University of Manchester who first introduced Problem based learning(PBL)to the UK medical education,and adopted this new curriculum in 1994.Notably,Cambridge and Oxford have always had a high proportion of student-centred and self-directed learning,and have therefore not introduced PBL.Other medical schools have followed the example of Manchester,now PBL has become the mainstream curriculum in British medical edacation.First,this article is going to introduce how PBL curriculum is structured at Manchester medical school,and then reflect and give some thoughts on its current practice.

Objective To investigate the role of TL1A in the generation and differentiation of peripheral blood Th17 in rheumatoid arthritis.Methods The peripheral blood mononuclear cells (PBMCs) of RA were isolated and stimulated with PHA in the presence or absence of TL1A.Naive CD4+ T cells from RA was cultured under Th17-polarizing conditions with or without TL1A.The percentage of Th17 was detected by flow cytometry (FCM) analysis.The DR3 expression on CD4+ T cells from PBMCs of RA patients and healthy controls (HC) were analyzed by using FCM.Data were analyzed with t test and U test.Results TL1A could significantly up-regulate the percentage of Th17 in PBMCs of RA [(7.5±2.3)％ vs (5.2±1.5)％,t=2.647,P＜0.05].Compared to the HC groups,TL1A could significantly induce Th17 differentiation from naive T cells [(37.7±1.9)％ vs (29.5±2.0)％,t=6.455,P＜0.05].The percentage of CD4+DR3+ T cell in PBMCs of RA [(0.56±0.87)％] was significantly higher than that of HC [(0.13±0.04)％,P＜0.05].The percentage of CD4+DR3+ T cell in PBMCs when stimulated with PHA was increased in RA patients,[(4.51±1.34)％ vs (1.11±0.29)％,t=2.915,P＜0.05],but no obvious increase in HC [(0.199±0.104)％ vs 0.072％±0.029)％,t=1.644,P=0.1988].Conclusion TL1A can promote the generation and differentiation of Th17 in the PBMCs of RA,and this effect may be mediated by the binding of TL1A with DR3.

Spontaneous miscarriage is the most common complication of the first trimester,among which 90% are early miscarriage that occurs prior to the 12th week of the gestation.Low progesterone level may be the main cause of the early miscarriage.This article discusses the incidence,pathogenesis,progesterone treatment,and prediction marker of early miscarriage to provide clues for the clinical work.

Objective To investigate the feasibility of differentiation between prostate cancer and prostatitis by using metabolic ratios provided by 3D 1H Magnetic Resonance Spectroscopic Imaging (MRSI). Methods Metabolic changes were evaluated in 42 voxels with prostate cancer and 30 voxels with prostatitis in the peripheral zone using MRSI. The results were based on the pathologic findings by biopsy. The (choline + creatine)/Citrate (CC/C) ratio and the changes of choline and citrate levels were evaluated in each voxel with cancer or prostatitis, t test was used to determine the power of the CC/C ratio in differentiation between prostate cancer and prostatitis. Results The CC/C ratio for cancer voxels (1.28±0.41) was significantly different from the ratio in the voxles with prostatitis (1.03±0.40), t=6.45, P<0.05, due to greatly increased choline level in the cancer voxels. When CC/C ratio of 0.8 was taken as the criteria for the diagnois of prostate cancer, the sensitivity, specificity and accuracy were 65.5%, 71.4% and 66.7%, respectively. Positive predictive value(PPV)and negative predictive value(NPV) were 90.5% and 33.3%, respectively. The CC/C ratio was higher than 0.86 in 66.7% voxels with prostatitis (20 voxels of total 30 voxels), which mostly depended on the level of choline. When citrate level was used as an auxiliary index to evaluate prostatitis (Cit/norm, Cit≥0.75), the misdiagnosis rate of prostate cancer was reduced to 26.6%(8 voxels of total 30 voxels). Conclusions The metabolic ratio of CC/C can be used to differentiate prostate cancer from prostatitis. The misdiagnosis rate is reduced when citrate is not or slightly decreased relative to normal citrate level (Cit/norm, Cit≥0.75).

