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Diabetic retinopathy （DR） is a common complication of diabetes， which causes a great threat to the health of human vision. Recent studies have shown that saponins， polysaccharides and flavonoids in Astragali Radix regulate phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway， silent information regulator 1/nuclear factor erythroid 2-related factor 2 pathway， B-cell lymphoma-2 and other signaling pathways by acting on nuclear factor-κB， hypoxia-inducible factor-1α， glial fibrillary acidic protein， glutamine synthetase， aldose reductase， multiple miRNA and other related targets， so as to exert anti- inflammatory， anti-microangiopathy， anti-neurodegenerative disease and anti-apoptosis， and then achieve the purpose of treating DR.
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After the compatibility of Astragali Radix and Atractylodis Macrocephalae Rhizoma, most of the effective components of Astragali Radix increase, and the bioavailability is improved. Compared with the application of the two drugs alone, it can enhance the effects of immune regulation, anti-tumor, diuresis, lung protection, regulation of flora, and intestinal protection. However, the optimal compatibility ratio of Astragali Radix- Atractylodis Macrocephalae Rhizoma pair to exert various pharmacological effects still needs to be clarified. The drug pair and related preparations are mostly used in the treatment of nephropathy, but its mechanism of action needs to be further elucidated.
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Objective:To analyze the risk factors for the occurrence of intradialytic hypotension (IDH) in elderly maintenance hemodialysis (MHD) patients based on longitudinal multidimensional data.Methods:This was a single-center, retrospective observational study. Data of MHD patients were retrospectively analyzed from April 3, 2017 to December 31, 2021 in the blood purification center of National Clinical Research Center for Kidney Diseases, General Hospital of Eastern Theater Command. IDH defined by the Kidney Disease Outcomes Quality Initiative was used as outcome indicator. Generalized estimating equations were used for univariate and multivariate regression analysis. The importance of each factor on the occurrence of IDH was evaluated by chi-square statistic minus degrees of freedom, and sensitivity analysis was performed by 5-fold interpolation of missing data.Results:A total of 156 elderly patients were enrolled, 91(58.3%) of whom were male, and 2 681 dialysis data recordings were included. The incidence of IDH from 2017 to 2021 fluctuated from 8.3% to 13.2%, with an average incidence of 11.0% by 2021. The results of multivariate regression showed pre-dialysis systolic pressure of 140-159 mmHg (1 mmHg=0.133 kPa, 90-139 mmHg as reference: OR=0.482, 95% CI 0.273-0.851, P=0.012), pre-dialysis diastolic pressure ≥ 90 mmHg (60-89 mmHg as reference, 90-99 mmHg: OR=4.081, 95% CI 2.132-7.809, P < 0.001; ≥ 100 mmHg: OR=8.547, 95% CI 3.233-22.597, P < 0.001), albumin (34-48 as reference, < 34 g/L: OR=2.677, 95% CI 1.592-4.502, P < 0.001; > 48 g/L: OR=2.692, 95% CI 1.102-6.577, P=0.030), C-reactive protein ≥ 8 mg/L (< 8 mg/L as reference: OR=1.787, 95% CI 1.216-2.628, P=0.003), hemodiafiltration as the dialysis mode (hemodialysis as the reference: OR=2.256, 95% CI 1.395-3.648, P=0.001), actual ultrafiltration volume/dry body mass (per 1% increase, OR=1.539, 95% CI 1.139-2.080, P=0.005), and ultrafiltration rate (per 100 ml/h increase, OR=1.641, 95% CI 1.389-1.939, P < 0.001) were independently associated with the occurrence of IDH. Contribution analysis showed that the top three factors related to IDH were ultrafiltration rate ( χ 2- df=32.798), pre-dialysis diastolic pressure ( χ 2- df=20.757) and albumin ( χ 2- df=19.971). The sensitivity analysis showed that the regression results were robust. Conclusions:The risk factors of IDH in elderly MHD patients are increasing ultrafiltration rate, higher pre-dialysis diastolic pressure(≥ 90 mmHg), lower albumin (< 34 g/L), HDF, higher c-reactive protein(≥ 8 mg/L) and increasing actual ultrafiltration volume/dry body mass. Higher pre-dialysis systolic pressure (140-159 mmHg) is a protective factor.
