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Objective:To investigate the incidence and risk factors of renal injury in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with poor immune reconstitution.Methods:The HIV infection/AIDS patients with poor immune reconstitution who were visited Second Department of Infection of Hangzhou Xixi Hospital from January to December 2021 were enrolled. The clinical data and laboratory examinations of the patients were collected, and the relevant risk factors were analyzed by logistic regression.Results:Among 303 HIV infection/AIDS patients with poor immune reconstitution, 59(19.5%) patients had renal injury. Logistic regression analysis showed that hypertension (odds ratio ( OR)=0.200, 95% confidence interval (95% CI) 0.065 to 0.618, P=0.005), taking tenofovir ( OR=0.275, 95% CI 0.130 to 0.580, P=0.001), hypoproteinemia ( OR=1.045, 95% CI 1.006 to 1.086, P=0.022), and low CD4 + T lymphocytes level ( OR=1.009, 95% CI 1.003 to 1.014, P=0.001) were risk factors for renal injury. Conclusions:The incidence of renal injury in HIV infection/AIDS patients with poor immune reconstitution is high. Hypertension, taking tenofovir, hypoproteinemia, and low CD4 + T lymphocytes level are risk factors for renal injury in patients.
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Objective:To detect the serum levels of SARS-CoV-2-specific IgM and IgG antibodies in patients infected with SARS-CoV-2 and recipients of inactivated vaccine in different periods for understanding their variation patterns in vivo. Methods:Chemiluminescence immunoassay was used to detect the levels of SARS-CoV-2-specific IgM and IgG antibodies in 144 serum samples of 44 COVID-19 patients, 381 serum samples of 118 asymptomatic infected cases and 398 serum samples of 273 inactivated vaccine recipients collected at different periods. The results were statistically analyzed together with basic characteristics and vaccination status.Results:The positive rates of IgM antibody in COVID-19 patients, asymptomatic infected cases and inactivated vaccine recipients were 52.27% (23/44), 23.73% (28/118) and 14.29% (39/273). The positive rate of IgM antibody was higher in COVID-19 patients than in asymptomatic infected cases and vaccine recipients (χ 2=12.106, P=0.001; χ 2=34.755, P<0.001). The positive rates of IgG antibody in the three populations were 100.00% (44/44), 97.46% (115/118) and 98.81% (166/168), and the differences were not statistically significant (χ 2=2.944, P=0.229). In COVID-19 patients, the concentration of IgM antibody in <40 years old group was lower than that in ≥40 years old group (Waldχ 2=6.609, P=0.010), and the concentration of IgG antibody in patients with vaccination was higher than that in patients without vaccination (Waldχ 2=12.402, P<0.001). In asymptomatic infected cases, the concentration of IgG antibody was higher in people with vaccination than in those without vaccination (Waldχ 2=4.530, P=0.033). In SARS-CoV-2 vaccine recipients, the concentration of IgG antibody in <40 years old group was higher than that in ≥40 years old group (Waldχ 2=9.565, P=0.002). Dynamic analysis of antibody levels showed that from week 1 to week 9, the concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and vaccine recipients. Conclusions:The concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and inactivated vaccine recipients. COVID-19 patients aged ≥40 years had higher level of IgM antibody. COVID-19 patients and asymptomatic infected cases who had received vaccination had higher concentration of IgG antibody. Inactivated vaccine showed good immunogenicity after whole course of immunization, and the IgG antibody level in <40 years old group was higher.
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Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45 + cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/ MPN patients is warranted.
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Administration of black raspberries (BRBs) and their anthocyanin metabolites, including protocatechuic acid (PCA), has been demonstrated to exert chemopreventive effects against colorectal cancer through alteration of innate immune cell trafficking, modulation of metabolic and inflammatory pathways, etc. Previous research has shown that the gut microbiome is important in the effectiveness of chemoprevention of colorectal cancer. This study aimed to assess the potency of PCA versus BRB dietary administration for colorectal cancer prevention using an Apc Min/+ mouse model and determine how bacterial profiles change in response to PCA and BRBs. A control AIN-76A diet supplemented with 5% BRBs, 500 ppm PCA, or 1,000 ppm PCA was administered to Apc Min/+ mice. Changes in incidence, polyp number, and polyp size regarding adenomas of the small intestine and colon were assessed after completion of the diet regimen. There were significant decreases in adenoma development by dietary administration of PCA and BRBs in the small intestine and the 5% BRB-supplemented diet in the colon. Pro-inflammatory bacterial profiles were replaced with anti-inflammatory bacteria in all treatments, with the greatest effects in the 5% BRB and 500 ppm PCA-supplemented diets ac-companied by decreased COX-2 and prostaglandin E 2 levels in colonic mucosa. We further showed that 500 ppm PCA, but not 1,000 ppm PCA, increased IFN-γ and SMAD4 levels in primary cultured human natural killer cells. These results suggest that both BRBs and a lower dose PCA can benefit colorectal cancer patients by inhibiting the growth and proliferation of adenomas and promoting a more favorable gut microbiome condition.
