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Cryptococcus gattii is a kind of Cryptococcus that infects the lungs and central nervous system through the inhalation of infectious particles such as spores or Cryptococcus yeast cells. The development of clinical disease of Cryptococcus gattii may be determined by the sex, immunity and genetics of the host factors, in which immune system factors play an important role in host injury. Their defects will have serious clinical consequences. Cryptococcus gattii mainly infects the population with normal immune, and the infection of immunosuppressed population is rare. The infection mechanism, molecular types, clinical characteristics, treatment and prognosis of Cryptococcus gattii meningitis were different between the two populations. This article reviews the main differences in different immune status with Cryptococcus gattii meningitis.
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A 19-year-old male patient who suffered from sudden and repeated multiple organ dysfunction syndrome one month after the bar removal procedure of Nuss surgery for pectus excavatum was admitted to our department. With organ function supportive treatment, the etiology was finally identified to be a bone spur located at the inner border of the left costa due to repeated friction between the implanted steel bar and the rib, which damaged the heart repeatedly and induced the consequent acute cardiac tamponade. After operation, the patient was successfully managed and discharged. Follow-ups till three years indicated a good recovery.
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Objective:To analyze the clinical characteristics and causes of death of 80 dead cases with confirmed coronavirus disease 2019 (COVID-19).Methods:The clinical data of 80 dead patients with COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 11 to February 11, 2020 were retrospectively analyzed.The laboratory examination indexes (including white blood cells, lymphocytes, procalcitonin (PCT), lactic acid, D-dimmer, fibrinogen degradation products, N-terminal pro-brain natriuretic peptide (N-proBNP), ultra sensitive-troponin I, lactate dehydrogenase (LDH) and CD4 + T lymphocyte) of the patients at the time of admission were compared with the indexes at the last time before death. Statistical analysis was conducted by using paired t test or Wilcoxon′s signed rank test. Results:The median age was 72 years old of the 80 patients, and 78.75%(63/80) of them were older than 60 years. Thirty-six cases (45.00%) were severe and 44(55.00%) were critical at admission. Fifty-eight cases (72.50%) had underlying diseases. The common underlying diseases were hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and chronic obstructive pulmonary disease. Comparing the patients′ first laboratory tests at admission with those before death, white blood cells increased (8.01(4.86, 12.29)×10 9/L vs 12.55(8.25, 17.66)×10 9/L), lymphocytes decreased (0.70(0.46, 0.88)×10 9/L vs 0.54(0.39, 0.75)×10 9/L), PCT increased (0.20(0.11, 0.74) μg/L vs 1.00(0.20, 1.99) μg/L), lactic acid increased (2.10(1.40, 3.10) mmol/L vs 3.10(2.60, 4.10) mmol/L), D-dimmer increased (4.33(0.97, 18.98) mg/L vs 15.29(5.17, 53.44) mg/L), fibrinogen degradation products increased (15.90(3.58, 76.60) mg/L vs 63.14(21.23, 110.67) mg/L), N-proBNP increased (1 078.00(347.35, 2 996.50) ng/L vs 3 439.50(1 576.00, 9 281.50) ng/L), ultra-sensitive troponin I increased (0.08(0.03, 0.17) μg/L vs 0.33(0.14, 2.47) μg/L), LDH increased (397.00(327.00, 523.50) U/L vs 624.00(481.00, 854.00) U/L) and CD4 + T lymphocyte decreased (137.00(104.00, 168.00)/μL vs 97.00(67.00, 128.00)/μL). The differences between the two groups were all statistically significant ( W=238.00, 1 053.50, 150.00, 152.00, 192.00, 190.00, 108.00, 57.00, 53.00 and 40.00, respectively, all P<0.05). All patients received antiviral and respiratory-support therapy and the main cause of death was respiratory failure caused by intractable hypoxemia and multiple organ failure. Among them, seven cases died in one day hospitalization, and 66 cases died in seven days hospitalization. Conclusions:Elderly patients with a variety of chronic underlying diseases have poor prognosis. It′s essential to pay more attention and deal with the above clinical characteristics at an early stage to improve the outcome of the COVID-19 patients.
