Determination of polymyxin B concentration in plasma and its application in critically ill patients / 中国药房

OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.

Prognostic analysis of macrophage infiltration in patients with pancreatic cancer and preliminary screening of differential genes / 中华肝胆外科杂志

Objective:To analyze the correlations between the prognosis of patients with pancreatic cancer and macrophage infiltration, and to find the differential gene correlated with macrophage infiltration in patients with pancreatic cancer through bioinformatics.Methods:A total of 32 patients with pancreatic cancer admitted to the First Hospital of Lanzhou University from June 2015 to December 2018 were selected as the research objects, including 19 males and 13 females, with the age of (61.8±2.8) years. Cancer tissues, adjacent tissues, and related clinical data were collected. F4/80 (macrophage marker) immunohistochemical staining was performed on the samples. The survival time was followed up and its correlation with the above indexes was analyzed. The pancreatic cancer data from The Cancer Genome Atlas (TCGA) database was used for bioinformatics analysis.Results:The survival time of pancreatic cancer patients was negatively correlated with degree of macrophage infiltration in cancer tissues ( r=-0.522, P=0.002), but not with adjacent tissues ( r=0.168, P=0.358). The degree of macrophage infiltration in cancer tissue combined with preoperative serum carbohydrate antigen 19-9 (CA19-9), tumor TNM stage and vascular invasion can predict survival up to 47.4% of the survival time ( R2=0.474). TCGA database bioinformatic analysis showed that in pancreatic cancer there were 95 differentially expressed genes significantly correlated with M2 macrophage infiltration, among which JPH3 (positive correlation) and IL17REL (negative correlation) were the main genes. Conclusion:The degree of macrophage infiltration in cancer tissue can be used as a prognostic factor for patients with pancreatic cancer, and the combination with preoperative serum CA19-9, tumor TNM stage and vascular invasion is more accurate in predicting the prognosis. The related mechanism of M2 macrophage infiltration can be studied around the differential genes such as JPH3 and IL17REL.

Mechanism of paeoniflorin inhibiting apoptosis of hippocampal neurons of rats induced by lead acetate / 中华劳动卫生职业病杂志

Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 μmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 μmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 μmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.

The correlation between frailty and cardiac autonomic nervous function in elderly patients / 中华老年医学杂志

Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.

Implantation of Bone Marrow Mesenchymal Stem Cells into Small Intestinal Submucosa Improves Bile Duct Injury in Rabbits

BACKGROUND@#Bile duct injury (BDI), which may occur during cholecystectomy procedures and living-donor liver transplantation, leads to life-altering complications and significantly increased mortality and morbidity. Tissue engineering, as an emerging method, has shown great potential to treat BDI. Here, we aimed to explore the application of small intestinal submucosa (SIS) matrix composites with bone marrow mesenchymal stem cells (BMSCs) to treat BDI in a rabbit model. @*METHODS@#Rabbit-derived BMSCs were used as seed cells. Porcine SIS was used as the support material. Five centimetres of the common bile duct was dissected, and 1/3–1/2 of the anterior wall diameter was transversely incised to construct the rabbit BDI model. Then, SIS materials without/with BMSCs were inserted into the common bile duct of the BDI rabbits. After 1, 2, 4, and 8 weeks of implantation, the common bile duct was removed. Haematoxylin and eosin (HE) staining was used to assess pathological alterations in the common bile duct, while immunohistochemical staining and western blotting were used to detect expression of the epithelial cell markers CK19 and E-cadherin. Scanning electron microscopy was used to evaluate BMSC growth. @*RESULTS@#Compared with BMSCs alone, SIS-attached BMSCs had increased growth. HE staining showed that the injured bile duct healed well and that the complex gradually degraded as the time from implantation increased. Immunohistochemical staining and western blotting showed that compared with the control group, the in vivo complex group had significantly elevated expression levels of CK19 and E-cadherin. @*CONCLUSION@#BMSC implantation into SIS could improve BDI in rabbits, which might have clinical value for BDI treatment.

