Epidemiological characteristics of pulmonary tuberculosis in Anhui Province, Eastern China from 2013 to 2018.

OBJECTIVE: Pulmonary tuberculosis (TB) is a severe infectious respiratory disease, the burden of which remains high in China. To provide scientific evidence for developing more targeted prevention and control strategies, this study aimed to determine the incidence trends and explore the epidemiological characteristics of pulmonary TB in Anhui Province, Eastern China between 2013 and 2018. METHODS: The retrospective study analyzed information regarding pulmonary TB cases reported by the National Infectious Disease Reporting System and census data collected from the Anhui Provincial Bureau of Statistics. RESULTS: Overall, 211,892 cases of TB patients were reported in Anhui Province, China between 2013 and 2018, with an average annual reported incidence rate of 57.7 per 100,000 persons. A significant decrease in the incidence rate of pulmonary TB (p < 0.001) was observed during the study period. Men had a higher incidence rate of pulmonary TB than women (p < 0.001). The highest annual average reported incidence rate was 204.2 per 100,000 persons in those aged 70-74 years. The number of farmers with pulmonary TB, i.e., 155,415, accounted for 73.4% of all cases. Moreover, the peak period of reported cases was from January to March. Four cities along the Yangtze River-Anqing, Tongling, Chizhou, and Wuhu-reported significantly higher incidence rates of pulmonary TB than other cities (p < 0.001). CONCLUSIONS: From 2013 to 2018, there was a significant decline in the incidence rate of pulmonary TB in Anhui Province, with peaks occurring from January to March. Prevention and control strategies targeting men, people aged 70-74 years, farmers, and the four cities along the Yangtze River should be strengthened.

Shear Stress Rescued the Neuronal Impairment Induced by Global Cerebral Ischemia Reperfusion via Activating PECAM-1-eNOS-NO Pathway.

Microvessel hypoperfusion following ischemic stress resulted in a decreased shear stress of brain microvascular endothelial cells (BMECs) and contributed to abnormal expression of PECAM-1 after global cerebral ischemia/reperfusion (I/R) injury. Here, we identified novel pathophysiologic and rehabilitative procedures specific to shear stress in microvascular endothelial cells in response to global cerebral I/R injury. We found that the decrease in cerebral blood flow of gerbils after global cerebral I/R injury reduces shear stress, and the abnormal change in shear stress leads to microvascular endothelial cell and neuron damage. Nevertheless, suitable high levels of shear stress contribute to rescuing the dysfunction and malformation of BMECs via regulating the PECAM-1-eNOS-NO pathway to enhance nitric oxide release, decrease the expression of caspase-3 to reduce apoptosis, and improve the shear-adaptability of endothelial cells, thereby playing a protective role in the gerbil brain.

Gene polymorphisms of DISC1 is associated with schizophrenia: Evidence from a meta-analysis.

BACKGROUND: Previous studies suggest an association between Disrupted in schizophrenia 1 (DISC1) polymorphisms and schizophrenia (SCZ). However, the available data are often inconsistent, regarding the difference in sample size, ethnicity, genotyping method, etc. Thus, we carried out a meta-analysis to determine whether DISC1 polymorphisms contributed susceptibility to SCZ. METHODS: A methodical literature review was operated using the English and Chinese core electronic databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the correlation between DISC1 gene polymorphisms and SCZ susceptibility. Subgroup analyses were carried out by stratification of ethnicity. P values were Bonferroni adjusted to account for multiple testing. Publication bias was evaluated by funnel plots, Egger's test and the trim and fill method. RESULTS: Meta-analyses results suggested that DISC1 polymorphisms (rs821616 and rs821597) increased SCZ risk in overall populations. In subgroups of ethnicity, DISC1 polymorphisms (rs821616 and rs821597) was associated with susceptibility to SCZ among the Chinese population (for rs821616: TT+AT vs. AA: OR=1.338, 95% CI=1.124-1.592, P=0.001; T vs. A: OR=1.300, 95% CI=1.124-1.504, P<0.000; for rs821597: AA+AG vs. GG: OR=1.508, 95% CI=1.268-1.794, P<0.001; A vs. G: OR=1.345, 95% CI=1.184-1.527, P<0.001). A positive correlation was also observed between the single marker rs821616 and SCZ among the Japanese population in the recessive model (TT vs. AT+AA: OR=1.524, 95% CI=1.185-1.959, P=0.001). There was no significant relationship between other DISC1 polymorphisms (rs3738401, rs2273890, rs3738398, rs3738402, rs2492367, rs843979, rs3737597, rs4658971, rs1538979, rs1000731 and rs3738399) and SCZ. CONCLUSIONS: DISC1 polymorphisms increased a risk of SCZ, especially in the Chinese population. In order to further corroborate our findings, large well-designed epidemiological studies are needed.

Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo.

The tumor suppressor p53 is one of the most frequently mutated genes in hepatocellular carcinoma (HCC). Previous studies demonstrated that CP-31398 restored the native conformation of mutant p53 and trans-activated p53 downstream genes in tumor cells. However, the research on the application of CP-31398 to liver cancer has not been reported. Here, we investigated the effects of CP-31398 on the phenotype of HCC cells carrying p53 mutation. The effects of CP-31398 on the characteristic of p53-mutated HCC cells were evaluated through analyzing cell cycle, cell apoptosis, cell proliferation, and the expression of p53 downstream genes. In tumor xenografts developed by PLC/PRF/5 cells, the inhibition of tumor growth by CP-31398 was analyzed through gross morphology, growth curve, and the expression of p53-related genes. Firstly, we demonstrated that CP-31398 inhibited the growth of p53-mutated liver cancer cells in a dose-dependent and p53-dependent manner. Then, further study showed that CP-31398 re-activated wild-type p53 function in p53-mutated HCC cells, which resulted in inhibitive response of cell proliferation and an induction of cell-cycle arrest and apoptosis. Finally, in vivo data confirmed that CP-31398 blocked the growth of xenografts tumors through transactivation of p53-responsive downstream molecules. Our results demonstrated that CP-31398 induced desired phenotypic change of p53-mutated HCC cells in vitro and in vivo, which revealed that CP-31398 would be developed as a therapeutic candidate for HCC carrying p53 mutation.

Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis.

OBJECTIVE: The aim of this paper is to review the anti-inflammatory cytokines IL-4 and IL-13 and their receptor signals; we discuss new insight into their possible roles in systemic sclerosis (SSc) and their overlapping function in SSc. INTRODUCTION: SSc is a connective tissue disease characterized by fibrosis. The exact etiology of SSc is unknown, and no therapy has been proved effective in modifying its course. Recently the roles of IL-4 and IL-13 in the development of SSc have been extensively considered. The possible roles of IL-4 and IL-13, especially their overlapping function, in SSc are not well documented. METHODS: A literature survey was performed using a PubMed database search to gather complete information regarding IL-4 and IL-13 and their role in inflammation. RESULTS AND CONCLUSIONS: The participation of complex pathways of IL-4 and IL-13 in the process of inflammation and fibrosis action in SSc is still not very clear, and some pathogenesis of regulation found in vitro needs to be further proved. There is still more work which could be done to achieve useful developments with therapeutic benefit in SSc.

The association between systemic sclerosis, arginine and asymmetric dimethylarginine.

Systemic sclerosis (SSc) is a kind of autoimmune disease characterized by inflammatory and endothelial dysfunction. Asymmetric dimethylarginine (ADMA), as an endogenous nitric oxide synthase inhibitor, can cause or contribute to the inflammatory syndrome and endothelial dysfunction. Recently, increased ADMA levels have been demonstrated in SSc, revealing that ADMA might play an important role for the associated manifestations of SSc. Besides, ADMA may play a significant role in the level of NO, which is produced by arginine. In the review, we discuss the role of arginine and ADMA in patients with SSc.

The association between vibration and vascular injury in rheumatic diseases: a review of the literature.

Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.

The epidemiology of alcohol consumption and multiple sclerosis: a review.

Alcohol consumption is accounted for a large proportion in patients with multiple sclerosis (MS) and may be a modifiable lifestyle factor that affects the risk of developing the disease. The epidemiological studies about the association between MS and alcohol consumption have got corresponding studies during the last decade. It has been suggested that alcohol consumption was associated with mood disorders, disability and even onset of MS, but a common theme is lacking. To make an understanding of the effect of alcohol consumption on MS, the related epidemiological evidence and potential mechanisms are reviewed.

Prevalence of HIV-1 subtypes among men who have sex with men in China: a systematic review.

