Profile of Autoantibodies and Clinical Symptoms in Guinean Patients with Connective Tissue Diseases

Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.

Research progress on the role of connective tissue growth factor in fibrosis of diabetic retinopathy

Diabetic retinopathy（DR） is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor（CTGF） is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.

Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

In order to investigate the effects of connective tissue growth factor （CTGF） antisense oligodeoxynucleotide （ODN） on plasminogen activator inhibitor-1 （PAI-1） expression in renal tubular cells induced by transforming growth factor β1 （TGF-β1） and to explore the role of CTGF in the degradation of renal extracellular matrix （ECM）, a human proximal tubular epithelial cell line （HKC） was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 （5 μg/L）, the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may he a novel way in preventing renal fibrosis.

Effects of transforming growth factor β2 and connective tissue growth factor on induction of epithelial mesenchymal transition and extracellular matrix synthesis in human lens epithelial cells

AIM:To Investigate the effects of transforming growth factorβ2(TGF-β2)and connective tissue growth factor(CTGF)on transdifferentiation of human lens epithelial cells(HLECs)cultured in vitro and synthesis of extracellular matrix(ECM).METHODS:HLECs were treated with TGF-β2(0,0.5,1.0,5,10μg/L)and CTGF(0,15,30,60,100μg/L)for different times(0,24,48,72h)in vitro and the expression ofα-smooth muscle actin(α-SMA),the main component of the extracellular matrix typeⅠcollagen(Col-1)and fibronectin(Fn)were measured by using real-time polymerase chain reaction(PCR)and western-blot.RESULTS:TGF-β2 and CTGF significantly increased expression ofα-SMA mRNA and protein(P【0.05,P【0.001),Fn mRNA and protein(P【0.001),Col-1 mRNA and protein(P【0.001).TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dosedependent manner(P【0.05,P【0.001).TGF-β2 and CTGF could induce HLECs to expressα-SMA,Fn and Col-1 in time-dependent manner.Each time of TGF-β2and CTGF induced HELCs expression ofα-SMA,Fn,Col-1 mRNA and protein was significant increase compared with control(P【0.05,P【0.001).CONCLUSION:TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis.

Association of Plasma Connective Tissue Growth Factor Levels with Hyperthyroid Heart Disease

Hyperthyroid heart disease(HHD)is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients.Early identification of patients at a higher risk of developing HHD can improve clinical outcomes through active surveillance and management.Connective tissue growth factor(CTGF),a secreted extracellular protein,plays a significant role in cardiac remodeling and dysfunction.We aimed to investigate the association between plasma CTGF level and the risk of HHD in this study.A total of 142 overt hyperthyroid patients without HHD and 99 patients with HHD were included.The plasma CTGF levels were measured using ELISA kits.Routine clinical medical data and echocardiography parameters were recorded for analysis.The plasma CTGF level was significantly higher in patients with HHD than in those without HHD(P=0.002).The plasma CTGF level was positively correlated with free triiodothyronin,tryrotropin receptor antibody,troponin I and lactate dehydrogenase levels and the left atrium diameters,right atrium diameters,and right ventricular end-diastolic diameters(all P<0.05).Logistic regression analysis showed that quartiles 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD(crude OR:2.529;95%CI:1.188-5.387).However,after adjustment for the potentially confounding variables,quartile 4 alone was significantly associated with the higher risk of HHD relative to quartile I.Hyperthyroid patients with HHD display higher plasma CTGF levels.Furthermore,CTGF is an independent risk factor for HHD.Therefore,the plasma CTGF level may be a potential biomarker for the risk of HHD.

