Long-term survival outcome of locally advanced gastric cancer patients who achieved a pathological complete response to neoadjuvant chemotherapy.

BACKGROUND: Long-term outcome of patients with locally advanced gastric cancer (LAGC) who achieved a pathological complete response (pCR) was scarcely discussed, and never had the factors affecting the prognosis of pCR patients been investigated. METHODS: We retrospectively reviewed all patients who achieved a pCR to neoadjuvant chemotherapy (NAC) in Jinling Hospital. The 3- and 5-year overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. Meanwhile, univariate and multivariate COX regression analysis was applied to identify prognostic factors affecting patients' survival. RESULTS: A total of 37 consecutive LAGC patients with pCR were included. The 3- and 5-year OS rates were 88.8% and 78.6%, and the 3- and 5-year PFS rates were 86.5% and 75.8%. In the multivariate COX model, NAC duration of more than 3 cycles (HR 0.11 [0.02-0.62], P = 0.013) and poorly differentiated tumor at diagnosis (HR 0.17 [0.03-0.95], P = 0.043) were detected as protective factors for patients OS. Whereas for PFS, NAC duration (HR 0.12 [0.02-0.67], P = 0.015) was the only protective factor confirmed, with tumor differentiation at diagnosis exhibiting marginal significance (HR 0.21 [0.04-1.09], P = 0.063). CONCLUSIONS: Patients with LAGC who achieved a pCR displayed favorable long-term survival outcome, especially those with adequate cycles (≥ 3) of NAC. Besides, poor differentiation at diagnosis might also predict the better OS when pCR achieved.

A Novel Spectrophotometric Method for Determination of Percarbonate by Using N, N-Diethyl-P-Phenylenediamine as an Indicator and Its Application in Activated Percarbonate Degradation of Ibuprofen.

Sodium percarbonate (SPC) concentration can be determined spectrophotometrically by using N, N-diethyl-p-phenylenediamine (DPD) as an indicator for the first time. The ultraviolet-visible spectrophotometry absorbance of DPD•+ measured at 551 nm was used to indicate SPC concentration. The method had good linearity (R2 = 0.9995) under the optimized experimental conditions (pH value = 3.50, DPD = 4 mM, Fe2+ = 0.5 mM, and t = 4 min) when the concentration of SPC was in the range of 0-50 µM. The blank spiked recovery of SPC was 95-105%. The detection limit and quantitative limit were 0.7-1.0 µM and 2.5-3.3 µM, respectively. The absorbance values of DPD•+ remained stable within 4-20 min. The method was tolerant to natural water matrix and low concentration of hydroxylamine (<0.8 mM). The reaction stoichiometric efficiency of SPC-based advanced oxidation processes in the degradation of ibuprofen was assessed by the utilization rate of SPC. The DPD and the wastewater from the reaction were non-toxic to Escherichia coli. Therefore, the novel Fe2+/SPC-DPD spectrophotometry proposed in this work can be used for accurate and safe measurement of SPC in water.

Suppression of microglial activation and monocyte infiltration ameliorates cerebellar hemorrhage induced-brain injury and ataxia.

Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C-C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia.

Severe Intestinal Dysbiosis in Rat Models of Short Bowel Syndrome with Ileocecal Resection.

BACKGROUND: Short bowel syndrome (SBS) resulting from extensive intestinal resection is thought to significantly affect gut microbiota. Data are limited on the signatures of the intestinal microbiome in SBS with different anatomical types. AIMS: The aim of our investigation was to characterize the composition and function of gut microbiota in SBS with or without ileocecal resection (ICR). METHODS: Six-week-old male Sprague-Dawley rats underwent 75% small bowel resection (SBR) with the ileocecal junction intact (SBR group, jejunoileal anastomosis, n = 10) or removed (ICR group, jejunocolic anastomosis, n = 10), or sham surgery (sham group, n = 10). Colonic contents of the rats were collected 28 days after operation, and 16S rRNA gene sequencing was performed on the MiSeq Illumina platform to analyze bacterial composition. RESULTS: Overall structures of the gut microbiome differed significantly among the three groups. The bacterial α-diversity of the ICR group was remarkably lower than that of the sham group. ICR rats were enriched with Lactobacillus and opportunistic pathogens from Proteobacteria but depleted of commensal genera belonging to the Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae families. Genera from the Bacteroidales S24-7 group, Porphyromonadaceae, Prevotellaceae, Rikenellaceae and Christensenellaceae were prevalent in SBR rats. Functional pathways of branched-chain and aromatic amino acid biosynthesis, lipopolysaccharide biosynthesis and infectious diseases were abundant in the ICR group, while SBR rats featured pathways of C5 branched dibasic acid metabolism, biotin metabolism and one carbon pool folate. CONCLUSIONS: ICR causes dramatically more severe intestinal dysbiosis than SBR only in SBS rat models, resulting in altered functional profiles of the gut microbiome.

