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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.
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Animals , Female , Humans , Male , Mice , Body Weight , Kidney , Leukocyte Count , Liver , Toxicity Tests, AcuteABSTRACT
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.
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Objective To observe the influences on prognoses and airway acid and base levels while using anti-inflammatory and anti-reflux therapies combined with "Hezhong Fuzheng massage" for treatment of infants with gastric volvulus (GV) and gastroesophageal reflux (GER)-induced pneumonia in order to provide evidence for clinical diagnosis and treatment of such infant disease. Methods Sixty infants 1-6 months old admitted to the Department of Integrated Traditional Chinese and Western Medicine of Wuhan Children's Hospital from January 2013 to December 2015 were diagnosed as pneumonia combined with GV and GER by the chest radiograph and radiography of upper gastrointestinal tract (UGT) with iodine, and according to difference in diagnostic methods, they were divided into an observation 1 group (30 cases) and an observation 2 group (30 cases). In observation 1 group, 24-hour pH value in upper digestive tract especially the distal esophagus was dynamically monitored, while in observation 2 group, 24-hour multichannel intraluminal impedance (MII) combined with pH monitoring of esophagus was carried out. Furthermore, two control groups were set up, each 30 cases; after radiography of the UGT with iodine, the control 1 group was diagnosed as GV and GER without pneumonia and control 2 group was diagnosed as only simple GV. Treatment of infant pneumonia was carried out in accordance with the guidelines for the management of community-acquired pneumonia in children; the treatment of GV and GER included postural, dietary, prokinetic and Hezhong Fuzheng massage [acupoint selection and massage was undertaken in 5 steps: push from the palmar crease to Banmen (rectilinear pushing manipulation) 300 times, push abdominal Yin and Yang (finger-pushing massage) 200 times, palpate the abdomen (clockwise) 100 times, poking of Tianshu 100 times, poke alternately bilateral Zusanli 100 times. Once-daily massage, (15±2) minutes each time, for consecutive 7 days]. The results of pH monitoring of the distal esophagus in observation 1 group was recorded; All GER data concerning pH monitoring of observation 2 group and the results of esophagus multi-channel intra-luminal impedance combined with pH monitoring in control group were compared. After 7 days of continuous treatment, the clinical efficacy of pneumonia and GV, hospitalization time, prognosis and the changes of sputum pH before and after treatment in the two observation groups were compared. Results In two observation groups, the main type of 60 cases with GV was organoaxial volvulus, accounting for 91.67% (55 cases), and more than 60% patients exhibited sputum pH <7.0. The distal esophagus 24-hour pH dynamic monitoring in observation 1 group showed that there were 26 cases with acid reflux (86.67%), 4 cases with GER negative (13.33%), the proportion of pH < 4 in GER negative patients was significantly lower than that in moderate acid reflux patients [3.35% (0.77% - 8.08%) vs. 26.23% (15.19% - 42.87%), P < 0.05], the number of long reflux (> 5 minutes) in GER negative patients was significantly reduced than that in mild acid reflux patients [times: 2 (0-5) vs. 7 (2-15), P < 0.05], the longest time of reflux in GER negative patients was significantly shorter than that in either mild or moderate acid reflux patients [minutes: 5.9 (2.5-10.0) vs. 19.2 (5.9-51.0), 41.6 (16.9-121.0), both P < 0.05]. The 24-hour MII-pH monitoring of esophagus in observation 2 group showed that there were 30 cases with pathological reflux, mainly mild acid reflux accounting for 90%, in which the percentage of proximal reflux events was 46.07% in the total reflux events. The numbers of acid reflux and proximal reflux in the observation 2 group were significantly higher than those in the control 1 and 2 groups [1 305 (37.72%) vs. 795 (25.69%) and 136 (18.89%), 1 594 (46.07%) vs. 687 (22.20%) and 154 (21.39%), both P < 0.05]; there were no significant differences in total effective rate (100% vs. 100%, P > 0.05) and hospitalization time (days: 7.58±1.09 vs. 7.67±1.12, P > 0.05) between the two observation groups. Conclusions For the diagnosis of infant pneumonia combined with GV and GER, the first selection of chest radiograph and radiography of the UGT with iodine can identify the severity of pneumonia, whether it is complicated with GV and its classification, and whether GER exists at the same time. The estimation of 24-hour pH dynamic monitoring of the acid reflux in the upper digestive tract especially the distal esophagus is consistent with that of the 24-hour MII-PH monitoring of esophagus. Moreover, 24-hour MII-PH monitoring of esophagus can also identify non-acid reflux, resulting in the GER diagnosis more accurate. Since the proximal reflux ratio of infants with GV combined with GER and pneumonia is relatively high and easy to cause cough and aspiration. attention should be paid on early diagnosis and timely intervention to such patients. The sputum acidity test can reflect the airway acid-base level and its manipulation is simple, so by that the real time disease situation can be estimated, and aspiration of sputum also can help the treatment. The therapeutic schedule formulated by our group can elevate the therapeutic effect, improve the airway acid-base environment and benefit prognosis.
