Characteristics of gastric microbiota in children and the relationship with Helicobacter pylori infection / 国际儿科学杂志

Helicobacter pylori (Hp) plays an important role in the development of a variety of digestive diseases in children, but in addition to Hp, there are many other gastric microbiota also critical for children′s health.At present, the characteristics of children′s gastric microbiota may be still relatively unclear.This artical summarizes the composition, succession process and function of children′s gastric microbiota, and reviews the relationship between gastric microbiota and Helicobacter pylori infection in children.

Application of Different Decision Analysis Models in the Economic Evaluation of Antitumor Drugs ：Taking CADTH in Canada as an Example / 中国药房

OBJECTIVE：To provide referenc e for selectin g antitumor drugs economic evaluation models and improving the quality of evidence for antitumor drugs economics evaluation in China. METHODS ：A systematic search of the antitumor drug health technology evaluation （pCODR）reports were conducted on the official website of the Canadian Agency for Drugs and Technologies in Health （CADTH）. The search time was limited to Jan. 1st，2015 to Sep. 6th，2020. The basic information ，model types and structure ，and key limitations were extracted and summarized. RESULTS & CONCLUSIONS ：A total of 185 pCODR reports were finally retrieved ，involving 114 types of tumor indications and 98 types of antitumor drugs. The number of CADTH antitumor drugs economics evaluations in the past 5 years had shown an increasing trend. Among 137 pCODR reports with final economic guidance report ，98 reports（71.5％）adopted the PartSA model ，21 reports（15.3％）used the Markov model ，and some reports（6 reports，4.3％）used both PartSA and Markov models to explore the uncertainty of the model structure. In terms of model health status setting ，86 reports（62.8％）used three-state models to evaluate the economy of different anti tumor drugs ，and 16 reports（11.7％）used no less than four health states to simulate the outcome of disease state. However ，there were still some problems in CADTH models ，such as the unreasonable choice of research time limit ，the unreasonable extrapolation method or uncertain extrapolation results of efficacy （survival）data，the uncertainty of efficacy data obtained by indirect comparison ，and some assumptions or parameter settings did not conform to the actual diagnosis and treatment environment. In view of the advantages of PartSA model ，it is suggested that PartSA model or Markov model combined with PartSA model should be used first to verify the uncertainty of model structure in the future economic evaluation of antitumor drugs ；reasonable settings of key model parameters should be considered to improve the quality of evidence for antitumor drugs economics evaluation in China.

Network Meta-analysis on efficacy and safety of non-steroidal anti-inflammatory drugs for osteoarthritis in middle aged and old people / 药学实践杂志

Objective To systematically evaluate the efficacy and safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in middle-aged and old Chinese patients with osteoarthritis(OA). Methods A systematic literature search was conducted through PubMed, Cochrane Library, CNKI, Wan Fang Data and VIP databases to collect randomized controlled trials with non-steroidal anti-inflammatory drugs in middle-aged to old Chinese OA patients. The search time was from the establishment of the database to November 17, 2020. Two researchers independently carried out literature screening, data extraction and literature quality evaluation. Bayesian network meta-analysis was conducted with R3.6.0 software. Results 28 RCTs were included with 2531 patients. Based on the last follow-up pain visual analogue scale (VAS) score, the ranking chart showed that Etoricoxib had the highest probability of having the lowest pain VAS score (88.55%). In terms of total effective rate, the ranking chart showed that the probability of Etoricoxib as first choice was the highest (92.49%). As far as safety, diclofenac sodium patch had the lowest adverse effects rate (59.10%). Conclusion The results of this study indicated that Etoricoxib was the most effective treatment for middle-aged and old Chinese OA patients. It can significantly reduce the OA pain. Diclofenac sodium patch had the least adverse effects.

Cost-utility Analysis of Pembrolizumab in the Second-line Treatment of Advanced Hepatocellular Carcinoma Based on Two Models / 中国药房