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Objective:To analyze the risk factors of fatal outcome in patients with severe COVID-19.Methods:The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression.Results:Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators ( P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient’s clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion:COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.
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Based on the introduction to the current situation of research on the standard for stroke syndrome of Traditional Chinese Medicine (TCM),the paper sorts out and collects related medical cases of stroke based on clinical data,builds models of the relationship between clinical information of TCM and syndrome categories through support vector machine after qualitative and quantitative analysis on the data standard in the clinical pathway of stroke,observes the predictive accuracy,and provides reasonable and reliable information support for clinical decision of stroke.
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<p><b>OBJECTIVE</b>To explore the effects of basic fibroblast growth factor (bFGF) on human bone marrow mesenchymal stem cell (hBMMSC) damaged by irradiation and its underlying mechanisms.</p><p><b>METHODS</b>hBMMSC was irradiated with 0, 6, 12 Gy X ray, then flow cytometry, cell counting kit-8 (CCK-8), Western blot and alizarin red staining were used to detect the effects of X ray on apoptosis, proliferation and osteogenic differentiation of hBMMSC; 0, 1, 5, 10, 20 ng/ml bFGF was added to hBMMSC irradiated with X ray for selecting the suitable bFGF reaction concentration; then the Western blot was used to detect the expression of PDGFRα so as to evaluate whether the expression of PDGFRα participated in bFGF-mediated recovery of hBMMSC proliferation and osteogenic differentiation after irradiation.</p><p><b>RESULTS</b>The proliferation and osteogenic differentiation of hBMMSC decreased remarkably after irradiation. bFGF promoted the recovery of proliferation and osteogenic differentiation of irradiated hBMMSC compared with untreated irradiated hBMMSC (P < 0.05); 5 ng/ml bFGF was identified as the optimal concentration. A significant difference in the number of apoptotic cells could be detected only between the 0 Gy group and 12 Gy group at the 24 h time point, while no differences were detected at later time points. Irradiated hBMMSC showed remarkable decrease of PDGFRα expression, while the PDGFRα expression increased after bFGF was added.</p><p><b>CONCLUSION</b>Irradiation dose not show significant effect on apoptosis of hBMMSC, but the bFGF displays a effect on repairing the irradiation damage of hBMMSC and promotes the recovery of hBMMSC proliferation and osteogenic differentiation. The damage of hBMMSC proliferation and osteogenic differentiation associates with downregulation of PDGFRα expression induced by irrediation. PDGFRα involves in repairing effect of bFGF on irradiation damage of hBMMSC.</p>
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Humans , Apoptosis , Bone Marrow Cells , Cell Differentiation , Cell Proliferation , Cells, Cultured , Fibroblast Growth Factor 2 , Mesenchymal Stem Cells , Osteogenesis , Receptor, Platelet-Derived Growth Factor alphaABSTRACT
The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane barriers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.
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The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane barriers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.
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Humans , Cell Membrane , Metabolism , Endosomes , Metabolism , Gene Transfer Techniques , Genetic Therapy , Genetic VectorsABSTRACT