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Objective:To investigate the biological essence of the content variation of differential primary and secondary metabolites in fresh<italic> </italic>roots of <italic>Scutellaria baicalensis </italic>under drought stress. Method:The changes of metabolites were analyzed by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass/mass （UHPLC-ESI-Q-TOF-MS/MS）. Result:A total of 11 differential compounds were identified from the roots of <italic>S. baicalensis</italic> （VIP≥2）. Under drought stress， citric acid content increased and shikimic acid content decreased， indicating that the drought stress weakened the primary metabolism but strengthened secondary metabolism. Drought stress raised the content and regulated the proportion of various secondary metabolites by modulating the biosynthesis and biotransformation of them. To be specific， the content of free flavonoids with many phenolic hydroxyl groups and high biological activity and pharmacological activity， such as baicalin， wogonoside， baicalein， wogonin， chrysin， eriodictyol， 5，2'，6'-trihydroxy-7，8-dimethoxyflavone， 5，8-dihydroxy-6，7-dimethoxyflavone， and 3，5，7，2'，6'-pentahydroxyflavanone， was significantly increased. The massive compounds， like an intricate buffer， maintain metabolism stable as quickly and accurately as possible through biosynthesis and biotransformation， thus responding to the changing environment， which reveals how the quality of genuine regional drugs is influenced and why compounds in herbal medicine are complex. Conclusion:Secondary metabolites with low content but high activity are important influencing factors of medicinal material quality and metabolites with high content and high activity are evaluation indicators of genuine regional drug quality.
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Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.
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OBJECTIVE@#To study insulin sensitivity and the serum level of adiponectin in infants with intrauterine growth retardation (IUGR) and the effect of breastfeeding on the insulin sensitivity through a follow-up study.@*METHODS@#A total of 106 full-term IUGR infants who were hospitalized from October 2014 to October 2018 were enrolled as the IUGR group, and 90 full-term appropriate for gestational age (AGA) infants who were born during the same period of time were enrolled as the AGA group. Birth weight and body length were recorded. Serum levels of fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and adiponectin were measured on day 7 after birth. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. According to the feeding pattern, the IUGR group was further divided into a breastfeeding group with 37 infants and a formula feeding group with 42 infants. The above serum indices and growth indices were also measured at the age of 3 and 6 months.@*RESULTS@#Compared with the AGA group, the IUGR group had significantly increased levels in serum insulin and HOMA-IR and a significantly decreased level of adiponectin (P0.05). In the breastfeeding group, serum insulin and HOMA-IR decreased and adiponectin level increased over the time of breastfeeding (P<0.05).@*CONCLUSIONS@#Insulin sensitivity decreases in the early stage after birth in IUGR infants, and breastfeeding can improve insulin sensitivity.
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Humans , Infant , Infant, Newborn , Adiponectin , Fetal Growth Retardation , Follow-Up Studies , Insulin , Insulin ResistanceABSTRACT
Objective: To explore the value of unenhanced MR lymphography (MRL) and CT after direct lymphangiography (DLG) in diagnosis of lympho-urinary fistula location and thoracic duct abnormalities in patients with chyluria. Methods: Data of 24 patients with chyluria were reviewed. The position of lympho-urinary fistula and signs related to obstruction of thoracic duct (TD) were analyzed. Dilated renal lymphatics and other retroperitoneal lymphatics, dilatation of TD, multiple tortuous dilated lymphatics around TD were evaluated with MRL, while contrast media reflux of renal lymphatic and urinary system, lymphatics in the outlet area of iliac trunk and thoracic duct were observed with CT after DLG. Results: MRL depicted lympho-urinary fistula in 19 cases (79.17%), including 2 cases in bilateral kidneys, 6 in left and 10 in right kidney, and 1 case in bladder. CT after DLG showed the level of lympho-urinary fistula, including 6 cases in bilateral kidneys, 7 in left and 10 in right kidney, also 1 case in bladder. The consistency between MRL and DLG plus CT was moderate (Kappa=0.601, P<0.001). There was significant difference of unilateral renal level lympho-urinary fistula between MRL and CT after DLG (χ2=22.463, P<0.001),the sensitivity and specificity of MRL was 68.97% and 100%, respectively. No contrast medium distribution at cervical section of TD was found neither with DLG nor CT after DLG, but was observed in one of them with MRL. MRL detected unilateral double renal pelvis and ureter in 2 cases misdiagnosed with CT after DLG. Conclusion: MRL can be used as a noninvasive preliminary examination for lympho-urinary fistula in patients with chyluria, combining with CT after DLG can provide comprehensive assessment of TD and lympho-urinary fistula.
