The Association of Socioeconomic Status with the Burden of Cataract-related Blindness and the Effect of Ultraviolet Radiation Exposure: An Ecological Study

Objective To assess the association of socioeconomic status with the burden of cataract blindness in terms of year lived with disability(YLD) rates and to determine whether ultraviolet radiation(UVR) levels modify the effect of socioeconomic status on this health burden.Methods National and subnational age-standardized YLD rates associated with cataract-related blindness were derived from the Global Burden of Disease(GBD) study 2017. The human development index(HDI) from the Human Development Report was used as a measure of socioeconomic status.Estimated ground-level UVR exposure was obtained from the Ozone Monitoring Instrument(OMI)dataset of the National Aeronautics and Space Administration(NASA).Results Across 185 countries, socioeconomic status was inversely associated with the burden of cataract blindness. Countries with a very high HDI had an 84% lower age-standardized YLD rate [95%confidence interval(CI): 60%–93%, P < 0.001] than countries with a low HDI;for high-HDI countries, the proportion was 76%(95% CI: 53%–88%, P < 0.001), and for medium-HDI countries, the proportion was48%(95% CI: 15%–68%, P = 0.010;P for trend < 0.001). The interaction analysis showed that UVR exposure played an interactive role in the association between socioeconomic status and cataract blindness burden(P value for interaction = 0.047).Conclusion Long-term high-UVR exposure amplifies the association of poor socioeconomic status with the burden of cataract-related blindness. The findings emphasize the need for strengthening UVR exposure protection interventions in developing countries with high-UVR exposure.

Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients

AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHODS： Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay （EUSA） method. RESULTS： We found a significant increased frequency of HLA-DQBI＊0401 allele in Hpylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10^-7, odds ratio （OR） = 4.96; 95% confidence interval （95% CI）, 3.87-6.35]. We also found a significant increased frequency of HLA-DQBI＊0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals （P = 1 × 10^4, OR = 13.07; 95% CI, 2.82-85.14）.CONCLUSION： HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and difffuse-type gastric adenocarcinoma in the Mexican Mestizo population.

New insights into the pathophysiology of achalasia and implications for future treatment

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter(LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents(herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.

Effect of family caregiver nursing education on patients with rheumatoid arthritis and its impact factors:A randomized controlled trial

BACKGROUND Rheumatoid arthritis(RA)is a common autoimmune disease.Nursing education for family caregivers is considered a workable and effective intervention,but the validity of this intervention in RA has not been reported.AIM To explore whether family caregiver nursing education(FCNE)works on patients with RA and the factors that influence FCNE.METHODS In this randomized controlled study,a sample of 158 pairs was included in the study with 80 in the intervention group and 78 in the control group.Baseline data of patients and caregivers was collected.The FCNE intervention was admi-nistered to caregivers,and inflammation level indicators,disease activity indicators and mood disorder indicators of patients were followed up and analyzed.RESULTS Baseline characteristics of the intervention and the control groups had no significant difference.Indicators were significantly reduced in the intervention group compared to the control group.The intervention group showed significant differences in stratification of relationship,education duration and age.CONCLUSION The effect of FCNE on RA is multifaceted,weakening inflammation level,alleviating disease activity and relieving mood disorder.Relationship between caregiver and patient,caregiver’s education level and patient’s age may act as impact factors of FCNE.

Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease

Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA "resistant") in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.

Rheumatic manifestations of inflammatory bowel disease

This article reviews the literature concerning rheu-matic manifestations of inflammatory bowel disease (IBD),including common immune-mediated pathways,frequency,clinical course and therapy. Musculoskel-etal complications are frequent and well-recognized manifestations in IBD,and affect up to 33% of pa-tients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations,notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen pre-sentation,aberrant recognition of self,the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues,and increased intestinal permeability. The response against microor-ganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic mani-festations of IBD have been divided into peripheral arthritis,and axial involvement,including sacroiliitis,with or without spondylitis,similar to idiopathic anky-losing spondylitis. Other periarticular features can oc-cur,including enthesopathy,tendonitis,clubbing,peri-ostitis,and granulomatous lesions of joints and bones.Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The manage-ment of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however,because of their possible harmful effects on intestinal integrity,perme-ability,and even on gut inflammation. Sulfasalazine,methotrexate,azathioprine,cyclosporine and lefluno-mide should be used for selected indications. In some cases,tumor necrosis factor-α blocking agents should be considered as first-line therapy.

