Objective To observe the clinical efficacy of self made Qinchai Kangdu mixture for treatment of infantile EB virus (EBV) infectious mononucleosis and explore its potential mechanism. Methods A prospective study was conducted. One hundred and twenty children with pediatric EBV infectious mononucleosis and traditional Chinese medicine (TCM) syndrome of flaring heat in Qifen and Yingfen in Wuhan Children Hospital were randomly divided into observation group and control group (each, 60 cases). Conventional western medical treatment was given to the two groups for 7-10 days;the observation group was additionally given Qinchai Kangdu mixture which included the following ingredients:Scutellariae Radix 10 g, Bupleuri Radix 10 g, Artemisiae Annuae Herba 10 g, Forsythiae Fructus 20 g, Arctii Fructus 10 g, Paeoniae Radix Rubra 10 g, Cinnamomi Ramulus 6 g, Moutan Cortex 10 g, Trionycis Carapax 10 g, Isatidis Radix 20 g, Citri Reticulatae Pericarpium 10 g, Glycyrrhizae Radix 10 g, orally, once daily for 7-10 days. The times of returning to normal for clinical symptoms and signs, white blood cell count (WBC), peripheral blood abnormal lymphocyte ratio and the level of alanine aminotransferase (ALT) were observed in the two groups. And the clinical efficacy, changes in score of TCM syndrome and adverse reactions were also investigated in the two groups. Results The total effective rate in the observation group was significantly higher than that in the control group [93.33%(56/60) vs. 76.67%(46/60), P<0.05]. In observation group, the duration of fever (days:6.9±2.3 vs. 7.7±3.4), and the recovery times to normal for body temperature (days:2.9±1.4 vs. 4.8±1.7), angina (days:7.2±3.3 vs. 8.0±3.2), lymph node reduction in size (days: 6.6±2.1 vs. 10.2±2.0), enlarged liver bounce back in size (days: 7.8±1.7 vs. 9.6±2.0), WBC (days:7.22±1.78 vs. 10.67±1.97), peripheral blood abnormal lymphocyte ratio (days:7.24±1.86 vs. 11.15±1.65), and ALT (days:8.44±1.83 vs. 11.43±2.65) were all significantly shorter than those in the control group (all P < 0.05). No adverse reactions occurred in the therapeutic course in the two groups. Conclusions Qinchai Kangdu mixture can effectively improve the clinical symptoms of infantile EBV infectious mononucleosis with TCM syndrome of flaring heat in Qifen and Yingfen. The mixture may also promote the enlarged liver and spleen to contract in size at early stage and peripheral blood abnormal lymphocyte ratio and other laboratory indexes return to normal in time.

Objective To explore the clinical manifestations and the characteristics of neonatal intrahepatic cholestasis caused by Citrin deficiency(NICCD)in Hubei province. Methods The biochemical indicators including liver function,blood lipid,lactic acid,blood ammonia,total bile acid,alpha feto protein,coagulogram,blood amino spec-trum,acylcrnitine spectrum,urine organic acid and SLC25A13 gene analysis of 20 cases with NICCD,who came from Wuhan Children's Hospital,during September 2010 to January 2013,were collected before treatment,then followed up for 1 year. Results Laboratory results of NICCD patients showed high blood bilirubin,elevated liver enzymes and bile acid,hyperlipidemia,high alpha feto protein,high lactic acidosis,high ammonia,hypoalbuminemia,hypoglycemia,disor-der of blood coagulation mechanism,variety of amino acids increase,mainly citrulline rose. Mainly long - chain acyl carnitine increased among acyl of carnitine. Abnormal increase of urine 4 - hydroxy benzene acetic acid,4 - hydroxy benzene lactic acid and 4 - hydroxy benzene pyruvic acid. Six mutations were detected in SLC25A13 gene analysis,and L477R,G639S of them were novel mutations,851del4,1638ins23,IVS6 + 5G ﹥ A were hot mutation. All the patients were eased in jaundice before they were 1 year old. Conclusions The early clinical criterion of the patients is disor-der. Hyperlipidemia has been detected in the early course of the disease,and L477R,G639S are the novel mutations.

