1.Impact of initial screening strategies on compliance with colonoscopy for colorectal carcinoma in residents aged 50 years and above
Fang XIANG ; Zhihao HU ; Yawei WANG ; Yiying ZHANG ; Fang HUANG ; Qian PENG ; Hongjie YU ; Chaowei FU
Shanghai Journal of Preventive Medicine 2025;37(2):140-144
ObjectiveTo compare colonoscopy compliance rates under different screening strategies, to explore ways to enhance colonoscopy compliance among residents with colorectal carcinoma. MethodsResidents aged between 50‒80 years were recruited through extensive community outreach and voluntary participation. A total of 210 630 residents who participated in the colorectal carcinoma screening program in Jiading District, Shanghai, between 2013 and 2019 were selected as the research subjects. All subjects underwent a colorectal carcinoma risk assessment questionnaire survey and two fecal occult blood tests (FOBT). Positive results in the initial screening were defined as a positive questionnaire survey or a positive result in at least one FOBT. Participants with positive initial screening results were advised to undergo colonoscopy screening in a hospital. Colonoscopy results were collected from hospital reports and physician follow-ups. Compliance with colonoscopy was analyzed under different screening strategies to identify possible factors influencing residents’ willingness to undergo the procedure. ResultsA total of 21 403 individuals (10.16%) were identified as positive with the questionnaire survey, 31 595 individuals (15.00%) tested positive with at least one FOBT. Combined questionnaire and FOBT positivity was observed in 3 501 individuals (1.66%). Among the 48 453 individuals with positive initial screening results, 17 230 (35.56%) underwent colonoscopy, and a total of 315 cases of colorectal cancer were detected. The sensitivity, specificity value of FOBT initial screening were 83.81% and 84.66%, respectively. According to the combined risk assessment and FOBT initial screening preliminary screening, the lowest colonoscopy compliance rate (25.63%) was observed among individuals with only a positive questionnaire, and the highest compliance rate (52.55%) was among those with both positive questionnaire survey and two positive FOBT results. Multivariate analysis revealed that FOBT positivity had the greatest impact on colonoscopy compliance. Those with one positive FOBT test result were 2.64 times more likely to undergo colonoscopy screening than those with negative FOBT results, while individuals with two positive FOBT results were 3.18 times more likely to do so. After adjusting for FOBT results, individuals with positive questionnaire survey results were 1.43 times more likely to undergo colonoscopy screening than those with negative results (95%CI: 1.34‒1.52). Compared to questionnaire-based risk assessment, FOBT results were more influential in determining compliance with colonoscopy. ConclusionThe choice of initial screening method significantly impacts residents’ compliance with colonoscopy. While implementing colorectal carcinoma screening programs, it is necessary to strictly adhere to screening protocols, including risk assessment and FOBT. Additionally, efforts should be made to raise public awareness, encouraging residents to actively participate in risk assessments and FOBT, thereby improving their compliance with colonoscopy.
