AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

Objective: To analyze and compare the distribution of the high-risk population of upper gastrointestinal (UGI) cancer and the factors influencing the compliance rate of endoscopic screening in urban China and rural China. Methods: From 2015 to 2017, an epidemiological survey was conducted on residents aged 40-69 in two rural areas (Luoshan county of Henan province, Sheyang county of Jiangsu province) and two urban areas (Changsha city of Hunan province, Harbin city of Heilongjiang province). As a result, high-risk individuals were recommended for endoscopic screening. Chi-square χ(2) test was used to compare the high-risk rate of UGI cancer between urban and rural residents. In addition, the multivariate logistic regression model was used to analyze the factors influencing the compliance rate of endoscopic screening. Results: A total of 48, 310 residents aged 40-69 were enrolled in this study, including 22 870 (47.34%) residents from rural areas and 25 440 (52.66%) residents from urban areas. A total of 23 532 individuals were assessed with a high risk of UGI cancer, with an overall risk rate of 48.71%. A higher proportion of participants with high risk was observed in rural China (56.17%, 12 845/22 870) than in urban China (42.01%, 10 687/25 440). A total of 10 971 high-risk individuals with UGI cancer participated in endoscopic screening, with an overall compliance rate of 46.62% (10 971/23 532), 45.15% (5 799/12 845) in rural China, and 48.40% (5 172/10 687) in urban China. In rural population, the compliance rate of endoscopic screening was higher in those of females, aged 50-69 years, primary school education or above, high income, a family history of UGI cancer, history of gastric and duodenal ulcer, history of reflux esophagitis, and history of superficial gastritis, but lower in smokers (P<0.05). Among the urban population, the compliance rate of endoscopic screening was higher in those aged 40-49 years, uneducated, low income, family history of UGI cancer, history of reflux esophagitis, history of superficial gastritis, but lower in smokers (P<0.05). Conclusions: The proportion of participants with high risk of UGI cancer in rural areas is higher than that of urban areas. The compliance rates of endoscopic screening in urban and rural areas are low, and influencing factors of endoscopic screening exhibit some differences in rural China and urban China.
China/epidemiology* ; Early Detection of Cancer ; Esophagitis, Peptic ; Female ; Gastritis ; Gastrointestinal Neoplasms/epidemiology* ; Humans ; Rural Population ; Urban Population

In view of the limitations of the existing moxibustion instruments, i.e. possible accidental injury when using moxibustion instruments, the negative effects of products from moxibustion instruments on treatment efficacy and health of medical staff and patients, a moxibustion instrument with multi-jointed manipulator is designed. This moxibustion instrument could accurately control the temperature, maintain a safe moxibustion distance, automatically process the burning ashes of moxa and selectively handle moxa smoke. The experimental results shows that this instrument could maintain the constant temperature of target acupoint, reduce the risk of empyrosis, and reasonably deal with the products of moxibustion. The purification rate of moxa smoke is 44.9%, which not only ensures the therapeutic effect of moxa smoke, but also reduces the negative effects of high-concentration moxa smoke on the health of medical staff and patients.
Acupuncture Points ; Humans ; Moxibustion ; Smoke/analysis* ; Temperature

Epithelial cell adhesion molecule (EpCAM) is a popular target for cancer therapy. In this research, 3 nanobodies with high specificity and endocytosis activity against EpCAM were developed, which provides a basis for the study of immunotoxin based on EpCAM. In our preliminary experiments, we have immunized a camel with EpCAM-Fc antigen and constructed a high-quality phage display library. Seventeen nanobodies with different complementarity determining region (CDR) 3 sequences have been screened after 3 rounds of biopanning by phage display technology. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. After purification, 7 nanobodies showed high cell binding activity by fluorescent activated cell sorting (FACS) identification. Furthermore, 3 nanobodies presented high endocytosis activity based on FACS and laser confocal microscopy, which also showed high affinity to EpCAM measured by ForteBio. According to this study, we aimed to provide a novel alternative approach to the EpCAM-targeted therapy and to provide guidance for the study of nanobody based immunotoxins for other targets.

BACKGROUND:Due to limited sources,poor hemocompatibility and poor anticoagulation performance,small-diameter tissue-engineered blood vessels cannot be applied in clinical practice.OBJECTIVE:To explore the physicochemical and mechanical properties of sheep carotid arteries after the decellularization in order to find appropriate materials for the preparation of tissue-engineered blood vessels.METHODS:Fresh carotid arteries from sheep were randomly divided into two groups:control group,in which,the sheep carotid arteries were cryopreserved for use after trimming and cleaning;experimental group,in which,after trimming and cleaning,the carotid arteries were decallularized by Triton X-100.sodium deoxycholate and EDTA for 24 hours,rinsed for 72 hours,digested with RNA/DNA enzymes for 24 hours,rinsed for 24 hours and reserved for later use.In both groups,blood samples were subjected to hematoxylin-eosin staining,collagen fiber staining,elastic fiber dyeing,and electron microscopy observation.The physical and chemical properties of the blood vessels are tested by tensile strength,wall tension and thickness.RESULTS AND CONCLUSION:(1) The collagen fibers in both two groups were neat and compact in alignment,with no obvious fracture.(2) Hematoxylin-eosin staining showed that:in the control group,the nuclei were distributed in the inner membrane,middle lamella and outer membrane of the vessels,and the fibers ran regularly;in the experimental group,the fibers ran in order but loosely,and there were no nuclei in the inner membrane,middle lamella and outer membrane of the vessels.(3) Elastic fibers in the control group were regular in alignment and mainly distributed in the middle lamella and outer membrane of the vessels,while in the experimental group,the elastic fibers ran regularly but loosely,and mainly distributed in the middle lamella and outer membrane of the vessels.(4) Under the scanning electron microscope,the originally formed vessels were observed in the experimental group,with no cell residues,and the collagen fibers ran orderly with no fracture and with uniform pore structure.(5) The vessel thickness was lower in the experimental group than the control group (P ＜ 0.01),but the tensile strength showed no difference between the two groups,which was 46.55 kPa in the two groups.To conclude,the decelluarized sheep carotid artery can retain the necessary mechanical properties of the blood vessels after achieving the maximum removal of antigenicity.

BACKGROUND: Mesenchymal stem cells are a kind of adult stem cells with self-renewal and multi-directional differentiation potential. These cells have the functions of immunoregulation, regulation of cell growth and repair of injury. In recent years, it has been found that when inflammatory injury occurs, mesenchymal stem cells can regulate the secretion of inflammatory factors, and function on the damaged region, thereby repairing and improving tissue damage caused by inflammation. OBJECTIVE: To review the immunoregulatory effects of mesenchymal stem cells on T lymphocytes, B lymphocytes, dendritic cells and natural killer cells when the body is in an inflammatory state. METHODS: A computer-based search of PubMed and CNKI was performed for articles published from 2000 to 2018 using the keywords of"inflammatory microenvironment, mesenchymal stem cell, immune response, T cell, B cell, DC, NK cell" in English and Chinese, respectively. Seventy-six articles related to the topic and with reliable arguments were finally included in result analysis. RESULTS AND CONCLUSION: The interaction between mesenchymal stem cells and inflammatory cells determines the result of tissue damage repair. In an inflammatory state, the biological characteristics of mesenchymal stem cells will undergo certain changes, but mesenchymal stem cells can still exert immunomodulatory effects by secretion of various soluble cytokines or via cell contact. There are still many problems to be further explored to facilitate better clinical application of mesenchymal stem cells.