OBJECTIVE To explore the transformation of the dispensing and drug pickup process in traditional Chinese medicine pharmacy （TCM Pharmacy） in our hospital based on data-intelligence-driven， aiming to improve pharmacists’ work efficiency and patients’ drug pickup experience. METHODS Value stream mapping and journey mapping were used to systematically identify non-value-added links in pharmacists’ dispensing process and key pain points in patients’ drug pickup under the traditional process. An intelligent dispensing and drug pickup system for the TCM Pharmacy was developed based on the C# and Android television platforms， and a machine-learning model was adopted to predict patients’ drug pickup waiting time. A comprehensive evaluation was performed from three perspectives： system performance， prediction accuracy， and satisfaction of pharmacists and patients. RESULTS The system successfully streamlined non-value-added links such as “waiting for writing on the board” and “searching for drugs”， and realized multimodal dynamic prompts of dispensing status through auditory （number calling） and visual （television terminal） channels. The constructed model for predicting drug pickup waiting time exhibited good fitting degree and generalization ability （mean absolute error＝4.28 min， R 2 ＝0.882）. The comprehensive satisfaction scores of pharmacists and patients in the traditional mode were significantly increased from （70.99±1.74） and （73.58±1.98） to （90.02±1.30） and （88.61±2.08） in the new system， respectively （ P ＜0.01）. CONCLUSIONS The transformation of the intelligent drug dispensing and pickup system for TCM pharmacy based on data-intelligence-driven effectively improves the efficiency of pharmacists’ dispensing work， realizes process transparency and waiting time predictability， and significantly enhances patients’ drug pickup experience.

Objective To construct mouse BaF3-FIP1L1-PDGFRA(F/P),BaF3-F/P-T674I and BAF3-F/P-D842V pre-B cell strains which stably express F/P fusion protein and its T674I and D842V mutants in order to e-valuate their activity by checking their responses to tyrosine kinase inhibitors(TKIs).Methods Lentivirus infected technique was used to transfect the target gene into BaF3 cells.RT-qPCR was used to detect mRNA expression,and CCK-8 method was used to detect the inhibitory effect of TKIs on the proliferation of stable cell strains.Results The constructed BaF3-F/P,BaF3-F/P-T674I and BAF3-F/P-D842V cell strains all transcripted FIP1L1 and PDGFRA mRNA.They exhibited malignant phenotypic characteristics of proliferation independent of IL-3 and sen-sitivity to corresponding TKIs.Conclusions The pre-B-cell strains stably expressing F/P and its T674I and D842V mutants are successfully constructed,which provide a good cell model for the development of compounds targeting at those molecules.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective:To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps.Methods:A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed.Results:Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ml and (135.865±98.470) pg/ml, respectively, which were higher than 2.369±1.306, (302.480±99.946) ng/ml and(110.694±76.044) ng/ml in non-polyp group, respectively ( P<0.05). Multivariate Logistic regression analysis showed that the gender ( OR=4.269, 95% CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ml: OR=2.385, 95% CI: 1.155-4.926) were independent factors of colorectal polyps. The gender ( OR=3.799, 95% CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ml: OR=2.290, 95% CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender( OR=6.725, 95% CI: 1.853-24.410) and fasting plasma glucose (≥6.5 mmol/L: OR=0.047, 95% CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender ( OR=3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender ( OR=5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ml: OR=2.502, 95% CI: 1.102-5.681), fasting plasma glucose (≥6.5 mmol/L: OR=0.282, 95% CI: 0.095-0.839) were independent factors of multiple polyps. The gender ( OR=3.416, 95% CI: 1.134-10.289) and fasting insulin (≥9.4 μU/ml: OR=9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender ( OR=3.151, 95% CI: 1.244-7.984) and fasting plasma glucose (≥6.5 mmol/L: OR=0.310, 95% CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender ( OR=22.649, 95% CI: 4.154-123.485), age (55 to 64 years old: OR=4.473, 95% CI: 1.070-18.704; ≥65 years old: OR=5.815, 95% CI: 1.300-26.009), BMI (≥28 kg/m 2: OR=5.310, 95% CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ml: OR=7.474, 95% CI: 1.903-29.351) were independent factors for colorectal polyps with size ≥ 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ml: OR=6.109, 95% CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ml: OR=6.401, 95% CI: 1.717-23.864). The age (55 to 64 years old: OR=3.783, 95% CI: 1.052-13.611) and VCAM-1 (≥352.8 ng/ml: OR=4.341, 95% CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR=5.743, 95% CI: 1.205-27.362, ≥65 years old: OR=6.885, 95% CI: 1.143-41.467), VCAM-1 (≥352.8 ng/ml: OR=6.313, 95% CI: 1.415-28.159) and IGF-1 (≥7.6 ng/ml: OR=5.621, 95% CI: 1.069-29.543) were independent factors of female adenoma. Conclusions:The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps.

