Outcomes of endoscopic sclerotherapy for jejunal varices at the site of choledochojejunostomy (with video): Three case reports

BACKGROUND Hemorrhage associated with varices at the site of choledochojejunostomy is an unusual,difficult to treat,and often fatal manifestation of portal hypertension.So far,no treatment guidelines have been established.CASE SUMMARY We reported three patients with jejunal varices at the site of choledochojejun-ostomy managed by endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection at our institution between June 2021 and August 2023.We reviewed all patient records,clinical presentation,endoscopic findings and treatment,outcomes and follow-up.Three patients who underwent pancre-aticoduodenectomy with a Whipple anastomosis were examined using conven-tional upper gastrointestinal endoscopy for suspected hemorrhage from the afferent jejunal loop.Varices with stigmata of recent hemorrhage or active he-morrhage were observed around the choledochojejunostomy site in all three patients.Endoscopic injection of lauromacrogol/α-butyl cyanoacrylate was carried out at jejunal varices for all three patients.The bleeding ceased and patency was observed for 26 and 2 months in two patients.In one patient with multiorgan failure and internal environment disturbance,rebleeding occurred 1 month after endoscopic sclerotherapy,and despite a second endoscopic sclero-therapy,repeated episodes of bleeding and multiorgan failure resulted in eventual death.CONCLUSION We conclude that endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoac-rylate injection can be an easy,effective,safe and low-cost treatment option for jejunal varicose bleeding at the site of choledochojejunostomy.

CD3ε of a pan T cell marker involved in mouse Aspergillus fumigatus keratitis

AIM:To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus(A.fumigatus)keratitis in mice and the role of innate and adaptive immunity in it.METHODS:Mice models of A.fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching.Subconjunctival injections of natamycin,wedelolactone,LOX-1 inhibitor(poly I)or Dectin-1 inhibitor(laminarin)were used to treat mice with A.fumigatus keratitis.Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε.We observed the corneal infection of mice under the slit lamp microscope and made a clinical score.The protein expression of CD3ε and interleukin-10(IL-10)was determined by Western blotting.RESULTS:With the disease progresses,the degree of corneal opacity and edema augmented.In the intrastromal injection models,CD3εprotein expression began to increase significantly on the 2^(nd) day.However,in the scraping epithelial method models,CD3ε only began to increase on the 3^(rd) day.After natamycin treatment,the degree of corneal inflammation in mice was significantly attenuated on the 3^(rd) day.After wedelolactone treatment,the severity of keratitis worsened.And the amount of CD3ε protein was also reduced,compared with the control group.By inhibiting LOX-1 and Dectin-1,there was no significant difference in CD3ε production compared with the control group.After inhibiting CD3ε,corneal ulcer area and clinical score increased,and IL-10 expression was downregulated.CONCLUSION:As a pan T cell marker,CD3ε participate in the adaptive immunity of A.fumigatus keratitis in mice.In our mice models,the corneas will enter the adaptive immune stage faster.By regulating IL-10,CD3ε exerts antiinflammatory and repairs effects in the adaptive immune stage.

普洱茶水浸液抑制牙釉质脱矿作用初探

目的探究普洱茶(生茶、熟茶)不同浓度水浸液抑制牙釉质脱矿的作用。方法检测经普洱茶不同浓度水浸液处理离体牙前后乳酸盐缓冲溶液中磷离子浓度的变化,计算出磷溶出率。设20 mg/L氟化钠组为阳性对照组,去离子水组为阴性对照组,评价普洱茶不同浓度水浸液抑制牙釉质脱矿的作用。结果普洱茶不同浓度组、氟化钠阳性对照组与去离子水阴性对照组比较差异有统计学意义(P<0.05)。普洱茶不同浓度组之间比较差异有统计学意义(P<0.05)。同浓度条件下,生茶组比熟茶组的作用强,且差异有统计学意义(P<0.05)。结论普洱茶不同浓度水浸液均具有抑制牙釉质脱矿的作用,且高浓度水浸液作用效果更强。

