Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

[Objective] To summarize the clinical manifestations, pathological characteristics, treatment options and prognosis of the world's first case of prostate ductal adenocarcinoma (PDA) complicated with prostate mucinous adenocarcinoma (PMA). [Methods] The clinical and follow-up data of a patient with PDA and PMA treated in Zhongnan Hospital of Wuhan University were retrospectively analyzed, and relevant literature in PubMed and CNKI databases was retrieved. [Results] The patient sought medical attention due to dysuria, frequent urination, urinary urgency and urinary pain for more than half a year, and was admitted to hospital 3 times in total.The initial diagnosis upon the first admission was benign prostatic hyperplasia complicated with prostatic abscess.After 2 months, the patient was readmitted due to worsening symptoms, received transurethral bladder neck incision+ cystoscopy+ transurethral plasma resection of the prostate, and postoperative diagnosis confirmed PDA with local PMA.Three months after surgery, the patient had bleeding.After auxiliary examinations revealed extensive metastasis, he received hormonal therapy.After 9 months, the patient died due to multiple lung metastases. [Conclusion] Early diagnosis has a significant impact on the treatment and prognosis, but there have been no previous reports of PDA combined with PMA, so the lack of specific biomarkers in the early stage has led to missed diagnosis or misdiagnoses.There is no specific treatment for PDA with PMA. Radical prostatectomy was not satisfactory in the treatment of this case.

Objective　 : To evaluate the implementation, application, and problems and suggestions of the Radiation Shield- ing Requirements in Room of Radiotherapy Installations—Part 1: General Principle (GBZ/T 201.1—2007) through a survey of relevant personnel in radiation health technical service institutions, and to provide a scientific basis for further revision and implementation of this standard. Methods: A questionnaire survey was conducted among randomly selected per- sonnel in radiation health technical services across China, which mainly investigated the awareness, training, application, and revision suggestions related to the GBZ/T 201.1—2007. The results were aggregated and analyzed. Results: A total of 184 evaluation questionnaires on the GBZ/T 201.1—2007 were collected from technical service staff in 25 provinces. Among the responders, 64.1% thought that the standard had been widely applied; 91.8% thought that the standard could meet work needs; only 54.3% ever received relevant training on the standard; 68.5% used the standard once or more per year; 33.7% thought that the standard needed to be revised. Conclusion The personnel in radiation health technical services have a high awareness rate of the GBZ/T 201.1—2007 and its contents, but their familiarity with and application of the standard need to be improved. Relevant departments should strengthen the training and promotion of the standard, and part of the standard should be revised.

Predicting the protein binding rate of drugs in plasma is helpful to us in understanding the pharmacokinetic characteristics of drugs, with much value of reference for early research on drug discovery. In this study, plasma protein binding rate information of 2 452 clinical drugs were collected.Two pieces of software, Molecular Operating Environment (MOE) and Mordred, were used to calculate molecular descriptors, which were used as input features of the model.Extreme gradient boosting (XGBoost) algorithm and random forest (RF) algorithm were then used to build a machine learning model.The results showed that, compared with MOE, the prediction performance of the constructed model was better using the molecular descriptor calculated by Mordred as the input of the model.The prediction performance results of the model constructed using the XGBoost algorithm and the RF algorithm were similar, and the R2 of the optimal model were both 0.715.According to the research results, it can be concluded that the drug plasma protein binding rate is closely related to some physical and chemical properties of the drug molecule, such as water solubility, octanol/water partition coefficient and conjugated double bonds.Using these parameters to predict the plasma protein binding rate of drugs has the advantages of convenience and efficiency, which can provide reference for related pharmacokinetic studies.

