Splenectomy versus splenic preservation in total gastrectomy for gastric cancer: a systematic review and meta-analysis comparing survival benefits and short-term complications.

BACKGROUND: There is an ongoing debate regarding the comparative merits of splenectomy (SP) and splenic preservation in the surgical management of gastric cancer. This systematic review and meta-analysis aims to shed light on potential differences in survival outcomes and postoperative complications associated with these two procedures. METHOD: An exhaustive literature search was conducted across multiple databases, namely PubMed, Embase, Cochrane Library, and Web of Science. We utilized a random-effects model via RevMan 5.4 software to conduct a meta-analysis of the hazard ratios (HRs) and risk ratios (RRs) associated with SP and spleen preservation. Subgroup analyses were based on various attributes of the included studies. We employed funnel plots to assess publication bias, and sensitivity analysis was conducted to gauge the stability of the combined results. Both funnel plots and sensitivity analysis were performed using Stata 12. RESULT: Our research incorporated 23 observational studies and three randomized controlled trials, involving a total of 6,255 patients. SP did not yield superior survival outcomes in comparison to splenic preservation, a conclusion that aligns with the combined results of the randomized controlled trials. No statistically significant difference in survival prognosis was observed between SP and splenic preservation, irrespective of whether the patients had proximal gastric cancer or proximal gastric cancer invading the stomach's greater curvature. SP exhibited a higher incidence of all postoperative complications, notably pancreatic fistula and intraabdominal abscesses. However, it did not significantly differ from splenic preservation in terms of anastomotic leakage, incision infection, intestinal obstruction, intra-abdominal bleeding, and pulmonary infection. No significant difference in postoperative mortality between SP and splenic preservation was found. Funnel plots suggested no notable publication bias, and sensitivity analysis affirmed the stability of the combined outcomes. CONCLUSION: Despite the lack of significant differences in certain individual complications and postoperative mortality, the broader pattern of our data suggests that SP is associated with a greater overall frequency of postoperative complications, without providing additional survival benefits compared to splenic preservation. Thus, the routine implementation of SP is not advocated.

When doctors perform surgery for gastric (stomach) cancer, they sometimes remove the spleen, a procedure known as splenectomy (SP). However, there's a debate on whether removing the spleen is better than preserving it. Our study aimed to compare these two methods in terms of patient survival and the risk of complications after surgery. To do this, we looked at data from 26 studies involving 6,255 patients. Our analysis was thorough, using advanced statistical methods to ensure accuracy. Here's what we found: patients who had their spleen removed did not live longer than those who kept their spleen. Whether the cancer was just in the upper part of the stomach or had spread to the nearby large curve of the stomach, the survival rates were similar for both groups. Patients who underwent SP faced more postoperative complications, especially issues like pancreatic fistula and intra-abdominal abscesses. However, for some complications like leakage from the surgical joint, infection of the wound, bowel obstruction, internal bleeding, and lung infections, there was no significant difference between the two groups. The chances of dying post-surgery were similar whether patients had their spleen removed or not. Our findings suggest that routinely removing the spleen during gastric cancer surgery does not improve survival rates and is linked to more postoperative complications. Therefore, it may be better to avoid removing the spleen unless absolutely necessary.

Proteomic study on nintedanib in gastric cancer cells.

