OBJECTIVE:To promote the normative management of clinical off-label drug use. METHODS:The degree of devi-ation from the drug instructions and the risk degree were comprehensively considered,and the off-label drug use were classified in-to three different situations for classifying approval and informed consent classifying;situation and effects after classifying were evaluated. RESULTS:The classifying included occasional or small amount off-label use on dosage and drugs solvent (the first), regular off-label use on route or administration(the second)and super-indications drug use with contraindications(the third). The approval was classified as follows as confirmed with signature by doctor,approved by medical department,approved by pharmaceu-tical committee and ethics committee accordingly;informed consent classifying were signing informed consent,informing and re-cording in medical record,informing orally. Off-label drug use approval process was officially initiated from Feb. 2014 to Jun. 2016 in our hospital,51 off-label drug use applications from 13 clinical departments were received,with 16 items belonging to the second situation,35 items belonging to the third. Finally 42 applications were approved and 9 were not. No relevant new/serious ad-verse drug reactions/ events occurred in process of the approved off-label drug use. And no off-label drug use not approved was found to continue to be used in our hospital. CONCLUSIONS:Classification management methods for off-label drug use in our hos-pital have shown high operability,improved the off-label drug use behavior of physicians.

Objective:To analyze the influence of comprehensive rehabilitation on postoperative functions in the elderly patients with femoral intertrochanteric fracture.Methods:From June 2015 to June 2019, 144 elderly patients were treated at Department of Orthopedics, China-Japan Friendship Hospital for femoral intertrochanteric fractures by internal fixation with proximal femoral nail anti-rotation (PFNA). Of them, 65 received comprehensive rehabilitation, including intervention measures for details, prevention and management of comorbidities and complications and active exercise of the injured limb, while 79 conventional rehabilitation. In the comprehensive rehabilitation group, there were 22 males and 43 females with an age of (76.6±6.7) years, and 18 cases of type 31-A1, 35 cases of type 31-A2 and 12 cases of type 31-A3 by the AO type. In the control group, there were 23 males and 56 females with an age of (75.2±7.0) years, and 25 cases of type 31-A1, 39 cases of type 31-A2 and 15 cases of type 31-A3 by the AO type. The 2 groups were compared in terms of visual analog scale (VAS), Harris hip score, Barthel index, postoperative ambulation time and complications at 6 months after operation.Results:The 2 groups were comparable because there was no significant difference between them in the preoperative or intraoperative general data ( P>0.05). The comprehensive rehabilitation group had a significantly lower VAS score (1.5±1.0), a significantly higher Harris hip score(83.9±5.4), a significantly higher Barthel index (81.6±5.4), significantly shorter postoperative ambulation time [(2.6±1.0) d], and a significantly lower incidence of complications [4.6% (3/65)] than the control group did [1.9±1.2, 80.2±7.9, 78.2±7.9, (3.2±1.4) d, 16.5%(13/79), respectively] (all P< 0.05). Conclusion:For elderly patients with femoral intertrochanteric fracture, comprehensive rehabilitation can significantly reduce complications, promote functional recovery of the hip, and speed up recovery of capabilities of daily living compared with conventional rehabilitation.

OBJECTIVETo explore the effects of the genetic and environmental factors on intelligence of children and adolescent from the Southwest China Prospective Twin Registry (SCPT).

METHODSThe intelligence was investigated by using the Wechsler Intelligence Scale for Children (C-WISC) in 333 twin pairs aged 6-16 years. The effects of genetic and environmental factors on IQ were analyzed by using structural equation modeling (SEM) and correlation analysis method. The effects in different sex and age groups in this population were also investigated.

RESULTSGenetic influence accounted for 0.43 of total IQ variance and 0.37 of verbal IQ in 6-16 years old children and adolescent, but there was no significant genetic effect on performance IQ. The heritability of children aged 10-16 years was higher than that of those aged 6-10 years (total IQ: 0.82 vs 0.00, verbal IQ: 0.80 vs 0.00, performance IQ:0.51 vs 0.00). In males the heritability of verbal IQ (0.47) was higher than that in females (0.05). The shared environmental influences accounted fo r the majority of variance of performance IQ in both males and females.