The distribution of prevalent HIV-1 strains are still complex in China. Men who have sex with men (MSM) play an important bridging role in spreading HIV. The aim of our study was to quantitatively evaluate the prevalence of HIV-1 subtypes among the MSM population in China from published studies. Relevant studies were searched by selection criteria from CNKI, CBM, Pubmed, etc. We computed the estimates of the pooled proportion of HIV-1 subtypes. Heterogeneity between studies was investigated and measured using Cochran's Q statistic and the I (2) statistic. All analyses were conducted by the R statistical package version 2.13.1. A meta-analysis was performed, which included 19 articles. For comprehensive analysis of env, gag and pol genes, the pooled estimates for the prevalence of subtype B was 28.25% (95% CI: 18.10-39.66%), CRF01_AE was 53.46% (95% CI: 46.11-60.74%), CRF07_BC was 18.66% (95% CI: 13.06-25.01%) and CRF08_BC was 5.85% (95% CI: 2.73-10.07%), respectively. In subgroup analysis, the proportion of subtype B decreased, while the proportion of CRF01_AE and CRF07_BC showed an increasing tendency. Beijing, Guangdong and Henan provinces had high proportions of subtype CRF01_AE while Guangdong and Hebei provinces had the highest proportions of subtype B and CRF07_BC, respectively. A high genetic variability of HIV-1 presents a serious challenge for HIV prevention and treatment strategies among MSM in China.

The association between systemic sclerosis and bone mineral density- a meta-analysis of observational studies.

Previous research has shown inconsistent effect of systemic sclerosis (SSc) on bone mineral density (BMD). The objective of this study was to perform a meta-analysis of previous articles to investigate the differences in BMD (g/cm(2) ) between SSc and non-SSc populations and to discuss potential underlying mechanisms. Twelve full-text articles (including an outlier study and two studies with identical data) with 662 SSc patients and 886 controls were identified by searching Medline prior to 10 September, 2013 using search terms 'Systemic sclerosis' OR 'scleroderma' and 'osteoporosis' OR 'bone density' OR 'bone mass'. BMD (mean and standard deviation), T-scores and Z-scores at lumbar spine, femoral neck and total hip measured by dual-energy X-ray absorptiometry were extracted. Meta-analysis showed that a lower level of BMD was found in SSc patients, with weighted mean difference of -0.343 (95% CI: -0.500 to -0.186) at femoral neck, -0.084 (95% CI: -0.110 to -0.057) at total hip and -0.104 (95% CI: -0.135 to -0.073) at the lumbar spine. We conclude that patients with SSc may have a lower BMD level than healthy controls.

Association of interleukin 1 family with systemic sclerosis.

Systemic sclerosis is a connective tissue disease characterized with fibrosis of skin and/or internal organs, and its specific pathological mechanism remains incompletely understood. IL-1 family, whose biological properties are typically pro-inflammatory and pro-fibrosis, has been associated with systemic sclerosis (SSc). Interleukin (IL)-1 family has 11 members, IL-1α, IL-1ß, IL-1Ra, IL-18, IL-33, IL-36α, IL-36ß, IL-36γ, IL-36Ra, IL-37, and IL-38. With the exception of IL-1Ra and IL-36Ra, each member has its own receptor signal. Abnormal expression of IL-1 and its potential role in the fibrosis process have been probed earliest, as well as its gene polymorphisms with SSc. IL-33 and IL-18 have also been discussed in the recent years, and IL-33 may contribute to the fibrosis of SSc, while IL-18 remains to be researched to confirm its role in fibrosis process. There is a lack of studies on the association of the other members of the IL-1 family, which might provide us the future study area; much more efforts need to be put on this matter.

Micronutrients, their potential effect on patients with systemic sclerosis.

Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases.

INTRODUCTION: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. AREAS COVERED: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. EXPERT OPINION: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.

The emerging role of miR-375 in cancer.

MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that are believed to play fundamental roles in various biological processes through regulation of gene expression at the level of posttranscription. MiR-375 was first identified as a pancreatic islet-specific miRNA regulating insulin secretion. However, further study revealed that miR-375 is a multifunctional miRNA participating in pancreatic islet development, glucose homeostasis, mucosal immunity, lung surfactant secretion and more importantly, tumorigenesis. Recently, miR-375 has been found significantly downregulated in multiple types of cancer, and suppresses core hallmarks of cancer by targeting several important oncogenes like AEG-1, YAP1, IGF1R and PDK1. The alteration of miR-375 in cancer is caused by a variety of mechanisms, including the dysregulation of transcription factors, aberrant promoter methylation and so on. Reduced expression of miR-375 in tissue or circulation may indicate the presence of neoplasia as well as a poor prognosis of many malignant cancers. Moreover, miR-375 stands for a promising direction for developing targeted therapies due to its capacity to inhibit tumor cell growth in vitro and in vivo. Here, we summarize the present understanding of the tumor suppressive role of miR-375 in cancer progression; the mechanisms underlying the dysregulation of miR-375; the potential use of miR-375 in prognosis and diagnosis and the therapeutic prospects of miR-375 in cancer.

Epidemiology of syphilis infection among drug users at methadone maintenance treatment clinics in China: systematic review and meta-analysis.

