The asialoglycoprotein receptor (ASGPR) was used to mediate drug carrier for hepatic targeted drug delivery, this article showed the enzyme-catalyzed esterification of galactose and vinyl stearate and a kind of ASGPR ligand-targeted which was used to insert the surface of liposome has been synthesized. The structure of product has been confirmed by TLC, ESI-MS and 1H NMR. The factors of types and quantity of enzyme, organic solvents, molar ratio of substrate, temperature and time of reaction have been studied. Results showed when using acetone as reaction medium, the quantity of Novozym 435 immobilized lipase was 30 mg mL(-1), molar ratio of galactose to vinyl stearate was 1:5, and reacted at 60 degrees C for 12 h, the transformation of vinyl stearate reached more than 70%. This study provides a novel and efficient route to the synthesis of ligand-targeted modifier.

Systems-based integrated course is the core and hot spot in current advanced medical education reform.An integrated organ-system oriented curriculum system of endocrinology and metabolism was applied in eight year clinical medicine and five year excellent doctor education.The teaching contents of endocrinology and metabolism from traditional Basic Medicine,Internal Medicine and Surgery were integrated and optimized to compile the integrated syllabus and teaching cases.Curriculum integration oriented PBL teaching and comprehensive morphology experimental teaching were implemented into the integrated endocrinology and metabolism system curriculum.This endocrinology and metabolism course integration based on organ-system based learning is conducive to establishing the organic connection between Basic Medicine and Clinical Medicine,and cultivating high-quality medical talents.

Objective To investigate Helicobacter pylori combined with N-methyl-N-nitrosourea (MNU) gavage for preparing balb/c mouse gastric cancer model.Methods Eighty balb/c mice were randomly divided into four groups after 1-week adaptive feed,normal group,model group Ⅰ,Ⅱ and Ⅲ,20 cases in each group.The model group Ⅰ,Ⅱ and Ⅲ were given Helicobacter pylori bacteria liquid (CFU=109/mL) gavage,once every other day for 5 times;then,the freshly configured MNU solution 0.15,0.3,0.6 mL gavages were in turn given,MNU and pure water allocation ratio was 5mg:3mL.Once gavage per week for continuous 10 weeks.Results The model group II had 66.67% adenocarcinoma,the model group I were gastritis with mild atypical hyperplasia,and all mice in the model group III died.Conclusion This method can prepare the gastric cancer model.

OBJECTIVETo investigate the effect of advanced oxidation protein products (AOPP) on proliferation, differentiation, and oxidative stress in rat osteoblasts.

METHODSThe cell proliferation and differentiation of osteoblasts isolated from neonatal SD rat skull were evaluated following treatment with different concentrations (50, 100, 200, and 400 µg/ml) of AOPP using CCK-8 kit and ALP assay kit, respectively. The levels of reactive oxygen species (ROS) in the treated cells were analyzed using 2', 7'-dichlorofluorescin diacetate, and the transcription levels of ALP, collagen I and RAGE were assessed using real-time PCR.

RESULTSCompared with the control group, AOPP-treated osteoblasts showed obviously inhibited proliferation and differentiation with down-regulated expressions of ALP and collagen I and increased ROS production and RAGE expression.

CONCLUSIONAOPP can inhibit the proliferation and differentiation of rat osteoblasts partially by up-regulating RAGE and inducing ROS production.

Advanced Oxidation Protein Products ; pharmacology ; Alkaline Phosphatase ; metabolism ; Animals ; Cell Differentiation ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Osteoblasts ; cytology ; drug effects ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism

