ON101 Cream Increases the Wound Healing Rate in Diabetic Patients with Uremia—Cases Report

Diabetic patients who underwent long-term dialysis may increase the prevalence of foot ulceration. In addition, diabetic foot ulcer (DFUs) patients with end-stage renal disease (ESRD) do not heal well, and the amputation rate is 6.5 - 10 times higher compared to the non-nephropathic diabetic population. Thus, a suitable therapeutic agent was needed. ON101 is a topical cream that promotes diabetic wound healing through a unique macrophage-regulating ability. In this case series, we included 5 diabetes patients (mean age 54.6 ± 8.7 years, 4 mal) with ESRD (mean eGFR 7.4 ± 3.35 mL/min/1.73m2) and had experienced dialysis for at least 4.5 years. These patients also have UT (University of Texas) grade 2A DFUs that have existed for at least 1.5 months (mean ulcer duration 8.3 ± 8.97 months). These subjects were applied ON101 twice daily for up to 20 weeks, and wound size was recorded during treatment. Among these subjects, three ulcers (patient No. 1, 2, and 3) completely healed within 10 weeks upon ON101 application, and one ulcer was 99% reduced at 20th weeks (patient No. 4). Only one ulcer didn’t show an obvious response that may due to poor compliance in wound care and glucose control. In summary, the overall healing rate was 60%, suggesting ON101 performed equivalence healing efficacy in dialysis patients compared with those who did not have dialysis.

Density of Helicobacterpylorimay affect the efficacy of eradication therapy and ulcer healing in patients with active duodenal ulcers

AIM: To evaluate the association of pre-treatment Helicobacter pylon(H, pylon) density with bacterial eradication and ulcer healing rates in patients with active duodenal ulcer. METHODS: One hundred and four consecutive duodenal ulcer outpatients with H. py/ori infection ascertained by gastric histopathology and 13C-urea breath test (UBT) were enrolled in this study. H. py/ori density was graded histologically according to the Sydney system (normal, mild, moderate, and marked). In each patient, lansoprazole (30mg b.i.d.), clarithromycin (500 mg b.i.d.) and amoxicillin (1g b.i.d.) were used for i week, then 30 mg lansoprazole once daily was continued for an additional 3 weeks. Followup endoscopy was performed at 4 weeks after completion of the therapy, and UBT was done at 4 and 8 weeks after completion of the therapy. RESULTS: The H. pylori eradication rates were 88.9 %/100.0 %, 94.3 %/100.0 %, and 69.7 %/85.2 %; and the ulcer healing rates were 88.9 %/100.0 %, 94.3 %/100.0 %,and 63.6 %/77.8 % (intention-to-treat/per protocol analysis) in the mild, moderate, and marked H. pyloridensity groups, respectively. The association of pretreatment H. pyloriderisity with the eradication rate and ulcer healing rate was both statistically significant (P=-0.013/0.006 and 0.002/<0.001, respectively; using results of intention-to-treat/per protocol analysis).CONCLUSION: Intragastric bacterial load may affect both the outcome of eradication treatment and ulcer healing in patients with active duodenal ulcer disease.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis. The aim of this prospective study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with this disease.METHODS: Eighteen HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. A course of chemotherapy consisted of daily cisplatin (10 mg for one hour) followed by 5-fiuorouracil (250 mg for five hours) zfor five continuous days within a given week. The patients were scheduled to receive four consecutive courses of HAIC.Responders were defined in whom either a complete or partial response was achieved, while non-responders were defined based on stable or progressive disease status. The prognostic factors associated with survival after treatment were analyzed.RESULTS: Six patients exhibited partial response to this form of HAIC (response rate = 33 %). The 3, 6, 9, 12 and 18-month cumulative survival rates for the 18 patients were 83 %, 72 %, 50 %, 28 %, and 7 %, respectively. Median survival times for the six responders and 12 non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months,respectively, It was demonstrated by both univariate and multivariate analyses that the therapeutic response and hepatic reserve function were significant prognostic factors.CONCLUSION: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful alternative for the treatment of patients with advanced HCC complicated with PVTT. There may also be survival-related benefits associated with HAIC.