Objective:To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps.Methods:A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed.Results:Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ml and (135.865±98.470) pg/ml, respectively, which were higher than 2.369±1.306, (302.480±99.946) ng/ml and(110.694±76.044) ng/ml in non-polyp group, respectively ( P<0.05). Multivariate Logistic regression analysis showed that the gender ( OR=4.269, 95% CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ml: OR=2.385, 95% CI: 1.155-4.926) were independent factors of colorectal polyps. The gender ( OR=3.799, 95% CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ml: OR=2.290, 95% CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender( OR=6.725, 95% CI: 1.853-24.410) and fasting plasma glucose (≥6.5 mmol/L: OR=0.047, 95% CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender ( OR=3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender ( OR=5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ml: OR=2.502, 95% CI: 1.102-5.681), fasting plasma glucose (≥6.5 mmol/L: OR=0.282, 95% CI: 0.095-0.839) were independent factors of multiple polyps. The gender ( OR=3.416, 95% CI: 1.134-10.289) and fasting insulin (≥9.4 μU/ml: OR=9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender ( OR=3.151, 95% CI: 1.244-7.984) and fasting plasma glucose (≥6.5 mmol/L: OR=0.310, 95% CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender ( OR=22.649, 95% CI: 4.154-123.485), age (55 to 64 years old: OR=4.473, 95% CI: 1.070-18.704; ≥65 years old: OR=5.815, 95% CI: 1.300-26.009), BMI (≥28 kg/m 2: OR=5.310, 95% CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ml: OR=7.474, 95% CI: 1.903-29.351) were independent factors for colorectal polyps with size ≥ 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ml: OR=6.109, 95% CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ml: OR=6.401, 95% CI: 1.717-23.864). The age (55 to 64 years old: OR=3.783, 95% CI: 1.052-13.611) and VCAM-1 (≥352.8 ng/ml: OR=4.341, 95% CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR=5.743, 95% CI: 1.205-27.362, ≥65 years old: OR=6.885, 95% CI: 1.143-41.467), VCAM-1 (≥352.8 ng/ml: OR=6.313, 95% CI: 1.415-28.159) and IGF-1 (≥7.6 ng/ml: OR=5.621, 95% CI: 1.069-29.543) were independent factors of female adenoma. Conclusions:The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps.

OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.

An 83-year-old male patient received IV infusions of linezolid 600 mg once per 12 hours and imipenem and cilastatin sodium 1 g once per 8 hours for incisional wound infection after cervical spinal fusion. Three days later, imipenem and cilastatin sodium was stopped according to the drug sensitive test result and linezolid was continued. Two weeks after the use of linezolid, the patient developed dry mouth, and abnormal sensation of tongue; and 18 days later, he developed black tongue coating in the center of the tongue, which could not relieved after drinking a lot of water. After that, the tooth root blackened and the denture pigmented gradually. It was considered as black hairy tongue, which might be associated with linezolid. Linezolid was stopped and compound chlorhexidine gargle was given for gargling. Twelve days later, the patient′s tongue coating returned to normal, the symptoms of dry mouth and thirst disappeared, and the color of tooth root became lighter.