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Objective To observe the clinical characteristics of infants with pertussis syndrome and the influence of gastroesophageal reflux (GER) on pertussis syndrome in small infants, and provide experience for improving curative effect. Methods ① The clinical data of 807 infants with pertussis syndrome treated at Wuhan Children's Hospital from January 2015 to June 2017 were retrospectively analyzed, in which their clinical characteristics including symptoms, signs and related physical and chemical examinations were summarized. ② Prospective randomized controlled trials were performed at the Children's Hospital of Wuhan from June 2017 to June 2018, there were 120 infants with ages < 6 months diagnosed as pertussis syndrome and simultaneously accompanied by gastric volvulus (GV) and GER, and they were randomly divided into a study group and a control group according to the date sequence of definite diagnosis, 60 cases in each group. The control group was given conventional medical treatment, while in the study group, additionally the infants received massage to restore gastric proper position and anti-reflux therapy. The clinical efficacies of two groups were observed. Results ① Retrospective analysis showed that clinically, pertussis syndrome commonly occurred in infants of ages < 6 months, accounting for 88.30% (713 cases); all cases had spastic cough, and 60.00% (484 cases) infants' coughing was severer at night. In laboratory examinations, 83.27% (672 cases) of the infants had elevated platelets (PLT), 25.03% (202 cases) had abnormal myocardial zymograms, and 70.38% (568 cases) had elevated white blood cells (WBC). In the pathogen examination, only were pathogens found in 34.8% infants, mainly single pathogen infection, accounting for 86.12%. Chest radiographs suggested 71.50% of infants with pneumonia, and 73.00% of infants with GER, among which 77.92% of infants were accompanied by GV. ② The prospective study showed that in the treatment of infants with pertussis syndrome accompanied by GV and GER, manual massage should be used timely to correct GV and simultaneously anti-reflux therapy should be given, in the aspects of time required to improve cough symptoms (days: 5.36±1.40 vs. 6.59±1.56, P < 0.01) and shortening of the hospital stay (days: 6.50±1.41 vs. 8.09±1.63, P < 0.01) in the study group were superior to those in the control group; the case of respiratory failure in the study group was lower than that in the control group [2 cases vs. 8 cases, P < 0.05]. Conclusions In pertussis syndrome, lymphocytes occupy the main proportion of WBC elevation that is an important differential criterion between pertussis syndrome and infantile pneumonia with gastric volvulus and gastroesophageal reflux. PLT elevation in pertussis syndrome suggests that attention should be paid to the elevation as that might be related to the disease prognosis. It is necessary to further investigate whether the positive pathogen discovered in the course of pertussis syndrome is a pathogenic one, and attention should also be paid to the medical examination of GV and GER in the small infants with pertussis syndrome, since early proper intervention to correct GV and GER can significantly improve their clinical efficacies.
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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.
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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.
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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.
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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.