Comparative study of clinical efficacy of laparoscopic proximal gastrectomy with double-channel anastomosis and tubular gastroesophageal anastomosis

BACKGROUND According to statistics,the incidence of proximal gastric cancer has gradually increased in recent years,posing a serious threat to human health.Tubular gastroesophageal anastomosis and double-channel anastomosis are two relatively mature anti-reflux procedures.A comparison of these two surgical procedures,tubular gastroesophageal anastomosis and double-channel anastomosis,has rarely been reported.Therefore,this study aimed to investigate the effects of these two reconstruction methods on the quality of life of patients with proximal gastric cancer after proximal gastrectomy.AIM To compare short-term clinical results of laparoscopic proximal gastrectomy with double-channel anastomosis vs tubular gastric anastomosis.METHODS Patients who underwent proximal gastrectomy at our hospital between January 2020 and January 2023 were enrolled in this retrospective cohort study.The patients were divided into an experimental group(double-channel anastomosis,33 cases)and a control group(tubular gastric anastomosis,30 cases).Baseline characteristics,surgical data,postoperative morbidities,and postoperative nutrition were recorded.RESULTS The differences in baseline data,surgical data,and postoperative complications(20.0%vs 21.2%)were not statistically significant between the two groups.There were no statistically significant differences in the levels of postoperative nutrition indicators between the two groups of patients during the preoperative period and at 3 months postoperatively.In addition,the levels of postoperative nutrition indicators in patients in the experimental group declined significantly less at 6 months and 12 months postoperatively compared with those of the control group(P<0.05).At 12 months postoperatively,the difference in anastomotic reflux esophagitis between the two groups was statistically significant(P<0.05)with the experimental group showing less reflux esophagitis.CONCLUSION Both double-channel anastomosis and tubular gastric anastomosis after proximal gastrectomy are safe and feasible.Double-channel anastomosis has a better anti-reflux effect and is more beneficial in improving the postoperative nutritional status.

Inhibition of metabotropic glutamate receptor-5 alleviates hepatic steatosis by enhancing autophagy via activation of the AMPK signaling pathway

BACKGROUND The global prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)has continued to increase annually.Recent studies have indicated that inhibition of metabotropic glutamate receptor 5(mGluR5)may alleviate hepatic steatosis.However,the precise mechanism warrants further exploration.AIM To investigate the potential mechanism by which mGluR5 attenuates hepatocyte steatosis in vitro and in vivo.METHODS Free fatty acids(FFAs)-stimulated HepG2 cells were treated with the mGluR5 antagonist MPEP and the mGluR5 agonist CHPG.Oil Red O staining and a triglyceride assay kit were used to evaluate lipid content.Western blot analysis was conducted to detect the expression of the autophagy-associated proteins p62 and LC3-II,as well as the expression of the key signaling molecules AMPK and ULK1,in the treated cells.To further elucidate the contributions of autophagy and AMPK,we used chloroquine(CQ)to inhibit autophagy and compound C(CC)to inhibit AMPK activity.In parallel,wild-type mice and mGluR5 knockout(KO)mice fed a normal chow diet or a high-fat diet(HFD)were used to evaluate the effect of mGluR5 inhibition in vivo.RESULTS mGluR5 inhibition by MPEP attenuated hepatocellular steatosis and increased LC3-II and p62 protein expression.The autophagy inhibitor CQ reversed the effects of MPEP.In addition,MPEP promoted AMPK and ULK1 expression in HepG2 cells exposed to FFAs.MPEP treatment led to the nuclear translocation of transcription factor EB,which is known to promote p62 expression.This effect was negated by the AMPK inhibitor CC.mGluR5 KO mice presented reduced body weight,improved glucose tolerance and reduced hyperlipidemia when fed a HFD.Additionally,the livers of HFD-fed mGluR5 KO mice presented increases in LC3-II and p62.CONCLUSION Our results suggest that mGluR5 inhibition promoted autophagy and reduced hepatocyte steatosis through activation of the AMPK signaling pathway.These findings reveal a new functional mechanism of mGluR5 as a target in the treatment of MASLD.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function