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<p><b>OBJECTIVE</b>To explore the effect of intrauterine growth retardation (IUGR) on insulin sensitivity in neonates and the relationship between insulin sensitivity and plasma adiponectin level.</p><p><b>METHODS</b>Eighty-two term neonates with IUGR and 90 term neonates born appropriate for gestational age (AGA) were enrolled. Weight, height, head circumference and abdomen circumference of the neonates were measured within 24 hours after birth. Fasting serum glucose (FG), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma insulin and adiponectin were detected in two groups on the 7th day after birth. Homeostasis model assessment for insulin resistance (HOMA-IR) index and insulin sensitivity index (ISI) were calculated.</p><p><b>RESULTS</b>There were no significant differences in the levels of FG, TG, HDL and LDL between the IUGR and AGA groups (P>0.05). The plasma insulin level in the IUGR group was higher than that in the AGA group, but the plasma adiponectin level was lower than that in the AGA group (P<0.05). HOMA-IR index in the IUGR group was higher than that in the AGA group, but ISI was lower than that in the AGA group (P<0.05). Both Pearson correlation analysis and multiple linear regression analysis showed HOMA-IR index was negatively correlated with plasma adiponectin level and birth weight (P<0.05).</p><p><b>CONCLUSIONS</b>The neonates with IUGR display a higher plasma insulin level and decreased insulin sensitivity. The decreased plasma adiponectin level may be associated with the decreased insulin sensitivity.</p>
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<p><b>OBJECTIVE</b>To evaluate the value of blood lactic acid (BLA) as a predictor for the severity and prognosis of neonatal shock.</p><p><b>METHODS</b>A total of 326 neonates with shock were enrolled and divided into three groups based on the severity, namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA level was measured during and early after (about 6 hours later) fluid resuscitation, and lactate clearance rate (LCR) was calculated. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of BLA in neonatal shock.</p><p><b>RESULTS</b>BLA level was high in all subjects prior to treatment, and was highest in the severe group and lowest in the mild group (P<0.01). BLA level was significantly higher among patients with septic shock than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05). BLA level was significantly reduced in patients in recovery after treatment (P<0.05). Mortality was significantly lower in patients with BLA level ≤4 mmol/L or LCR ≥10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at 11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe shock. BLA at 10.65 mmol/L had 88.9% sensitivity and 74.1% specificity in predicting the prognosis (survival or dead) of newborns with shock.</p><p><b>CONCLUSIONS</b>In neonates with shock, arterial BLA level increases as the disease severity increases and is associated with prognosis, so it is a useful predictor of the severity and prognosis of neonatal shock.</p>
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BACKGROUND:The roles of osteocyte and osteoblast apoptosis in steroid-induced avascular necrosis of the femoral head (ANFH) have arouse much attention,and its pathogenesis has been understood gradually.But there is a lack of knowledge about the mechanisms underlying osteocyte and osteoblast apoptosis.Meanwhile,hormones have been shown to enhance the Dickkopf-1 expression in Wnt signaling pathway.OBJECTIVE:To investigate the roles of Dickkopf-1 and cell apoptosis in steroid-induced ANFH,and to understand their correlations with steroid-induced ANFH.METHODS:Necrotic femoral head samples were removed from 14 patients with steroid-induced ANFH after total hip arthroplasty (experimental group),and normal femoral heads were from 8 patients with femoral neck fracture (control group).The cellular morphology was observed using transmission electron microscope;the number of empty lacunae was counted through hematoxylin-eosin staining;the cell apoptosis was detected by TUNEL assay;the expression level of Dickkopf-1 was detected by immunohistochemistry.Moreover,the correlation between the Dickkopf-1 positive rate and apoptosis index of osteocytes was analyzed by Spearman rank correlation analysis.RESULTS AND CONCLUSION:The number of empty lacunae,expression level of Dickkopf-1,and apoptosis index of osteocytes in the experimental group were significantly higher than those in the control group (P ＜ 0.05).In the experimental group,the Dickkopf-1 positive rate was positively correlated to the apoptosis index of osteocytes (r=0.623).These results indicate that Dickkopf-1 and osteocyte apoptosis both play key roles in steroid-induced ANFH,and increased Dickkopf-1 level may promote the development of ANFH.