Background: Gastric cancer is a very common gastrointestinal tumor with a high mortality rate. Nintedanib has been shown to significantly reduce tumor cell proliferation and increase apoptosis in gastric cancer cells in vitro. However, its systemic action mechanism on gastric cancer cells remains unclear. A high-throughput proteomic approach should help identify the potential mechanisms and targets of nintedanib on gastric cancer cells. Methods: The effects of nintedanib on the biological behavior of gastric cancer cells were evaluated. A cytotoxic proliferation assay was performed to estimate the half maximal inhibitory concentration (IC50). AGS cells were divided into control, and nintedanib-treated groups (5 µM, 48 h), and differential protein expression was investigated using tandem mass tags (TMT) proteomics. The molecular mechanisms of these differentially expressed proteins and their network interactions were then analyzed using bioinformatics, and potential nintedanib targets were identified. Results: This study identified 845 differentially expressed proteins in the nintedanib-treated group (compared to the control group), comprising 526 up-regulated and 319 down-regulated proteins. Bioinformatics analysis revealed that the differentially expressed proteins were primarily enriched in biological pathways for branched-chain amino acid metabolism, steroid biosynthesis, propionate metabolism, fatty acid metabolism, lysosome, peroxisome, and ferroptosis. Key driver analysis revealed that proteins, such as enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), isocitrate dehydrogenase 1 (IDH1), acyl-CoA oxidase 1 (ACOX1), acyl-CoA oxidase 2 (ACOX2), acyl-CoA oxidase 3 (ACOX3), and acetyl-CoA acyltransferase 1 (ACAA1) could be linked with nintedanib action. Conclusion: Nintedanib inhibits the proliferation, invasion, and metastasis of gastric cancer cells. The crossover pathways and protein networks predicted by proteomics should provide more detailed molecular information enabling the use of nintedanib against gastric cancer.

Association between immune-related hub genes CD36, CXCL13, FGFR4, GABBR1, LAMP3, MMP12, and PPM1H and colorectal cancer prognosis.

The present study aims to identify immune-related prognostic genes in colorectal cancer (CRC), and to explore potential mechanisms through which these genes regulate CRC progression. We first constructed a prognostic risk model based on seven gene signatures [cluster of differentiation-36 (CD36), chemokine (C-X-C-motif) ligand 13 (CXCL13), fibroblast growth factor receptor 4 (FGFR4), gamma-amino-butyric acid type B receptor 1 (GABBR1), lysosome-associated membrane glycoprotein 3 (LAMP3), recombinant matrix metalloproteinase 12 (MMP12), and protein phosphatase 1H (PPM1H)] using integrated bioinformatic analyses. FGFR4, GABBR1, and LAMP3 were highly expressed in CRC cell lines (in comparison with a normal colonic epithelial cell line), while CD36, CXCL13, MMP12, and PPM1H were weakly expressed. These in vitro expression results were largely consistent with our bioinformatic analysis. A prognostic model was generated to identify a high-risk group with worse survival outcome based on Kaplan-Meier analysis. Our prognostic model showed superior accuracy in both the training and test cohorts. In addition, we found that the low-risk subgroup exhibited greater infiltration by M1 macrophages, CD8+ T cells, CD4+ T cells, and activated NK cells. In conclusion, our findings provide evidence that seven immune-related hub genes can be considered as gene signatures to predict CRC prognosis and to differentiate CRC patient benefit, ultimately serving as a guide for individualized immunotherapy.

The significance of preoperative neutrophil-to-lymphocyte ratio in predicting short-term complications and survival benefits of pancreaticoduodenectomy: A systematic review and meta-analysis.

BACKGROUND: The established association between the inflammatory marker, neutrophil-lymphocyte ratio (NLR), and both long-term surgical prognosis and short-term postoperative complications is well-recognized. However, its prognostic value in pancreaticoduodenectomy (PD) is yet to be ascertained. This meta-analysis investigates the prognostic relevance of preoperative NLR in PD patients. METHOD: We systematically searched electronic databases to identify studies exploring the relationship between pre-treatment blood NLR levels and overall survival (OS), disease-free survival (DFS), and immediate postoperative complications in PD patients. Statistical evaluations, using RevMan 5.4 and Stata 12, focused on hazard ratios (HRs) and risk ratios (RRs). Additionally, subgroup analyses, publication bias tests, and sensitivity analyses were performed. RESULT: Our analysis encompassed 18 retrospective studies, with NLR cutoff values ranging from 2 to 3.8. The meta-analysis revealed that PD patients with elevated NLR had diminished OS and DFS, evidenced by an HR of 1.35 (95% CI: 1.11-1.64, p â€‹= â€‹0.003) and 1.62 (95% CI: 1.15-2.27, p â€‹= â€‹0.005), respectively. Moreover, NLR emerged as an independent determinant of immediate postoperative complications, indicated by an OR of 1.91 (95% CI: 1.01-3.59, p â€‹= â€‹0.013) and an HR of 2.15 (95% CI: 1.23-3.73, p â€‹< â€‹0.01). CONCLUSION: NLR serves as a significant prognostic indicator for both OS and DFS following PD and is a reliable predictor of postoperative complications. Preoperative Neutrophil-to-Lymphocyte Ratio (NLR) is a significant prognostic indicator for overall survival (OS) and disease-free survival (DFS) in patients undergoing pancreaticoduodenectomy (PD).

