With more and more international medical students studying medicine in China,international medical education becomes an important part of Chinese medical education.By integration of basic and clinical pharmacology,the teaching mode of theory,experiment,problem based learning and seminar was applied to the international medical students according to their characteristics and specificity.75％,80％ and 70％ of the total international medical students respectively passed the two consecutive final exams and one pharmacology group exam.Through the teaching of pharmacology for international medical students major in MBBS,this author aims to explore the teaching mode of pharmacology for the international medical students.

Objective To establish a modified dynamic 99Tcm-pertechnetate salivary gland scintigraphy(SGS) method,and to evaluate the value in the diagnosis of Sj(o)gren's syndrome(SS) by comparing SGS with labial gland biopsy (LGB).Methods A total of 204 patients (21 males,183 females,age range 20-85 years) with suspected SS who underwent the modified dynamic SGS and LGB were enrolled in this prospective study.Uptake ratio (UR) and excretion fraction (EF) of the left parotid gland (LPG),the right parotid gland (RPG),the left submandibular gland (LSG) and the right submandibular gland (RSG)were calculated.Two-sample t test was used for data analysis.The sensitivity,specificity,accuracy of the modified dynamic SGS and LGB were calculated,and x2 test was used for data analysis.Results SS was confirmed in 113 patients,including 79 patients with primary SS and 34 patients with secondary SS.SS was excluded in 88 patients.The UR and EF of the SS group (LPG:1.95±1.04 and (52.2±19.5)％,RPG:1.96±1.06 and (55.0±21.1)％,LSG:2.65±1.12 and (25.9±14.1)％,RSG:2.72±1.30 and (29.7± 14.7) ％) were significantly lower than those of the non-SS group (LPG:3.08± 1.10 and (65.9± 12.7) ％,RPG:3.26±1.16 and (66.4±12.6)％,LSG:3.71±1.31 and (43.2±12.3)％,RSG:3.74±1.39 and (46.6± 11.5) ％;t=4.40-9.00,all P＜0.05).The sensitivity,specificity,accuracy of the modified dynamic SGS were 99.1％ (112/113),72.7％ (64/88),87.6％ (176/201),respectively,while those of LGB were 83.2％ (94/113),96.6％ (85/88),89.1％ (179/201),respectively.The sensitivity and specificity of SGS method were significantly different from those of LGB (x2 =15.9,17.5,both P＜0.05).Conclusions The modified dynamic SGS can reduce the acquisition time and has a high sensitivity for SS.When combined with LGB,it will improve the diagnostic accuracy for SS.

Objective To evaluate transport efficiency and safety by process management during the handover of patients with tracheal intubation post-operation. Methods Prospective studies were performed between patients with or without process management during the handover. The time of handover were recorded and compared. The difference between systolic and diastolic blood pressure, heart rate, and arterial oxygen saturation were also recorded and compared. The adverse events during the handover were also investigated. Results It costed less time in the handover of patients under process management with significant difference[(4.75±0.54) min vs. (7.05±0.88) min, t=-17.21, P<0.01]. The incidence rate of harmful cases in the handover of patients under process management was significantly declined than that without process management[ 1.67%(1/60) vs. 13.33%(8/60),Χ2=4.324 3,P<0.05 ]. Conclusions Process management may facilitate the handover of patients with tracheal intubation post-operation and improve its safety.

Objective To evaluate and compare the diagnosis and treatment quality of 15 tertiary hospitals in Beijing with the quality-evaluation model of STEMI.Methods The quality-evaluation model has been formatted with the document analysis method and expert consultation method,with the indicators weighted by analytic hierarchy process.By collecting the data of 15 hospitals,we can get the values of indicators,then synthetically evaluate and compare the diagnosis and treatment quality at these 15 hospitals with the method of WRSR.Results In the diagnosing and treating the cases of STEMI at the hospitals,gaps are found between the clinical guidelines and the tests,patient evaluation,reperfusion treatment and drug therapy,with some indicators falling even below 22％.Also,there are significant differences in the diagnosis and treatment quality among hospitals.All hospitals are consistent on the five dimensions-tests,patient evaluation,reperfusion treatment,drug therapy and prognosis.Conclusion The quality-evaluation model of STEMI can comprehensively reflect the diagnosis and treatment quality of cardiovascular medicine,and partly reflect hospital's overall management level,so as to provide operating methods in improving hospital diagnosis and treatment quality.

