Objective:To explore the effects of applying peer-assisted learning (PAL) combined with modular teaching in physiology education, and to explore a more suitable mode for physiology teaching and learning.Methods:We selected a total of 89 undergraduate medical students of grade 2022 from a university offering physiology courses from February 28 to June 30, 2022. They were assigned using a random number table into experimental class (44 students) and control class (45 students). The experimental class adopted PAL with modular teaching, while the control class adopted the online and offline hybrid teaching method. The two classes were compared for teaching effects in terms of the completion rate of task points, final assessment scores, and questionnaire results. SPSS 19.0 was used to perform the independent samples t-test and the chi-square test. Results:The final exam scores for the objective questions of the experimental class and the control class were (43.04±3.25) and (40.24±8.64), respectively; the scores for the subjective items were (44.49±2.80) and (39.21±5.71), respectively; and the total scores were (87.53±4.24) and (79.40±12.08), respectively, all with significant differences between the two classes. There were significant differences in students' learning autonomy, micro-video preview rate, problem discussion participation rate, unit self-test participation rate, and after-class homework completion rate. The questionnaire survey showed that students in the experimental class believed that this teaching model was helpful for improving students' comprehensive qualities.Conclusions:PAL combined with modular teaching can effectively improve physiology teaching effects and students' learning autonomy and comprehensive abilities.

Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe²⁺) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H₂O₂ concentration would induce hydroxyl radical (·OH) and oxygen (O₂) generation through Fenton reaction by Fe²⁺. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.

Objective To observe the curative effect of autologous bone marrow stem cells implantation to bone inducing active material combined with core decompression in the treatment of early femoral head osteonecrosis (FHON).Methods From April,2010 to March,2012,in Department of Orthopaedics,the First Affiliated Hospital of Zhengzhou University,a total of 79 adult patients with 108 hips suffered from the early stage FHON were treated with autologous bone marrow stem cells implantation to bone inducing active material combined with core decompression through the core of the femoral canal,male of 65 cases,female of 14 cases,the mean age was 29.5 (20-50) years old.According to the etiology classification:the alcohol-induced FHON was in 54 patients with 66 hips,steroid-induced FHON in 14 patients with 20 hips,steroid and alcohol-induced ONFH was in 11patients with 22 hips.According to association research circulation osseous (ARCO)classifying,Ⅰ-A,Ⅰ-B,Ⅱ-A,Ⅱ-B phases were 6,16,8,and 78 hips,respectively.There were 43 hips in left side and 65 hips in the right side.Results All patients were followed up from 4 to 6 (4.8 ± 0.6) years.Compared with before operation,the scores of all patients were significantly increased (P ＜ 0.05).All patients with hip pain symptoms were relieved or disappeared.The healing tine of the patients in all age groups was statistically significant (P ＜ 0.05),and with the increase of age,the healing time was prolonged.The excellent and good rates of Ⅰ-A,Ⅰ-B,Ⅱ-Aand Ⅱ-B were 100％ (6 / 6),100％ (16/16),100％ (8/8),and 98.7％ (77/78).The X-ray showed that coarse channel osteogenic phenomenon is obvious,there is 1 case collapse of femoral head of stage Ⅱ-B,the rest were not collapse.Conclusion The treatment of early osteonecrosis of the femoral head with autologous bone marrow stem cells implantation to bone inducing active material combined with core decompressionis definitely effective,especially in patients with ARCO:Ⅰ-A,Ⅰ-B and Ⅱ-A phase,and the effect of ARCO:Ⅰ-A and Ⅱ-A is the best.

Background and objective Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KARS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to beneift from molecular target ther-apy treatment. Methods hTe mutation status of EGFR, EML4-ALK fusion gene, ROS1 and AKRS gene were determined by Real-time PCR, the relationship between clinical pathologic features and concomitant gene were analyzed withχ2 test by SPSS sotfware 19.0. Results A total of 514 specimens from Shandong tumor hospital were collected from NSCLC patients between January 2014 and May 2016. The total mutation rate of EGFR gene was 36.70%, major occurred in exon 19 (36.61%) and exon 21 (51.36%), respectively, and EGFR mutations usually occurred in female, non-smoking and adenocarcinoma patients (P<0.05). hTe total rearrangements rate of EML4-ALK fusion gene was 9.37%, EML4-ALK fusion gene usually occurred in younger age (≤60 yr) and non-smoking patients (P<0.05). Mutations were not related to gender and pathological type (P>0.05). ROS1 fusion gene was detected in 136 cases, the positive rate was 3.67%, all patients were 60 years old, and the difference was statistically signiifcant (P<0.05). Only 23 samples were tested AKRS gene mutations, two of them were positive and the posi-tive rate was 8.70%. hTey all occurred in non-smoker and adenocarcinoma patients. No mutation was detected to coexist in EGFR, EML4-ALK and AKRS gene mutation. Conclusion EGFR, EML4-ALK, ROS1 and KARS deifnes different molecular subset of NSCLC with distinct characteristic, which provides a new option for the clinical treatment of patients with NSCLC.