Implantation of Bone Marrow Mesenchymal Stem Cells into Small Intestinal Submucosa Improves Bile Duct Injury in Rabbits

BACKGROUND@#Bile duct injury (BDI), which may occur during cholecystectomy procedures and living-donor liver transplantation, leads to life-altering complications and significantly increased mortality and morbidity. Tissue engineering, as an emerging method, has shown great potential to treat BDI. Here, we aimed to explore the application of small intestinal submucosa (SIS) matrix composites with bone marrow mesenchymal stem cells (BMSCs) to treat BDI in a rabbit model. @*METHODS@#Rabbit-derived BMSCs were used as seed cells. Porcine SIS was used as the support material. Five centimetres of the common bile duct was dissected, and 1/3–1/2 of the anterior wall diameter was transversely incised to construct the rabbit BDI model. Then, SIS materials without/with BMSCs were inserted into the common bile duct of the BDI rabbits. After 1, 2, 4, and 8 weeks of implantation, the common bile duct was removed. Haematoxylin and eosin (HE) staining was used to assess pathological alterations in the common bile duct, while immunohistochemical staining and western blotting were used to detect expression of the epithelial cell markers CK19 and E-cadherin. Scanning electron microscopy was used to evaluate BMSC growth. @*RESULTS@#Compared with BMSCs alone, SIS-attached BMSCs had increased growth. HE staining showed that the injured bile duct healed well and that the complex gradually degraded as the time from implantation increased. Immunohistochemical staining and western blotting showed that compared with the control group, the in vivo complex group had significantly elevated expression levels of CK19 and E-cadherin. @*CONCLUSION@#BMSC implantation into SIS could improve BDI in rabbits, which might have clinical value for BDI treatment.

Clinical effects of ultrasound-guided intra-articular and coracohumeral ligament injections on frozen shoulder in the elderly / 中华老年医学杂志

Objective:To compare the clinical effects of ultrasound-guided intra-articular and coracohumeral ligament glucocorticoid injections versus ultrasound-guided intra-articular glucocorticoid injections alone on frozen shoulder in the elderly.Methods:A total of 44 patients with frozen shoulder admitted to the rehabilitation department of the Affiliated Hospital of Sichuan Nursing Vocational College from September 2019 to June 2020 were enrolled.They were randomly divided into the experimental group and the control group, with 22 patients in each group.The experimental group received two consecutive ultrasound-guided intra-articular injections and two coracohumeral ligament injections, while the control group received two consecutive ultrasound-guided intra-articular injections.The shoulder's passive range-of-motion(PROM), the 11-point numeric rating scale(NRS)as well as the Shoulder Pain and Disability Index(SPADI)were conducted before treatment, 1 week after the first treatment(1 week), 1 week after the second treatment(2 weeks)and 10 weeks after the second treatment(12 weeks).Results:There was no significant difference in baseline characteristics between the two groups(all P>0.05). Flexion, abduction, extension and external rotation increased whereas NRS and SPADI decreased after treatment, compared with pre-treatment in the experimental group( F=11.341, 20.965, 20.403, 32.470, 82.970 and 102.154, all P<0.05)and in the control group( F=7.012, 8.937, 23.265, 31.966, 52.500 and 41.356, all P<0.05). Compared with the control group, extension( t=0.365, 0.143 and 0.236, all P<0.05)and external rotation( t=0.205, 0.620 and 2.751, all P<0.05)increased at 1, 2 and 12 weeks after treatment.SPADI scores were lower in the experimental group than in the control group at 12 weeks after treatment( t=2.063, P=0.045). There was no significant difference in NRS, flexion or abduction between the two groups at any time point after treatment(all P>0.05). No serious adverse reactions occurred during treatment in either group. Conclusions:Both ultrasound-guided intra-articular injections plus coracohumeral ligament injections and ultrasound-guided intra-articular injections can effectively alleviate pain and improve function in elderly patients with frozen shoulder, but the former has better effects on extension.For patients with clear restricted extension and external rotation, ultrasound-guided intra-articular injections combined with coracohumeral ligament injections may achieve better clinical effects.