OBJECTIVE：To evaluate the econo mics of pembrolizumab in the second-line treatment of advanced hepatocellular carcinoma in China. METHODS ：From the perspective of Chinese healthcare system ，a three-state PartSA model and Markov model were established ；the cost and utility for the second-line treatment of advanced hepatocellular carcinoma in China were compared between pembrolizumab and placebo. The circulation cycle of the model was 3 weeks and the study time limit was lifetime；one-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS ：PartSA results showed that the ICER for the second-line treatment of advanced hepato- cellular carcinoma with pembrolizumab was 1 266 846.18 yuan/QALY，which is far more than 1-3 times of China ’s per capita GDP in 2020. The results of one-way sensitivity analysis showed that the three parameters that had the greatest impact on ICER were the PFS status utility of the placebo group ，the PFS status utility of the pembrolizumab group ，and the cost of pembrolizumab. The results of probability sensitivity analysis verified the robustness of the base-case analysis. The scenario analysis showed that the treatment cost of pembrolizumab had dropped significantly when the charity donation of pembrolizumab was considered. Although it was still not economical ，ICER was close to 3 times of per capita GDP of China in 2020. When WTP threshold was 1 and 3 times of China ’s per capita GDP ，the economic prices of pabolizumab （100 mg）were 4 157.67 and 5 829.24 yuan，respectively. The results of Markov model were similar to those of PartSA model. CONCLUSIONS ：Under the WTP threshold of 1-3 times China ’s per capita GDP in 2020，pembrolizumab is not economical for second-line treatment of advanced hepatocellular carcinoma.

Mechanisms of peroxisome proliferator-activated receptor gamma coactivator 1α in high-fat diet-induced skeletal muscle mitochondrial dysfunction in rats / 中华老年医学杂志

Objective To investigate the role of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) in high-fat diet-induced insulin resistance (IR) and mitochondrial degeneration in skeletal muscle.Methods Wistar rats were randomly divided into a normal chow (NC)group (n =10) and a high-fat diet(HFD)group (n =10).After eight weeks,fasting plasma glucose(FBG) levels,fasting insulin(FINS) levels and glucose infusion rates (GIR) in each group were measured (n=3).Samples of rat skeletal muscle were harvested.L6 myoblasts were divided into a control group,a PA group (cells were cultured in palmitic acid),a pcDNA3 group (cells were transfected by the plasmid pcDNA3)and a pcDNA3-PGC1α group (cells were transfected by the PGC1α-overexpressiorn plasmid).Expression levels of PGC1α,nuclear respiratory factor 1 (NRF1),uncoupling protein 3 (UCP3),and cytochrome C oxidase 1 (COX1) in skeletal muscle and L6 myoblasts were measured by real-time PCR and Western blotting.Results Levels of FBG and insulin were higher and those of GIR were lower in the HFD group than in the NC group,(6.0±0.7)mmol/L vs.(5.0±0.4)mmol/L、(23.3±3.0)mU/L vs.(12.9±1.8)mU/L、(14.2±1.8)％ vs.(22.6±2.4)％ (t =-3.578,-6.679,6.265,respectively,P ＜ 0.05).Expression levels of PGC1α,NRF1,UCP3,and COX1 were down in skeletal muscle in the HFD group compared with those in the NC group(P ＜0.05).In L6 myoblasts cultured with palmitic acid,the expression of PGC1 α,NRF1,UCP3,and COX1 were down compared with their expression in the NC group (P ＜ 0.05).However,the altered expression of PGC1α,NRF1,UCP3,and COX1 was reversed by transfecting with PGC1α-overexpression plasmids (F =30.079,96.883,226.772,respectively,P ＜ 0.001).Conclusions High-fat diets can lead to insulin resistance and decreased expression of mitochondrial energy metabolism-related genes,which can be reversed by PGC1α.The decreased expression of PGC1α may mediate the high-fat diet-induced mitochondrial dysfunction and IR.

The role of type 2 innate lymphoid cells in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the type 2 innate lymphoid cells (ILC2s) in eosinophilic nasal polyps, non-eosinophilic nasal polyps and controls, and to compare the characteristics of ILC2s indifferent types of nasal polyp.@*Methods@#Flow cytometric analysis was used to quantify the ILC2s and Th2 cells in tissues from 19 patients with chronic rhinosinusitis with nasal polyp (CRSwNP) and 6 controls. The patients were classified into two groups as eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) based on eosinophil counts under hematoxylin-eosin staining. ILC2 and Th2 cell frenquencies, measured as a percentage of CD45+ cells, were compared among ECRSwNP group (n=9), non-ECRSwNP group (n=10) and control group (n=6) using Mann-Whitney U test .The correlation between ILC2, Th2 cell frequencies and eosinophil count in tissues was analyzed using Pearson correlation coefficient.@*Results@#ILC2 frequencies in ECRSwNP group were significantly higher than non-ECRSwNP group and controls ((0.051±0.025) vs (0.011±0.017), (0.051±0.025) vs (0.004±0.004), Z value was -3.185, -3.186, respectively, both P<0.05). There was no significant difference between ILC2 frequencies in non-ECRSwNP and controls ((0.011±0.017) vs (0.004±0.004), Z=-0.712, P=0.492). Th2 cell frequencies in ECRSwNP and non-ECRSwNP group were significantly higher than controls ((0.500±0.437) vs (0.106±0.102), (0.275±0.170) vs (0.106±0.102), Z value was -2.946, -2.278, respectively, both P<0.05). There was no significant difference between Th2 frequencies in non-ECRSwNP group and ECRSwNP group ((0.275±0.170) vs (0.500±0.437), Z=-1.306, P=0.211). ILC2 frequencies significantly correlated with Th2 cell frequencies (r=0.571, P=0.011) and tissue eosinophilia (r=0.579, P=0.009). Th2 cell frequencies significantly correlated with tissue eosinophilia (r=0.844, P=0.001). There was no significant association between ILC2 and allergic status.@*Conclusion@#ILC2s are elevated in ECRSwNP, and not influenced by allergic status, suggesting that ILC2s play an important role in ECRSwNP without allergic diseases.

