Research on hsa-miR-155-3p and hsa-miR-155-5p as biomarkers for systemic sclerosis and their role in regulating biological behavior

Objective: This study was to investigate the role of hsa-miR-155-3p and hsa-miR-155-5p as biomarkers and regulators of biological behavior in Systemic Sclerosis. Methods: A total of 10 SSc patients and 10 healthy controls were selected for the study. The expression levels of hsa-miR-155-3p and hsa-miR-155-5p in peripheral blood mononuclear cells of SSc patients and healthy controls were measured using RT-qPCR. The diagnostic value of these miRNAs was explored using Receiver Operating Characteristic curve analysis. Pearson or Spearman correlation analysis was performed to assess the correlation between miRNAs and clinical indicators in SSc patients. Potential target genes of hsa-miR-155-3p and hsa-miR-155-5p were predicted using miRDB, Targetscan, and miRDIP databases. GO functional annotation, KEGG pathway enrichment analysis, protein-protein interaction network construction, and selection of central genes were conducted. Results: The expression levels of hsa-miR-155-3p and hsa- miR-155-5p were significantly higher in PBMCs of SSc patients compared to healthy controls (P<0.001). The ROC curve analysis showed that hsa-miR-155-3p and hsa-miR-155-5p had a high diagnostic value for SSc (AUC=1, P<0.001). Correlation analysis revealed that hsa- miR-155-3p, hsa-miR-155-5p, and clinical indicators such as high-resolution CT, neutrophil percentage, lymphocyte percentage, and albumin to globulin ratio were correlated (P<0.05). The signaling pathways enriched with target genes of hsa-miR-155-3p and hsa-miR-155- 5p were closely associated with the occurrence and development of SSc fibrosis, immunity, and inflammation. Conclusions: hsa-miR-155-3p and hsa-miR-155-5p may be involved in regulating the occurrence and development of SSc fibrosis, immunity, and inflammation. They have the potential to serve as biomarkers for clinical diagnosis and treatment of SSc.

Juvenile Systemic Sclerosis: About 9 Cases

Scleroderma is a rare disease with two primary forms: localized scleroderma (LS) and systemic sclerosis (SSc). Both are chronic conditions that can manifest in various patterns (subtypes) and are linked to extracutaneous involvement in pediatric patients. Juvenile SSc poses a higher risk of morbidity and mortality, with patients facing life-threatening complications such as lung, heart, and visceral organ fibrosis, and vasculopathy. In contrast, mortality is extremely rare in juvenile LS, but patients are susceptible to significant morbidity, leading to severe disfigurement and functional impairment. Treatment for scleroderma aims to control inflammation and address specific issues. An early diagnosis significantly enhances the overall outcome. This study conducts a retrospective descriptive analysis aiming to document the clinical manifestations, management approaches, and outcomes of systemic sclerosis in a cohort of nine children receiving treatment for juvenile systemic sclerosis at Pediatric B department of Mohammed VI University, Hospital Center in Marrakech, Morocco.

Adipose-derived stem cells:Pathophysiologic implications vs therapeutic potential in systemic sclerosis

Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions.Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients.However,currently available data indicate that ADSCs may represent a double-edged sword in SSc,as they may exhibit a pro-fibrotic and anti-adipogenic phenotype,possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process.Thus,in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications,it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive,anti-inflammatory,anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs.In light of the dual role that ADSCs seem to play in SSc,this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and,at the same time,will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.

Cardiac manifestations in systemic sclerosis

Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.

Is spleen circulation impaired in systemic sclerosis and what is the role of liver fibrosis?

AIM:To investigate the spleen vascular involvement and the presence of liver fibrosis in a population of subjects with established systemic sclerosis(SSc).METHODS:In a cross-sectional fashion,17 patients with SSc were compared with 18 patients suffering from hepatitis C virus(HCV) -related liver cirrhosis,grade A and B Child-Pugh classification.Eighteen non elderly subjects,apparently healthy,were used as the control group.Splenic artery resistivity index(SARI) at doppler ultraSound,transient elastography of liver and nailfold capillaroscopy were the main outcomes.RESULTS:Transient elastography values of SSc patients were similar to those of controls;5.2±1.1 vs 4.5 ±1,(P=0.07).Median Alanine amino transferase(ALT) concentrations of cirrhotic patients were greater than those of controls and SSc patients,i.e.66.5(36-89) U/L vs 29(22-34) U/L and 31(22-41) U/L,respectively,(P =0.005).SARI determinations in cirrhotic patients,although significantly higher than those found in controls and SSc patients,showed some degree of overlap with SSc patients,i.e.0.59 vs 0.52 and 0.57,respectively,(P =0.04).Mean systolic blood pressure was significantly higher in SSc patients than in cirrhotics and controls,i.e.142 mmHg vs 128.2 mmHg and 127 mmHg,respectively,(P=0.005).Mean diastolic blood pressure behaved in a similar fashion,i.e.84 mmHg vs 72.2 mmHg and 76.9 mmHg(P=0.005).Nailfold Capillaroscopy grades and diastolic blood pressure values correlated well with SARI results.CONCLUSION:An enhanced resistivity of the splenic artery was found in patients suffering from SSc;they did not have evidence of splenomegaly as well as no liver fibrosis or any other form of liver damage.