Endoscopic hemoclip treatment for bleeding peptic ulcer

AIM To evaluate the efficacy of endoscopichemoclip in the treatment of bleeding pepticulcer.METHODS Totally,40 patients with F1a andFib hemorrhagic activity of peptic ulcers wereenrolled in this uncontrolled prospective studyfor endoscopic hemoclip treatment.We used anewly developed rotatable clip-device for theapplication of hemoclip(MD850)to stopbleeding.Endoscopy was repeated if there wasany sign or suspicion of rebleeding,and re-clipping was performed if necessary andfeasible.RESULTS Initial hemostatic rate by clippingwas 95%,and rebleeding rate was only 8%.Ultimate hemostatic rates were 87%,96%,and93% in the Fla and Flb subgroups,and totalcases,respectively.In patients with shock onadmission,hemoclipping achieved ultimatehemostasis of 71% and 83% in F1a and F1bsubgroups,respectively.Hemostasis reached100% in patients without shock regardless ofhemorrhagic activity being F1a or F1b.Theaverage number of clips used per case was 3.0(range 2-5).Spurting bleeders required moreclips on average than did oozing bleeders(3.4versus 2.8).We observed no obviouscomplications,no tissue injury,or impairmentof ulcer healing related to hemoclipping.CONCLUSION Endoscopic hemoclip placementis an effective and safe method.With theimprovement of the clip and application device,the procedure has become easier and much moreefficient.Endoscopic hemoclipping deservesfurther study in the treatment of bleeding pepticulcers.

TT viral infection through blood transfusion:retrospective investigation on patients in a prospective study of post-transfusion hepatitis

AIM To investigate the role of bloodtransfusion in TT viral infection(TTV).METHODS We retrospectively studied serumsamples from 192 transfusion recipients whounderwent cardiovascular surgery and bloodtransfusion between July 1991 and June 1992.Allpatients had a follow-up every other week for atleast 6 months after transfusion.Eightyrecipients received blood before screeningdonors for hepatitis C antibody(anti-HCV),and112 recipients received screened blood.Recipients with alanine aminotransferase level】2.5 times the upper normal limit were testedfor serological markers for viral hepatitis A,B,C,G,Epstein-Barr virus and cytomegalovirus.TTV infection was defined by the positivity forserum TTV DNA using the polymerase chainreaction method.RESULTS Eleven and three patients,whoreceived anti-HCV unscreened and screened'blood,respectively,had serum ALT levels】90 IU/L.Five patients(HCV and TTV:1;HCV,HGV,and TTV:1;TTV:2;and CMV and TTV:1)were positive for TTV DNA,and four of them hadsero-conversion of TTV DNA.CONCLUSION TTV can be transmitted viablood transfusion.Two recipients infected byTTV alone may be associated with the hepatitis.However,whether TTV was the causal agentremains unsettled,and further studies arenecessary to define the role of TTV infection inchronic hepatitis.

Coinfection of TT virus and response to interferon therapy in patients with chronic hepatitis B or C

AIM: To investigate the serum positive percentage of TTvirus (TTV) in patients with chronic hepatitis B or C and theresponse of the coinfected TTV to interferon (IFN) duringIFN therapy for chronic hepatitis B and C.METHODS: We retrospectively studied the serum samples of70 patients with chronic hepatitis who had received IFN-alfatherapy from January 1997 to June 2000, which included 40cases of hepatitis B and 30 hepatitis C. All the patients hadbeen followed up for at least 6 months after the end of IFNtherapy. The serum TTV DNA was detected using thepolymerase chain reaction (PCR) before and every monthduring the course of IFN treatment.RESULTS: TTv infection was detected in 15 % (6/40) of thechronic hepatitis B group and 30 % (9/30) of the chronichepatitis C group. Loss of serum TTV DNA during IFNtherapy occurred in 3 of 6 patients (50 % ) and 6 of 9 (67 % )of hepatitis B and C groups, respectively. Seronegativity ofTTV was found all during the first month of IFN therapy inthe 9 patients. There was no correlation between theseroconversion of TTv and the biochemical changes of thepatients.CONCLUSION: TTV is not infrequently coinfectsd in patientswith chronic hepatitis B and C in Taiwan, and more thanhalf of the TTv infections are IFN-sensitive. However, theloss of serum TTV DNA does not affect the clinical course ofthe patients with chronic hepatitis B or C.

