The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicenter Real-world clinical study.

BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analysed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% versus [vs.] 59.0%; P<0.001), pathological complete response rate (14.36% vs. 6.41%; P=0.002) and major pathological response rate (39.49% vs. 26.15%; P=0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P=0.694) and proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P=0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P=0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence (odds ratio 0.62 [95% CI 0.41-0.92]; P=0.018). No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P=0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates, and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.

Lysine acetylome profiling in mouse hippocampus and its alterations upon FMRP deficiency linked to abnormal energy metabolism.

Loss of fragile X retardation protein (FMRP) leads to fragile X syndrome (FXS), a common cause of inherited intellectual disability. Protein lysine acetylation (K-ac), a reversible post-translational modification of proteins, is associated with the regulation of brain development and neuropathies. However, a comprehensive hippocampal K-ac protein profile in response to FMRP deficiency has not been reported until now. Using LC-MS/MS to analyze the enriched K-ac peptides, this study identified 1629 K-ac hits across 717 proteins in the mouse hippocampus, and these proteins were enriched in several metabolic processes. Of them, 51 K-ac hits across 45 proteins were significantly changed upon loss of FMRP. These altered K-ac proteins were enriched in energy metabolic processes including carboxylic acid metabolism process, aerobic respiration and citrate cycle, linking with several neurological disorders such as lactic acidosis, Lewy body disease, Leigh disease and encephalopathies. In the mouse hippocampus and the hippocampal HT-22 cells, FMRP deficiency could induce altered K-ac modification of several key enzymes, decrease in ATP and increase in lactate. Thus, this study identified a global hippocampal lysine acetylome and an altered K-ac protein profile upon loss of FMRP linked to abnormal energy metabolism, implicating in the pathogenesis of FXS. SIGNIFICANCE: Fragile X syndrome (FXS) is a common inherited neurodevelopment disorder characterized by intellectual disability and an increased risk for autism spectrum disorder. FXS is resulted from silencing of the FMR1 gene, which induces loss of its encoding protein FMRP. Molecular and metabolic changes of Fmr1-null animal models of FXS have been identified to potentially contribute to the pathogenesis of FXS. Here, we used a TMT-labeled quantitative proteomic analysis of the peptides enriched by anti-K-ac antibodies and identified a global K-ac protein profile in the mouse hippocampus with a total of 1629 K-ac peptides on 717 proteins. Of them, 51 K-ac peptides regarding 45 proteins altered in response to loss of FMRP, which were enriched in energy metabolic processes and were implicated in several neurological disorders. Thus this study for the first time provides a global hippocampal lysine acetylome upon FMRP deficiency linked to abnormal metabolic pathways, which may contribute to pathogenic mechanism of FXS.

Efficacy assessment of acupuncture in improving symptoms of uterine fibroids: A randomized controlled trial.

INTRODUCTION: Uterine fibroids are a common benign genital tumor disease in gynecological diseases. It is mainly a change in physical function caused by the growth of smooth muscle cells in the factor uterus. Modern medicine's treatment of this disease is based on the dependence of uterine fibroids on sex hormones. Treatment with antiprogestin and estrogen drugs can reduce the volume of fibroids or slow the rate of increase in volume, thereby achieving the goal of alleviating clinical symptoms. In order to meet the needs of the majority of women of childbearing age and to maintain fertility, acupuncture treatment of uterine fibroids has a broad prospect for development. METHODS/DESIGN: This study plans to select 60 cases that meet the corresponding selection criteria. According to the random principle, they will be divided into intervention group and control group, with 30 cases in each group. The general information, fibroid size, and TCM syndrome scores of the two groups of patients will be compared before treatment. In terms of treatment, the intervention group will be given acupuncture combined therapy; the control group will be given Chinese patent medicine. The treatment cycles in both groups will be three menstrual cycles. After the treatment is completed, the data of the relevant curative effect indicators are analyzed by using SPSS software to draw conclusions. DISCUSSION: We aim to provide higher evidence-based medical evidence for acupuncture treatment of uterine fibroids. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000030438, Registered on March 01, 2020.

Cyclic Dipeptides Mediating Quorum Sensing and Their Biological Effects in Hypsizygus Marmoreus.