OBJECTIVE:To explore the effects of dobutamine on hemodynamics,tissue perfusion and respiratory function in patients with ARDS caused by septic shock. METHODS:Totally 26 patients with ARDS caused by septic shock were given Dobu-tamine hydrochloride injection 5 μg/(kg·min) by continuous pump for 20 min ,increasing by 5 μg/(kg·min) every 20 min to 15μg/(kg·min)for 6 h. Mean artery pressure(MAP)maintained at about 65 mmHg during continuous pump. Hemodynamic index-es [HR,MAP,cardiac output(CO),stroke volume(SV),total end diastolic volume(GEDV),intrathoracic blood volume index (ITBI),extravascular lung water index (ELWI),systemic vascular resistance index (SVRI)],tissue perfusion indexes (norepi-nephrine,urine volume,blood oxygen saturation,blood lactate)and ventilator parameter indexes(positive breathing pressure,min-ute ventilation volume,respiratory rate,peak inspiratory pressure and plateau pressure)of all patients were recorded before medica-tion,6,24,48 h after medication. RESULTS:There were no statistical significances in HR,MAP,GEDV,ITBI,blood oxygen saturation,blood lactate and respiratory rate before and after treatment (P>0.05). CO,SV,urine volume and minute ventilation volume of all patients 6,24,48 h after medication were significantly higher than before medication,and those indexes increased gradually as medication time. ELWI,SVRI,positive breathing pressure,peak inspiratory pressure and plateau pressure of all pa-tients after medication were significantly lower than before medication,and those indexes decreased gradually as medication time, with statistical significance(P<0.05). The levels of norepinephrine in all patients 24,48 h after medication were significantly low-er than before medication and 6 h after medication,with statistical significance(P<0.05);but there was no statistical significance between before medication and 6 h after medication(P>0.05). CONCLUSIONS:The early application of dobutamine ELWI,tis-sue perfusion and respiratory function in patients with ARDS caused by septic shock,and can keep hemodynamics stable.

Accidents, Traffic ; Forensic Medicine ; Hoarseness ; Humans

OBJECTIVETo explore the ability of interictal diffusion-weighted imaging (DWI) to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy (TLE).

METHODSTwenty-seven patients with intractable TLE considered for surgery and 19 healthy volunteers were studied with conventional magnetic resonance imaging (MRI) and DWI. Apparent diffusion coefficients (ADCs) of bilateral hippocampi in both TLE patients and control subjects were obtained. Lateralization to either temporal lobe with hippocampal ADC was based on the threshold values derived from +/- SD of right/left ratios in normal subjects. And the postoperative pathology was reviewed.

RESULTSHippocampal ADCs were higher on the side of surgery compared with those on the contralateral side as well as the ipsilateral side in control subjects [resected side (109.8 +/- 7.3) x 10(-5) cm2/s, contralateral side (91.7 +/- 4.7) x 10(-5) cm2/s, control subjects (81.6 +/- 5.2) x 10(-5) cm2/s, all P < 0.01]. Right/left hippocampal ADC ratio and conventional MRI lateralized to the operated temporal lobe in 21 of 27 (77.8%) and in 18 of 27 (66.7%) patients. Lateralization to the surgical side was not associated with postoperative seizure control with right/left hippocampal ADC ratio (P > 0.05).

CONCLUSIONSConventional MRI is a sensitive method to detect hippocampal sclerosis. Accuracy of the right/left hippocampal ADC ratio for lateralizing to the side of surgery is very high, but it isn't a better predictor of surgical outcome.

Adolescent ; Adult ; Brain ; anatomy & histology ; metabolism ; Child ; Diffusion Magnetic Resonance Imaging ; methods ; Epilepsy, Temporal Lobe ; diagnosis ; physiopathology ; surgery ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Prognosis ; Seizures ; physiopathology ; Treatment Outcome ; Young Adult

OBJECTIVETo quantitatively evaluate the metabolic changes of benign prostatic hyperplasia (BPH) and prostate cancer in the transitional zone using magnetic resonance spectroscopic imaging (MRSI), and to analyze the characteristics and differences of the spectra in this zonal area.

METHODSEighteen patients with prostate cancer in the transitional zone underwent magnetic resonance imaging (MRI)/MRSI examinations. The (Choline + Creatine)/Citrate (CC/Ci) ratio and the Choline/Creatine (Cho/Cr) ratio were evaluated in each voxel with cancer or BPH confirmed by pathological results. Discriminant analysis was used to determine the power of the two ratios in differentiation between cancer and BPH.

RESULTSThe CC/Ci ratio and Cho/Cr ratio for cancer voxels were significantly higher than those in the voxels with BPH in the transitional zone (CC/Ci: 2.36 +/- 1.31 vs. 0.85 +/- 0.29, P < 0.01; Cho/Cr: 4.14 +/- 1.79 vs. 1.26 +/- 0.45, P < 0.01). As for the discriminant function with the CC/Ci ratio and the Cho/Cr ratio, the specificity, sensitivity, and accuracy were 98.6%, 85.7%, 92.9% respectively for the differentiation between cancer and BPH.