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The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human natural defense mechanisms against SARS-CoV-2 are largely unknown. Serine proteases (SPs) including furin and TMPRSS2 cleave SARS-CoV-2 spike protein, facilitating viral entry. Here, we show that FXa, a SP for blood coagulation, is upregulated in COVID-19 patients compared to non-COVID-19 donors and exerts anti-viral activity. Mechanistically, FXa cleaves the SARS-CoV-2 spike protein, which prevents its binding to ACE2, and thus blocks viral entry. Furthermore, the variant B.1.1.7 with several mutations is dramatically resistant to the anti-viral effect of FXa compared to wild-type SARA-CoV-2 in vivo and in vitro. The anti-coagulant rivaroxaban directly inhibits FXa and facilitates viral entry, whereas the indirect inhibitor fondaparinux does not. In a lethal humanized hACE2 mouse model of SARS-CoV-2, FXa prolonged survival while combination with rivaroxaban but not fondaparinux abrogated this protection. These preclinical results identify a previously unknown SP function and associated anti-viral host defense mechanism and suggest caution in considering direct inhibitors for prevention or treatment of thrombotic complications in COVID-19 patients.
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The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response. One Sentence SummaryA herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression
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Chimeric antigen receptors (CARs) are artificial receptors introduced mainly into T cells. CAR-induced immune cell (CARi) products have achieved impressive success rates in treating some difficult-to-treat hematological malignancies. Here, we describe effects of the global COVID-19 pandemic on CARi publication landscape. Due to the pandemic, the total number of publications decreased in 2020 compared to 2019 in all fields of cancer immunotherapy except CARi. Nearly exponential increases in the number of CARi publications slowed-down in 2020 for the first time in the past 11 years. There were more CARi than coronavirus publications until 2020 when coronavirus publications increased over 5,000% compared to 2019 (575 publications in 2019 vs. 30,390 in 2020). Unlike cancer immunotherapy where the majority of the publications consist of conference abstracts and review articles, majority of the coronavirus publications are original research articles. There are more coronavirus publications in Pubmed than Embase. The opposite is true for CARi publications. Our analysis of the data from the FDA Adverse Event Reporting System (FAERS) show significantly higher death rate in patients treated with Kymirah than Yescarta (28.14% vs. 16.02%). Kymirah and Yescarta are the two main CAR T cell products for treatment of DLBCL and/or B-ALL. However, despite being highly significant, this result is not easily interpretable due to multiple confounding variables in the FAERS data. Our analysis additionally suggest that the significant effects of co-stimulatory domains (4-1BB vs. CD28) consistently reported in preclinical studies do not translate into clinical results. Our manual curation of the CARi publications in PubMed shows that only 5.2% of the publications report results from CARi clinical trials, although we found 663 clinical trials listed on ClinicalTrials.gov database. In conclusion, publication landscape in CARi as well as other fields of cancer immunotherapy has changed due to the global COVID-19 pandemic. This trend will likely continue in the near future. CARi research is now in need of increased measures by publishers to reduce repetitive and/or duplicate publications and more stringent criteria for data entry into public databases including PubMed, Embase, ClinicalTrials.gov, and FAERS to advance this important field of medical research.
