1.Toxicokinetics and tissue distribution of alpha-amanitin in rats
Yumei LU ; Xuxian FU ; Fang LUO ; Enjin ZHU ; Gen XIONG ; Jinyang ZHAO ; Tinghao FU ; Shengjie NIE ; Rui WANG ; Shuhua LI
Chinese Journal of Pharmacology and Toxicology 2024;38(1):39-45
OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.
2.Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fifth Edition)updated for the Omicron variant
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Yunxiao SHANG ; Baoping XU ; Zhisheng LIU ; Gen LU ; Jikui DENG ; Guanghua LIU ; Xiaochuan WANG ; Jianshe WANG ; Luzhao FENG ; Wei LIU ; Yi ZHENG ; Sainan SHU ; Min LU ; Wanjun LUO ; Miao LIU ; Yuxia CUI ; Leping YE ; Adong SHEN ; Gang LIU ; Liwei GAO ; Lijuan XIONG ; Yan BAI ; Likai LIN ; Zhuang WEI ; Fengxia XUE ; Tianyou WANG ; Dongchi ZHAO ; Zhengyan ZHAO ; Jianbo SHAO ; Wong Wing-kin GARY ; Yanxia HE ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(1):20-30
China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.
3.Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells
Yi-wen GUO ; Bao-ning LIU ; Jia YU ; Xin-hua CHANG ; Mao-gen CHEN ; Yi MA ; Su-xiong DENG ; Rong-hai DENG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):958-964
BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells, resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However, little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells (GMSCs) in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose, observed the survival of pancreatic β-cells by immunohistochemistry, and detected the change of immune cells in the spleen of mice by flow analysis. Finally, the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice, with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group, P=0.013. The percentage of Follicular B cells(FO B cell) in the spleen of GMSCs-treated mice decreased from (52.2±4.1)% to (43.2±5.3)%, P=0.008, while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells, which could continuously produce insulin to control blood glucose. Finally, we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.
4.Establishment of a risk model for severe adenovirus pneumonia and prospective study of the timing of intravenous immunoglobulin therapy in children.
Sha CAI ; Chun-Hui ZHU ; Fang-Gen CHEN ; Fei LIU ; Mei-Ling GAO ; Yan XIONG
Chinese Journal of Contemporary Pediatrics 2023;25(6):619-625
OBJECTIVES:
To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP.
METHODS:
Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment.
RESULTS:
Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (P>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (P<0.05).
CONCLUSIONS
The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.
Child
;
Humans
;
Immunoglobulins, Intravenous/therapeutic use*
;
Prospective Studies
;
Retrospective Studies
;
Adenoviridae Infections/drug therapy*
;
Pneumonia, Viral/drug therapy*
;
Adenoviridae
5.Expert consensus on the diagnosis, treatment and prevention of monkeypox in children
Rongmeng JIANG ; Yuejie ZHENG ; Lei ZHOU ; Luzhao FENG ; Lin MA ; Baoping XU ; Hongmei XU ; Wei LIU ; Zhengde XIE ; Jikui DENG ; Lijuan XIONG ; Wanjun LUO ; Zhisheng LIU ; Sainan SHU ; Jianshe WANG ; Yi JIANG ; Yunxiao SHANG ; Miao LIU ; Liwei GAO ; Zhuang WEI ; Guanghua LIU ; Gang LIU ; Wei XIANG ; Yuxia CUI ; Gen LU ; Min LU ; Xiaoxia LU ; Runming JIN ; Yan BAI ; Leping YE ; Dongchi ZHAO ; Adong SHEN ; Xiang MA ; Qinghua LU ; Fengxia XUE ; Jianbo SHAO ; Tianyou WANG ; Zhengyan ZHAO ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(13):964-973
Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.
