1.A multicenter study of R-ISS staging combined with frailty biomarkers to predict the prognosis and early death in newly diagnosed elderly multiple myeloma patients
Yingjie ZHANG ; Hua XUE ; Mengyao LI ; Jianmei XU ; Xinyue LIANG ; Weiling XU ; Xiaoqi QIN ; Qiang GUO ; Shanshan YU ; Peiyu YANG ; Mengru TIAN ; Tingting YUE ; Mengxue ZHANG ; Yurong YAN ; Zhongli HU ; Nan ZHANG ; Jingxuan WANG ; Fengyan JIN
Chinese Journal of Geriatrics 2023;42(10):1207-1212
Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.
2.Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis.
Nazi SONG ; Hongjiao XU ; Jiahua LIU ; Qian ZHAO ; Hui CHEN ; Zhibin YAN ; Runling YANG ; Zhiteng LUO ; Qi LIU ; Jianmei OUYANG ; Shuohan WU ; Suijia LUO ; Shuyin YE ; Runfeng LIN ; Xi SUN ; Junqiu XIE ; Tian LAN ; Zhongdao WU ; Rui WANG ; Xianxing JIANG
Acta Pharmaceutica Sinica B 2022;12(5):2443-2461
Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.
3.Epidemiological characteristics and antibiotics susceptibility of Streptococcus pneumoniae isolated from children in Suzhou area during 2010 to 2017
Changpeng LIU ; Xuejun SHAO ; Shuang FENG ; Yunzhen TAO ; Yunzhong WANG ; Jian XUE ; Yongdong YAN ; Jianmei TIAN ; Genming ZHAO ; Tao ZHANG
Chinese Journal of Infectious Diseases 2021;39(2):97-102
Objective:To explore the epidemiological characteristics and the antibiotic resistance of Streptococcus pneumoniae isolates, and to provide the evidence for the rational use of antimicrobial agents to treat Streptococcus pneumoniae infection. Methods:The positive microbiological laboratory identification and antimicrobial susceptibility testing of Streptococcus pneumoniae from sputum of children with respiratory infections during January 2010 to December 2017 in Children′s Hospital of Soochow University were retrospectively analyzed. The positive rates of Streptococcus pneumoniae of different genders, ages, years and seasons were compared. The annual detection rates and trends of drug resistance of Streptococcus pneumoniae to penicillin, amoxicillin and cefotaxime were analyzed by Mann-Kendall trend test. The seasonal decomposition of time series was conducted to assess the association between Streptococcus pneumoniae detection rate and season. Enumeration data was compared using χ2 test. Results:Of the 88 480 sputum specimens, the total positive rate of Streptococcus pneumoniae was 10.3%(9 081/88 480). The detection rates of Streptococcus pneumoniae in children aged 0 to <0.5 years old, 0.5 to <2 years old, 2 to <3 years old, 3 to <5 years old, and 5 to <15 years old were 4.2%(1 407/33 224), 13.1%(3 191/24 390), 14.9%(2 417/16 252), 17.9%(1 474/8 246) and 9.3%(592/6 368), respectively. The difference was statistically significant ( χ2=2 421.6, P<0.01). The detection rates were 8.1%(1 321/16 306) from January to March, 10.9%(2 194/20 207) from April to June, 8.5%(2 141/25 058) from July to September, and 12.7%(3 425/26 909) from October to December. The discrepancy of positive rates in different seasons showed statistical significance ( χ2=311.5, P<0.01). During 2010 to 2017, significant decreases in antibiotic resistant rates of Streptococcus pneumoniae to penicillin, amoxicillin and cefotaxime were detected (tau=-0.93, -0.93 and -0.71, respectively, all P<0.05). Conclusions:The detection rate of Streptococcus pneumoniae in sputum of children with respiratory infections may present seasonal pattern and vary between different ages of children. The resistance to β-lactam antibiotics has declined.
4.Progress of coxsackievirus A10
International Journal of Pediatrics 2021;48(5):335-339
Hand, foot and mouth disease(HFMD)is a common class C infectious disease for children under 5 years of age in our country, which pathogens are multiple enteroviruses.Recent studies have found that coxsackievirus A10(CVA10)has become one of the main pathogens of HFMD gradually, and its infection is on the rise.Moreover, enterovirus 71(EV71), coxsackievirus A16(CVA16), coxsackievirus A6(CVA6), and CVA10 co-circulate has appeared.The CVA10 cell receptor is recombinant kringle containing transmembrane protein 1(KRM1), and the specific neutralizing antibody is named 2G8.The vaccines in related animal models are inactivated vaccines and virus-like particle vaccines.This paper reviews on aspects of cell receptors, neutralizing antibodies, vaccines researches and animal models about CVA10, providing some ideas for the prevention and control of HFMD.
