[The influence of diet therapy and regular physical trainings on monocyte chemoattractant protein-1 (MCP-1) secretion by monocytes among obese patients with coronary heart disease].

Chronic systemic inflammation is one of the leading pathogenetic pathways for the development of atherosclerosis in obese patients. In this regard, it seems promising to evaluate the effect of the diet and physical exertion on the proinflammatory activity of monocytes. The purpose of this research was to evaluate the effect of the diet and regular physical trainings on the secretion of monocyte chemotactic factor 1 (MCP-1) by monocytes in obese patients with coronary artery disease. Material and methods. 27 obese participants (body mass index >30 kg/m2) with a confirmed diagnosis of coronary heart disease were recruited. All participants were prescribed with 12 weeks of a specialized diet with a restriction of simple carbohydrates and salt, a 500-kcal daily energy deficit, and with inclusion of cruciferous (200 g per day), seasonal dark berries (70 g per day) and green tea (200 ml per day). The regular assisted physical trainings were also administered. The body composition, blood biochemical parameters and MCP-1 secretion rates in the primary culture of monocytes isolated from blood samples via the immunomagnetic separation method were assessed before and after the intervention. Results. As a result, after the 12-weeks intervention the reliable body weight loss (-4.0%), waist circumference (-4.2%), visceral fat (-5.4%), total cholesterol (-9.8%), LDL-cholesterol (-16.6%) and triglycerides (-26.0%), an improvement in the results of the 6-minute walk test (+10.33%) was achieved, as well as an LPS-stimulated monocytes secretion of MCP-1 decreased by 2.8 times (p=0.005). Conclusion. Overall, the results suggest that diet and regular physical activity in patients with obesity and coronary heart disease may decrease the functional "proinflammatory" activity of monocytes.

First case report of PLA2R-related monotypic (IgG-κ positive) membranous nephropathy concurrent with leukocyte chemotactic factor 2 amyloidosis.

BACKGROUND: Membranous nephropathy (MN) is a major pattern of nephrotic syndrome (NS) in adults. Some MN have secondary causes and some may be accompanied with other glomerular diseases. MN patients coexisting with amyloidosis are very rare, and mostly was polytypic MN. Herein, we describe the first report which identifying monotype PLA2R-MN (κ light chain) concurrent with leukocyte chemotactic factor 2 amyloidosis (ALECT2). This rare case highlights the importance of renal pathology for diagnosis. CASE PRESENTATION: We describe a case of a 60-year-old male patient with persistent proteinuria and low serum albumin for nine months. No monoclonal component was revealed by serum and urine immunofixation electrophoresis but serum PLA2R antibody was positive. The patient was empirically treated with Leflunomide and Losartan, but edema was not improved. The diagnosis of renal pathology is PLA2R-related monotypic (IgG-κ positive) MN concurrent with ALECT2. Methylprednisolone, cyclosporine A and anticoagulant (rivaroxaban) were prescribed resulting in a complete remission of NS. CONCLUSIONS: MN patients concurrent with ALECT2 presented massive proteinuria or NS. When nephrotic range proteinuria is present in ALECT2, it is important to consider that it may be due to a concomitant underlying nephropathy especially MN and treated according to MN will get good therapeutic effect.

From lymphatic endothelial cell migration to formation of tubular lymphatic vascular network.

During development, lymphatic endothelial cell (LEC) progenitors differentiate from venous endothelial cells only in limited regions of the body. Thus, LEC migration and subsequent tube formation are essential processes for the development of tubular lymphatic vascular network throughout the body. In this review, we discuss chemotactic factors, LEC-extracellular matrix interactions and planar cell polarity regulating LEC migration and formation of tubular lymphatic vessels. Insights into molecular mechanisms underlying these processes will help in understanding not only physiological lymphatic vascular development but lymphangiogenesis associated with pathological conditions such as tumors and inflammation.

Concurrence of leukocyte chemotactic factor 2-associated amyloidosis and autoimmune diseases: A case report.