2.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
3.Effects of paeonol on activation and inflammation of NLRP3 inf lammasome in mice with endometriosis
Xiufang DU ; Hongjie YANG ; Xiaobei KANG ; Changna FU ; Tao YANG
Immunological Journal 2024;40(8):646-654
Objective To investigate the effects of paeonol on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway and pyroptosis levels in ectopic lesion tissues of endometriosis(EMS)mice and mouse endometrial epithelial cells(mEECs).Methods An allograft transplantation method was used to establish an EMS mouse model.Thirty-five Balb/c mice were divided into a sham group,a model group,a 12.5 mg/kg paeonol group,a 25 mg/kg paeonol group,a 50 mg/kg paeonol group,a 0.5 mg/kg gestrinone group(positive control group),and a 50 mg/kg paeonol+Nrf2 inhibitor ML385(30 mg/kg)group,with 5 mice in each group.mEECs were divided into a cell control group,a 10 ng/ml transforming growth factor-β1(TGF-β1)or 100 ng/ml lipopolysaccharide(LPS)model group,a 50 μmol/Lpaeonol group,a 100 μmol/L paeonol group,and a 100 μmol/L paeonol+ML385 group.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and IL-18 in the serum of EMS mice and the culture supernatant of mEECs.Hematoxylin and eosin(H&E)staining was used to detect histopathological changes in ectopic lesion tissues of mice.Western blot experiments were conducted to detect the protein expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),caspase-1,gasdermin D protein N-terminal fragment(GSDMD-N),Nrf2,heme oxygenase-1(HO-1),and quinone oxidoreductase-1(NQO-1)in ectopic lesion tissues and mEECs.The MTT method was used to detect the cell survival rate of mEECs,and the EdU staining method was used to detect the proliferation ability of mEECs.Wound healing assay and Transwell chambers were used to detect the migration and invasion abilities of mEECs,respectively.The FAM-FLICA? Caspase-1 kit was used to detect Caspase-1 levels in mEECs.AutoDock Vina software was used for molecular docking of paeonol with Nrf2 to evaluate their binding ability.Results Compared with the model group,the paeonol groups and the gestrinone group showed reduced ectopic lesion volumes in EMS mice(P<0.05),decreased serum levels of TNF-α,IL-6,IL-1β,and IL-18,decreased expression of pyroptosis marker proteins NLRP3,ASC,Caspase-1,and GSDMD-N in ectopic lesion tissues,and increased expression levels of Nrf2,HO-1,and NQO-1.Compared with the TGF-β1 model group,the paeonol group showed reduced proliferation,migration,and invasion abilities of mEECs.Compared with the LPS model group,the paeonol group showed decreased levels of inflammatory factors TNF-α,IL-6,IL-1β,and IL-18 in mEECs,decreased expression levels of NLRP3,ASC,Caspase-1,and GSDMD-N,and increased expression levels of Nrf2,HO-1,and NQO-1.In the EMS mouse model,the Nrf2 inhibitor ML385 reversed the inhibitory effects of 50 mg/kg paeonol on pyroptosis and inflammatory levels in ectopic lesion tissues.In the in vitro cell model,ML385 reversed the effects of 100 μmol/L paeonol on mEECs.The binding score of paeonol with Nrf2 was-6.1 kcal/mol,and paeonol formed hydrogen bonds with the VAL-604 and LEU-365 amino acid residues of Nrf2.Conclusion Paeonol can alleviate inflammatory responses in EMS mice,reduce NLRP3 inflammasome activation and pyroptosis levels in ectopic lesion tissues,and activate the Nrf2/HO-1 signaling pathway in ectopic lesion tissues of EMS mice.
4.Effects of paeonol on activation and inflammation of NLRP3 inf lammasome in mice with endometriosis
Xiufang DU ; Hongjie YANG ; Xiaobei KANG ; Changna FU ; Tao YANG
Immunological Journal 2024;40(8):646-654