Laryngopharyngeal reflux in patients with reflux esophagitis

AIM: To assess the prevalence of laryngopharyngeal reflux (LPR) in patients with reflux esophagitis and dis-close factors contributing to the development of LPR. METHODS: A total of 167 patients who proved to have reflux esophagitis by endoscopy were enrolled. They received laryngoscopy to grade the reflux find-ings for the diagnosis of LPR. We used validated ques-tionnaires to identify the presence of laryngopharyn-geal symptoms, and stringent criteria of inclusion to increase the specificity of laryngoscopic findings. The data of patients were analyzed statistically to find out factors related to LPR. RESULTS: The prevalence rate of LPR in studied sub-jects with reflux esophagitis was 23.9%. Age, hoarse- ness and hiatus hernia were factors significantly as-sociated with LPR. In 23 patients with a hiatus hernia, the group with LPR was found to have a lower trend of esophagitis grading. CONCLUSION: Laryngopharyngeal reflux is present in patients with reflux esophagitis, and three predicting factors were identified. However, the development of LPR might be different from that of reflux esophagi-tis. The importance of hiatus hernia deserves further study.

Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7and 1A1 genes

AIM: To investigate the relationship between single nucleotide polymorphisms in the uridine-diphosphoglucuronosyltransferase (UGT) UGT1A7 and UGT1A1 genes and patients suffering from colorectal cancer (CRC). METHODS: A case-control study was designed in order to investigate the genotypes of the UG71A7 and UGT1A1 genes, which were identified by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) method, for 268 CRC patients and 441 healthy controls. RESULTS: The results of simple logistical regressions revealed odds ratios (ORs) of 1.97 (P＜0.001), 1.91 (P＜0.001), and 2.03 (P＜0.00L) for patients who carried the UGT1A7*1/*3 genotype, UGT1A7*3 allele, andvariant-211 UGT1A1 allele. The interaction of UGT1A7*3allele and variant-211 LGT1A1 allele produced an additiveeffect on the risk for the development of CRC [observed OR (2.34) greater than expected OR (1.59)]. For the 268patients, the results of simple logistical regressions indicated that the OR of developing metastases was 4.90 (P＜0.001) and 4.89 (P＜0.001) for the individuals possessing UGT1A7*3 allele and variant-211 UGT1A1 allele, respectively. The results of multivariate logistical regressions confirmed these findings (OR = 2.51, P= 0.01;and OR = 2.71, P = 0.01, respectively). The interactionof these two variants resulted in an additive effect on the risk for metastases amongst patients [observed OR (6.83) greater than expected OR (4.56)].CONCLUSION: In conclusion, carriage of the UGT1A7*3allele, as well as variant-211 UGT1A1 allele represents a risk factor for the development of, and a determinant for, metastases associated with CRC patients.

Portal vein pulsatility index is a more important indicator than congestion index in the clinical evaluation of right heart function

瞄准：在充血心力衰竭学习门血流的变化。方法：我们用超声的 Doppler 与充血心力衰竭的改变的度在病人学习了拥挤索引(CI ) 和门静脉 pulsatility 索引(PI ) 。十个病人与(平均数) 在就，伊朗的银币迫使(RA )【 10 毫米汞柱作为组 1 被分类并且留下有 RA 】 或 = 的 10 个病人是的 10 毫米汞柱组 2。结果：心指数上没有差别(嗨， P=0.28 )，主动脉压( AO ， P=0.78 )，左室的结束心脏舒张的压力( LVED ， P=0.06 )，(最大) i 妈妈门血速度( Vmax ， P=0.17 )，(平均数)门血速度( Vmean ， P=0.15 )并且门血流体积( PBF ， P=0.95 )在二个组之间。组 2 病人有更高肺的楔压力( PW ， 29.9+/-9.3 毫米汞柱对 14.6+/-7.3 毫米汞柱， P=0.002 )，肺的动脉压( PA ， 46.3+/-13.2 毫米汞柱对 25.0+/-8.2 毫米汞柱， P=0.004 )， RA ( 17.5+/-5.7 毫米汞柱对 4.7+/-2.4 毫米汞柱， P【0.001 )，恰好室的结束心脏舒张的压力( RVED ， 18.3+/-5.6 毫米汞柱对 6.4+/-2.7 毫米汞柱， P【0.001 )， CI ( 8.7+/-2.4 对 5.8+/-1.2 ， P=0.03 )，并且 PI (87.8+/-32.3%对27.0+/-7.4%， P【0.001 )与组织 1 比。 CI 与 PI ( P【0.001 )被相关， PW ( P【0.001 )， PA ( P【0.001 )， RA ( P=0.043 )， RVED ( P=0.005 )，嗨( P【0.001 )， AO ( P【0.001 )，公司( P【0.001 )， LVED ( P【0.001 )， Vmax ( P【0.001 )， Vmean ( P【0.001 )，主要的门静脉( P【0.001 )的代表性的区域和 PBF ( P【0.001 )。CI 能在有 RA 【 的病人象 8.3 一样高 10 毫米汞柱并且与 RA 】 或 = 象 5.9 一样在那些低 10 毫米汞柱。结论：我们 RI 比在高 RA 】 或 = 的临床的评估的 CI 是更重要的指示物的数据表演 10 毫米汞柱，而 CI 比在对左心的评价的 PI 好，工作。