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AIM:To investigate the protective effect of non-mitogenic fibroblast growth factor 1 (nFGF1) on the aortic vascular function in streptozotocin (STZ)/high-fat diet (HFD)-induced type 2 diabetic rats and its underlying mechanisms. METHODS:Five-week-old male SD rats (n=30) were randomly divided into 3 groups (n=10 in each group),including normal control group,type 2 diabetic group and nFGF1 treatment group(type 2 diabetic rats were intra-peritoneally injected with 0.5 mg/kg nFGF1 every other day for 4 weeks). After the rats were sacrificed, blood glucose, cholesterol and triglyceride levels,aorta diastolic function and superoxide dismutase(SOD) level in the aorta of each group were measured. Besides,the protein levels of cyclooxygenase-2(COX-2),phosphorylated extracellular signal-regulated ki-nase (p-ERK) and endothelial nitric oxide synthase (eNOS) in the aorta were determined by Western blot. RESULTS:nFGF1 markedly lowered blood glucose, cholesterol and triglyceride levels, enhanced aorta SOD activity and upregulated protein level of eNOS in the type 2 diabetic rats. Furthermore,the increased protein levels of COX-2 and p-ERK in the type 2 diabetic rats were largely abrogated by nFGF1. CONCLUSION:nFGF1 effectively attenuates aortic vascular dysfunction in the type 2 diabetic rats,which may be associated with decreasing blood glucose,cholesterol and triglyceride levels,re-ducing inflammation and oxidative stress response,and activating eNOS signaling pathway.
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Objective To explore the correlation of circRNAs' expression level to the negative-and positive symptoms of patients with schizophrenia (SZ).Methods Gene chip screening was performed with the peripheral blood samples from each five of SZ patients and normal controls.Nine circRNAs showing differentiate expression were confirmed,and further verification was done by real-time fluorescence quantitative PCR in 102 SZ patients and 103 normal controls.All the SZ patients were assessed with Positive and Negative Symptom Scale (PANSS).Results It was revealed that the expression levels of circRNA_102101,circRNA_102315,circRNA_104597,circRNA_101835 and circRNA_101836 were significantly down-regulated (P＜0.01 or P＜0.05),and circRNA_103102 and circRNA_103704 were up-regulated in SZ group (P＜0.01).The ACT value of circRNA_102101 and circRNA_103102 was positively correlated to the positive symptoms (P＜0.01 or P＜0.05),and the ACT value of circRNA_103704 also showed positive correlation with positive symptoms and general psychopathological symptoms (P＜0.01 or P＜0.05).The ACT values of circRNA_102101,circRNA_103102,circRNA_102315,circRNA_103704 and circRNA_102802 were correlated with thinking disorder (P＜0.01 or P＜0.05),and the ACT values of circRNA_102101,circRNA_103102,circRNA_104597,circRNA_103704 and circRNA_102802 were correlated with the activation (P＜0.01 or P＜0.05).The ACT values of circRNA_102101,circRNA_103102,circRNA_103704 and circRNA_102802 were positively correlated with paranoid (P＜0.01 or P＜0.05),and of circRNA_102101,circRNA_103102,circRNA_103704 and circRNA_102802 were markedly correlated with assault (P＜0.01 or P＜0.05).Therefore,circRNA_103704 was chosen into regressive equation of positive symptoms (P＜0.01),and circRNA_103704 and circRNA_102315 were chosen into regressive equation of general pathological findings (P＜0.01 or P＜0.05).Conclusion The expression levels of circRNA_103704 and circRNA_103102 are obviously up-regulated in SZ patients than in normal controls,and markedly correlated with the negative and positive SZ symptoms,so might be the dominant regulatory factors in the pathological process of schizophrenia.
