Metabolomics analysis revealed the neuroprotective role of 2-phosphoglyceric acid in hypoxic-ischemic brain damage through GPX4/ACSL4 axis regulation.

Hypoxic-ischemic brain damage (HIBD) is a cerebral injury resulting from the combination of ischemia and hypoxia in neonatal brain tissue. Presently, there exists no efficacious remedy for HIBD. A mounting body of evidence indicates that dynamic metabolites formed during metabolic procedures assume a vital role in neuronal maturation and recuperation. However, it remains unclear whether any endogenous metabolites are involved in the pathogenesis of HIBD. Here, an untargeted metabolomics analysis was conducted by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry (GC/LC-MS) in OGD/R (oxygen-glucose deprivation/reoxygenation)-induced HT-22 cells. We observed that ferroptosis signaling plays an essential role in HI-induced neuronal injury. Interestingly, we also found that the differentially expressed metabolite, 2-phosphoglyceric acid, significantly improved the neuronal cell survival of OGD/R HT-22 cells by inhibiting ferroptosis. Moreover, 2-phosphoglyceric acid effectively rescued the cell activity of HT-22 cells treated with the ferroptosis inducer RSL-3. Furthermore, 2-phosphoglyceric acid alleviated cerebral infarction and reduced HIBD-induced neuronal cell loss of the central nervous system in neonatal rats by regulating GPX4 expression. Taken together, we found that 2-phosphoglyceric acid, which was downregulated in HT-22 cells induced by OGD/R, exerted neuronal protective effects on OGD/R-treated HT-22 cells and HIBD-induced neonatal rats by inhibiting hypoxic-ischemic-induced ferroptosis through the regulation of the GPX4/ACSL4 axis.

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.

Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD-induced zebrafish.

BACKGROUND: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people's quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity. AIMS: However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear. METHODS: We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography-mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA. RESULTS: We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1. CONCLUSIONS: Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.

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.

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.

Electrohydrodynamically Printed d-f Transition Cerium(III) Complex.

The d-f transition rare earth complexes have recently emerged as a promising candidate for display applications due to the parity-allowed transition, high photoluminescence quantum yield (PLQY), short excited lifetime, and tunable emissions. Besides, inkjet printing has been regarded as an important technique for realizing full-color display. However, inkjet-printed d-f transition rare earth complexes have not been investigated. Herein, for the first time, we explored d-f transition cerium(III) complex 2-Me as the luminescent material by inkjet printing. With 1,2-dichlorobenzene as solvent and polystyrene as an additive, 2-Me film exhibits a similar emission peak and excited-state lifetime with 2-Me powder and a high PLQY of 45%, demonstrating the excellent stability of 2-Me ink. Finally, we suppressed the coffee ring effect and prepared the first inkjet-printed pattern ''HUST'' composed of d-f transition rare earth complex ink with uniform blue fluorescence. Our pioneering work provides a promising alternative for inkjet printing inks.

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.

Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high-fat diet-induced obesity.

Obesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound-healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high-fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis-mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2-ACSL4 axis.

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.

Vacuum-deposited Rb3CeI6 for deep-blue-light-emitting diodes.

Recently, perovskite light-emitting diodes (PeLEDs) have exhibited outstanding performance in next-generation high-definition display applications. However, compared with green and red PeLEDs, the development of efficient and stable blue PeLEDs to meet the requirement for a wide color gamut has been a challenge. Herein, we vacuum thermally deposited a film of the lead-free rare earth halide Rb3CeI6, which shows deep blue emission with peaks at 427 nm and 468 nm. Due to the parity-allowed 5d-4f transition of Ce(III), the excited-state lifetime is as short as 22.3 ns (427 nm) and 25 ns (468 nm), respectively. The photoluminescence quantum yield (PLQY) is optimized to 51% by regulating the nucleation and growth of Rb3CeI6 grains. In a prototype rare earth light-emitting diode (ReLED) device, a thin insulating Al2O3 layer (5 nm) is inserted between the electron transport layer (ETL) and the emitting layer (EML, Rb3CeI6) to balance the carriers and reduce the dark current. The device shows a maximum luminance and EQE of 98 cd m-2 and 0.67%, respectively, and the electroluminescence (EL) spectrum maintains stability with changes in the operating voltage. In addition, the corresponding CIE coordinate is (0.15, 0.06), which closely matches the Rec. 2020 standard (0.131, 0.046).

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.