Objective:To examine the efficacy and experience of staged and segmented two hybrid surgeries for total repair of Debakey type Ⅰ aortic dissection (TIAD).Methods:This study was a retrospective case series. The clinic data of 10 patients with acute TIAD who were admitted to the Department of Cardiac Surgery, Second Hospital of Lanzhou University or the First People′s Hospital of Lanzhou, between January 2016 and August 2022, were retrospectively studied. Ten patients underwent hybrid surgeries in two hospitalizations (stages), including 7 males and 3 females with an age of (60±7) years (range: 49 to 71 years). In stage 1, the first type Ⅱ hybrid arch repair was performed to treat the ascending, total arch, and descending thoracic aorta for acute TIAD without circulatory arrest. In stage 2, the second hybrid surgery including infrarenal abdominal aorta replacement, visceral arteries bypass and endovascular thoracoabdominal aortic repair was performed to treat residual thoracoabdominal aortic dissection after the first hybrid operation (segmented). Basic data, preoperative concomitant diseases, high-risk factors, surgical approaches and postoperative complications of all important organs, as well as CT imaging were analyzed.Results:There was no death in the 20 hybrid surgical procedures. In stage 1 type Ⅱ hybrid surgery, 4 cases underwent reconstruction of the aortic sinutubular junction, while Bentall and David surgery was performed for 3 cases, respectively. A patient received coronary artery bypass grafting. Then all patients were sequentially treated with arch debranching and thoracic aortic endovascular repair. Postoperative complications included renal insufficiency (4/10), hemofiltration (1/10), hypoxemia (4/10), neurologic event (1/10) and type Ⅱ endoleak (1/10). Complete false lumen thrombosis occurred in 9/10 of the patients. All complications recovered successfully at discharge and the average hospital stay was (21±4) days (range: 16 to 28 days) in the first hospitalization. At stage 2, the second hybrid surgery was successfully performed in all patients. No paraplegia, hepatic or renal insufficiency, or endoleak occurred. However, branch graft embolism of the left renal artery was found in one patient 3 days after laparotomy, as well as of superior mesenteric artery in another. Superior mesenteric artery occlusion was successfully treated by endovascular recanalization. Complete false lumen thrombosis occurred in all patients. Although all patients had different degrees of intestinal dysfunction, they were gradually relieved at discharge, and the average hospital stay was (19±2)days (range:16 to 21 days) in the second hospitalization. During follow-up, CT angiography showed aortic remodeling in all patients.Conclusion:Staged and segmented two hybrid surgeries are safe and feasible for total repair of Debakey type Ⅰ aortic dissection and are associated with acceptable early and midterm outcomes.

Objective:To examine the efficacy and experience of staged and segmented two hybrid surgeries for total repair of Debakey type Ⅰ aortic dissection (TIAD).Methods:This study was a retrospective case series. The clinic data of 10 patients with acute TIAD who were admitted to the Department of Cardiac Surgery, Second Hospital of Lanzhou University or the First People′s Hospital of Lanzhou, between January 2016 and August 2022, were retrospectively studied. Ten patients underwent hybrid surgeries in two hospitalizations (stages), including 7 males and 3 females with an age of (60±7) years (range: 49 to 71 years). In stage 1, the first type Ⅱ hybrid arch repair was performed to treat the ascending, total arch, and descending thoracic aorta for acute TIAD without circulatory arrest. In stage 2, the second hybrid surgery including infrarenal abdominal aorta replacement, visceral arteries bypass and endovascular thoracoabdominal aortic repair was performed to treat residual thoracoabdominal aortic dissection after the first hybrid operation (segmented). Basic data, preoperative concomitant diseases, high-risk factors, surgical approaches and postoperative complications of all important organs, as well as CT imaging were analyzed.Results:There was no death in the 20 hybrid surgical procedures. In stage 1 type Ⅱ hybrid surgery, 4 cases underwent reconstruction of the aortic sinutubular junction, while Bentall and David surgery was performed for 3 cases, respectively. A patient received coronary artery bypass grafting. Then all patients were sequentially treated with arch debranching and thoracic aortic endovascular repair. Postoperative complications included renal insufficiency (4/10), hemofiltration (1/10), hypoxemia (4/10), neurologic event (1/10) and type Ⅱ endoleak (1/10). Complete false lumen thrombosis occurred in 9/10 of the patients. All complications recovered successfully at discharge and the average hospital stay was (21±4) days (range: 16 to 28 days) in the first hospitalization. At stage 2, the second hybrid surgery was successfully performed in all patients. No paraplegia, hepatic or renal insufficiency, or endoleak occurred. However, branch graft embolism of the left renal artery was found in one patient 3 days after laparotomy, as well as of superior mesenteric artery in another. Superior mesenteric artery occlusion was successfully treated by endovascular recanalization. Complete false lumen thrombosis occurred in all patients. Although all patients had different degrees of intestinal dysfunction, they were gradually relieved at discharge, and the average hospital stay was (19±2)days (range:16 to 21 days) in the second hospitalization. During follow-up, CT angiography showed aortic remodeling in all patients.Conclusion:Staged and segmented two hybrid surgeries are safe and feasible for total repair of Debakey type Ⅰ aortic dissection and are associated with acceptable early and midterm outcomes.

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

OBJECTIVE To compare the efficacy and safety of Cefazolin sodium for injection， Cefuroxime sodium for injection， and Ceftazidime for injection from nationally organized centralized drug procurement （hereinafter referred to as “centralized procurement”） and non-centralized procurement in patients with bacterial infection. METHODS The case data of hospitalized patients who had used 3 kinds of Cephalosporins for injection from centralized procurement or non-centralized procurement in the treatment of bacterial infections were retrospectively collected from 19 medical institutions in Kunming from January 2020 to September 2022. After balancing the baseline differences between the groups with the propensity score matching method， the effectiveness and safety differences of 3 kinds of Cephalosporins for injection from centralized procurement or non- centralized procurement were compared respectively. RESULTS After balancing the baseline differences among the groups， 394 cases in each group of Cefazolin sodium for injection from centralized procurement or non-centralized procurement， 472 cases in each group of Cefuroxime sodium for injection from centralized procurement or non-centralized procurement， 504 cases in group of Ceftazidime for injection from centralized procurement and 590 cases in group of non-centralized procurement were included in the analysis. In terms of effectiveness， there were no significant differences in clinical response rate， 72 h response rate， bacterial clearance rate， and the recovery rate of body temperature， white blood cell count， neutrophil count， neutrophil percentage， C-reactive protein， procalcitonin recovery between the centralized procurement group and non-centralized procurement group of Cefazolin sodium for injection and Cefuroxime sodium for injection （P＞0.05）. The proportion of patients in centralized procurement group of Ceftazidime for injection with C-reactive protein restored to normal reference range was significantly higher than that in non-centralized procurement group （46.9% vs. 27.9%， P＜0.05）， but there were no statistically significant differences in other effectiveness indicators among groups （P＞0.05）. In terms of safety， there was no statistical difference in the incidence of adverse drug reactions between centralized procurement group and non-centralized procurement group of 3 kinds of Cephalosporins for injection （P＞0.05）； the incidence of platelet count reduction in centralized procurement group of Cefazolin sodium for injection was significantly higher than non-centralized procurement group （20.7% vs. 7.1%， P＜0.05）， the incidence of eosinophilia elevation in centralized procurement group of Ceftazidime for injection was significantly higher than non-centralized procurement group （5.3% vs. 1.9%， P＜0.05）. In addition， there was no statistically significant difference in the abnormal rates of other laboratory indicators among the three types of injection Cephalosporins （P＞ 0.05）. CONCLUSIONS The efficacy of 3 kinds of Cephalosporin for injection from centralized procurement is not inferior to non- centralized procurement varieties， and the safety is equivalent to that of non-centralized procurement varieties.

Objective To establish a new patient-derived xenograft (PDX) model of human liver cancer by inoculating the complex of human primary liver cancer cells and a novel microcarrier (microcarrier 6) into mice with normal immune function. Methods Primary liver cancer cells were isolated and extracted from the fresh human liver cancer tissue of five patients and were then co-cultured with microcarrier 6 to construct a three-dimensional tumor cell culture model in vitro . According to the type of graft, 75 male C57BL/6 mice were divided into cell control group, microcarrier control group, and experimental group (each sample corresponded to three groups, with 15 groups in total and 5 mice in each group). The liver cancer cell-microcarrier complex was implanted into the mice by subcutaneous inoculation, and tumor formation time, tumor formation rate, and histopathological manifestations were observed. The Fisher's exact test was used for comparison of categorical data between two groups. Results As for the liver cancer cells from the five patients, tumor formation was observed in the mice corresponding to three patients. In these three experiments, tumor formation was not observed in the control groups and was only observed in the experimental groups, and 12 of the 15 mice in the experimental groups had successful tumor formation, with a tumor formation rate as high as 80%, which was significantly different from that in the cell control groups and the microcarrier control groups (all P < 0.05). The tumor formation time was 5-7 days; the xenograft tumor grew rapidly, and HE staining showed nested or flaky cells with obvious heteromorphism, with the presence of pathological mitosis; immunohistochemical staining showed positive CK8/18, Hep, and Gpc-3, which was in accordance with the characteristics of human liver cancer cells. Conclusion This experiment successfully establishes a new PDX model of human liver cancer based on the complex of microcarrier 6 and human primary liver cancer cells in mice with normal immunity. This model can be used to better elucidate the mechanism of the development and progression of liver cancer in the body with normal immunity, and besides, it also provides a new animal model with higher value for the precise treatment of liver cancer.