An 83-year-old male patient received IV infusions of linezolid 600 mg once per 12 hours and imipenem and cilastatin sodium 1 g once per 8 hours for incisional wound infection after cervical spinal fusion. Three days later, imipenem and cilastatin sodium was stopped according to the drug sensitive test result and linezolid was continued. Two weeks after the use of linezolid, the patient developed dry mouth, and abnormal sensation of tongue; and 18 days later, he developed black tongue coating in the center of the tongue, which could not relieved after drinking a lot of water. After that, the tooth root blackened and the denture pigmented gradually. It was considered as black hairy tongue, which might be associated with linezolid. Linezolid was stopped and compound chlorhexidine gargle was given for gargling. Twelve days later, the patient′s tongue coating returned to normal, the symptoms of dry mouth and thirst disappeared, and the color of tooth root became lighter.

OBJECTIVE： To systematically evaluate the efficacy and safety of Clonidine tansdermal patch for child tic disorders in children， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Medline， Embase， Cochrane library， CNKI， VIP， CBM and Wanfang database， randomized controlled trials （RCTs） about Clonidine tansdermal patch （trial group） versus other therapies （control group， including placebo group， thiopride group， haloperidol group） for child tic disorders were collected from datbase estallishment to July 2018. The literatures met inclusion criteria were summarized. After quality evaluation with Cochrane system evaluation manual 5.1.0， Meta-analysis of reduction rate （amount） of YGTSS， the incidence of ADR and response rate was performed by using Rev Man 5.3 statistical software. Descriptive analysis was performed on indicators of groups that were unable to perform Meta-analysis. RESULTS： A total of 8 RCTs involving 1 320 patients were included. Among them， 2 RCTs involved placebo in control group； 2 RCTs involved thiopride， 3 RCTs involved haloperidol， and 1 RCT involved thiopride and haloperidol. Results of Meta-analysis showed that reduction rate of YGTSS in trial group were significantly higher than haloperidol group [MD＝21.94， 95％CI（21.03， 22.86）， P＜0.001]， but there was no statistical significance compared with thiopride group [MD＝10.66， 95％CI（－15.68， 37.00）， P＝0.43]. The incidence of adverse events （mainly including skin itching， redness， dry mouth， dizziness， decreased blood pressure， abnormal electrocardiogram） in trial group were significantly lower than thiopride group [OR＝0.42， 95％CI（0.22， 0.82）， P＝0.01] and haloperidol group [OR＝0.17， 95％CI（0.09， 0.32）， P＜0.001]， but there was no statistical significance compared with placebo group [OR＝0.61， 95％CI（0.29， 1.29）， P＝0.20]. There was no statistical significance in response rate of trial group compared with thiopride group [OR＝1.29，95％CI（0.38， 4.39）， P＝0.69] and haloperidol group [OR＝1.63， 95％CI（0.89， 2.96）， P＝0.11]. The results of descriptive analysis showed that reduction rate （amount） of YGTSS in trial group was significantly higher than that of placebo group （P＜0.05）， and response rate of trial group was significantly higher than that of placebo group （P＜0.01）. CONCLUSIONS： For child tic disorders in children， Clonidine tansdermal patch is better than placebo and haloperidol in reduction rate （amount） of YGTSS， and is similar to thiopride. Response rate of Clonidine tansdermal patch is better than that of placebo， and is similar to those of thiopride and haloperidol. The safety of Clonidine tansdermal patch is better than those of thiopride and haloperidol， and is similar to that of placebo.

Medication safety officer (MSO) is an expert and manager of medication safety. Management of medication safety by MSO has been popularized and plays an important role in the medical institutions of the United States (US)and the United Kingdom (UK). The results of systematic search and analysis of literature showed that the setting of MSO in US and UK was mainly based on various characteristics of the adverse drug events (for example,the large number,high possibility for patient damage and economic loss,poor quality of the reports,inadequate management and preventability),and aimed to reduce its occurrence and then to guarantee the medication safety in patients. In US and UK,the MSOs mainly worked in large hospitals or large health care provider organizations,while the position level was not clearly defined. Responsibilities of MSOs mainly included the formulation and practice of a medication safety program,supervision and improvement of medication safety system,providing professional advice on medication safety,management and reporting of medication safety information in internal medical institution, receiving and transmitting medication safety information outside and carrying out medication safety training. In addition,the US put forward some specific qualification requirements for the position,including educational background,practicing qualification,related training experience,etc. The setting of MSO may be one of the effective measures to solve the problem of medication safety. It is suggested to set up a MSO management system in China′s medical institutions and actively explore a novel management mode of medication safety in China.