1.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
		                        		
		                        			
		                        			Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
		                        		
		                        		
		                        		
		                        	
2.Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children.
Sha-Sha DONG ; Ruo-Chen CHE ; Bi-Xia ZHENG ; Ai-Hua ZHANG ; Chun-Li WANG ; Mi BAI ; Ying CHEN
Chinese Journal of Contemporary Pediatrics 2023;25(7):705-710
		                        		
		                        			OBJECTIVES:
		                        			To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children.
		                        		
		                        			METHODS:
		                        			A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed.
		                        		
		                        			RESULTS:
		                        			The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Fibroblast Growth Factor-23
		                        			;
		                        		
		                        			Fibroblast Growth Factors
		                        			;
		                        		
		                        			Familial Hypophosphatemic Rickets/diagnosis*
		                        			;
		                        		
		                        			Rickets, Hypophosphatemic/diagnosis*
		                        			
		                        		
		                        	
3.Correlation between the integrity of interdigitation zone defect and visual function before and after idiopathic macular epiretinal membrane surgery
Shu-Wei BAI ; Feng-Zhi LI ; Chun-Chao BI ; Juan SHAO ; Rong ZENG
International Eye Science 2023;23(1):153-157
		                        		
		                        			
		                        			 AIM: To explore the correlation between the integrity of the macular microstructures and the visual outcomes before and after idiopathic macular epiretinal membrane(IMEM)surgery.METHODS: A total of 43 patients(43 eyes)with IMEM who were treated in our hospital between January 2017 and December 2019 were selected. The best corrected visual acuity(BCVA)of each patient was examined preoperatively and at 3, 6, 9mo after surgery. Moreover, metamorphopsia(M-chart)examination was given, and spectral domain-optical coherence tomography(SD-OCT)was used to measure central foveal thickness(CFT), subfoveal choroidal thickness(SFCT), the thickness of ganglion cells-inner plexiform layer(GC-IPL)and the length of interdigitation zone(IZ)defect.RESULTS: The BCVA and the metamorphopsia were gradually improved at postoperative 3, 6 and 9 mo(all P<0.05). Moreover, the BCVA was positively correlated with CFT and the length of the IZ defect(P<0.05), while it was not correlated with SFCT and the thickness of GC-IPL(P>0.05). The metamorphopsia assessment was positively correlated with the CFT at postoperative 3, 6, and 9mo(P<0.05), while it was not correlated with SFCT, the thickness of GC-IPL and the length of IZ defect(P>0.05).CONCLUSIONS: The CFT and the length of IZ defect were significantly correlated with the BCVA after IMEM surgery, which can be used as indicators to predict the recovery of visual function after IMEM surgery. 
		                        		
		                        		
		                        		
		                        	
4.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
		                        		
		                        			
		                        			Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Brain Abscess
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Escherichia coli
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrocephalus
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Meningitis, Bacterial/epidemiology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Streptococcus agalactiae
		                        			;
		                        		
		                        			Streptococcus pneumoniae
		                        			;
		                        		
		                        			Subdural Effusion
		                        			;
		                        		
		                        			beta-Lactamases
		                        			
		                        		
		                        	
5.Characterization of Changes and Driver Microbes in Gut Microbiota During Healthy Aging Using A Captive Monkey Model
Wei ZHI-YUAN ; Rao JUN-HUA ; Tang MING-TIAN ; Zhao GUO-AN ; Li QI-CHUN ; Wu LI-MING ; Liu SHAO-QIANG ; Li BI-HAI ; Xiao BAI-QUAN ; Liu XING-YIN ; Chen JIAN-HUAN
Genomics, Proteomics & Bioinformatics 2022;20(2):350-365
		                        		
		                        			
		                        			Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.
		                        		
		                        		
		                        		
		                        	
6.Analysis of surgical strategy of percutaneous endoscopic lumbar discectomy in young and middle-aged double-segment patients with lumbar disc herniation.
Lei YUE ; Yue Tian WANG ; Chun Bi BAI ; Hao CHEN ; Hao Yong FU ; Zheng Rong YU ; Chun De LI ; Hao Lin SUN
Journal of Peking University(Health Sciences) 2021;53(4):734-739
		                        		
		                        			OBJECTIVE:
		                        			To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation.
		                        		
		                        			METHODS:
		                        			Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications.
		                        		
		                        			RESULTS:
		                        			The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups(P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment (P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up (P < 0.05). There was no significant difference in radiographic parameters at baseline (P>0.05). MSU scale for the primary segment was significantly lowered after both operations (P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups (P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group(P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group.
		                        		
		                        			CONCLUSION
		                        			For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.
		                        		
		                        		
		                        		
		                        			Diskectomy
		                        			;
		                        		
		                        			Diskectomy, Percutaneous
		                        			;
		                        		
		                        			Endoscopy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Intervertebral Disc Degeneration/surgery*
		                        			;
		                        		
		                        			Intervertebral Disc Displacement/surgery*
		                        			;
		                        		
		                        			Lumbar Vertebrae/surgery*
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
7.Factors associated with adherence to screening before diagnosis of hepatocellular carcinoma related to chronic hepatitis B
JIE Bin ; BAI Chun Hua ; BI Hua Qiang ; QIU Yan
Journal of Preventive Medicine 2021;33(5):433-437
		                        		
		                        			Objective:
		                        			To investigate the factors associated with the patient's adherence to screening in the five years before the diagnosis of hepatocellular carcinoma (HCC) related to chronic hepatitis B ( CHB ), so as to provide reference for improving the screening rate.
		                        		
