Local resection versus radical resection after neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer: a propensity-score matched cohort analysis.

BACKGROUND: We aimed to address the shortage of evidence regarding the safety of the local resection approach by comparing long-term oncological outcomes between patients managed by local resection and those who underwent radical resection. METHODS: This was a propensity-score matched cohort analysis study that included patients of all ages diagnosed with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) at the Fujian Medical University Union Hospital and Fujian Medical University Affiliated Zhangzhou Hospital, China, between Jan 10, 2011, to Dec 28, 2021. Partial patients with a significant downstage of the tumor were offered management with the local resection approach, and most of the rest were offered radical resection if eligible. FINDINGS: One thousand six hundred ninety-three patients underwent radical resection after nCRT, and another 60 patients performed local resection. The median follow-up times were 44.0 months (interquartile range = 4-107 months). After propensity-core matching (PSM), in the Kaplan-Meier curves, local resection (n = 56) or radical resection (n = 211) was not significantly associated with 1-, 3-, and 5-year cumulative incidence of overall survival (OS) (HR = 1.103, 95% CI: 0.372 ~ 3.266), disease-free survival (DFS) ((HR = 0.972, 95% CI: 0.401 ~ 2.359), local recurrence (HR = 1.044, 95% CI: 0.225 ~ 4.847), and distant metastasis (HR = 0.818, 95% CI: 0.280 ~ 2.387) (all log-rank P > 0.05). Similarly, multivariate Cox regression analysis indicates that local excision still was not an independent risk factor for OS (HR = 0.863, 95% CI: 0.267 ~ 2.785, P = 0.805) and DFS (HR = 0.885, 95% CI: 0.353 ~ 2.215, p = 0.794). CONCLUSION: Local resection can be a management option in selected patients with middle-low rectal cancer after nCRT for LARC and without loss of oncological safety at five years.

Research Progress of Nitrite Metabolism in Fermented Meat Products.

Nitrite is a common color and flavor enhancer in fermented meat products, but its secondary amines may transfer to the carcinogen N-nitrosamines. This review focuses on the sources, degradation, limitations, and alteration techniques of nitrite. The transition among NO3- and NO2-, NH4+, and N2 constitutes the balance of nitrogen. Exogenous addition is the most common source of nitrite in fermented meat products, but it can also be produced by contamination and endogenous microbial synthesis. While nitrite is degraded by acids, enzymes, and other metabolites produced by lactic acid bacteria (LAB), four nitrite reductase enzymes play a leading role. At a deeper level, nitrite metabolism is primarily regulated by the genes found in these bacteria. By incorporating antioxidants, chromogenic agents, bacteriostats, LAB, or non-thermal plasma sterilization, the amount of nitrite supplied can be decreased, or even eliminated. Finally, the aim of producing low-nitrite fermented meat products is expected to be achieved.

Development and validation of neoadjuvant rectal score-based signature nomograms to predict overall survival and disease-free survival in locally advanced rectal cancer: a retrospective, double center, cohort study.

AIM: To evaluate the prognostic significance of the NAR score and develop nomograms for locally advanced rectal cancer (LARC) treated after neoadjuvant chemo-radiotherapy (nCRT) combined with total meso-rectal excision (TME) surgery to predict prognostic. METHODS: Retrospective collection among LARC patients treated at Fujian Medical University Union Hospital (training cohort) and Fujian Medical University Affiliated Zhangzhou Hospital (external validation cohort) between Jan 10, 2011 and Dec 28, 2021. The NAR score was calculated by formula: [5pN-3(cT-pT) + 12]^2/9.61. NAR score low (< 8), intermediate (8-16), and high (> 16). RESULTS: 1665 patients in the training cohort and 256 patients in the external validation cohorts were enrolled. Lower NAR score was significantly associated with better cumulative incidence of OS, DFS, local recurrence (LR), and distant metastasis (DM) (all P < 0.001). Multivariate Cox regression analysis indicates that NAR score, distance to the anal verge, no.253 LN metastasis, post-CRT carbohydrate antigen 19-9, tumor regression grade, and surgery method are independent predictors of OS and DFS (all P < 0.001). Among these independent factors, the NAR score had the highest area under the curve (AUC) and the nomograms to predict OS and DFS were generated. The AUCs for the accuracy of the prediction OS were 1 year = 0.742, 3 years = 0.749, 5 years = 0.713; prediction DFS were 1 year = 0.727, 3 years = 0.739, 5 years = 0.718, the models have good accuracy. CONCLUSIONS: The NAR score can effectively classify patients with LARC into groups with varying outcomes of OS, DFS, LR, and DM. Moreover, the novel nomograms comprising the NAR score were developed and validated to help predict OS and DFS.

Heterologous expression and biological characteristics of UGPases from Lactobacillus acidophilus.