Objective To develop measurement methodology using film for the positioning accuracy of MLC leaves in IMRT.Methods The solid water phantom of 30 cm x 30 cm was scanned and the scanned images were transferred to TPS for treatment plan formulation.The five MLC strip picket fence pattern was formed by MLC leaves,each 3.0 cm long × 6.0 mm wide.The separation between strip and strip is 3.0 cm.SAD is 100 cm at dmax for 6 MV X-ray,with 250 MU per MLC strip.EBT2 radiochomic film was put on the phantom for delivery of IMRT,for each MLC strip.The present study focused on 30 accelerators of Varian,Elekta and Siemens designs at 27 hospitals with highly skilled physicists all over Jiangsu,Sichuan,Hubei and Henan provinces.The study was conducted in the same way as used in international multi-radiotherapy center (IMRC).The irradiated films were sent respectively to IAEA dosimetry laboratory and external audit group (EGA) of China for measurement,analysis and calculation.Results According to IAEA requirements,the differenc of film-measured and TPS-planned of MLC leaf position for each strip should be within ±0.5 mm.China had participated in the research of IMRC,with the result of 0.3,0.2,0.0,-0.1,and-0.2 mm,respectively.For 30 accelerators in four provinces involved in the study,the IAEA's verification results of MLC leaf position were within 0.6-1.0 mm for 5 accelerators and within ± 0.5 mm for other 25 ones.Whereas the verification results of EAG were within 0.6-1.0 mm for 6 accelerators and within ±0.5 mm for other 24 ones.According to IAEA requirements,the film-measured MLC leaf position deviation for each pair of leaves and average all pairs of leaves should be within ±0.5 mm.China had participated in IMRC's research,with the measured result being 0.04 mm.The verification result of EGA for 30 accelerators showed the measured MLC leaf position deviations were all ＜0.3 mm per strip,consistent with IAEA requirements.The IAEA's result showed the measured deviations of MLC leaf position for 29 accelerators were within ±0.5 mm,with only other one being-0.7 mm not consistent with the IAEA requirements.As required by IAEA,the difference of film-measured difference of MLC opening width should be within ±0.75 mm between each pair and average all pairs of leaves.China's result in research of IMRC showed the difference of minimum width to mean width was-0.2 mm whereas the difference of maximum width to mean width was 0.4 mm.For 30 accelerators involved in IAEA'verification study,the measured result shown that the difference between maximum and average of filmmeasured of MLC leaf width,and between minmum and average,were within ± 0.75 mm for 24 accelerators,in line with the IAEA requirements.For other 6 ones,the values were beyond ±0.75 mm,not in line with the IAEA requirements.For the verification result of EAG,the difference between maximum and average widths and between minmum and average widths for 25 accelerators were within ±0.75 mm as required by IAEA,whereas for other 5 ones the value were beyond ±0.75 mm,not consistent with IAEA requirements.The standard deviation of film-measured MLC opening width between each pair and average all pairs should be within 0.3 mm as required by IAEA.China's IMRC result was 0.12 mm.The verification result of IAEA shown the standard deviation of MLC opening position were ＜0.3 mm for 26 accelerators and ＞ 0.3 mm for other 4 accelerators.EAG verification result were the same as IAEA result.Conclusions The method using radiochromic film for measuring accuracy of MLC leaf position is convenient and practicable as a quality audit.It is suitable for quality verification in medical institutions owing to easy to post and repeated measurements.

Objective To discuss the impacts of stroke center construction upon therapeutic indexes for di-agnosing and treating patients with acute ischemic stroke. Methods Patients were divided into a control group (180 patients)and a formal group(245 patients)based on the time of stroke center construction.Patients in both groups were recorded time points in the course of diagnosis and treatment,and compared in number of cases with intravenous thrombolysis,number of cases receiving intravascular interventional therapies,DTN(door-to-needle) time,number of deaths,National Institutes of Health Stroke Scale(NIHSS)scores upon grouping,NIHSS scores after four weeks,NIHSS scores after 3 months,days of hospital stay and hospital charges.Results After the con-struction of the stroke center,time spent in different links were decreased.The number of cases with pure intrave-nous thrombolysis and DTN time(shorter than 60 min)were increased,and the difference were statistically signifi-cant(P<0.01).The number of cases who only received intravascular interventional therapies is increased,mean-while,DTN time was decreased,NIHSS scores after 4 weeks was increased and NIHSS scores after 3 months were also increased(P < 0.05)in these cases. No statistically significant differences existed in number of cases who were treated by bridging with intravenous thrombolysis in combination with intravascular interventional therapies and death cases(P=0.153,P=0.247).There were no statistically significant differences in days of hospital stay and hospital charges(P=0.152,P=0.406).Conclusions After the stroke center construction,it is helpful for significantly improving medical institutions′diagnosis and treatment of stroke,reducing time of such diagnosis and treatment in different links,shortening DTN time,increasing thrombolysis rate,improving patients′prognosis and bringing more benefits to patients with acute ischemic stroke by optimizing procedures for diagnosing and treating stroke.

