OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

ObjectiveTo develop a standardized living will manual suitable for promotion in China， combining existing literature and the current implementation status of living will both domestically and internationally as well as the characteristics of modern medicine. MethodsA pool of manual entries was constructed through hospital interviews and literature retrieval. A Delphi method expert correspondence was conducted to modify and supplement the manual entry settings. The results of the correspondence were statistically analyzed to verify the reliability and scientific validity of the manual and the correspondence. ResultsThis study constructed a pool of manual entries by conducting interviews in four hospitals in Beijing and retrieving and including 155 pieces of literature，and developed a preliminary version of the manual with a total of 40 entries in four sections， namely medicine， psychology， society， and farewell. The manual items were revised through two rounds of the Delphi method correspondence with a total of 88 experts. The expert response rates in the two rounds of the correspondence questionnaires were 100% and 90%， respectively； the expert authority coefficients were 0.84 and 0.865， respectively； and Kcndall W was 0.141 and 0.077， respectively. In terms of the reliability test， the Cronbach’s α coefficients of the two rounds of correspondence were 0.941 and 0.969， respectively， and the Guttman coefficients were 0.862 and 0.857， respectively. As for the validity test， the Pearson correlation coefficient for 39 entries was R>0.4 in the first round of correspondence， and for 41 entries was R>0.4 in the second round of correspondence； a total of 20 entries in the first round of correspondence had an I-CVI ≥ 0.780， and the scale’s S-CVI was 0.786； a total of 31 entries in the second round of correspondence had an I-CVI ≥ 0.780， and the scale’s S-CVI was 0.846. Meanwhile， this study developed a legal instrument section of the manual including personal information， effective time， modification and revocation， witnesses， and other contents by reviewing relevant laws and regulations both domestically and internationally. ConclusionThe standardized living will manual is comprehensive， reliable， and scientific， which makes it suitable for promotion and further improvement.

BACKGROUND:Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown. OBJECTIVE:To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique. METHODS:The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.The βvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages. RESULTS AND CONCLUSION:A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with age:age-unspecified bone mineral density[β=0.038,95%confidence interval(CI):1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI:1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI:1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI:0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI:0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI:0.96-1.04,P=0.716).Similar results were obtained from the MR-Egger regression and weighted median estimator analyses.These findings indicate that type 2 diabetes mellitus may be one of the protective factors of bone mineral density,and there is a correlation with age.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Objective:To compare the clinical outcomes between modified percutaneous kyphoplasty (PKP) and conventional PKP in the treatment of Kümmell disease.Methods:A retrospective cohort study was conducted of the 57 patients with single level kummell disease who had undergone PKP between January 2015 and December 2017 at Department of Spinal Surgery, Jiangmen Hospital Affiliated to Sun Yat-sen Uni-versity.Of them, 36 received modified PKP and 21 conventional PKP.In the modified PKP group, there were 24 males and 12 females with an age of 73.9 years±9.4 years and a course of disease of 2.2 months±1.5 months; the disease was located at a thorocic vertebra in 20 cases and at a lumbar vertebra in 16.In the conventional PKP group, there were 15 males and 6 females with an age of 72.6 years±11.9 years and a course of disease of 1.8 months±1.1 months; the disease was located at a thorocic vertebra in 10 cases and at a lumbar vertebra in 11.The 2 groups were compared in terms of operation time, bone cement volume, cement leakage, visual analogue scale (VAS), Oswestry disability index (ODI), anterior and middle heights and cobb angle of injured vertebra at postoperative 3 days, 1 and 3 months, and final follow-up.Results:There were no significant differences in the general clinical data between the 2 groups, showing compatibility between groups ( P>0.05).All the operations were accomplished uneventfully with no such serious complications as spinal cord nerve injury, wound infection, pulmonary embolism, bone cement poisoning reaction or death. There was no significant difference between the 2 groups in operation time or bone cement volume ( P>0.05).The rate of cement leakage in the modified PKP group [33.3%(9/27)] was significantly lower than that [52.4%(11/21)] in the conventional PKP group ( P<0.05).There were no significant differences be-tween the 2 groups in VAS, ODI, anterior or middle height of injured vertebra or cobb angle at postoperative 3 days or one month ( P>0.05), but the postoperative values were improved compared to the preoperative ones.At postoperative 3 months and final follow-up, the modified PKP group was significantly better in all the indexes than the conventional PKP group ( P<0.05). Conclusion:Compared with conventional PKP, the modified PKP may lead to better outcomes for Kümmell disease.

