OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides （BCP） on acute liver injury （ALI） in mice. METHODS Overall 40 mice were randomly divided into normal group， model group， positive control group （Baogan tablet， 550 mg/kg）， BCP high-dose and low-dose groups （400， 100 mg/kg）， with 8 mice in each group. The drug was administered intragastrical once a day for 7 days. One hour after the last administration， except for the normal group， mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model. After injection of concanavalin A solution for 12 h， the liver and spleen indexes of mice were measured， and the pathological changes of liver and spleen tissue were observed； the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） were detected， and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissue were detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum and liver tissue of mice were determined， as well as the protein expression levels of nuclear factor-κB （NF-κB）， Toll-like receptor 4 （TLR4）， nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were also detected. RESULTS Compared with the normal group， the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells； spleen enlargement， increased bleeding and decreased lymphocytes were observed， liver and spleen indexes were increased significantly （P＜0.01）； the serum levels of AST， ALT and LDH， the levels of TNF-α， IL-6 and IL-1β in serum and liver tissue， as well as the MDA level， protein expressions of TLR4， NF- κB and HO-1 in liver tissue were all increased significantly （P＜0.05 or P＜0.01）. The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly （P＜0.05）. Compared with the model group， the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups， and most of liver and spleen indexes， the above indexes of serum and liver tissue were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS BCP has a protective effect on ALI， the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.

Objective:To investigate the correlation between serum uric acid/high density lipoprotein cholesterol (URH) and diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM) .Methods:According to urinary albumin creatinine ratio, 171 patients with T2DM were divided into simple T2DM group (group A1), microalbuminuria group (group A2) and macroalbuminuria group (group A3). The general data, HbA1c, biochemical indices were compared, and URH was calculated.Results:The systolic blood pressure, diastolic blood pressure, SUA, TG and URH of A1 group were lower than those of the other two groups [ (129.7±15.78) vs (141.65±16.04) vs (147.31±17.01) mmHg, (78.9±10.71) vs (83.79±10.67) vs (84.61±12.19) mmHg, 291.5 (253.75, 351.25) vs 346 (280, 409) vs 344.5 (274.75, 425.75) μmol/L, 26.12 (19.71,32.96) vs 33.45 (26.55,42.2) vs 33.45 (26.55,42.2) ] ( P<0.05). HDL-C was higher than those of the other two groups [1.19 (1.02,1.29) vs1.02 (0.87,1.21) vs 1.07 (0.93,1.25) mmol/L] ( P<0.05), the course of disease and SCr of group A3 were higher than those of the other two groups [10.5 (7.25, 15) vs 8.5 (4,12) vs 8 (3,11) years; 82.5 (70.57,101.75) vs 66 (52.75,73.75) vs 64 (51, 84) μmol/L ] ( P<0.05), and eGFR was lower than those of the other two groups [91.63 (67.09, 112.21) vs 116.7 (96.6, 142.53) vs 109.85 (85.64, 152.39) ml/min/1.73 m 2] ( P<0.05). There were no significant differences in gender, smoking history, drinking history, age, BMI, TC, LDL-C, BUN, FPG or HbA1c among different groups (P> 0.05). Correlation analysis showed that the course of disease, systolic blood pressure, diastolic blood pressure, TG, SUA, URH were positively correlated with UACR, while HDL-C was negatively correlated with UACR. Logistic regression analysis showed that course of disease was a risk factor for macroproteinuria, while systolic blood pressure and URH were risk factors for microproteinuria and macroproteinuria. ROC curve showed that the AUC value of URH was the highest, and the accuracy rate was 69.3%. Conclusions:URH is closely related to the occurrence of DKD and is a risk factor of DKD. Dynamic monitoring of URH in T2DM patients is helpful for early screening of DKD, which is superior to SUA and HDL-C.

