BACKGROUND: Ligustrazine possesses the effect to reduce ototoxicity of gentamicin, whether does it antagonize the ototoxicity of gentamicin through influencing the expression of heat shock protein (HSP) 70 in cochlea of guinea pigs with gentamicin induced ototoxicity? BJECTIVE: To investigate the effect of ligustrazine on the expression of HSP70 in cochlea of guinea pigs with gentamicin induced ototoxicity through immunohistochemistry and image analysis technique in combination with the measurement of auditory brainstem response (ABR).DESIGN: A randomized controlled study, and linear correlation analysis. ETTING: Physiological Department of Shenyang Medical College and Audiological Laboratory of China Medical University.MATERIALS: Totally 40 white and red-eye healthy guinea pigs of lean grade and with keen auricle reflect, weighing 200 - 250 g, of either gender, were at random divided as gentamicin group, ligustrazine + gentamicin group, ligustrazine group, and normal control group, with 10 in each group.METHODS: Ligustrazine injection 140 mg/kg was intraperitoneally at the left side given for animals in ligustrazine + gentamicin group, and at the same time gentamicin sulfate injection 100 mg/kg was given intraperitoneally at the right side. The same dosage of gentamicin sulfate injection was intraperitoneally given for animals in gentamicin group. The same dosage of ligustrazine was intraperitoneally give for animals in ligustrazine group. The normal saline 2.5 mL/kg was intraperitoneally given for animals in normal control group. Administration was consecutively given for 10 days for each group, once a day. The body mass was measured every day for regulating the dosage. Before starting and after finishing the administration, the thresholds of ABR of all animals in each group were measured respectively. After finishing administration, all animals in each group were put to death, and the conditions of expressions of HSP70 in cochlea of guinea pigs were investigated by SABC immunohistochemistry and image analysis technology.MAIN OUTCOME MEASURES: ① the thresholds of ABR of all animals in each group; ② expressions of HSP70 in cochlea of guinea pigs in each group.RESULTS: ① The thresholds of ABR of guinea pigs: The thresholds in ligustrazine + gentamicin group and gentamicin group were obviously higher than that in normal control group [(21.09±4.50) dBnHL, (36.55±6.13)dBnHL, (2.50±2.75) dBnHL, t=15.764-22.665, P ＜ 0.001]. The threshold in ligustrazine + gentamicin group was obviously lower than that in gentamicin group (t=9.092, P ＜ 0.001). ② The expressions of HSP70 in each part of cochlea of guinea pigs: The mean gray values of cellular HSP70 positive reaction products in Corti's organ, vascular stria and spiral ligament, spiral limbus and spiral ganglion in gentamicin group were lower than those in normal control group (88.24±4.34, 96.85±1.05; 121.24±0.92,128.76±1.59; 96.15±1.10, 98.78±0.54; 117.73±1.18, 120.51±0.80, t=6.097-18.307, P ＜ 0.001). The mean gray values of cellular HSP70 positive reaction products in ligustrazine + gentamicin group were lower than those in gentamicin group (92.53±2.25, 88.24±4.34; 125.20±1.43, 121.24±0.92;98.71±0.91, 96.15±1.10, 118.91±0.46, 117.73±1.18, t=3.925-10.415, P＜ 0.001).③ The mean gray value of cellular HSP70 positive reaction products in each part of cochlea of guinea pigs was highly correlated with the threshold of ABR (r=-0.814 1 to -0.984 1, P ＜ 0.001).CONCLUSION: Ligustrazine could reduce the threshold of ABR and the expression of HSP70 in cochlea with gentamicin toxicosis so as to relieve gentamicin ototoxic injury, hence improving auditory function.