<p><b>OBJECTIVE</b>To investigate anticancer effects of 5-fluorouracil (5-FU) combined with CL, extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma cell line (JEC).</p><p><b>METHODS</b>JEC cells cultured in vitro in the logarithmic growth phase were seeded in the culture plate and divided into the control group (RPMI 1640), the positive group (10(-4) mol/L 5-FU), the CL groups (at the dose of 0.01, 0.1, 1, 10, and 100 microg/mL), and the CL (0.01, 0.1, 1, 10, and 100 microg/mL) combined with 5-FU groups. Effects of 5-FU combined with CL on JEC cell growth were drawn and measured by MTT and growth curves. Effects of CL combined with 5-FU on the JEC cell differentiation was analyzed by detecting the reduction capability of nitrobenzene thiocyanate (NBT) and lactate dehydrogenase (LDH) contents in the cultured medium. Effects of CL combined with 5-FU on the JEC cell apoptosis and cell proliferation cycle were detected by acridine orange (AO)/ethidium bromide (EB) fluorescent staining and flow cytometry (FCM).</p><p><b>RESULTS</b>The proliferation inhibitory effect of CL combined with 5-FU on JEC cells was enhanced when compared with that of CL or 5-FU alone (P<0.05). The percentages of NBT positive JEC cells and apoptotic JEC cells increased in the 5-FU combined with CL groups when compared with 5-FU group or the CL group alone (P<0.05). The LDH concentration of the JEC cell culture supernate decreased in 5-FU combined with CL groups (P<0.05). Furthermore, the percentage of G0-G1 phase JEC cells treated by 5-FU combined with CL was higher than that of 5-FU or CL alone (P<0.05).</p><p><b>CONCLUSION</b>CL could enhance anticancer effects of 5-FU. Its mechanisms might be correlated with reinforcing the cytotoxicity of 5-FU, inducing cell differentiation and apoptosis, and inhibiting cell proliferation and division.</p>
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Female , Humans , Adenocarcinoma , Pathology , Cell Differentiation , Cell Line, Tumor , Cell Proliferation , Endometrial Neoplasms , Pathology , Fluorouracil , Pharmacology , Herb-Drug Interactions , Plant Extracts , Pharmacology , Rosa , ChemistryABSTRACT
Objective: To observe the effect of leptin on proliferation and invasion of human hepatocellular carcinoma cell line Huh-7 and explore its possible molecular mechanism. Methods: Huh-7 cells were cultured and treated with leptin at different concentrations of 5, 10, 50, 100 and 200 ng/mL for 12, 24 and 48 h. Huh-7 cells without leptin treatment were used as control group. The proliferation rate of the Huh-7 cells was measured by MTT assay. The change of cell cycle was detected by flow cytometry analysis. Transwell chamber assay was performed to determine the effect of leptin 100 ng/mL on the invasion capability of Huh-7 cells 24 h later. The effect of leptin on mRNA expression of matrix metalloproteinase (MMP) of Huh-7 cells was detected by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: Leptin significantly promoted the proliferation of Huh-7 cells. The effect was dose-dependent in certain degree. Flow cytometry analysis found that leptin significantly induced decrease in proportion of cells in G0/1 phase and significantly increased cell proportion in S phase. The invasion capability of Huh-7 cells was significantly increased after leptin 10 ng/mL treatment for 24 h (P <0.01). The number of cells penetrated polycarbonate membrane were (41.80 ± 3.19) and (18.20 ± 2.86), respectively. Real time fluorogentic quantitative PCR analysis revealed that the expression level of MMP-2 and MMP-9 mRNA expression were 4.25-fold and 2.73-fold as the control group (P <0.01), respectively. Conclusion: Leptin significantly increases the proliferation and invasion capabilities of Huh-7 cells in vitro. The possible mechanism may be related with up-regulation of MMPs level.
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<p><b>OBJECTIVE</b>To investigate anticancer effects and potential mechanisms of CL, extract of Rosa roxburghii.</p><p><b>METHOD</b>In vitro anticancer effect was observed in Ehrlich's ascites carcinoma (EAC) mice model. Cell toxicity of CL on human endometrial adenocarcinoma cell line JEC (JEC) cells was measured by MTT reduction test and growth curves drawing by trypan blue dye exclusion method. Lactate dehydrogenase (LDH) concentration of cultured medium was detected by auto-biochemistry-meter. Cell differentiation was showed by detection of NBT reduction ability. Apoptosis was showed by AO/EB fluorescent staining and flow cytometer detection. Cell proliferation cycle was detected by flow cytometer.</p><p><b>RESULT</b>Comparing with the negative group, life span of EAC mice treated with CL was prolonged (P <0.05), and thymus index and spleen index of them were raised (P <0.05). The inhibitory effect of CL on JEC cells was in concentration-and time-dependent manner. IC50 of CL on JEC cells was 0.05 microg mL(-1) in 96 hours. Growth curves showed right-shift with CL concentration increasing. The number of NBT positive JEC cells increased and the LDH concentration of cultured medium declined with CL increasing. Apoptosis of JEC cells with CL treated was induced in concentration-dependent manner, apoptotic percentage of CL 10 microg mL(-1) on JEC cells was 25.59% in 24 hours. CL arrested JEC cells in G2-M phase (P <0.05).</p><p><b>CONCLUSION</b>CL has certainly anticancer effects in vivo and in vitro. Anticancer effect of CL in vivo was in relation to enhancing immune function of EAC mice; anticancer mechanisms of CL on JEC cells may be its direct cytotoxic effect, inducing cell apoptosis and inhibiting cell segmentation.</p>