Objective To explore the early diagnostic value of carcino-embryonic antigen (CEA) immunocytochemistry examination combined with laser scanning confocal microscope (LSCM) in the patients with meningeal carcinomatosis (MC).Methods The patients were divided into experimental group (patients with MC) and control group (patients without MC).Thermo electron corporation shandon cytospin 4 centrifuge was used in the cytologic examination of cerebrospinal fluid (CSF),whose function was to produce a monolayer of cells onto a glass slide from CSF.Giemsa staining was used in 42 cases.The CEA immunocytochemistry staining was used in 29 cases and 20 controls.The double immunofluorescence staining was used in 17 cases and 20 controls.SP staining method was used in the CEA and the results were observed under the light microscope.Nuclear DNA and CEA were stained with fluorescent probe DAPI and Cy5 respectively and the results of double immunofluorescenee staining were observed by the laser scanning confocal microscope.Results There was a high positive rate in cytologic examination of CSF,and malignant cells were found in all of 42 cases for repeated CSF testing.The positive rate of routine CSF cytologic examination and CEA immunecytochemistry examination was 85.7% (36/42) and 79.3% (23/29) respectively in the first CSF specimens.There were 17 cases using double immunofluorescence staining and observed by LSCM,and the positive rate was 13/17.Compared with experimental group and control group,fluorescent value both nuclear DNA (CEA(+) 1694.04±478.06,CEA(-)1543.04±364.71,control group 603.72±178.04,t=21.386,23.144,both P<0.01) and CEA (CEA(+)1407.04±275.30,control group 202.51±54.05,t=42.934,P<0.01) were significantly different.Conclusion Immunocytochemistry examination of CSF is an important early qualitative diagnosis method for MC.LSCM improved the level of locating,qualitative and quantitative diagnosis of MC.

Objective:To observe the clinical effect of oxycodone hydrochloride sustained-release tablets in the treatment of pain in advanced malignant tumors.Methods:One hundred patients with advanced malignant tumor pain admitted to Hangzhou Cancer Hospital from June 2017 to August 2018 were selected.They were grouped according to the admission order.The observation group (50 cases) implemented oxycodone hydrochloride sustained-release tablets.The control group (50 cases) was treated with morphine sulfate sustained-release tablets.The onset time, analgesic effect, adverse reaction and KPS score were compared between the two groups.Results:The onset time [(0.79±0.22)h] of the observation group was significantly shorter than that of the control group [(2.56±1.02)h]( t=11.995, P<0.05). The total effective rate of analgesia in the observation group (98.00%) was higher than that in the control group(74.00%)( t=11.960, P<0.05). The incidence of adverse reactions in the observation group was 4.00%(2/50), which was lower than 30.00%(15/50) in the control group, (χ 2 =11.977, P<0.05). The KPS score after treatment in patients with advanced malignant tumor pain in the observation group[(79.45±1.23)points] was higher than that in the control group[(65.34±1.92)points] ( t=43.756, P<0.05). Conclusion:Oxycodone hydrochloride sustained-release tablets have significant effects in the treatment of advanced malignant tumor pain, and it is safe.

Objective To investigate the application value of indomethacin in pancreatitis after endoscopic retrograde cholan-giopancreatography(ERCP)in the patients with choledocholithiasis.Methods Ninety elderly patients with choledocholithiasis were divided into the observation group and control group according to the random number table method,45 cases in each group.The two groups received the therapy of conventional ERCP scheme.The control group used diazepam,pethidine and anisodamine before op-eration.The observation group was preoperatively added with indomethacin on the basis of the control group.The therapeutic effects were analyzed and compared between the two groups.Results The number of intraoperative gastric peristalsis and operation time in the observation group were significantly lower than those in the control group(P<0.05).The level of serum amylase at postoperative 6,24 h in the observation group was significantly lower than that in the control group(P<0.05).The level of serum CRP and MMP-9 at postoperative 24 h in the observation group was significantly lower than that in the control group(P<0.05). The incidence rates of pancreatitis and hyperamylasemia in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Indomethacin can effectively reduce the number of intraoperative gastric peristalsis,postoperative hy-peramylasemia and incidence rate of acute pancreatitis,reduces the level of serum inflammatory factors,and has fewer adverse reac-tions,which is worthy of application.