Leukocyte chemotactic factor 2-associated (ALECT2) amyloidosis is one of the recently reported types of amyloidosis, which is caused by the extracellular deposition of leukocyte chemotactic factor 2 (LECT2). There have not been any reports involving the concurrence of ALECT2 amyloidosis with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE)s. Herein, we report a case of a 68-year-old Chinese woman presenting with long duration of sicca symptoms. The clinical evaluation and laboratory findings showed that she had SS overlapped with SLE. Kidney biopsy revealed a membranoproliferative glomerulonephritis (MPGN) with glomerular deposition of dominant IgG3-kappa by immunofluorescene, which was related to SS/SLE. Furthermore, patchy congophilic amyloid deposits in the tubulointerstitium were detected, which were positive for LECT2 protein by immunohistochemical staining and immunoelectron microscopy. This is the first case of ALECT2 amyloidosis that coexisted with SS/SLE, and the causal relationship between ALECT2 amyloidosis and autoimmune diseases remain unclear.

Clinicopathological characteristics of renal amyloid leukocyte chemotactic factor 2 amyloidosis / 中华肾脏病杂志

Objective:To investigate the clinicopathological characteristics of renal leukocyte chemotactic factor 2 amyloidosis (ALECT2).Methods:The patients with renal ALECT2 diagnosed by renal biopsy in Peking University First Hospital, Shanxi Medical University Second Hospital and Shanxi Bethune Hospital from January 2001 to October 2021 were retrospectively enrolled. According to whether the patients had concurrent glomerular diseases, they were classified into two groups: isolated ALECT2 group and ALECT2 with concurrent renal diseases group. Clinicopathological data of the two groups were compared. Light microscopy, immunofluorescence and immunoelectron microscopy were applied to investigate pathological characteristics of renal tissues. Mass spectrometry was used to analyze the composition of renal amyloid deposits. Gene sequencing was employed to detect the leukocyte chemotactic factor 2 ( LECT2) gene sequence in peripheral blood of the patients. Results:Sixteen patients with ALECT2 were enrolled in this study and nine of them had concurrent renal diseases. The age of 16 patients was (65.00±8.45) years old. The sex ratio of males to females was 7 to 9. Most of patients were Han ethnicity (15/16). Eight patients came from Shanxi province. Fifteen patients presented with varying degree of proteinuria [2.16(1.07, 4.72) g/24 h]; 5 patients had nephrotic syndrome; 11 patients had renal insufficiency; 12 patients had microscopic hematuria. Part of patients also had hypertension (12/16) and diabetics (6/16). Compared with isolated ALECT2, the ALECT2 group with concurrent renal diseases had a higher proportion of nephrotic syndrome (5/9 vs 0/7, P=0.034). Renal biopsy results showed that all patients (16/16) had amyloid deposits in the interstitium of renal cortex with varying degree of inflammatory cell infiltration and fibrosis, and glomeruli (12/16) and arterioles (14/16) were involved by amyloid deposits. The amyloid deposits were strongly congophilic and immunohistochemistry for LECT2 was positive. By semi-quantitative analysis, the proportions of glomerular and overall amyloid loads in ALECT2 with concurrent renal diseases group were lower than those in isolated ALECT2 group (both P<0.05). Electron microscopy revealed randomly oriented and non-branching fibrils with a diameter of 8-12 nm. The LECT2 peptides were detected by mass spectrometry in renal amyloid deposits of 8 patients, and homozygous G allele of LECT2 was found in 7 patients by gene sequencing. Complete follow-up data of 13 patients showed that 2 patients died, 1 patient developed end-stage renal disease at the time of renal biopsy, and most of the rest patients had stable renal function (8/10). Conclusions:Patients with renal ALECT2 mainly present with proteinuria, along with a high incidence of renal insufficiency, microscopic hematuria, and concurrent renal diseases. The pathologic feature is the preferential deposition of amyloid in renal cortical interstitium.

Leukocyte chemotactic factor 2-related amyloidosis presenting with severe jaundice and hepatic encephalopathy.

Amyloidosis is a well-known disease with various types and subtypes. One of the most recently identified types is leukocyte chemotactic factor 2 amyloidosis (LECT 2), which was found to be common in certain ethnic backgrounds. It is suggested that the diagnosis of this type is vital to prevent any therapy-related complications when it is erroneously diagnosed as AL amyloidosis. The clinical presentation is usually slowly progressive kidney disease and mild hepatic impairment. We report a case of LECT2 amyloidosis, which presented with severe painless cholestasis and hepatic encephalopathy alongside progressive kidney disease.