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Objective:TThe aim of this study was to observe the changes of the volume and distribution of body fluid after abdominal surgery,and further to explore its characteristics and influence factors.Methods:Sixtyone patients were included between March and June in 2016.The volume of intracellular water (ICW),extracellular water (ECW) and total body water (TBW) was estimated by InbodyS 10 on preoperative day 1 (PreD 1) and postoperative day (POD) 1,3,5 and 7.Furthermore,the patients were grouped according to the age,sex,type of operation,operation time and the daily liquid input,and the influence factors of postoperative fluid volume were analyzed in each subgroup.Results:Comparing to that of PreD1,the ICW,ECW,and TBW,mainly ECW,were increased significantly on POD1 (P＜ 0.05),and the level of postoperative fluid volume was decreased to that of PreD1 between POD3 and POD7.It showed that there was difference in the net increasing of body fluid on POD1 between different type of the patients.Obviously,the net increasing of fluid volume in woman on POD 1 was more than that in man.The net increasing of fluid volume on POD1 was correlated with the operation time and net liquid input.Conclusion:The fluid retention was found in the early stage of postoperative patients,and mainly exists in ECW.The main influence factors resulting postoperative fluid retention were prolonged operation time and increased net fluid input.
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AIM:To investigate the effect of Eph receptor A2 (EphA2) on drug resistance of colorectal carci-noma cells and its possible mechanisms .METHODS:Real-time PCR and Western blot were used to detect the expression of EphA2 at mRNA and protein levels in LoVo and LoVo/5-FU cells.EphA2 siRNA was transfected to down-regulate the EphA2 expression in LoVo/5-FU cells, and the drug sensitivity was calculated by CCK-8 assay.Meanwhile, cell migration and invasion were measured by wound healing assay and Transwell assay , and the protein levels of E-cadherin,β-catenin, N-cadherin, vimentin, Notch and Snail were determined by Western blot .RESULTS: The expression of EphA2 at both mRNA and protein levels was significantly up-regulated in LoVo/5-FU cells (P<0.05).Knockdown of EphA2 suppressed the cell viability, and migration and invasion abilities , but promoted drug sensitivity of LoVo/5-FU cells.Up-regulation of E-cadherin and β-catenin, and down-regulation of N-cadherin and vimentin were observed , indicating that the epithelial-mesenchymal transition ( EMT) process was suppressed .Knockdown of EphA2 decreased the expression levels of Notch and Snail.CONCLUSION:Down-regulation of EphA2 partly reverses drug resistance of LoVo/5-FU cells.The mechanism may be related to suppressing cell growth , migration, invasion and EMT process via Notch/Snail signaling pathway .
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Objective To verify the feasibility of Chlamydia trachomatis(CT),Neisseria gonorrhoeae(NG),Ureaplasma urealyticum(UU)detection by automatic nucleic acid extraction workstation(MagX).Methods The test samples of CT (159),NG(128)and UU(144)were collected.The samples were extracted of nucleic acid two methods:manual extraction, which entailed manually preparing PCR reaction system and MagX automatic nucleic acid extraction workstation,which au-tomatically prepared the reaction system.The two parts of nucleic acids proceeded to the Simultaneous Amplification and Testing(SAT).The result of manual extraction was set as the golden standard and the Kappa consistency analysis was con-ducted.Meanwhile,the sensitivity,specificity,accuracy and carry pollution experiments of MagX were verified.Results The sensitivity of MagX automatic nucleic acids extraction workstation were 92.59%(CT),100.00%(NG)and 93.33%(UU).The specificity were 98.48%(CT),98.18%(NG)and 95.24%(UU).The accuracy were 97.48%(CT),98.44%(NG)and 94.44%(UU).The results of kappa consistency analysis were greater than 0.8(CT:Kappa=0.910 6,NG:Kap-pa=0.938 3,UU:Kappa=0.885 6).MagX detected the precision of CT,NG and UU:Coefficient of Variation(CV)<5%. There was no pollution phenomenon.Conclusion MagX automatic nucleic acids extraction workstation could be used to test three kinds of sexually transmitted pathogen in clinical settings.