Peptidomics insights: neutrophil extracellular traps (NETs) related to the chronic subdural hemorrhage.

Chronic subdural hemorrhage (CSDH) refers to a hematoma with an envelope between the dura mater and the arachnoid membrane and is more common among the elderly. It was reported that the dura mater, which is highly vascularized with capillary beds, precapillary arterioles and postcapillary venules play an important role in the protection of the central nervous system (CNS). Numerous evidences suggests that peptides play an important role in neuroprotection of CNS. However, whether dura mater derived endogenous peptides participate in the pathogenesis of CSDH remains undetermined. In the current study, the peptidomic profiles were performed in human dura of CSDH (three patients) and the relative control group (three non-CSDH samples) by LC-MS (liquid chromatography-mass spectrometry). The results suggested that a total of 569 peptides were differentially expressed in the dura matter of CSDH compared with relative controls, including 217 up-regulated peptides and 352 down-regulated peptides. Gene Ontology (GO) analysis demonstrated that the precursor proteins of those differentially expressed peptides were involved in the various biological processes. Interestingly, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that NETs participated in the pathogenies of CSDH. Further investigate showed that H3Cit was significantly elevated in the dural and hematoma membranes of patients with CSDH compared to patients without CSDH. Taken together, our results showed the differentially expressed peptides in human dura mater of CSDH and demonstrated that NETs formation in the dural and hematoma membranes might be involved in the pathogenesis of CSDH. It is worth noting that pharmacological inhibition of NETs may have potential therapeutic implications for CSDH.

Identification of potential functional peptides involved in demyelinating injury in the central nervous system.

Multiple sclerosis (MS) is a chronic inflammatory neurologic disease characterized by the demyelinating injury of the central nervous system (CNS). It was reported that the mutant peptide came from myelin proteolipid protein (PLP) and myelin basic protein (MBP) might play a critical role in immunotherapy function of MS. However, endogenous peptides in demyelinating brain tissue of MS and their role in the pathologic process of MS have not been revealed. Here, we performed peptidomic analysis of freshly isolated corpus callosum (CC) from the brains of CPZ-treated mice and normal diet controls of male C57BL/6 mice by LC-MS/MS. Identified a total of 217 peptides were expressed at different levels in MS mice model compared with controls. By performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, we found that the precursor protein of these differently expressed peptides (DEPs) were associated with myelin sheath and oxidative phosphorylation. Our study is the first brain peptidomic of MS mice model, revealing the distinct features of DEPs in demyelination brain tissue. These DPEs may provide further insight into the pathogenesis and complexity of MS, which would facilitate the discovery of the potential novel and effective strategy for the treatment of MS.

LINC00938 alleviates hypoxia ischemia encephalopathy induced neonatal brain injury by regulating oxidative stress and inhibiting JNK/p38 MAPK signaling pathway.

Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death. Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases. LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease. However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway. Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N-acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl2-induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.

ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis.

Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a potential predictive and prognostic biomarker for colorectal cancer (CRC), but its predictive efficacy in detecting CRC liver metastasis (CLM) remains unclear. Additionally, its utility in the clinical setting needs further investigation. We conducted a meta-analysis to determine the utility of ctDNA as a biomarker for predicting the prognosis of CLM and investigate the relationship between CLM and ctDNA positivity. A literature search was performed in electronic databases to identify relevant studies published up to March 19, 2022. We retrieved data on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for both ctDNA-positive and ctDNA-negative colorectal liver metastasis (CLM) patients from the selected articles. Hazard ratios (HRs) were also calculated for these survival outcomes analysis was also performed. The stability of the combined meta-analysis was verified by sensitivity analysis and publication bias evaluation. Ten trials were included, and 615 patients were evaluated. In patients with CLM, pooled HRs revealed a substantial link between ctDNA positivity and RFS/DFS. Subgroup analysis revealed that ctDNA had a prospective detection value. Sensitivity analysis and publication bias evaluation indicated stable results. Although the results on pooled HR for OS suggested that ctDNA-positive patients had a shorter survival time, their pooled HRs had a relatively evident heterogeneity, and sensitivity analysis and publication bias evaluation indicated that pooled HRs were extremely unstable. In conclusion, our results demonstrate that ctDNA appears to be a prognostic biomarker for resectable CLM patients.