Percutaneous transcatheter closure of mitral paravalvular leak via transarterial retrograde approach

重复外科通常被认为第一种选择解决修复术的阀门的 paravalvular 漏缝，但是它带高起作用的风险，高死亡率和增加的风险为重新漏。如此的缺点的经皮的闭合可能、不同途径和设备被用于这个目的。为僧帽形的 paravalvular 漏缝，为通过一条 antegrade 途径交付闭合设备构造一个动静脉的电线环是最通常使用的技术。Transcatheter 闭合能也通过一条 transapical 途径被执行或后退 transfemoral 动脉的途径。我们在场有成功地用 Amplatzer ® 管 Occluder II 被关上的一条僧帽形的 paravalvular 漏缝的 68 岁的人的一个盒子，经由后退 transfemoral 在三维的 transesophageal echocardiographic 指导下面的动脉的途径，没有一个电线环的使用。穿过 paravalvular 缺点的起始的尝试是失败的，但是障碍被介绍复杂 interventional 技术最后克服。

Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

AIM: To test the hypothesis that the variant UDPglucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis.METHODS: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups,respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency.RESULTS: Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)6TAA/A(TA)7TAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, χ2 test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0±6.5 and 12.7±2.9 μmol/L, respectively; P＜0.001, Student's ttest).CONCLUSION: Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese.

Effects of ethanol on antioxidant capacity in isolated rat hepatocytes

AIM: To investigate dose-response and time-course of the effects of ethanol on the cell viability and antioxidant capacity in isolated rat hepatocytes.METHODS: Hepatocytes were isolated from male adult Wistar rats and seeded into 100-mm dishes. Hepatocytes were treated with ethanol at concentrations between 0 (C), 10 (E10), 50 (E50), and 100 (E100) mmol/L (dose response) for 12, 24, and 36 h (time course). Then,lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) concentration, glutathione (GSH) level, and activities of glutathione peroxidase (GPX), glutathione reductase (GRD), superoxide dismutase (SOD), and catalase (CAT) were measured.RESULTS: Our data revealed that LDH leakage was significantly increased by about 30% in group E100 over those in groups C and E10 at 24 and 36 h, The MDA concentration in groups C, E10 and E50 were significantly lower than that in group E100 at 36 h. Furthermore,the concentration of MDA in group E100 at 36 h was significantly higher by 4.5- and 1.7-fold, respectively,than that at 12 and 24 h. On the other hand, the GSH level in group E100 at 24 and 36 h was significantly decreased, by 32% and 28%, respectively, compared to that at 12 h. The activities of GRD and CAT in group E100 at 36 h were significantly less than those in groups C and E10. However, The GPX and SOD activities showed no significant change in each group.CONCLUSION: These results suggest that longtime incubation with higher concentration of ethanol (100 mmol/L) decreased the cell viability by means of reducing GRD and CAT activities and increasing lipid peroxidation.

