BACKGROUND:Mesenchymal stem cell-derived exosomes may play a crucial role in tissue damage repair,and miRNA is an important component of exosomes for therapeutic effects.Among them,miR-29b-3p has the effect of reducing cell apoptosis,promoting axonal regeneration,and angiogenesis. OBJECTIVE:To study the protective effect of adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p on a neural cell injury model simulated by H2O2-treated PC12 cells,and explore the relevant mechanisms. METHODS:(1)First,the collagenase digestion method was used to extract rat adipose-derived mesenchymal stem cells.Adipose-derived mesenchymal stem cells were transfected with miR-29b-3p mimics and inhibitors.Exosomes were extracted from the culture supernatant by ultracentrifugation and identified so as to construct adipose-derived mesenchymal stem cell-derived exosomes with high expression and knockdown miR-29b-3p.(2)By constructing a neural cell injury model simulated by PC12 cells treated with H2O2,the relevant mechanisms of the protective effect of adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p on the simulated neuronal cell injury model were studied. RESULTS AND CONCLUSION:(1)Adipose-derived mesenchymal stem cell-derived exosome had a typical cup-shaped shape and a diameter distribution in the range of 50-140 nm,expressed membrane proteins Alix,CD63,and TSG101,which were specific markers on the surface of exosomes,and could be successfully ingested by PC12 cells.(2)Adipose-derived mesenchymal stem cell-derived exosome pretreatment could reduce cell apoptosis induced by H2O2 treatment in PC12 cells,and this protective effect was enhanced with the increase of miR-29b-3p expression in the exosomes and weakened with the decrease of miR-29b-3p expression in the exosomes.The mechanism of its effect was related to adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p promoting the expression of anti-apoptotic protein Bcl-2 and inhibiting the expression of apoptotic protein Bax.

Objective:To evaluate the curative effect of Sun's procedure using sutureless artificial blood vessel replacement technique on acute type A aortic dissection.Methods:Retrospective analysis was performed on 40 patients with acute type A aortic dissection who underwent Sun's procedure in The First People's Hospital of Nanning from May 2019 to April 2023. According to the surgical method, the patients were divided into sutureless group (20 cases) and traditional group (20 cases).The time of stopping circulation, cardiopulmonary bypass, recovery time, intubation time, blood loss 12 h after operation, cerebral infarction and acute renal failure were compared between the two groups.Patients older than 70 years, patients with preoperative malperfusion syndrome, or patients who did not undergo Sun's procedure were excluded.Results:The time of stopping circulation[( 13.6±3.3)min vs. ( 28.2±5.6)min, P<0.001] and the time of cardiopulmonary bypass[(116.0±34.8)min vs.(219.1±46.3 )min, P<0.001]and blood loss at 12 h after operation[( 474.5±301.0)ml vs. (422.7±389.8)ml, P<0.001] in the sutureless group were significantly lower than those in the traditional group.All patients survived and were discharged from hospital. There were no significant differences in recovery time, intubation time, cerebral infarction and acute renal failure between the two groups. Conclusion:Sutureless artificial blood vessel replacement technique can significantly shorten the time of stopping circulation and cardiopulmonary bypass, effectively protect the function of the whole body organs, and reduce the occurrence of postoperative complications.Moreover, it is easy to carry out in primary hospitals, and it is a safe and effective new surgical strategy for treating acute type A aortic dissection with Sun's surgery.

ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg^-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Objective:To investigate the safety and dose of 4D template (real-time adjustable angle template) in the treatment of advanced malignant tumors with 125I seeds. Methods:98 patients with advanced malignant tumors admitted to Department of Thoracic Surgery of Shaanxi Provincial Tumor Hospital were treated with 4D template-navigated radioactive 125I seed implantation from June 2018 to December 2019. Preoperative TPS plan, intraoperative optimization, postoperative verification of immediate dose and postoperative evaluation of implantation dose were performed. The treatment results were observed. Results:All 98 patients completed the seed implantation. The implantation dose of GTV of implantation site receiving external irradiation was (12 489±414) cGy and the dose of no external irradiation was (15 036±514) cGy. V 100% was 84.7%-94.1%, and 88.2%-93.7%. The implantation dose of CTV was (7 450±621) cGy, and (9 080±761) cGy. The quality of dose implantation was evaluated as: excellent in 89 cases (91%, 89/98), good in 7 cases (7%, 7/98), fair in 2 cases (2%, 2/98), and poor in 0 case, respectively. The symptom relief rate of patients with pain was 92%(36/39). The 1-and 2-year local control rates were 61%, 36% and 82%, 54% in patients treated with and without external irradiation, respectively. The difference was statistically significant ( P=0.02). The incidence rates of pneumothorax and hemoptysis were 19%(9/48) and 10%(5/48). No corresponding complications were observed in other parts of the patients. Conclusion:4D template-assisted 125I seed therapy is safe and effective for malignant tumors, and intraoperative adjustment of needle angle and dose optimization can realize the precise control of implantation dose.

Objective:To summarize the status and trends of papers published by Chinese scholars on the combination teaching model in the area of medical education in China.Methods:Literature retrieval was performed on CNKI, WanFang, and VIP database, and studies regarding to combination teaching model in medical education were selected and analyzed. BICOMS-2 analysis software was used to extract and sort out keywords, provinces, authors and their organizations and generate co-occurrence matrix and/or word matrix. NetDraw and gCLUTO software were used to draw the network relationship diagram and cluster analysis respectively.Results:Totally 99 articles were included this study, and the number of articles published each year showed an increasing trend. Authors from 15 provinces contributed to these articles, with uneven development and limited cooperation across regions. The authors were divided into 4 main groups, but the communication among these groups was not enough. And there were 3 main research topics.Conclusion:The number of articles on combination teaching model in medical education in China is increasing, covering many authors, teams, institutions and regions. However, the communication and cooperation among these authors and institutions needs to be strengthened; and the research topics should be expanded.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

Objective:To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas.Methods:A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions.Results:The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender ( P<0.001), smoking history ( P<0.001), age ( P<0.001), pathological type ( P<0.001), and whether the Xuanwei area ( P=0.027), but not related to the nationality ( P=0.748) and family history of lung cancer ( P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males ( P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females ( P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority ( P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area ( P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area ( P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area ( P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history ( P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history ( P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history ( P=0.008). Conclusions:The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

Objective:To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas.Methods:A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions.Results:The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender ( P<0.001), smoking history ( P<0.001), age ( P<0.001), pathological type ( P<0.001), and whether the Xuanwei area ( P=0.027), but not related to the nationality ( P=0.748) and family history of lung cancer ( P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males ( P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females ( P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority ( P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area ( P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area ( P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area ( P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history ( P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history ( P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history ( P=0.008). Conclusions:The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.