CONCLUSIONSThe prostate cancer is characterized by higher CC/Ci ratio and Cho/Cr ratio compared to BPH in the transitional zone. Both CC/Ci ratio and Cho/Cr ratio have high specificity, sensitivity, and accuracy in their discriminative power between cancer and BPH in this zonal area.

Adult ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Prostatic Hyperplasia ; diagnosis ; pathology ; Prostatic Neoplasms ; diagnosis ; pathology

Objective To explore the feasibility of amide proton transfer (APT) MR imaging for the detection of basal ganglia abnormalities in patients with Parkinson' s disease (PD).Methods Twentyseven patients with PD and twenty-three age-matched normal control subjects underwent cerebral APT and structural MR imaging.The magnetic resonance ratio asymmetry (MTRasym) values at 3.5 ppm of bilateral globus pallidus,putamen and caudate were measured on APT images.MTRasym (3.5 ppm) values of cerebral structures between PD patients and control subjects were compared with independent-samples t test.Paired-samples t test was used to compare the difference of MTRasym (3.5 ppm) between the side of onset and contralateral side in patients with PD.The difference of MTRasym (3.5 ppm) among normal controls,early-stage PD,and advanced-stage PD patients was assessed with one-way analysis of variance.Results Compared to normal controls,MTRasym(3.5 ppm) values of globus pallidus,putamen and caudate were significantly increased in PD patients ((0.89 ±0.12)％ vs (0.57 ±0.16)％,(1.05 ± 0.11)％ vs (0.82 ± 0.15)％,(1.15 ±0.13)％ vs (0.78 ±0.19)％; t =3.311,2.562,3.277 respectively,all P values ＜ 0.05).Significant differences in MTRasym (3.5 ppm) values of these cerebral structures were observed among normal controls,early-stage PD and advanced-stage PD patients.And MTRasym (3.5 ppm) values in globus pallidus,putamen and caudate were significantly higher in early-stage PD patients than normal controls.In PD patients,even not statistically significant,MTRasym (3.5 ppm)values of sides of onset were slightly lower than contralateral sides.Conclusions APT MR imaging can sensitively identify the difference of MTRasym (3.5 ppm) in the basal ganglia between PD patients and normal controls.APT might be a useful tool to evaluate abnormal metabolite in basal ganglia of PD patients.

Objective To evaluate the mechanism of reduction of protection induced by hypoxic postconditioning (HPO) in diabetic myocardiocytes subjected to hypoxia-reoxygenation (H/R),and the relationship with DJ-1 expression.Methods H9c2 cells cultured in normal culture atmosphere were randomly divided into 6 groups (n=36 each) using a random number table:control group (group C),group H/R,group HPO,plasmid carrying DJ-1 gene transfection group (group D),plasmid carrying DJ-1 gene transfection + H/R group (group DH),and plasmid carrying DJ-1 gene transfection + H/R + HPO group (group DHH).H/R was induced by 4 h of hypoxia followed by 2 h of reoxygenation.H9c2 cells were cultured in high glucose culture medium (30 mmol/L) for 48 h in C,H/R and HPO groups.H/R model was established in H/R and HPO groups.HPO was induced by 3 cycles of 5 min reoxygenation and 5 min hypoxia before the onset of reoxygenation in group HPO.In D,DH and DHH groups,the plasmid carrying DJ-1 gene (pEX-2-EGFP-DJ-1) was transfected into the cells,and then the cells were cultured in high glucose culture medium and subjected to H/R and HPO,respectively.At 2 h of reoxygenation,the cell survival rate was measured using the cell counting kit-8 assay,and the level of lactate dehydrogenase (LDH) in the supernatant was detected by enzyme-linked immunosorbent assay,the autophagosomes were examined with a transmission electron microscope,and the expression of DJ-1 and p62 and ratio of microtubule-associated protein 1 light chain 3 Ⅱ / Ⅰ (LC3 Ⅱ / Ⅰ) in cells were detected by Western blot.Results Compared with group C,the cell survival rate and DJ-1 expression were significantly decreased,and the LDH activity was significantly increased in H/R and HPO groups (P＜0.01).There was no significant difference in the parameters mentioned above between H/R and HPO groups (P＞0.05).Compared with group D,the cell survival rate was significantly decreased,and the LDH activity was significantly increased in group DH (P＜0.01).Compared with group DH,the cell survival rate,the number of autophagosomes and LC3 Ⅱ / Ⅰ ratio were significantly increased,and the LDH activity and p62 expression were significantly decreased in group DHH (P＜0.01).There was no significant difference in the parameters mentioned above between H/R and DH groups (P＞0.05).Conclusion The mechanism of reduction of protection induced by HPO in diabetic myocardiocytes subjected to H/R is related to high glucose-induced inhibition of DJ-1 expression and decrease in autophagy.