ObjectiveTo explore the meridian tropism of components in Bupleuri Radix （Chaihu， CH） based on the model of nonalcoholic steatohepatitis （NASH） and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan （XYS） by means of principal component analysis. MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups， with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient （MCS） diet， the other mice were fed with methionine choline-deficient （MCD） diet for 4 weeks to establish the nonalcoholic steatohepatitis （NASH） model. After the established model was confirmed by hematoxylin-eosin （HE） staining， the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically， the 8 groups were XYS group （2.874 g·kg^-1）， XYS-CH group （2.445 g·kg^-1）， XYS-CH+volatile oils （Vol， 0.163 mg·kg^-1） group， XYS-CH+polysaccharides （Pol， 24.067 mg·kg^-1） group， XYS-CH+flavones （Fla， 2.241 mg·kg^-1） group， and XYS-CH+saponins （Sap， 2.746 mg·kg^-1） group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration， the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay （ELISA） kits were used to determine the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL） in serum as well as malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice. ResultCompared with the blank control group， the modeling led to hepatocyte swelling， increased fat vacuoles， and appearance of inflammatory cells. Further， the modeling elevated the levels of ALT， AST， TG， TC， and LDL and lowered the HDL level in serum， and it increased the MDA level and decreased the SOD， CAT， and GSH-Px levels in liver. Compared with the model group， the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver （P<0.05）. The comprehensive score of the pharmacological efficacy was in a descending order as follows： XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH， Sap had the best effect. ConclusionSap lowers the blood lipid level， regulates the abnormal lipid metabolism， and alleviates the oxidative damage of liver， which is the substance basis for CH to exert the meridian tropism in liver.

Objective:To explore the method of ultrasonography for detecting the fetal umbilical vein diameter, blood flow volume and normalized volume blood flow and establish normal reference ranges with umbilical vein diameter, blood flow volume and normalized blood flow and Z-scores for umbilical vein diameter and blood volume flow.Methods:This was a prospective study on 907 normal fetuses in the Second Xiangya Hospital, Central South University and Women and Children Healthcare Hospital of Zhuzhou from March 2019 to December 2020. The umbilical vein diameter (Duv), umbilical vein blood flow volume (Quv) and normalized volume blood flow (nQ = Quv/estimated fetal weight) of the free loop of umbilical vein (FUV) and fetal intra-abdominal umbilical vein (IUV) were collected. And the mean values and 90% confidence intervals of Duv, Quv and nQ in two segments of umbilical veins at different gestational ages were calculated. Regression analysis of Duv, Quv and nQ were performed with gestational age (GA), and the parameters of umbilical vein in different segments were compared. Finally, with gestational age (GA) as the independent variable, Z-scores of the Duv and Quv were built.Results:The mean values and 90% confidence intervals of Duv, Quv, and nQ in 858 (94.6%) normal fetal umbilical veins were successfully obtained. The Duv, Quv of the FUV and IUV increased as pregnancy progressed. The Quadratic curve of Duv and Linear curve of Quv were of the highest fitnesses, respectively( r=0.951, 0.941, 0.986, 0.982; all P<0.001). While nQ increased with GA followed by a decreased trend, and the Quadratic curve was the highest fitting curve of nQ( r=0.610, 0.611; all P<0.001). Duv-FUV was greater than Duv-IUV( P<0.001), nQ-FUV was bigger than Quv-IUV( P=0.001), and he difference was not statistically significant between Quv-FUV and Quv-IUV( P=0.133). Z-scores models of Duv and Quv were successfully established, and all Z-scores were Gaussian distribution. Conclusions:The normal ranges and Z-scores of umbilical vein parameters are useful to improve the evaluation of placental circulation and provide a strong basis for the monitoring of fetus-related diseases and the evaluation of pregnancy prognosis. The choice of FUV or IUV umbilical vein to evaluate placental circulation may depend on the actual situation in clinical application.

Objective To explore the risk factors of postoperative pulmonary infection in patients with craniocerebral injury and establish a nomogram model to predict the risk of postoperative pulmonary infection after craniocerebral injury.Methods The clinical data of 169 patients with craniocerebral injury,admitted to and underwent craniotomy in our hospital from January 2013 to December 2018,were retrospectively analyzed.The clinical data of patients with postoperative pulmonary infection and without postoperative pulmonary infection were compared.The risk factors of postoperative pulmonary infection were analyzed by multivariate Logistic regression.R language was used to establish a nomogram model to predict the risk of postoperative pulmonary infection after craniocerebral injury.Receiver operating characteristic (ROC) curve was used to explore the prediction efficiency of the nomogram model for pulmonary infection after craniocerebral injury.Results Among the 169 patients,74 (43.8％) were complicated with pulmonary infection and 95 (56.2％) were not complicated with pulmonary infection.As compared with non-pulmonary infection group,pulmonary infection group had significantly higher percentages of patients with open craniocerebral injury and Glasgow coma scale (GCS) scores＜7,significantly higher American Society of Anesthesiologists (ASA) grading,lower albumin level one week after surgery,statistically longer operation time,and significantly higher percentages of patients with conscious disorder,patients accepted intraoperative blood transfusion,patients used breathing machine,and patients stayed in bed for 4 weeks or more (P＜0.05).Multivariate Logistic regression analysis showed that GCS scores (OR=0.243,95％CI:0.122-0.497,P=0.000),ASA grading (OR=3.349,95％CI:2.233-5.021,P=0.000),disturbance of consciousness (OR=3.185,95％CI:1.217-8.334,P=0.018),and useofventilator (OR=3.376,95％CI:1.590-7.167,P=0.002) were independent risk factors for postoperative pulmonary infection in patients with craniocerebral injury.The scores of the nomograrn model were 13.7,100.0,38.0 and 27.5 in GCS scores,ASA grading,disturbance of consciousness and use of ventilator,respectively.The consistency index of the nomogram model for predicting postoperative pulmonary infection in patients with craniocerebral injury was 0.835.ROC curve showed that the area under the curve predicted by nomogram model for postoperative pulmonary infection in patients with craniocranial injury was 0.840 (95％CI:0.778-0.901).Conclusion Based on the risk factors for pulmonary infection after craniocerebral injury,a nomogram model for predicting the risk of pulmonary infection is established,which has a good differentiation degree and prediction effect,and can provide a reference for medical staffto identify high-risk patients at an early stage,so as to take more targeted intervention measures.