Expression of Connective Tissue Growth Factor in Renal Tubulointerstitial Fibrosis in Rats and Its Pathogenic Role

Summary： In order to explore the role of connective tissue growth factor （CTGF） in the pathogenesis of renal tubulointerstitial fibrosis, 48 Wistar rats were randomly divided into sham-operated and unilateral ureteral obstruction （UUO） group. On the postoperative day 1, 3, 7 and 14, the rats were killed and the kidneys were removed. The renal tubulointerstitial injury index was evaluated according to the MASSON staining. The mRNA levels of CTGF, transforming growth factor β1 （TGF-β1）. collagen [ （col I ）, and plasminogen activator inhibitor-1 （PAI 1） were detected using rexerse transcriptional-polymerase chain reaction （RT PCR）. Immunohistochemistry was performed to evaluale the protein expression of the above factors, and the relations among them were analyzed. Quantitative expression of CTGF protein in the kidneys was also assessed using Western blot. The results showed that TGF-β1 mRNA level was increased at first day after UUO, followed by a marked elevation of CTGF mRNA level, which began to increase 3 days after UUO （P〈0.01）. With the progression of the disease, the mRNA expression of CTGF, col I and PAI-1 was increased progressively. Immunohistochemistry revealed that the CTGF protein expression was significantly increased in fibrotic areas and tubular epithelial cells 3 days after UUO. On the post-UUO day 7, the protein level of CTGF was positively related to the renal tubulointerstitial injury index （r =0.62, P〈0.01）, the expression of TGF-β1 （r=0.85, P〈0.01）, colI （r=0.78, P〈0.01）, and PAI-1（r=0.76, P〈0.01）. Upon Western blot analysis, CTGF protein expression began to increase 3 days after UUO, and appeared progressively throughout the time course （P〈0.01, as compared with sham-operated group）. It is concluded that CTGF can be induced by TGF-β and mediate various profibrotic actions of this cytokine, such as increasing extracellular matrix （ECM） synthesis and decreasing ECM degradation. The increased expression of CTGF may play a crucial role in the development and progression of tubulointerstitial fibrosis.

The Effect of Connective Tissue Growth Factor on Human Renal Tubular Epithelial Cell Transdifferentiation

To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of α-smooth muscle actin (α-SMA) were assessed by indirect immuno-fluorescence, and the percentage of α-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of α-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of α-SMA were markedly stronger than that in negative controls. The percentages of α-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9 %, 65.5 % vs 2.4 %, P<0.01) .α-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).

Expression of transcription factors Slug in the lens epithelial cells undergoing epithelial-mesenchymal transition induced by connective tissue growth factor

AIMTo investigate the expression of transcription factors Slug in human lens epithelial cells (HLECs) undergoing epithelial-mesenchymal transition (EMT) induced by connective tissue growth factor (CTGF).METHODSHLECs were treated with CTGF of different concentrations (20, 50 and 100 ng/mL) or without CTGF (control) for 24h. The morphological changes of HLECs were analysed by microscopy. The expression and cellular localization of Slug was evaluated by immumo-fluorescence. Expressions of Slug, E-cadherin and alpha smooth muscle actin (&#x003b1;-SMA) were further determined by Western blot analysis.RESULTSHLECs showed spidle fibrolasts-like characteristics and loosely connected each other after CTGF treatment. The immuno-fluorescence staining indicated that Slug was localized in the nuclei and its expression was induced by CTGF. The relative expressions of Slug protein were 1.64&#x000b1;0.11, 1.96 &#x000b1;0.03, 3.12 &#x000b1;0.10, and 4.08&#x000b1;0.14, respectively, in response to control group and treatment with CTGF of 20, 50 and 100 ng/mL (F=443.86, P&#x0003c;0.01). The increased Slug protein levels were correlated well with up-expression of &#x003b1;-SMA (0.78&#x000b1;0.05, 0.85&#x000b1;0.06, 2.17&#x000b1;0.15, 2.86&#x000b1;0.10; F=449.85, P&#x0003c;0.01) and down-expression of E-cadherin (2.50&#x000b1;0.11, 1.79&#x000b1;0.26, 1.05&#x000b1;0.14, 0.63&#x000b1;0.08; F=101.55, P&#x0003c;0.01).CONCLUSIONTranscription factor Slug may be involved in EMT of HLECs induced by CTGF in vitro.