CONCLUSIONThere is moderate heritability on the total IQ and verbal IQ, while shared environmental factors played important roles on the variance of performance IQ. The heritability of IQ, verbal IQ and performance IQ are higher in older children and adolescent than that in younger children.

Adolescent ; Age Factors ; Child ; Child Development ; physiology ; Environment ; Female ; Humans ; Intelligence ; genetics ; Male ; Psychomotor Performance ; physiology ; Reaction Time ; genetics ; Sex Characteristics ; Sex Factors ; Twins ; genetics ; Wechsler Scales

Data mining method based on the traditional Chinese medicine(TCM) inheritance system(V2.5) was adopted to analyze professor Lin Yi's experience for metastasis breast cancer(MBC) by analysing the high frequency medicine, drug categories，drug properties，the key symptoms and key drugs of different metastasis regions and different syndromes, drug symptom analysis in the effective prescriptions for treating MBC by Lin from January 2013 to December 2017. A total of 89 MBC patients, 5 syndromes and 117 prescriptions were involved. The first 10 most frequently used were Atractylodis Macrocephalae Rhizoma, Poria, Dioscoreae Rhizoma, Coicis Semen, Crataegi Fructus, Hordei Fructus Germinatus, Galli Gigerii Endothelium Corneum, Hedyotis Diffusa, Codonopsis Radix, Astragali Radix. The warm and placid property was higher, the most herbs had Gan taste, the first two channel tropisms were spleen and the stomach. Drug symptom analysis in 5 different metastasis regions and 6 different syndromes were also been done. The conclusion showed that professor Lin's experience as: recognizing the basis of diseases,differentiating the syndrome, combinating disease and syndrome, cautiously grasping pathogenesis,combinating tonification and purgation together, regulating balance, treating the symptoms and origin, regulating spleen and stomach, caring for the postnatal throughout, prefering ancient prescription,rational compatibility, using medicine gently.

OBJECTIVE To study the effects of yunaconitine on myocardial injury in rats and its mechanism related to mitochondrial apoptosis pathway rats. METHODS Forty SD rats were divided into normal group （normal saline）， yunaconitine high-dose and low-dose groups（0.14， 0.09 mg/kg）and aconitine group （positive control， 0.88 mg/kg） by random number method， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 7 days. The levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， superoxide dismutase （SOD） and malondialdehyde （MDA） in serum as well as the level of reactive oxygen species （ROS） in myocardial tissue were detected. The pathomorphological changes of myocardium and ultrastructural changes of myocardial mitochondria were all observed. The apoptosis of cardiomyocytes was determined. The protein relative expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 were determined in myocardium of rats. RESULTS Compared with normal group， the serum levels of LDH， CK， CK-MB and MDA， the apoptotic numbers of cardiomyocytes， the level of ROS and protein expression of caspase-3 in myocardium were increased significantly in yunaconitine high-dose and low- dose groups （P＜0.05 or P＜0.01）； serum level of SOD and Bcl-2/Bax ratio in myocardium were all decreased significantly （P＜ 0.01）； the protein relative expressions of caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 in myocardium were significantly increased in yunaconitine high-dose group （P＜0.05）； some pathomorphological changes were found in 2 groups， such as myocardial fiber disorder， mitochondrial swelling. CONCLUSIONS Yunacotine could cause myocardial injury in rats. Its mechanism might be related to destroying the integrity of cardiomyocyte membrane， causing oxidative stress of cardiomyocyte， and inducing the apoptosis of myocardial cells through mitochondrial pathway.