Objective To investigate the effects of paeonol on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway and pyroptosis levels in ectopic lesion tissues of endometriosis(EMS)mice and mouse endometrial epithelial cells(mEECs).Methods An allograft transplantation method was used to establish an EMS mouse model.Thirty-five Balb/c mice were divided into a sham group,a model group,a 12.5 mg/kg paeonol group,a 25 mg/kg paeonol group,a 50 mg/kg paeonol group,a 0.5 mg/kg gestrinone group(positive control group),and a 50 mg/kg paeonol+Nrf2 inhibitor ML385(30 mg/kg)group,with 5 mice in each group.mEECs were divided into a cell control group,a 10 ng/ml transforming growth factor-β1(TGF-β1)or 100 ng/ml lipopolysaccharide(LPS)model group,a 50 μmol/Lpaeonol group,a 100 μmol/L paeonol group,and a 100 μmol/L paeonol+ML385 group.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and IL-18 in the serum of EMS mice and the culture supernatant of mEECs.Hematoxylin and eosin(H&E)staining was used to detect histopathological changes in ectopic lesion tissues of mice.Western blot experiments were conducted to detect the protein expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),caspase-1,gasdermin D protein N-terminal fragment(GSDMD-N),Nrf2,heme oxygenase-1(HO-1),and quinone oxidoreductase-1(NQO-1)in ectopic lesion tissues and mEECs.The MTT method was used to detect the cell survival rate of mEECs,and the EdU staining method was used to detect the proliferation ability of mEECs.Wound healing assay and Transwell chambers were used to detect the migration and invasion abilities of mEECs,respectively.The FAM-FLICA? Caspase-1 kit was used to detect Caspase-1 levels in mEECs.AutoDock Vina software was used for molecular docking of paeonol with Nrf2 to evaluate their binding ability.Results Compared with the model group,the paeonol groups and the gestrinone group showed reduced ectopic lesion volumes in EMS mice(P<0.05),decreased serum levels of TNF-α,IL-6,IL-1β,and IL-18,decreased expression of pyroptosis marker proteins NLRP3,ASC,Caspase-1,and GSDMD-N in ectopic lesion tissues,and increased expression levels of Nrf2,HO-1,and NQO-1.Compared with the TGF-β1 model group,the paeonol group showed reduced proliferation,migration,and invasion abilities of mEECs.Compared with the LPS model group,the paeonol group showed decreased levels of inflammatory factors TNF-α,IL-6,IL-1β,and IL-18 in mEECs,decreased expression levels of NLRP3,ASC,Caspase-1,and GSDMD-N,and increased expression levels of Nrf2,HO-1,and NQO-1.In the EMS mouse model,the Nrf2 inhibitor ML385 reversed the inhibitory effects of 50 mg/kg paeonol on pyroptosis and inflammatory levels in ectopic lesion tissues.In the in vitro cell model,ML385 reversed the effects of 100 μmol/L paeonol on mEECs.The binding score of paeonol with Nrf2 was-6.1 kcal/mol,and paeonol formed hydrogen bonds with the VAL-604 and LEU-365 amino acid residues of Nrf2.Conclusion Paeonol can alleviate inflammatory responses in EMS mice,reduce NLRP3 inflammasome activation and pyroptosis levels in ectopic lesion tissues,and activate the Nrf2/HO-1 signaling pathway in ectopic lesion tissues of EMS mice.
5. Relationship of PAHs metabolites,DNA oxidative damage and RING2 expression in coke oven workers
Yanli LIU ; Hongjie ZHANG ; Baolong PAN ; Huitao ZHANG ; Yingying NIU ; Ye FU ; Jin YANG
China Occupational Medicine 2018;45(01):7-11
OBJECTIVE: To investigate the relationship of polycyclic aromatic hydrocarbons( PAH) metabolites,DNA oxidative damage and ring finger protein 2( RING2) expression in coke oven workers. METHODS: A judgment sampling method was used to select 497 coke oven workers in a steel plant as exposure group and 175 water treatment workers in the same plant as control group. The levels of urinary 1-hydroxypyrene, 2-hydroxynathalene, 2-hydroxyfluorene,9-hydroxyphenanthrene and 8-hydroxy deoxyguanosine(8-OHd G) were detected by high performance liquid chromatography.The RING2 expression in whole blood was measured by reverse transcription-polymerase chain reaction. RESULTS: The relative expression of urinary 1-hydroxypyrene,2-hydroxynathalene,2-hydroxyfluorene,9-hydroxyphenanthrene and RING2 in exposure group were higher than that in control group( P < 0. 01). The logistic regression analysis indicated that the higher the level of 1-hydroxypyrene,the higher the risk of high-RING2 expression( P < 0. 05) after adjusting for factors such as sex,age,smoking status,alcohol drinking,2-hydroxynathalene,2-hydroxyfluorene and 9-hydroxyphenanthrene.In 1-hydroxypyrene middle and high level groups,the 8-OHd G concentration of high-RING2 expression workers was significantly higher than those of low-RING2 expression workers( P < 0. 05). CONCLUSION: With the increase of urinary1-hydroxypyrene,the risk of high-RING2 expression was elevated,the degree of DNA oxidative damage was gradually increased.