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer

BACKGROUND Connective tissue growth factor(CTGF)is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling,inflammatory processes and fibrosis in various illnesses including cancer.AIM To investigate the role of CTGF in colorectal cancer(CRC)progression and to compare the CTGF expression with different clinicopathological parameters.METHODS Real-time polymerase chain reaction,immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16.RESULTS CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens.The higher protein expression levels showed a significant association with smoking,staging,tumor grade,invasion depth,necrosis of tumor tissue,and both lymphovascular and perineural invasion.As per the cox regression model and classification tree analysis,tumor-nodemetastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients.Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival.CONCLUSION Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients.These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

Activation of PPAR-γ Inhibits Differentiation of Rat Osteoblasts by Reducing Expression of Connective Tissue Growth Factor

Long-term treatment with an agonist of peroxisome proliferator-activated receptor （PPAR）-γ is associated with bone fractures in the clinical practice. However, the mechanisms underlying the frac- tures are not fully understood. This study was aimed to examine the effect of rosiglitazone （an agonist of PPAR-T） of different doses on the proliferation, differentiation, and transforming growth factor beta 1 （TGF-131）-induced expression of connective tissue growth factor （CTGF） in primary rat osteoblasts in vitro. Osteoblasts were isolated from newly born SD rats and treated with different doses of rosiglita- zone （0-20 gmol/L）. The proliferation and differentiation of osteoblasts were measured by MTT assay and NPP assay, respectively. The expression of CTGF was determined by RT-PCR and Western blotting. The results showed that most isolated osteoblasts displayed strong alkaline phosphatase （ALP） activity and treatment with different doses of rosiglitazone did not affect their proliferation, but significantly in- hibited the differentiation of osteoblasts in a dose-dependent manner. Moreover, treatment with different doses of rosiglitazone significantly reduced the TGF-131-induced CTGF mRNA transcription and protein expression in a dose-dependent manner in rat osteoblasts. It was concluded that the activation of PPAR-y may inhibit the differentiation of osteoblasts by reducing the TGF-131-induced CTGF expres- sion in vitro.

Hydroxychloroquine-induced renal phospholipidosis resembling Fabry disease in undifferentiated connective tissue disease: A case report

BACKGROUND Fabry disease is a kind of lysosomal storage disease resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A(GLA). A mutation in the GLA gene leads to a loss of activity of alpha-galactosidase A. Some drugs,such as hydroxychloroquine, can cause pathological changes similar to those usually seen in Fabry disease.CASE SUMMARY We report the case of a 41-year-old female patient who was diagnosed with undifferentiated connective tissue disease in 2008. Hydroxychloroquine treatment started 2 years ago, and proteinuria and hematuria increased. Renal biopsy demonstrated renal phospholipidosis. Zebra bodies and myelin figures were found by renal electron microscopy and were initially thought to be indicators of Fabry disease. A genetic analysis of the patient and her family members did not reveal mutations in the GLA gene, supporting a diagnosis of hydroxychloroquine-induced renal phospholipidosis.CONCLUSION This report reveals one of the adverse effects of hydroxychloroquine. We should pay more attention to hydroxychloroquine-induced renal phospholipidosis.

Connective Tissue Growth Factor Expression in Rabbit Corneal Fibroblast and Its Effect on Fibroblast Proliferation In Vitro

The connective tissue growth factor (CTGF) expression in cultured corneal fibroblasts and its effect on corneal fibroblasts proliferation in vitro were examined. Total RNA was extracted from early passaged rabbit corneal fibroblasts by guanidine isothiocyanate one-step method and mRNA was reversely transcripted into complementary DNA (cDNA). Specific CTGF primers were used in the PCR reaction and the products were analyzed by electrophoresis to determine the expression of mRNA for CTGF against DNA marker. House-keeping gene GAPDH was used as control. Different concentrations of CTGF (0.5, 5, 50, 500, 5 000, 50 000 ng/ml) were added into the third passaged corneal fibroblast culture system, and its effect on corneal fibroblast proliferation was measured by MTT method. The results showed that compared with a GAPDH 450 bp band, CTGF RT-PCR product showed a specific 120 bp band as expected. CTGF produced a dose-dependent increase in the proliferation of corneal fibroblasts but it inhibited fibroblast proliferation at higher concentrations (5 000 and 50 000 ng/ml). It was concluded that proliferating corneal fibroblasts produce CTGF and CTGF helps to promote corneal fibroblast proliferation. The results indicated that CTGF might be involved in the corneal wound healing after photorefractive keratectomy in which corneal fibroblasts are activated to proliferate and secrete growth factors that in turn promote corneal fibroblast proliferation.