Objective:To explore the psychological state and affected factors of elderly patients with hip fractures.Methods:A retrospective analysis of 156 elderly hip fracture patients(>65 years) admitted to the Department of Orthopaedics, the First Affiliated Hospital of Harbin Medical University from January 2016 to August 2019 was performed. General and psychological information were collected by questionnaire.General information included age, gender, education, whether surgery, length of stay.SCL-90, a self-assessment scale, was chosen as the psychological test to analyzed the elderly hip fracture patients′ psychological status during hospitalization and the norms of SCL-90 in Chinese which were established in 1986 were used as the control group. The prognostic factors were examined by univariate and multivariate analysis.Results:Somatization, interpersonal sensitivity, depression, anxiety, paranoid factor scores, and total scores of the elderly hip fracture patients were significantly higher than control group(all P=0.00).Univariate analysis and logistic regression analysis showed that non-surgery treatment and more than 10 days of hospitalization were independent prognostic factors that affected the psychological state of elderly hip fracture patients (all P=0.00). Conclusion:Elderly patients hospitalized with osteoporosis and hip fractures are prone to have negative emotional and psychological changes.The length of hospitalization and the choice of treatment can affect patients′ psychological state, suggesting that effective psychological intervention is necessary.

Objective:To explore the psychological state and affected factors of elderly patients with hip fractures.Methods:A retrospective analysis of 156 elderly hip fracture patients(>65 years) admitted to the Department of Orthopaedics, the First Affiliated Hospital of Harbin Medical University from January 2016 to August 2019 was performed. General and psychological information were collected by questionnaire.General information included age, gender, education, whether surgery, length of stay.SCL-90, a self-assessment scale, was chosen as the psychological test to analyzed the elderly hip fracture patients′ psychological status during hospitalization and the norms of SCL-90 in Chinese which were established in 1986 were used as the control group. The prognostic factors were examined by univariate and multivariate analysis.Results:Somatization, interpersonal sensitivity, depression, anxiety, paranoid factor scores, and total scores of the elderly hip fracture patients were significantly higher than control group(all P=0.00).Univariate analysis and logistic regression analysis showed that non-surgery treatment and more than 10 days of hospitalization were independent prognostic factors that affected the psychological state of elderly hip fracture patients (all P=0.00). Conclusion:Elderly patients hospitalized with osteoporosis and hip fractures are prone to have negative emotional and psychological changes.The length of hospitalization and the choice of treatment can affect patients′ psychological state, suggesting that effective psychological intervention is necessary.

Objective To investigate the protective effect and mechanism of serum containing Euonymus fortunei on the rat pancreatic islet cells. Methods Forty male SD rats were randomly divided into 5 groups (n=8 in each group), including the control group (normal rat islet cells were cultured with normal rat serum), ischemic preconditioning group (abdominal aorta was blocked first and then re-opened before the pancreas was obtained, and the pancreatic islet cells were cultured with normal rat serum), Euonymus fortunei treatment group (normal rat islet cells were cultured with rat serum containing Euonymus fortunei), Euonymus fortunei group and blank group (normal rats were administered orally with Euonymus fortunei extract or distilled water for the preparation of rat serum). Diphenylthiocarbazone (DTZ) staining was utilized to observe and calculate the quantity of islets. Acridine orange (AO)/propidium iodide (PI) staining was adopted to calculate the survival rate of islet cells. The insulin release experiment was performed to calculate the stimulation index (SI) and evaluate islet cell function. The concentration of glutathione (GSH) and nitric oxide (NO) in islet cells was detected using GSH and NO kits. The expression level of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) was quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Islet cells were observed in specifically scarlet color after DTZ staining. The quantity of islet cells did not significantly differ among different groups (all P>0.05). Along with the prolongation of culture time, the activity of islet cells in each group was gradually decreased. At 72 h after isolation and culture, compared with the control group, the survival rate of the cells was significantly higher in the Euonymus fortunei treatment group (P<0.05). The insulin release test results demonstrated that compared with the control group, the SI of the ischemic preconditioning and Euonymus fortunei treatment groups was significantly increased (both P<0.05). Compared with the control group, the GSH contents of pancreatic islet cells in the ischemic preconditioning and Euonymus fortunei treatment groups were considerably enhanced, the NO content was significantly decreased, and the expression level of iNOS mRNA was significantly down-regulated (all P<0.05). Conclusions Euonymus fortunei can increase the survival rate of islet cells and enhance the function of pancreatic islets by increasing the level of GSH, down-regulating the expression of iNOS and decreasing the NO production.