6.RhoA/ROCK pathway of neural stem cells under mild hypothermia
Chao LI ; Hongjie FU ; Jianjun ZHANG ; Dong WANG
Chinese Journal of Tissue Engineering Research 2017;21(13):2094-2099
BACKGROUND:Mild hypothermia can effectively ease secondary brain and spinal cord injuries, which has a definite protective effect on the central nervous system. Meanwhile, mild hypothermia is conducive to the proliferation, activation and growth of transplanted cells by improving the microenvironment of the injured spinal cord.OBJECTIVE:To investigate whether mild hypothermia intervention can regulate the proliferation and apoptosis of neural stem cells through the RhoA/ROCK pathway.METHODS:The neural stem cell injury model was prepared and randomly divided into two groups:normothermia group and mild hypothermia group. The mild hypothermia group was treated with mild hypothermia [(32.0±0.5) ℃] for 4 hours. Expression of RhoA, RHOCK, Nogo-A and NgR in neural stem cells was detected by RT-PCR and western blot assay. RhoA/RHOCK positive cells were observed by fluorescence microscope. The intracellular Ca2+ concentration in neurons was measured by laser scanning confocal microscopy.RESULTS AND CONCLUSION:The expression of RhoA, RHOCK, Nogo-A and NgR in neural stem cells at mRNA and protein levels was significantly lower in mild hypothermia group than in the normothermia group (P < 0.05). The intracellular Ca2+ concentration in the neural stem cells was lower in the mild hypothermia group than in the normothermia group (P < 0.05). The number of RhoA/RHOCK positive cells in the brain tissue of rats was significantly lower in the mild hypothermia group than in the in the mild hypothermia group (P < 0.05). To conclude, mild hypothermia regulates the proliferation and apoptosis of neural stem cells by inhibiting the RhoA/ROCK pathway.
7.The clinical features of patients with lymphoplasmacytic diseases harboring MyD88 L265P mutation
Yuan REN ; Biqi ZHOU ; Yang XU ; Chengcheng FU ; Hongjie SHEN ; Zixuan DING ; Depei WU
Chinese Journal of Hematology 2016;37(12):1054-1059
Objective To explore the clinical features oflymphoplasmacytic diseases with MyD88 L265P mutation.Methods To analyze the distribution of MYD88 L265P mutation in patients with lymphoplasmacytic diseases by using of ARMS PCR-CE.Results There were 25(30.9%) MyD88 L265P mutated patients in 81 patients.The mutation was frequently observed in 14 patients with WM (77.8%,14/ 18),2 patients with lymphoplasmacytic lymphoma (66.7%,2/3),1 acute lymphocytic leukemia patient (50.0%,1/2),3 multiple myeloma patients (30.0%,3/10),1 patient with monoclonal gammopathy of undetermined significance (25%,1/4),3 patients with chronic lymphocytic leukemia (13.0%,3/23) and 1 lymphoma patient (4.8%,1/21).20 (80%,20/25) patients were identified with IgM subtype.Compared with wild-type group of 56 cases,mutated patients were older (median age:67 years vs 55 years,P< 0.001),with lower WBC count (median count:5.23 × 109/L vs 10.80× 109/L,P=0.001),lower HGB level (median count:85 g/L vs 119 g/L,P<0.001).Conclusion MyD88 L265P mutation was mainly observed in patients with IgM subtype lymphoplasmacytic diseases,and Waldenstrom's macroglobulinemia was the most common disease.Compared with the wild-type group,patients with MyD88 L265P mutation were older and had lower WBC count,lower level of HGB.However,further studies were needed to test the prognostic value of MyD88 L265P mutation.