Obesity, but not high-fat diet, is associated with bone loss that is reversed via CD4+CD25+Foxp3+ Tregs-mediated gut microbiome of non-obese mice.

Osteoporosis is characterized by decreased bone mass, microarchitectural deterioration, and increased bone fragility. High-fat diet (HFD)-induced obesity also results in bone loss, which is associated with an imbalanced gut microbiome. However, whether HFD-induced obesity or HFD itself promotes osteoclastogenesis and consequent bone loss remains unclear. In this study, we developed HFD-induced obesity (HIO) and non-obesity (NO) mouse models to evaluate the effect of HFD on bone loss. NO mice were defined as body weight within 5% of higher or lower than that of chow diet fed mice after 10 weeks HFD feeding. NO was protected from HIO-induced bone loss by the RANKL /OPG system, with associated increases in the tibia tenacity, cortical bone mean density, bone volume of cancellous bone, and trabecular number. This led to increased bone strength and improved bone microstructure via the microbiome-short-chain fatty acids (SCFAs) regulation. Additionally, endogenous gut-SCFAs produced by the NO mice activated free fatty acid receptor 2 and inhibited histone deacetylases, resulting in the promotion of Treg cell proliferation in the HFD-fed NO mice; thereby, inhibiting osteoclastogenesis, which can be transplanted by fecal microbiome. Furthermore, T cells from NO mice retain differentiation of osteoclast precursors of RAW 264.7 macrophages ex vivo. Our data reveal that HFD is not a deleterious diet; however, the induction of obesity serves as a key trigger of bone loss that can be blocked by a NO mouse-specific gut microbiome.

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.

Zebrafish sox2 Is Required for the Swim Bladder Inflation by Controlling the Swim-Up Behavior.

The swim bladder functions to maintain the fish balance at a certain position under water. Although the motoneuron-dependent swim-up behavior is important for swim bladder inflation, the underlying molecular mechanism remains largely unknown. We generated a sox2 KO zebrafish using TALEN and found that the posterior chamber of the swim bladder was uninflated. The tail flick and the swim-up behavior were absent in the mutant zebrafish embryos and the behavior could not be accomplished. As the tail flick behavior is absent, the mutant larvae therefore cannot reach the water surface to gulp air, ultimately leading to the uninflation of the swim bladder. To understand the mechanism underlying the swim-up defects, we crossed the sox2 null allele in the background of Tg(huc:eGFP) and Tg(hb9:GFP). The deficiency of sox2 in zebrafish resulted in abnormal motoneuron axons in the regions of trunk, tail, and swim bladder. To identify the downstream target gene of sox2 to control the motor neuron development, we performed RNA sequencing on the transcriber of mutant embryos versus wild type embryos and found that the axon guidance pathway was abnormal in the mutant embryos. RT-PCR demonstrated that the expression of sema3bl, ntn1b, and robo2 were decreased in the mutants.

Analysis of LAP+ and GARP+ Treg subsets in peripheral blood of patients with neuromyelitis optica spectrum disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP+ or GARP+ Treg subsets in NMOSD may help us deeply understand their immune mechanism. METHODS: This study reviewed 22 NMOSD patients and 20 normal controls. Flow cytometric analysis was utilized to detect subsets of Treg cells expressing Foxp3, Helios, LAP, or GARP in peripheral blood. ELISA was used to detect plasma TGF-ß1 and IL-10. In addition, changes in the proportion of Treg cell subsets before and after glucocorticoid treatment in 10 patients were analyzed. RESULTS: Compared with healthy controls, LAP and GARP expressions were significantly downregulated in the peripheral blood of NMOSD patients. TGF-ß1 expression in NMOSD patients was lower and was positively correlated with the ratio of CD4+GARP+ Treg cells. After treatment with glucocorticoid, LAP and GARP expressions in the peripheral blood of NMOSD patients were upregulated. CONCLUSIONS: The proportion of Treg cells expressing LAP and GARP is downregulated, implying that Treg cells with the best inhibitory function are insufficient to maintain autoimmune homeostasis in NMOSD patients. Upregulation of Treg cells expressing LAP and GARP in NMOSD patients may be one of the mechanisms of glucocorticoid treatment.

Methionine sulfoxide suppresses adipogenic differentiation by regulating the mitogen-activated protein kinase signaling pathway.

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal-related kinase (P-ERK) of the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P-ERK1/2 agonist Ro 67-7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug.