In order to adapt to teaching reform of Medical Immunology and create a"golden course",through teaching prac-tice,our research group proposes a"three-dimensional curriculum teaching system",which organically combines teaching concepts with teaching design and process,with construction of various resources(material libraries),and finally,multi-level teaching evalua-tion is completed to achieve overall unity of teaching.

In order to adapt to teaching reform of Medical Immunology and create a"golden course",through teaching prac-tice,our research group proposes a"three-dimensional curriculum teaching system",which organically combines teaching concepts with teaching design and process,with construction of various resources(material libraries),and finally,multi-level teaching evalua-tion is completed to achieve overall unity of teaching.

Objective:To establish a patient-derived xenograft (PDX) model of gallbladder carcinoma (GBC) and to screen mutated genes associated with GBC with the aim to provide an effective preclinical model with novel therapeutic targets for individualized patient treatment.Methods:The PDX model of GBC was established by transplantation of fresh GBC tissues from 10 patients into subcutaneous tissues of nude mice. In two of these mice, the PDX tumor tissues were stained with HE, Ki67 immunohistochemical staining and whole exome sequencing (WES). The biological characteristics of the PDX tumor tissues were compared with those of the primary donor tumors in histological structure and molecular pathology, and a high-throughput screening of tumor mutation genes was then carried out.Results:In this study, the success rate of the PDX model of GBC was 70% (7/10). The pathological and growth characteristics of PDX tumor tissues and donor tumors were basically similar. In the 2 modeled cases sequenced by WES, the same rates between the harmful mutant genes in the PDX model and primary donor tumor were 71.4% (15/21) and 65.2% (15/23), and the same genes accounted for 93.8% (15/16) and 71.4% (15/21) in the harmful mutant gene of the PDX model. The 22 mutated genes, including TP53, ABCC4 and AMPD1, were involved both in the two donor tumors, and the model tumor tissues. Ten genes including TP53 and ABCC4 were screened out and they might be closely related to development of GBC by bioinformatics analysis.Conclusions:The PDX model of GBC could effectively be used in patients with GBC in this preclinical study on individualized patient treatment. In addition, 10 mutated genes, including TP53 and ABCC4 and the like, may be used as new potential therapeutic targets for GBC.

Objective:To explore the regulatory role and mechanism of tribbles pseudokinase 3 (TRB3) on hepatocarcinoma (HCC) cells proliferation, apoptosis and migration.Methods:Immunohistochemistry and Western blot were used to detect TRB3 expression in cancerous and adjacent cancerous liver tissues of HCC patients. TRB3 expression was detected in vitro in HepG2 and Huh7 hepatocarcinoma cell lines. Simultaneously, CCK8 and EdU were used to detect cell proliferation after TRB3 targeted inhibition with small interfering RNA. CCK8 and EdU were used to detect cell proliferation. Flow cytometry assay was used to detect apoptosis. Transwell assay was used to evaluate migration ability. Simultaneously, Western blot was used to detect changes in apoptosis, migration-related proteins and AKT phosphorylation activity. The mean comparison between the two groups was performed by t-test, and the comparison between multiple groups was performed by one-way analysis of variance.Results:Western blot showed that the expression of TRB3 was significantly up-regulated in HCC tissues. Compared with normal liver tissues adjacent to cancer, the relative expression levels were 0.78 ± 0.12 and 0.29 ± 0.09, respectively, P < 0.01, and the difference was statistically significant. After interfering siRNA inhibited TRB3, CCK8 and EdU tests showed that the proliferation activity of HepG2 and Huh7 cells were significantly weakened ( P < 0.05). Flow cytometry results showed that the apoptotic proportions of HepG2 and Huh7 cells was significantly increased ( P < 0.01). Western blot also showed that the expression of apoptosis regulatory proteins BAX and BIM were significantly increased ( P < 0.01). Transwell assay results showed that the migration ability of HepG2 and Huh7 cells was decreased ( P < 0.05), and the expression of migration regulatory proteins MMP4 and MMP9 was also significantly down-regulated. Western blot results showed that the AKT phosphorylation level was significantly increased. Conclusion:TRB3 regulates hepatocarcinoma cells proliferation, apoptosis and migration by inhibiting the AKT phosphorylation activity. Therefore, TRB3 may be a potential target site for the liver cancer treatment.