6.Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fourth Edition)
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Yunxiao SHANG ; Baoping XU ; Zhisheng LIU ; Gen LU ; Jikui DENG ; Guanghua LIU ; Xiaochuan WANG ; Jianshe WANG ; Luzhao FENG ; Wei LIU ; Yi ZHENG ; Sainan SHU ; Min LU ; Wanjun LUO ; Miao LIU ; Yuxia CUI ; Leping YE ; Adong SHEN ; Gang LIU ; Liwei GAO ; Lijuan XIONG ; Yan BAI ; Likai LIN ; Zhuang WEI ; Fengxia XUE ; Tianyou WANG ; Dongchi ZHAO ; Zhengyan ZHAO ; Jianbo SHAO ; Kwok-keung Daniel NG ; Wing-kin Gary WONG ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(14):1053-1065
Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.
7.Experts′ consensus on severe acute respiratory syndrome coronavirus-2 vaccination of children
Yuejie ZHENG ; Xiaochuan WANG ; Luzhao FENG ; Zhengde XIE ; Yi JIANG ; Gen LU ; Xingwang LI ; Rongmeng JIANG ; Jikui DENG ; Miao LIU ; Baoping XU ; Zhuang WEI ; Gang LIU ; Xiaoxia LU ; Runming JIN ; Zhisheng LIU ; Yunxiao SHANG ; Sainan SHU ; Yan BAI ; Min LU ; Guanghua LIU ; Wanjun LUO ; Yuxia CUI ; Leping YE ; Likai LIN ; Dongchi ZHAO ; Adong SHEN ; Jianbo SHAO ; Lijuan XIONG ; Liwei GAO ; Tianyou WANG ; Zhengyan ZHAO ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(18):1361-1367
At present, severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still rampant worldwide.As of September 10, 2021, there were about 222 million confirmed cases of corona virus disease 2019(COVID-19)and more than 4.6 million deaths worldwide.With the development of COVID-19 vaccines and the gradual vaccination worldwide, the increasing number of cases in children and unvaccinated young people has drawn attention.According to World Health Organization surveillance data, the proportion of COVID-19 infection cases in children gradually increased, and the proportion of cases in the age groups of under 5 years and 5-14 years increased from 1.0% and 2.5% in January 2020 to 2.0% and 8.7% in July 2021, respectively.At present, billions of adults have been vaccinated with various COVID-19 vaccines worldwide, and their protective effects including reducing infection and transmission, reducing severe disease and hospitalization, and reducing death, as well as high safety have been confirmed.Canada, the United States, Europe and other countries have approved the emergency COVID-19 vaccination in children and adolescents aged 12 to 17 years, and China has also approved the phased vaccination of COVID-19 vaccination in children and adolescents aged 3 to 17 years. For smooth advancement and implementation of COVID-19 vaccination in children, academic institutions, including National Clinical Research Center for Respiratory Diseases, National Center for Children′s Health, and The Society of Pediatrics, Chinese Medical Association organized relevant experts to reach this consensus on COVID-19 vaccination in children.
8.Twenty key issues on severe acute respiratory syndrome coronavirus-2 vaccination in children
Baoping XU ; Zhuang WEI ; Gen LU ; Yuejie ZHENG ; Xiaochuan WANG ; Luzhao FENG ; Zhengde XIE ; Gang LIU ; Yi JIANG ; Xingwang LI ; Rongmeng JIANG ; Jikui DENG ; Miao LIU ; Xiaoxia LU ; Runming JIN ; Zhisheng LIU ; Yunxiao SHANG ; Sainan SHU ; Yan BAI ; Min LU ; Guanghua LIU ; Wanjun LUO ; Yuxia CUI ; Leping YE ; Likai LIN ; Dongchi ZHAO ; Adong SHEN ; Jianbo SHAO ; Lijuan XIONG ; Liwei GAO ; Tianyou WANG ; Zhengyan ZHAO ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(18):1368-1372
Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still worldwide.As a vulnerable group, severe and dead pediatric cases are also reported.Under this severe epidemic situation, children should be well protected.With the widespread vaccination of SARS-CoV-2 vaccine in adults, the infection rate have decreased.Therefore, SARS-CoV-2 vaccine inoculation for children groups step by step is of great significance to the protection of children and the prevention and control of corona virus disease 2019(COVID-19) as a whole.But the safety of children vaccinated with SARS-CoV-2 vaccine is a main concern of parents.Therefore, in order to ensure the safety of vaccination and the implementation of vaccination work, National Clinical Research Center for Respiratory Diseases, National Center for Children′s Health and the Society of Pediatrics, Chinese Medical Association organized experts to interpret the main issue of parents about SARS-CoV-2 vaccine for children, in order to answer the doubts of parents.