The correlation between the hearing frequency and staging of Meniere′s disease / 中华耳鼻咽喉头颈外科杂志

Objective@#To study the relationship between the average hearing of different frequencies and the audiometry staging in patients with Meniere′s disease.@*Methods@#A total of 259 patients from 1996 to 2016 were collected .All patients underwent pure tone audiometry, of which 93 patients underwent 3 000 Hz audiometry. The patients were divided into five groups according to the frequencies of hearing(Ⅰ: 500, 1 000, 2 000, 3 000 Hz; Ⅱ: 250, 500, 1 000, 2 000, 3 000 Hz; Ⅲ: 250, 500, 1 000, 2 000; Ⅳ: 500, 1 000, 2 000, 4 000 Hz; Ⅴ: 500, 1 000, 2 000 Hz), then calculated the average audiometry and made the hearing staging. The obtained data were analyzed by chi-square test and Bonferroni correction was performed among the groups, P<0.05 was defined as a statistically significant criterion.@*Result@#There were no significant difference between the five groups(P=0.441>0.05).@*Conclusions@#The choice of different pure tone audiometry frequency has no significant effect on the hearing staging. It would be more likely upstaging when plus 250 Hz. There is no statistically significant difference in staging between the latest guidelines and the 1995 guidelines.500, 1 000 and 2 000 Hz are recommended when 3 000 Hz examine is not available.

Effects of 5-aminoimidazole-4-carboxamide ribonucleotide on the palmitic acid-induced expression of mitochondrial function-related proteins in C2 C12 skeletal muscle cells / 中华老年医学杂志

Objective To investigate the effects of activated protein kinase(AMPK)agonists on the expression of peroxisome proliferator-activated receptor γ coactivator 1α(PGC1a),mitofusin 2 (Mfn2) and nuclear respiratory factor1 (NRF1)in the process of lipid-induced mitochondrial dysfunction of skeletal muscles.Methods The expression of PGC1α,Mfn2 and NRF1 in C2C12 skeletal muscle cells after intervention with palmitic acid was detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting.The effect of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on Mfn2 and NRF1 and,the expression of Mfn2 and NRF1 in C2C12 cells induced by a PGC1α activator and PGC1α-siRNA were assessed by Western blotting.Results Palmitic acid decreased the mRNA and protein expression of PGC1α,Mfn2 and NRF1 in C2C12 cells (P＜0.05).Additionally,AICAR,rosiglitazone and metformin up-regulated PGC1α expression,regardless of the presence of palmitic acid and,AICAR reversed lipid-induced PGC1α,Mfn2 and NRF1 attenuation in C2C12 cells.Furthermore,Mfn2 and NRF1 protein expression increased with PGC1α over-expression,and decreased with down-regulated PGC1α expression.Conclusions AICAR can relieve the adverse effects of palmitic acid on PGC1α,Mfn2 and NRF1 in skeletal muscle cells.Moreover,it appears that AICAR can up-regulate Mfn2 and NRF1 expression through activating PGC1α.

