Mechanism of Liu Junzitang in Treatment of Muscle Atrophy in Mice with Lung Cancer Cachexia Through Regulating STAT3/Ubiquitin Proteasome Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3（STAT3）/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group， a model group， a Liu Junzitang group， an inhibitor group （stattic group），and a Liu Junzitang + inhibitor group （combination group）， with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation， the mice in the corresponding groups received Liu Junzitang （9.56 g·kg-1·d-1） by gavage and intraperitoneal injection of stattic ［25 mg·kg-1·（2 d）-1］. After three weeks of drug intervention， the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin （HE） staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 （p-STAT3）， STAT3， muscle atrophy F-box （MAFbx）， and muscle RING finger protein 1 （MuRF1） in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT3， MAFbx， and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group， the model group showed lightened body and the gastrocnemius muscle， reduced cross-sectional area of gastrocnemius muscle fibers， and increased protein expression of p-STAT3， STAT3， MAFbx， and MuRF1 and mRNA expression of STAT3， MuRF1， and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the model group， the Liu Junzitang group showed increased body weight， gastrocnemius muscle weight， and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and decreased protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and reduced protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the combination group showed increased body weight and gastrocnemius muscle weight （P<0.05），and decreased protein expression of p-STAT3， STAT3， MuRF1， and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the Liu Junzitang group， the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle （P<0.05）. ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia， and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.

Association of different activity behaviors with body composition among children aged 6 to 12 years in Guangzhou / 中国学校卫生

Objective@#To investigate the associations of reallocating sedentary time to different activity behaviors with body composition, and to provide a reference for prevention and control of childhood obesity.@*Methods@#By using cluster random sampling, 1 621 students from 5 urban primary school in Guangzhou were selected in 2017. Vigorous intensity physical activity (VPA), moderate intensity physical activity (MPA), walking, sedentary behavior, and sleeping were measured by self-reported questionnaire. Inbody 230 was used to assess body composition. Multiple linear regression models were applied to examine isotemporal substitution effect of activity behaviors.@*Results@#In younger children group (aged 6-9 years), replacing 30 min/day sedentary with VPA was associated with a 0.9% lower fat-free mass index(FFMI)(β=0.11, P=0.00). In older children group (aged 10-12 years), replacing 30 min/day sedentary with VPA was associated with a 1.0% lower FFMI(β=0.13, P=0.04); replacing 30 min/day sedentary to walking was associated with both a 2.9% lower percentage of body fat(PBF)(β=-0.65, P<0.01) and a 4.0% lower fat mass index(FMI)(β=-0.18, P=0.00).@*Conclusion@#Replacing sedentary with other intensities of physical activity is crucial for improving fatness status among children aged 6 to 12 years, especially among children aged 10 to 12 years. This current study suggests that children should increase physical activity while reducing sedentary for reducing risk of childhood obesity.

Manual reduction and traction fixation for the treatment of metacarpal neck fractures under ultrasound-guided / 中国骨伤

<p><b>OBJECTIVE</b>To study clinical efficacy of manual reduction and traction fixation for the treatment of metacarpal neck fracture under ultrasound-guided.</p><p><b>METHODS</b>From April 2013 to August 2016, 30 patients with metacarpal neck fractures were treated with manual reduction and traction fixation under ultrasound-guided, including 26 males and 4 females aged from 14 to 56 years old with an average of (25.6±1.6) years old, the courses of diseases ranged from 7 h to 5 d with an average of (2.7±0.6) d. Twenty patients were the fifth metacarpal neck fracture, 7 patients were the 4th and 5th metacarpal neck fractures, 3 patients were the second metacarpal neck fracture. Fracture healing, angle of bilateral head shaft angle and active range of metacarpophalangeal joints was measured, and DASH score was applied to evaluate function.</p><p><b>RESULTS</b>Twenty-seven patients were followed up from 6 to 11 months with an average of(7.2±0.8) months. Fracture were healed from 5 to 8 weeks with an average of (5.6±0.4) weeks. The affected shaft angle was (15.1±1.8)°, and health head shaft angle was (13.5±2.8)°, while there was no significant difference (=1.54, >0.05). The affected range motion of metacarpophalangealjoint was(86.3±2.6)°, health active range motion of metacarpophalangeal joint was(91.8±1.6)°, and no significant difference between both side (=1.16, >0.05). DASH score was 4.3±1.5 at 7 months after operation.</p><p><b>CONCLUSIONS</b>Manual reduction and traction fixation for the treatment of metacarpal neck fracture under ultrasound-guided could dynamic observe fracture position in time, high patients' acceptability and is a feasible method for the treatment of metacarpal neck fracture.</p>

Limited sampling strategy to estimate pharmacokinetic parameters of orally administered metformin hydrochloride / 药学学报

The present study was to estimate pharmacokinetic parameters of metformin hydrochloride in 20 Chinese healthy volunteers with a limited sampling strategy (LSS), which will provide scientific data for bioequivalence and clinical application. A single dose of metformin was administrated to 20 healthy volunteers. The concentration of metformin in whole blood was determined by validated high performance liquid chromatography (HPLC) method. Multi-linear regression analysis was performed to establish a model to estimate AUC(0-24 h) and Cmax of metformin by LSS method. The LSS models were validated by the Jackknife method. The result indicated: the linearity relationship between AUC(0-24 h) or Cmax and single concentration point was poor. Several models for metformin AUC(0-24 h) or Cmax, estimation were better (r2 > 0.9, P < 0.05). Validation tests indicated that most informative sampling points (C2, C6 for AUC(0-24 h), C1.5, C2 for Cmax) provided accurate estimations of these parameters. So, a multi-linear regression model for estimation pharmacokinetic parameters of metformin by using LSS method is feasible.

A limited sampling strategy of phenotyping probe midazolam to predict inhibited activities of hepatic CYP3A in rats / 药学学报

The present study was to evaluate feasibility of a limited sampling strategy (LSS) in the prediction of inhibited hepatic CYP3A activity with systemic clearance of midazolam (MDZ), a hepatic CYP3A activity phenotyping probe. Rats were pretreated with a serial doses of ketoconazole, a selective inhibitor on CYP3A. Blood samples were collected and detected for MDZ at specified time points after intravenous injection of MDZ. Stepwise regression analysis and a Jack-knife validation procedures were performed in one group of rats as training set to establish the most informative LSS model for accurately estimating the clearance of MDZ. Another group of rats with same treatment was used as validation set to estimate the individual clearance based on predictive equations derived from the training set. Bland-Altman plots showed a good agreement between the systemic clearance calculated from DAS (CLobs) and corresponding parameter that was derived from three LSS models (CLest). LSS models derived from two or three sampling time points, including 60, 90 min, 30, 60, 90 min and 30, 60, 120 min, exhibited a good accuracy and acceptable error for estimating the CLobs of MDZ to evaluate hepatic CYP3A activity, especially the 60, 90 min LSS model is most accurate and convenient. The results supported that limited plasma sampling to predict the systemic clearance of MDZ is easier than the usual method for estimating CYP3A phenotyping when the hepatic activity of CYP3A is reduced in the rat. The present study provided theoretical basis and laboratory evidence for LSS to clinically evaluate metabolizing function of liver and