Comparison of Efficacy and Safety of Laparoscopic Holmium laser Lithotripsy and Laparoscopic Bile Duct Exploration for Bile Duct Stones: A Systematic Review and Meta-Analysis.

BACKGROUND: Laparoscopic holmium laser lithotripsy (LHLL) has been used to treat bile duct stones with unclear outcomes. A meta-analysis was conducted to investigate the LHLL and laparoscopic bile duct exploration (LBDE) efficacy and safety in treating bile duct stones. METHODS: The correlational studies were searched databases, such as PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP, to identify eligible studies from inception to July 2022. The dichotomous and continuous outcomes were evaluated using odds ratio (OR), risk difference (RD) and weighted mean difference (WMD) with 95% confidence intervals (CIs). Stata 15.0 and Review Manager 5.3 software helped in data analyses. RESULTS: A total of 23 studies with 1,890 patients, primarily from China, were included. The results indicated that operation time (WMD = - 26.94; 95% CI:(- 34.30, - 19.58); P < 0.00001), estimated blood loss (WMD = - 17.97; 95% CI: (- 22.94, - 13.00); P = 0.002), rate of residual stone (OR = 0.15, 95%CI: (0.10, 0.23); P < 0.00001), length of hospital stay (WMD = - 2.88; 95% CI:(- 3.80, - 1.96); P < 0.00001) and time to bowel function recovery (WMD = - 0.59; 95% CI: (- 0.76, - 0.41); P < 0.00001) had statistically significant differences between the two groups. In postoperative complications, biliary leakage (RD = -0.03; 95% CI: (- 0.05, -0.00); P = 0.02), infection (RD = - 0.06; 95% CI: (- 0.09,- 0.03); P < 0.00001) and Hepatic injury (RD = - 0.06; 95% CI: (- 0.11, - 0.01); P = 0.02) revealed statistically significant differences. However, no significant differences were observed in biliary damage (RD = - 0.03; 95% CI: (- 0.06, 0.00); P = 0.06) and hemobilia (RD = - 0.03; 95% CI: (- 0.06, 0.00); P = 0.08). CONCLUSION: The current meta-analysis indicated that LHLL could be more effective and safer than LBDC. However, these results should be confirmed with a larger sample size and rigorously designed randomized controlled trials.

The value of postoperative radiotherapy in thymoma patients with myasthenia gravis.

INTRODUCTION: Surgery is the first-line treatment for patients with thymoma associated with myasthenia gravis (MG); however, the value of radiotherapy among these patients remains debatable. Herein, we examined the impact of postoperative radiotherapy (PORT) on the efficacy and prognosis of patients with thymoma and MG. METHODS: This retrospective cohort study included 126 patients with thymoma and MG who were enrolled in the Xiangya Hospital clinical database between 2011 and 2021. Demographic and clinical data were collected including sex, age, histologic subtype, Masaoka-Koga staging, primary tumor, lymph node, metastasis (TNM) staging, and therapeutic modalities. To evaluate short-term MG symptom improvement following PORT, we examined changes in the quantitative myasthenia gravis (QMG) scores within 3 months post-treatment. Minimal manifestation status (MMS) was the main endpoint for assessing long-term improvement in MG symptoms. Overall survival (OS) and disease-free survival (DFS) were primary endpoints to determine the impact of PORT on prognosis. RESULTS: Effects of PORT on MG symptoms: QMG scores significantly differed between the non-PORT and PORT groups (χ2 = 6.300, p = 0.012). The median time to achieve MMS was significantly shorter in the PORT group than that in the non-PORT group (2.0 years vs. 4.4 years; p = 0.031). Multivariate analysis revealed that radiotherapy was associated with a reduced time to achieve MMS (hazard ratio [HR] 1.971, 95% confidence interval [CI]:1.102-3.525, p = 0.022). Effects of PORT on DFS and OS: The 10-year OS rate of the entire cohort was 90.5%, whereas OS rates for the PORT and non-PORT groups were 94.4 and 85.1%, respectively. The 5-year DFS rates for the whole cohort, PORT group, and non-PORT group were 89.7, 95.8, and 81.5%, respectively. PORT was associated with improved DFS (HR 0.139, 95% CI: 0.037-0.533, p = 0.004). In the high-risk histologic subgroup (type B2, B3), patients who received PORT had better OS (p = 0.015) and DFS (p = 0.0053) than those who did not receive PORT. PORT was associated with improved DFS (HR 0.232, 95% CI: 0.069-0.782, p = 0.018) in Masaoka-Koga stages II, III, and IV disease. CONCLUSIONS: Overall, our findings indicate that PORT positively impacts thymoma patients with MG, particularly those with a higher histologic subtype and Masaoka-Koga staging.

