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OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.
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Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.
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Objective:To explore the regulatory effects of cow milk with the addition of breast milk equivalent dose of somatostatin (SST) and motilin (MTL) on food allergy and food intolerance.Methods:Young Brown Norway (BN) rats were divided into 5 groups and fed with pure breast milk(breast milk group), cow milk(cow milk group), cow milk added with SST(SST group), cow milk added with MTL(MTL group) and cow milk added with both SST+ MTL(SST+ MTL group). Allergic irritation was enhanced with skin smear at the same time.Clinical damages were quantified weekly.Levels of serous total Immunoglobulin E (IgE) and fecal calprotectin (FC) were detected by the enzyme-linked immunosorbent assay (ELISA). Gastric emptying ratio and intestinal propulsion ratio were measured by method of dextran blue.Results:In breast milk group, cow milk group, SST group, MTL group and SST + MTL group, the levels of IgE were (45.75±5.05) μg/L, (580.42±45.24) μg/L, (290.38±22.88) μg/L, (424.26±22.17) μg/L, (209.49±17.59) μg/L, respectively; FC level were (149.07±24.78) μg/g, (458.85±33.81) μg/g, (343.63±34.97) μg/g, (407.79±29.62) μg/g, (296.83±28.77) μg/g, respectively; the total score of clinical damage were (0.50±0.61) scores, (9.37±1.04) scores, (6.83±1.49) scores, (7.00±1.14) scores, (5.37±1.19) scores, respectively.The cow milk group had the highest scores of clinical damages.Compared with the cow milk group, the clinical damage score, IgE and FC of the SST, MTL and SST+ MTL groups had significantly lower levels, and there was significant difference among them (all P<0.01). The general status of the SST + MTL group was most similar to the breast milk group.The gastric emptying rate of MTL group was the closest to that of breast milk group [(92.52±6.27)% vs.(100.00±9.70)%, P<0.05]. There were obvious diarrhea and fast small intestinal propulsion in cow milk group, the small intestinal propulsion ratio in breast milk group was (39.32±2.61)%, and (71.96±4.43) % in cow milk group, the difference was statistically significant between the 2 groups ( P<0.01). The intestinal motility of SST+ MTL group was decreased, but it just prevented diarrhea caused by milk allergy, the small intestine propulsion ratio in SST+ MTL group was (38.90±2.65)% vs.breast milk group (39.32±2.61)%( P>0.05). Conclusions:The cow milk added with SST and MTL decreased allergic reaction and increased food tolerance in gastrointestinal tract, which was more similar to breast milk.SST was beneficial to relieving allergic immune reaction, MTL contributed to improving the gastrointestinal tolerance of cow milk.The combination of SST and MTL may achieve an antagonistic and balanced mechanism on gastrointestinal regulation, which could synergistically improve the gastrointestinal tolerance of cow milk.
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Currently, pediatric tuberculosis is still a serious infectious disease endangering pediatric health, and anti-tuberculosis (TB) therapy is the major treatment for this disease.The course of anti-TB treatment in children is generally long and requires multi-drug combination, which significantly increases the risk of adverse drug reactions(ADRs). Therefore, it is important for pediatricians to have an intimate knowledge of ADRs and countermeasures.The common ADRs in children include anti-TB drug-induced liver injury, skin adverse reactions, gastrointestinal reactions, drug fever, and post-bulbous neuritis.For children with mild and tolerable ADRs, symptomatic treatment should be performed and anti-TB treatment continued.If the adverse reaction is serious or cannot be tolerated, the drug should be stopped in time.If ADRs are complex, serious or rare, multidisciplinary discussion should be conducted to make the best clinical decision.