BACKGROUND Hepatectomy is the first choice for treating liver cancer.However,inflammatory factors,released in response to pain stimulation,may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies.AIM To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.METHODS Clinical data from patients with liver cancer admitted to Suzhou Ninth People’s Hospital from January 2020 to December 2023 were retrospectively analyzed.Thirty-five patients underwent laparoscopic hepatectomy for liver cancer(liver cancer resection group)and 35 patients underwent medical image-guided microwave ablation(liver cancer ablation group).The short-term efficacy,complications,liver function,and immune function indices before and after treatment were compared between the two groups.RESULTS One month after treatment,19 patients experienced complete remission(CR),8 patients experienced partial remission(PR),6 patients experienced stable disease(SD),and 2 patients experienced disease progression(PD)in the liver cancer resection group.In the liver cancer ablation group,21 patients experienced CR,9 patients experienced PR,3 patients experienced SD,and 2 patients experienced PD.No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups(P>0.05).After treatment,total bilirubin(41.24±7.35 vs 49.18±8.64μmol/L,P<0.001),alanine aminotransferase(30.85±6.23 vs 42.32±7.56 U/L,P<0.001),CD4+(43.95±5.72 vs 35.27±5.56,P<0.001),CD8+(20.38±3.91 vs 22.75±4.62,P<0.001),and CD4+/CD8+(2.16±0.39 vs 1.55±0.32,P<0.001)were significantly different between the liver cancer ablation and liver cancer resection groups.CONCLUSION The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar,but liver function recovers quickly after microwave ablation,and microwave ablation may enhance immune function.

Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats

Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.

Compensatory recombination phenomena of neurological functions in central dysphagia patients

We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-depen- dent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex （BA4）, insula （BA13）, premotor cortex （BA6/8）, supramarginal gyrus （BA40）, and anterior cingulate cortex （BA24/32） were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In re- current cerebral infarction patients with central dysphagia, BA4, BA13, BA40 aild BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex （BA23/31）, visual association cortex （BA18/19）, primary auditory cortex （BA41） and parahippocampal cortex （BA36）. Somatosen- sory association cortex （BA7） and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental findings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimu- late swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.

Kinetic behaviour of TiB particles in Al melt and their effect on grain refinement of aluminium alloys

Solidification experiments were carried out to investigate the kinetic behaviour of TiB2 particles in Al melt and their effect on the grain refinement of commercially-pure Al.A model was proposed to describe the kinetic behaviour of TiB2 particles during the whole process from the addition of TiB2 to the melt to the freezing of the melt.The results indicate that TiB2 particles are not stable in Al melt.They may dissolve and coarsen during the holding period and grow during the cooling period of the melt.The kinetic behaviour of TiB2 particles in the melt has a great influence on their number density and the grain refinement.Solute Ti addition can suppress the dissolution,Ostwald ripening and growth behaviours of TiB2 particles.

Effect of a poloxamer 407-based thermosensitive gel on minimization of thermal injury to diaphragm during microwave ablation of the liver

AIM To assess the insulating effect of a poloxamer 407(P407)-based gel during microwave ablation of liver adjacent to the diaphragm.METHODS We prepared serial dilutions of P407, and 22.5%(w/w) concentration was identified as suitable for ablation procedures. Subsequently, microwave ablations were performed on the livers of 24 rabbits(gel, saline, control groups, n = 8 in each). The P407 solution and 0.9% normal saline were injected into the potential space between the diaphragm and liver in experimental groups. No barriers were applied to the controls. After microwave ablations, the frequency, size and degree of thermal injury were compared histologically among the three groups. Subsequently, another 8 rabbits were injected with the P407 solution and microwave ablation was performed. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN) and creatinine(Cr) in serum were tested at 1 d before microwave ablation and 3 and 7 d after operation. RESULTS In vivo ablation thermal injury to the adjacent diaphragm was evaluated in the control, saline and 22.5% P407 gel groups(P = 0.001-0.040). However, there was no significant difference in the volume of ablation zone among the three groups(P > 0.05). Moreover, there were no statistical differences among the preoperative and postoperative gel groups according to the levels of ALT, AST, BUN and Cr in serum(all P > 0.05).CONCLUSION Twenty-two point five percent P407 gel could be a more effective choice during microwave ablation of hepatic tumors adjacent to the diaphragm. Further studies for clinical translation are warranted.