Latent tuberculosis infection in myasthenia gravis patients on immunosuppressive therapy: high incidence yet moderate reactivation rate.

BACKGROUND: Immunosuppressive therapies (ISTs) are mainstays for management of myasthenia gravis (MG). Meanwhile, latent tuberculosis infection (LTBI) is common in the setting of high-burden countries. However, the prevalence of LTBI among MG patients and whether receiving ISTs for MG would aggravate LTBI reactivation remain unknown. METHODS: We retrospectively analyzed the frequency of LTBI via interferon-gamma release assay (IGRA) positivity among hospitalized MG patients from both rural and urban areas in a tertiary hospital, and those receiving ISTs were followed up to investigate the reactivation risk of LTBI. RESULTS: A total of 300 MG patients with determinate IGRA results were enrolled, where the frequency of LTBI was 35.0%. Male (OR = 1.910, 95% CI: 1.181-3.089, p = .008) and elderly (OR = 1.044, 95% CI: 1.027-1.061, p < .001) patients were prone to LTBI. Of those with LTBI, 78 individuals on ISTs were successfully followed up for a median duration of 18.3 (8.5-24.0) months, of which 25 (32.1%) received anti-tuberculosis (TB) treatments. The rate of various degrees of adverse events was 82.1% over the course of the follow-up, but was not different between individuals with and without therapies against TB (χ2 < 0.001, p > .999). Only 1 patient eventually reported lymph node and intestinal TB, with the incidence rate of LTBI reactivation preliminarily estimated to be 0.81 per 100 person years. CONCLUSION: The frequency of LTBI is high in our MG cohort, especially among those with advanced age and males. However, receiving immunosuppressives seems not to increase the risk of LTBI reactivation. LTBI screening is strongly recommended for all MG patients ready to receive ISTs, while preventive anti-TB chemotherapy should be prescribed after weighing potential benefits against the risk of side effects in those with LTBI. In-depth investigation is still entailed to further verify these findings due to the limitation of the retrospective single-center design of our study.

Characteristics of myasthenia gravis in elderly patients: a retrospective study.

BACKGROUND: The incidence of myasthenia gravis (MG) is increasing, and its characteristics in elderly patients are believed to differ from those in younger patients. However, only a few studies have focused on elderly patients with MG. OBJECTIVE: To review the characteristics of MG in elderly patients and evaluate whether older age is an independent factor associated with achieving minimal manifestation status (MMS). METHODS: This retrospective cohort study included 367 patients (319 non-elderly and 48 elderly patients) with MG enrolled at Xiangya Hospital from September 1, 2016, to December 31, 2018. We collected demographic data and information regarding comorbidities, antibody status, Myasthenia Gravis Foundation of America classification, affected muscle groups, thymoma, and treatment. MMS was defined as the primary outcome. RESULTS: Comorbidities were more common in elderly than in younger patients with MG. Anti-acetylcholine receptor antibody was the dominant subtype, whereas anti-muscle-specific tyrosine kinase antibody was rare and detected only in non-elderly patients. Elderly patients were more likely than younger patients to have generalized MG, but the frequency of thymoma was lower (28.5% vs. 10.4%, p = 0.0078). MMS or better was achieved in 154 (48.3%) and 13 (27.1%) non-elderly and elderly patients, respectively. Older age did not appear to be an independent factor associated with MMS (hazard ratio = 0.625; 95% confidence interval, 0.345-1.131). CONCLUSIONS: Older age was not an independent factor for a worse prognosis in patients with MG. The treatment of elderly patients with MG should be individually tailored.

