Objective To explore the methods of labeling exogenous microglia with superparamagnetie iron oxide(SPIO)particles,and to monitor the labeled cells after transplantation into the normal rat and Alzheimer's disease(AD)model rat with MR scanning.Methods Microglia was labeled with SPIO particles by using transfection agent,hemagglutinating virus of Japan envelope(HVJ-E).Then the microglias which were labeled with SPIO were injected into the internal carotid artery of normal rat (n=5)and AD model rat(n=5).Three days after transplantation,follow-up serial T2*-weighted gradient-echo MR imaging was performed at 7.0T MRI system.MR images were correlated with histological findings.Results In the brain of normal rat,the labeled microglias were demonstrated as several dotty signalintensity decrease on T2*-weighted MR images.The dotty spots were sporadic around the brain.Histological analysis showed that most prussian blue staining-positive cells were well correlated with the area where a signal intensity decrease was observed in MRI.MR could detect the signal intensity change caused by a few labeled cells.In the brain of AD model rat,MR scan showed a well-defined hypointensity area in the region of Aβ42 iniection.Signal intensity decrease was not obvious in the region of saline injection.The number of iron-positive cells(454±47)/mm2 at sites of Aβ42 injection was much higher than that(83±13)/mm2 of saline injection(P＜0.05). Conclusion MR can be used as a non-invasive means of detecting transplanted labeled microglia in vivo,with the potential for future clinical application in cell therapy of AD.

Objective To study the mechanism of miR?200c in regulating RMP7?induced increases of blood?tumor barrier(BTB)permeability by targeting Ras homolog gene family member A(RhoA). Methods Endogenous expression of miR?200c was detected by real?time PCR in hu?man cerebral microvascular endothelial cell line hCMEC/D3(ECs)after RMP7 treatment. miR?200c mimic and miR?200c inhibitor were transfect?ed into GECs(ECs with U87 glioma cells co?culturing),respectively. Transfection efficiency of miR?200c mimic and miR?200c inhibitor were de?termined by real?time PCR. HRP flux and TEER assays revealed BTB permeability. The protein expression level of RhoA was assessed by West?ern blotting. The distribution of RhoA was assessed by immunofluorescence microscopy. RhoA luciferase assays were performed using the Dual?Lucif?erase reporter assay system. Results RMP7 significantly induced a decrease in miR?200c expression in GECs of BTB. miR?200c mimic and miR?200c inhibitor were successfully transfected into GECs. Overexpression of miR?200c inhibited endothelial leakage and restored normal transendo?thelial electric resistance values. Simultaneously ,overexpression of miR?200c significantly reduced the protein expression level of RhoA. In addi?tion,immunofluorescence analysis revealed that the distribution of RhoA in the cytoplasm and nuclei of GECs were decreased in miR?200c mimic group. RhoA was one of the direct targets of miR?200c with the specific binding site being located at the seed sequence. The results of miR?200c si?lencing were opposite to that of the miR?200c overexpression group. Conclusion miRNA?200c regulated RMP7?induced increases in BTB perme?ability by targeting RhoA.

Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

Objective:To investigate the clinical efficacy of extended hepatectomy for hilar cholangiocarcinoma (HCCA) of Bismuth-Cor-lette typesⅢandⅣ(the longitudinal invasion degree along the biliary system is the main criteria). Methods:The clinical data of 61 patients with HCCA of Bismuth-Corlette types III and IV admitted in the Department of Hepatobiliary Surgery of the First Affiliated Hos-pital of Bengbu Medical College from January 2008 to May 2015 were analyzed retrospectively. Among the 61 cases, 22 underwent hepatectomy with half or over half of the liver removed or hepatic caudate lobectomy (regarded as the extended hepatectomy group), whereas 39 cases underwent irregular hepatectomy on the hepatic hilar region (regarded as the limited hepatectomy group). Results:Compared with those in the limited hepatectomy group, the patients in the extended hepatectomy group underwent longer duration of operation and experienced more bleeding during the procedure. The complication incidence rate for the extended hepatectomy group was lower than that for the limited hepatectomy group. No patient died during the perioperative period in the extended hepa-tectomy group, whereas two patients died in the limited hepatectomy group. Moreover, R0 resection was performed on 21 cases in the extended hepatectomy group, with a resection rate of (21/22) 95.5%, and on 20 cases in the limited hepatectomy group (P<0.05), with a resection rate of (20/39) 51.3%. Actuarial 1-, 3-, and 5-year survival rates were 77.27%, 36.36%, and 13.64%, respectively, in the extended hepatectomy group, and 69.23%, 20.51%, and 1.64%, respectively, in the limited hepatectomy group (P<0.05). Conclusion:Extended hepatectomy for patients with HCCA of Bismuth-Corlette typesⅢandⅣcould effectively increase the resection rates of R0 and the survival rate. Meanwhile, the prognosis of patients could be improved.