Advances in Preparation and Evaluation of Non-vascular Drug-eluting Stents / 中国医疗器械杂志

In recent years, the application of stent intervention in the treatment of non-vascular stenosis caused by benign and malignant factors has been widely concerned by researchers at home and abroad. The high incidence of malignant tumor diseases, further promotes the development of stent intervention. The conventional bare stents are prone to irritate luminal mucosa and produce restenosis and other complications. The emergence of drug-eluting stent is expected to solve this problem and become one of the important development trends of non-vascular stents. In this paper, the drug loading materials, drug loading layer drugs, preparation technology and quality evaluation methods of non-vascular drugeluting stent are described based on the recent research and clinical application documents, so as to provide basis and direction for the follow-up research and development.

Periprostatic fat thickness measured on MRI correlates with lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia progression / 亚洲男科学杂志(英文版)

This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.

The mediating effect of self-esteem between childhood trauma and aggressive behavior in patients with major depressive disorder / 中华行为医学与脑科学杂志

Objective:To explore the relationship between childhood trauma and aggressive behavior in patients with major depressive disorder(MDD), and the mediating role of self-esteem in childhood trauma and aggression.Methods:A total of 241 MDD patients with childhood trauma were investigated by Chinese version of the Buss & Perry aggression questionnaire(AQ-CV) and self-esteem scale (SES). Data were analyzed by SPSS 23.0 and AMOS 24.0.Pearson correlation analysis was used to assess the correlation of childhood trauma, aggressive behavior and self-esteem.The Bootstrap method was applied to test the mediating effect of self-esteem between childhood trauma and aggressive behavior.Results:The total score of attack questionnaire, self-esteem and childhood trauma were (48.81±18.81), (24.91±5.29)and(53.87±10.43), respectively. Self-esteem of MDD patients was negatively correlated with aggressive behavior and childhood trauma ( r=-0.45, -0.24, P<0.01). Childhood trauma was positively correlated with aggressive behavior ( r=0.42, P<0.01). The direct effect of childhood trauma on aggressive behavior was 0.438(95% CI: 0.305, 0.579). Self-esteem played a partly mediating effect between childhood trauma and aggressive behavior, and the mediating effect value was 0.161 (95% CI: 0.080, 0.256), accounted for 26.9% of the total effect. Conclusion:Self-esteem plays a partly mediating role between childhood trauma and aggressive behavior.Childhood trauma can directly and through the part of mediating role of self-esteem affect aggressive behavior.

Clinical effect of robot-assisted laparoscopic hepatectomy versus open hepatectomy in treatment of liver diseases: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect and safety of robot-assisted laparoscopic hepatectomy (RALH) versus open hepatectomy (OH) in the treatment of liver diseases. MethodsWeb of Science, PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and Wanfang Data were searched for Chinese and English articles on RALH versus OH in the treatment of liver diseases published up to February 2020. The quality of the articles included was assessed, and RevMan 5.1 was used to perform the meta-analysis. ResultsSeven studies were included, with a total of 754 patients (328 patients in the RALH group and 426 in the OH group). The meta-analysis showed that compared with the OH group, the RALH group had a significantly longer time of operation (mean difference ［MD］=59.41, 95% confidence interval ［CI］: 9.74-109.08, P=0.02), significantly higher blood transfusion rate (relative risk ［RR］=2.24, 95%CI: 1.04-4.82, P=0.04) and rate of hepatic portal occlusion (RR=2.27, 95%CI: 1.37-3.75, P=0.001), a significantly shorter length of hospital stay (MD=-3.87, 95%CI: -5.63 to -2.12,P＜0.001), and significantly lower overall incidence rate of postoperative complications (RR=0.58, 95%CI: 0.41-0.81, P=0.001) and incidence rates of major postoperative complications (RR=0.45, 95%CI: 0.22-0.91, P=0.03). There was no significant difference in intraoperative blood loss between the two groups (P＞0.05). ConclusionFor hepatectomy, RALF can shorten the length of hospital stay and reduce postoperative complications, creating conditions for minimally invasive hepatectomy and rapid recovery.