Effects of Simvastatin on the Function of Dendritic Cells in Patients with Rheumatic Arthritis

The present study examined the functional profile of dendritic cells (DCs) in patients with rheumatoid arthritis (RA) and the effects of simvastatin on the function of DCs.A total of 40 patients who was recently diagnosed as having RA were equally assigned to two groups:the routine treatment group (group R) and the routine treatment plus simvastatin group (group R+S).Twenty healthy individuals served as control.The peripheral blood mononuclear cells (PBMCs) were isolated before and 4 weeks after the treatment and then cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM-CSF) to prepare mature DCs.The expression of co-stimulating factor CD86 on the surface of DCs was assessed by flow cytometry.And the stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR).The contents of cytokines in culture supernatants of DCs in MLR were detected by ELISA.Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were detected.The relationship between the expression of CD86 and the blood CRP level was also investigated.The results showed that,as compared with the control group,the CD86 expression and the level of cytokines secreted by DCs were significantly increased in RA patients and greater stimulating capacity of DCs in MLR was demonstrated in RA patients.T lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2,IL-17,TNF-α and INF-γ) and lower level of anti-inflammation cytokine (IL-10).The function of DCs was markedly weakened and the level of hs-CRP and low-density lipoprotein was substantially lowered in group R+S in comparison to group R.The CD86 expression was positively correlated with hs-CRP.It was concluded that DCs in RA are highly activated and DC-initiated immune reaction may play an important role in the pathogenesis of RA.Simvastatin administration can significantly inhibit the DCs function and reduce the level of hs-CRP,indicating the suppression on inflammatory reaction may be one of the mechanisms by which simvastatin exerts its effect in treating RA.

Lessons from Sj?gren's syndrome etiopathogenesis:Novel cellular and molecular targets

Sjogren’s syndrome （SS） is a systemic autoimmune disease that affects primarily the lacrimal and salivary glands. In addition to a systemic autoimmune response directed against ubiquitous antigens （such as Ro and La antigens）, patients with SS mount a localized response that affects the epithelial component of exocrine glands leading to the establishment of a destructive inflammatory infiltrate comprised of activated T and B cells. Local chemokine and cytokine production drive the recruitment and local activation of immune cells that cause injury to acinar cells. CD4 T cells with different functional differentiation programs including Th1 （IFN-γ）, Th2 （IL-13, IL-4） and Th17 （IL-17, IL-21, IL-22） as well as diverse cytokine signaling pathways, are involved at the initiation, perpetuation, and progression of the disease. Which factors initiate this response and allow it to become chronic are unknown. Proposed mecha-nisms include viral infections and acinar cell apoptosis. Moreover risk-conferring genetic variants, probably through the facilitation of innate and adaptive immune activation, most certainly contribute to the creation of an underlying environment that fosters tolerance loss and facilitates perpetuation of the autoimmune response. In this review, we describe the mechanisms through which the immune response causes SS and emphasize the pathways that are amenable of being targeted with therapeutic purposes.

Effects of Gancao Nourish-Yin Decoction on Liver Metabolic Profiles in hTNF-αTransgenic Arthritic Model Mice

Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.