The clinical study of dynamic detection of lymphocyte subsets in children with septic shock / 国际儿科学杂志

Objective To investigate the dynamic changes of lymphocyte subsets (lymphocyte count, CD3 +T,CD4 +T,CD8 +T,CD19 +B,CD56 +NK)in children with septic shock.Methods Peripheral blood lymphocyte subsets were analysed in 25 cases with severe septic shock and 24 cases with mild septic shock on day 1 ,3,8,and compared with those of 25 healthy volunteers.Children with severe septic shock were divided in-to survival group and dying group according to the outcome.The detection data were compared.Results In the first day of admission,peripheral blood lymphocyte subsets in children with septic shock decreased significantly compared with the normal children,and there was significant difference in the three groups(P 0.05),but children with severe septic shock had statistical increase of CD4 +T,CD3 +T and lymphocyte count(P <0.05).There were 5 cases died who had se-vere septic shock in day 2 to day 5 after admission.The count of lymphocyte subsets were detected significantly lower in dying group than survival group in the third day of admission(P <0.05).Conclusion The continuous low level of lymphocyte subsets indicates bad outcome.The patientˊs condition improved with increase of CD4 +T,CD3 +T,lymphocyte count.CD4 +T is the most sensitive.Dynamic detection of lymphocyte subsets in the pe-ripheral blood of children with septic shock is of great clinical significance in judging the severity of disease and cura-tive effect.

Anticoagulant chitosan nanoparticles：synthesis, characterization and biological safety / 中国组织工程研究

BACKGROUND:Studies have shown that chitosan and other natural polysaccharides have heparin-like anticoagulant function after sulfonated modification. Sulfonated chitosan has good anticoagulant property because the sulfonate group formed by sulfonated chitosan is similar with the active group of heparin. OBJECTIVE: To prepare the anticoagulant chitosan nanoparticles and to detect its morphology, physical and chemical properties and biological security. METHODS: Chitosan nanoparticles were synthesized by emulsion-chemical cross link. Sulfonated chitosan nanoparticles were synthesized by sulfonation reaction. Its morphology was described by transmission electron microscope. The peak-value change of its specific groups was observed by infrared spectroscopy. (1) Coagulation experiment: Heparin, chitosan nanoparticles and 10, 30 and 50 mg of sulfonated chitosan nanoparticles were added into the blood of Spraque-Dawley rats. The coagulation indicators were detected. (2) Hemolysis experiment: deionized water, physiological saline and 10, 30, 50 g/L sulfonated chitosan nanoparticles extracts were added into 2% red blood cel suspension of rabbits. The hemolysis rate was detected. (3) Cytotoxicity experiments: DMEM medium containing fetal bovine serum and 10, 30, 50 g/L sulfonated chitosan nanoparticle extracts were used to culture human umbilical vein endothelial cels. Cel relative growth rate and toxicity grading were detected after 72 hours. RESULTS AND CONCLUSION: Scanning electron microscopy showed that sulfonated chitosan nanoparticles had good morphology, with a diameter of 50 nm. Infrared spectroscopy showed that the sulfonated replacement occurred.In vitro coagulation experiments showed that sulfonated chitosan nanoparticles had significant anticoagulant effects in a dose-dependent manner. Sulfonated chitosan nanoparticles meet the national safety standard for hemolysis rate of less than 5%, non-induced hemolysis property. Cytotoxicity assays showed that sulfonated chitosan nanoparticles extracts had no significant cytotoxicity, and its biological safety was in line with the national standards.

The effects of Saccharomyces boulardii powder on preventing antibiotic-associated diarrhea in children with pneumonia / 国际儿科学杂志

Objective The aim of this randomized,double-blind,placebo-controlled trial was to evaluate the efficacy of the Saccharomyces boulardii (S.boulardii) power in preventing antibiotic-associated diarrhea (AAD) in hospitalized children with pneumonia.Methods Two hundred and forty-five hospitalized children with pneumonia were randomly divided into two groups,group 1 treated with antibiotics and S.boulardii power (n =104),and group 2 with antibiotics and placebo,along with S.boulardii power and zinc when suffered from diarrhea (n =141).All children received montmorillonite powder and fluid replacement therapy for diarrhea.The stool frequency and consistency were observed.Diarrhea incidence,diarrhea and pneumonia duration of treatment,and therapeutic effect were recorded.Results AAD is more prevalent in group 2 than in group 1 (P ＜0.05).A 55.7％ relative risk reduction in AAD was seen in group 1 compared with group 2 (RR =0.443,95％CI 0.233 ～ 0.845,P =0.012).Patients with preventive treatment of S.boulardii power in broup 1 had lower AAD incidence compared with those in group 2 (P ＜ 0.05).Both the diarrhea and pneumonia duration of treatment in group 1 were shorter than that in group 2(P =0.001 for diarrhea duration,P =0.030 for pneumonia duration,respectively).No drug related adverse reactions were found during the observation period.Conclusion Preventive use of S.boulardii power may effectively reduce the risk of AAD,improve therapeutic effect,and shorten hospital stays for hospitalized children with pneumonia.