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Objective To explore the virulence of enterovirus 71 from infected children in neonatal mice. Methods Three strains of EV71 were isolated from the mild, severe and dead patients. Symptoms, weight and death of mice were recorded throughout 14 days. The mice were sacrificed on the first, third, fifth, seventh and ninth days post infection to gain the tissue virus load including the liver, spleen, lung, intestine, brain and muscle tissue which were used to detect the virus tilter by real-time RT-QPCR, and pathological lesions using HE staining. Results As to the severity of symptoms, no significant difference was found between the severe and mild groups (P＝0. 693), which were more serious than that of the fatal group. (P＝0. 000 ＜ 0. 05/6, P＝0. 000 ＜ 0. 05/6). The survival rate of the mice with mild, severe and fatal virus infection was 77. 2%, 81. 7% and 97. 8%, respectively, and there was a significant difference among the three groups (P＝0. 0010 ＜ 0. 05, P＝0. 001 ＜ 0. 05, P＝0. 0004 ＜ 0. 05). Lung hemorrhage of the mild group was the most serious, and there were no significant differences in pathological lesions of the brain, muscle, spleen and intestine. Virus titer in the liver and muscle was higher than the other tissues and that in mild group of different tissues tended to be higher than the other two groups. Conclusions Neonatal mice infected with the mild strain of enterovirus 71 presents heaviest symptoms, which are not consistent with the outcomes of humans. It is considered to be related to the virus gene, host and other factors.
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Gut microbiota means a highly diverse and dense microbiota which inhabits in the gastrointestinal tract of humans.It plays a vital role in many important physiological processes including exerting nutritional and metabolic activities,regulating the immune system,and protecting against pathogens.Recent studies suggested that the gut microbiota was associated with the development of many lung diseases,such as pneumonia,asthma and tuberculosis.There is a gut-lung axis in human body.Now,the relationship between the gut microbiota and the gut-lung axis is reviewed.
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Objective@#To evaluate the efficacy and safety of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea (AAD) in infants and young children.@*Method@#From November 2012 to September 2013, ten research units of large teaching hospitals or children′s hospitals participated in this multicenter randomized controlled clinical trial. Hospitalized young children aged between 1 month and 3 years (nongastrointestinal infection and antibiotic therapy required)were involved in our study. The children were randomly divided into control group and prevention group by means of block random allocation method. The control group received antibiotic therapy and other conventional treatment. The prevention group was given additional Saccharomyces boulardii (250 mg/d) orally. Diarrhea rates of two groups were compared both during the usage of antibiotics and within 14 days after the antibiotics withdrawal. The adverse reactions of Saccharomyces boulardii were observed all through this study. The results were analyzed by χ2 test or Kruskal-Wallis test or t test.@*Result@#Totally 408 cases (213 cases in prevention group and 195 cases in control group) were enrolled. The age ranged from 1 month to 3 years, with an average age of 1.14 years. The basic diseases were parenteral infections: 368 cases with different kinds of respiratory tract infections or pneumonia, 10 cases of bacterial meningitis, 9 cases with septicemia or sepsis, 6 cases with pertussis or pertussis like syndrome, 5 cases with urinary infection, 5 cases with skin or subcutaneous tissue infections, 3 cases of Kawasaki disease, one with scarlet fever and one with congenital syphilis. During the administration of antibiotics, the incidence of AAD in prevention group was 10.3% (22 cases), which was significantly lower than that of control group (57 cases, 29.2%, χ2=23.296, P<0.05). Within 14 days after the discontinuation of antibiotics, the percent of new diarrhea cases in prevention group (2.4%, 5/213) was also significantly lower than that in control group (16.4%, 32/195, χ2=23.4, P<0.05). Further analysis revealed that the rate of AAD in children less than or equal to 1 year old (25.1%, 52/207) was significantly higher than that of over 1 year old (13.4%, 27/201, χ2=8.922, P<0.05). The incidence of AAD in children treated with antibiotics for more than 5 days was 22.2%(60/270), which