Cardiac autonomic nerve function in elderly patients with frailty / 中华全科医师杂志

Objective:To assess the cardiac autonomic nervous function in elderly patients with frailty.Methods:Patients aged ≥ 65 years old admitted in Beijing Hospital from September 2018 to August 2019 were enrolled in this study. Clinical frailty score was used to assess the frailty. The cardiac autonomic modulation was evaluated by sinus heart rate turbulence analysis through 24 h electrocardiogram recording.Results:A total of 129 elderly patients were finally enrolled in this study with a mean age of (77.5±6.4) years, 58.1% of them were male. There were 53 patients in frail group and 76 patients in non-frail group. The age of the frailty group was significantly higher than that of the non-frailty group [(80.5±5.5) vs.(75.3±6.2)]; the prevalence of hypertension [84.9%(45/53)], heart failure [32.1%(17/53)] and peripheral vascular diseases [32.1%(17/53)] in the frailty group was significantly higher than that in the non-frailty group [65.8%(50/76), 1.3%(1/76), 17.1%(13/76); t=5.001, χ 2=5.879, 24.606, 3.921; all P<0.05]. Compared with non-frailty group, turbulence onset (TO) [-0.05(-0.92, 0.82)% vs. -0.74(-1.58, 0)%; Z=2.616, P=0.009] was significantly higher in frailty group, while turbulence slope (TS) [2.34(1.30, 5.00)ms/RR vs. 4.34(2.66, 6.39)ms/RR; Z=-3.048, P=0.002] was significantly lower. The rate of TO abnormality [49.1% (26/53) vs. 26.3%(20/76), χ 2=7.038, P=0.008] and TS abnormality [34.7%(29/53) vs. 21.0%(16/76); χ 2=15.579, P<0.001] in the frailty group was significantly higher than that in the non-frailty group. Multivariate logistic regression analysis showed that TO abnormality( OR=2.970, P=0.010, 95 %CI:1.300-6.785) and TS abnormality( OR=3.618, P=0.003, 95 %CI:1.565-8.364) were correlated with frailty. Conclusion:Cardiac autonomic nerve function may be impaired in elderly frail patients, and decreased vagal nerve tension may be presented.

Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway / 中国实验方剂学杂志

Objective: To study inhibitory effect of total flavonoids from Ampelopsis grossedentata (TF) on transplanted tumors of human hepatocellular carcinoma in nude mice, and predict that its mechanism may be related to relevant factors regulating phosphatidylinositol 3 kinase (PI3K)/protein kinases B(Akt)/p53 pathway in apoptosis. Method: The nude mice transplanted BEL-7404 hepatoma model was established and divided into model group, 5-fluorouracil (5-FU) group (1.0 g·L-1) and TF (30, 15, 7.5 g·L-1) groups. Nude mice were put to death after two weeks of administration. The tumor tissues were excised, and tumor inhibition rate (IR) and relative tumor proliferation rate (T/C) were calculated. Reverse transcription PCR(RT-PCR) was used to detect PI3K, Akt1, p53 gene(p53), Caspase-3, B cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) mRNA expressions, immunohistochemical method was used to detect expressions of relevant proteins PI3K, Akt1, p53, Caspase-3, Bcl-2, Bax. Result: The establishment of xenograft tumor in mice showed that TF was administered orally once per day for two consecutive weeks. IRs were 53.26%, 35.94%, and 26.74%, respectively. T/Cs were 59.74%, 69.66%, and 84.82%, respectively. RT-PCR experiments showed that compared with model group, when TF concentration was 30 g ·L-1, mRNA expressions of PI3K, Akt1, and Bcl-2 were significantly down-regulated, and mRNA expressions of tumor suppressor genes p53, Capsase-3, and Bax were significantly up-regulated. Immunohistochemical method results showed that compared with model group, at TF concentrations of 30, 15 g·L-1, all PI3K, Akt1, Bcl-2 protein expressions were significantly down-regulated, while p53, Capsase-3, Bax protein expressions were significantly increased. Conclusion: TF has an obvious anti-liver cancer activity in vivo. Its mechanism may be correlated with up-regulation of expressions of p53, Caspase-3, and activation of apoptosis PI3K/Akt/p53 pathway, thereby inhibiting Bcl-2, increasing expression of Bax, and promoting hepatocellular apoptosis.