Objective To investigate the clinical effect of S-1 combined with oxaliplatin (SOX regimen) in treatment of the patients with advanced pancreatic cancer. Methods A total of 106 patients with advanced pancreatic cancer in Qingdao Fuwai Hospital from April 2015 to June 2017 were randomly divided into the treatment group (53 cases) and the control group (53 cases) according to the random number table method. Patients in the control group were treated with S-1 combined with cisplatin treatment, and patients in the treatment group were treated with SOX regimen. The cell proportion of CD3+, CD4+, CD8+and CD4+/CD8+before treatment and after 2 cycles of treatment were detected by using flow cytometry of both groups. The clinical curative effects, immunity and adverse reactions of both groups were compared by usingχ2 test and t test. Kaplan-Meier method was used to make the survival analysis. Results After two cycles of treatment, there were 4 cases of complete remission (CR), 23 cases of partial remission (PR), 17 cases of stable disease (SD), 9 cases of progression disease (PD) in the treatment group, and 0 case of CR, 18 cases of PR, 20 cases of SD, 15 cases of PD in the control group. The rate of CR+PR in the treatment group was higher than that in the control group [50.94％(27/53) vs. 33.96％(18/53)], and there was a statistical difference (χ2=5.936, P<0.05). There was a significant difference in the cell proportion of CD4+and ratio of CD4+/CD8+between the two groups before and after treatment [the treatment group: (27.31±2.48)％ vs. (37.05±2.53)％, χ2= 6.491,P< 0.01; 0.91 ±0.23 vs. 1.53 ±0.50, χ2 = 5.913, P< 0.01; the control group: (27.43 ±2.47)％ vs. (30.32 ± 2.41)％,χ2= 11.214, P<0.01; 0.90±0.22 vs. 1.22±0.34,χ2=7.992, P<0.01]. After 2 cycles of treatment, the cell proportion of CD4+and ratio of CD4+/CD8+of the treatment group were higher than those of the control group, and there were statistical differences (χ2=5.309, P<0.01;χ2= 7.112, P< 0.01). The incidence rate of side effects had no significant difference in both groups after two cycles of treatment [22.64％ (12/53) vs. 18.87％ (10/53), χ2= 1.924, P> 0.05]. The progression-free survival time in the treatment group was longer than that in the control group (P<0.05). Conclusions SOX regimen has a favorable effect on the patients with advanced pancreatic cancer. It can help to improve the immunity and prolong the survival time of the patients.

Objective To explore the role of serum inflammatory factors in prediction of infection following internal fixation of closed fractures and its significance for surgical timing and infection prophylaxis.Methods A retrospective study was conducted of the 100 patients who had been treated by internal fixation for closed fracture from January 2014 through July 2016.They were 52 men and 48 women,aged from 24 to 76 years (average,45 years).There were 14 femoral fractures,19 tibial plateau fractures,25 patella fractures,8 pilon fractures,22 tibiofibular shaft fractures,and 12 calcaneal fractures.Of them,21 were inflicted by wound infection.The preoperative and postoperative infection indexes,CRP,ESR,PCT and leukocyte count,were recorded.Logistic regression analysis was conducted to test the correlation between the infection indexes and postoperative infection.The optimal cut-off value was determined by the receiver operating characteristic curve.Results CRP showed a significant correlation with postoperative infection while other indexes did not.The optimal cut-off value was 25 mg/L at one day before operation.Conclusions Preoperative determination of CRP may predict the risk of postoperative infection.CRP ＞ 25 mg/L at one day before operation may indicate the following day is not suitable for surgery and active infection prophylaxis should be conducted after surgery.

Objective To investigate the effect and safety of different polyethylene glycol 4000 (PEG)oral regimen on cleanliness of bowel preparation.Methods 280 patients received painness colonoscopy examination were randomly divided into A,B and C groups:group A which drank 1 L of PEG solution the day before colonoscopy and the rest 3 L in the morning at the day of colonoscopy;group B drank 2 L of PEG solution the day before colonoscopy and the rest 2 L in the morning at the day of colonoscopy;group C drank 4 L of PEG solution in the morning at the day of colonoscopy.Bowel cleanliness after taking the drug,stool frequency and adverse events before colonoscopy were observed.Results Group A had better bowel preparation compare with group B (P＜0.05),which was similar to that of group C(P＞0.05);But group A had lower incidence of abdominal distension(abdominal pain),nausea(vomiting) than group C(P＜0.05);and group B had worse sleep quality and more defecate frequency than the other two groups(P＜0.05).Conclusion Drink 1 L of PEG solution the day before colonoscopy and the rest 3 L in the morning at the day of colonoscopy provided a better quality preparation and with less adverse reaction,especially suitable for patients with poor quality of sleep,poor health and severe constipation.