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Animals , Female , Humans , Mice , Adenocarcinoma , Metabolism , Pathology , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Carcinoma, Ehrlich Tumor , Pathology , Cell Cycle , Cell Line, Tumor , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Pharmacology , Endometrial Neoplasms , Metabolism , Pathology , L-Lactate Dehydrogenase , Metabolism , Plants, Medicinal , Chemistry , Random Allocation , Rosa , ChemistryABSTRACT
In this paper, we studied the relationship between the prostaglandin F(2alpha) (PGF(2alpha))-induced cardiac hypertrophy and calcineurin (CaN) signal transduction pathway in vivo and in vitro. Male Sprague-Dawley rats were given a single i.p. injection with monocrotaline (MCT) (60 mg/kg) and then given orally with celecoxib (20 mg/kg) or vehicle once a day for 14 d before (from d 1 to d 14) or after (from d 15 to d 28) right ventricular hypertrophy (RVH) was formed. Body weight (BW), right ventricular weight (RV), left ventricular with septum weight (LV), as well as lung weight were determined. RVH index (RVHI=RV/LV), RV/BW, and lung weight/BW were calculated and histological changes were observed with transmission electron microscope. PGF(2alpha) level, atrial natriuretic peptide (ANP) and CaN mRNA expressions, expression of CaN and its downstream effectors, NFAT(3) and GATA(4) protein were assayed by EIA kit, RT-PCR, and Western blotting, respectively. The cardiomyocyte hypertrophy in primary culture induced by PGF(2alpha) (0.1 micromol/L) was evaluated by measuring the cell diameter, protein content, and ANP mRNA as well as CaN mRNA expressions. It was found that 14 d or 28 d after MCT was given, the RVHI, RV/BW, and lung weight/BW were significantly increased by 47%, 53% and 118%, and by 64%, 94% and 156%, respectively; at the same time PGF(2alpha) levels in RV tissue were increased by 44% and by 51% with increasing RVHI, and elevated expressions of ANP and CaN mRNA, as well as CaN, NFAT(3) and GATA(4) proteins in a positive correlation manner. Furthermore, some histological injuries were found in RV tissue. Celecoxib, a cyclooxygenase inhibitor, obviously blunted the elevation of RVHI, RV/BW, and lung weight/BW no matter it was given before or after RVH. In vitro experiments showed that 0.1 micromol/L PGF(2alpha) significantly increased the cardiomyocyte diameter and protein content, and promoted ANP and CaN mRNA expressions, which was blocked by cyclosporin A, a CaN inhibitor. Our results indicate that PGF(2alpha) may be involved in cardiac hypertrophy induced by MCT in rats through CaN signal transduction pathway.
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Animals , Male , Rats , Calcineurin , Genetics , Metabolism , Physiology , Cells, Cultured , Dinoprost , Metabolism , Physiology , Hypertrophy, Right Ventricular , Metabolism , Monocrotaline , Myocytes, Cardiac , Metabolism , Pathology , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Signal Transduction , PhysiologyABSTRACT
Objective:To explore the effect of leptin on proliferation of human hepatocellular carcinoma cells Huh 7 and its probable molecular mechanism.Methods:The human hepatocellular carcinoma cells Huh 7 cultured in vitro was treated with leptin at different concentrations.The proliferation of the cells was measured by MTT assay.The cell cycle was monitored by flow cytometry analysis(FCM).The expression of cell cycle regulatory proteins Cyclin D1 and P21waf1 were determined by immunocytochemistry and imageanalysis system,and real-time quantitative PCR.Results:Leptin significantly raised the proliferation rate of Huh 7 cells.The effect was dose and time-depended partly.Leptin promoted Huh 7 cells in entering the S phase from the G0/G1 phase.mRNA of Cyclin D1 in the leptin treated Huh 7 cells was increased,as compared with that in the control cells(P