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Quinacrine has been identified as a potent DR5-inducing agent that sensitizes cancer cells to TRAIL-induced apoptosis. In the current study, we found that quinacrine increased DR5 mRNA levels significantly in ovarian cancer cell lines regardless of p53 status. Further study showed the half-life of DR5 in quinacrine-treated cells was significantly prolonged, indicating that DR5 protein degradation was inhibited by quinacrine. We tested if the combination of TRAIL and quinacrine could be effective in ovarian cancer treatment in vitro and in ovarian cancer xenograft mouse models. We found that quinacrine enhanced TRAIL sensitivity or reversed TRAIL resistance in all the ovarian cancer cell lines tested. Mice treated with quinacrine and TRAIL remained disease-free for up to 20 weeks, however, mice treated with TRAIL or quinacrine alone and in control group died within ~8 weeks after treatment. Intraperitoneal delivery of quinacrine and TRAIL is rational and practical with extraordinary synergistic anti-cancer effects in preclinical models of ovarian cancer. Clinical investigation of combining quinacrine with TRAIL for ovarian cancer treatment is warranted.
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BackgroundThe first case of COVID-19 atypical pneumonia was reported in Wuhan, China on December 1, 2019. Since then, at least 33 other countries have been affected and there is a possibility of a global outbreak. A tremendous amount of effort has been made to understand its transmission dynamics; however, the temporal and spatial transmission heterogeneity and changing epidemiology have been mostly ignored. The epidemic mechanism of COVID-19 remains largely unclear. MethodsEpidemiological data on COVID-19 in China and daily population movement data from Wuhan to other cities were obtained and analyzed. To describe the transmission dynamics of COVID-19 at different spatio-temporal scales, we used a three-stage continuous-time Susceptible-Exposed-Infectious-Recovered (SEIR) meta-population model based on the characteristics and transmission dynamics of each stage: 1) local epidemic from December 1, 2019 to January 9, 2020; 2) long-distance spread due to the Spring Festival travel rush from January 10 to 22, 2020; and 3) intra-provincial transmission from January 23, 2020 when travel restrictions were imposed. Together with the basic reproduction number (R0) for mathematical modelling, we also considered the variation in infectivity and introduced the controlled reproduction number (Rc) by assuming that exposed individuals to be infectious; we then simulated the future spread of COVID across Wuhan and all the provinces in mainland China. In addition, we built a novel source tracing algorithm to infer the initial exposed number of individuals in Wuhan on January 10, 2020, to estimate the number of infections early during this epidemic. FindingsThe spatial patterns of disease spread were heterogeneous. The estimated controlled reproduction number (Rc) in the neighboring provinces of Hubei province were relatively large, and the nationwide reproduction number - except for Hubei - ranged from 0.98 to 2.74 with an average of 1.79 (95% CI 1.77-1.80). Infectivity was significantly greater for exposed than infectious individuals, and exposed individuals were predicted to have become the major source of infection after January 23. For the epidemic process, most provinces reached their epidemic peak before February 10, 2020. It is expected that the maximum number of infections will be approached by the end of March. The final infectious size is estimated to be about 58,000 for Wuhan, 20,800 for the rest of Hubei province, and 17,000 for the other provinces in mainland China. Moreover, the estimated number of the exposed individuals is much greater than the officially reported number of infectious individuals in Wuhan on January 10, 2020. InterpretationThe transmission dynamics of COVID-19 have been changing over time and were heterogeneous across regions. There was a substantial underestimation of the number of exposed individuals in Wuhan early in the epidemic, and the Spring Festival travel rush played an important role in enhancing and accelerating the spread of COVID-19. However, Chinas unprecedented large-scale travel restrictions quickly reduced Rc. The next challenge for the control of COVID-19 will be the second great population movement brought by removing these travel restrictions.
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COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 if of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004-0.07) in Hubei. Every 1{degrees}C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04{degrees}C to 8.2{degrees}C. However, these associations were not consistent throughout Mainland China.
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Objective To study the effect of Interleukin-22 (IL-22) on murine asthmatic airway inflammation and airway remodeling, observe the effect of budesonide on IL-22 of asthmatic mouse model, explore the mechanism of budesonide in the treatment of asthma.Methods Ovalbumin(OVA) was used as an allergen to sensitize and challenge the mice.24 female specific-free (SPF) BALB/c mice aged four weeks were randomly divided into 3 groups:control group, asthma group and budesonide treatment group (BUD group).For Histopathological Examination, HE staining was used to measure the inflammation scores, AB-PAS staining was used to measure the hyperplasia of goblet cells and mucin.Enzyme-linked immunosorbent assay(ELISA) was used to analyze IL-22 levels in bronchoalveolar lavage fluid (BALF).Quantitative Real-time PCR was performed to analyze the effects of budesonide on IL-22 mRNA levels in lung tissue.Results The inflammation scores of asthma group were elevated compared with the control group.An overall change towards less severe asthmatic airway inflammation by the end of the trial was observed in the BUD group.IL-22 levels in BALF were significant decreased after the treatment of budesonide, the mRNA levels of IL-22 were obviously decreased in BUD group, too.A significant positive correlation was observed between the mRNA levels of IL-22 and airway inflammation.Conclusions The increasing IL-22 secretion can lead to the occurrence of airway inflammation of asthma.Budesonide can inhibit the expression of IL-22, thereby Budesonide could inhibit the development of airway inflammation of asthma.