Investigation of stressful life events in patients with systemic sclerosis

Objective: To assess the occurrence of stressful life events in the year before the initiation of systemic sclerosis. Methods: A consecutive series of 40 patients with systemic sclerosis (mean age (56.3±11.9) years, mean disease duration (4.3±3.1) years; 32 females and 8 males), including 28 with diffuse cutaneous scleroderma and 12 with limited cutaneous scleroderma, were evaluated. A control group of 40 healthy subjects free of systemic sclerosis also was included. Socioeconomic status was inves- tigated and Paykel's interview for recent life events (a semi-structured research interview covering 64 life events) was conducted. Results: Patients with systemic sclerosis showed higher percentages of lower education (72.5%) and working class (82.5%), and reported more stressful life events (P<0.05), such as exits (P<0.05), undesirable events (P<0.01), and uncontrolled events (P<0.001), when compared with the control. More events that had an objective negative impact (P<0.001) were also reported in systemic sclerosis patients than in the control. These results are in accordance with a multifactorial model of pathogenesis in systemic sclerosis. Conclusion: We reported a strong relationship between stressful life events and the initiation of systemic sclerosis. Our findings are consistent with current understanding of the extensive links of behavioral responses to stress with neurophysiological and biochemical processes.

Transforming growth factor-β signaling in systemic sclerosis

Systemic sclerosis（SSc） is a complex, multiorgan autoimmune disease of unknown etiology. Manifestation of the disease results from an interaction of three key pathologic features including irregularities of the antigen-specific immune system and the non-specific Immune system, resulting in autoantibody production, vascular endothelial activation of small blood vessels, and tissue fibrosis as a result of fibroblast dysfunction. Given the heterogeneity of clinical presentation of the disease, a lack of universal models has impeded adequate testing of potential therapies for SSc. Regardless, recent research has elucidated the roles of various ubiquitous molecular mechanisms that contribute to the clinical manifestation of the disease. Transforming growth factor β（TGF-β） has been identified as a regulator of pathological fibrogenesis in SSc. Various processes, including cell growth, apoptosis, cell differentiation, and extracellular matrix synthesis are regulated by TGF-β,a type of cytokine secreted by macrophages and many other cell types. Understanding the essential role TGF-β pathways play in the pathology of systemic sclerosis could provide a potential outlet for treatment and a better understanding of this severe disease.

Gastrointestinal manifestations of systemic sclerosis:An updated review

Systemic sclerosis is an autoimmune disease characterized by vascular disease,fibrosis of the skin,and internal organ dysfunction.Gastrointestinal involvement is the most frequent complication of internal organs,impacting up to 90%of patients.Gastrointestinal involvement can affect any region of the gastrointestinal tract from the mouth to the anus,with a predominance of disorders being observed at the level of the upper digestive tract.The gastrointestinal involvement primarily involves the esophagus,small bowel,and rectum.The severity of gastrointestinal involvement affects quality of life and is a marker of worse prognosis and mortality in these patients.In this review,we describe the current findings regarding gastrointestinal involvement by this entity.

Expression of MMP-9 and TIMP-1 in Lesions of Systemic Sclerosis and Its Implications

In order to investigate the role of MMP-9 and TIMP-1 in the pathogenesis of systemic sclerosis, the expression of MMP-9 and TIMP-1 was immunohistochemically detected in skin lesions of the patients with diffuse cutaneous systemic sclerosis, skin lesions of the patients with limited cutaneous systemic sclerosis, and skin tissues of normal subjects. The results showed that the expression of MMP-9 in lesions of diffuse cutaneous systemic sclerosis was significantly lower than that of normal skins （P〈0.05）. However, no significant difference in the level of MMP-9 in the limited cutaneous systemic sclerosis and normal skin was found. Meanwhile, the expression of TIMP-1 in lesions of diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis were significantly higher than that of normal skins （both P〈0.05）. It was suggested that the expression of MMP-9 and TIMP-1 might play an important role in the development of systemic sclerosis.