Lysophosphatidylglucoside is a GPR55 -mediated chemotactic molecule for human monocytes and macrophages.

Neutrophils undergo spontaneous apoptosis within 24-48 h after leaving bone marrow. Apoptotic neutrophils are subsequently phagocytosed and cleared by macrophages, thereby maintaining neutrophil homeostasis. Previous studies have demonstrated involvement of lysophosphatidylglucoside (lysoPtdGlc), a degradation product of PtdGlc, in modality-specific repulsive guidance of spinal sensory axons, via its specific receptor GPR55. In the present study, using human monocytic cell line THP-1 as a model, we demonstrated that lysoPtdGlc induces monocyte/macrophage migration with typical bell-haped curve and a peak at concentration 10-9 M. Lysophosphatidylinositol (lysoPtdIns), a known GPR55 ligand, induced migration at higher concentration (10-7 M). LysoPtdGlc-treated cells had a polarized shape, whereas lysoPtdIns-treated cells had a spherical shape. In EZ-TAXIScan (chemotaxis) assay, lysoPtdGlc induced chemotactic migration activity of THP-1 cells, while lysoPtdIns induced random migration activity. GPR55 antagonist ML193 inhibited lysoPtdGlc-induced THP-1 cell migration, whereas lysoPtdIns-induced migration was inhibited by CB2-receptor inverse agonist. SiRNA experiments showed that GPR55 mediated lysoPtdGlc-induced migration, while lysoPtdIns-induced migration was mediated by CB2 receptor. Our findings, taken together, suggest that lysoPtdGlc functions as a chemotactic molecule for human monocytes/macrophages via GPR55 receptor, while lysoPtdIns induces random migration activity via CB2 receptor.

Rap1 Is Essential for B-Cell Locomotion, Germinal Center Formation and Normal B-1a Cell Population.

Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM+ cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.

Chemokine CCL21 in anterior cingulate cortex is involved in chronic neuropathic pain in a rat model / 中国组织工程研究

BACKGROUND: The pathogenesis of chronic pathological pain is yet unknown. Some studies have shown that after spinal cord injury, CCL21 can activate microglia in the central nervous system and is expressed only in damaged neurons, promoting the formation of chronic pathological pain. OBJECTIVE: To investigate whether the anterior cingulate cortex is involved in the formation of chronic pathological pain after inferior orbital nerve ligation in rats, and whether blocking chemokine CCL21 in the anterior cingulate cortex can reduce the chronic neuropathic pain. METHODS: A total of 80 male Sprague-Dawley rats were randomly divided into 4 groups with 20 rats in each group. In the sham group, only the infraorbital nerve of the rats was exposed; in the model group, the left infraorbital nerve was ligated; in the anti-CCL21 group, CCL21 neutralizing antibodies was administered to the anterior cingulate cortex of the rats on the 7th day after surgery; and in the PBS control group, PBS solution was given into the anterior cingulate cortex of rats on the 7th day after surgery. Rats in the sham and model groups were subjected to behavioral tests on the 3rd, 5th, 7th, and 14th days after surgery, and those in the anti-CCL21 and PBS control groups were subjected to the behavioral test at 6 hours after administration. All rats were sacrificed under anesthesia after behavioral tests. The cortical tissues were taken from the anterior cingulate, and the protein content of CCL21 was determined by western blot and immunofluorescence. RESULTS AND CONCLUSION: The pain threshold of the rats in the model group was lower than that in the sham group, and the expression of CCL21 in the anterior cingulate cortex was significantly higher in the model group than the sham group. After the administration of CCL21 neutralizing antibody, the expression of CCL21 was reduced to some extents, and the rat pain threshold was increased accordingly. These findings reveal that the anterior cingulate cortex of rats may be involved in the production of chronic pathological pain, and the administration of CCL21 neutralizing antibody can relief the pain.

Research progress of cytokines in wound healing / 中国临床药理学与治疗学

A variety of cytokines work synergistically to participate in wound healing. Although there are many studies on cytokines, the current clinical use of cytokines to treat wounds has not achieved the desired effect. The sequential administration of cytokines or the study of its drug delivery system may be its strategy to promote chronic wound healing. This article reviews the research progress of major growth factors, chemokines and inflammatory factors in wound repair in recent years.

Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis.

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is the third most common cause of amyloid nephropathy presenting with chronic kidney disease and variable proteinuria. We report a novel mutation in the FAN1 gene causing KIN and to our knowledge, the first case of concurrent KIN and ALECT. CASE PRESENTATION: We describe the case of 44 year old Pakistani woman, presenting with stage four non-proteinuric chronic kidney disease, and a brother on dialysis. Renal biopsy demonstrated KIN and concurrent ALECT2. Genetic sequencing identified a novel FAN1 mutation as the cause of her KIN and she is being managed conservatively for chronic kidney disease. Her brother also had KIN with no evidence of amyloidosis and is being worked up for kidney transplantation. CONCLUSION: This case highlights two rare causes of chronic kidney disease considered underdiagnosed in the wider population due to their lack of proteinuria, and may contribute to the cohort of patients reaching end stage renal disease without a renal biopsy. We report a novel mutation of the FAN1 gene causing KIN, and report the first case of concurrent KIN and ALECT2. This case highlights the importance of renal biopsy in chronic kidney disease of unclear aetiology which has resulted in a diagnosis with implications for kidney transplantation and family planning.

Renal leukocyte chemotactic factor 2 (ALECT2)-associated amyloidosis in Chinese patients.

Background: Leukocyte chemotactic factor 2 (ALECT2) amyloidosis is one of the recently described types of amyloidosis. In this study, we reported the first large case series of renal ALECT2 amyloidosis in Chinese patients.Methods: We studied the prevalence, clinical characteristics, renal pathology, outcome and genetic features among seven patients diagnosed with renal ALECT2 amyloidosis at Peking University First Hospital of China from 2000 to 2018.Results: Seven patients were diagnosed with ALECT2 amyloidosis, representing 1.9% of the renal biopsy-proven amyloidosis cases. The mean age at diagnosis was 68 years without gender preference. The patients mainly manifested with varying impaired kidney function with a mean estimated glomerular filtration rate of 42.7 mL/min/1.73 m2 (range 8.0-80.5) and proteinuria at 3.9 g/24 h (range 0.4-11.3). There were four ALECT2 amyloidosis patients with concurrent membranous nephropathy (MN), who presented a higher proteinuria (6.4 ± 4.0 g/24 h vs. 2.0 ± 1.8 g/24 h) and higher frequency of nephrotic syndrome (50% vs. 0) than patients with isolated ALECT2 amyloidosis. Renal biopsy showed strongly congophilic amyloid deposits distributed mainly in the renal cortical interstitium, as well as the glomerular mesangium, the inner layer of glomerular basement membrane (GBM), and vascular walls. Two patients with concurrent ALECT2 amyloidosis and MN showed mild amyloid deposits, which have not been identified as ALECT2 amyloidosis by IHC and LMD/MS methods. All patients were corroborated by immunoelectron microscopy to exhibit the specific location of LECT2 in the amyloid fibrils. Genetic analysis revealed no mutations but homozygosity for the G allele encoding valine at position 40 in the mature protein in all patients. Except for one patient who died 8 years later after he was diagnosed with ALECT2 amyloidosis, the others presented with relatively stable renal function during the mean follow-up period of 12.5 months.Conclusions: ALECT2 amyloidosis was the third most common type of renal amyloidosis in Chinese patients from a single centre. The majority of ALECT2 amyloidosis patients were of Han ethnicity, with a high rate of concurrent MN. The recognition and accurate diagnosis of renal ALECT2 amyloidosis should be considered in Chinese patients.

Association between potentially functional polymorphisms of chemokine family members and the survival of esophageal cancer patients in a Chinese population.