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This report presents 3 cases of Castleman's disease in the head and neck.The clinical symptom,pathlogical and imaging features of the Castleman's disease are introduced.
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Objective To design a data management solution based on geographic information system for health service units to deal with health resources of subordinate medical institutions.Methods The whole solution was developed with layer logic function of data service, application and presentation. Storage, transformation and relationship of both spatial data and health service data were totally managed by relational database.Results The system was able to import, export, maintain, sum, query and analyze geography spatial information and health service information.Conclusion A new method is provided to improve capability of health support and health service management efficiency.
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BACKGROUND:Hemodialysis therapy is an important means for the treatment of acute renal failure, which aims to remove excess water and toxins and maintain acid-base balance of a patient, creating conditions for medication and nutrition therapy while avoiding multiple organ failure. OBJECTIVE:To compare bicarbonate-and lactate-buffered solutions for acute continuous hemodiafiltration in acute renal failure. METHODS:A computer-based search was performed in PubMed, EMBASE, SCI, Cochrane Library, Chinese Biomedical Literature Database, China Journal Ful Text Database, Chinese Medical Association Journals for randomized control trials related to bicarbonate-versus lactate-buffered solutions for hemodiafiltration in acute renal failure published before January 2014. The quality of the included studies was evaluated by Cochrane Handbook, and data were analyzed by RevMan 5.1 from the Cochrane Col aboration. RESULTS AND CONCLUSION:Four studies (171 patients) met inclusion criteria. Overal , patients treated with bicarbonate-buffered solutions had fewer cardiovascular complications and symptomatic hypotension events as wel as lower serum lactate levels than patients who received lactate-buffered solutions (P<0.05). There were no differences in mortality, serum bicarbonate levels, serum creatinine, serum pH, carbon dioxide partial pressure. The current evidence shows that patients undergoing bicarbonate-buffered solutions may experience fewer cardiovascular complications and symptomatic hypotension. Given the limited research, it is insufficient to recommend for clinical use.
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Objective To explore the relationship between traditional Chinese medicine (TCM) syndromes of state of evil domination and clinical and laboratory indicators of IgA nephropathy. Methods A prospective study was used to collect data on clinical and laboratory examination of IgA nephropathy in multi clinical centers. Patients’ TCM syndrome types were determined according to the national diagnostic criteria at the same time. Totally 266 patients with IgA nephropathy were included in the study to establish a database for analyzing the relationship between TCM syndrome of state of evil domination and clinical and laboratory indicators. Results In the relationship between syndromes of state of evil domination distribution and clinical subtypes, patients of wind-heat syndrome had more macroscopic hematuria;patients of phlegm-damp syndrome had more nephrotic syndrome;patients of damp-heat syndrome had more chronic nephritis type Ⅰ;patients of blood stasis syndrome had more chronic nephritis type Ⅱ. In the relationship between syndrome of state of evil domination distribution and clinical manifestation, the incidence of hypertension was higher in patients of blood stasis syndrome than in other three types. It was more serious for hematuresis in the patients of wind-heat syndrome. For patients of phlegm-damp syndrome, the incidence of heave proteinuria was highest. In the relationship between syndrome of state of evil domination distribution and laboratory examination, 24-hour urinary protein quantification was higher than in patients of wind-heat and damp-heat syndrome, but the level of blood albumin was lowest. For patients of blood stasis syndrome, serum creatinine level was significantly higher than in other three types;the level of eGFR was just the opposite. The levels of blood cholesterol and triglyceride in patients of phlegm-damp syndrome were higher than in other three types. The activated partial thromboplastin time (APTT) levels in patients of blood stasis and phlegm-damp syndrome were lower than in other patients, but the FIB level was the exact opposite of APTT. In the relationship between syndrome of state of evil domination distribution and the stages of chronic kidney disease (CKD), patients of wind-heat syndrome were more in the first stage of CKD;patients of blood stasis syndrome were more in the third stage of CKD. Conclusion There is relative correlation between TCM syndromes of state of evil domination and clinical and laboratory indicators in IgA nephropathy, which would provide some reference to narrow the gap in the information of the four methods of TCM with clinical and laboratory indicators to enhance accurate diagnosis of TCM syndrome.