Objective:To investigate the correlation of age with diffusion tensor imaging (DTI) values as fractional anisotropy (FA), apparent diffusion coefficient (ADC) and contrast to noise ratio (CNR) of three-dimensional nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation imaging (3D SHINKEI) of the brachial plexus in normal adults.Methods:A total of 54 adult healthy volunteers and 6 patients with Guillain-Barre syndrome were prospectively enrolled from October 2018 to April 2019. Healthy volunteers were divided into 3 groups according to age as 21-40 years old group ( n=20), 41-60 years old group ( n=20), and ≥61 years old group ( n=14). All of them underwent MRI examination of the brachial plexus, including DTI and 3D SHINKEI sequences. The average FA and ADC values of the brachial plexus were measured and calculated through the fusion of DTI and 3D SHINKEI by 2 physicians independently. The contrast to noise ratio (CNR) of brachial plexus nerve was measured in 3D SHINKEI sequence images. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two physicians. A simple linear regression model and Pearson correlation analysis were used to detect the correlation between FA, ADC, CNR and age. One-way analysis of variance was used to compare the differences of FA, ADC and CNR in different age groups. The FA and ADC values in different genders were compared by independent sample t-test. Results:Inter-observer agreements of the 2 physicians were good for FA and ADC values with ICC values of 0.811 and 0.901, respectively. For different groups, FA values were 0.397±0.023, 0.368±0.023, and 0.334±0.018 and ADC values were (1.376±0.072) × 10 -3 mm 2/s, (1.466±0.086) × 10 -3 mm 2/s, (1.486±0.080) × 10 -3 mm 2/s, for 21-40, 41-60, and ≥61 years old groups, respectively with statistical significant difference ( F=25.311, P<0.001; F=9.948, P<0.001). The CNR of the brachial plexus were 510.583±192.846, 502.581±128.821, and 426.782±113.648 for 21-40, 41-60, and ≥61 years old group without statistical difference ( F=1.429, P=0.249). The FA value of brachial plexus was highly negatively correlated with age ( r=-0.745, P<0.001), while the ADC value was moderately positively correlated with age ( r=0.596, P<0.001). The CNR of 3D SHINKEI sequence was negatively correlated with age ( r=-0.292, P=0.033). There was no statistically significant difference in brachial plexus FA and ADC values between male and female subjects ( t=1.496, P=0.141; t=-1.557, P=0.126). The FA value of Guillain-Barre syndrome patients was lower than that of healthy volanteers in the same age group ( t=6.129, P<0.001), and the ADC value had no statistical diference ( t=-1.335, P=0.186). Conclusion:The values of FA, ADC and CNR of brachial plexus in normal adults change with age. Among them, FA value is more significant.

Objective:To analyze the patterns of antibacterial agents in Chinese children surveyed by the China multi-center monitoring network for the application of antibacterial agents in children and neonates in 2019 by using World Health Organization (WHO) Access, Watch, Reserve and Not-recommended (AWaRe) and typical anatomical/therapeutic/chemical (ATC) in this study.Methods:The cross-sectional method was adopted.A multi-center cross-sectional survey was conducted on one day from September to December 2019.The information of all inpatients taking antibiotics was uploaded to the network-based data collection system (https: //garpec-31.mobilemd.cn/login.aspx? relogin=true). This study covered 13 hospitals from 10 provinces and cities in China.All hospitalized children in the Respiratory Department, Infectious Disease Department, General Surgery Department, Pediatric Intensive Care Units, Neonatal Intensive Care Units and Neonatology joined in this survey.The clinically used antibacterial agents were classified by AWaRe and ATC, and the AWaRe and ATC distributions of antibacterial agents prescribed for Chinese children and neonates were described.Results:Of the 2 644 antibiotic prescriptions included from 13 hospitals, 2 134 (80.71%) were for children and 510 (19.29%) were for neonates.Of all antibiotic prescriptions, there were 368 (13.92%) Access antibiotics prescriptions, 1 973 (74.62%) Watch prescriptions, 60 (2.27%) Reserve prescriptions and 243 (9.19%) Not-recommended prescriptions.The top-five antibiotics prescribed for children and neonates were third-generation cephalosporins (1 056, 39.94%), macrolides (492, 18.61%), carbapenems (275, 10.40%), beta lactam-beta lactamase inhibitors (246, 9.30%), and second-generation cephalosporins (136, 5.14%). The use ratios of Access, Watch, Reserve and Not-recommended antibiotics in each center ranged from 0 to 30.00%, 36.67% to 97.20%, 0 to 17.02% and 0 to 33.33%, respectively.In 1 360 antibiotic prescriptions for children and neonates with pneumonia, there were 152 (11.18%) Access antibiotics, 1 051 (77.28%) Watch antibiotics, 37 (2.72%) Reserve antibiotics, and 120 (8.82%) Not-recommended antibiotics.The top-five antibiotics prescribed for children with pneumonia were third-generation cephalosporins (522, 38.38%), macrolides (388, 28.53%), beta lactam-beta lactamase inhibitors (141, 10.37%), carbapenems (117, 8.6%) and penicillins (49, 3.60%).Conclusions:Watch antibiotics and broad spectrum antibiotics such as third-generation cephalosporins and macrolides prone to induce resistance are the main antibacterial agents used in Chinese children and neonates with pneumonia.Broad-spectrum antibiotics may be overused in Chinese children and neonates.