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Objectives: To explore the clinical feathers and prognosis of primary malignant pericardial mesothelioma (PPM) reported in inland China. Methods: We searched Chinese data bases and collected medical records of PPM from 1981 to 2015 for patients' clinical, imaging, pathological, diagnostic and therapeutic information to explore the possible impact factors for prognosis. Results: A total of 186 patients were enrolled including 122 (65.6％) male, the mean age was (40.9±14.5) years at the range of (2-79) years. There were 108/166 (65.1％) patients suffered from dyspnea which was the most common symptom, 17 (10.2％) were complicated with cardiac tamponade and 48 (28.9％) complicated with constrictive pericarditis. 65 patients were misdiagnosed and 40 (61.5％) of them were diagnosed for tubercular pericarditis. 94 patients died and 30 (31.9％) of them died during hospitalization. 86 patients were discharged and received the follow-up study at the median of 6 months, 64 (74.4％) of them died. Multivariate Cox regression analysis did not find the meaningful clinical, imaging or pathological parameters to predict patients' mortality. Conclusion: PPM is a rare and highly aggressive pericardial malignant tumor, mainly involving middle-age males. Pathological combining immunohistochemical examinations are helpful for PPM diagnosis. Effective therapy has been lacking and comprehensive individualized therapy may improve the patients' prognosis.
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Objectives: To explore the clinical feathers and prognosis of primary malignant pericardial mesothelioma (PPM) reported in inland China. Methods: We searched Chinese data bases and collected medical records of PPM from 1981 to 2015 for patients' clinical, imaging, pathological, diagnostic and therapeutic information to explore the possible impact factors for prognosis. Results: A total of 186 patients were enrolled including 122 (65.6％) male, the mean age was (40.9±14.5) years at the range of (2-79) years. There were 108/166 (65.1％) patients suffered from dyspnea which was the most common symptom, 17 (10.2％) were complicated with cardiac tamponade and 48 (28.9％) complicated with constrictive pericarditis. 65 patients were misdiagnosed and 40 (61.5％) of them were diagnosed for tubercular pericarditis. 94 patients died and 30 (31.9％) of them died during hospitalization. 86 patients were discharged and received the follow-up study at the median of 6 months, 64 (74.4％) of them died. Multivariate Cox regression analysis did not find the meaningful clinical, imaging or pathological parameters to predict patients' mortality. Conclusion: PPM is a rare and highly aggressive pericardial malignant tumor, mainly involving middle-age males. Pathological combining immunohistochemical examinations are helpful for PPM diagnosis. Effective therapy has been lacking and comprehensive individualized therapy may improve the patients' prognosis.
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<p><b>OBJECTIVE</b>To investigate the influence of thrombelastography index changes on its sensitivity and specificity for diagnosis of disseminated intravascular coagulation (DIC) in children.</p><p><b>METHODS</b>A total of 149 children with DIC in our hospital from June 2013 to June 2016 were selected in DIC group, while 106 cases of non-DIC, including healthy children and children with diseases easily confused with DIC, were selected as non-DIC(control) group. The thrombelastography, D-dimer, coagulation functions including prothrombintime (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and fibin degradation product (FDP), congental coagulation disorders and platelet count were detected in DIC and non-DIC groups; the statistics of data was performed and the sensitivity and specificity of thromelastraphy indexes such as R time, α angle MA value and A value were evaluated; the relationship of DIC with indexes was analyzed. Moreover, the result difference of thromelastography and routine coagulation function test was compared at diagnosis of DIC.