8.Effects of invigorating spleen and eliminating dampness granules on CGRP in rat D-IBS model
Congmin FU ; Ye WANG ; Yinghan WANG ; Yuling LIU ; Xiaofeng ZHANG ; Hongjie GUO
Chongqing Medicine 2015;44(12):1603-1605
Objective To observe the effectof Invigorating Spleen and Eliminating DampnesGranuleon calcitonin gene related peptide(CGRP) in ramodelof diarrhepredominanirritable bowel syndrome (D-IBS) .Method60 Wistaratwere ran-domly divided into the control group(n=10) and the constructing model group (n=50) .Then ,the constructing model group warandomly re-divided into the model group (n= 10) ,positive control group (n= 10) ,invigorating spleen and eliminating dampnesGranulelow ,middle and high dose groups(n=10 each) .The D-Ibramodel waestablished by the restrainstresstimulation and gavage of folium sennae decoction fo2 week.The expression of CGRP in small intestinal mucosal membrane in each group wadetected by the immunohistochemical method .ResultIn the model group ,the CGRP positive arewadecreased ,which showed the statistical difference compared with the control group (P<0 .05);the CGRP positive arein varioutreatmengroupwaincreased ,which showed the statistical difference compared with the model group (P<0 .05);in the invigorating spleen and e-liminating dampnesgranulemiddle and low dose group,the CGRP positive arewaincreased with the statistical difference com-pared with the positive control group (P<0 .05) ,while withouthe statistical difference compared with the invigorating spleen and eliminating dampnesgranulehigh dose group (P>0 .05) .Conclusion Invigorating spleen and eliminating dampnesgranulea-chievethe therapeutical effecby increasing the level of CGRP in local intestinal tissue .
10.Clinical and genetic analysis of two Chinese patients with isovaleric acidemia and review of literature
Xi FU ; Hongjie GAO ; Tingting WU ; Wendi ZHANG ; Lihong LIAO ; Xiaoping LUO
Chinese Journal of Applied Clinical Pediatrics 2014;29(8):599-604
Objective To discuss the clinical features and treatment of isovaleric academia (IVA) patients,and to gain more comprehensive understanding of isovaleryl-CoA dehydrogenase(IVD) mutation in 2 siblings in order to raise awareness to prevent the occurrence of IVA.Methods The clinical history and laboratory test of 2 cases of children with IVA were carried out.The exons and neighboring introns of IVD gene of the whole family were PCR-amplified for DNA sequencing.The literature review of IVA in China was also conducted.Results Organic acid analysis of urine by GC/MS for both siblings showed extremely elevated concentrations of isovaleric glycine.For the older sibling,an acute episode of IVA caused severe metabolic stress and eventually death in the neonatal period.However,the disease was well-controlled for the younger sibling due to timely treatment and follow-up care for 2 years.The DNA sequencing of the IVD gene in the family revealed a novel c.1016G > A(C339Y) heterozygous mutation in mother and both of the siblings.No IVD mutation was detected in father or in any of the 50 cases of healthy controls.According to literature review,15 cases of IVA were reported in recent 15 years in China,including neonatal onset (11 cases),acute episode (12 cases),odor of sweaty feet (12 cases),pancytopenia (9 cases),hyperammonemia (5 cases),hypocalcemia (6 cases),and 6 cases of death were reported.Additionally,5 cases that received treatment of BCAA-free formula milk showed positive outcome.However,only 2 cases were followed up for more than 2 years.Conclusions Two new IVA patients carrying c.1016G > A(C339Y) mutation were reported in China.The mutation may lead to conformational change and functional deficient of the IVD protein.It is also necessary to point out that using direct DNA sequencing can not identify all patients with IVA due to limitations of this technology,and thus clinicians should be aware of the possibility of genetic misdiagnosis.Moreover,there is a trend of increasing IVA in China in recent years.

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