Effects and mechanism of miR-214 on hepatocellular carcinoma

Objective:To explore the role of miR-214 in the progression of hepatocellular carcinoma（HCC） and its inhibitory mechanisms in depressing the signaling pathway of j3-catenin.this study was conducted.Methods:We ectopically expressed miR-214 in HepG2 cells to obtain cell lines Lv-miR-214-HepG2 and their control Lv-control-HepG2.Differences between the two cell lines were compared in cell growth,proliferation,colony forming ability and cell cycles.RT-PCR method was applied for the quantification of β-catenin mRNA expression.Western-blot method was applied for the determination of the protein level of β-catenin and their downstream targets（ie.Cyclin D1,c-Myc and TCF-1）.The effect of miR-214 on cells was further explored through RNA interference and restoring miR-214 expression.Results:In comparison with negative（Lv-control-HepG2） and blank（HepG2） control,a significant inhibition of cell growth and proliferation caused by miR-214 was observed after 4872h of cell culture experiments（P【0.05）.The miR-214 treatment resulted in a colony forming efficiency of（23.28±3.26）%,which was significantly lower than that of negative control[（51.31±3.97）%]（P【0.05）.According to FCM results,the experimental group,compared with control,showed a higher proportion of cells in G0/G1 phase[（70.32±3.12）%]but a lower proportion in S phase[（18.42±2.90）%]（P【0.05）.The MTT assay demonstrated a significant inhibition of the proliferation and β-catenin expression of HCC cells compared with control（P【0.05）.while no significant difference was observed after HCC cells being transfected withβ-catenin overexpression plasmid（P】0.05）.By comparing to the RT-PCR and Western-blot results of control,the miR-214 treatment led to a slightly decrease in the β-catenin mRNA expression（P】0.05）.but an extremely inhibition in the protein level of β-catenin and its downstream targets Cyclin Dl,c-Myc.and TCF-1（P【0.05）.Conclusions:miR-214 functions as a suppressor during the progression of HCC,and its inhibitory role was achieved by downregulating β-catenin signaling pathway.

S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer:A meta-analysis

AIM: To assess the efficacy and safety of combination therapy based on S-1, a novel oral fluoropyrimidine, vs S-1 monotherapy in advanced gastric cancer (AGC).

Advances in neovascularization after diabetic ischemia

With the high incidence of diabetes around the world,ischemic complications cause a serious influence on people’s production and living.Neovascularization plays a significant role in its development.Therefore,neovascularization after diabetic ischemia has aroused attention and has become a hot spot in recent years.Neovascularization is divided into angiogenesis represented by atherosclerosis and arteriogenesis characterized by coronary collateral circulation.When mononuclear macrophages successively migrate to the ischemia anoxic zone after ischemia or hypoxia,they induce the secretion of cytokines,such as vascular endothelial growth factor and hypoxia-inducible factor,activate signaling pathways such as classic Wnt and phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathways,trigger oxidative stress response,activate endothelial progenitor cells or enter the glycolysis or lactic acid process and promote the formation of new blood vessels,remodeling them into mature blood vessels and restoring blood supply.However,the hypoglycemic condition has different impacts on neovascularization.Consequently,this review aimed to introduce the mechanisms of neovascularization after diabetic ischemia,increase our understanding of diabetic ischemic complications and their therapies and provide more treatment options for clinical practice and effectively relieve patients’pain.It is believed that in the near future,neovascularization will bring more benefits and hope to patients with diabetes.