A novel quorum sensing (QS) system was discovered in Serratia odorifera, the symbiotic bacterium of Hypsizygus marmoreus. This system uses cyclo(Pro-Phe), cyclo(Pro-Tyr), cyclo(Pro-Val), cyclo(Pro-Leu), cyclo(Tyr-Leu), and cyclo(Tyr-Ile) as autoinducers. This discovery is the first attempt to characterize cyclic dipeptides as QS signaling molecules in S. odorifera and improves the classical QS theory. Significantly, except for cyclo(Tyr-Leu), these QS autoinducers can increase the transcription level of lignin-degrading enzyme genes of H.marmoreus. The cyclo(Pro-Phe) can increase the activity of extracellular laccase (1.32-fold) and manganese peroxidase (20%), which may explain why QS potentially regulates the hyphal growth, primordium formation, and fruit body development of H. marmoreus. Furthermore, it was demonstrated that the cyclo(Tyr-Ile) biosynthesis in S. odorifera was catalyzed by the nonribosomal peptide synthetase (NRPS). This study supports exploring the growth and development of H.marmoreus promoted by its symbiotic bacteria at QS signal transduction level.

Polyvinyl alcohol degradation by Bacillus cereus RA23 from oil sludge sample.

A novel polyvinyl alcohol (PVA)-degrading strain Bacillus cereus RA23 was isolated from an oil sludge sample and environmental factors affecting its PVA degradation efficiency were optimized in detail. Inorganic nitrogen source, ammonium chloride (NH4Cl), was found to be the best nitrogen source and enhanced the PVA degradation rate greatly. The optimal medium for PVA biodegradation consisted of (g/L) PVA 1, NH4Cl 1, K2HPO4 1.6, MgSO4·7H2O 0.05, FeSO4·6H2O 0.02, CaCl2 0.05, NaCl 0.02. The optimal temperature and pH for PVA biodegradation by strain RA23 was 28 °C and 7.0, respectively, and 85% of 0.1% PVA was degraded after 5 days under these conditions. FTIR studies showed that the carboxylic acids (possibly including aldehyde or ketone) could be the intermediate product of PVA biodegradation. The investigation of strain RA23 for PVA degradation will provide important information to facilitate the removal of wastewater pollution in industrial zones.

Degradation of polyvinyl alcohol by a novel bacterial strain Stenotrophomonas sp. SA21.

In this study, polyvinyl alcohol (PVA)-degrading bacteria were screened from oil sludge using PVA as a sole source of carbon in the culture medium. A novel strain, SA21, was obtained and identified as a member of the Stenotrophomonas genus based on the analysis of a partial 16S rDNA nucleotide sequence, morphological and biochemical characteristics, and phylogenetic analysis. This Stenotrophomonas isolate had not previously been reported as a PVA-degrading bacterium. Stenotrophomonas sp. strain SA21 degraded 90% of the PVA present in the culture medium after 4 days. The effect of nitrogen sources on the production of PVA-degrading enzyme involved in the biodegradation process was significant, and the enzymatic activity reached 82 U/ml when ammonium nitrate or urea was used in the optimized medium. The information obtained in this study will provide a foundation for improving industrial wastewater treatment. ABBREVIATIONS: DCW: dry cell weight; FTIR: Fourier Transform Infrared Spectroscopy; NCBI: National Center for Biotechnology Information; PCR: polymerase chain reaction; PVA: polyvinyl alcohol; SEM: scanning electron microscope.

The response of Serratia marcescens JG to environmental changes by quorum sensing system.

Many bacterial cells are known to regulate their cooperative behaviors and physiological processes through a molecular mechanism called quorum sensing. Quorum sensing in Serratia marcescens JG is mediated by the synthesis of autoinducer 2 (AI-2) which is a furanosyl borate diester. In this study, the response of quorum sensing in S. marcescens JG to environment changes such as the initial pH, carbon sources and boracic acid was investigated by a bioreporter and real-time PCR analysis. The results show that glucose can affect AI-2 synthesis to the greatest extent, and 2.0 % glucose can stimulate S. marcescens JG to produce more AI-2, with a 3.5-fold increase in activity compared with control culture. Furthermore, the response of quorum sensing to changes in glucose concentration was performed by changing the amount of luxS RNA transcripts. A maximum of luxS transcription appeared during the exponential growth phase when the glucose concentration was 20.0 g/L. AI-2 production was also slightly impacted by the low initial pH. It is significant for us that the addition of boracic acid at microdosage (0.1-0.2 g/L) can also induce AI-2 synthesis, which probably demonstrated the feasible fact that the 4,5-dihydroxy-2, 3-pentanedione cyclizes by the addition of borate and the loss of water, is hydrated and is converted to the final AI-2 in S. marcescens JG.