Delayed Airway Obstruction in Posterior Fossa Craniotomy with Park-Bench Position—A Case Report and Review of the Literatures

Background: Park-bench position is a commonly used position in patients operated with cerebellopontine tumor, microvascular decompression, or lesions of cerebellar hemisphere and vertebral artery. Several complications associated with this positioning have been described. However, the delayed airway complication resulting from park-bench position has been rarely reported in the literatures. Herein, we report a rare case of delayed airway obstruction after a posterior-fossa craniotomy with park-bench position for acoustic neuroma. Case presentation: A 43-year-old woman, who has a right acoustic neuroma, was placed in the park-bench position for a posterior-fossa craniotomy. The anesthesia and operation were performed smoothly. However, progressive swelling in the left neck with extending to left face occurred two hours after endo-tracheal extubation. Computed tomographic scan of neck revealed diffuse swelling of the muscles and deep soft tissue in the left side. No obvious embolization of vascular system including jugular vein was found in the sonography. Because of obstruction in upper airway, orotracheal intubation and a head-up position were performed. The clinical symptoms improved gradually since the third post-operative day. She was discharged with obvious complications on the 23rd day after the operation. Conclusion: The possible mechanisms may originate from the kinking of the jugular vein due to hyper-flexed neck position during surgery. To prevent such complication, we must take great care of the anesthetized patients when placed in the forced neck position and always keep this rare but so critical complication in mind.

Peripheral T-Cell Lymphoma of Cervical Spine

Peripheral T-cell lymphoma is a rather uncommon non-Hodgkin’s lymphoma with the initial manifestation of spinal cord compression. Herein, we reported a 74-year-old woman with sustained neck pain radiating into the right shoulder and arm and weakness of the right upper extremity. A mass that had invaded the C5 and C6 vertebral bodies, causing a kyphotic curvature and compressing the spinal cord, was discovered with magnetic resonance imaging. The patient then underwent anterior corpectomy at C5 and C6, and reconstruction with a titanic rod and bone cement. The pathology confirmed a diagnosis of peripheral T-cell lymphoma after serial H & E and immunohistochemical staining. She recovered well from her profound neurological deficit. Both chemotherapy and radiotherapy were used postoperatively. Surgical intervention is indicated in these cases to decompress the cord, remove the majority of the tumor mass, stabilize the spine and obtain tissue for pathological diagnosis.

The impact of individualized care after artificial knee replacement surgery for patients with valgus deformity of the knee

Objective:To evaluate the perioperative nursing of total knee arthroplasty for patients with valgus deformity of the knee.Methods:Seventy-six patients who underwent surgical treatment were enrolled in the study from March 2014 to March 2018.The patients in the control group were treated with routine nursing.The experimental group was treated not only with routine nursing but also with health education,psychological care,family social support,and other nursing intervention.Hospital for special surgery and Pittsburgh sleep quality index were used to evaluate the effect of nursing intervention on patients after operation.Results:All the index scores of the experimental group were lower than those of the control group(P<0.05),indicating that the function of the diseased limb and the patient's sleep status improved significantly after the intervention.Conclusions:Individualized nursing can improve the recovery of limb function and improve the patients'quality of life.It is very effective for nurses to implement individualized nursing measures for patients after surgery.

Features of Glucose Metabolism in Pleomorphic Hyalinizing Angiectatic Tumor (PHAT)

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare mesenchymal neoplasma. It is a pathological term describing a heterogeneous group of neoplasms of undetermined tumorigenesis and undefined malignancy. Based only on the morphological findings of histopathology, the biological potential of the tumor is indeterminate. Determination of glucose metabolism using FDG-PET revealed mildly increased FDG uptake in the tumor. We propose that FDG accumulation in the ectatic vessel, increased uptake of the pleomorphic cells and/or associated inflammatory cells, and increased permeability of the stroma lead to the imaging feature.