Objective To define the effect of hypothyroidism on oxidative stress,p38 and c-Jun N-terminal kinases (JNK) mRNA expression in testicular mitochondria of male rats,and to explore the mechanism of hypothyroidism on reproduction.Methods According to body weight (240-270 g),30 male Wistar rats were divided into control group (C group,1 ml/kg normal saline by intragastric administration),low-dose group (L group,0.1 mg/kg propylthiouracil 1 ml/kg by intragastric administration) and high-dose group (H group,10.0 mg/kg propylthiouracil 1 ml/kg by intragastric administration),10 rats in each group,body mass was weighed once every 3 days.After 60 days,all rats were killed.The levels of thyroid hormones [total triiodothyronine (TT3),total thyroxine (TT4),and thyroid stimulating hormone (TSH)] were measured by radioimmunoassay.The activities of superoxide dismutase (SOD) and catalase (CAT) in the testicular mitochondria were determined with spectrophotometric assay.The mRNA expression levels of p38 and JNK in testicular mitochondria were detected by real-time quantitative PCR.Results The weights of H group in 30 and 60 days [(265.73 ± 5.10),(253.72 ± 5.09) g] were significantly decreased in comparison with those of C group [(344.62 ± 4.69),(395.33 ± 8.36) g] and L group [(333.66 ± 3.53),(386.08 ± 7.70) g,P ＜0.05].While,testis organ coefficient of H group [(1.20 ± 0.05) g/100 g] were significantly increased compared with those of L group [(0.93 ± 0.03) g/100 g] and C group [(0.88 ± 0.03) g/100 g,P ＜ 0.05].The serum levels of TT3 [(0.39 ± 0.01) nmol/L] and TT4 [(15.47 ± 1.21) nmol/L] in H group were found to be significantly decreased compared with those of C group [(0.86 ± 0.07),(45.56 ± 1.52) nmol/L] and L group [(0.79 ± 0.06),(39.02 ± 1.33) nmol/L,P ＜ 0.05];whereas the level of TSH [(0.65 ± 0.09) mU/L)] was increased in comparison with those of the C group [(0.18 ± 0.06) mU/L] and L group [(0.27 ± 0.05) mU/L,P ＜ 0.05].In addition,the level of SOD in H group [(60.37 ± 3.14) U/mg prot] was decreased compared with that of C group [(75.18 ± 6.13) U/mg prot,P ＜ 0.05];the level of CAT in H group [(1.46 ± 0.25) U/mg prot] and L group [(1.67 ± 0.39) U/mg prot] decreased significantly compared with that of C group [(3.79 ± 0.44) U/mg prot,P ＜ 0.05].And compared with C (1.000 0 ± 0.000 0) and L (1.114 2 ± 0.124 1) groups,p38 mRNA expression in H group (1.387 4 ± 0.122 0) was significantly increased (P ＜ 0.05).However,there was no significant change in JNK mRNA expression between groups (F =0.95,P ＞ 0.05).Conclusion Hypothyroidism may induce oxidative stress of testicular mitochondria leading to the change of p38 cell signal path and then damage the reproductive system in male rats.

Brucella is an intracellular pathogen that invades a host and settles in its immune cells; however, the mechanism of its intracellular survival is unclear. Modification of small ubiquitin-related modifier (SUMO) occurs in many cellular activities. E2 conjugating enzyme 9 (Ubc9) is the only reported ubiquitin-conjugating enzyme that links the SUMO molecule with a target protein. Brucella's intracellular survival mechanism has not been studied with respect to SUMO-related proteins and Ubc9. Therefore, to investigate the relationship between Brucella melitensis 16M and SUMO, we constructed plasmids and cells lines suitable for overexpression and knockdown of SUMO1 and Ubc9 genes. Brucella 16M activated SUMO1/Ubc9 expression in a time-dependent manner, and Brucella 16M intracellular survival was inhibited by SUMO1/Ubc9 overexpression and promoted by SUMO1/Ubc9 depletion. In macrophages, Brucella 16M-dependent apoptosis and immune factors were induced by SUMO1/Ubc9 overexpression and restricted by SUMO1/Ubc9 depletion. We noted no effect on the expressions of SUMO1 and Ubc9 in B. melitensis 16M lipopolysaccharide-prestimulated mouse RAW264.7 macrophages. Additionally, intracellular survival of the 16M△VirB2 mutant was lower than that of Brucella 16M (p < 0.05). VirB2 can affect expression levels of Ubc9, thereby increasing intracellular survival of Brucella in macrophages at the late stage of infection. Collectively, our results demonstrate that B. melitensis 16M may use the VirB IV secretion system of Brucella to interact with SUMO-related proteins during infection of host cells, which interferes with SUMO function and promotes pathogen survival in host cells.
Animals ; Apoptosis ; Brucella melitensis ; Brucella ; Immunologic Factors ; Macrophages ; Mice ; Plasmids

The rapid changes in the research and development environment of new anti-tumor drugs in China have brought various challenges to drug innovation. How to explore the clinical advantages of new drugs in the early phase, and design scientific, reasonable and efficient pivotal clinical trials for drug registration accordingly, is one of the key challenges. This article takes innovative new drugs for hematological malignancies as an example, comprehensively elaborates the considerations on the timing for entering the pivotal clinical trial and the key elements of the trial design from the perspective of clinical reviewers.