Thymol Protects against Aspergillus Fumigatus Keratitis by Inhibiting the LOX-1/IL-1βSignaling Pathway

Objective To explore the anti-inflammatory effects and mechanisms of action of thymol in Aspergillus fumigatus(A.fumigatus)keratitis.Methods The minimum inhibitory concentration of thymol against A.fumigatus was detected.To characterize the anti-inflammatory effects of thymol,mouse corneas and human corneal epithelial cells were pretreated with thymol or dimethyl sulfoxide(DMSO)before infection with A.fumigatus spores.Slit-lamp microscopy,immunohistochemistry,myeloperoxidase detection,quantitative real-time polymerase chain reaction,and Western blotting were used to assess infection.Neutrophil and macrophage recruitment,in addition to the secretion of LOX-1 and IL-1β,were quantified to evaluate the relative contribution of thymol to the inflammatory response.Results We confirmed that the growth of A.fumigatus was directly inhibited by thymol.In contrast with the DMSO group,there was a lower degree of inflammation in the mouse corneas of the thymol-pretreated group.This was characterized by significantly lower clinical scores,less inflammatory cell infiltration,and lower expression of LOX-1 and IL-1β.Similarly,in vitro experiments indicated that the production of LOX-1 and IL-1βwas significantly inhibited after thymol treatment,in contrast with the DMSO-pretreated group.Conclusion Our findings demonstrate that thymol exerted a direct fungistatic activity on A.fumigatus.Furthermore,thymol played a protective role in fungal keratitis by inhibiting LOX-1/IL-1βsignaling pathway and reducing the recruitment of neutrophils and macrophages.

CCPG1 involved in corneal Aspergillus fumigatus infection

AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1(CCPG1) is involved in the corneal antifungal immune response.METHODS: Human corneal epithelial cells(HCECs) and human myeloid leukemia mononuclear cells(THP-1) macrophages stimulated by Aspergil us fumigatus(A. fumigatus) were used as cell models. The expression of CCPG1 m RNA was detected by q RT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β(IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1(CLEC-1) in THP-1 macrophages.RESULTS: The expression of CCPG1 started to increase at 4 h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages.CONCLUSION: As a specific autophagy protein of noncanonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus.

NR4A1 agonist cytosporone B attenuates neuroinflammation in a mouse model of multiple sclerosis

Nuclear receptor subfamily 4 group A1(NR4A1)is an orphan nuclear receptor,which is expressed in the majority of cells.NR4A1 expression in peripheral blood mononuclear cells is low during the preclinical stage of multiple sclerosis.Knockout of the Nr4a1 gene in mice can aggravate the symptoms of experimental autoimmune encephalomyelitis(EAE),which is an animal model of multiple sclerosis.In this study,we intragastrically administered the NR4A1 agonist cytosporone B(Csn-B)to mice after inducing EAE.After treatment with Csn-B,the clinical symptoms in the EAE mice were substantially attenuated compared with that in PBS-treated control mice.The percentages of CD4+T cells and F4/80+cells in the central nervous system were decreased.In addition,interferon-γand interleukin-17 production by proinflammatory Th1/Th17 cells in the central nervous system and interferon-γlevels in splenocytes were decreased after Csn-B treatment.These findings suggest that the NR4A1 agonist Csn-B can alleviate nerve injury after EAE induction,and,therefore,may be useful as a potential treatment for multiple sclerosis.