5.Analysis of the clinical features, prognosis and early warning indicators of severe hand, foot and mouth disease
Hong JI ; Qinghui CHEN ; Xuefeng ZHANG ; Chao SHI ; Jun BI ; Jing AI ; Huan FAN ; Jianmei TIAN ; Changjun BAO ; Yu JIN
Chinese Journal of Experimental and Clinical Virology 2021;35(1):89-95
Objective:To explore the type distribution and severity of central nervous system(CNS) complications in severe hand, foot and mouth disease (HFMD) cases prior to the introduction of human enterovirus A group 71 type (EV-A71) vaccine, and provide scientific data for early clinical intervention.Methods:A total of 3 583 laboratory-confirmed severe HFMD cases in Jiangsu province during 2010-2016 were collected and analyzed retrospectively. Related early warning signs of increased HFMD severity were estimated with logistic regression analyses.Results:The severity-fatality rate, severity-pediatric intensive care unit(PICU) admission rate, and sequelae rate were 8.09‰(29/3 583), 11.75% (421/3 583)and 5.30‰(19/3 583). Of them, 39.02% (1 398/3 583) patients suffered from mild CNS involvement, 59.22% (2 122/3 583) patients suffered from severe CNS involvement, 1.76%(63/3 583) suffered from critical CNS involvement. The rates of the cases whose age of onset was 6-11 months, the rates of cases with atypical rash, respiratory-related signs and symptoms (shortness of breath, slowed breathing, dyspnea, etc), neurological-related signs and symptoms [(hand and foot shaking, convulsions, lethargy(sleepiness), etc], circulatory-related system signs and symptoms (faster heart rate, abnormal skin color, arrhythmia, cold limbs), laboratory-related indicators (increased white blood cell count, increased lymphocyte count, increased platelet count, increased C-reactive protein, etc), clinical auxiliary examination [electroencephalogram(EEG), brain CT, chest X-ray)] were highest in the critical CNS involvement group, and the differences were significant ( P<0.05). Multivariate logistic regression analysis showed that with the increase of proportion of convulsions, slowed breathing, vomiting, meningeal irritation and other 7 variables, the severity of CNS complications increased ( P<0.05). Conclusions:The indicators such as easily startled, slow breathing, vomiting, elevated lymphocytes, abnormal EEG and other indicators have important clinical significance for children with severe HFMD to progress to CNS complications of different severity.
6.Study on clinical symptoms and influencing factors of influenza-associated severe acute respiratory illness in children younger than 5 years old in Suzhou of China, 2011-2017
Wanqing ZHANG ; Liling CHEN ; Fangfang CHENG ; Zirui DAI ; Shuang FENG ; Jun ZHANG ; Jianmei TIAN ; Tao ZHANG ; Genming ZHAO
Chinese Journal of Epidemiology 2021;42(6):1044-1049
Objective:To study the influencing factors of influenza-associated severe acute respiratory illness (SARI) in children younger than 5 years of old in Suzhou, and to provide evidence to support the improvement of prevention and control strategies for influenza in children.Methods:We conducted a prospective influenza surveillance for hospitalized SARI and outpatient influenza-like illness (ILI) at Children′s Hospital of Soochow University from April 2011 to March 2017. We compared the clinical and other characteristics of influenza-positive patients with SARI to those with ILI to find the differences and to identify influencing factors of influenza-associated SARI, using χ2 test and unconditional logistic regression. Results:We found 786 cases of influenza-associated ILI and 413 cases of influenza-associated SARI during the study period. Cough, runny nose, shortness of breath, asthma or wheezing were more common in influenza-associated SARI than in influenza-associated ILI ( P<0.01). Univariate and multivariate logistic regression showed that the influencing factors which significantly associated with increased risk of influenza-associated SARI were as follows: younger age (<6 months OR=3.6, 6-23 months a OR=2.5), respiratory infection history within 3 months (a OR=4.5), chronic lung disease history ( OR=3.4), fever above 39.0 ℃ (39.0-39.9 ℃ a OR=2.4, ≥40.0 ℃ a OR=6.0), and the presence of A/H1N1 (a OR=2.3), A/H3N2 (a OR=1.9). Conclusion:Children younger than 2 years old, with a history of chronic lung disease, a history of respiratory infection within 3 months, or with a fever peak above 39.0 ℃ should seek medical advice as soon as possible or receive annual influenza vaccination to reduce the incidence of influenza-associated serious outcomes.