OBJECTIVE： To provide reference for rational use of estradiol （E2） preparation in clinic. METHODS： The medical records of outpatients receiving assisted reproductive technology （ART） and E2 preparation [Estradiol valerate tablets （EV）， Complex packing estradiol tablets/estradiol and dydrogesterone tablets （EP）， Estradiol gel （EG）] were collected from the reproductive medicine center of a hospital during Jan. 2016-Mar. 2017. Taking drug instruction as standard， the rationality of medical records was evaluated from aspects of indication， route of administration， contraindication， usage and dosage， treatment course， etc. At the same time， these patients were followed up by telephone or outpatient service， and their pregnancy outcomes and ADR were summarized. RESULTS： A total of 12 646 prescriptions were collected， and 7 222， 3 912， 181 and 1 331 prescriptions used EV， EP， EG and EV+EP， respectively. The types of off-label use included over-indication， over-route and over-contraindication， and the rates of off-label use rates were 100％， 11.73％ and 43.60％， respectively. A total of 5 868 ART patients were involved； 439 patients received fresh embryo transplantation， and 5 429 patients received frozen-thawed embryo transplantation， involving 720 and 11 926 prescriptions， respectively. The rates of off-label use of above E2 preparations were 100％ （except for fresh embryo transplantation patients using EG）. As of Feb. 2018， the infant-holding rates of ART patients using EV， EP， EG and EV+EP were 85.29％， 85.37％， 86.36％ and 85.45％， respectively. No relevant ADR and neonatal birth defect was found. CONCLUSIONS： The phenomenon of off-label use of E2 preparations is widespread in the reproductive medicine center of the hospital. Although there is no indication of related safety risks， evidence-based evaluation should be carried out by enlarging the sample size in clinical practice， and careful use.

OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS ：Totally 32 rats were randomly divided by random number table method into normal control group ，yunacotine low-dose and high-dose groups （0.09，0.14 mg/kg），aconitine group （positive control ，0.88 mg/kg），with 8 rats in each group. Administration groups were given the corresponding drugs once a day ，and normal control group was given the constant volume of normal saline ，for consecutive 7 d. After last intragastric administration ，the changes of electrocardiogram （ECG） were observed. The contents of adenosine triphosphate（ATP）in myocardial tissue and Ca 2+ in myocardial cells ，the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2（RyR2）and Ca 2+-ATPase（SERCA2）in myocardial tissue were determined. RESULTS：Compared with normal control group ，time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells ， the ATP contents ， the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly （P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly （P＜ 0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged （P＜0.01）；the content of Ca 2+ in myocardial cells was increased significantly （P＜0.01）；ATP content ，the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase，and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS ： Yunaconitine can induce arrhythmia in rats ，the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.

OBJECTIVE To investigate the antibacterial activities of flavaspidic acid BB against the main pathogens of skin and soft tissue infections such as methicillin -resistant Staphylococcus aureus （MRSA）and methicillin -sensitive Staphylococcus aureus （MSSA） in vitro and in vivo . METHODS Microdilution method was used to determine the minimum inhibitory concentration（MIC）and minimum bactericidal concentration （MBC）of flavaspidic acid BB on 10 strains of MRSA and 13 strains of MSSA ；time-kill curves of MRSA 11 and MSSA 23 strains were drawn by plate method ；the checkerboard dilution method was used to determine the combined antibacterial effect of flavaspidic acid BB and mupirocin ；the skin abscess model of mice was established to evaluate the antibacterial effects of 0.5%，1%，2% flavaspidic acid BB cream on MRSA 11 or MSSA 23 strains in vivo；scanning electron microscopy was used to observe the effects of flavaspidic acid BB on the morphology of MRSA 11 or MSSA23 strains. The contents of nucleic acid leakage and extracellular protein were also determined . RESULTS MIC and MBC ranges of flavaspidic acid BB against 10 strains of MRSA were 6.30-80.00 μg/mL and 40.00-640.00 μg/mL；MIC and MBC ranges of 13 strains of MSSA were 40.00-80.00 μg/mL and 63.50-126.99 μg/mL，respectively. The bactericidal rate of MRSA 11 and MSSA23 strains were 99.9% after interfered with plavaspidic acid BB for 36 h. The combination of flavaspidic acid BB and mupirocin showed an additive effect on MRSA strain and an additive or synergistic effect on MSSA strain . The 0.5%，1% and 2% flavaspidic acid BB cream could reduce the volume of abscess and the bacterial load of skin abscess model mice to some extent （P＜0.05），and improved the pathological changes of skin inflammation in skin abscess site of mice . Flavaspidic acid BB could make MRSA 11 and MSSA 23 cells shrinkage and rupture ，and significantly increase the contents of nucleic acid leakage and extracellular protein （P＜0.01）. CONCLUSIONS Flavaspidicacid BB shows good antibacterial effect on MRSA and MSSAE-mail：tchp66@163.com in vitro and in vivo ，the mechanism of which may be related to the change of membrane permeability .