The action mechanism of Rhizoma Imperatae for pediatric epistaxis management using a network pharmacology approach

Background:Pediatric epistaxis is one of the most common and frequently occurring diseases,while its pathogenesis is complicated and remains to be fully elucidated.Objective:This work aims to explore the therapeutic effect and action mechanism of Rhizoma Imperatae in the treatment of pediatric epistaxis in a network pharmacology approach and to provide a practical reference for treating epistaxis in children.Methods:The active ingredients of Chinese herb Rhizoma Imperatae were obtained from the TCMSP database,and the targets of chemical compounds were subsequently predicted using the Swisstargetprediction database;the disease targets of epistaxis were exported from the Genecards database;the obtained overlapped genes were applied for protein-protein interaction(PPI)analysis,Gene Ontology(GO)anlysis and KEGG analysis.Results:There were 128 targets of Rhizoma Imperatae were predicted,and 500 disease targets were collected,with 19 overlapped targets between the drug and the disease.The five genes matrix metallopeptidase 9(MMP9),EGFR,JUN,PTGS1,and ESR1 had the most connections based on the PPI analysis.The GO analysis indicated that positive regulation of vascular smooth muscle cell proliferation and positive regulation of smooth muscle cell proliferation were greatly associated with MMP9,EGFR,and JUN genes in biological processes(BP)and positive regulation of lipid kinase activity and nitric-oxide syntheses activity affected EGFR and ESR1 genes mostly in molecular function(MF).Conclusion:The present research results demonstrated that Rhizoma Imperatae might play a role in alleviating pediatric epistaxis using a network pharmacology technique,hoping to figure out its action mechanism of the drug against the disease.

CD23 mediated the induction of pro-inflammatory cytokines Interleukin-1 beta and tumor necrosis factors-alpha in Aspergillus fumigatus keratitis

To the Editor:Fungal keratitis is primarily caused by pathogenic fungi species,such as Fusarium solani and Aspergillus fumigatus.The incidence of A.fumigatus has been increased worldwide.[1]Although new therapies have been used for fungal keratitis,the efficacy of antifungal drugs remains unsatisfactory at present.[2]Fungal keratitis is still a challenge for ophthalmologists because of its difficult and delayed diagnosis,as well as the lack of effective drugs and treatment.

A Facile Method for Preparation of Cardo Poly(aryl ether sulfone) Bearing Pendent Sulfoalkyl Groups as Proton Exchange Membranes

A series of cardo poly（aryl ether sulfone） copolymers bearing pendent sulfonic acid groups （SPES-X） have been prepared by a facile chemical graft method. The structure was confirmed by 1H-NMR spectra. The side-chain-type SPES-X membranes show significantly reduced swelling behavior and excellent mechanical properties as well as appropriate proton conductivity compared to the main-chain-type sulfonated polymers with similar ion exchange capacity （IEC） value. Moreover, they show methanol permeability in the range of 0.6 × 10^-7-5.7 × 10^-7 cmE/s which is lower than that of Nafion 117. All the results indicate that the SPES-Xmembranes are promising candidates for the direct methanol fuel cells.

Biosynthesis of(R)-2-hydroxy-3-phenylpropionic acid using whole recombinant Escherichia coli cells in an aqueous/n-octane biphasic system

（R）-2-hydroxy-3-phenylpropionic acid （PIP,） is an ideal antimicrobial compound with broad-spectrum activity against a wide range of Gram-positive bacteria, some Gram-negative bacteria, and fungi. We studied the bioconversion of phenylpyruvate （PPA） to PLA using whole recombinant Escherichia coli cells in a series of buffer/organic solvent systems. Octane was found to be the best organic solvent. The optimum volume ratio of the water phase to the n-octane phase, conversion temperature, substrate concentration, and cell concentration were 6：4, 40 ℃, 12.5 g/L, and 30 g/L wet cells, respectively. Under the optimized conditions, the average PLA productivity in the aqueous/ n-octane system was 30.69% higher than that in the aqueous system, and 32.31 g/L PLA was obtained with the use of a stirred reactor （2-L scale）. Taken together, our findings indicated that PLA biosynthesis was more efficient in an aqueous/n-octane biphasic system than in a monophasic aqueous system. The proposed biphasic system is an effective strategy for enhancing PLA yield and the biosynthesis of its analogues.