Objective To investigate SLC25A13gene mutation in neonatal intrahepatic cholestasis caused by citrin defi-ciency (NICCD). Method A total of 17 children with NICCD were collected. PCR-RFLP method was used to analyze the most common eight mutations of SLC25A13 gene in Chinese populations and results were analyzed together with routine laboratory examinations. Results In the 17 NICCD patients, there were six cases of homozygous mutation, three cases of compound heterozy-gous mutation and eight cases of single heterozygous mutation in SLC25A13 gene. Three kinds of mutations detected were 851del4 (73.1%), 1638ins23 (11.5%) and IVS6+5G>A (15.4%). The seventeen cases showed classical NICCD symptoms of low birth weight, pathological jaundice. And laboratory data suggested liver dysfunction, hyperbilirubinemia, hyperbileacidemia, hy-poproteinemia, hypoglycemia, coagulation disorders, hyperlactacidemia and hyperammonemia. Conclusions 851del4, 1638ins23 and IVS6+5G>A are hot spots of SLC25A13 gene mutation in Chinese populations. PCR-RFLP is a rapid, convenient and reliable technology for NICCD molecular diagnosis.

Objective To observe the clinical efficacy of Linda mixture self made by combination of disease with syndrome pattern for treatment of neonatal intrahepatic cholestasis disease caused by Citrin defects (NICCD) and to provide an experience in early diagnosis and treatment of NICCD.Methods The clinical features of 20 patients with NICCD was confirmed by NICCD common genetic loci detection during hospitalization admitted to the Department of Integrated Traditional and Western Medicine in Wuhan Children Hospital from June 2012 to June 2015 were retrospectively analysed.The clinical efficacy of Chinese medicine Linda mixture for treatment of NICCD,before and after treatment,the index changes of liver function and coagulation function were observed and Color Doppler ultrasound was used to detect the situation of hepatosplenomegaly in the patients.Results There were 20 cases all their pathological jaundice occurring within 3 months old,after treatment,15 cases of them obtained clinical recovery and 5 cases were getting better,the average length of stay in hospital was (14.67 ± 1.56) days.After the treatment,the levels of serum total bilirubin (TBil),direct bilirubin (DBil),alanine aminotransferase (ALT),total bile acid (TBA) were markedly lower compared with those before treatment [TBil (μmol/L):64.0 ± 39.5 vs.173.5 ± 54.1,DBil (μmol/L):37.7±24.8 vs.80.9±46.4,ALT (U/L):42.1±25.8 vs.55.0±32.2,TBA (μnol/L):67.5±20.3 vs.195.0±61.3,all P ＜ 0.05],albumin (Alb) and total albumin (GLB) were significantly higher compared with those before treatment [Alb (U/L):37.9 ± 4.7 vs.33.1 ± 4.7,GLB (g/L):17.3 ± 4.0 vs.14.6 ± 2.8,both P ＜ 0.05],activated partial thromboplastin time (AP'TT) of coagulation function was significantly reduced (s:38.2± 8.3 vs.63.1±24.0,P ＜ 0.05).Color Doppler ultrasound examination showed that hepatosplenomegaly was shrunk after treatment [hepatomegaly (cm):2.12 ± 0.70 vs.3.04 ± 0.25,splenomegaly (cm):0.25 ± 0.03 vs.0.58 ± 0.32,both P ＜ 0.05].After 1 month of follow up,the infants' body weights were almost normal,the average increase in weight being (1.01±0.32) kg,the color and frequency of stool were distinctly better compared with those before treatment,the stool color in 15 cases was golden,pale yellow in 5 cases and no one,pottery clay in color.The stool frequencies of 18 cases were kept under 5 times,and fatty diarrhea situation was ameliorated.Conclusion Using Chinese medicine for treatment of NICCD can obtain significant clinical effects.