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Objective To evaluate the effects of angiotensin Ⅱreceptor antagonist (ARB) on expression of plasminogen activator inhibitor(PAI)-1 in the human renal biopsy of patients with chronic kidney disease(CKD)and analyse its clinical significance.Methods PAI-1 expression of 63 specimens with CKD was detected by immunohistochemistry and quantitative analysis was achieved by image analysis system. meanwhile, the patients'clinical data were collected,and PAI-1 expression of 63 specimens with CKD was compared with that of normal renal tissue(19 cases).Results Compared with the normal renal tissue,the expression of PAI-1 in CKD 1,2 and 3 stage wag respectively drastically increased(P<0.05).The expression of PAI-1 in CKD 3 stage was higher than that in CKD 1 and 2 stage(P<0.05).The expression of PAI-1 in the patients treated by valsartan[renal corpuscle(4.73±1.18)%,renal tubule(37.16±6.81)%]was lower than that with no treatment[renal corpuscle(5.81±1.95)%,renal tubule(43.22 ±10.25)%](P<0.05).Conclusions It suggests that the abnormal expression of PAI-1 in CKD play an important role in the progression of glomerular and tubulointerstitiai sclerosis in patients with CKD.ARB may prevent the development of renal inflammation and sclerosis by inhibiting the production of PAI-1.ARB may contribute to the prevention and therapy of CKD.
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Objective To study the effect of Qingfei oral liquid contained serum on the transforming growth factor-?1 (TGF-?1) and platelet-derived growth factor-BB (PDGF-BB) mRNA gene expression of human embryonic lung fibroblast cells infected by adenovirus (ADV) type 3I and 7b. Method TGF-?1 and PDGF-BB mRNA expression of human embryonic lung fibroblast cells infected by ADV type 3I and 7b were determined by in situ hybridization before and after treated with Qingfei oral liquid contained serum. Results ADV could up-regulate TGF-?1 and PDGF-BB mRNA of human embryonic lung fibroblast cells (P
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Objective:To study the effect ofQingfei Oral Liquid medicated serum on the tumor necrosis factor-?(TNF-?) mRNA gene expression ofhuman embryonic lung fibroblasts induced by adenovirus Type3I, 7b.Methods:We determined the TNF-? mRNA ofADV-infected human embryonic lung fibroblasts before and after adding the medicated serum by in situ hybridization.Results:Adenovirus could up-regulate the TNF-?mRNA ofhuman embryonic lung fibroblasts(P
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This thesis studies professor WANG Shou-chuan’s clinical experience in treating atopic dermatitis with traditional Chinese medicine (TCM). Professor Wang believes that the key pathogeneses of atopic dermatitis are wind, dampness and toxins. The main therapy is clearing away wind, resolving dampness and removing toxins. It is differentiated as infant period, child period and adult period according to the patients’ age. Xiaofeng san, Bixieshenshi tang and Yangxuedingfeng tang are three main prescriptions in treating this disease. It is emphasized that toxin is the most important pathogenesis of atopic dermatitis, and removing toxins should be used in every period. Moreover, professor Wang is good at using insect medicine to clear away wind and stop itch.
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OBJECTIVE:To evaluate the expression on plasminogen activator inhibitor-1 (PAI-1) in the human renal biopsy of patients with CKD and analyze its clinical significance.METHODS:The expression of PAI-1 in 63 specimens of patients with CKD(CKD group) and 19 normal renal tissue(Control group) were detected by immuno-histochemistry.The expression of PAI-1 in the normal renal tissue were compared with the each phase CKD group.Meanwhile,The expression of PAI-1 in 16 patients with CKD treated by valsartan were compared with 47 cases not treated.RESULTS:Compare with the control group,the expression of PAI-1 in each phase CKD group was respectively drastically increased (P
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Reccent investigations demonstrated that genetically modified tumor cells could be used as vaccines against cancer. In this light, we introduced human interleukin -2 (IL-2) gene into a poorly immunogenic rat fibrosarcoma cell line WBT, a human lung abenocarcinoma cell line AGZY and a highly metastatie sub - cell line Anip973 derived from AGZY. The transduced cells showed no obvious changes in morphology, growth and colony - forming ability in soft agar.Transduction with IL-2 gene rendered the cells more sensitive than the parental cells and cells transduced with NeoR gene alone to the lysis by cytotoxic lymphocytes. High levels of IFN and TNF were detected in the supernatants of cocultured lymphocytes and tumor cells containing IL-2 gene. Tumorigenicity of WBT/IL-2 cells was greatly reduced in syngeneic rats. Metastatic capacity of Anip973 in nude mice was blocked by the transduction of IL-2 gene, but not the transduction of NeoR gene alone. Inoculation of WBT/IL-2 cells conferred rats resistance to the challenge of parental WBT cells.Splenocytes from WBT/IL-2-inoculated rats restimulated with WBT cells in vitro showed high CTL activity against WBT cells. Our results demonstrated the potential application of tumor cells transduced with IL— gene as active vaccine against cancer.