Herein, two genes (LBA0625 and LBA1719) encoding UGPases (UDP-glucose pyrophosphorylase) in Lactobacillus acidophilus (L. acidophilus) were successfully transformed into Escherichia coli BL21 (DE3) to construct recombinant overexpressing strains (E-0625, E-1719) to investigate the biological characteristics of UGPase-0625 and UGPase-1719. The active sites, polysaccharide yield, and anti-freeze-drying stress of L. acidophilus ATCC4356 were also detected. UGPase-0625 and UGPase-1719 belong to the nucleotidyltransferase of stable hydrophilic proteins; contain 300 and 294 amino acids, respectively; and have 20 conserved active sites by prediction. Αlpha-helixes and random coils were the main secondary structures, which constituted the main skeleton of UGPases. The optimal mixture for the high catalytic activity of the two UGPases included 0.5 mM UDP-Glu (uridine diphosphate glucose) and Mg2+ at 37 °C, pH 10.0. By comparing the UGPase activities of the mutant strains with the original recombinant strains, A10, L130, and L263 were determined as the active sites of UGPase-0625 (P < 0.01) and A11, L130, and L263 were determined as the active sites of UGPase-1719 (P < 0.01). In addition, UGPase overexpression could increase the production of polysaccharides and the survival rates of recombinant bacteria after freeze-drying. This is the first study to determine the enzymatic properties, active sites, and structural simulation of UGPases from L. acidophilus, providing in-depth understanding of the biological characteristics of UGPases in lactic acid bacteria.Key points• We detected the biological characteristics of UGPases encoded by LBA0625 and LBA1719.• We identified UGPase-0625 and UGPase-1719 active sites.• UGPase overexpression elevates polysaccharide levels and post-freeze-drying survival.

Production of a Class IIb Bacteriocin with Broad-spectrum Antimicrobial Activity in Lactiplantibacillus plantarum RUB1.

Bacteriocins produced by lactic acid bacteria have potential use as natural food preservatives, which may alleviate current problems associated with the overuse of antibiotics and emerging multi-drug-resistant microbes. In this work, Lactiplantibacillus plantarum RUB1 was found to produce a class IIb bacteriocin with strong antibacterial activity. Except for plnXY encoding putative proteins, L. plantarum RUB1 contains most genes in five operons (plnABCD, plnGHSTUVW, plnMNOP, plnIEF, and plnRLJK) related to bacteriocin synthesis. Adding low (100 and 500 ng/mL) and medium (1 µg/mL) concentrations of PlnA to broth promoted bacteriocin production and upregulated bacteriocin gene plnA, while high concentrations (50 and 200 µg/mL) inhibited expression of these genes. Co-culturing L. plantarum RUB1 with Enterococcus hirae 1003, Enterococcus hirae LWS, Limosilactobacillus fermentum RC4, L. plantarum B6, and even Listeria monocytogenes ATCC 19111 and Staphylococcus aureus ATCC 6538 enhanced bacteriocin activity and expression of bacteriocin-related genes. This study verifies that PlnA can indeed upregulate the expression of bacteriocin genes, and also bacteriocin production can be induced by co-culture with some specific bacteria or their cell-free supernatants. Bacteriocin production by L. plantarum RUB1 is mediated by a quorum sensing mechanism, directly influenced by autoinducing peptide or specific strains. The findings provide new methods and insight into bacteriocin production mechanisms.

[Application of intracorporeal uncut Roux-en-Y anastomosis in digestive tract reconstruction after laparoscopic total gastrectomy].

