Objective To discuss on the application of innovative quality control circle in optimizing pharmaceutical care,design pharmaceutical care model according to needs,and improve the quality of pharmaceutical care.Methods Using 10 steps of innovative quality control circle,the quality function development(QFD)was carried out by multidimensional quality tools,and the demand for pharmaceutical services was analyzed in the form of"House of Quality"Combined with PDCA cycle management tool,the situation of pharmaceutical services before and after improvement was analyzed and evaluated.Results After the implementation of the activities,many contents hd been improved,such as the dispensing time for outpatient pharmacy patients decreased from 16 min to 8 min,the finished product infusion configuration time in pharmacy intravenous admixture services decreased from 15 min to 7 min,the surgery pharmacy special management drug report automatically generated number increased from 2 copies to 6 copies,the daily order review time for each department of pharmacy decreased from 80 min to 20 min,the perfection rate of pharmaceutical care digital module increased from 65.23％to 80.34％,and the multidimensional quality tool adoption rate increased from 60.00％to 93.00％.In addition,a number of additional benefits and intangible results were obtained.Conclusion Adopting the management mode of QFD combined with PDCA cycle can effectively reconstruct the management mode of pharmaceutical care,and effectively promote the scientific and fine management of pharmaceutical care.

Objectives:To explore the clinicopathological characteristics and prognostic risk factors in differentiated thyroid cancer (DTC) patients with lung metastasis.Methods:Patients of differentiated thyroid cancer with lung metastasis in Tianjin Medical University Cancer Institute & Hospital were enrolled from Jan 1, 2010 to Dec 31, 2016. The clinicopathological characteristics and risk factors affecting the prognosis were analyzed retrospectively.Results:A total of 65 DTC patients with lung metastasis were collected in this study, including 56 patients with papillary thyroid carcinoma and 9 patients with follicular thyroid carcinoma; 23 patients died and 42 patients survived. Median follow-up time was 99.4 months. There were 18 males, 47 females. Age 14-73 years, median age 51.0 years. High incidence of DTC lung metastasis was 50-59 years for males and 40-49 years for females. Based on AJCC 8th edition TNM staging, there were 37 patients in stage Ⅱ (age <55 years) and 28 patients in stage Ⅳb (age ≥55 years). The number of 131Ⅰ treatments performed ranged from 1 to 13 times, with a mean of 3.9 times. Firty-five patients were with lung metastasis alone, and 10 patients with lung metastasis and distant metastasis in other organs. Eleven patients suffered from hypoparathyroidism after 131Ⅰ treatment. COX multifactorial regression analysis found that age was independent risk factor affecting prognosis, multiple organs distant metastasis and pathologic subtype were relative risk factors affecting prognosis. There was no correlation between gender, number of 131Ⅰ treatments and poor prognosis. Conclusions:DTC has a high survival even with the occurrence of lung metastasis, but the prognosis is poor when combined with multi-organ metastasis. Age and multiple organ distant metastatic are independent risk factors affecting prognosis.

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Objective:To investigate the value of a preoperatively MRI-based deep learning (DL) radiomics machine learning model to distinguish low-grade and high-grade soft tissue sarcomas (STS).Methods:From November 2007 to May 2019, 151 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled as training sets, and 131 patients in the Affiliated Hospital of Shandong First Medical University and the Third Hospital of Hebei Medical University were enrolled as external validation sets. According to the French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) system, 161 patients with FNCLCC grades Ⅰ and Ⅱ were defined as low-grade and 121 patients with grade Ⅲ were defined as high-grade. The hand-crafted radiomic (HCR) and DL radiomic features of the lesions were extracted respectively. Based on HCR features, DL features, and HCR-DL combined features, respectively, three machine-learning models were established by decision tree, logistic regression, and support vector machine (SVM) classifiers. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each machine learning model and choose the best one. The univariate and multivariate logistic regression were used to establish a clinical-imaging factors model based on demographics and MRI findings. The nomogram was established by combining the optimal radiomics model and the clinical-imaging model. The AUC was used to evaluate the performance of each model and the DeLong test was used for comparison of AUC between every two models. The Kaplan-Meier survival curve and log-rank test were used to evaluate the performance of the optimal machine learning model in the risk stratification of progression free survival (PFS) in STS patients.Results:The SVM radiomics model based on HCR-DL combined features had the optimal predicting power with AUC values of 0.931(95%CI 0.889-0.973) in the training set and 0.951 (95%CI 0.904-0.997) in the validation set. The AUC values of the clinical-imaging model were 0.795 (95%CI 0.724-0.867) and 0.615 (95%CI 0.510-0.720), and of the nomogram was 0.875 (95%CI 0.818-0.932) and 0.786 (95%CI 0.701-0.872) in the training and validation sets, respectively. In validation set, the performance of SVM radiomics model was better than those of the nomogram and clinical-imaging models ( Z=3.16, 6.07; P=0.002,<0.001). Using the optimal radiomics model, there was statistically significant in PFS between the high and low risk groups of STS patients (training sets: χ2=43.50, P<0.001; validation sets: χ2=70.50, P<0.001). Conclusion:Preoperative MRI-based DL radiomics machine learning model has accurate prediction performance in differentiating the histopathological grading of STS. The SVM radiomics model based on HCR-DL combined features has the optimal predicting power and was expected to undergo risk stratification of prognosis in STS patients.