BACKGROUND:Deep vein thrombosis and pulmonary embolism are certainly related to seasons.
OBJECTIVE:To analyze whether there is a seasonal pattern for deep venous thrombosis (DVT) after total hip and knee arthroplasty.
METHODS:We retrospected 866 patients (1 114 joints) underwent total hip and knee arthroplasty. There were 506 cases of total hip arthroplasty, including 287 male cases and 219 female cases, and 608 cases of total knee arthroplasty, including 133 male cases and 475 female cases. The average age was (60.98±0.87) years. After arthroplasty, patients were given color Doppler ultrasound in the deep veins of the lower limbs and pelvis to analyze the correlation between occurrence of deep vein thrombosis and seasons.
RESULTS AND CONCLUSION:There was a significant difference in the incidence of deep vein thrombosis in summer and winter (χ2=7.190, P=0.007), in summer and spring (χ2=6.995, P=0.008), as wel as in summer and autumn (χ2=5.663, P=0.017). No statistical differences were tested in spring and autumn, in autumn and winter, and in spring and winter (P>0.05). These findings indicate that there is a seasonal variation of deep venous thrombosis after arthroplasty, and the highest incidence of deep vein thrombosis is in winter.

The dialysis method was employed to prepare blank and doxorubicin (DOX) loaded micelles formed by temperature- and pH- sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol-co-polyDL-lactide-co-glycolide-co-polyhistidine (PHis-b-PLGA-b-PEG-b-PLGA-b-PHis). The critical micelle concentrations (CMC) of the copolymers were measured with Pyrene Fluorescent Probe Technique. The temperature- and pH- sensitive properties of the blank micelles solution were investigated by optical transmittance measurement. The morphology and diameter of DOX micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The entrapment rate and drug-loading rate were determined with dialysis method. The in vitro release study was further performed to examine the temperature- and pH-responsive drug release behavior from DOX-loaded micelles. The results indicated that the CMC, entrapment efficiency and drug-loaded amount of the micelles were 7.5 x 10(-3) g x L(-1), 85.2 +/- 3.1% and 10.4 +/- 4.5%, respectively. The DOX micelle was globular-shaped with a mean diameter of 91.1 +/- 15.8 nm. The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH. In comparison to the drug release profile at physiological conditions (37 degrees C, pH 7.4), the DOX-loaded micelles showed faster drug release rate at higher temperature (41 degrees C), lower pH (pH 7.0, pH 6.5, pH 5.0) or higher temperature and lower pH (41 degrees C, pH 5.0). This indicated that the micelles showed a temperature and pH-triggered drug release pattern. Base on the above results, it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature- and pH- triggered drug release.

Objective To investigate the effects of sevoflurane delayed preconditioning on caspase recruitment domain (ARC) expression during myocardial ischemia-reperfusion (I/R) in rats. Methods Sixty-four adult male SD rats weighing 270-350 g were randomly divided into 4 groups ( n = 16 each): sham operation (group S); myocardial I/R group; sevoflurane + sham operation group (group S-S) and sevoflurane delayed preconditioning + myocardial I/R group (group S-I/R) . Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h of reperfusion in groups I/R and S-I/R. Group S-S inhaled 33% oxygen for 2 h, and sham operation was performed 24 h later. Group S-I/R inhaled 2.5% sevoflurane for 2 h, and then myocardial I/R was induced 24 h later. Eight animals were sacrificed at the end of 2 h reperfusion in each group and the hearts removed for determination of myocardial infarct size (IS) as a percentage of area at risk (AAR) by triphenyl tetrazolium chloride staining (IS/AAR) . Myocardial apoptosis was detected using TUNEL and apoptosis index was calculated. Another 4 animals were sacrificed immediately before ischemia and at the end of 2 h reperfusion to determine the expression of ARC and Caspase-8 in myocardium by Western blot. Results Compared with group S, the infarct size and apoptosis index were significantly increased in groups I/R and S-I/R, and ARC expression was up-regulated immediately before ischemia in groups S-S and S-I/R, and Caspase-8 expression was up-regulated at 2 h of reperfusion in group I/R ( P ＜ 0.05) . Compared with group I/R, the infarct size and apoptosis index were significantly decreased in group S-I/R, and ARC expression was up-regulated, while Caspase-8 expression was down-regulated at 2 h of reperfusion in groups S-S and S-I/R ( P ＜ 0.05) . Conclusion Sevoflurane delayed preconditioning can attenuate myocardial I/R injury through up-regulating the ARC expression and decreasing the myocardial apoptosis.