Objective To study the effects of early application of integrated traditional Chinese medicine (TCM)and western medicine and massage on the incidence and severity of pneumonia and prognosis in the therapeutic course of infants with cytomegalovirus(CMV)infection infantile cholestatic hepatopathy(ICH)accompanied by gastric volvulus(GV). Methods A prospective randomized controlled trial was conducted. 120 infants 1-6 months old with CMV infection ICH and complicated with GV inpatients were divided into treatment group and control group (each,60 cases). The TCM Lidanheji(consisting of artemisiae capillaris 30 g,weeping forsythia 30 g,Chinese goldthread 5 g,prepared rhubarb 5 g,unpeeled root of herbaceous peony 30 g,cassia 5 g,fruit of citron or trifoliate orange 10 g,large-headed atractylodes 10 g,fruit of Chinese magnoliavine 10 g,pangolin scale 3 g and licorice root 5 g)for oral administration or enema and ganciclovir intravenous injection were given to both groups. In the control group,based on the above treatment,postural and diet therapy,prokinetics(domperidone)were given in cases with GV. The massage treatment was only applied for treatment of GV in treatment group. The pneumonia in both groups was treated in accord to the conventional diagnosis and treatment for infantile pneumonia,bronchiolitis,severe pneumonia and the guide and management of infantile community acquired pneumonia. The total number of cases with pneumonia and its severity occurring before and after treatment in the course of the disease,the clinical therapeutic effects of ICH, GV and infantile pneumonia,the clinical physical signs,biochemical indexes and the time of hospitalization were observed and compared between the two groups. Results Compared with control group,after treatment the curative rate and total effective rate of ICH,GV,infant pneumonia in treatment group were significantly higher〔the curative rate of ICH:83.05%(49/59)vs. 71.93%(41/57),total effective rate:96.61%(57/59)vs. 91.23%(52/57);the curative rate of GV:72.88%(43/59)vs. 51.79%(29/56),total effective rate:96.61%(57/59)vs. 78.57%(44/56);the curative rate of infant pneumonia:81.08%(30/37)vs. 67.44%(29/43),total effective rate:100%(37/37)vs. 100%(43/43),P<0.05 or P<0.01〕. In the treatment group,the total number of cases with pneumonia occurring in the therapeutic course and the incidence of severe pneumonia were significantly less than those in the control group〔the occurrence of pneumonia:12 cases vs. 21 cases,the incidence of severe pneumonia:16.67%(2/12) vs. 42.86%(9/21),P<0.05 or P<0.01〕. The enlargement of liver and spleen,the level of total bilirubin(TBil), direct bilirubin(DBil),total bile acids(TBA)and alanine aminotransferase(ALT)in two groups after treatment were significantly lower than those before treatment,the changes being more marked in treatment group(P<0.05 or P<0.01). The time of stay in hospital in treatment group was remarkably shortened(days:21.32±3.26 vs. 27.38±6.09, P<0.05). Conclusion Early interference with combined TCM and western medicine and massage for treatment of infants with CMV infection ICH accompanied by GV can significantly decrease the incidence of pneumonia and its severity occurring in the disease course,therefore this therapeutic method is beneficial to the treatment and prognosis of infants with CMV infection ICH.

Objective To systemically evaluate the clinical therapeutic effect and safety of traditional Chinese medicine on Kawasaki disease. Methods Through retrieval of the reports in PubMed, the Cochrane Library, China National Knowledge Internet (CNKI), VIP database, Wanfang database by computer, the correlative articles of clinically randomized controlled trials (RCTs) published in China during the period from 1990 to 2013 were collected, and their quality evaluation was made. All the articles were screened according to inclusion and exclusion criteria, in which interventions were traditional Chinese medicine therapy and conventional western treatment. The articles selected were assessed with the software of RevMan 5.2. Results There were 212 articles searched out, but only 13 articles, 656 children with Kawasaki disease were conformed to the inclusion criteria. The Meta analysis indicated that the total effective rate in the traditional Chinese medicine group was superior to the group treated with western medicine. The difference in the curative effects between the two groups had notable significance [odds ratio (OR) = 3.58, 95%confidence interval (95%CI) was 2.16-5.93, test for overall effect Z=4.94, P<0.000 01]. No difference was seen in the curative effect of improving coronary artery changes between the traditional Chinese medicine group and western medicine control group (OR=2.03, 95%CI was 0.74-5.62, test for overall effect Z=1.37, P=0.17). Conclusion The clinical therapeutic effect of traditional Chinese medicine on Kawasaki disease is superior to that treated by western medicine.