Objective To explore the effect of topical application of sodium hyaluronate on preventing perivascular adhesion of the vein grafts in rabbits. Methods Thirty-six male New Zealand white rabbits, aged 5 months, were randomly and equally divided into 2 groups: groups A and B. Arterial defect model was established by cutting about 1cm artery from the middle part of the dissected left common carotid artery. A section about 3cm was cut from the right external jugular vein, and the harvested vein was inverted and anastomosed end-to-end to the artery defect. After the anastomosis, the adventitia and two anastomoses of the grafted veins in group A were coated locally with 0.2ml sodium hyaluronate. The grafted veins were obtained 1, 2 and 4 weeks after the operation, with the perivascular adhesion of the vein grafts being examined macroscopically before the resection. HE staining and Masson staining were preformed for histological changes of grafted vein wall and the perivascular adhesion of the vein grafts. At 2, 4 weeks postoperation, the perivascular adhesions of the vein grafts were graded by the grading criteria of adhesion in macroscopic evaluation and histological evaluation. Result At 1, 2 and 4 weeks postoperatively, the macroscopic and histological observation found that the perivascular adhesions in group A were looser than those in group B. The macroscopic grade and histological grade were lower in group A than in group B, there was a significant difference between the two groups at 2 and 4 weeks postoperation (P<0.05). Conclusion Topical application of sodium hyaluronate can reduce the perivascular adhesion and is an ideal treatment strategy for preventing perivascular adhesion of vein grafts.

Objective To study the anatomic data of the first metatarsal dorsal artery and to provide anatomical basis for clinical tissue transplantation based on the first metatarsal dorsal artery.Methods The 16 adult cadaver specimens with 32 feet were dissected and meas-ured by vernier caliper.Then the anatomic data of the first metatarsal dorsal artery were analyzed.Results Through the examinations of 32 feet sample,the first metatarsal dorsal artery were classified into 5 types.Type Ⅰ:the first metatarsal dorsal artery runs at the surface of the first dorsal interosseous muscle (13 sides,40.6%).Type Ⅱ:the first metatarsal dorsal artery runs in the interior of the first dorsal interosse-ous muscle (11sides,34.4%).Type Ⅲ:the first metatarsal dorsal artery runs underneath the first dorsal interosseous muscle (6 sides, 18.8%).Type Ⅳ:the first metatarsal dorsal artery is slender (1 side,3.1%).TypeⅤ:the first metatarsal dorsal artery is absent (1 side, 3.1%).Distance relationship was measured between the first metatarsal bone and the first metatarsal dorsal artery:the vertical distance be-tween the origin of the posterior branch of the first metatarsal dorsal artery and base of the first metatarsal bone was (2.4 ±0.3)mm,the ver-tical distance between the origin of the posterior branch of the first metatarsal dorsal artery and head of the first metatarsal bone was (10.1 ±1.0)mm;the vertical distance between the origin of the anterior branch of the first metatarsal dorsal artery and the first metatarso-phalangeal joint was (7.6 ±2.7)mm.Conclusion The first metatarsal dorsal artery has clinical reference significance for the hands and feet’s trauma and skin flap transplantation such as thumb reconstruction.

Objective To compare the incidence of limb dysfunction, sensory disturbance and lymphedema after different treatment methods in breast cancer patients, and evaluate the clinically relevant factors of limb dysfunction. Methods According to the different processing operation of axillary lymph nodes, 235 patients with breast cancer during 2005 to 2012 were divided into axillary lymph node dissection group in Mastoscopy (group A, n=120) and routine axillary lymph node dissection group (group B, n=115). The flexion, extension, abduction, adduction activity of the ipsilateral shoulder were compared with the contralateral, and the circumference of the up-and-down 15 cm of both upper limbs olecroanon were measured. The incidence of limb dysfunction of the patients was followed up in 6 months, 1 year and 2 years. Results There was no significant difference in limb activity and sensory disturbance between 2 groups 6 months, 1 year and 2 years after operation (P>0.05), the incidence of limb lymphedema was higher in group B than in group A (P<0.05). Radiotherapy was related with limb lymphedema in both groups (P<0.05). Conclusion Compared with the conventional axillary lymph node dissection, endoscopic axillary lymph node dissection can reduce the incidence of limb lymphedema after operation, but there was no significant difference in the limb activity and sensory disturbance between 2 groups. Postoperative radiotherapy is a risk to increase the occurrence of limb lymphedema.