Illicit drug trade has re-emerged in China since 1979 and the number of drug addicts had increased. Syphilis is mainly spread through sexual contact and blood. The incidence of syphilis is high among drug users. Methadone maintenance treatment (MMT) clinics have been implemented in China since 2004. The aim of this study was to estimate the prevalence and risk factors of syphilis among drug users at MMT clinics in China between 2004 and 2013. Chinese and English databases (CBM, CNKI, Weipu, Pubmed) of literature were searched for studies reporting syphilis among drug users in MMT clinics from 2004 to 2013. The prevalence estimates and risk factors were summarized through a systematic review and meta-analysis of published literatures. In all, 29 eligible articles with a total of 8899 drug users, were selected in this review. The pooled prevalence of syphilis infection was 7.78% (95%CI: 5.83%-9.99%). The meta-analyses demonstrated significant differences in syphilis infection rates between men and women (OR = 0.34 [95%CI: 0.26-0.45]) but not between drug users and non-intravenous drug users (OR = 0.82 [95%CI: 0.51-1.32]). Enhanced detection of syphilis and health promotion is warranted in MMT clinics in China.

The effect of TGF-ß1 polymorphism on systemic sclerosis: a systematic review and pooled analysis of available literature.

Transforming growth factor-ß1 (TGF-ß1) plays an important role in the pathogenesis of systemic sclerosis (SSc). To investigate whether TGF-ß1 gene promoter polymorphisms were associated with the susceptibility of SSc, we performed a meta-analysis based on all available studies through PubMed, Elsevier Science Direct, Embase, and Chinese Biomedical, China National Knowledge Infrastructure and Google Scholar with the last report up to March 15, 2013. Crude odds ratios with 95% confidence intervals were used to estimate the strength of the association. A fixed or random effects model was adopted according to heterogeneity test. Heterogeneity among studies was evaluated using I (2) . Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Begg's and Egger's test. Totally, seven papers with 663 SSc patients and 908 healthy controls were subjected to the final analysis. These studies encompass seven for TGF-ß1 codon 10, three for codon 25 and three for -509C/T. We failed to detect any association of these promoter polymorphism with SSc susceptibility. For TGF-ß1 codon 10 polymorphism, subgroup analyses by race, genotype testing method and classification of SSc were further performed. Similarly, no association was observed. Significant heterogeneity was detected among the studies in all genetic models of TGF-ß1 codon 10 polymorphism. Publication bias was absent. Taken together, our meta-analysis did not provided an evidence of confirming association between TGF-ß1 (codon 10, codon 25, -509C/T) gene polymorphism and SSc. Nevertheless, due to smaller sample sizes, larger sample studies including different ethnic groups should be considered in future to confirm our results.

The risk of cancer development in systemic sclerosis: a meta-analysis.

OBJECTIVES: Systemic sclerosis is a multi-system disorder of connective tissue characterized by Raynaud's phenomenon and fibrosis of various organs. The risk of development of cancer in systemic sclerosis (SSc) has been extensively investigated with inconclusive results. To shed some light on the controversy, we conducted a meta-analysis of all published articles linking SSc to the risk of cancer development. METHODS: Relevant electronic databases were searched for English-language studies characterizing the association of cancers in patients with SSc. Standardized incidence rate (SIR) with its 95% confidence interval (CI) of each study was combined using a fixed/random effect model. RESULTS: A total of seven papers including 7183 SSc patients were identified, of which 7 reported the SIR for lung cancer, 4 for non-Hodgkin's lymphoma (NHL) and 4 for hematopoietic cancer and 7 for breast cancer. Compared with the general population, the combined SIR was 3.14 (95% CI: 2.02-4.89), 2.68 (95% CI: 1.58-4.56), 2.57 (95% CI: 1.79-3.68) and 1.09 (95% CI: 0.86-1.38), respectively. Significant heterogeneity was observed in lung cancer group (Q=26.13, P<0.001, I(2)=77%). Potential publication bias was absent. CONCLUSIONS: This present meta-analysis demonstrated an increased risk of lung, non-Hodgkin's lymphoma and hematopoietic cancers among patients with SSc, but not for breast cancer. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

Association of TGF-ß1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

Many case-control studies have investigated the role of TGF-ß1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95% confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-ß1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR=0.65, 95% CI=0.48-0.88, P=0.005; CC vs. CT+TT: OR=0.56, 95% CI=0.45-0.69, P=0.000; C vs. T: OR=0.81, 95% CI=0.71-0.93, P=0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-ß1 +869C/T promoter polymorphism and RA, especially in Asian population.

Matrix metalloproteinases: a review of their structure and role in systemic sclerosis.

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.