was significantly higher than that of less than or equal to 5 days (13.8%, 19/138, χ2=4.180, P<0.05). Although no significant difference was observed, the AAD rate of patients with combined use of two antibiotics was higher than that of using one. During the antibiotic therapy, compared with the control group, the risk of AAD in children under 1 year old was reduced by 52% (χ2=9.217, P<0.05), and 91% (χ2=20.35, P<0.05) in the children over 1 year old in prevention group. The risk of AAD of prevention group decreased by 66% (χ2=13.67, P<0.05) in patients treated with one antibiotics, and 65% in children with combined use of antibiotics (χ2=10.57, P<0.05). In patients treated with antibiotics for less than or equal to 5 days, the risk of AAD decreased by 74% in prevention group (χ2=7.38, P<0.05); and 63% if the course lasted for over 5 days (χ2=16.87, P<0.05). Within 14 days after the withdrawal of antibiotics, compared with the control group, the risk of diarrhea in the prevention group decreased by 82% (χ2=13.35, P<0.05) in infants (≤1 year old) and 93% (χ2=12.00, P<0.05) in children (>1 year old); the risk of diarrhea was reduced by 86% (χ2=9.57, P<0.05) and 87% (χ2=17.71, P<0.05) respectively in prevention group with single and combined use of antibiotics. In patients treated with antibiotics for more than 5 days, the risk of diarrhea in prevention group was reduced by 63% (χ2=22.79, P<0.05), while there was no significant difference if the antibiotics course was less than or equal to 5 days (χ2=2.97, P>0.05). No adverse effects related with Saccharomyces boulardii were observed in our study.@*Conclusion@#Saccharomyces boulardii is effective and safe to prevent AAD of infants and young children both during the usage of antibiotics and up to 14 days after drug discontinuance. It can be one of the drugs of for choice prevention of AAD in infants and young children. Trial registration Chinese Clinical Trial Tegister, ChiECRCT-2012-25.
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Objective@#To explore the clinical characteristics of drug-resistant tuberculosis (TB) in children and to study the effectiveness of second-line anti-TB therapy for children and to examine the incidence of adverse drug reactions.@*Method@#Retrospective research was conducted. The clinical records of children in West China Second Hospital diagnosed as drug-resistant TB from January 2010 to June 2014 were investigated.The clinical characteristics and risk factors were analyzed retrospectively. Treatment effect at discharge was examined as a short-term outcome indicator to evaluate the effectiveness of second-line anti-TB therapy and the incidence of adverse drug reactions. χ2 test was used.@*Result@#Forty-six patients were diagnosed as drug-resistant TB in 443 children infected with TB, with a 10.4% resistance rate. The 46 children included 26 male and 20 female patients, aged from one month and 28 days to 17 years and 5 months, with the average age (8.4±4.5) years, >7 to 14 years old patients as the biggest part(25 patients, 54.3%). Among the 46 children, 20 patients(43.5%)had close contact with TB patients, of whom 12 patients (60.0%) contacted with family members (including parents, brothers and sisters and grandparents living together) and 8 patients(40.0%) contacted with patients from outside family (such as relatives or neighbors). Moreover, 11 cases (23.9%) were under initial treatment and 35 cases (76.1%) were retreated.From 2010 to 2014, the number of cases of initial and retreated patients had no significant difference(0 and 1, 1 and 13, 4 and 7, 4 and 11, 2 and 3 cases, χ2=3.255, P=0.196). Among retreated patients, 31.4% (11/35) had irregular treatment before.Until discharge, the effective rate was 87.0% (40/46), while the incidence rate of adverse drug reaction was 10.9%(5/46).@*Conclusion@#The therapy for drug-resistant TB is effective and the incidence of adverse drug reaction is relatively low.
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Objective To summarize the clinical features of Pseudomonas aeruginosa sepsis in children. Methods We retrospectively review the clinical data of a baby boy with Pseudomonas aeruginosa sepsis and summarize its clinical character-istics. Results A ten-month male infants with onset symptom of fever, irritability, drowsiness, cough and sputum was diagnosed as Pseudomonas aeruginosa sepsis through blood and sputum culture. The baby recovered well after anti-infection treatment. Conclusions Timely and appropriate use of sensitive antibiotics can decrease severe complications and mortality rate of Pseu-domonas aeruginosa sepsis in children.