Background: The chemokine family plays an important role in the growth, invasion, and metastasis of tumors. However, most studies have only focused on a few genes or a few gene loci, and thus could not reveal the associations between functional polymorphisms of chemokine family members and tumor progression. This study aimed to determine the associations between single nucleotide polymorphisms (SNPs) of chemokine family members and the prognosis of esophageal cancer (EC). Methods: The Cox risk proportional model and log-rank test were used to analyze the associations of 16 potentially functional SNPs in 13 genes from the chemokine family with the survival of 729 Chinese patients with EC. Results: Prognostic analysis on the 16 SNPs showed that different genotypes of 5 SNPs were associated with patients' survival and the risk of death. Multivariate Cox regression analysis showed that the risk of death was higher in CCL26rs2302009 genotype A/C carriers than in A/A carriers and it was also higher in CX3CL1rs2239352 genotype T/T carriers than in C/C carriers. Stepwise Cox regression analysis showed that CCL26rs2302009 genotype A/C was an independent prognostic factor of EC, and its association with increased risk of death was stronger in patients who were ≤60 years old, female, with tumors located in the middle part of esophagus, with undifferentiated or poorly differentiated tumors, with early-stage pathologic type disease, with the longest diameter of tumor ≤5cm than in their counterparts. Conclusion: These findings suggest that CCL26rs2302009 may be a candidate biomarker for EC and its effect on death risk are associated with the histological grade, pathologic type, and the longest diameter of tumor.

The Vitamin D Binding Protein and Inflammatory Injury: A Mediator or Sentinel of Tissue Damage?

Neutrophils are the most abundant type of white blood cell in most mammals including humans. The primary role of these cells is host defense against microbes and clearance of tissue debris in order to facilitate wound healing and tissue regeneration. The recruitment of neutrophils from blood into tissues is a key step in this process and is mediated by numerous different chemoattractants. The neutrophil migratory response is essential for host defense and survival, but excessive tissue accumulation of neutrophils is observed in many inflammatory disorders and strongly correlates with disease pathology. The vitamin D binding protein (DBP) is a circulating multifunctional plasma protein that can significantly enhance the chemotactic activity of neutrophil chemoattractants both in vitro and in vivo. Recent in vivo studies using DBP deficient mice showed that DBP plays a larger and more central role during inflammation since it induces selective recruitment of neutrophils, and this cofactor function is not restricted to C5a, as prior in vitro studies indicated, but can enhance chemotaxis to many chemoattractants. DBP also is an extracellular scavenger for actin released from damaged/dead cells and formation of DBP-actin complexes is an immediate host response to tissue injury. Recent in vitro evidence indicates that DBP bound to G-actin, and not free DBP, functions as an indirect but essential cofactor for neutrophil migration. DBP-actin complexes always will be formed regardless of what initiated an inflammation, since release of actin from damaged cells is a common feature in all types of injury and DBP is abundant and ubiquitous in all extracellular fluids. Indeed, these complexes have been detected in blood and tissue fluids from both humans and experimental animals following various forms of injury. The published data strongly supports the premise that DBP-actin complexes are the functional neutrophil chemotactic cofactor that enhances neutrophil chemotaxis in vitro and augments neutrophilic inflammation in vivo. This review will assess the fundamental role of DBP in neutrophilic inflammation and injury.

LECT2 Amyloidosis in Kidney Transplantation: A Report of 5 Cases.

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently recognized entity that often affects the kidneys. Little information is available regarding kidney transplant outcomes in patients with LECT2 amyloidosis or who received kidney allografts containing LECT2 amyloid. We present clinical findings and allograft outcomes of 5 patients who received kidneys with donor-derived LECT2 amyloidosis. In all 5, LECT2 amyloidosis was discovered during protocol biopsies or in evaluation of suspected rejection. Less than 10% of kidney parenchyma was involved, with mostly interstitial and vascular deposits. Allograft function was not impaired and the amyloid deposits persisted for up to 8 years of follow-up. We conclude that kidneys with limited and localized LECT2 amyloid deposits that are otherwise suitable for transplantation need not be automatically discarded.

De novo leukocyte chemotactic factor 2 amyloidosis in a pediatric renal allograft, 15 years post-transplant.

Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a recently described form of systemic amyloidosis, which most commonly affects the kidney and liver. The LECT2 protein is produced during inflammatory processes, but its precise function in renal diseases in unclear. ALECT2, however, is known to be a relatively common form of renal amyloidosis, after amyloid light chain and serum amyloid A types and is most often seen in patients of Hispanic ethnicity. ALECT2 can occur de novo or as recurrent disease in kidney transplants. We present the first case, to our knowledge, of de novo ALECT2 in a pediatric kidney transplant patient, 15 years post-transplant.