Innate Immunity in the Development of Connective Tissue Dysplasia: Pilot Study in Children with Congenital Hip Dislocation

Introduction: Observing and treatment of hip dysplasia in children have always been in the sphere of interest of modern molecular medicine. The role of molecular factors in the formation of connective tissue dysplasia in children is considered crucial for such multisystem disorders, and connective tissue dysplasia progressing involves immune system parameters and biochemical markers. The aim of this work was to establish the relationship between immune status indicators and biochemical markers of connective tissue using bioinformatics and modeling methods. Materials and Methods: 27 patients with congenital hip dislocation, admitted to the University Clinic of Privolzhsky Research Medical University, Department of children orthopedics for surgical treatment, were examined. Determination of 10 blood parameters was conducted by modern biochemical and immunological methods. Statistica 12.0 software from StatSoft was used for statistical data processing. Methods of nonparametric statistics were used since the samples in the control group partially follow the normal distribution. Correlation methods and regression modeling methods were used to evaluate the relationship of indicators. Results and Conclusion: In our investigation we have shown the presence of statistical and mathematical interactions between the parameters of innate immunity and indicators of connective tissue metabolism. The leading role of the immune system in the development of pathologies associated with connective tissue dysplasia is assumed. In further investigations it is necessary to clarify the role hypoxia in HIF-1 stimulated control of skeletal dysplasia, collagen modification, connective tissue dysplasia development.

Effects of connective tissue growth factor and collagen type Ⅰ scleroderma

Objective： To investigate the effects of connective tissue growth factor（CTGF） and collagen type I（COL-I） on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Methods： 12 mice model of scleroderma was established by the injection of Bleomycin. The level of CTGF and COL-I were detected by immunohistochemical method. The relationship was analyzed between CTGF and COL-I level. As control group, 12 healthy mice were selected. Results： The levels of CTGF and COL-I in sclerotic models were higher than in normal controls （P 〈 0.05）. It was found that there was a correlation between the level of CTGF and COL-I. Conclusion： CTGF and COL-I played an important role in the hardening process of the skin lesions of the mice model, which may be involved in the pathogenesis of scleroderma.

Connective Tissue Diseases on the Elderly Population in Dakar Hospital Setting

Introduction: Immunosenescence contributes to the development of auto-antibodies. However, while the prevalence of some autoantibodies increases with age, the incidence of connective tissue diseases decreases with age. This study aims to determine the clinical and paraclinical characteristics of connective tissue diseases in the elderly population. Materials and Methods: We conducted a retrospective and descriptive study, from March 2010 to March 2021, in the Internal Medicine Department of Aristide Le Dantec Hospital, including all the medical records of patients followed up for connective tissue disease and whose symptomatology began at an age greater than or equal to 65 years. Epidemiological, clinical, paraclinical, therapeutic and evolutionary data were collected from a pre-established survey form and then processed using SPSS software. Results: Overall, 22 cases were collected out of 275 seen on consultation. They involved 16 women and 6 men, aged between 65 and 85 years with a median of 70 years. The mean duration of the clinical picture was 15.7 months with extremes of 1 and 96 months. The clinical symptoms were joint pain in 21 patients associated with dry eye and mouth syndrome in seven cases and one patient underwent isolated dry eye and mouth syndrome. Joint involvement was deforming in 13 patients. Poor general condition was noted in 20 patients. Biology showed anemia in 14 patients, hyperleukocytosis (2 patients) and thrombocytosis (5 patients). The sedimentation rate (SR) was accelerated in 9 patients and the C-reactive protein (CRP) was positive in 12 patients. Immunology showed a positive Latex test (3 patients/6), Waaler-Rose reaction (8 patients/13), anti-cyclic citrullinated peptides (anti-CCP) antibodies (11 patients/11), anti-nuclear antibodies (2 patients/4). Anti-extractable nuclear antigens (anti-ENA) antibody testing in 4 patients showed positive anti-U1RNP (1 case), anti-SSA and anti-SSB (1 case). Plain X-Rays of the hands, wrists and feet showed destructive lesions in 16 patients. The diagnosis of rheumatoid arthritis (RA) was set in 21 patients, one of which was associated with Sjogren’s syndrome (SS) and one with primary Sjogren’s syndrome. Treatment was based on prednisone (21 cases), methotrexate (17 patients), and hydroxychloroquine (9 patients). The evolution was remarkable in 10 patients. Conclusion: Autoimmune diseases in the elderly are uncommon compared to the young adult population. In our study, we only found cases of rheumatoid arthritis and Sjogren’s syndrome. As the population ages, connective tissue diseases may be increasingly diagnosed.