Dectin-1 expression at early period of Aspergillus fumigatus infection in rat's corneal epithelium

AIM:To investigate the expression of dendritic cell-associated C-type lectin-1 (dectin-1) at the early period of Aspergillus fumigatus infection in rat’s corneal epithelium. ·METHODS:A total of 72 Wistar rats were randomly divided into three groups:A, B and C. The right eyes were chosen as experimental eyes. Group A was control group. Rats in group B were not inoculated with Aspergillus fumigatus. Group C was taken as Aspergillus fumigatus keratitis model. Rats in group B and C (six from each group) were executed randomly at 4, 8, 16 and 24 hours after experimental model being established to assess the expression of dectin-1 mRNA through real-time PCR. Another six rats in group B and C were executed randomly at 24 hours to assess the expression of dectin-1 protein through immunohistochemistry. ·RESULTS:The results of real-time PCR indicated that dectin-1 mRNA expression was low in corneal epithelium of normal rats’. There was no significantly difference of dectin-1 mRNA expression in group A and B (P 】0.05). The expression of Aspergillus fumigatus infected corneal epithelium increased gradually after 8 hours in group C. The synchronous expression of group A and C had significant difference (P 【0.01). Immunohistochemisty discovered that dectin-1 receptor existed in normal rat’s corneal epithelium . Dectin-1 protein increased after 24 hours in group C. There was a significant difference of synchronous expression in group B and C(P【0.01). · CONCLUSION:Dectin-1 exists in rat’s cornealepithelium and its expression significantly increases at the early period of Aspergillus fumigatus infection. Dectin-1 is a pattern recognition receptor that expresses in corneal epithelium and involves in immune response to Aspergillus fungal keratitis.

Feasibility study on expanded indication for endoscopic submucosal dissection of intramucosal poorly differentiated early gastric cancer

AIM: To identify clinicopathological factors predictive of lymph node metastasis(LNM) in intramucosal poorly differentiated early gastric cancer(EGC), and further to expand the possibility of using endoscopic submucosal dissection(ESD) for the treatment of intramucosal poorly differentiated EGC.METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios(ORs) with 95% confidence intervals(CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component.RESULTS: Tumor size(OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement(OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component(OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7(8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors.CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.

Mesencephalic astrocyte-derived neurotrophic factor ameliorates steatosis in HepG2 cells by regulating hepatic lipid metabolism

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a global metabolism-associated liver disease.Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly discovered secreted protein that is involved in metabolic homeostasis.However,much remains to be discovered about its function in hepatic lipid metabolism;thus,we assessed whether MANF could regulate hepatic metabolism.AIM To establish in vivo and in vitro NAFLD models to explore the role of MANF in hepatic lipid metabolism.METHODS HepG2 cells treated with free fatty acids (FFAs) and ob/ob mice were used as NAFLD models.Liver tissues collected from wild type and ob/ob mice were used to detect MANF expression.Cells were treated with FFAs for different durations.Moreover,we used lentiviral constructs to establish overexpression and knockdown cell models in order to interfere with MANF expression levels and observe whether MANF influences hepatic steatosis.Western blot analysis and quantitative real-time PCR were used to detect protein and gene expression,and oil red O staining was used to visualize intracellular lipid droplets.RESULTS Hepatic MANF protein and mRNA expression in wild type mice were 10-fold and 2-fold higher,respectively,than those in ob/ob mice.The MANF protein was temporarily increased by 1.3-fold after stimulation with FFAs for 24 h and gradually decreased to 0.66-fold that of the control at the 72 h time point in HepG2 cells.MANF deficiency upregulated the expression of genes involved infatty acid synthesis,cholesterol synthesis,and fatty acid uptake and aggravated HepG2 cell steatosis,while MANF overexpression inhibited fatty acid synthesis and uptake and cholesterol synthesis,and rescued HepG2 cells from FFAsinduced steatosis.Furthermore,a significant decrease in triglyceride levels was observed in the MANF overexpression group compared with the control group(0.4288±0.0081 mmol/g vs 0.3746±0.0121 mmol/g,P <0.05) upon FF As treatment.There was also a 17%decrease in intracellular total cholesterol levels between the MANF overexpression group and the control group (0.1301±0.0059mmol/g vs 0.1088±0.0009 mmol/g,P <0.05) upon FF As treatment.Moreover,MANF suppressed lipid deposition in HepG2 cells.CONCLUSION Our findings indicate that MANF improves the phenotype of liver cell steatosis and may be a potential therapeutic target in hepatic steatosis processes.