</p><p><b>RESULTS</b>According to statistical analysis of clinical data in 2 groups, the average R time in non-DIC group was significantly less than that in DIC group (P<0.05); the average α angle in non-DIC group was larger than that in DIC group (P<0.05), both the MA and A values in the non-DIC group were significantly higher than those in DIC group (P<0.05). The specificity of routine coagulation function test for diagnosis of DIC was as follow: PT-27.2%, APTT-42.2%, international normalized ratio(INR)-47.9%, FIB-44.4%, FDP-42.7% and D-dimer-68.3%, which were significantly lower than that of R time,α angle and MA value for diagnosis of DIC (85.1%, 74.1% and 73%). The α angle and MA value of healthy children were greater than those of children with severe liver disease(P<0.05). while the average R time of healthy children was less than that of children with severe liver disease(P<0.05), but the difference of A value between them did not statistically significant (P>0.05) . The average R time of healthy children was less than that of children with congenital coagulation disorders (P<0.05). but there was no significant differences in α angle MA and Avalues between them.</p><p><b>CONCLUSION</b>As compared with routine coagulation function test, the thrombelastography shows more high specificity for diagnosis of DIC, and can more precisely diagnose the DIC; moreover, the thrombelastography combined with roatime coagulation function test can more early find and diagnose the DIC in children, therefore it can improve the survival rate of children with DIC.</p>
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<p><b>OBJECTIVE</b>To explore the effect of Caspase 1 inhibitor Ac-YVAD-CMK on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) and its mechanism.</p><p><b>METHODS</b>Experiments were divided randomly into 3 groups: allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion group (TS group, n=12), allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion plus injection of low dose Caspase 1 inhibitor group (TS+low dose of C group, n=16) and plus high dose Caspase1 inhibitor (TS+high dose of C group, n=19). The body weight of mice in each group was dynamically detected, and the clinical manifestation of GVHD and score of aGVHD were determined, and the chimerism rate of mice was detected after transplantation for 14 days. Th1, Th2 and Th17 cells in peripheral blood were examined by flow cytometry. Peripheral proinflammatory cytokines IL-1β, IFN-γ, IL-1α and IL-18 were examined by enzyme-linked immunosorbent assay(ELISA). The tissues sections of GVHD target organs (liver, lung, colon and skin) were stained with HE for histopathologic examination and histopathologic score.</p><p><b>RESULTS</b>Ac-YVAD-CMK could alleviate murine aGVHD and pathological injury, decreare the incidence and severity of aGVHD in recipient mice. The detection of Th cell subsets in peripheral blood by flow cytometry showed that compared with TS group, the Th1 cell ratio in TS+low dose of C and TS+high dose of C groups was significantly reduced (P<0.05), while the Th2 and Th17 cell ratio was significantly enhanced (P<0.05) in TS+low dose of high dose of C groups. The detection of peripheral inflamematory cytokines by ELISA demonstrated that the inflammatory cytokines including IL-1β,IFN-γ,IL-18 and IL-1α were reduced significantly (P<0.05).</p><p><b>CONCLUSION</b>Ac-YVAD-CMK can improve aGVHD by inhibiting Caspase 1 and reducing the release of some inflammatory cytokines, thereby alleviated the aGVHD pathological damage.</p>
ABSTRACT
The aim of this study was to construct the eukaryotic expression vector of pCMV-Myc-NOVA1 based on NOVA1 gene, and to screen the optimum expression condition after transfecting to PC12 cells, and further to explore the distribution of NOVA1 protein in PC12 cells using cell immunohistochemistry, and to identifyits anti-hypoxia activity. According to the NOVA1 gene sequence of NCBI database, we designed the upstream and downstream primers, and performed polymerase chain reaction (PCR) to amplify the full length cDNA coding sequence using pCR4-TOPO-NOVA1 as a template. The products were digested by restriction endonuclease SalⅠand XhoⅠ, and conjugated to the eukaryotic expression vector ofpCMV-Myc followed by validating by digestion and direct sequencing. Subsequently, the validated pCMV-Myc-NOVA1 was transfected to PC12 cells followed by optimizing of transfection ratio and transfection time, and identified by qPCR, Western blotting and cell immunohistochemistry respectively. After validation by digestion and direct sequencing, the eukaryotic expression vector of pCMV-Myc-NOVA1 was correctly constructed. The optimum transfection ratio of plasmid to Lipo 2000 was 1:2.5, and the optimum transfection time was 72 h. At the optimum transfection condition, the expression level of NOVA1 mRNA and protein significantly increased, and after transfection of pCMV-Myc-NOVA1, NOVA1 protein mainly distributed in cell nucleus and cytoplasm. After 6 h hypoxia, the cell proliferation activity was significantly increased compared to that of the control and pCMV-Myc group. Our findings provided a reference for exploring the mechanism of NOVA1, and also a technical support for potential drug development of NOVA1.