COVID-19 Induced Mixed Connective Tissue Disease (MCTD)—Case Report

Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder that damages multiple organs simultaneously and is associated with chronic inflammation, in which the signs of systemic sclerosis, systemic lupus erythematosus, and polymyositis can co-occur. Its distinctive feature and the basis for the diagnosis of MCTD is the presence of an antibody against the uridine-rich RNP of the cell nucleus (Anti-U1-RNP). It has been observed that intercurrent infections can trigger autoimmune diseases, however, the fact that viral infections—such as SARS-CoV-2—induce them is currently poorly understood. The present study raises the etiological role of the SARS-CoV-2 virus in the development of the disease. Authors describe the case of a 38-year-old patient in good general condition, who was diagnosed with mixed connective tissue disease three months after COVID-19 infection.

Targeted treatment strategy for patients with severe pulmonary hypertension secondary to connective tissue diseases

Background:Pulmonary arterial hypertension(PAH)associated with connective tissue diseases(CTD)(CTD-PAH)remains a difficult challenge in clinical practice.We aimed to evaluate the effects of targeted vasodilators in patients with severe CTD-PAH.Methods:The data of 53 patients with severe CTD-PAH hospitalized at the Department of Rheumatology and Immunology,The Affiliated Drum Tower Hospital of Nanjing University Medical School,were retrospectively reviewed.Patients were followed up for an average of 2 years to track their outcomes.The efficacy of treatment and the survival rate of patients with severe CTD-PAH were determined.Results:Among the causes of severe CTD-PAH,systemic lupus erythematosus(SLE)was the most common(39.6%),and the age at onset in patients with SLE-PAH was younger than that of patients with other CTD.Bosentan was more effective than sildenafil in reducing pulmonary artery pressure,improving cardiac function,and increasing survival time.Combination therapy with targeted vasodilators significantly improved the prognosis of patients with severe CTD-PAH compared with monotherapy.Conclusions:Patients with severe CTD-PAH should be treated early with targeted vasodilators.In this study,bosentan was superior to sildenafil.Combined treatment might be an option for severe CTD-PAH.

Metagenomic next-generation sequencing for pneumocystis jirovecii pneumonia in patients with connective tissue disease

Background:Accurate diagnosis of Pneumocystis jirovecii pneumonia(PJP)is challenging,and the delayed diagnosis of PJP is associated with high mortality in patients with connective tissue disease(CTD).Metagenomic next-generation sequencing(mNGS)technology facilitates etiological diagnosis of various infectious diseases,with promising application in diagnosing PJP.This study aimed to investigate the value of mNGS using bronchoalveolar lavage fluid(BALF)for diagnosing PJP infection.Methods:Data from 55 patients with CTD and suspected pulmonary infection was retrospectively collected and analysed.A PJP group and non-PJP group were formed.The clinical manifestations,laboratory test results,treatment methods,and outcomes were summarized.BALF mNGS results were compared with traditional pathogen tests(TPT)and serum 1,3-beta-D-glucan(BDG)testing.Results:The mean age of PJP patients was 54 years,and 59%(10/17)of the patients were female.A significant difference was found between the average daily dose of prednisone administered to the PJP group and non-PJP group(25 mg vs.16 mg,P<0.001).The PJP group had a significantly higher incidence of dyspnoea(88%[15/17]vs.16%[6/38],P<0.001)and elevated serum BDG level(167.73 vs.30.67 pg/mL,P<0.001).BALF mNGS was more sensitive than both TPT(100%[95%confidence interval{CI}:77.1%-100%]vs.11.8%[95%CI:2.1%-37.7%],P<0.001)and serum BDG(100%[95%CI:77.1%-100%]vs.85.7%[95%CI:42%-99.2%],P<0.001).BALF mNGS was more specific than serum BDG(89.5%[95%CI:74.3%-96.6%]vs.46.7%[95%CI:22.3%-72.6%],P=0.493).Co-infection with cytomegalovirus(CMV)was more common in the PJP patients than in the non-PJP patients(59%[10/17]vs.11%[4/38],respectively,P<0.001).Conclusion:BALF mNGS technology is highly effective for diagnosing PJP in patients with CTD and identifying co-infections.