Evaluation of outcome measures for myasthenia gravis subgroups.

INTRODUCTION: Disease evaluation and long-term follow-up of myasthenia gravis (MG) patients rely on disease-specific measures. We evaluated four widely used MG-specific assessments, and compared the response to disease change in different MG subgroups. METHODS: We used the Cronbach's α coefficient to test reliability, Pearson correlation coefficients to test construct validity, as well as one-way ANOVA and independent-sample t-tests to access discriminant validity. Analyses of similar items between QMG and MG-ADL included paired-sample t-tests and mean score comparisons. Pearson correlation coefficients were used to describe the correlation between changes of QMG, MG-ADL, MG-QOL15r and MGC. The Wilcoxon matched-pairs signed-ranks test was performed to compare the outcomes. RESULTS: 872 MG patients were enrolled. QMG, MG-ADL, MG-QOL15r, and MGC all exhibited high reliability. All four scales displayed good discriminant validity according to the MGFA classification and MGC score. MG-ADL showed significant differences between patients grouped by age and gender, and MG-QOL15r showed significant differences between patients grouped by age. Analyses of similar items showed that MG-ADL achieved higher scores in bulbar items, whereas QMG produced higher scores in limb items. For patients in remission or minimal manifestation status, QMG exhibited significantly greater improvement than MG-QOL15r. In patients of MGFA I, II, III, and IV, QMG showed significantly greater improvement than MG-ADL. CONCLUSIONS: Patient-reported scale is an important supplement for a given period. MG-ADL has a better response to severe disease, and MG-QOL15r is more comprehensive for patients in remission or minimal manifestation status.

Type 2 Nep1-Like Proteins from the Biocontrol Oomycete Pythium oligandrum Suppress Phytophthora capsici Infection in Solanaceous Plants.

As a non-pathogenic oomycete, the biocontrol agent Pythium oligandrum is able to control plant diseases through direct mycoparasite activity and boosting plant immune responses. Several P. oligandrum elicitors have been found to activate plant immunity as microbe-associated molecular patterns (MAMPs). Necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are a group of MAMPs widely distributed in eukaryotic and prokaryotic plant pathogens. However, little is known about their distribution and functions in P. oligandrum and its sister species Pythium periplocum. Here, we identified a total of 25 NLPs from P. oligandrum (PyolNLPs) and P. periplocum (PypeNLPs). Meanwhile, we found that PyolNLPs/PypeNLPs genes cluster in two chromosomal segments, and our analysis suggests that they expand by duplication and share a common origin totally different from that of pathogenic oomycetes. Nine PyolNLPs/PypeNLPs induced necrosis in Nicotiana benthamiana by agroinfiltration. Eight partially purified PyolNLPs/PypeNLPs were tested for their potential biocontrol activity. PyolNLP5 and PyolNLP7 showed necrosis-inducing activity in N. benthamiana via direct protein infiltration. At sufficient concentrations, they both significantly reduced disease severity and suppressed the in planta growth of Phytophthora capsici in solanaceous plants including N. benthamiana (tobacco), Solanum lycopersicum (tomato) and Capsicum annuum (pepper). Our assays suggest that the Phytophthora suppression effect of PyolNLP5 and PyolNLP7 is irrelevant to reactive oxygen species (ROS) accumulation. Instead, they induce the expression of antimicrobial plant defensin genes, and the induction depends on their conserved nlp24-like peptide pattern. This work demonstrates the biocontrol role of two P. oligandrum NLPs for solanaceous plants, which uncovers a novel approach of utilizing NLPs to develop bioactive formulae for oomycete pathogen control with no ROS-caused injury to plants.