Exploring the treatment of Systemic Sclerosis with Danggui (Angelica sinensis, AS)-Sini Decoction using GEO combined with Network pharmacology and Molecular docking

Background:To explore the relevant targets of the Chinese herbal medicine compound Danggui-Sini Decoction(DGSND)for the treatment of systemic sclerosis(SSc).Method:We used TCMSP to enlist ingredients and Swiss Target Prediction for targets fishing,and the protein names by UniProt for organized as gene symbol.Strawberry Perl was used to integrate the active ingredients and the drugs action target of DGSND,with Cytoscape 3.9.0 software to construct"Active ingredient-Drug target"network.Then,GEO database,GeneCards database,TTDdatabase,DisGENent database and MalaCards database for SSc-related disease target prediction,and then analyzed the active drug targets of DGSND and SSc-related targets of Danggui-Sini Decoction treat SSc.Then,the above results we combined with STRING database to visualize the Protein-protein interaction(PPI)network for the core targets of SSc,and performed Gene ontology(GO)functional analysis and Kyoto Encyclopedia of Genomics(KEGG)signaling pathway enrichment analysis for SSc-related targets treated with DGSND Result:DGSND contains 223 active ingredients including Sitogluside,Benzoylpaeoniflorin,(-)-Asarinin Palbinone,Glycyro,4'DMEP etc.which acts on Signal transducer and activator of transcription 3(STAT3),Tumor Necrosis Factor(TNF),Vascular endothelial growth factor(VEGFA),Nuclear factor kappa-B(NFκB1),Interleukin(IL1β,IL17),Mitogen-activated protein kinase(MAPK)and Janus Kinase(JAK)and many other genes totaling 176,mainly involved in 4 more biological processes 3 molecular functions and 3 cellular components.Conclusion:DGSND is primarily used to treat SSc by regulating calcium homeostasis,inflammatory signaling pathways and neural cell repair and apoptosis-related pathways within the body.

Network pharmacological study and molecular docking verification of Capparis spinosa in the treatment of systemic sclerosis

Objective:To explore the molecular mechanism of Capparis spinosa in the treatment of systemic sclerosis((SSC))based on network pharmacology.Methods:GEO,Genecards,Pharmgkb,TTD and Drugbank databases were used to obtain SSC targets,related literatures and Swisstargetprediction databases were used to obtain the main components of Citrus and their corresponding targets,and intersection was used to obtain prediction targets.Log in to the String database to analyze the protein interaction of the prediction target(PPI),further used Cytoscape to obtain the core gene by network topology analysis,and the core gene was docked with the main components of Capparis spinosa.The prediction targets were analyzed by gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis using R software.Results:A total of 15 active components and their targets were obtained,3171 SSC targets were obtained,and 66 predicted targets were obtained by intersection.Ten PPI core genes such as VEGFA,TNF,AKT1,PTGS2 and MMP9 were obtained by topological analysis.GO analysis involved many biological processes such as reactive oxygen species metabolic process、protein kinase B signaling、regulation of inflammatory response、phosphatidylinositol 3-kinase signaling and so on.KEGG pathway analysis showed PI3K-Akt signaling pathway,Proteoglycans in cancer,Focal adhesion,Rap1 signaling pathway and other signaling pathways.Conclusion:The molecular mechanism of Capparis spinosa in the treatment of SSC is predicted by the method of network pharmacology,which provides theoretical basis and data support for the basic research of Citrus officinalis in the treatment of SSC.