Objective:This study aimed to compare the detection efficacy of transrectal ultrasound-guided transrectal cognitive fusion targeted+ systematic prostate biopsy and transperineal cognitive fusion targeted + systematic biopsy in patients with suspected prostate cancer (PCa). In addition, the relative clinical characteristics of PCa were evaluated.Methods:A total of 385 patients with suspected prostate cancer in the affiliated hospital of Qingdao University from May 2019 to November 2019 were retrospectively analyzed. All patients met the prostate biopsy criterion, who underwent transrectal(n=275)and transperineal(n=110)prostate biopsy respectively. There were no significant differences of mean age [(70.7±7.3)years vs.(69.2±8.4) years], PSA [(55.12±116.96)ng/ml vs. (63.41±315.34)ng/ml], prostate volume [(55.96±35.26)ml vs. (64.35±55.99)ml] between two groups. According to preoperative prostate magnetic resonance imaging combined with intraoperative ultrasound, 2-4 needles targeted puncture of suspected lesion were performed, followed by 12 needle systematic prostate biopsy. The detection rate of prostate cancer between two biopsy ways were compared. The related factors of PCa including age, prostate volume and PSA level were collected for univariable and multivariable logistic analysis. The cancer detection rate was compared and logistic regression was used to assess the impact of patient characteristics on PCa detection.Results:For all patients, the detection rate with cancer between transrectal group and transperineal group were 121/275(40.0%) and 67/110(60.9%), respectively. The transperineal group detected a higher rate of PCa ( P=0.003)and more clinically significant prostate cancers (csPCa) (54.6% vs.36.7%, P=0.001) than that of the transrectal group, there were significant differences between two groups ( P<0.05). Univariate and multivariate logistic regression analysis revealed that PSA( OR=1.025, P=0.001) and prostate volume( OR=0.984, P=0.001)were two independent factors for the detection rate of prostate cancer between two biopsy ways( P<0.05). The effect of age on the detection rate of PCa in the transperieal group was significantly lower than that of the transrectal group( OR=0.037, P=0.238 vs. OR=0.053, P=0.002). Conclusion:The transperieal biopsy could find more PCa than the transrectal biopsy. PSA level and prostate volume could affect the detection rate of cancer between two prostate biopsy ways.