9.Diagnosis, treatment and prevention of 2019 novel coronavirus infection in children: experts′ consensus statement (Third Edition)
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Baoping XU ; Zhisheng LIU ; Likai LIN ; Yunxiao SHANG ; Sainan SHU ; Yan BAI ; Min LU ; Gen LU ; Jikui DENG ; Wanjun LUO ; Lijuan XIONG ; Miao LIU ; Yuxia CUI ; Leping YE ; Liwei GAO ; Yongyan WANG ; Xuefeng WANG ; Jiafu LI ; Tianyou WANG ; Dongchi ZHAO ; Jianbo SHAO ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(10):721-732
2019 novel coronavirus(2019-nCoV) outbreak is one of the public health emergency of international concern.Since the 2019-nCoV outbreak, China has been adopting strict prevention and control measures, and has achieved remarkable results in the initial stage of prevention and control.However, some imported cases and sporadic regional cases have been found, and even short-term regional epidemics have occurred, indicating that the preventing and control against the epidemic remains grim.With the change of the incidence proportion and the number of cases in children under 18 years old, some new special symptoms and complications have appeared in children patients.In addition, with the occurrence of virus mutation, it has not only attracted attention from all parties, but also proposed a new topic for the prevention and treatment of 2019-nCoV infection in children of China.Based on the second edition, the present consensus further summarizes the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of treatment of 2019-nCoV infection in children.
10. Psychological influence of mini-invasive Carisolv III gel for caries removal in primary teeth
Min YAO ; Ai-xiu GONG ; Shu ZHOU ; Liang-yuan LIN ; Hao-ran MA ; Fen MIAO ; Zi-han LIU ; Gen-xiong TANG
Journal of Medical Postgraduates 2019;32(2):167-170
Objective Mini-invasive Carisolv is an aid to treat dental caries for patients with dental phobia. The article was to investigate the level of pain in caries removal using mini-invasive Carisolv III gel and mechanical methods with four psychological indicators. Methods We collected 120 primary molar tooth caries of 60 children treated in our hospital. Two primary molar tooth caries of each child were respectively treated with Carisolv III gel (Group A) and mechanical method (Group B) for caries removal. Psychological indicators including the visual analog scale (VAS), the Frank1 behavior rating scale (Frank1), the Kuttner law (Kuttner), and the Houpt behavior rating scale (Houpt) were used to assess the level of pain, degree of cooperation, pain tolerance and comfort. The clinical efficiency after six months and treatment time were compared between the two groups. Results There was no statistically significant difference before treatment between the two groups using the four psychological indicators (P>0.05) , while significant differences were found during and after the treatment between the two groups (P<0.05). Then, Carisolv III gel and mechanical groups for careis removal were compared before, during and after treatment themselves. In the Carisolv III gel group, there was no statistically significant difference using the four psychological indicators (P>0.05). In the mechanical group, there were statistically significant differences before and during treatment or before and after treatment using the four psychological indicators (P<0.05). The treatment time in Carisolv III gel group was longer than in mechanical group (P=0.001). There was no statistical difference between the two groups in filling examination after six months (P=0.082). Conclusion Carisolv III gel for caries removal can effectively avoid pain, improve comfort and decrease fear in children, which can be promoted in clinical application.

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