent laparoscopic sigmoid or rectal cancer surgery between August 2016 and May 2020. They were divided into two groups according to the pathological results of the IMA LNs: IMA-LN negative (n = 248) and IMA-LN positive (n = 17). RESULTS: The IMA-LN negative group had significantly better overall survival (OS) (p = .020) and disease-free survival (DFS) (p = .000) than did the IMA-LN positive group. IMA-LN metastasis was associated with worse OS and DFS regardless of the pN stage. Patients with IMA-LN metastasis had a higher risk of postoperative recurrence, especially liver (p = .000) and lung (p = .025) metastasis, than did those without metastasis. However, there was no significant difference in the local recurrence rate between the two groups. CONCLUSIONS: IMA-LN metastasis is an independent risk factor for poor prognosis in sigmoid and rectal cancer. Dissecting and evaluating IMA-LN separately is a more accurate and practical method for predicting prognosis.

Impact of microsatellite status on negative lymph node count and prognostic relevance after curative gastrectomy.

BACKGROUND AND OBJECTIVES: The impact of microsatellite instability-high (MSI-H) phenotype on lymph node yield after lymphadenectomy has never been discussed in gastric cancer (GC). In this study, we aimed to assess the association of microsatellite status with negative lymph node count (NLNC) as well as its prognostic value. METHODS: We retrospectively analyzed 1491 GC patients and divided them into two groups: MSI-HGC (n = 141 [9.5%]) and microsatellite stability (MSSGC ) (n = 1350 [90.5%]). The NLNC and survival data were compared between the two groups. The log odds of positive lymph nodes (LNs) to negative LNs and the target lymph node examined threshold (TLNT) were calculated in both groups. RESULTS: A statistically significant difference was found in median NLNC (26 vs. 23, p < .001) between MSI-HGC and MSSGC patients. MSI status was an independent factor for NLNC (p < .001). NLNC showed positive prognostic value for cases with metastatic lymph node (LN+ ) in both MSI-HGC and MSSGC groups. The TLNT(90%) for MSI-HGC and MSSGC were 33 and 26, respectively. CONCLUSIONS: MSI-HGC was associated with higher NLNC in GC patients and this was independent of the presence of LN+ . However, more LNs are needed during pathological examination to capture LN+ cases in MSI-HGC.

Staged laparoscopic management of locally advanced gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult. OBJECTIVE: We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable. METHODS: Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed. RESULTS: R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively. CONCLUSION: This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.

Effect of different reinforcement methods on anastomotic leakage prevention after laparoscopic double anastomosis.

BACKGROUND AND OBJECTIVES: To investigate the effects of different suture reinforcement methods for anastomotic leakage and other postoperative complications after the use of a laparoscopic double stapling technique (DST). METHODS: We collected the data of 124 patients who underwent laparoscopic radical resection of colorectal cancer from July 2017 to September 2018 at our institution. Patients were divided into three groups according to the suture reinforcement methods: intermittent, continuous suture reinforcement, and non-reinforcement (n = 41, 41, and 42, respectively). One-way analysis of variance, χ2 , Fisher's exact, and nonparametric tests were used for statistical analysis. RESULTS: Among the 124 patients, there were no statistically significant differences in operation times, intraoperative blood loss, postoperative hospital stays and recovery of bowel movement. Nine patients were diagnosed with anastomotic leakage (AL). The incidences of serious AL in the intermittent and continuous suture reinforcement groups were lower than that in the control group, with lower reoperation rate, shorter average lengths of stay and lower treatment costs of two experimental groups. CONCLUSION: Intermittent and continuous sutures after laparoscopic DST is effective, safe, and feasible on anastomotic leakage prevention. These procedures could be popularized in rectal surgery on patients with high risk of AL.

Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

BACKGROUND AND OBJECTIVES: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature. METHODS: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence. RESULTS: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches. CONCLUSIONS: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.

Pelvic peritoneum closure reduces postoperative complications of laparoscopic abdominoperineal resection: 6-year experience in single center.