The levels of serum myocardial enzymes and high density lipoprotein cholesterol in children with septic shock / 中国小儿急救医学

ObjectiveTo investigate the changes of serum myocardial enzymes and high density lipoprotein cholesterol(HDL-C) in children with septic shock.MethodsFifty-two children with septic shock in our hospital from Jan 2006 to Mar 2011 were divided into severe septic shock group( n =27 ) and mild septic shock group ( n =25 ).The serum creatine kinase-MB ( CK-MB ),α-hydroxybutyrate dehydrogenase (α-HBDH),lactic dehydrogenase(LDH) and HDL-C were analysed in both two groups on 1,2,4,7,10,15 d,and compared with 32 normal children as control group.Meanwhile,the children's condition,death cases and cured time were recorded.ResultsThe levels of serum CK-MB [ ( 32.084 ± 4.595 ) U/L,( 61.481 ±5.639) U/L],α-HBDH/LDH(0.694 ±0.080,0.884 ±0.079) in mild and severe septic shock groups were higher than those of normal control group[ (21.675 ± 3.453) U/L ] and (0.443 ± 0.065 ) ( P ＜ 0.01 ) ;the levels of serum HDL-C[ (0.646 ±0.067) mmol/L,(0.310 ± 0.124) mmol/L ] in the two septic shock groups were decreased significantly than that of control group[ ( 1.012 ±0.156) mmol/L] (P ＜0.01 ).Five cases died in the severe septic shock group while no cases died in mild septic shock group.The times of CK-MB recovered[ (9.82 ±1.76) d vs (4.68 ± 1.22) d],α-HBDH/LDH recovered[ (7.23 ± 1.38) d vs (3.76 ± 0.83 ) d] and HDL recovered[ ( 12.14 ± 2.21 ) d vs ( 6.48 ± 1.33 ) d ] were more slowly in severe septic shock group than those of mild septic shock group( P ＜ 0.01 ).ConclusionThe higher of the serum CK-MB and α-HBDH/LDH,and the lower of HDL-C in septic shock children,the disease is more severe,the recovery time is longer and a worse prognosis may occur.

Effects of high-fat diets and rosiglitazone treatment on expressions of peroxisome proliferator-activated receptor-γ coactivator-1α and mitofusin-2 in skeletal muscle of aged rats / 中华老年医学杂志

Objective To investigate the effects of high-fat diets and rosiglitazone treatment on the expressions of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitofusin-2 (Mfn2) in skeletal muscle of aged rats. Methods Male wistar rats aged 21-23 months were randomly divided into old control group (OC; n=20), high-fat diets group (HF; n=20) and high-fat diets plus rosiglitazone treatment group (RSG; n=20). Male wistar rats aged 4-5 months were selected as young control group (YC; n=20). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique at the end of the 4th and 8th week. The expressions at mRNA and protein levels of PGC-1α and Mfn2 in skeletal muscle were determined by polymerase chain reaction and Western blotting technique. Results (1)After 8 weeks, the levels of free fatty acid [(0. 68±0. 18)mmol/L, (0.82±0. 23) mmol/L and (1. 53±0.40) mmol/L], triglyceride [(0.53±0.13) mmol/L,(0. 63±0. 17) mmol/L and (1.08±0.30) mmol/L]and muscle triglyceride [(1.09±0.17) mmol/L,(1.34±0. 20) mmol/L and (2.07±0. 30) mmol/L]in YC group, OC group and HF group were significantly increased and glucose infusion rate [(30.4±4. 2) mg·kg~(-1)·min~(-1), (20.9±2.2) mg·kg~(-1)·min~(-1) and (12. 0±1.9) mg·kg~(-1)·min~(-1)]was significantly decreased as compared with pre-high fat diet, respectively. The levels of fasting free fatty acid [(0.93±0.29) mmol/L], triglyceride [(0.62±0.12) mmol/L]and music triglyceride [(1.68±0.28) mmol/L]in RSG group were significantly decreased and glucose infusion rate [(16.7±1.7) mg·kg~(-1)·min~(-1)]was significantly higher than in HF group. (2)In skeletal muscle, the expressions at mRNA and protein levels of PGC-1α and Mfn2 decreased in OC group compared with YC group (all P<0.01). The expressions of PGC-1α and Mfn2 were lower significantly in HF group than in OC group, and were higher significantly in RSG group than in HF group (all P<0.01). Conclusions The aged rats fed the high-fat diets develop insulin resistance with decreased expressions of PGC-1α and Mfn2 in skeletal muscle. Insulin sensitivity is improved with rosiglitazone treatment by increasing expressions of PGC-1α and Mfn2 in skeletal muscle.