Diagnosis, pathogenesis and outcome in leucocyte chemotactic factor 2 (ALECT2) amyloidosis.

Introduction: Renal biopsy series from North America suggest that leucocyte chemotactic factor 2 (ALECT2) amyloid is the third most common type of renal amyloid. We report the first case series from a European Centre of prevalence, clinical presentation and diagnostic findings in ALECT2 amyloidosis and report long-term patient and renal outcomes for the first time. Methods: We studied the clinical features, diagnostic investigations and the outcome of all patients with ALECT2 amyloidosis followed systematically at the UK National Amyloidosis Centre (NAC) between 1994 and 2015. Results: Twenty-four patients, all non-Caucasian, were diagnosed with ALECT2 amyloidosis representing 1.3% of all patients referred to the NAC with biopsy-proved renal amyloid. Diagnosis was made at median age of 62 years, usually from renal histology; immunohistochemical staining was definitive for ALECT2 fibril type. Median estimated glomerular filtration rate (GFR) at diagnosis was 33 mL/min/1.73 m2 and median proteinuria was 0.5 g/24 h. Hepatic amyloid was evident on serum amyloid P component (SAP) scintigraphy in 11/24 cases but was not associated with significant derangement of liver function. No patient had evidence of cardiac amyloidosis or amyloid neuropathy. Median follow-up was 4.8 (range 0.5-15.2) years, during which four patients died and four progressed to end-stage renal disease. The mean rate of GFR loss was 4.2 (range 0.5-9.6) mL/min/year and median estimated renal survival from diagnosis was 8.2 years. Serial SAP scans revealed little or no change in total body amyloid burden. Conclusions: ALECT2 amyloidosis is a relatively benign type of renal amyloid, associated with a slow GFR decline, which is reliably diagnosed on renal histology. Neither the molecular basis nor the factors underlying the apparent restriction of ALECT2 amyloidosis to non-Caucasian populations have been determined.

Inhibitory effects of apolipoprotein M on inflammatory factors induced by high glucose in human retinal vascular endothelial cells / 中华实验眼科杂志

Objective To observe the expressing changes of apolipoprotein M (ApoM),tumor necrosis factor-α(TNF-α) and monocyte chemoattractant protein-1 (MCP-1) in human retinal vascular endothelial cells (HRECs) under the high glucose culture condition and investigate the inhibitory effects of ApoM overepression on the expressions of TNF-α and MCP-1.Methods HRECs were cultured in DMEM containing 10％ fetal bovine serum and 5.5 mmol/L D-glucose and assigned to 6 groups.The cells in the normal control group were cultured in above culture medium;the cells in the high glucose group were treated using the DMEM with 30 mmol/L D-glucose;ApoM was transfected into the cells using lentiviral vector in the ApoM transfected group;lentiviral vector without ApoM sequence was transfected in the empty vector group;the cells transfected by empty vector were cultured in high glucose culture medium in the empty vector+high glucose group;the cells in the ApoM transfection+high glucose group were treated by ApoM sequence transfection and high glucose incubation.The relative expression of ApoM,TNF-α and MCP-1 mRNA was detected using real-time quantitative PCR,and the relative expression of ApoM protein was evaluated using Western blot assay.Results Compared with the normal control group,the mRNA expression levels of ApoM,TNF-α and MCP-1 in the high glucose group were significantly increased (t=5.517,3.295,2.555;all P＜0.05).HRECs grew well after infected with lentivirus.The relative expression level of ApoM mRNA in the ApoM transfected group was 236.400±39.270,which was significantly higher than 1.000±0.153 in the empty vector group (t=5.995,P＜0.01).An enhanced protein band of ApoM was seen in the ApoM transfected group,and the protein band was absent in the empty vector group.The relative expression band in the ApoM transfected group was 1.000± 0.249 and 2.978 ± 0.285 in the cells cultured with normal culture medium or high glucose culture medium,respectively,with a significant difference between them (t =5.056,P＜0.01).The relative expressions of TNF-α and MCP-1 in the mRNA levels were significantly different among the empty vector group,empty vector+high glucose group,ApoM transfected group and ApoM transfection + high glucose group (F =5.966,P =0.026;F =14.410,P =0.002).Compared with the empty vector+high glucose group,the relative expressions of TNF-α and MCP-1 mRNA were considerably reduced in the ApoM transfection+high glucose group (P=0.017,0.004).Conclusions High glucose environment up-regulates the expression of ApoM,MCP-1 and TNF-α in HRECs.Overexpression of ApoM inhibits the up-regulation of MCP-1 and TNF-α expression induced by high glucose.