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A comprehensive analysis and characterization of a SARS-CoV-2 infection model that mimics non-severe and severe COVID-19 in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18-hACE2 mouse model expressing human (h)ACE2 in mice, controlled by the human keratin 18 (K18) promoter, in epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found that intranasal inoculation with higher viral doses (2x103 and 2x104 PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lungs, liver, and kidney, while lower doses (2x101 and 2x102 PFU) led to less severe tissue damage and some mice recovered from the infection. In this humanized hACE2 mouse model, SARS-CoV-2 infection damaged multiple tissues, with a dose-dependent effect in most tissues. Similar damage was observed in biopsy samples from COVID-19 patients. Finally, the mice that recovered after infection with a low dose of virus also survived rechallenge with a high dose of virus. Compared to other existing models, the K18-hACE2 model seems to be the most sensitive COVID-19 model reported to date. Our work expands the information available about this model to include analysis of multiple infectious doses and various tissues with comparison to human biopsy samples from COVID-19 patients. In conclusion, the K18-hACE2 mouse model recapitulates both severe and non-severe COVID-19 in humans and can provide insight into disease progression and the efficacy of therapeutics for preventing or treating COVID-19. ImportanceThe pandemic of COVID-19 has reached 112,589,814 cases and caused 2,493,795 deaths worldwide as of February 23, 2021, has raised an urgent need for development of novel drugs and therapeutics to prevent the spread and pathogenesis of SARS-CoV-2. To achieve this goal, an animal model that recapitulates the features of human COVID-19 disease progress and pathogenesis is greatly needed. In this study, we have comprehensively characterized a mouse model of SARS-CoV-2 infection using K18-hACE2 transgenic mice. We infected the mice with low and high doses of SARS-CoV-2 virus to study the pathogenesis and survival in response to different infection patterns. Moreover, we compared the pathogenesis of the K18-hACE2 transgenic mice with that of the COVID-19 patients to show that this model could be a useful tool for the development of anti-viral drugs and therapeutics.
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Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (ApcMin/+). FFAR2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, ApcMin/+, and ApcMin/+-Ffar2-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the ApcMin/+-Ffar2-/- mice compared to the ApcMin/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, longchain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that FFAR2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.
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Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (ApcMin/+). FFAR2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, ApcMin/+, and ApcMin/+-Ffar2-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the ApcMin/+-Ffar2-/- mice compared to the ApcMin/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, longchain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that FFAR2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.
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A high-resolution understanding of the antibody response to SARS-CoV-2 is important for the design of effective diagnostics, vaccines and therapeutics. However, SARS-CoV-2 antibody epitopes remain largely uncharacterized, and it is unknown whether and how the response may cross-react with related viruses. Here, we use a multiplexed peptide assay ( PepSeq) to generate an epitope-resolved view of reactivity across all human coronaviruses. PepSeq accurately detects SARS-CoV-2 exposure and resolves epitopes across the Spike and Nucleocapsid proteins. Two of these represent recurrent reactivities to conserved, functionally-important sites in the Spike S2 subunit, regions that we show are also targeted for the endemic coronaviruses in pre-pandemic controls. At one of these sites, we demonstrate that the SARS-CoV-2 response strongly and recurrently cross-reacts with the endemic virus hCoV-OC43. Our analyses reveal new diagnostic and therapeutic targets, including a site at which SARS-CoV-2 may recruit common pre-existing antibodies and with the potential for broadly-neutralizing responses.
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Freshwater snail is an important biological group in aquatic ecosystem and an intermediate host of many parasites. Intestinal flora plays an important role in animal energy metabolism and resistance to pathogens. We analyzed the intestinal microbiota diversity of Radix auricularia (RA) and Planorbella trivolvis (PL) by 16S rRNA high-throughput sequencing. At the phylum level, RA had 23 phyla, including Proteobacteria (33.63%), Cyanobacteria (15.33%), Chloroflexi (13.95%), and Actinomycetes (12.99%). PL had 13 phyla, including Proteobacteria (54.88%), Bacteroidetes (28.49%), and Actinomycetes (7.65%). At the genus level, there were 445 genera in RA, including Pleurocapsa, Thiodictyon, Leptotrichia, and Nocardioides. There were 238 genera in PL, including Cloacibacterium, OM60NOR5_clade, Pseudomonas, and Rhodobacter. Ninety-three genera were the common core flora of the two snail species (all the samples were present), and 27 genera had an abundance greater than 0.5%. The structure of intestinal microbiota was significantly different between the two groups (P=0.027). We performed the functional prediction of intestinal microbiota using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and the results show that the KEGG functional composition of the intestinal flora of the two snails was similar, and the abundance of the amino acid metabolism, carbohydrate metabolism and membrane transport were large. In summary, the intestinal microbiota of the two snails was high in diversity and significantly different, but there were a large number of common core flora.