Objective To examine the efficacy and safety of 125Iseed implantation for treating neuroblastoma (NB) in animal models.Methods A total of 45 nude mice models of neuroblastoma were constructed and divided into the 125Igroup.control group.and blank group at 15 mice per group.The long and short diameters of the tumor were measured every 3 days.and the tumor inhibition rate was calculated every 9 days.Apoptotic and proliferative protein expression levels in tumor tissue and peritumoral tissue.as well as endocrine markers and bone marrow of the nude mice.were analyzed.The independent sample t test was used to compare the mean scores.and ANOVA was used for comparison between multiple groups.Results Tumor volume inhibition rate was significantly higher in the 125Igroup than in the control group and blank group on days 9.18.and 27(all P<0.05).Caspase-3 expression in tumor tissues was significantly higher in the 125Igroup than in the control group and blank group (all P<0.05).whereas proliferating cell nuclear antigen (PCNA) expression was significantly lower in the 125Igroup than in the control group and blank group (all P<0.05).There was no significant difference in Caspase-3 and PCNA expression between the control group and blank group (all P>0.05).In addition.no significant difference in the expression of Caspase-3 and PCNA in peritumoral tissue was observed between the 125Igroup.control group.and blank group (all P>0.05).Cell apoptosis in tumor tissue was significantly lower in the blank group and control group than in the 125Igroup (all P<0.05).while there was no significant difference between the blank group and the control group (P>0.05).There was no significant difference in endocrine markers between the three groups (P>0.05).There was no significant bone marrow suppression in the 125Igroup.and this observation was similar to those in the control group and blank group (all P>0.05).Conclusions 125Iseeds have significant toxicity to NB.125Iseed implantation is safe in nude mice with NB within the therapeutic doses.

Background:CDK14 is a novel cyclin-dependent kinase,which is overexpressed in a variety of cancer and related to their malignant behavior. Aims:To investigate the effect of CDK14 on proliferation of human esophageal carcinoma cells and its possible mechanism. Methods:Expressions of CDK14 and two cell proliferation markers,PCNA and Ki-67 were estimated in 8 fresh-frozen specimens of esophageal squamous cell carcinoma(ESCC),96 paraffin-embedded specimens of ESCC,and human ESCC cell line Eca-109 by Western blotting and immunohistochemistry. Correlations of CDK14 expression with the clinicopathological characteristics and prognosis of ESCC were analyzed. Serum starvation and release assay was performed to evaluate the relationship between CDK14 expression and cell cycle progression in Eca-109 cells. Furthermore,Eca-109 cells were transiently transfected with shRNA-CDK14 to reduce CDK14 protein level,and then the phosphorylation of tumor suppressor protein Rb,cell cycle progression and proliferation capability of Eca-109 cells were determined. Results:CDK14 was highly expressed in both ESCC tissue and cell line,which was paralleled with the expressions of PCNA and Ki-67 and correlated significantly with the tumor size,histological grade,invasiveness and metastasis of ESCC(P < 0. 05). The overall survival was poor in patients with high CDK14 expression than those with low CDK14 expression(P < 0. 05). Serum starvation and release assay showed that the expression of CDK14 was cell cycle-dependent. Knockdown of CDK14 reduced the expression level of phosphorylated Rb,induced significant G1 phase arrest and resulted in less colony formation in Eca-109 cells(P all < 0. 05). Conclusions:CDK14 is highly expressed in ESCC. It may promote cell cycle progression by phosphorylating downstream Rb protein,thus enhancing the proliferation of tumor cells,and ultimately participating in the occurrence and development of ESCC.