Effect of calcitriol combined with Kuntai capsule on serum monocyte chemotactic factor -1 and leptin and pregnancy rate of prognosis in patients with polycystic ovary syndrome / 中国综合临床

Objective To investigate the application effect of calcitriol combined with Kuntai capsule in patients with polycystic ovary syndrome. Methods Ninety-seven cases with polycystic ovary syndrome were enrolled in the study and were randomly divided into two groups, 48 cases in the control group were given clomifene citrate capsules, and 49 cases in the observation group were treated with calcitriol combined with Kuntai capsule on the basis of the control group. The treatment effect,endometrial thickness,number of mature follicles,cervical mucus score and sex hormones (luteinizing hormone (LH),androgen,testosterone (T),follicle stimulating hormone (FSH),estradiol (E2)) before and after the treatment,the serum monocyte chemotactic factor -1 (MCP-1) and Leptin level of the two groups were observed and compared. And the rate of pregnancy and the incidence of adverse reactions were recorded. Results The total efficiency of the observation group was 95.92%(47/49),higher than that of the control group (79.17%(38/48))(χ2 ＝6.277,P＝0.012).The endometrial thickness,the number of mature follicles and the cervical mucus score of the observation group were significantly higher than those of the control group(t＝4. 978,7. 175,7. 387,P＜0. 05). After 3 months,the serum levels of T,FSH,LH,MCP-1 and Leptin in the observation group were lower than those in the control group,and the serum E2 level was higher than in the control group(P＜0. 05). The pregnancy rate of the observation group the was 69. 39%( 34/49 ), higher than that of the control group ( 47. 92%( 23/48 )), the difference was statistically significant (χ2＝4. 613,P＝0. 032). The incidence of adverse reactions was 12. 24%(6/49) in the observation group and 8. 33%(4/48) in the control group. There was no significant difference between the two groups(P＞0. 05). Conclusion Calcitriol combined with Kuntai capsule can improve the serum MCP-1,Leptin levels and sex hormone levels in patients with polycystic ovary syndrome,and improve the prognosis of pregnancy rate. Besides,the effect is remarkable with high medication safety.

Hemolytic Uremic Syndrome in Pregnancy and Postpartum.

BACKGROUND: Pregnancy is associated with various forms of thrombotic microangiopathy, including hemolytic uremic syndrome. A previous small French study suggested that pregnancy-associated hemolytic uremic syndrome was to be included in the spectrum of atypical hemolytic uremic syndrome linked to complement alternative pathway dysregulation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We sought to retrospectively analyze the presentation, outcome, and frequency of complement alternative pathway gene variants in a larger international (France, United Kingdom, Italy) cohort of patients with pregnancy-associated hemolytic uremic syndrome. RESULTS: Eighty-seven patients with pregnancy-associated hemolytic uremic syndrome were included. Hemolytic uremic syndrome occurred mainly during the first pregnancy (58%) and in the postpartum period (76%). At diagnosis, 56 (71%) patients required dialysis. Fifty-six (78%) patients underwent plasma exchanges, 21 (41%) received plasma infusions, and four (5%) received eculizumab. During follow-up (mean duration of 7.2 years), 41 (53%) patients reached ESRD, 15 (19%) had CKD, and 18 (28%) patients experienced hemolytic uremic syndrome relapse. Twenty-four patients (27%) received a kidney transplant and a recurrence of hemolytic uremic syndrome occurred in 13 (54%) patients. Variants in complement genes were detected in 49 (56%) patients, mainly in the CFH (30%) and CFI genes (9%). CONCLUSIONS: Pregnancy-associated hemolytic uremic syndrome and atypical hemolytic uremic syndrome nonrelated to pregnancy have the same severity at onset and during follow-up and the same frequency of complement gene variants.