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Objective Through retrospective data analysis,we tried to further understand the epide-miological characteristics,clinical feature and death factors of infant and young children with severe pneumo-nia. Methods The study objects were inpatients( age between≥28 days and≤3 years) who were diagnosed severe pneumonia from 1 January,2011 to 31 December,2013 of the Chengdu Women′s and Children′s Cen-tral Hospital. We used retrospective case study to understand the epidemiology,clinical feature,death factors of infant and young children with severe pneumonia. And we used chi-square test and Logistic multivariate regression analysis to analyze the death factors of infants and young children with severe pneumonia. Results (1) Among 1 411 cases of severe pneumonia,the ratio of male and female was 1. 8∶1,and the ratio of urban and rural areas was 1∶3. 62. The proportion of less than 3 months old infant was 46. 00%. And 62. 93% infant and young children with severe pneumonia occurred in the spring and winter. (2) Average hospitalization time was (9. 99 ± 6. 27 ) days, longer than the hospitalization time of mild pneumonia patients. ( 3 ) A total of 64. 21% of infant and young children with severe pneumonia had basic diseases. (4)A total of 91. 99% of the infant and young children with severe pneumonia had complications. (5) The most common etiology of infant and young children with severe pneumonia was bacteria,the second was virus. (6) In all cases,there were 44 cases died. The mortality of infant and young children with severe pneumonia was 3. 12%. And 72. 73% of the death cases were infants less than 3 months old. (7) The results of Logistic multiple regression analysis showed that there were significant differences in age, congenital heart diseases, repeating infection history, multiple drug-resistant strains infection, surgical history, multiple organ dysfunction, internal environment disorder. Conclusion Infant and young children with severe pneumonia have the following characteristics:most of them occurred in the winter and spring, and come from rural more than from the city. The smaller the age, the incidence of a disease is higher,and the mortality is higher. Most of infant and young children with severe pneu-monia have basic diseases. Most of the infant and young children with severe pneumonia have complications. If having one of the following high-risk factors:less than 3 months old,congenital heart diseases,repeating infec-tion history,multiple drug-resistant strains infection,surgical history,multiple organ dysfunction,internal envi-ronment disorder,the infant with severe pneumonia should be intensively monitored and actively treated.
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Objective To investigate therapeutic autcomes of using telomerase inhibitors to treat cancer at the presumably most and least opportune circadian stages basing on our earlier study. Methods Twenty-four BALB/C nude mice were synchronized to a regimen of LD12:12 for 4 wk. Hepatic cancer cells (SMMC-7721) were implanted into both flanks of each mouse.Two weeks after transplantation,the hTERT-5'RZ was used to treat the hepatic cancer transplanted into the nude mice daily for two weeks,the injection times being either 9 or 21 HALO.Results The tumorinhibition ratio of mice treated at 21 HALO (65%) was statistically significantly higher than that of mice treated at 9 HALO (48%). Telomerase activity was also reduced to a greater extent in mice treated withhTERT-5'RZ at 21 than at 9 HALO, that was at the time of maximal circadian telomerase activity. Conclusion Injection of ribozyme targeted to telomerase during the tumor's DNA synthesis is associated with a betterinhibition of tumor growth and a better therapeutic outcome in hepaticcancer.
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Objective To compare the characters of circadian rhythm of the cardiovascular function between full-term and premature infants.Methods Blood pressure(BP),aortic blood velocity(ABV),aortic blood acceleration(ABA) and aortic strok distance(ASD) were continuously measured in full-term and premature infants for 48 h.Each time series was analyzed with 24-hour cosine curve-fitting method.Results The parameters of cardiovascular function in most of the full-term infants,including BP,ABV,ABA and ASD showed robust circadian rhythm,but most of premature infants did not show obvious circadian rhythm.The averages of those parameters were not different in full-term and premature infants,whereas the amplitude were significant different in the two groups.Conclusion It is indicated that the functions of the cardiovascular system was not different in full-term and premature infants,but circadian rhythm of cardiovascular system in premature infants has not perfectly developed.