Clinical Efficacy and Safety of Bathing with Chinese Medicine Taohong Siwu Decoction(桃红四物汤) for Treatment of Diffuse Cutaneous Systemic Sclerosis:A Randomized Placebo-Controlled Trial

Objective：To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction（桃红四物汤,TSD） in the treatment of early-stage,mild-moderate diffuse cutaneous systemic sclerosis（dc SSc）.Methods：This randomized,placebo-controlled trial enrolled 148 men and women（18–60 years） with dc SSc（disease duration 12 months） and baseline modified Rodnan skin score（MRSS） 10.Patients were randomized into a TSD group（71 cases bathing with TSD plus oral prednisone） or control group（71 cases bathing with placebo plus oral prednisone）.Bathing（40 ℃,30 min） of the upper and lower limbs was carried out once daily for 12 consecutive weeks.The primary outcome measure was MRSS;secondary outcomes were Raynaud＇s phenomenon（RP） score,quality of life（QOL）,physician visual analogue scale（VAS）,patient VAS,percent predicted diffusing capacity for carbon monoxide（DLCO）,percent predicted forced vital capacity（FVC）,erythrocyte sedimentation rate（ESR）,C-reactive protein（CRP） level and overall treatment effect.Results：The final analysis included 135 patients（control group,68 cases;TSD group,67 cases）.Primary and secondary outcome measures after 2 weeks of treatment showed no improvement（versus baseline） in both groups,with no differences between groups.At 12 weeks,QOL,physician VAS,patient VAS,ESR and CRP were improved in both groups,but MRSS and RP score were improved only in the TSD group（all P〈0.05）.MRSS,RP score,QOL,physician VAS,patient VAS,ESR and CRP differed significantly between groups（all P〈0.05）.Meanwhile,the overall treatment effect was significantly higher in the TSD group than in the control group（P〈0.05）.Adverse events in the two groups were similar（P〉0.05）.Conclusions：Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcS Sc and is not associated with serious adverse events.

Clinical heterogeneity in autoimmune acute liver failure

AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids.

Gene therapy and genome editing for primary immunodeficiency diseases

In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells(HSCs)transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases(PIDs).Despite of some pitfalls at early stage clinical trials,the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety,preparatory regime for manufacturing high quality virus,automated CD34 cell purification.Hence,the overall outcome from the clinical trials for the different PIDs has been very encouraging.In addition to the viral vector based gene therapy,the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of PIDs.This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X,ADA-SCID,WAS,X-CGD,and the recent developments in genome editing technology applied in HSCs for developing potential therapy,particular in the key studies for PIDs.

Complementary and Alternative Medicine in Rheumatoid Arthritis

There are studies that have evidence for and are against to suggest that some of the complementary and alternative medicines （CAM） are effective against rheumatoid arthritis （RA）. However, there are no adequate studies that have evaluated the role that can be played by CAM in the management of RA. A focused approach in defining the role and limitation as well as the possible adverse events and safety should help in integrating both CAM and mainstream treatment of RA. This review discussed the limitations in the available literature and the direction for future research, which can accelerate the defining role of CAM in RA.

CD4^(+)CD25^(+)but not CD4^(+)Foxp3^(+) T cells as a regulatory subset in primary biliary cirrhosis

Increasing evidence indicates a role for regulatory T cells(Tregs)in the immune response and in autoimmune diseases,but the role of Tregs and cytokines in autoimmune hepatic diseases remains largely unclear and controversial,especially in patients with primary biliary cirrhosis(PBC).This study was undertaken to investigate Tregs and different cytokines in the liver and peripheral blood of PBC patients.We found that these patients demonstrated a reduction of CD4^(+)CD25^(+) T cells but elevated CD4^(+)Foxp3^(+) T cells in peripheral blood mononuclear cells(PBMCs)and CD41 T cells.The percentage of CD4^(+)CD25^(+) T cells in PBMCs was negatively correlated with elevated plasma interferon(IFN)-c levels.A liver-specific analysis showed that the frequency of Foxp31 Tregs,transforming growth factor(TGF)-b1 and IFN-c were increased in PBC patients.Our findings suggest that an imbalance between CD4^(+)CD25^(+) Tregs and cytotoxic cytokines plays a crucial role in the pathogenesis of PBC while the role of Foxp3 needs further investigation.