A randomized controlled study on factors influencing the curative effect of sequential combined interferon and lamivudine therapy in children with immune-tolerant phase chronic hepatitis B / 中华肝脏病杂志

Objective@#To investigate the curative effect of antiviral therapy and related factors influencing the curative affect in children with immune-tolerant phase chronic hepatitis B.@*Methods@#From May 2014 to April 2015, 46 children with chronic hepatitis B, aged 1 to 16 years with immune-tolerant phase were enrolled as the treatment group. All cases in the treated group either received interferon alpha (3-5 MIU/m2, once daily) in lamivudine combination (if HBV DNA decreased < 2 log10) or repeatedly received interferon-alpha alone (if HBV DNA decreased >2 log10) for 12 weeks. Interferon was discontinued at 72 weeks and followed-up period was continued with lamivudine for 24 weeks. At the same time, data of 23 cases of untreated children with immune-tolerant phase chronic hepatitis B were collected as the control group. The treatment group and the control group were divided into two age groups: 1-7 years old and 7-15 years old. Data measurements were compared using t-test, analysis of variance and single factor analysis methods, and the count data were analyzed by χ 2 test. Multiple logistic regression analysis was used to analyze the effects of different factors on response.@*Results@#(1) There were 22 cases aged 1-7 years in the treatment group (47.8%) and 12 cases aged 1-7 years in the control group (52.2%). The cases of mother-to-child transmission (MTCT) in treatment and control group were 34 (73.9%) and 17 (73.9%), while children with normal baseline ALT in the treatment and control group were 18 (39.1%) and 10 (43.5%). (2) At the end of follow-up, 15 cases in the treatment group (32.6%) had HBeAg serological conversion. Among them, nine (19.6%) cases had HBsAg clearance or HB-Ag seroconversion with anti-HBs, and one (2.2%) case had HBsAg clearance, but both HBeAg and anti-HBe were positive. In the control group, one case had HBV DNA lower than the lower limit of detection level, and one case had HBeAg seroconversion without HBsAg clearance. (3) At the end of follow-up, the seroconversion rates of HBeAg in patients aged 1 to 7 years and patients aged 7 to 15 years were 45.5% and 20.8%, respectively (P = 0.078) and the clearance rates of HBsAg were 36.4% and 8.3% (P = 0.023). The serum conversion rates of normal and abnormal baseline alanine aminotransferase levels were 5.6% and 50.0% (P = 0.005), and the clearance rates of HBsAg were 5.6% and 32.1% (P = 0.077), respectively. There was no statistically significant difference in gender, mother-to-child transmission, HBV DNA genotyping and baseline HBsAg level in antiviral efficacy among children (P > 0.05). (4) HBsAg and HBeAg clearance occurred in 100% of patients at the end of follow-up who had HBsAg < 3 000 IU/ml at 24 weeks of treatment. (5) Multivariate logistic regression analysis showed that serum HBeAg conversion rate had relation with non-MTCT transmission and abnormal baseline alanine aminotransferase. Furthermore, HBsAg clearance rate was associated with the age of children.@*Conclusion@#Sequential combination of interferon and lamivudine with a prolonged course can improve the HBV DNA negative conversion rate, HBeAg seroconversion rate, HBsAg loss rate and mild ALT abnormalities at baseline in children under the age of 7 years with immune-tolerant phase chronic hepatitis B.

Self-reported Hypoglycemia in insulin-treated patients with Diabetes: Results from the Philippine Cohort of the International Operations Hypoglycemia Assessment Tool (IO HAT) study / Journal of the ASEAN Federation of Endocrine Societies

Objective@#To determine the frequency of hypoglycemia in insulin-treated patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the non-interventional International Operations Hypoglycemia Assessment Tool (IO HAT) study. @*Methodology@#This sub-analysis included Filipino patients with T1DM or T2DM, aged 18 years and older, treated with insulin for more than 12 months, who completed the two-part self-assessment questionnaires (SAQ1 and SAQ2) and patient diaries that recorded hypoglycemia during retrospective (6 months/4 weeks before baseline) and prospective period (4 weeks after baseline (ClinicalTrials.gov number: NCT02306681).@*Results@#A total of 671 patients were enrolled and completed the SAQ1 (62 patients with T1DM and 609 patients with T2DM). Almost all patients (100% in T1DM and 99.3% in T2DM) experienced at least 1 hypoglycemic event prospectively. The incidence of any hypoglycemia was also high in the prospective period compared to retrospective period (72.6 [95% CI: 64.8, 80.9] events PPY and 43.6 [95% CI: 37.8, 49.9] events PPY; p=0.001, respectively) in T1DM patients.@*Conclusion@#Among insulin-treated patients, higher rates of hypoglycemia were reported prospectively than retrospectively. This indicates that the patients in real-life setting often under-report hypoglycemia. Patient education can help in accurate reporting and appropriate management of hypoglycemia and diabetes.