Chlamydial-Secreted Protease Chlamydia High Temperature Requirement Protein A (cHtrA) Degrades Human Cathelicidin LL-37 and Suppresses Its Anti-Chlamydial Activity.

BACKGROUND Chlamydia trachomatis is an obligate intracellular pathogen that can cause severe reproductive tract complications while ascending infection occurs. When spreading from cell to cell in a host, C. trachomatis utilizes various survival strategies to offset host defense mechanisms. One such strategy is to degrade host antimicrobial defense proteins before they can attack the invading C. trachomatis cells. MATERIAL AND METHODS We expressed and purified recombinant chlamydia high temperature requirement protein A (cHtrA) including 2 cHtrA mutants (MT-H143A and MT-S247A), and also extracted endogenous cHtrA. Proteins were identified and their purity evaluated by SDS-PAGE and Western blot. The anti-chlamydial activity and degradation of 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) by cHtrA and 2 cHtrA mutants (MT-H143A and MT-S247A) were tested by immunoassay and Western blot. RESULTS Of the 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) tested, cathelicidin LL-37 showed the strongest anti-chlamydial activity. Interestingly, cHtrA effectively and specifically degraded LL-37, suppressing its anti-chlamydial activity. The 2 cHtrA mutants (MT-H143A and MT-S247A) were unable to degrade LL-37. Comparison of cHtrA activity from C. trachomatis D, L2, and MoPn strains on LL-37 showed similar responses. CONCLUSIONS cHtrA may contribute to C. trachomatis pathogenicity by clearing the passage of invasion by specific LL-37 degradation.

Increased KIF21B expression is a potential prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: The kinesin superfamily protein member KIF21B plays an important role in regulating mitotic progression; however, the function and mechanisms of KIF21B in cancer, particularly in hepatocellular carcinoma (HCC), are unknown. AIM: To explore the role of KIF21B in hepatocellular carcinoma and its effect on prognosis after hepatectomy. METHODS: First, data on the differential expression of KIF21B in patients with HCC from The Cancer Genome Atlas database was analyzed. Subsequently, the expression levels of KIF21B in HCC cell lines and hepatocytes were detected by reverse transcription-polymerase chain reaction, and its biological effect on BEL-7404 cells was evaluated by KIF21B knockdown. Immunohistochemical analysis was used to validate the differential expression of KIF21B in HCC tissues and adjacent normal tissues from 186 patients with HCC after hepatectomy. The Kaplan-Meier method was used to assess prognosis significance. RESULTS: KIF21B expression levels were significantly higher in HCC tissues than in corresponding adjacent normal tissues. The expression levels of KIF21B in four HCC cell lines were higher than that in normal liver cells. Functional experiments showed that KIF21B knockdown remarkably suppressed cell proliferation and induced apoptosis. Moreover, immunohistochemistry results are consistent with The Cancer Genome Atlas analysis, with KIF21B expression levels being increased in HCC tissues compared to adjacent normal tissues. Univariate and multivariate analyses revealed KIF21B as an independent risk factor for overall survival and disease-free survival in patients with HCC after hepatectomy. CONCLUSION: Taken together, our results provide evidence that KIF21B plays an important role in HCC progression and may be a potential diagnostic and prognostic marker for HCC.

Application of multiple Roux-en-Y hepaticojejunostomy reconstruction by formation of bile hilar duct lake in the operation of hilar cholangiocarcinoma.

BACKGROUND: Hilar cholangiocarcinoma is the most common malignant tumor of the extrahepatic bile duct. Until now, radical resection has been the most effective method for the long-term survival of patients with the disease. However, many problems have emerged in the field of hepatobiliary surgery for a long time, including complex surgical procedures, low resection rate, and postoperative complications. We have adopted the "multiple Roux-en-Y hepaticojejunostomy reconstruction by formation of a bile duct lake" technique in the treatment of hilar cholangiocarcinoma since 2008, and obtained satisfactory short- and long-term results. AIM: To examine the feasibility of the application of multiple Roux-en-Y hepaticojejunostomy reconstruction by formation of a bile duct lake in the operation of hilar cholangiocarcinoma. METHODS: A retrospective analysis was performed for the clinical data, surgical methods, and results of 76 patients with hilar cholangiocarcinoma who were treated with hilar bile duct lake-forming multiple Roux-en-Y hepaticojejunostomy reconstruction at Gansu Provincial Hospital. RESULTS: In all 76 cases, the operation was successful and no operative death occurred. The mean (range) operation time was 215.4 ± 53.5 min (124-678 min), and the amount of bleeding during the operation was 428.2 ± 63.8 mL (240-2200 mL). The overall 1-year survival rate was 78.9%, and the 3-year survival rate was 32.8%. CONCLUSION: The multiple Roux-en-Y hepaticojejunostomy reconstruction technique with formation of a bile duct lake is safe and effective for the surgical treatment of hilar cholangiocarcinoma.

