Association analysis of BclI with benign lymphoepithelial lesions of the lacrimal gland and glucocorticoids resistance

AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism(SNP)genotypes.The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin(HE)and Masson staining analysis.The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed.The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids(GCs)sensitivity.RESULTS:There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity(P>0.05);BclI GC genotype was closely related to GCs resistance(P=0.03)as is the minor allele C(P=0.0017).The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis(P<0.05),especially for GCs-dependent patients(P<0.0001).Meta-analysis showed that BclI was not significantly associated with GCs responsiveness.CONCLUSION:The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression.The results may guide the clinical treatment strategy for the LGBLEL patients.

Association of the macrophage migration inhibitory factor promoter polymorphisms with benign lymphoepithelial lesion of lacrimal gland

AIM： To identify the association of the macrophage migration inhibitory factor （MIF） gene polymorphism with the susceptibility of benign lymphoepithelial lesions （BLEL） of the lacrimal gland. METHODS： A total of 40 BLEL of lacrimal gland cases were matched with 40 healthy subjects （HS）. Extraction the plasma and whole blood DNA of patients of lacrimal gland BLEL and HS. Elisa and polymerase chain reaction was used to determine in plasma contents of MIF and MIF gene SNP-173G〉C and STR -794 CATT（8） polymorphism, respectively. RESULTS： The MIF levels in plasma were significantly higher in patients with lacrimal gland BI.EL versus HS （P〈0.001）. The -173 G〉C MIF polymorphism was significantly associated with lacrimal gland BLEL, with a significantly higher frequency of the C allele in lacrimal gland BLEL patients compared with HS （OR=2.38, 95% C1=1.07-5.31, P=0.032）, and the -173 C/x is more frequent in patients than in HS, P=0.037. Besides, we found that the carriage rate of the MIF -173C/x is associated with higher plasma levels of MIF in the BLEI. of lacrimal gland. CONCLUSION： MIF -173G/C variants play an insidious role in susceptibility of BLEL of lacrimal gland. Otherwise,there is no statistically significant correlation exists between MIF-794 CATT （） and BLEL of lacrimal gland.

IgG4 and IgE co-positive group found in idiopathic orbital inflammatory disease

AIM： To reveal the cytokines involved in idiopathic orbital inflammatory disease（IOID） and the relationship between Th17 cells, IgE and IOID pathogenesis.METHODS： Whole blood samples were processed immediately after collection and serological IgG4, IgG, and IgE antibodies were tested using ELISA. IOID and orbital cavernous hemangioma（CH） tissue samples underwent Bio-Plex multiplex cytokine detection. Hematoxylin-Eosin（HE） staining of all paraffin samples suggested the histological features of IOIDs, and expressions of IgG4 and IL-17 A in affected tissues were detected by immunohistochemistry. RESULTS： Among 40 IOID plasma samples, 52.5%（21/40） were positive for IgG4 and 25%（10/40） were positive for IgE. Overlapped IgG4 or IgE positive samples accounted for 22.5%（9/40）. Therefore, IOID samples were separated into three groups. The IgE＋/IgG4＋ group had a relevantly lower level of pro-inflammatory cytokine expression. IL-4（Th2 cell related）, IL-10 and TGF-β1（Treg cell immunity related） were elevated in all three groups. Some of the Th17 cell related cytokines（i.e. IL-17 A/F, IL-25, IL-23, and IL-33） displayed higher expression levels in the IgE-/IgG4-group compared to the other two groups.CONCLUSION： We discovered an IgG4-IgE co-positive group as well as Th17 cell immune involvement in IgG4-IgE co-negative subgtroup in IOID for the first time. The pathogenesis of IOID could differ from different subgroups according to the IgG4 and IgE detection. Therefore, we recommend that, Treatment stratagy should be made according to the clinical assessment of IgG4-IgE and Th17 profile detection.

Risk factors for esophagogastric variceal-related poor outcomes in primary biliary cholangitis:A prospective cohort study

Background and aims:Esophagogastric varices(EGV)are common complications of primary biliary cholangitis(PBC).We examined the risk factors for variceal bleeding-related liver transplantation(LT)or death.Methods:This prospective observational cohort study involved PBC in our hospital from 1 January 2005 to 1 January 2020.The clinical endpoints were variceal bleeding-related LT and death.Survival analysis was performed using the Kaplan-Meier estimate,cox regression analysis was performed to investigate risk factors.Results:PBC with EGV had significantly shorter survival than those without(p?0.002).Endoscopic prophylaxis significantly improved poor outcomes in PBC with EGV(p<0.001).Risk factors in patients with EGV included:cholinesterase(CHE)of<1.0upper limit of normal(ULN),international normalized ratio(INR)of>1.2ULN at baseline,total bilirubin of>1.2ULN,aspartate aminotransferase(AST)of>2.3ULN after 1 year of ursodeoxycholic acid(UDCA)treatment,non-biochemical responders according to the Paris criteria,and no history of endoscopic therapy.In PBC without EGV,risk factors included AST of>2.3ULN,INR of>1.2ULN at baseline,CHE of<1.0ULN after 1 year of UDCA treatment,and GLOBE score of>1.125.Conclusion:This study provides evidence that AST,INR and CHE are major risk factors for variceal bleedingrelated poor outcomes in PBC.For PBC with EGV,a good biochemical response to UDCA and endoscopic prophylaxis may improve survival.These findings can aid for guiding initial PBC risk stratification and screening endoscopy in patients without EGV.