OBJECTIVE：To study ongoing change characteristics of the contents of syringin and total flavonoids in different medicinal parts （root bark ，tree bark ，leaf）of Toricellia angulata from Guizhou ，and to provide reference for the development and application of T. angulata . METHODS ：The root bark ，tree bark and leaf parts of T. angulata during different harvesting periods （Jan.-Dec.） were taken as the research samples. The content of syringin was determined by HPLC. The determination was performed on Agela Promosil C 18 column with mobile phase consisted of 0.5％ phosphoric acid solution-acetonitrile （gradient elution）at the flow rate of 1.0 mL/min. The detection wavelength was set as 210 nm，and column temperature was 35 ℃. The sample size was 5 μL. The content of total flavonoids was determined by UV-visible spectrophotometry under detection wavelength of 510 nm. RESULTS ：The linear range of syringin and total flavonoids were 0.095 9-1.150 8 mg/mL（r＝0.999 6）and 0.072 2- 1.083 0 mg/mL（r＝0.999 9），respectively. RSDs of precision ，stability and repeatability tests were all less than 3％（n＝6）. The average recoveries were 101.74％（RSD＝2.36％ ，n＝6）and 99.63％（RSD＝2.19％ ，n＝6），respectively. During different harvesting periods ，the contents of syringin in root bark ，tree bark ，leaf of T. angulata collected on Aug. ，May and Sept. were the highest，and the contents of total flavonoids in samples collected on Feb. ，Dec. and Sept. were the highest. The contents of syringin in different medicinal parts of T. angulata were in descending order as follows as tree bark ＞root bark ＞leaf，and the content of syringin was commonly relatively high in tree bark part ；the content of total flavonoids in different medicinal parts of T. angulata were in descending order as follows as root bark ＞tree bark ＞leaf，and the contents of total flavonoids in three medicinal parts was generally low. The content of total flavonoids in root bark was the highest in Feb. of that year ，and the content of syringin in root bark at same month was second only to Aug. of that year ；the content of syringin in tree bark was the highest in May ，and the content of total flavonoids in tree bark at same month was second only to Oct. and Dec. of that year ；the contents of total flavonoids and syringin in leaf were the highest in Sept. of that year. CONCLUSIONS ：It is suggested that Feb. is the best time for harvesting root bark ，May for tree bark and Sept. for leaf of T. angulata .

ObjectiveTo carry out the clinical comprehensive evaluation of Biantong capsules and Biantong tablets in the treatment of constipation guided by the clinical value of drugs， and to provide a scientific basis for the rational pricing， rational use， and cataloging of Biantong capsules/tablets. MethodThe available evidence and survey data were used for the clinical comprehensive evaluation of Biantong capsules/tablets and three control drugs in the treatment of constipation in terms of the six dimensions including effectiveness， safety， economics， innovation， suitability， and accessibility. ResultIn terms of effectiveness， Biantong capsules/tablets can improve the response rate， with clear pharmacological mechanism. In terms of safety， the absence of toxic reaction， the mild adverse reactions， and the favorable prognosis indicate high safety. In terms of economics， the average daily cost of Biantong capsules/tablets is the lowest among the tested drugs， which indicates a cost-effectiveness advantage. In terms of innovation， Biantong capsules/tablets have been authorized patents in China and listed as members in the third category of new drugs of traditional Chinese medicine/ninth new drugs of traditional Chinese medicine. In terms of suitability， Biantong capsules/tablets are convenient to store and take and have good suitability in terms of drug technical characteristics and drug usage. In terms of accessibility， Biantong capsules/tablets have a wide coverage in hospitals， sufficient capacity， low patient burden， extensive drug catalogue coverage， and no major environmental risk for long-term application. The comprehensive values of the tested drugs follow a descending order of control drug B （84.27 score）， Biantong capsules/tablets （82.47 score）， control drug A （70.47 score）， and control drug C （59.46 score）. The recommendations of the expert panel are Class A （18/18）， which can be directly converted into decision-making. ConclusionBiantong capsules/tablets demonstrate a high clinical comprehensive value in the treatment of constipation， providing a reference for the rational pricing， rational use， and cataloging of drugs.

OBJECTIVE：To provide reference for the quality control of the leaves of Toricellia angulata . METHODS ：HPLC method was adopted. The determination was performed on Agela Promosil C 18 column with 0.2％ phosphoric acid solution-acetonitrile（gradient elution ）as mobile phase at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 35 ℃. The sample size was 10 μL. HPLC fingerprint of 10 batches of the leaves of T. angulata was established and similarity evaluation was conducted by using Similarity Evaluation System of TCM Chromatographic Fingerprint（2004 edition）. The chromatographic peak was identified by comparing with the chromatogram of reference substance. Cluster analysis ，PCA and PLS-DA were used to identify chemical patterns ，and the quality differential markers were screened. The contents of hyperoside and isoquercitrin were determined by the same HPLC. RESULTS ：The similarities of HPLC fingerprint of 10 batches of the leaves of T. angulata with control fingerprint were 0.923-0.983. A total of 11 common peaks were identified ，and the peaks 4 and 5 were hyperoside and isoquercitrin ，respectively. Results of cluster analysis ，PCA and PLS-DA showed that 10 batches of leaves of T. angulata could be divided into two categories ，Y10 was clustered into one category ，and others were clustered into one category. PLS-DA analysis showed that 6 common peaks （peaks 4，3，10，2，6 and 11） with variable importance projection （VIP）greater than 1 were selected. Average contents of hyperoside and isoquercitrin in 10 batches of the leaves of T. angulata were 0.47-6.97，0.21-1.87 mg/g，respectively. CONCLUSIONS ：Established HPLC fingerprint and the method for content determination are stable and reliable ，and can be used for the quality control of the leaves of T. angulata from different areas. Six quality differential markers including hyperoside in the leaves of T. angulata from different areas are qnyz202034） preliminarily screened.