OBJECTIVE: To explore the safety, feasibility and short-term efficacy of intracavitary uncut Roux-en-Y (URY) anastomosis in digestive tract reconstruction following laparoscopic total gastrectomy (LTG). METHODS: From November 2015 to January 2018, 67 gastric cancer patients underwent intracavitary URY following LTG to reconstruct the digestive tract at Oncological Surgery Department of Fujian Provincial Hospital. There were 41 males and 26 females with age of 50 to 81 (61.9±7.4) years and body mass index (BMI) of (23.4±3.2) kg/m². Among 67 patients, 19 were gastric cardia carcinomas, 33 were gastric body carcinomas, and 15 were gastric fundus carcinomas; tumor size was (3.4±2.3) cm; 22 were Borrmann type I, 15 were type II, 21 were type III, and 19 were type IV; 29 were highly or moderately differentiated adenocarcinoma, 23 were lowly differentiated adenocarcinoma, and 15 were signet-ring cell carcinoma. After conventional laparoscopic D2 radical gastrectomy, the duodenum was closed and dissociated at 2 cm below the pyloric ring using the Echelon-flex endoscopic articulated linear Endo-GIA stapler, and the esophagus was dissociated above the esophagogastric junction (EGJ).URY and digestive tract reconstruction were performed under the direct vision of laparoscope: (1) Side-to-side esophagojejunostomy: An incision of 0.5 cm was made in the left lower edge of the esophageal closed end; jejunum about 25 cm distal away from the Treitz ligament was elevated to the lower end of esophagus; another incision of 0.5 cm was made in the contralateral of mesenteric side; both arms of the linear Endo-GIA stapler were inserted into the windows opened through esophagus and jejunum respectively to complete side-to-side anastomosis. The common opening of esophagus and jejunum was closed to complete esophagojejunostomy, forming the chyme outflow tract. (2) Side-to-side Braun jejunojejunostomy: Incisions of 0.5 cm were made in the proximal jejunum about 10 cm away from the esophagojejunal anastomosis and 35-40 cm away from the contralateral of mesenteric side of distal jejunum respectively for proximal-distal side-to-side jejunojejunostomy. The common opening was closed to form the biliopancreatic duodenal juice outflow tract. (3) Closure of the input loop jejunum in the esophagojejunal anastomosis: The input loop jejunum 2-3 cm away from the esophagojejunal anastomosis was closed using the non-blade linear stapler (ATS45NK), and the biliopancreatic duodenal juice reflux was blocked. Clinical data of these patients were collected for retrospective case series study. Surgical and digestive tract functional recovery, perioperative complications, as well as postoperative nutritional status were observed. Moreover, related indexes, such as anastomosis function and tumor recurrence were evaluated through endoscopic and imaging examinations during postoperative follows-up. RESULTS: All the 67 patients completed the surgery successfully. The mean operative time was (259.4±38.5) minutes, digestive tract reconstruction time was (38.2±13.2) minutes, intraoperative blood loss was (73.4±38.4) ml, and number of harvested lymph node was 36.2±14.2. The mean distance from upper resection margin to upper tumor edge was (3.3±1.2) cm, distance from upper resection margin to dentate line was (1.2±0.7) cm, and 1 case had positive upper incisal margin, which became negative after the second resection. Moreover, the average length of the auxiliary incision was (3.2±0.4) cm. The mean postoperative intestinal exhaust time was (52.8±26.4) hours, time to liquid diet was (64.8±28.8) hours, and postoperative hospital stay was (8.4±2.5) days. The morbidity of postoperative complication was 10.4%(7/67). Among these 7 cases, 4 cases were grade IIIa of Clavien-Dindo classification, including 2 with esophagojejunal anastomosis leakage, 1 with duodenal stump leakage, and 1 with abdominal infection, and all these patients were recovered after conservative treatment. All the 67 patients were followed up. The mean nutrition index 12 months after surgery was 53.4±4.2, diameter of esophagojejunal anastomosis was (3.9±0.6) cm, the incidence of Roux-en-Y stasis syndrome was 3.0% (2/67), and the incidence of reflux esophagitis was 4.5% (3/67). No patient had recanalization of the closed input loop of esophagojejunal anastomosis, anastomotic stenosis, obstruction, or tumor recurrence at anastomosis. CONCLUSION: Intracavitary URY anastomosis following LTG for digestive tract reconstruction is safe and feasible, leading to fast postoperative recovery of digestive tract function and favorable short-term efficacy.

TFIIB co-localizes and interacts with α-tubulin during oocyte meiosis in the mouse and depletion of TFIIB causes arrest of subsequent embryo development.

TFIIB (transcription factor IIB) is a transcription factor that provides a bridge between promoter-bound TFIID and RNA polymerase II, and it is a target of various transcriptional activator proteins that stimulate the pre-initiation complex assembly. The localization and/or attachment matrix of TFIIB in the cytoplast is not well understood. This study focuses on the function of TFIIB and its interrelationship with α-tubulins in a mouse model. During oocyte maturation TFIIB distributes throughout the entire nucleus of the germinal vesicle (GV). After progression to GV breakdown (GVBD), TFIIB and α-tubulin co-localize and accumulate in the vicinity of the condensed chromosomes. During the MII stage, the TFIIB signals are more concentrated at the equatorial plate and the kinetochores. Colcemid treatment of oocytes disrupts the microtubule (MT) system, although the TFIIB signals are still present with the altered MT state. Injection of oocytes with TFIIB antibodies and siRNAs causes abnormal spindle formation and irregular chromosome alignment. These findings suggest that TFIIB dissociates from the condensed chromatids and then tightly binds to microtubules from GVBD to the MII phase. The assembly and disassembly of TFIIB may very well be associated with and driven by microtubules. TFIIB maintains its contact with the α-tubulins and its co-localization forms a unique distribution pattern. Depletion of Tf2b in oocytes results in a significant decrease in TFIIB expression, although polar body extrusion does not appear to be affected. Knockdown of Tf2b dramatically affects subsequent embryo development with more than 85% of the embryos arrested at the 2-cell stage. These arrested embryos still maintain apparently normal morphology for at least 96h without any obvious degeneration. Analysis of the effects of TFIIB in somatic cells by co-transfection of BiFC plasmids pHA-Tf2b and pFlag-Tuba1α further confirms a direct interaction between TFIIB and α-tubulins.