Objective:To discuss the research progress in the field of coronavirus (CoVs) treatment based on the visualization analysis of knowledge graph.Methods:The related literatures in the field of CoVs treatment were retrieved from the establishment of Web of Science core collection database to February 15th, 2020, and the literature analysis tool of Web of Science database was used to count the annual trend of published literatures. The VOSviewer software was used to analyze the relationship among countries, institutions, authors, clustering and density of subject words. The HistCite software was used to screen important documents and to draw the evolution process of hot spots. The CiteSpace software was used to analyze the breakout points of subject words, so as to find the front and hot spots in this field.Results:A total of 1 747 data were retrieved, with the exception of 17 duplicate data, and 1 730 data were retained for visualization analysis. In terms of literature volume, the literatures on CoVs therapy rose after 2003 and 2012, and the number of published literatures had remained high since 2014. In terms of countries, the main countries that carried out the research on the treatment of CoVs were the United States ( n = 613), China ( n = 582), Germany ( n = 122), Canada ( n = 99), etc., and the cooperation among countries was close. In terms of institutions, the number of papers issued by Chinese Academy of Sciences in the field of CoVs treatment ranked first ( n = 82), followed by University of Hong Kong of China ( n = 74) and Chinese University of Hong Kong of China ( n = 58), followed by National Institute of Allergy and Infectious Diseases ( n = 37), and the cooperation among various institutions was close. In terms of literature authors, there were two high-yielding authors in the United States [Ralph S. Baric ( n = 21) and Kuochen Chou ( n = 17)], two Chinese authors [Yuen Kwok-yung ( n = 17) and Jiang Shibo ( n = 16)] and one Dutch author [Eric J. Snijder ( n = 17)]. In terms of the cluster analysis of authors, the authors were closely related in reverse genetics, respiratory infection, receptor binding domain, etc., and the 15 top-cited papers came mainly from China, the United States, Netherlands and other countries, and the literature content represented the frontiers and hot spots in different periods. The treatment hot spots focused on preventing virus adsorption, inhibiting the virus gene nucleic acid replication, transcription and translation. The main subject words were divided into three main categories, namely, CoVs epidemiology, basic research and drug development, in which basic research and drug development were strongly correlated. In the subject words breakthrough analysis, there were time-related breakthrough points in 1991, 1996 and 2002, and the "diagnosis" and "sequence" were continuous hot spots. Conclusions:Through the visualization analysis of knowledge graph, the development trend and hot spots of CoVs therapy research could be well observed. In this study, the degree of attention in the field of CoVs treatment showed periodic changes, related to the outbreak of new CoVs, and the country, institutions and the author were closely related. The treatment hot spots focused on preventing virus adsorption, inhibiting the virus gene nucleic acid replication, transcription and translation in order to develop new targets of drug.