Lower Extremity Ulcers in Patients with Systemic Sclerosis

Introduction: Cutaneous manifestations of systemic sclerosis (SSc) include skin ulceration;4% - 12% of patients with SSc develop lower extremity ulcers of various etiologies. Limited data, significant morbidity, and substantial cost of wound care led us to undertake this study to describe and identify risk factors. Methods: After Institutional Review Board approval, we identified 30 patients with SSc and lower extremity ulcers over a 10-year period at a single center with an SSc clinic, which were included in a descriptive analysis. Results: Median age of onset of lower extremity ulcers was 59.5 years (range 20 - 84). Ninety percent of patients were female, 60% were Caucasian, 63% had limited SSc, 13% diffuse SSc and 23% an overlap syndrome. Immunomodulators or steroids were prescribed in 53%;hypercoagulable state identified in 16%. Ulcers were attributed to venous stasis (27%), SSc (20%), trauma (20%), arterial disease (17%), and multifactorial/unknown (17%). In patients with ulcers attributed to SSc, age at onset was lower (45.5 vs 59.5 years). Biopsies generally did not contribute to management. Multidisciplinary treatment was routine;20% required amputation, 10% endovascular intervention, 20% frequent surgical debridement, 10% hyperbaric oxygen, 26% local treatment and antibiotics and 13% received immunosuppression for wound treatment. Conclusion: Lower extremity ulcers are a serious clinical problem in patients with SSc. The clinical exam, venous dopplers, ankle-brachial indices and assessment of vascular risk factors helped define causality. In younger patients, ulcers were more frequently attributed to SSc and these patients were more likely to be on immunosuppressants/DMARDS, possibly indicating severe phenotype of SSc.

Detection of Ⅴ,Ⅲ and Ⅰ Type Collagens of Dermal Tissues in Skin Lesions of Patients with Systemic Sclerosis and Its Implication

This study investigated the contents and distribution of collagen Ⅴ （Col Ⅴ） in skin lesions of the patients with systemic sclerosis （SSc） and its roles in the pathogenesis. The contents and distribution for α1 chain of collagen type Ⅰ, Ⅲ and V [α1 （Ⅰ）, α1 （Ⅲ） and α1 （Ⅴ）] in skin lesions of 36 patients with SSc （9 cases of mild fibrosis, 14 moderate, and 13 severe） were detected by using im- munohistochemical SP method. Six cases of normal skin tissues served as controls. The results showed that there was diffuse distribution for three kinds of collagens in dermis. The deep staining α1 （Ⅰ） and α1 （Ⅲ） masses or bands were seen in reticular layer, while α1 （Ⅴ） was distributed more ho- mogeneously. From control to weak, moderate and severe fibrosis stages, α1 （Ⅰ）, α1 （Ⅲ） and α1 （V） showed a gradually increased trend in skin lesions （P〈0.05）. α1 （Ⅴ） was obviously elevated in skin lesions at early stage and persisted in whole fibrotic process and risen in greater contents, while α1 （Ⅰ） and α1 （Ⅲ） were to go higher late and were apparently elevated at moderate and late stages. Com- pared with α1 （Ⅰ）, α1 （Ⅴ） took leading increase at early stage in skin lesions （P〈0.01）, and had more elevated contents than α1 （Ⅲ） at moderate and late stages. The fibrotic changes in dermal reticular layer occurred earlier than those in papillary layer, and the abnormalities of α1 （Ⅴ）/α1 （I） ratio ap- peared before α1 （Ⅲ）/α1 （Ⅰ） ratio. It was concluded that a lot of α1 （Ⅴ） began to deposit in greater contents prior to α1 （Ⅰ） and α1 （Ⅲ） at early stage in SSc and persisted in whole fibrotic process. The changes of α1 （Ⅴ） contents in reticular layer occurred earlier than those in papillary layer, and it sug- gested that the fibrosis in reticular layer appeared earlier.

Causes and predictors of mortality in South Africans with systemic sclerosis

Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Methods:A retrospective records review of clinicodemographic,laboratory,and outcome data of SSc patients attending a state-funded tertiary Rheumatology service in South Africa.Results:Most of the 164 patients were Black(92.7%)and female(87.8%).The mean(SD)age at diagnosis and follow-up duration were 42.6(12.9)and 5.5(5.6)years,respectively.The majority(75.6%)had diffuse cutaneous SSc(dcSSc);and digital pits/ulcers,interstitial lung disease(ILD),and pulmonary hypertension(PH)were documented in 73.6%,55.0%,and 38.3%,respectively.There were 56 known deaths and an equal number of patients were lost to follow-up.Deaths resulted from ILD complicated by PH(42.9%),infections(8.9%),cardiac disease(7.1%),and malignancies(3.6%).Estimated 5-and 10-year survival rates for patients with known outcomes were 58%and 42%,respectively.Independent predictors of death were renal dysfunction and cor pulmonale.Conclusion:Most patients in this study of South Africans had dcSSc and poor outcomes.Known deaths resulted from cardiorespiratory complications of ILD complicated by PH.Cor pulmonale and renal dysfunction were independent predictors of death.