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AIM:To investigate atrial natriuretic peptide(ANP) circadian in the encapsulated human ANP(hANP) cDNA transfected cells,to alter the ANP circadian by artificial control to achieve the objective of effectively treat hypertension or congestive heart failure(CHF). METHODS:ANP cDNA was transfected into Chinese hamster ovary(CHO) cells,which were encapsulated in polycarprolactone(PCL) tubes.The longterm survival of transfected CHO cells and the levels of ANP secreted were detected.Circadian rhythm of ANP secreted by encapsulated transfected cells was also studied,which was regulated by melatonin. RESULTS:During culturing,the ANP level secreted by transfected CHO cells in 2 mL of culture medium within 24 hours could reach 210.3 ng/L in a 20 mm-long and 2 mm-diameter PCL tube.The section of ANP displayed a circadian variation:higher in daytime,but lower at night.The acrophase of circadian rhythm was 4:15 but could be shifted to 7:55 after melatonin management. CONCLUSION:ANP cDNA transfected CHO cells that encapsulated into PCL tube can secret ANP,which might be suitable for the future implantation into human body.Our research provides a new approach in the treatment of hypertension and CHF by ANP.
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A technique based on release of the human atrial natriuretic peptide (hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO) cells encapsulated in polycaprolactone (PCL)-capsules was used for a potential therapeutic approach to hypertension or congestive heart failure (CHF). The plasmid combining with hANP cDNA was transfected into CHO cells, and then encapsulated plasmid hANP cDNA transfected CHO cells were implanted into two-kidney, one-clip (2K1C) hypertensive rats intraperitoneally. The morphological changes, histological changes were investigated after the implantation of PCL-capsules in 2K1C hypertensive rats. The results showed that the implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase after the encapsulated cells being implanted in 2K1C hypertensive rats. These effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions, tubular damage and renal arterial thickening, comparing with control group. The plasma levels of hANP in 2K1C rats implanted with the PCL-capsules containing hANP-producing cells were higher than that of the control rats. These results demonstrated the usefulness of encapsulated hANP gene transfected cells as a new tool for hANP gene delivery in studying renovascular hypertension and cardiovascular diseases, thus implying the potential of using gene transfected cells as therapeutic agents in the treatment of cardiovascular diseases.
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Animals , Cricetinae , Humans , Male , Rats , Atrial Natriuretic Factor , Genetics , Therapeutic Uses , CHO Cells , Capsules , Cell Transplantation , DNA, Complementary , Genetics , Genetic Therapy , Methods , Hypertension, Renovascular , Pathology , Therapeutics , Kidney , Pathology , Plasmids , Rats, Wistar , Recombination, Genetic , Transfection , TransgenesABSTRACT
Objective A number of cardiovascular variables exhibit a circ adian rhythm. Whethe r myocardial contractile response and gene expression of the contractile protein also show changes with a similar period was here investigated. Method Circadi an variabilities in the left ventricular developed pressure (LVP) and contractil ity (LV dp/dt max) were measured in 24 Sprague-Dawley r ats by directly left ve ntricular catheterizing and compared with changes in the gene expression of α- myosin heavy chain (α-MHC) in myocytes obtained from the same animals by dot b lottin g analysis. Results A circadian rhythm was seen in the variabili ty of LVP (P<0.001), LV dp/dt max (P<0.001) and the bio chemically measured expression of the α- MHC gene (P<0.01). As compared to the amplitude of the rhythm i n α-MHC gene exp ression, the amplitude of the contractility rhythm was large (P< 0.01) and the ci rcadian amplitude of the LVP(P<0.001) was the largest, represent ing perhaps a co mposite of intracardiac plus any extracardiac contributions. Conclusion One of factors determing the circadian rhythm of myocardial contractile function is α -MHC gene expression level.
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AIM:To determine the relationship between microhistology and cardiac contractility in myocarditis animal model. METHODS:Setting up myocarditis animal model by injecting Coxsackivevirus B 3 (CVB 3) into mice, then observed myocardial morphological changes and measured left ventricular function of mice at the time of first three days and two weeks after injecting CVB 3.RESULTS:Subcellular structure (mitochondria) changed at the first three days after injecting CVB 3. The left ventricular pressure (LVP) and the rate of intraventricular pressure development (d p /d t ) which is the index of reflecting cardiac contractility depressed in this stage (14.2?0.8) kPa and (273.1?10.0)kPa/s, respectively. There were (17.1?0.7)kPa and (359.8?9.3)kPa/s in normal mice, respectively ( P