Objective:To explore the related factors affecting the prognosis of children with parenteral nutrition-associated cholestasis (PNAC).Methods:Twenty children with PNAC admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2020 were selected as research objects by retrospective study. According to prognosis, children were divided into good (15 cases) and poor prognosis group (5 cases). Clinical data such as general condition, intravenous nutrition duration, related biochemical examination indexes and main treatment methods of children in the two groups were collected. Spearman correlation analysis was used to quantify the correlation between alanine aminotransferase (ALT) and poor prognosis. Univariate analysis was used to analyze the risk factors affecting the prognosis of children with PNAC, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of ALT on the prognosis of children.Results:There were no significant differences in gender, body weight, gestational age, age, feeding mode, duration of intravenous nutrition, direct bilirubin (DBil), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), total protein (TP), serum albumin (Alb), globulin (GLB), alkaline phosphatase (ALP), platelet count (PLT), white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), lymphocyte count (LYM), urine culture, AST/PLT ratio (APRI) and main treatment methods between the two groups. Total bilirubin (TBil), ALT, neutrophil count (NEU) and monocyte count (MONO) in the good prognosis group were significantly lower than those in the poor prognosis group [TBil (μmol/L): 120.00±48.63 vs. 175.26±29.14, ALT (U/L): 73.25±44.29 vs. 145.30±74.33, NEU (×10 9/L): 2.55±1.29 vs. 5.08±4.10, MONO (×10 9/L): 1.23±0.87 vs. 2.13±0.60, all P < 0.05]. Logistic regression analysis showed that ALT was the risk factor affecting the prognosis of children with PNAC, when ALT increased by 1 U/L, the probability of poor prognosis increased by 3.6% [odds ratio ( OR) = 1.04, 95% confidence interval (95% CI) was 1.00-1.07, P = 0.04]. Spearman correlation analysis showed that the incidence of poor prognosis was positively correlated with ALT ( r = 0.49, P = 0.03). ROC analysis showed that ALT had certain predictive value for the prognosis of children with PNAC [area under ROC cure (AUC) = 0.83, 95% CI was 0.00-1.00, P = 0.03]; when the cut-off value was 121.50 U/L, its sensitivity was 80% and specificity was 93%, suggesting that ALT could be used as the main indicator for clinical prediction of poor prognosis for PNAC. Conclusion:ALT is an independent risk factor of poor prognosis in children with PNAC.

OBJECTIVE: To observe the acute toxic reaction of the Li-Dan-He-Ji granules, and to evaluate its safety. METHODS: Sixty C57BL6/J mice were randomly divided into normal control group, vehicle group and drug treatment group, with 10 females and 10 males in each group. According to the Technical guidelines for the study of toxicity of single drug administration, the maximum administration dosage (MAD) was used to intragastric administration of Li-Dan-He-Ji granules 0.04 mL/g (42.8 g/kg), three times within 24 hours, with an interval of 6 hours. The vehicle group was fed with the same pure water. The normal control group received no treatment. The mice were observed continuously for 14 days, and the appearance characteristics, behavioral activities, body weight changes and the number of deaths in each group were recorded. At the 14 days, blood samples were collected from the eyeballs, and routine blood tests such as white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), lymphocyte percentage (LYM%), neutrophil percentage (NEU%), red blood cell count (RBC), hemoglobin (Hb), and platelet count (PLT) were performed. And alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and other biochemical indicators. The mice were then sacrificed, and the histopathological changes of liver and kidney were observed by hematoxylin-eosin (HE) staining. The organ indexes of heart, liver, spleen, lung, kidney and thymus were calculated. RESULTS: The median lethal dose (LD₅₀) of Li-Dan-He-Ji granules were not obtained. During the MAD experiment, the animals in each group did not die, their behavioral activities were normal, and there was no significant change in liver and kidney histopathological examination. There were no significant differences in body weight, blood routine, biochemical indexes and organ index among all groups (all P > 0.05). The body weight (g) of normal control female and male group, vehicle female and male group and drug female and male group before administration were 18.96±1.14, 19.65±1.45, 19.33±1.30, 19.53±1.22, 19.28±1.69 and 19.48±1.28; 14 days after administration were 27.69±0.81, 28.19±2.22, 27.77±1.00, 27.88±1.85, 27.92±1.33 and 28.07±1.93, respectively. CONCLUSIONS The Li-Dan-He-Ji granules have low oral toxicity, combined with clinical observation, can be safely used in infants.