7.Estimation of hospitalization rate of Haemophilus influenzae associated community-acquired pneumonia in children under 5 years in Suzhou, 2010-2014
Zirui DAI ; Xuejun SHAO ; Yunzhen TAO ; Si SHEN ; Shuang FENG ; Shaolong REN ; Lin LUAN ; Jun ZHANG ; Jianmei TIAN ; Tao ZHANG ; Genming ZHAO
Chinese Journal of Epidemiology 2021;42(7):1246-1251
Objective:To estimate the hospitalization rate of Haemophilus ( H.) influenzae associated community-acquired pneumonia in children under 5 years in Suzhou. Methods:From 2010 to 2014, medical records and bacteriology results of children under 5 years hospitalized with community-acquired pneumonia in Children's Hospital of Soochow University were collected, retrospectively. Detection rate of H. influenzae was describe. The hospitalization rate of H. influenzae associated community-acquired pneumonia was estimated using the number of local children in urban area of Suzhou, which was obtained from the immunization platform of Suzhou Center for Disease Prevention and Control. Results:A total of 28 043 hospitalized pneumonia cases were included from 2010 to 2014, in which 19 526 (69.63%) had bacteriological examination. The overall detection rate of H. influenzae was 11.06% (2 160/19 526), and children aged 12-23 months had the highest positive rate (14.29%, 550/3 850), and the rate was higher during winter-spring than during summer-autumn ( χ 2=455.11, P<0.01). The average hospitalization rate of H. influenzae associated pneumonia in children under 5 years was 760.36/100 000 (95% CI: 733.70/100 000-787.01/100 000), which was higher in winter and spring (898.79/100 000 and 1 249.52/100 000) than in summer and autumn (514.35/100 000 and 359.04/100 000), and the hospitalization rate was higher in boys (942.12/100 000) than in girls (563.76/100 000), the differences were all significant ( P<0.01). The highest hospitalization rate was observed in children aged 1-5 months (2 478.31/100 000) and the hospitalization rate decreased with age ( χ 2=2 129.80, P<0.01). Conclusion:There was a considerable burden of H. influenzae associated community-acquired pneumonia in children under 5 years in Suzhou, especially in children under 6 months.
8. Hospitalization rates for influenza-associated severe acute respiratory illness in children younger than five years old in Suzhou of China, 2016-2018
Wanqing ZHANG ; Jia YU ; Liling CHEN ; Fangfang CHENG ; Rui ZHANG ; Junmei GAO ; Jun ZHANG ; Gemming ZHAO ; Jianmei TIAN ; Tao ZHANG
Chinese Journal of Preventive Medicine 2019;53(10):1056-1059
We analyzed the influenza surveillance data of Children′s Hospital of Suzhou University from 2016 to 2018 and estimated the hospitalization burden of children under 5 years old due to influenza infection in Suzhou. The results showed that the influenza virus positive rate of 1 451 severe acute respiratory infection (SARI) cases in Children′s Hospital of Suzhou University was 13.6% (95
9.Hospitalization rates for influenza?associated severe acute respiratory illness in children younger than five years old in Suzhou of China, 2016-2018
Wanqing ZHANG ; Jia YU ; Liling CHEN ; Fangfang CHENG ; Rui ZHANG ; Junmei GAO ; Jun ZHANG ; Gemming ZHAO ; Jianmei TIAN ; Tao ZHANG
Chinese Journal of Preventive Medicine 2019;53(10):1056-1059
We analyzed the influenza surveillance data of Children′s Hospital of Suzhou University from 2016 to 2018 and estimated the hospitalization burden of children under 5 years old due to influenza infection in Suzhou. The results showed that the influenza virus positive rate of 1 451 severe acute respiratory infection (SARI) cases in Children′s Hospital of Suzhou University was 13.6% (95%CI :11.8%?15.3%;197 cases), among which the influenza pandemic intensity in 2017?2018 was relatively high, and A/H1N1 was the main pandemic virus. It was estimated that the hospitalization rate of influenza?related SARI in children under 5 years old in Suzhou was 6.9‰ (95%CI : 6.6‰?7.2‰), among which the hospitalization rate of children aged<6 months was higher, up to 11.4‰(95%CI: 9.9‰?12.8‰).
10.Hospitalization rates for influenza?associated severe acute respiratory illness in children younger than five years old in Suzhou of China, 2016-2018
Wanqing ZHANG ; Jia YU ; Liling CHEN ; Fangfang CHENG ; Rui ZHANG ; Junmei GAO ; Jun ZHANG ; Gemming ZHAO ; Jianmei TIAN ; Tao ZHANG
Chinese Journal of Preventive Medicine 2019;53(10):1056-1059
We analyzed the influenza surveillance data of Children′s Hospital of Suzhou University from 2016 to 2018 and estimated the hospitalization burden of children under 5 years old due to influenza infection in Suzhou. The results showed that the influenza virus positive rate of 1 451 severe acute respiratory infection (SARI) cases in Children′s Hospital of Suzhou University was 13.6% (95%CI :11.8%?15.3%;197 cases), among which the influenza pandemic intensity in 2017?2018 was relatively high, and A/H1N1 was the main pandemic virus. It was estimated that the hospitalization rate of influenza?related SARI in children under 5 years old in Suzhou was 6.9‰ (95%CI : 6.6‰?7.2‰), among which the hospitalization rate of children aged<6 months was higher, up to 11.4‰(95%CI: 9.9‰?12.8‰).

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