Effects of Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra on Level of Nogo-A/NgR/RhoA/ROCK mRNA in Acute Cerebral Infarction Rats / 世界科学技术-中医药现代化

Objective: To investigate effects of Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra on the relative expression of Nogo-A/NgR/RhoA/ ROCK mRNA in acute cerebral infarction rats. Methods: Healthy male SD rats were randomly divided into sham operation group, blank group, low dose, medium dose and high dose Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra group, Ginkgo biloba group, Nimodipine group, and each group was divided into 3 days, 7 days, 14 days three time points. Real-Time quantitative polymerase chain reaction (PCR) was used to detect Nogo-A/NgR/RhoA/ROCK mRNA relative expression changes of acute cerebral infarction rats. Results: Compared with the blank group and the sham operation group, the relative expression level of Nogo-A/NgR/RhoA/ROCK mRNA was increased in the model group both at 3 days, 7 days and 14 days (P ＜ 0.05). After the treatment of Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra, other than there was no significant difference between the low-dose group and the model group except for 7 days, the relative expression level of Nogo-A/NgR/RhoA/ROCK mRNA in Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra groups was lower than that in the model group (P ＜ 0. 05). Conclusion: The relative expression level of Nogo-A/NgR/RhoA/ROCK mRNA in acute cerebral infarction rats can be reduced by Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra.

Effects of Shengmai Injection on Physiological Indices, C-reactive Protein and NO Levels in Experimental Beagle Dogs with Myocardial Ischemia / 世界科学技术-中医药现代化

This study was aimed to explore the effects of Shengmai(SM) injection on blood pressure (BP),heart rate (HR),electrocardiogram (ECG),and serum C-reactive protein (CRP) and NO levelin Beagle dogs with myocardial ischemia (MI).A total of 30 Beagle dogs were divided into 5 groups,which were the blank control group,model control group,SM injection low-dose group (0.80 mL· kg-1),SM injection high-dose group (3.20 mL· kg-1) and isosorbidemononitrate group (0.07 mL· kg-1).The MI model was established by the subcutaneous injection of isoprenaline hydrochloride,and the drug treatments were given at the same time.At 1 h,6 h,12 h,24 h after administration,changes of BP,HR and ECG were recorded;serum CRP and NO content were detected.The results showed that compared with the blank control group,the mean arterial pressure (MBP) was significantly decreased (P＜0.01),HR was significantly increased (P＜0.01,or P＜0.05),the ECG△ST value was significantly increased (P＜0.01) in the model group.SM injection could improve symptoms mentioned above,but the effectswereslow.SM injection had a significant antagonistic effect on the decreasing of CRP content and the increasing of NO content,compared with the model group.The difference was statistically significant (P＜0.01,or P＜0.05).It was concluded that SM injection could improve the physiological indices of Beagle dogs with MI,which might be related to the regulation of CRP and the inhibition of NO secretion.

Effect of Anshen Navel Plaster on Spontaneous Activities And Levels of GABA, 5-HT in Insomnia Rats Caused by PCPA / 世界科学技术-中医药现代化