Objective To investigate weight, ghrelin changes following transcatheter left gastric artery embolization in rabbit model of obesity, and evaluate its safety. Methods Thirty New Zealand rabbits were randomly divided into three groups, ten New Zealand rabbits in each group, group A:left gastric artery embolization using gelatin sponge, group B:left gastric artery and gastroduodenal artery embolization using gelatin sponge, group C (control group): left gastric artery and gastroduodenal artery perfusion using normal saline. Ghrelin, weight and liver and kidney function were measured at preoperative and postoperative 1, 2, 3, 4 weeks. T test was used to compare the differences in the levels of preoperative and postoperative average ghrelin, weight, alanine transaminase (ALT), aspartate transaminase (AST), creatinine and urea in each group. The ANOVA of repeated measurement was used to compare the difference of preoperative and postoperative each time points between the three groups. Results The preoperative and postoperative ghrelin levels in group A were (4057±61)and (3708±141) pg/ml with statistically significant differences (t=4.5, P<0.05). The preoperative and postoperative ghrelin levels in group B were (4137 ± 89) and (3608 ± 239) pg/ml with statistically significant differences (t=6.8, P<0.05). The preoperative and postoperative ghrelin levels in the control group were (3986 ± 82)and (4044 ± 72) pg/ml with no statistically significant differences (t=0.7, P>0.05). The level of ghrelin in group B decreased significantly compared with group A and the difference was statistically significant (t=3.8, P<0.05). There was a statistically significant difference in postoperative ghrelin levels between the three groups (F=15.6, P<0.05). The preoperative and postoperative weight in group A were (6.12±0.38)and (5.66±0.39) kg with statistically significant differences (t=2.7, P<0.05). The preoperative and postoperative weight in group B were (5.99 ± 0.57)and (5.24 ± 0.61) kg with statistically significant differences (t=3.1, P<0.05). The preoperative and postoperative weight in the control group were (5.94 ± 0.45)and (6.24 ± 0.42) kg with no statistically significant differences (t=1.2, P>0.05). The weight loss of group B was significantly greater than that of group A and the difference was statistically significant (t=5.2, P<0.05). There was a statistically significant difference in postoperative weight between the three groups (F=5.1, P<0.05). There were no statistically significant differences in ALT, AST, creatinine and urea levels at preoperative and postoperative each time points in each group (P>0.05). Conclusion Left gastric artery embolization can become a safe and effective minimally invasive treatment for obesity and left gastric artery and gastroduodenal artery embolization at the same time could achieve more weight loss.

Objective To explore the diagnostic value of radial ultrasound (EBUS) combined with virtual navigation (VBN) in peripheral pulmonary nodules.Methods Two hundreds and forty cases of peripheral pulmonary nodules(0.8 cm≤diameter≤3 cm) in the respiratory department of our hospital from July 2014 to July 2015 were included and according to the different guide de vices,which were divided into the radial ultrasound combined with virtual navigation group (EBUS+ VBN group),radial ultrasound group (EBUS group),virtual navigation group (VBN group) and control group.The diagnostic rates were compared among the four groups and among different sizes of lesion.The time of lesion location and operating time were also compared between the EBUS+ VBN group and EBUS group.Results Among 240 cases,the diagnostic rate in the EBUS+VBN group was highest(81.67％),and the diagnostic rates had statistically significant difference among the four groups (x2=19.344,P=0.00);the diagnostic rates of lesions less than 2 cm in diameter were lower than that of lesions ＞2 cm in the EBUS+-VBN group and EBUS group,but without statistically significant difference (x2 =2.04,3.40,P =0.15,0.07);the locating lesions time and operating times in the EBUS+ VBN group were shorter than those in the EBUS group,but the difference between them was not statistically significant (P=0.03,0.04).Conclusion EBUS combined with VBN could improve the diagnostic rate of peripheral pulmonary nodules and shorten the time of lesion location and operating time.