Influence of copper element distribution and speciation on the color of Chinese underglaze copper-red porcelain in the Yuan dynasty

A shard of Chinese underglaze copper-red porcelain from the Yuan dynasty (AD 1271–1368) made in the Jingdezhen kiln was measured by synchrotron radiation- induced X-ray fluorescence mapping and X-ray absorption near-edge spectroscopy to investigate the influence of copper element distribution and speciation on the color of porcelain. In black-colored region, copper accumulates at the interface between the body and glaze layers with metallic copper particles as the main speciation. In contrast, Cu is irregularly distributed in the red-colored region with multi-valence speciation. The differences in Cu distribution and speciation in black- and red-colored regions indicate that they are the main factors influencing the different colors of copper-red underglaze porcelain.

Nonalcoholic fatty liver disease shows significant sex dimorphism

Nonalcoholic fatty liver disease(NAFLD),which has been renamed metabolic dysfunction-associated fatty liver disease,is a growing global medical problem.The incidence of NAFLD and its associated end-stage liver disease is increasing each year,and many research advancements have been achieved to date.This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences.Studies have revealed significant sex differences in the prevalence,influencing factors,pathophysiology,complications and therapies of NAFLD.Men have a higher incidence than women.Compared with women,men exhibit increased visceral fat deposition,are more susceptible to leptin resistance,lack estrogen receptors,and tend to synthesize fatty acids into fat storage.Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer.However,once NAFLD occurs,women show a faster progression of liver fibrosis,higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men.In general,men have more risk factors and more severe pathophysiological reactions than women,whereas the development of NAFLD is faster in women,and the treatments for women are more limited than those for men.Thus,whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.

Modified Tong Xie Yao Fang relieves solitary rectal ulcer syndrome:A case report

BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disorder characterized by bloody mucus in the stool,difficulty in defecation,pain,and anal swelling.To date,the etiology of this syndrome remains not well understood and the diagnosis is frequently confused with other disorders,making treatment a clinical challenge.CASE SUMMARY A 50-year-old woman presented to our hospital with a 40-d history of bloody mucus in the stool and anal swelling.SRUS was suspected.Rectoscopy revealed a large,severe ulcerous lesion.Histologically,the lesion was characterized as chronic ulcer without clear tumor cells,and the final diagnosis of SRUS was made.The patient was treated with Chinese medicine therapy,with administration of Tong Xie Yao Fang.After 3 wk of treatment,the symptoms improved significantly.At 2-mo follow-up,rectoscopy in a local hospital showed healed ulcer scars without obvious protrusion 3 cm from the anal verge.CONCLUSION Chinese medicine therapy represents a potential treatment of SRUS with predominant rectal bleeding,mucinous discharge,and anal swelling pain.

Regulation of interleukin 33/ST2 signaling of human corneal epithelium in allergic diseases