Objective To investigate the clinical efficacy and feasibility of 125I seeds implantation combined with high intensity focused ultrasound (HIFU) for portal vein tumor thrombus (PVTF) from HCC.Methods Nineteen cases of PVTT from HCC (17 males,2 females;average age:50 years,stage:Ⅰ-Ⅲ)undergoing 125I seeds implantation combined with HIFU from March 2011 to October 2013 were retrospectively studied.The radioactivity of each 125I seed was 18.5 MBq and the matched peripheral dose was 90-120 Gy.HIFU parameters were set as follows:ultrasound wave frequency,0.85 mHz;output power,300-400 W;total treatment duration,33-70 min.During the follow-up of 3-24 months,the change of PVTT size,postoperative complications and survival rate were recorded.Kaplan-Meier method was used to analyze the survival rate.Results The treatment was successfully completed in all patients and no serious complications were observed.After 1 month of follow-up,the tumor thrombi shrank in all patients.Among 19 patients,9 achieved PR,4 SD,6 PD.The one-year and two-year survival rates were 47.4％ and 7.9％,respectively.The mean survival was 11.6±3.0 months (range:3-24 months).The median postoperative survival for stages Ⅰ,Ⅱ,Ⅲ was 13.5,7.0,4.0 months,respectively.Conclusion 125I seeds implantation combined with HIFU could be a safe and effective therapy for PVTT from HCC.

Objective To compare the effect of L-T4 taken in the morning vs bedtime on serum thyroid hormone in patients with hypothyroidism.Methods Seventeen patients with primary hypothyroidism were prospectively included.They took L-T4 in the morning for 2 months followed by L-T4 taken during the bedtime for 2 months.Thyroid hormone levels and cholesterol,triglyceride,albumin,creatinine and heart rate were measured.Wilcoxon test and paired t test were used to compare the data.The correlation between the changes of TSH and FT3,FT4 was analyzed respectively by Pearson correlation analysis.Results TSH,FT3,FT4 were:(12.10±7.19) vs (3.90±3.47) mU/L,(4.14±0.86) vs (5.24±1.11) pmol/L,(12.72± 4.40) vs (18.48±2.87) pmoL/L for L-T4 taken in the morning and during the bedtime respectively (t value:6.371,-3.166,-5.435,all P＜0.01).There was no correlation between the changes of TSH and FT3,FT4(r=O.12,0.22,both P＞0.05),respectively.The averaged changes were (8.20±5.31) mU/L,(1.09± 1.42) pmol/L and (5.76±4.37) pmol/L.Triglyceride,cholesterol,albumin,creatinine levels and heart rate were not significantly different with L-T4 taken in the morning and during bedtime (t=0.240,0.017;z=0;t=-0.610,1.588,all P＞0.05).Conclusions L-T4 taken during the bedtime by patients with hypothyroidism would reduce TSH and increase FT3,FT4 levels.This method can maintain the stability of TSH level with no need to increase the dose.

Aim To observe the neuroprotective effect of sinomenine on hippocampal neurons from injury in-duced by oxygen glucose deprivation ( OGD ) and its underlying mechanism. Methods Hippocampal neu-rons were exposed to OGD for 4 h followed by 24 h re-oxygenation ( OGD-R) . Then cell viability was detec-ted by MTT. LDH release was detected by LDH kit. Cell apoptosis was detected by Hoechst stain. The ex-pression of Bax, Bcl-2 and caspase-3 were detected by Western blot. [ Ca2+] i of hippocampal neurons was detected by calcium imaging. Acid-sensing ion chan-nels ( ASICs ) current was detected by patch clamp technique. Results SN increased cell viability and reduced LDH release. SN also inhibited neuron apop-tosis and increased ratio of Bcl-2/Bax and reduced the expression of caspase-3 . OGD-induced increase of [ Ca2+] i was inhibited by SN. Furthermore, SN inhib-ited ASIC1 a current and also inhibited OGD induced increase of ASICs current in hippocampal neurons. Conclusion SN protects hippocampal neurons against OGD-R-induced injury. The inhibitory effect of SN on ASIC1 a and calcium overload was involved in the pro-tective effect of SN.