		                        			Methods:
		                        			From June 2016 to April 2018, the patients with newly diagnosed HCC and a history of CHB for more than five years in Southwest Hospital in Chongqing were interviewed. The information about socio-demographic characteristics, health status, medical care and HCC screening in the past five years were collected. A multivariate logistic regression model was used to analyze the factors associated with adherence to screening. 
		                        		
		                        			Results:
		                        			Among 420 participants, 140 ( 33.33% ) adhered to HCC screening, 124 ( 29.53% ) had irregular/incomplete screening, while 156 ( 37.14% ) never had screening. The proportion of early-stage HCC at diagnosis was significantly higher in patients who adhered to screening ( 77.14% ) than that in patients who had irregular/incomplete screening (35.48%) or no screening ( 12.82% ) and the differences were statistically significant ( P<0.05 ). The multivariate analysis demonstrated that five factors were significantly associated with patient's adherence to screening, including education level of high school and above ( OR=2.346, 95%CI: 1.370-4.017), family history of HCC ( OR=2.795, 95%CI: 1.457-5.362 ), history of chronic diseases ( OR=3.860, 95%CI: 2.052-7.262), acceptance of antiviral therapy ( OR=17.816, 95%CI: 9.702-32.716 ) and specialized clinic visits ( OR=8.332, 95%CI: 1.588-43.710 ).
		                        		
		                        			Conclusions
		                        			Adherence to screening is conducive to the early detection of HCC, but the screening rate is low in the patients with CHB. Education level, history of HCC, health status and medical status are significantly related to screening adherence.
		                        		
		                        		
		                        		
		                        	
8.Feasibility of Hei Xiaoyaosan in Preventing and Treating Alzheimer's Disease Based on Theory of 'Correlation of Liver and Kidney' Based on Ca2+-CaM/CaMKⅡ-CREB Signal Pathway
Chun-lin MA ; Xiao-xuan FANG ; Bi-yun GAO ; Yue-qin BAI ; Hong-yan WU ; Zhi-xuan ZHANG ; Yong-qiang DUAN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(23):193-199
		                        		
		                        			
		                        			Alzheimer's disease(AD) is an incipient aging neurodegenerative disease, which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures, it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. 'Correlation of Liver and Kidney' is one of the core plates of the theory of 'Correlation of Five Organs', which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes, and guiding the prescription of clinical syndrome. Hei Xiaoyaosan, as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney' in our team, can play the effects of prevention and treatment by soothing liver and nourishing blood, strengthening spleen and tonifying kidney, and promoting brain collaterals and dredging viscerab spirit. Based on the theory of 'Correlation of Liver and Kidney', this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine, and puts forward the methods and ideas of the preventing and treating of AD from Ca2+-calcium/calmodulin dependent protein (CaM)/calcium/calmodulin dependent protein kinaseⅡ(CaMKⅡ)-cyclic adenosine phosphate reactive element binding protein (CREB) cell signal transduction pathway by consulting literatures and previous studies.
		                        		
		                        		
		                        		
		                        	
9.Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer:a multicenter,randomized,double-blinded,placebo-controlled,phaseⅡclinical trial
Xu RUI-HUA ; Shen LIN ; Wang KE-MING ; Wu GANG ; Shi CHUN-MEI ; Ding KE-FENG ; Lin LI-ZHU ; Wang JIN-WAN ; Xiong JIAN-PING ; Wu CHANG-PING ; Li JIN ; Liu YUN-PENG ; Wang DONG ; Ba YI ; Feng JUE-PING ; Bai YU-XIAN ; Bi JING-WANG ; Ma LI-WEN ; Lei JIAN ; Yang QING ; Yu HAO
Chinese Journal of Cancer 2017;36(12):677-685
		                        		
		                        			
		                        			Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promis-ing anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were rand-omized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium
		                        		
		                        		
		                        		
		                        	
10.A20 regulates the inflammatory responses of alveolar macrophage
Xiao-Dan ZHU ; Ying WANG ; Jing BI ; Lin TONG ; Jie LIU ; Yuan-Lin SONG ; Chun-Xue BAI
Chinese Journal of Clinical Medicine 2016;23(6):715-719
		                        		
		                        			
		                        			Objective:To study the effects of A20 on the inflammatory response of alveolar macrophages and its regulation mechanism through establishing A 20 over‐expressing alveolar macrophage cell lines .Methods :Lentivirus‐mediated expression vector carrying A20 gene was constructed ,then it was transfected into rat alveolar macrophage cell lines (NR8383) , and the cell lines which stably overexpressed A20 gene were screened and cultured in vitro .Lipopolysaccharide (LPS ,1 μg/mL) was added into the medium to intervene ,the culture supernatants and cells were collected 0 .5 ,1 ,2 ,4 hours after stimulation ,ELISA method was used to determine the activity of cytokines (TNF‐α,IL‐1β) and nuclear factor (NF‐κB) . Western blotting method was used to detect A20 protein and nuclear p65 content ,and real‐time fluorescence quantitative PCR method was used to determine the content of A20 mRNA .Results:After LPS stimulation ,the levels of A20 protein and mRNA in A20 overexpression group (A20 group) and the normal control group (VEC group) both increased and reached the peak at 1 h ,and then gradually decreased .The A20 level of A20 group was significantly higher than that of VEC group (P<0 .05) .Compared with VEC group ,the levels of cytokines (TNF‐α,IL‐1β) in culture supernatants of A20 group significantly reduced (P<0 .05) ,and the DNA binding activity of NF‐κB and nuclear p65 content of A20 group also significantly reduced (P<0 .05) .Conclusions :A20 can inhibit the activity of NF‐κB and the secretion of TNF‐α and IL ‐1β,and then inhibit the inflammatory reaction activity of alveolar macrophages , thereby reducing the inflammatory response of acute respiratory distress syndrome (ARDS) .
		                        		
		                        		
		                        		
		                        	
            

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