Drugs sharing similar therapeutic function may not bind to the same group of targets. However, their targets may be involved in similar pathway profiles which are associated with certain pathological process. In this study, pathway fingerprint was introduced to indicate the profile of significant pathways being influenced by the targets of drugs. Then drug-drug network was further constructed based on significant similarity of pathway fingerprints. In this way, the functions of a drug may be hinted by the enriched therapeutic functions of its neighboring drugs. In the test of 911 FDA approved drugs with more than one known target, 471 drugs could be connected into networks. 760 significant associations of drug-therapeutic function were generated, among which around 60% of them were supported by scientific literatures or ATC codes of drug functional classification. Therefore, pathway fingerprints may be useful to further study on the potential function of known drugs, or the unknown function of new drugs.
Drug Interactions ; Metabolic Networks and Pathways ; Pharmaceutical Preparations ; metabolism

Health literacy serves as the foundation of health for all. Hence the authors introduced the connotation and extension of health literate health care organization(HLHO) and related concepts. On such basis, the paper presented the construction method of HLHO from the perspective of health policy, healthcare organizations and inter-institutional cooperation, in order to improve the health literacy of the Chinese people and implement the Healthy China initiative(2019—2030).

Objective:To translate the health literate healthcare organization 10 item questionnaire(HLHO-10) into Chinese and examine its reliability and validity.Methods:The Chinese version of HLHO-10 questionnaire(HLHO-10-C) was developed by following the Brislin translation model of translation, back translation, cultural adaptation and questionnaire epistemological survey.Five experts and 1 071 medical staff from 24 healthcare organizations in Zhejiang province were selected to conduct the validity and reliability test of the HLHO-10-C.Results:The content validity indices at the item level and total questionnaire level of HLHO-10-C were from 0.8 to 1.0 and 0.96 respectively, and the results of the exploratory factor analysis showed good structural validity.Conclusions:HLHO-10-C proves adequate reliability and validity to serve as a tool for healthcare organizations in evaluating and becoming HLHO. It can also help the implementation of the Healthy China Initiative(2019—2030), which is a performance assessment mechanism for health education and promotion of healthcare providers and health care organizations.

Through consulting the ancient materia medica and medical books， combined with modern literature， this paper made a textual research on the name， origin， producing area， harvesting time and processing method of Piperis Kadsurae Caulis， in order to provide basis for the development of the famous classical formulas containing this herb. According to textual research， it is shown that the earliest name for Piperis Kadsurae Caulis as medicine was Nanteng in Bencao Shiyi， and there were other names such as Dinggongteng and Shinanteng in the ancient materia medica. The name of Haifengteng should appear in the Ming dynasty. Before the Song dynasty， the origin of Piperis Kadsurae Caulis was probably derived from caulis of Piper wallichii. After the Song dynasty， the main origins should be some species in Piper， such as P. kadsura and P. hancei， and its origin in the successive editions of Chinese Pharmacopoeia was only P. kadsura. Combining the original plant research， market survey and distribution of wild resources， it is suggested that the Haifengteng used in the famous classical formulas apart form the P. kadsura， the P. hancei should be add as original plant. Due to climate change and the heat-loving habit of Piper， the producing area of Haifengteng gradually moved from the Qinling Mountains to the southern areas rich in Piper， and Quanzhou area of Fujian province has been recommended since the Ming dynasty. The harvesting period of Piperis Kadsurae Caulis is from July to August in the lunar calendar， the above-ground parts are dried by removing fibrous roots， thin stems and leaves. In the past dynasties， there are few records on the processing of this herb， so it is suggested that Piperis Kadsurae Caulis in famous classical formulas without special processing requirements should be used as raw products.