Animals ; Female ; Humans ; Male ; Mice ; Body Weight ; Kidney ; Leukocyte Count ; Liver ; Toxicity Tests, Acute

Objective To investigate the regulation effect of emodin on human embryonic liver L02 cells strain farnesoid X receptor (FXR) pathways.Methods By using Guggulsterones,FXR genes were intervened with in L02 cells as model group,in three different concentrations of emodin (50.0 μ mol/L,25.0 μmol/L,12.5 μmol/L) of emodin in the model group cells,FXR,small heterodimer parter (SHP),UDP-glucuronosyltransferase 2B4 (UGT2 B4),bile salt export pump(BSEP) mRNA and protein expressions were detected by real-time fluorescent quantitative PCR and Western blot test.Results (1) The relative expressions of FXR mRNA and protein in the model group (0.240 ± 0.021,0.385 ±0.119) decreased significantly than those of control group (1.000 ± 0.088,1.000 ± 0.223),the differences were statistically significant (t =14.62,4.21,all P ＜ 0.01).Compared with the model group,the relative expressions of FXR mRNA in the high,the middle and the low-dose emodin groups (0.755 ±0.083,0.817 ±0.097,0.547 ± 0.080) were significantly higher (t =10.42,10.03,6.39,all P ＜ 0.01).The relative expressions of FXR protein in the medium-dose group (0.865 ± 0.203) increased significantly (t =3.53,P ＜ 0.01).The relative expressions of FXR mRNA in the high and the medium-dose groups (0.755 ± 0.083,0.817 ± 0.097) were higher than those in the low-dose group (0.547 ± 0.080),the differences were statistically significant (t =3.11,3.70,all P ＜ 0.01).(2)The relative expressions of SHP,UGT2B4,BSEP mRNA and protein in the model group (0.148 ±0.025,0.205 ± 0.039,0.184 ± 0.020;0.458 ± 0.130,0.255 ± 0.170,0.303 ± 0.100) were significantly lower than those in the control group (1.000 ±.0.099,1.000 ±0.104,1.000 ±0.125;1.000 ±0.129,1.000 ±0.157,1.000 ±0.162),the differences were statistically significant (t =14.50,12.44,11.19,5.13,5.57,6.33,all P ＜ 0.01).The relative expressions of SHP,UGT2B4 and BSEP mRNA in the high,the middle and the low-dose groups (0.610 ± 0.058,0.514 ± 0.041,0.707 ± 0.062;0.755 ± 0.108,0.800 ± 0.086,0.727 ± 0.076;0.470 ± 0.070,0.582 ± 0.050,0.500±0.108) were significantly lower than those in the model group (0.148 ± 0.025,0.205 ± 0.039,0.184 ± 0.020),the differences were statistically significant (t =12.75,9.38,13.94,9.46,10.90,11.96,7.53,10.31,5.00,all P ＜0.01).The relative expressions of SHP,UGT2B4 and BSEP mRNA in the high and the middle-dose emodin group (0.658 ±0.091,0.624 ±0.113,0.607 ±0.097;0.868 ±0.194,0.883 ±0.099,0.913 ±0.131) were significantly higher than those in the low-dose group (0.458 ±0.130,0.255 ±0.170,0.303 ±0.100),the differences were statistically significant (t =2.18,3.13,3.78,3.05,5.53,6.41,all P ＜ 0.01).The relative expression of SHP and BSEP protein in the low-dose group (0.645 ±0.135,0.572 ±0.076) increased,the differences were statistically significant (t =1.73,P ＜ 0.05,t =3.72,P ＜ 0.01).The relative expression of BSEP protein in the high and the medium-dose groups (0.607 ±0.097,0.913 ± 0.131) was significantly higher than those in the low-dose group (0.572 ± 0.076),the differences were statistically significant (t =1.99,3.90,all P ＜ 0.01).The relative expressions of SHP and UGT2B4 mRNA in the high and the low-dose group (0.610 ±0.058,0.470 ±0.070;0.514 ± 0.041,0.582 ± 0.050) were significantly lower than those in the medium-dose group (0.800 ± 0.086),the differences were statistically significant (t =3.75,6.47,3.83,3.42,all P ＜ 0.01).The expression levels of UGT2B4 and BSEP in the high and the low-dose groups (0.624 ± 0.113,0.644 ± 0.097;0.607 ± 0.097,0.572 ± 0.076) were significantly lower than those in the medium-dose group (0.883 ± 0.099,0.913 ± 0.131),the differences were statistically significant (t =4.27,2.98,6.30,3.90,all P ＜ 0.01).Conclusions Guggulsterones can inhibit FXR and downstream genes SHP,UGT2B4,BSEP expressions in L02,and emodin can enhance FXR gene expression,promote SHP,UGT2B4,BSEP gene expression,inhibit cholestasis pathway,protection of liver cell,which shows a dosage discreapancy.