Effect of hydrogen intervention on refractory wounds after radiotherapy:A case report

BACKGROUND Patients with keloids who receive radiotherapy(RT)after surgery can develop refractory wounds that cannot be healed by the patient's own repair system.Such chronic wounds are uneven and complex due to persistent abscess and ulceration.Without external intervention,they can easily result in local tissue necrosis or,in severe cases,large area tissue resection,amputation,and even death.CASE SUMMARY This article describes the use of hydrogen to treat a 42-year-old female patient with a chronic wound on her left shoulder.The patient had a skin graft that involved implanting a dilator under the skin of her left shoulder,and then transferring excess skin from her shoulder onto scar tissue on her chest.The skin grafting was followed by two rounds of RT,after which the shoulder wound had difficulty healing.For six months,the patient was treated with 2 h of hydrogen inhalation(HI)therapy per day,in addition to application of sterile gauze on the wound and periodic debridement.We also performed one deep,large,sharp debridement to enlarge the wound area.The wound healed completely within 6 mo of beginning the HI treatment.CONCLUSION After HI therapy,the patient showed superior progress in reepithelialization and wound repair,with eventual wound closure in 6 mo,in comparison with the previous failures of hyperbaric oxygen and recombinant bovine basic fibroblast growth factor therapies.Our work showed that HI therapy could be a new strategy for wound healing that is cleaner,more convenient,and less expensive than other therapies,as well as easily accessible for further application in clinical wound care.

Large focal nodular hyperplasia is unresponsive to arterial embolization: A case report

BACKGROUND Focal nodular hyperplasia(FNH)commonly occurs in women;it is usually asymptomatic and sometimes difficult to differentiate from hepatocellular carcinoma(HCC).CASE SUMMARY A large space-occupying lesion in the right lobe of the liver was incidentally detected in an adult man and diagnosed as HCC.Transcatheter arterial chemoembolization was applied once monthly for 2 years,but the lesion did not decrease in size.It was revealed by biopsy to be FNH.Eleven years later,the patient underwent liver resection due to hemorrhage and the pathological examination confirmed FNH.CONCLUSION For a space-occupying lesion,it is prerequisite to pathologically confirm the diagnosis and the corresponding intervention can be effective.

Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap

Objective: Skin damage induced by ischemia/reperfusion (I/R) is a multifactorial process that often occurs in plastic surgery. The mechanisms of I/R injury include hypoxia, inflammation, and oxidative damage. Hydrogen gas has been reported to alleviate cerebral I/R injury by acting as a free radical scavenger. Here, we assessed the protective effect of hydrogen-rich saline (HRS) on skin flap I/R injury. Methods: Abdominal skin flaps of rats were elevated and ischemia was induced for 3 h; subsequently, HRS or physiological saline was administered intraperitoneally 10 min before reperfusion. On postoperative Day 5, flap survival, blood perfusion, the accumulation of reactive oxygen species (ROS), and levels of cytokines were evaluated. Histological examinations were performed to assess inflammatory cell infiltration. Results: Skin flap survival and blood flow perfusion were improved by HRS relative to the controls. The production of malondialdehyde (MDA), an indicator of lipid peroxidation, was markedly reduced. A multiplex cytokine assay revealed that HRS reduced the elevation in the levels of inflammatory cytokines, chemokines and growth factors, with the exception of RANTES (regulated on activation, normal T-cell expressed and secreted) growth factor. HRS treatment also reduced inflammatory cell infiltration induced by I/R injury. Conclusions: Our findings suggest that HRS mitigates I/R injury by decreasing inflammation and, therefore, has the potential for application as a therapy for improving skin flap survival.

Synergistic effect of hyperbaric oxygen preconditioning and hydrogen-rich saline in ameliorating rat flap ischemia/reperfusion injury

Aim:This study was conducted to evaluate the synergistic effects of hyperbaric oxygen(HBO)preconditioning and hydrogen-rich saline(HRS)treatment on skin flap survival and apoptosis in a rat ischemia/reperfusion(IR)skin flap model.Methods:Male Sprague-Dawley rats were randomly divided into five groups:one sham surgery group(sham group)and four surgery groups(IR group,HBO group,HRS group,and HBO+HRS group).An extended epigastric adipocutaneous flap(6 cm×9 cm)was raised over the abdomen in each animal of all five groups.The last four groups underwent 6 h of IR management and were treated,respectively,with normal saline,HBO,HRS(HRS,0.8 mmol/L),or a combined approach(HBO and HRS).On the 3rd postoperative day,flap survival rate and perfusion condition,apoptotic index,caspase-3 activity,protein expression of pASK1 and Bcl-2/Bax ratio,and Bcl-2 messenger RNA(mRNA)expression were assessed.Results:Prior studies have shown the protective effects of HBO and HRS,both of which have been associated with an increase in flap survival.Compared to the IR group,the flaps in the HBO,HRS,and HBO+HRS groups showed better perfusion and a larger survival area with a low number of apoptotic cells,low caspase-3 activity and pASK1 expression,and a high Bcl-2/Bax ratio and Bcl-2 mRNA expression.Of these groups,the HBO+HRS group showed the best flap survival.Conclusion:Both HBO and HRS treatments increase the rate of flap survival,while the synergistic application of HBO and HRS showed a higher survival rate as compared to individual treatments of each.The potential regulation of apoptosis with the use of these two modalities may improve skin flap survival.