Micro RNAs Regulating Signaling Pathways:Potential Biomarkers in Systemic Sclerosis

Systemic sclerosis （SSc） is a multisystem fibrotic and autoimmune disease. Both genetic and epigenetic elements mediate SSc pathophysiology. This review summarizes the role of one epigenetic element, known as microRNAs （miRNAs）, involved in different signaling pathways of SSc pathogenesis. The expression of key components in transforming growth factor-β （TGF-β） signaling pathway has been found to be regulated by miRNAs both upstream and downstream of TGF-β. We are specifically interested in the pathway components upstream of TGF-β, while miRNAs in other signaling pathways have not been extensively studied. The emerging role of miRNAs in vasculopathy of SSc suggests a promising new direction for future investigation. Elu- cidation of the regulatory role of miRNAs in the expression of signaling factors may facilitate the discovery of novel biomarkers in SSc and improve the understanding and treatment of this disease.

MSCs-laden injectable self-healing hydrogel for systemic sclerosis treatment

As a novel cellular therapy, the anti-inflammatory and immunomodulatory virtues of mesenchymal stem cells (MSCs) make them promising candidates for systemic sclerosis (SSc) treatment. However, the clinical efficacy of this stratagem is limited because of the short persistence time, poor survival, and engraftment of MSCs after injection in vivo. Herein, we develop a novel MSCs-laden injectable self-healing hydrogel for SSc treatment. The hydrogel is prepared using N, O-carboxymethyl chitosan (CS-CM) and 4-armed benzaldehyde-terminated poly-ethylene glycol (PEG-BA) as the main components, imparting with self-healing capacity via the reversible Schiff-base connection between the amino and benzaldehyde groups. We demonstrate that the hydrogel laden with MSCs not only promoted the proliferation of MSCs and increased the cellular half-life in vivo, but also improve their immune-modulating functions. The tube formation assay indicates that the MSCs could significantly pro-mote angiopoiesis. Moreover, the MSCs-laden hydrogel could inhibit fibrosis by modulating the synthesis of collagen and ameliorate disease progression in SSc disease model mice after subcutaneous injection of bleo-mycin. All these results highlight this novel MSCs-laden hydrogel and its distinctive functions in treatment of chronic SSc, indicating the additional potential to be used widely in the clinic.

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.

Mesenchymal stem cell as a novelapproach to systemic sclerosis;currentstatus and future perspectives

Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelialcells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs.According to epidemiological data, women’s populations are more susceptible to systemic sclerosis than men. Untilnow, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-basedtreatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stemcells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemicsclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects.Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantationfor systemic sclerosis.

Systemic sclerosis with portal hypertensive ascites responded to corticosteroid treatment

We describe a case of systemic sclerosis （SSc） complicated with portal hypertensive ascites which did not improve with diuretics and ascitic drainage. When corticosteroid added, her ascites diminished dramatically. Though portal hypertension can be imputed to other causes, such as polycystic liver in this case, it can occur in limited SSc with positive anti-centromere antibody and respond to corticosteroid treatment.

Implications for the therapeutic role of Imatinib in systemic sclerosis: a single-arm meta-analysis

Sclerotic chronic graft-versus-host disease (ScGVHD) or systemic sclerosis (SSc) is one of the most severe manifestations of chronic graft-versus-host disease (cGVHD) since the involvement of major organs significantly affects the mortality and morbidity of SSc patients. Currently, there are no effective therapeutic approaches or standard “second-line” therapy for SSc. Imatinib, a clinical tyrosine kinase inhibitor used to treat chronic myeloid leukemia and gastrointestinal tumor, has shown potential therapeutic effects in treating ScGVHD or SSc. Due to the current limitations of clinical trials using Imatinib in the treatment of SSc, the results vary among different studies, and the applications of Imatinib in SSc is still in vagueness. Here we conducted a single-arm meta-analysis to quantitatively and systematically interpret the results of previous studies, as to evaluate the potential therapeutic effect of Imatinib in SSc. The pooled clinical response rate (CRR) showed that Imatinib had higher CRR in SSc patients with longer disease duration (CRR = 0.550) and lung involvement (CRR = 0.601) than those without (P<0.001). Therefore, it was encouraging to con duct future clinical studies regarding Imatinib therapy in SSc patients, since the global response rate of Imatinib was higher than expected in specific subgroup patients.