BACKGROUND: To investigate feasibility of laparoscopic abdominoperineal resection with pelvic peritoneum closure (LAPR-PPC) for lower rectal cancer. METHODS: LAPR-PPC has been used for lower rectal cancer in our institution since 2014. In this study, we retrospectively analyzed the data from 86 patients who underwent LAPR-PPC and compared with the data from 96 patients who underwent laparoscopic APR without PPC (LAPR) from January 2013 to December 2018. RESULTS: The rate of perineal surgical site infection (SSI) (18.75% (18/96) vs. 5.81% (5/86), p < 0.01), delayed (> 4 weeks) perineal healing (12.50% (12/96) vs. 3.49% (3/86), p = 0.027), ileus (7.29% (7/96) vs 1.16% (1/86), p = 0.044), and postoperative perineal hernia (PPH, 5.21% (5/96) vs. 0% (0/86), p = 0.032) were significantly lower in LAPR-PPC group than LAPR group. The patients in LAPR-PPC group had shorter hospitalization time (21.32 ± 11.95 days vs. 13.93 ± 11.51 days, p < 0.01). CONCLUSIONS: PPC procedure enabled the reduction in perineal wound complications, ileus, PPH, and consequently shortened hospitalization time. LAPR-PPC is beneficial for the patients with lower rectal cancer.

METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulation in eukaryotic cells. However, understanding of m6A in colorectal cancer (CRC) is very limited. We designed this study to investigate the role of m6A in CRC. METHODS: Expression level of METTL14 was extracted from public database and tissue array to investigate the clinical relevance of METTL14 in CRC. Next, gain/loss of function experiment was used to define the role of METTL14 in the progression of CRC. Moreover, transcriptomic sequencing (RNA-seq) was applied to screen the potential targets of METTL14. The specific binding between METTL14 and presumed target was verified by RNA pull-down and RNA immunoprecipitation (RIP) assay. Furthermore, rescue experiment and methylated RNA immunoprecipitation (Me-RIP) were performed to uncover the mechanism. RESULTS: Clinically, loss of METTL14 correlated with unfavorable prognosis of CRC patients. Functionally, knockdown of METTL14 drastically enhanced proliferative and invasive ability of CRC cells in vitro and promoted tumorigenicity and metastasis in vivo. Mechanically, RNA-seq and Me-RIP identified lncRNA XIST as the downstream target of METTL14. Knockdown of METTL14 substantially abolished m6A level of XIST and augmented XIST expression. Moreover, we found that m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. Consistently, XIST expression negatively correlated with METTL14 and YTHDF2 in CRC tissues. CONCLUSION: Our findings highlight the function and prognostic value of METTL14 in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology.

Resolution of the Ongoing Challenge of Estimating Nonpoint Source Neonicotinoid Pollution in the Yangtze River Basin Using a Modified Mass Balance Approach.

Neonicotinoid insecticides have been widely consumed worldwide, particularly in China. There is a growing interest in the environmental research community about the occurrence, fates, sources, and risks of neonicotinoids. Nine neonicotinoids in river/lake water were measured at 12 sites along the Yangtze River Basin during the dry and wet seasons in 2016, and nonpoint sources were also identified based on a modified mass balance method. A significantly higher concentration of neonicotinoids was found during the dry season probably due to the dilution effect and insecticide consumption. The high pollution levels are due to posing high ecological risks compared with the recommended thresholds. In 2016, 1190 (95% confidence interval (CI) = 822-1690) tons of neonicotinoids were transferred into the adjacent sea. Nonpoint source pollution (1700 (CI = 1200-2370) tons) was the major contributor (91.3%) to the total input of neonicotinoids into the system. Composition profiles identifying specific neonicotinoid sources indicated some changes in usage patterns from old to new types of neonicotinoids. This spatial and seasonal field study and source identification is expected to fill the data gap regarding the limited information on neonicotinoid use patterns and to inform further effective policy-making and intervention programs in China that should be urgently promoted in the near future.

Completely medial access by page-turning approach for laparoscopic right hemi-colectomy: 6-year-experience in single center.

BACKGROUND: To investigate the safety and feasibility of the completely medial access by page-turning approach (CMAP) for laparoscopic right hemi-colectomy. METHODS: In this retrospective study, the data from 72 patients who underwent laparoscopic right hemi-colectomy with CMAP were analyzed and compared with data from 124 patients who underwent the conventional medial approach performed by the same surgical team from September 2011 to March 2017. RESULT: Complete mesocolic excision (CME) was achieved in 67 of 72 patients (93.1%) with laparoscopic CMAP. The average operation time, blood loss, and specimen length was 135.9 ± 28.3 min, 63.2 ± 32.2 ml, and 23.9 ± 4.7 cm, respectively. The number of lymph nodes harvested was 20.6 ± 7.7, the time-to-flatus was 2.5 ± 0.8 days, the time-to-fluid intake was 3.2 ± 0.8 days, and the average hospital stay was 8.9 ± 4.7 days. No intra-operative complications occurred in this study. The vessel-related complication and total post-operative complication rate was 2.78% (2/72) and 6.94% (5/72), respectively. CONCLUSIONS: Laparoscopic CMAP was an alternative approach for CME in laparoscopic right hemi-colectomy, which was proved safe and feasible for right colon cancer.