Objective: To detect the possible molecular mechanisms of the formation of vessels that encapsulated tumor clusters (VETC) and identify the relationship between vimentin protein expression in endothelial cells and contrast-enhanced ultrasound characters in VETC (+ ) hepatocellular carcinoma (HCC). Methods: A total of 64 paraffin embedded HCC tissue samples were collected, all of which the tumor diameters were between 2 cm and 5 cm measured by the preoperative ultrasound. Immunohistochemistry staining for CD34 was used to detect the formation of VETC and the expressions of angiopoietin-2 (Ang-2) and vimentin were also determined. Human umbilical vein endothelial cells (HUVECs) were treated with 150 ng/ml recombinant human Ang-2 protein (rhAng-2) at various times and the protein expression of vimentin was detected by western blot assay. The contrast-enhanced ultrasound characters were also analyzed in both VETC (+ ) and VETC (-) HCC. Results: Tumor clusters encapsulated by vessels to form cobweb-like networks, which were identified as VETC phenotype, were observed in 27 HCC tissues (42.18%). In VETC (+ ) HCC tissues, Ang-2 was overexpressed in tumor cells and endothelial cells while vimentin was only upregulated in endothelial cells. With the treatment of 150 ng/ml rhAng-2 protein, the expression of vimentin in HUVECs was 0.878±0.102 and 0.918±0.092 at 12 h and 36 h, significantly upregulated when compared to the 0.322±0.061 at 6 h (P<0.01). In contrast-enhanced ultrasound, a crack and tendon-like filling character was observed in VETC (+ ) HCC during the arterial-phase, while the large scale and diffuse-like filling character was observed in VETC (-) HCC. The filling time of unit diameter in VETC (+ ) HCC was (3.95±0.22)s, significantly longer than (2.28±0.27)s of VETC (-) HCC (P<0.01). Conclusions The overexpressions of Ang-2 and vimentin are positively correlated with the formation of VETC and considered as potential therapeutic targets of VETC (+ ) HCC. The crack and tendon-like filling characters in arterial-phase of contrast-enhanced ultrasound indicates the VETC (+ ) HCC.

The course of pharmaceutical analysis for pharmacy undergraduate students in National University of Singapore and China Pharmaceutical University was compared, in terms of curriculum, lecturing, assessment and practical teaching.This study provides in-depth analysis by the lecturers from both universities,and can provide reference for teaching reform and course construction of pharmaceutical analysis.

Objective To evaluate the serum 25?hydroxy vitamin D3 level in patients with multiple sclerosis(MS)and normal healthy population,as well as the correlation between addition of oral 1,25?hydroxy vitamin D3 and the prevention of MS relapse and progression. Methods There were 60 cases in the relapsing?remitting MS(RRMS)group and 68 cases in the healthy group,respectively;and the differences in the sex,age, serum 25?hydroxy vitamin D3 level of the two groups were counted and evaluated. In addition ,the 60 cases of patients were divided randomly into the hormone therapy group and the addition treatment group ,with 30 cases in each group;the addition treatment group was added oral calcitriol soft capsules on the basis of the hormone therapy group;EDSS score evaluation was conducted on the two groups 6,12 and 24 months after treatment,the relapse frequency was counted after 24 months,and the relapse interval was calculated. Results The serum 25?hydroxy vitamin D3 levels in the patient group and the healthy group were(18.75 ± 8.35)nmol/L and(23.28 ± 9.31)nmol/L, respectively. There were statistically significant differences in the relapse frequency (P < 0.01),the relapse interval(P < 0.05),and EDSS score(after 24 months)(P < 0.05)between the hormone therapy group and the addition treatment group after treatment;while the differences in the EDSS score (after 6 months)(P = 0.457) and the EDSS score(after 12 months)(P = 0.118)between the two groups showed no statistically significance. Conclusion The serum 25?hydroxy vitamin D3 level in MS patients was markedly lower than that in normal healthy population. Addition of 1,25?hydroxy vitamin D3 contributes to preventing the relapse rate of MS and extending the relapse interval;in addition,maintaining long?term of oral 1,25?hydroxy vitamin D3 facilitates to delaying the progression of disabled disease.

Objective To construct the Hut78 cell line with EZH2 gene knocked into by CRISPR/Cas9 system. Methods The EZH2 expression vector pMD-18T-EZH2 with homologous arm and the sgRNA expression vector pSpCas9 (BB)-2A-Puro-sgRNA, which could cut the double stranded genomic DNA, were constructed, and the two vectors were co-transfected into Hut78 cells. Then the expression of EZH2 mRNA was detected by qPCR, and the expressions of EZH2 and H3K27me3 proteins were detected by Western blot assay. Results The pMD-18T-EZH2 and pSpCas9(BB)-2A-Puro-sgRNA recombinant vectors were confirmed by DNA sequencing. When Hut78 cells were transfected with the two recombinant plasmid, qPCR results showed that the expression of EZH2 mRNA was significantly increased, and Western blot analysis showed that the expressions of EZH2 and H3K27me3 proteins were significantly increased. Conclusion EZH2 gene is successfully knocked into Hut78 cells by CRISPR/Cas9 system.