This experiment was aimed to mainly observe the effect of Anshen navel plaster on autonomic activities and to compare neurotransmitter gamma-aminobutyric acid (GABA) and monoamine neurotransmitter (5-HT) contents change of insomnia rats.The rats were treated by P-chlorophenylalanine (PCPA),which can make healthy rats lose sleep.The rat model of insomnia was prepared by intraperitoneal injection of PCPA.The healthy SD rats were randomly divided into the blank control group,model control group,low dosage of Anshen navel plaster group,high dosage of Anshen navel plaster group and Tongren Anshen pill group according to the random number table.EthoVision were used to record the rat's autonomic activities.Content changes of 5-HT and GABA of rats in each group were measured by enzyme-linked immunosorbent assay (ELISA).The results showed that rat's autonomic activities were decreased in the Anshen navel plaster group and Tongren Anshen pill group,which indicated that the Anshen navel plaster had a good sedative effect.Intraperitoneal injection of PCPA can remarkably change rat's serum neurotransmitter expression levels,especially GABA and 5-HT.After the intervention of experimental drugs,compared with the model group,the expression levels of GABA and 5-HT were increased significantly.It was concluded that Anshen navel plaster has obvious sedative effect.It can regulate the contents of sleep factors such as GABA and 5-HT.

Influence of interferon-α therapy on height and weight of chronic hepatitis B children / 中华传染病杂志

Objective Retrospectively study of the effects of interferon-α therapy on height and weight of children with chronic hepatitis B (CHB).Methods Total of 116 hospitalized cases of CHB children in Adolescent Liver Centre, 302 Military Hospital of China from January 2010 to December 2011 were respectively studied.Heights and weights of all the subjects at baseline, 24 weeks, 48 weeks, 72 weeks and 96 weeks of treatment, and 24 weeks, 48 weeks and 96 weeks of follow-up were measured.The weight Z score (WAZ), height Z score (HAZ) and body mass index (BMI) Z score of subjects with hepatic fibrosis (S) 0.05).At 48 weeks of treatment, the median HAZ was 0.50, and the median WAZ was 0.20;after a follow-up period of 24 weeks, the median HAZ was-0.32, and the median WAZ was-0.18;after a follow-up period of 48 weeks, the median HAZ was 0.09 and the median WAZ was 0.06.All the above median values of HAZ and WAZ were significantly different from those at baseline (all P<0.05).The difference of HAZ at baseline and 96 weeks of treatment in group aged 6-16 years was significantly different from that in group aged 1-6 years (-0.74±0.69 vs-0.53±0.35, t=1.85, P<0.05).Also, the difference of WAZ at baseline and 96 weeks of treatment in group aged 6-16 years was significantly different from that in group aged 1-6 years (-0.69±0.41 vs-0.17±0.75, t=3.74, P<0.05).The difference of HAZ at baseline and 96 weeks after treatment in group aged 6-16 years was significantly different from that in groups aged 1-6 years (-1.12±0.81 vs-0.05±0.69, t=2.06, P=0.022).Conclusions Interferon-α treatment for children with chronic hepatitis B does have influence on their height and weight, which restores to some degree after the treatment finished.Physicians should pay more attention to the influence of interferon-α treatment on height and weight in children aged 6-16 years.

Clinical characteristics and outcomes of drug-induced liver injury in children: a study of 184 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical characteristics and outcomes of drug-induced liver injury (DILI) in children, and to improve the understanding of DILI in children. MethodsOne hundred and eighty-four children with DILI who were under 16 years and hospitalized in our hospital from January 2004 to January 2014 were enrolled as subjects, and their clinical and pathological data were retrospectively analyzed. ResultsDILI might occur at any age in children, even at the infant stage, and the youngest patient was only 2 months old. There were 143 patients (77.7%) with clinical symptoms, including loss of appetite, jaundice, and yellow urine. The drugs causing DILI included traditional Chinese medicine (28.3%), antibiotics (24.5%), and anti-inflammatory drugs (19.6%). The pathological characteristics of DILI in children included eosinophils-based inflammatory cell infiltration (78.7%), mixed hepatic steatosis (73.5%), and cholangiolar cholestasis (38.7%). Four patients (2.2%) developed autoimmune hepatitis; twenty-nine patients(158%) had liver failure, and three of them died of liver failure. After treatment, 177 patients (96.2%) recovered normal liver function and were discharged. ConclusionDILI may occur at any age in children, and a majority of drugs causing DILI are traditional Chinese medicine, antibiotics, and anti-inflammatory drugs. The pathological examination of liver provides an important basis for the diagnosis of DILI in children. In spite of the benign prognosis in most patients, the incidence of liver failure still needs to be taken into account, and regular follow-up is necessary.