Ocular Response Analyzer to Assess Age-Related Biomechanical Characteristics of the Cornea in a Taiwan Residents Population

Purpose: To investigate biomechanical properties of the cornea as measured using a Reichert ocular response analyzer (ORA) in a Taiwan Residents population. Methods: Basic demographic data were recorded for 1875 Taiwan Residents subjects. Corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT), Goldmann-equivalent intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) were measured with an ORA. Descriptive statistics and multiple regression analyses were used to assess and compare relevant factors of the CRF and CH. Results: In total, 1817 eyes were included in this study. The mean patient age was 21.4 ± 17.01 years. The mean (±SD) CH and CRF values were 10.6 ± 1.81 and 10.6 ± 1.99 mmHg, respectively. The mean CCT was 560.4 ± 38.53 μm. CH was correlated with IOPcc, CRF, and CCT. In the multiple linear-regression model, CH was associated with and affected by IOPcc, CRF, and CCT. In another multiple linear-regression model, CRF was associated with and affected by IOPcc, CH, and CCT. Conclusions: Measuring biomechanical properties by Reichert ORA, we found that CH and CRF values of a Taiwan Residents population were similar to those other Asian populations and other races. Our findings provided fundamental data of CH and CRF in a Taiwan Residents (ethic Chinese) and also Asian population.

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

Hepatitis B virus （HBV） reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor （TNF） blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-a blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-a blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose- and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-a blockage therapy occurred at early time points after HBV infection. In addition, TNF-a blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death （PD）- 1highCD127low exhausted T cells. Furthermore, TNF-a blockade abolished Toll-like receptor 9 （TLR9） ligand-induced facilitation of HBV viral clearance. Taken together, TNF-a blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-a blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during theraoy with TNF-a-blocking agents.

An apoptosis-independent role of TRAIL in suppressing joint inflammation and inhibiting T-cell activation in inflammatory arthritis

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation ofinflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocytes andinfiltrating lymphocytes. The aim of this study was to investigate the immunomodulatory mechanism and role ofTRAIL in inflammatory arthritis. We created an animal model of inflammatory arthritis and demonstrated that TRAILsignificantly inhibited joint inflammation and reduced the severity of arthritis. The suppression of joint inflammationwas not due to the TRAIL-mediated induction of apoptosis in T cells, macrophages or synovial fibroblasts. Incontrast, TRAIL directly inhibited T-cell proliferation and suppressed the production of cytokines, which indicatedthat TRAIL exerted its anti-inflammatory effects by direct inhibition of T-cell activation. Moreover, TRAIL receptor(TRAIL-R)-knockout mice developed more severe disease, and the protective effects of TRAIL were abolished in theexperimental arthritis model in TRAIL-R knockout mice. From these results, we conclude that TRAIL suppressesjoint inflammation via an apoptosis-independent pathway and directly inhibits T-cell activation. Our results providea novel apoptosis-independent, immune regulatory role for TRAIL in suppressing inflammatory arthritis and shedlight on the development of effective new therapies for autoimmune inflammatory diseases.

Asialo GM1-positive liver-resident CD8 T cells that express CD44 and LFA-1 are essential for immune clearance of hepatitis B virus

Persistent hepatitis B virus(HBV)infection results in chronic liver diseases that may progress to chronic hepatitis,liver cirrhosis,and subsequent hepatocellular carcinoma.Previous studies demonstrated that adaptive immunity,in particular CD8 T cells,is critical in HBV elimination.Recent studies have revealed a distinct tissue-localized T cell lineage,tissue-resident memory(TRM)cells,that is crucial for protective immunity in peripheral tissues.In this study,we showed that treatment with an anti-asialo GM1(ASGM1)antibody(Ab),which depletes NK cells,led to impairment of HBV clearance in a mouse animal model.Unexpectedly,the ability to clear HBV was not significantly impaired in NFIL3 KO mice,which are deficient in NK cells,implying that other non-NK ASGM1-positive immune cells mediate HBV clearance.We isolated intrahepatic ASGM1-positive cells from NFIL3 KO mice and analyzed the immune phenotype of these cells.Our results demonstrated a distinct population of CD44+LFA-1hi CD8 T cells that were the major intrahepatic ASGM1-positive immune cells in NFIL3 KO mice.Importantly,transcriptome analysis revealed that these ASGM1-positive CD8 T cells had distinct gene profiles and shared a similar core gene signature with TRM cells.In addition to both transcriptional and phenotypic liver residency characteristics,ASGM1-positive CD8 T cells were able to home to and be retained in the liver after adoptive transfer.Taken together,our study results indicate that these ASGM1-positive liver-resident CD8 T cells are the major effector immune cells mediating anti-HBV immunity.