Efficacy and Safety of Endoscopic Balloon Dilation for Upper Gastrointestinal Strictures of Crohn's Disease.

BACKGROUND: Few articles focused on endoscopic balloon dilation (EBD) in the management of Crohn's strictures in the upper gastrointestinal (GI) tract. AIMS: The purpose of this study was to evaluate the long-term efficacy and safety of EBD for Crohn's strictures in the upper GI tract and to determine early predictors of response and surgical intervention. METHODS: All eligible patients who underwent EBD for Crohn's strictures in the upper GI tract were retrospectively reviewed. The long-term success was defined as the recovery of normal diets without surgical intervention over the follow-up period. In order to seek early predictors, patients who achieved long-term success were compared with those who didn't. RESULTS: A total of 67 dilations of upper GI strictures were performed between June 2011 and March 2015 on 24 patients (mean age 25.6 ± 6.7, 20 male) with Crohn's disease. Technical success was achieved in 62 of 67 dilations (92.5 %) with a complication rate of 3 %. After the median follow-up period of 23.0 months (range 6.2-51.2 months), nine patients underwent surgical intervention, nine patients were still depending on tube feeding; in the meantime, only six (25 %) patients achieved long-term success. Additionally, patients who remained 1 month intervention-free (55.6 vs. 5.9 %, P = 0.015) were more likely to achieve long-term success. CONCLUSIONS: EBD was a safe procedure, but not a potent therapy for Crohn's upper GI strictures. Meanwhile, 1-month response could serve as an early predictor of the long-term response.

Spiradiclisliboensis (Rubiaceae), a new species from limestone mountain areas in Guizhou, China.

Spiradiclisliboensis L. Wu & W. J. Liu, a new species in tribe Ophiorrhizeae of Rubiaceae from limestone mountain areas of Guizhou, south-western China, is described and illustrated. It is similar to S.guangdongensis and S.jingxiensis, but differs from the latter two by the following traits: stipule triangular, inflorescence sessile or with peduncle up to 0.5 mm long, pedicel 0.8-2.2 mm long, corolla white, salverform, corolla tube 1.6-2.2 cm long, corolla tube of long-styled morph inside with a villous ring and stigmas positioned at the throat of the corolla tube. The conservation status is assessed as "Vulnerable" (VU) according to the IUCN Red List Categories and Criteria.

A comparative study of vestibular improvement and gastrointestinal effect of betahistine and gastrodin in mice.

Betahistine and gastrodin are the first-line medications for vestibular disorders in clinical practice, nevertheless, their amelioration effects on vestibular dysfunctions still lack direct comparison and their unexpected extra-vestibular effects remain elusive. Recent clinical studies have indicated that both of them may have effects on the gastrointestinal (GI) tract. Therefore, we purposed to systematically compare both vestibular and GI effects induced by betahistine and gastrodin and tried to elucidate the mechanisms underlying their GI effects. Our results showed that betahistine and gastrodin indeed had similar therapeutic effects on vestibular-associated motor dysfunction induced by unilateral labyrinthectomy. However, betahistine reduced total GI motility with gastric hypomotility and colonic hypermotility, whereas gastrodin did not influence total GI motility with only slight colonic hypermotility. In addition, betahistine, at normal dosages, induced a slight injury of gastric mucosa. These GI effects may be due to the different effects of betahistine and gastrodin on substance P and vasoactive intestinal peptide secretion in stomach and/or colon, and agonistic/anatgonistic effects of betahistine on histamine H1 and H3 receptors expressed in GI mucosal cells and H3 receptors distributed on nerves within the myenteric and submucosal plexuses. Furthermore, treatment of betahistine and gastrodin had potential effects on gut microbiota composition, which could lead to changes in host-microbiota homeostasis in turn. These results demonstrate that gastrodin has a consistent improvement effect on vestibular functions compared with betahistine but less effect on GI functions and gut microbiota, suggesting that gastrodin may be more suitable for vestibular disease patients with GI dysfunction.

How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease?

Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory condition of the intestine without any efficient therapeutic regimens. Gut microbiota, which plays an instrumental role in the development and maturation of the immune system, has been implicated in the pathogenesis of IBD. Emerging evidence has established that early-life events particularly maternal influences and antibiotic treatment are strongly correlated with the health or susceptibility to disease of an individual in later life. Thus, it is proposed that there is a critical period in infancy, during which the environmental exposures bestow a long-term pathophysiological imprint. This notion sheds new light on the development of novel approaches for the treatment, i.e., early interventions, more precisely, the prevention of many uncurable chronic inflammatory diseases like IBD. In this review, we have integrated current evidence to describe the feasibility of the "able-to-be-regulated microbiota," summarized the underlying mechanisms of the "microbiota-driven immune system education," explored the optimal intervention time window, and discussed the potential of designing early-probiotic treatment as a new prevention strategy for IBD.

Corrigendum: How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease?

[This corrects the article DOI: 10.3389/fnut.2021.690073.].