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Animais , Auricularia , Ecossistema , Água Doce , Microbioma Gastrointestinal/genética , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , RNA Ribossômico 16S/genética , CaramujosRESUMO
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, with a steadily rising prevalence in Western and newly industrialized countries. UC patients have a cancer incidence as high as 10% after 20 years of the disease. Although the importance of fruits and vegetables in defense against UC is beginning to be appreciated, the mechanisms remain largely unclear. In the current study, we reported that dietary black raspberries (BRBs) decreased colonic inflammation in the mucosa and submucosa of interleukin (IL)-10 knockout (KO) mice. We then used colon, spleen, and plasma from those mice to investigate whether BRBs exert their anti-inflammatory effects by correcting dysregulated toll-like receptor (TLR)-4 signaling to downregulate prostaglandin E2 (PGE2). Other studies reported that spleen is the reservoir of macrophages and depletion of macrophages in IL-10 KO mice prevents the development of colitis. Our results showed that BRBs decreased the percentages of macrophages in spleens of IL-10 KO mice. Moreover, mechanistically, the BRB diet corrected dysregulated TLR-4 signaling in cells from the colon and spleen, decreased PGE2 and prostaglandin I2, and increased 15-lipoxygenase and its product, 13-S-hydroxyoctadecadienoic acid, in plasma of IL- 10 KO mice. Therefore, we have elucidated one of the anti-inflammatory mechanisms of BRBs, and have identified biomarkers that could be indicators of response in UC patients treated with them. Our findings with BRBs could well apply to many other commonly consumed fruits and vegetables.
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Objective@#To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF.@*Methods@#We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis.@*Results@#(1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation.@*Conclusions@#The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.
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Objective To study the feasibility and safety of individual laparoscopic pancreatectomy for patients with pancreatic neuroendocrine neoplasm(pNEN).Methods 16 patients with pNEN admitted from Jan.2007 to Nov.2016 undergoing individual laparoscopic pancreatectomy were retrospectively analyzed.Results The operations were successfully accomplished in all the 16 patients,including 2 cases of local excision,2 cases of bundling method excision,2 cases of central pancreatectomy and pancreaticojejunostomy,4 cases of spleen-preserving distal pancreatectomy and 6 cases of distal pancreatectomy combined with splenectomy.The operation time was ranging from 60 to 260 mins,and the blood loss was from 50 to 300 ml.Three cases suffered from level A postoperative pancreatic leakage.The cases of grade G1,G2,G3 were 10,5,1,respectively.The follow-up period was from 3 to 121 months.One case of grade G2 died 46 months postoperatively and 1 case of grade G3 died 36 months postoperatively.Conclusion Individual laparoscopic pancreatectomy is safe and feasible for early pNEN.
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Objective To investigate the effect of triptolide (TP) on the apoptosis of ovarian cancer cell line SKOV-3 and its molecular mechanism.Methods Ovarian cancer cell line SKOV-3 was cultured and treated with different doses of TP (1 × 10-6 mg/ml,1 × 10-5 mg/ml,1 × 10-4 mg/ml,1 × 10-3 mg/ml),Iscoves modification of DMEM (IMEM) medium without TP was negative control.At the 12 h,24 h and 48 h after treatment,apoptosis rate was determined by terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) kit.At the 48 h after treatment,mRNA expression of apoptosis molecules and invasion molecules were determined by fluorescence quantitative polymerase chain reaction (PCR) kit.Results (1) At the 12 h,24 h,and 48 h after treatment with different doses of TP,at the same treatment time,the higher the TP dose was,the higher the apoptosis rate of SKOV-3 cells was;at the same treatment dose,the longer the treatment time was,the higher the apoptosis rate of SKOV-3 cells was;and TP increased the apoptosis rate on dose dependent and time dependent manner;(2) After 48 h treatment with different doses of TP,the higher the TP dose was,the higher the mRNA expression of cytochrome C (CytC),Bax,and Caspase-3 was,the lower the mRNA expression of Bcl-2,matrix metalloproteinases (MMP)2,MMP7,MMP9,N-cadherin,and vimentin was;TP increased mRNA expression of CytC,Bax,and Caspase-3 and decreased mRNA expression of Bcl-2,MMP2,MMP7,MMP9,N-cadherin,and vimentin on dose dependent manner.Conclusions TP can induce the apoptosis of ovarian cancer cells,activation of mitochondrial apoptosis pathway and inhibition of cell invasion are molecular mechanism of TP promoting apoptosis.