ObjectiveTo evaluate the effectiveness and safety of high frequency electronic associating stents insertion and subsequent radiotherapy guided by fiberoptic bronchoscope in treating tracheobronchial stenosis caused by lung and esophagus carcinoma.MethodsFifty-two patients which were ascertained with serious stenosis in trachea or bronchi by fiberoptic bronchoscope were subjected to the study.Fiberoptic bronchoscope was used to investigate the location,extent,blood supply and the degree of tracheobronchial stenosis before the study.After the focus in the airways was cleared up with high frequency electronic,electrocoagulation and snare under the guide of the euthyphoria of fiberoptic bronchoscope,Ni-Ti memory alloy stents were placed into the stenosis airways.The 52 patients were divided into two groups with 26 cases each:the stent group and the stent associating radiotherapy group(radiotherapy group).The later group accepted subsequent radiotherapy after the therapy.The following indexes of the two groups were investigated:short-time clinical effect,dyspnea index class,rate and average time of airway restenosis,life span and survival rate.ResultsAfter therapy,the 52 patients had obvious improvements in dyspnea and the diameter of the stenosis airways.The short-time total effective rate was 100.0％ (52/52),but there was not significant difference between the two groups(P＞ 0.05 ).After therapy,there was significant difference in two groups in dyspnea index class(P ＜ 0.01 ).Although there was not significant difference in the rate of airway restenosis between the two groups(P＞0.05),the average time of airway restenosis in the radiotherapy group was obviously longer than that in the stent group(P＜ 0.01 ).The survival rate of the radiotherapy group in the 6th and 9th month after therapy was higher than that in the stent group (P ＜ 0.05),but there was no significantdifferenee in the 3rd and 12th month (P ＞0.05).ConclusionHigh frequency electronic associating stents insertion and subsequent radiotherapy guided by fiberoptic bronchoscope is an effective and safe treatment for the patients suffering tracheobronchial stenosis caused by lung and esophagus carcinoma.

Objective To observe the effect of intermedin (IMD) preconditioning on cyclin D1, cyclin E and CDKs expression, and explore its role in.promoting kidney tissue regeneration after renal ischemiareperfusion injury. Methods One hundred and forty-four healthy male Wistar rats were randomly divided into four groups: sham operation (S) group, ischemia-reperfusion injury (IR) group, empty plasmid (EP) group and IMD group. In the IR group, after the right kidney was excised, the aorta abdominalis and left renal artery were bluntly dissected in EP and IMD group, empty plasmid and IMD plasmid were transfected into the left kidney using ultrasound-micro-bubble (SonoVue) mediated system, respectively. One week later, renal IRI model was made by clasping the left renal artery for 45 min. After 1, 2, 3, 4, 7 and 14 day of reperfusion, the kidney in each group was collected to detect the expression of cyclin D1, cyclin E, CDK4 and CDK2 by western blot analysis or enzyme-linked immunosorbent assay (ELISA). Results Compared with S group, the expression of cyclin D1, cyclin E, CDK4 and CDK2 was significantly up-regulated in day 1, 2,3, 4, 7 and 14 in IR group. And the above index increased gradually after reperfusion, and reached the peak at day 7 (F=54.92, 69.60, 61.28, 77.38, P＜0.05). While in IMD group, these indexes reached the peak at day 1, then progressively declined, and could not be detected at day 14 (compared with the IR group, F=54.92, 69.60, 61.28, 77.38, P＜0.05). Conclusion IMD preconditioning can up-regulate the expression of cyclin D1, cyclin E, CDK2 and CDK4 in the early phase of renal ischemia-reperfusion injury that may accelerate repair of renal tissue, at least by part, by enhancinge cell proliferation.

ObjectiveTo explore the effect of intermedin pretreatment on repair and regeneration process of renal ischemia reperfusion (IR) injury.Methods Male Wistar rats were randomly divided into four groups: sham group,IR group,empty plasmid group and IMD group.One week after removing the right kidney,eukaryotic expression vector encoding rat IMD gene was transfected into the left kidney using an ultrasound-microbubble-mediated system,and transfection effect was detected by Western blotting and RT-PCR.After successful transfection,renal IR injury model was induced by clamping left renal arteries for 45 minutes followed by reperfusion.BUN and Scr were tested.Renal pathology was observed by PAS and HE staining.The proliferation of tubular epithelial cells was detected by SABC immunohistochemical method.Results (1)The expression of IMD protein and mRNA in IMD group was significantly up-regulated compared to empty plasmid group(P＜0.05),reaching the peak at day 7,and the difference was not significant with that at day 4.(2)Compared with sham group,BUN and Scr were obviously increased at day 1and 2 in IR group(P＜0.05).However,compared with IR group,BUN and Scr in IMD group decreased obviously(P＜0.05).Differences between IR group and empty plasmid group were not significant(P＞0.05).(3)Kidney tubules in IR group,IMD group and empty plasmid group were injuryed,but the injury in IMD group was less serious compared with that in IR group and empty plasmid group.The injury in three groups was the most severe at day 2 after reperfusion.(4)The number of PCNA positive cells evidently increased at day 7 in IR group and empty plasmid group,but the number of PCNA positive cell evidently increased at day 3 in IMD group.Compared with IR group 1 to 4 days after perfusion,PCNA positive cells in IMD group increased obviously (P＜0.05).Compared with IR group day 7,PCNA expression in IMD group 7 d was obviously decreased(P＜ 0.05).Conclusion IMD pretreatment can induce tubular epithelial cells proliferative and accelerate the repair and regeneration progress in IR injury kidneys.