Effect of high glucose, angiotensin Ⅱ and receptor antagonist Losartan on the expression of connective tissue growth factor in cultured mesangial cells

To observe the effect of high glucose, angiotensin Ⅱ (AngⅡ) and Losartan on the expression of connective tissue growth factor (CTGF) mRNA in cultured mesangial cells (MCs) Methods MCs of SD rats were isolated and cultured High glucose (30 mmol/L) and AngⅡ (10 -9 , 10 - 7 , and 10 -5 mol/L) were added to the medium for 72 hours to observe the influence on CTGF mRNA expression Losartan of 10 -5 mol/L and AngⅡ of 10 -5 mol/L were added to the medium to observe the effects of Losartan on CTGF mRNA expression stimulated by AngⅡ The expressions of CTGF mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR) Results RT-PCR showed that high glucose and AngⅡ up-regulated the expression of CTGF mRNA, and AngⅡ stimulated the expression in a dose-dependent manner Expression of CTGF mRNA induced by AngⅡwas partially suppressed by 10 -5 mol/L Losartan (P<0 05) Conclusions High glucose and AngⅡ can enhance the expression of CTGF mRNA and thus be involved in the process of renal fibrosis Losartan can have a partial fibrogenesis-inhibiting effect, with implications for the treatment of renal fibrosis

Connective tissue growth factor is associated with the early renal hypertrophy in uninephrectomized diabetic rats

Background Renal hypertrophy has been regarded as the early feature of diabetic nephropathy （DN）, which may eventually lead to proteinuria and renal fibrosis. However, the exact mechanism of renal hypertrophy is still unclear. The aim of this study was to investigate the possible association of connective tissue growth factor （CTGF） with renal hypertrophy in uninephrectomized diabetic rats. Methods Seventy-two Sprague-Dawley （SD） rats were randomly divided into two groups： control group （group C, n=32） and diabetic nephropathy （group DN, n=40）. Each group was re-divided into 4 subgroups according to the experimental period. The rats were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Diabetes was induced by intraperitoneal injection of streptozotocin （STZ） after rats had received uninephrectomy. Blood glucose （BG）, body weight （BW）, 24-h urinary albumin excretion （24hUalb）, kidney weight （KW）, KW/BW, glomerular tuft area （AG）, glomerular tuft volume （VG）, proximal tubular area （AT） at each time point, the width of glomerular basement membrane （GBM） and tubular basement membrane （TBM） at week 8 were measured when the rats were sacrificed. Renal expression of CTGF and p27kipl were detected by immnnohistochemical staining. The relationship between CTGF expression and increasing of VG and AT was analyzed. Results There was a significant increase of 24hUalb, KW, and KW/BW from week 1 onward in diabetic rats compared to those in group C （P〈0.05, respectively）, diabetic rats also had a significant increase of AG, VG, and AT from week 1 onward. It was also shown that diabetic rats had a thickening of GBM [（245.7±103.0） nm vs （121.8±19.1） nm, P〈0.01] and TBM [（767.7±331.1） nm vs （293.0±110.5） nm, P〈0.01] at week 8. There was a weak expression for CTGF and p27kipl in normal glomeruli and tubuli, while a significant increasing expression of CTGF and p27kipl was found in glomeruli and tubuli in diabetic kidney from week 1 onward （P〈0.05, respectively）, and the extent of CTGF expression was positively correlated with AG （r=0.92, P〈0.05）, VG （r=0.86, P〈0.05）, AT （r=0.94, P〈0.01） and positively correlated with the expression of p27kipl （r=0.96, P〈0.01）. Conclusion The expression of CTGF increases in diabetic rat kidney at the early stage, which might be an important mediator of renal hypertrophy through arresting cell cycling.