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Objective To investigate the applicative value of enhanced 3D multi-echo GRE T2*-weighted angiography(ESWAN) sequence phase values in evaluating brain gray nuclei iron content in idiopathic restless legs syndrome(RLS) patients, providing imaging basis in diagnosis and treatment of idiopathic RLS. Methods In our institute from June 2012 to September 2016,forty-five RLS patients were selected as the RLS group, and 45 healthy volunteers as the control group. ESWAN sequence was performed and serum ferritin values were obtained in all patients and volunteers. The raw data of ESWAN was postprocessed , where the phase maps were obtained. Phase analysis was performed on localized brain gray nuclei regions of interest (substantia nigra, red nucleus, dentate nucleus, thalamus, pallidum, putamen and caudate nucleus ) selected on phase maps. Differences between the 2 subject groups were evaluated using ANCOVA including age as a covariate. Results The phase values of the substantia nigra, thalamus, pallidum and putamen in the RLS group were (-0.087 ± 0.021), (-0.053 ± 0.012), (-0.161 ± 0.008), (-0.125 ± 0.019) radians , respectively. The phase values of the substantia nigra, thalamus, pallidum and putamen in the control group were (-0.127 ± 0.007), (-0.066 ± 0.007), (-0.166 ± 0.007), (-0.150 ± 0.010) radians, respectively. There were significant differences between the two groups (F=142.492, 37.988, 10.558, 60.725;P0.05). Conclusions Phase values can make a quantitative assessment of brain gray nuclei iron content in RLS patients, our results supported the hypothesis of reduced brain iron content in RLS patents , which may have an important role in the pathogenesis of the disorder. However, iron content change in some brain regions was not correlated with serum ferritin concentration changes.
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Objective@#To investigate the clinical features and reliable diagnostic method in HIV/AIDS patients with smear negative pulmonary tuberculosis (TB).@*Methods@#Clinical data of 112 HIV/AIDS patients complicated with smear negative pulmonary TB who were treated in our hospital from January 2013 to September 2015 were retrospectively analyzed. These clinical data includeded clinical symptom, blood routine test, blood biochemistry, T lymphocyte subsets classification, sputum acid-fast bacillus smear, mycobacterium tuberculosis culture, purified protein derivatives tuberculin (PPD) test, interferon gamma-release assay for Mycobacterium tuberculosis (T-SPOT.TB), TB-DNA and chest computed tomography (CT). Diagnostic specificity and sensitivity of these parameters were analyzed.@*Results@#No specific clinical manifestation of these patients was identified. The chest CT feature was also atypical. The positive rates including T-SPOT, TB, TB-DNA and PPD test were all low. The positive rates of T-SPOT.TB and PPD test in patients with a CD4+ cell count >200 cells/μl was significantly higher than that of patients with a CD4+ cell count ≤50 cells/μl and 51≤CD4≤200 cells/μl (P<0.01).@*Conclusions@#The clinical feature of smear negative pulmonary TB in HIV/AIDS patients is atypical. For a definite diagnosis, a comprehensive analysis with clinical manifestations, laboratory test, imaging examination and etiologic detection is required.
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Objective@#To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT).@*Methods@#Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy.@*Results@#Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up.@*Conclusion@#This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.
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Objective To explore the clinical value of high‐sensitive troponin I detection in the diagnosis of early myocardial inju‐ry .Methods Totally 240 type 2 diabetes mellitus (T2DM ) patients (study group) and 40 healthy people(healthy control group) were chosen as subjects .The serum level of HbA1c ,AST ,CK ,CK‐MB and hs‐cTnI were measured among the two groups ,respec‐tively .Results Hs‐cTnI level in T2DM group was significantly higher than in healthy control group(P 0 .05) .Hs‐cTnI level and positive rate in HbA1c ≥ 6 .5% group was significantly higher than in HbA1c ≤ 6 .4% group(P 0 .05) .There was a positive correlation between the level of HbA1c and that of serum hs‐cTnI in T2DM group(r= 0 .471 ,P< 0 .05) .Conclusion The hs‐cTnI level detection has important clinical value in the diagnosis of early myocardial injury in T2DM patients ,and HbA1c is positively correlated with hs‐cTnI .