AIM:To identify the function of ST2 and explore the role of IL-33/ST2 signaling in regulating the pro-allergic cytokine production in human corneal epithelial cells (HCECs). METHODS:Human corneal tissues and cultured primary HCECs were treated with IL-33 in different concentrations without or with different inhibitors to evaluate the expression, location and signaling pathways of ST2 in regulating production of pro-allergic cytokine and chemokine. The expression of mRNA was determined by reverse transcription and real time PCR, and protein production was measured by enzyme-linked immunosorbent assay (ELISA), immunohistochemical and immunofluorescent staining. ST2 protein was detected in donor corneal epithelium, and ST2 signal was enhanced by exposure to IL-33. ·RESULTS:IL-33 significantly stimulated production of pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and chemokine (CCL2, CCL20, CCL22) in HCECs at both mRNA and protein levels. These stimulated productions of pro-allergic mediators by IL-33 were blocked by ST2 antibody or soluble ST2 protein(P 【0.05). Interestingly, the IκB-α inhibitor BAY11-7082 or NF-κB activation inhibitor quinazoline blocked NF-κB p65 protein nuclear translocation, and also suppressed the productions of these pro-allergic cytokines and chemokine induced by IL-33. CONCLUSION:These findings demonstrate that IL-33/ ST2 signaling plays an important role in regulating IL-33 induced pro-allergic responses. IL-33 and ST2 could become novel molecular targets for the intervention ofallergic diseases in ocular surface.

Effectiveness of drug interventions in nonalcoholic fatty liver disease:A network meta-analysis

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a major chronic liver disorder worldwide,and there is no established treatment for this disease.We conducted a network meta-analysis(NMA)to compare existing treatments,which include four classes of antidiabetic drugs,and examined the optimum treatments for NAFLD.AIM To compare the effectiveness of different treatments for NAFLD.METHODS An NMA was conducted using Stata 14.0(Corporation LLC,College Station,United States)and R(X643.6.3 version)in this study.Eligible randomized controlled trials(RCTs)were searched in the PubMed,Cochrane Library,Embase,Medline and Web of Science databases from database inception to April 2021.Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria.The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies.The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference,respectively.An inconsistency model and“nodesplitting”technique were used to test for inconsistency.Funnel plots were used to evaluate publication bias.RESULTS Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis.Data were pooled using a random-effects model.Our NMA results revealed that glucagon-like peptide-1 receptor agonists(GLP-1RAs)were the most effective treatment,yielding improvements in hepatic fat content(HFC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serumγ-glutamyl transferase(GGT)and body weight[surface under the cumulative ranking curve(SUCRA)=99.6%,92.6%,82.8%,92.3%and 99.6%,respectively],while thiazolidinediones(TZDs)were the best intervention for reducing the NAFLD activity score(NAS;SUCRA=98.9%).In addition,moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups(SUCRA=25.1%,66.2%,63.5%,58.2%and 71.9%for HFC,ALT,AST,GGT and body weight,respectively).However,metformin performed poorly according to most indicators(SUCRA=54.5%,0.3%,19.5%,33.7%,57.7%and 44.3%for HFC,NAS,ALT,AST,GGT and body weight,respectively).CONCLUSION GLP-1RAs may be the optimum choice for most patients with NAFLD.However,TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.

CD137 signaling aggravates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated NLRP3 inflammasome activation

BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.

Maturity-onset diabetes of the young type 9 or latent autoimmune diabetes in adults:A case report and review of literature

BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.Currently,there are limited reports on PAX4-MODY,and its clinical characteristics and treatments are still unclear.In this report,we described a Chinese patient with high autoimmune antibodies,hyperglycemia and a site mutation in the PAX4 gene.CASE SUMMARY A 42-year-old obese woman suffered diabetes ketoacidosis after consuming substantial amounts of beverages.She had never had diabetes before,and no one in her family had it.However,her autoantibody tested positive,and she managed her blood glucose within the normal range for 6 mo through lifestyle interventions.Later,her blood glucose gradually increased.Next-generation sequencing and Sanger sequencing were performed on her family.The results revealed that she and her mother had a heterozygous mutation in the PAX4 gene(c.314G>A,p.R105H),but her daughter did not.The patient is currently taking liraglutide(1.8 mg/d),and her blood glucose levels are under control.Previous cases were retrieved from PubMed to investigate the relationship between PAX4 gene mutations and diabetes.CONCLUSION We reported the first case of a PAX4 gene heterozygous mutation site(c.314G>A,p.R105H),which does not appear pathogenic to MODY9 but may facilitate the progression of latent autoimmune diabetes in adults.