Primary intestinal extranodal natural killer/T-cell lymphoma, nasal type: A case report.

BACKGROUND: Primary intestinal extranodal natural killer/T-cell lymphoma, nasal type (PI-ENKTCL) is a rare non-Hodgkin's lymphoma (NHL) subtype, and its prognosis is extremely poor. Clinical characteristics of the disease are not obvious and easily misdiagnosed. In this case report, we describe a patient with PI-ENKTCL who presented with intermittent hematochezia. The advantages of positron emission tomography/computed tomography (PET-CT) as a useful diagnostic tool and the role of surgery as an important therapy are highlighted. CASE SUMMARY: A 45-year-old man, hospitalized due to intermittent hematochezia, underwent gastroscopy, colonoscopy, biopsy and CT, but no cause was found. Hence, we carried out a multidisciplinary team (MDT) discussion on the causes and treatment of this patient, and it was decided to perform PET-CT imaging with a MDT discussion of the results. PET-CT demonstrated a diagnosis of lymphoma and it was decided to surgically resect the lesion, and a R0 resection was successfully performed. Postoperative pathology showed negative resection margins, and examination of the lesion confirmed the diagnosis of PI-ENKTCL. After surgery, the patient underwent a follow-up period of 6 mo and received 6 cycles of gemcitabine, oxaliplatin and L-asparaginase. No recurrence or metastasis occurred. CONCLUSION: PI-ENKTCL is rare, and MDT discussion is required during diagnosis. PET-CT can be performed for imaging diagnosis. Treatment is based on surgical resection, and the best treatment regimen is determined according to postoperative pathological results to improve prognosis and to extend survival in patients.

Multiple genetic factors affecting the pharmacokinetic and pharmacodynamic processes of tacrolimus in Chinese myasthenia gravis patients.

PURPOSE: Tacrolimus is a novel effective immunosuppressant for myasthenia gravis (MG) patients. However, the narrow therapeutic window, and high inter- and intrapatient variation in bioavailability largely limited its clinical application. This article intended to find the SNPs influencing clinical outcome and discover the possible mechanisms. METHODS: Based on the tagSNPs genotyped by Improved Multiple Ligase Detection Reaction, Plink 1.07 was used to find the SNPs having close interaction to tacrolimus serum concentration, QMG score changes or even reasonable drug dose. Then we searched several databases to predict the possible miRNA binding rs15524 sequence. Based on the prediction, dual-luciferase reporter assay and miRNA transfection were used to discover the mechanism of how SNP rs15524 controls tacrolimus serum concentration through influencing CYP3A5 expression. RESULTS: In this article, we found multiple SNPs on CYP3A4, CYP3A5, FKBP1A, NFATC2 genes were predicted closely related to tacrolimus serum concentration, therapeutic effect which reflected by QMG score changes or even reasonable drug dose. After in silico miRNA selection, possible relationship between hsa-miR-500a and rs15524 was found. With the help of dual-luciferase reporter assay, wild-type rs15524 (T allele) was found having a stronger binding affinity for hsa-miR-500a. Higher expression of CYP3A5 may also led by lower hsa-miR-500a level. CONCLUSIONS: SNP rs15524 may control CYP3A5 expression by affecting the binding affinity between CYP3A5 3'UTR and hsa-miR-500a. Wild type (T allele) 3'UTR of CYP3A5 has stronger binding affinity to hsa-miR-500a and cause lower CYP3A5 expression and higher tacrolimus serum concentration.