OBJECTIVE To determine the contents of N-nitroso impurities in raw materials/formulations of propranolol， metoprolol， atenolol， esmolol and bisoprolol， and clarify the attention threshold. METHODS Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q/Orbitrap HRMS）was adopted. An ACE Excel 3 C18-AR column was used for the separation and a mixture of 0.2% formic acid solution with 0.01 mol/L ammonium acetate and methanol was employed as the mobile phase by gradient elution， at a flow rate of 0.60 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The heated electrospray ionization source was employed in the positive full mass spectra-selected ion monitoring mode. The contents of N-nitroso impurities in raw materials/formulations of 15 batches of β-blockers from 10 manufacturers were determined by this method. Discovery Studio software was applied to predict the toxicity of the impurities and estimate the attention threshold. RESULTS Among 5 kinds of β-blockers， the linear ranges of N-nitroso propranolol， N-nitroso metoprolol， N-nitroso atenolol， N-nitroso esmolol and N-nitroso bisoprolol were 1.01-503.38， 1.02-508.38， 0.97-483.63， 1.11-554.27 and 1.05-523.92 ng/mL， respectively （r＞0.999）. The limits of quantitation were 1.04， 0.25， 0.05， 0.55 and 1.05 ng/mL， and the limits of detection were 0.52， 0.08， 0.02， 0.17 and 0.52 ng/mL， respectively. RSDs of precision， reproducibility， recovery， stability and durability tests were all lower than 7.5% （n＝6 or n＝5）. Among the 15 batches of samples， except for 1 batch， N-nitroso propranolol （1.07-8.91 ng/mg）， N-nitroso metoprolol （1.43-3.37 ng/mg）， N-nitroso atenolol （1.33 ng/mg）， N-nitroso esmolol （0.19 ng/mg） and N-nitroso bisoprolol （1.27 ng/mg） were detected in all other batches. According to predictions， the above 5 impurities had varying degrees of reproductive toxicity， mutagenicity and carcinogenicity， with attention thresholds of 1.0， 0.4， 4.3， 0.2 and 46.7 ng/mg， respectively. CONCLUSIONS The established method is simple， rapid， sensitive and specific， the estimated attention thresholds are clear， which can be used for the control of N-nitroso impurities in various β-blockers.

Through consulting the ancient herbal books and modern literature， this paper has carried out the textual research on the name， origin， place of origin， harvesting and processing， and other contents of Bruceae Fructus， combed its ancient and modern medicinal history， so as to provide reference for the development of famous classical formulas containing Bruceae Fructus. Through the herbal textual research， It can be verified that， since the Qing dynasty， Bruceae Fructus has been recorded in the materia medica， most of the materia medica in previous dynasties took Bruceae Fructus as its proper name， and Laoyadan， Kushenzi and Yadanzi as the aliases. The main origin of Bruceae Fructus is Brucea javanica， its medicinal part is the fruit， which is harvested from August to October every year， the fruit can be harvested when it is ripe. Bruceae Fructus was first distributed in Fujian， Guangdong and Guangxi， and gradually expanded to the south of China with the change of time. The traditional processing method of Bruceae Fructus is mainly to remove the shell and kernel， and remove the oil by frosting. The 2020 edition of Chinese Pharmacopoeia stipulates that its processing method is to remove the shell and impurities. Based on the research results， it is suggested that the dried mature fruit of B. javanica should be selected for the development of famous classical formulas containing this herb， and the raw products can be used if the original formula does not specify the processing requirements.