The aim of this paper is to explore the practical measures of integrating “ideological and political course” into “Psychiatry”. “Ideological and political course” is a key measure to foster character and civic virtue in colleges and universities， and a crucial link of “three -full education”. Based on the characteristics of the course “Psychiatry” and the practical experience of the course “ideological and political work” in the faculty of mental health， North Sichuan Medical College， this paper puts forward the strategies of implementing “ideological and political course” from four aspects： improving teachers’ understanding and practical ability of “ideological and political course”， constructing the integration point of ideological and political course in “Psychiatry”， choosing the teaching methods of “ideological and political course” and evaluating the teaching effect， thus providing references for the implementation of “ideological and political course” in the follow-up professional courses.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method:BALB/c mice were randomly divided into six groups according to their weight grade： normal group， HCoV-229E infection group， cold and damp group， a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome， and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar （0.128，0.064 g·kg^-1） was administrated by gavage for 3 days from the day of infection. The observation indexes included： general state observation of mice， inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in the lung tissues of mice. Serum levels of motilin（MTL）， gastrin （GAS）， and cytokines interleukin（IL）-10，IL-6， tumor necrosis factor-α（TNF-α）and interferon-γ（IFN-γ） in lung tissue of mice were determined by enzyme-linked immunosorbent assay（ELISA）. The percentages of CD4⁺ T lymphocytes，CD8⁺ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group， model group mice lung index increased significantly （P<0.01）， nucleic acids significantly increased expression of lung tissue in mice （P<0.01）， significantly higher serum MTL content in mice， GAS content significantly decreased （P<0.05，P<0.01）， lung tissue cells in the immune factor TNF-α， IL-10 and IL-6 were significantly increased （P<0.01）， peripheral blood lymphocyte CD4⁺ T cells in mice， The percentages of CD8⁺ T cells and B cells were significantly decreased （P<0.01）. Compared with model group， in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower （P<0.01）， the lung tissue of mice express nucleic acid decreased significantly （P<0.01）， MTL content decreased significantly （P<0.01）， the lung tissue of mice in the IL-6， IL-10， the TNF-α， IFN-γ levels were significantly lower （P<0.01）， in vitro cultivation bezoar high dose group can significantly increase the CD4⁺ T cell percentage （P<0.05）， in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation， pulmonary interstitial edema， as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice， improving the pathological damage of the lung tissue， adjusting the immune effective and inhibiting the clearing of inflammatory factors， and to provide a laboratory basis for clinical medication.

Objective:To verify the accuracy of the International Warfarin Pharmacogenetics Consortium(IWPC)model, identify the effects of genetic and clinical factors on steady-state doses of Warfarin, and establish a Warfarin dose prediction model for the Han-Chinese population aged 75 years and over under the guidance of pharmacogenetics.Methods:A total of 544 Han-Chinese patients receiving Warfarin therapy for atrial fibrillation were divided into two groups: those aged 75 years and over(n=164)and those aged below 75 years(n=380). Data for the whole population and the two age groups were each substituted into the IWPC prediction model for accuracy verification.Demographic and clinical characteristics of 164 patients aged 75 years and over were recorded, and the genotypes of CYP2 C9 and VKORC1- G1639 A were detected by polymerase chain reaction.A new pharmacogenetic-guided dosing algorithm for the elderly was obtained by stepwise multiple linear regression.The accuracy of the new model was compared with that of the IWPC model. Results:The predictive accuracy of IWPC for steady-state dosing of warfarin was 35.47% in all subjects, 33.75% in 164 subjects aged below 75 years, and only 28.70% in subjects aged 75 years and over, respectively.In 164 subjects aged 75 years and over, three genotypes of *1/*1, *1/*3 and *1/*2 were detected in CYP2 C9 polymorphism, and the CYP2 C9*1/*1 genotype was the most common one, with a frequency of 87.80%(144/164), followed by the CYP2 C9*1/*3 genotype, at 11.59%(19/164). GG, GA and AA genotypes were detected in VKORC1 polymorphism, among which the AA genotype accounted for 82.32%(135/164)and the GG genotype accounted for only 1.83%(3/164). The steady state dose for Warfarin in patients with the wild-type CYP2 C9*1/*1 was higher than in those with the heterozygote CYP2 C9*1/*3 and *1/*2(3.18±0.86 mg/d vs.2.27±0.51 mg/d, t=5.637, P<0.05). Patients with a mutant homozygotic AA genotype of VKORC1 required lower maintenance doses than those with the heterozygotic GA and GG genotypes(2.96±0.66 mg/d vs. 3.59±1.43 mg/d, t=-2.092, P<0.05). The steady-state dose for Warfarin in subjects carrying CYP2 C9 (*1/*2 or *3)and VKORC1 (GA and GG)was(2.00±0.63)mg/d, lower than in those carrying other genotype combinations( P<0.05). We established a new Warfarin dosing algorithm for elderly subjects aged 75 years and over containing height, creatinine, amiodarone usage, CYP2 C9 and VKORC1 mutants, and the accuracy of the new model was 56.0%, which could explain 56.0% of individual variability, and the accuracy was higher than that of the IWPC algorithm(56.0% vs. 45.8%, P<0.05). Conclusions:Polymorphisms of CYP2 C9 and VKORC1 clearly affect the steady-state dose for Warfarin in the elderly Han-Chinese population aged 75 years and over.A combination of pharmacogenomics with clinical factors can better guide warfarin medication in Han-Chinese people aged 75 years and over.

Objective:To improve awareness about infratentorial dural arteriovenous fistula (DAVF).Methods:Three cases of DAVF in the First Affiliated Hospital of Soochow University from September 2017 to September 2019 were retrospectively analyzed in terms of clinical features, cerebrospinal fluid (CSF) analysis, brain imaging and treatment, and followed up through telephone call.Results:Case 1: A 43-year-old woman, in chronic but acute aggravated course, presented with weakness of both lower limbs and urination and defecation dysfunction. Brain magnetic resonance imaging (MRI) revealed abnormal signal in medulla. CSF analysis demonstrated aquaporin-4 antibodies positive. Misdiagnosed as neuromyelitis optica spectrum disorders, the treatment was poor. Then digital subtraction angiography (DSA) showed DAVF at the left infratentorial area, and endovascular treatment was operated. Relapse was not observed in two-year follow up. Case 2: A 57-year-old woman, in chronic progressive course, mainly manifested as memory loss, but progressed with dysphagia, fever, coma. Treatment as “central nervous infection” was poor. Then DSA showed DAVF at the bilateral transverse-sigmoid sinus area, and endovascular treatment was operated with embolized partial fistulas. The patient died from lung infection within two months. Case 3: A 52-year-old man, in subacute course, was treated in the Gastroenterology Department with clinical manifestion of stubborn nausea and vomiting. Brain MRI revealed abnormal signal in medulla, with prominent vessel flow voids nearby. Then DSA showed DAVF at the craniocervical junction, and endovascular treatment was operated. Relapse was not observed in six-month follow up.Conclusions:DAVF has a variety of clinical manifestations, and infratentorial DAVF can manifest as acute neurological dysfunction involving the brain stem, cerebellum, spinal cord, which may be easily misdiagnosed. When brain MRI showed intracranial abnormal signal, the possibility of DAVF should be considered. DSA remains the gold standard to diagnose DAVF. Endovascular embolization is the main treatment of infratentorial DAVF at present. Prognosis depends on clinical presentation and fistula classification.

Objective: To explore the effect of hypoxia inducible factor 1α (HIF-1α) gene silencing in rat bone marrow mesenchymal stem cells (BMMSCs) under mechanical distraction on the expression of bone sialoprotein (BSP) and osterix and to provide a new idea for repairing bone defects with BMMSCs. Methods : The shRNA sequence was designed according to the rat HIF-1α gene, and the pGMLV-SC1RNAi lentiviral vector was cloned after PCR amplification. After screening positive clones and identifying competent transformed cells by sequencing, 293T cells were packaged and titered, rat BMMSCs were transfected and cultured in vitro. Clones with stably silenced HIF-1α expression were screened by inverted fluorescence microscopy. The RNAi response experiment was divided into four groups: the blank control group, the HIF-1α shRNA group, the negative control group, and the response group. Western blot was used to detect the expression of HIF-1α protein in the four groups to verify the response of the target genes and exclude off-target effects. A Flexcell FX-5000T cell stress loading system was used to intervene in the mechanical stretch of the cells. qRT-PCR and Western blot were used to detect the expression of BSP and osterix in the blank control group, HIF-1α shRNA group, and negative control group. Results: The HIF-1α shRNA lentiviral vector was successfully constructed. The results of the RNAi response showed no significant difference in the expression of HIF-1α between the response and the blank control group (P > 0.05). The recombinant lentivirus could effectively silence HIF-1α in BMMSCs. After mechanical distraction of the BMMSCs, compared with the blank and negative control groups, the HIF-1α shRNA group showed significantly increased mRNA and protein expression of the bone-related factors BSP and osterix (P < 0.05); there was no significant difference in the mRNA and protein expression of BSP or osterix between the blank and negative control groups (P > 0.05). Conclusion Silencing HIF-1α in BMMSCs under mechanical distraction can promote the expression of BSP and osterix.