Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Reform of clinical medical talents cultivation model based on post competency: a case study of Guangxi Medical University / 中华医学教育探索杂志

Through the reform and practice of the "four-in-one" cultivation model of clinical medical talents, the training mode of applied high-quality medical and health talents with different orientations is established, and the curriculum teaching system suitable for the development of modern medical education is constructed to promote the reform of education and teaching. It solves the problems of single medical talents training mode, fragmentation of curriculum system, single teaching and training in teaching, and insufficient support for talent training. This reform established a set of curriculum system, teaching methods and evaluation methods to strengthen the cultivation of medical students' post competency, and achieved the goal of improving the quality of clinical medical personnel training in local medical colleges.

Influencing Factors of HIV/ AIDS Death Based on Bayesian Cox Proportional Hazard Regression Model / 中山大学学报(医学科学版)

ObjectiveTo understand the composition of related characteristics of HIV/AIDS cases in Lanzhou and analyze the influencing factors of AIDS-related deaths. MethodsThe information of HIV/AIDS cases reported in Lanzhou from 2011 to 2019 was collected， the method of survival was used analysis and Bayesian Cox Proportional Hazard Regression Model was constructed to analyze the related factors of death. ResultsA total of 2 312 HIV/AIDS patients were selected in this study， including 45 AIDS-related deaths. The results of multivariate regression showed that the older the patients were， the higher the risk of death was； the risk of death of AIDS patients at the time of diagnosis was 13.91 times higher than that of HIV-infected patients； Patients who received CD4 testing had a lower risk of death than those who did not； The risk of death was 0.22 times higher among those who received antiretroviral therapy than those who did not receive antiretroviral therapy. ConclusionsAge at diagnosis， course of disease， antiviral therapy were the influencing factors of AIDS-related death in HIV/AIDS patients in Lanzhou. Therefore， it is necessary to strengthen health education for AIDS-related groups， advocate early detection， early diagnosis， and early treatment， expand the coverage of AIDS testing and treatment， prolong the survival time of AIDS patients.

Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease: Soil and seeds / 中华医学杂志(英文版)

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.

Practice on the characteristic curriculum construction of undergraduate clinical medicine in Sino-foreign cooperative education program / 中华医学教育探索杂志

As one of the first institutions to carry out integrated education in China, the Shanghai Jiao Tong University School of Medicine has carried out a pilot reform of the organ system centered vertical single cycle integrated curriculum in the undergraduate medical education (five-year English stream) based on the Sino-foreign cooperative education program. The curriculum has been formed with multi-disciplinary single cycle integrated courses, longitudinal integrated courses, and three-dimensional specialized expansion electives. The curriculum focuses on the competency training of medical student. The aim is to highlight the teaching concept of early contact with clinic, attach importance to the cultivation and shaping of medical personality, achieve effective connection with post-graduation education, and realize the intersection and deep integration of social, humanities and medical professional courses through the construction of a series of course modules.

Exploration and practice of organ system integration curriculum reform / 中华医学教育探索杂志

Introducing the concept of integration into medical curriculum reform is an important measure to promote the development of medical education. This research discusses the advantages and disadvantages of various teaching models by comparing the models of organ system integration courses at home and abroad, combining with the review of the development of integrated courses in Shanghai Jiao Tong University Medical College and the analysis of questionnaires from teachers and students, proposes a curriculum reform plan optimized with the concept of "Medical discipline in the new era", and puts forward targeted suggestions from the aspects of curriculum system setting, teacher security, etc., thus providing research support for the future development of organ system integration curriculum.

Exploration and practice of clinical medicine "4+4" program for the cultivation model of innovative talents: taking Shanghai Jiao Tong University School of Medicine as an example / 中华医学教育探索杂志

Since the enrollment in 2002, the cultivation model of "4+4" program of clinical medicine in Shanghai Jiao Tong University School of Medicine has been continuously explored and practiced. With the goal of cultivating high-level compound outstanding medical innovative talents with multi-disciplinary cross-capacity, through strengthening the heuristic teaching, establishing the medical-engineering cross-course, emphasizing the training of scientific research ability, and taking teaching reform in the basic clinical single-circulation organ system integration course, we have established a talent training system with the characteristics of Shanghai Jiao Tong University School of Medicine, which is characterized by "thick foundation, strong practice, re-transformation, shaping norms, and international integration", and intend to make further exploration in the field of post-graduation education convergence.

Thinking of medical major setting under the background of "New Medicine" / 中华医学教育探索杂志

National education, medical industry demand and external environment all put forward the demand of training "medical + X" compound medical talents. In recent years, the development of "medical + X" has provided a foundation for the establishment of related majors in the undergraduate stage. This paper analyzes the current situation of medical interdisciplinary development at home and abroad, summarizes the existing "medical + X" training model at the undergraduate level, and argues that the new "medical + X" majors should be supported by optimizing the system design and focusing on the interdisciplinary frontier. At the same time, the setting of new majors of "Medical + X" should also pay attention to the three characteristics of livelihood, faculty and employment.

Wogonoside alleviates high glucose-induced dysfunction of retinal microvascular endothelial cells and diabetic retinopathy in rats by up-regulating SIRT1 / 南方医科大学学报

OBJECTIVE@#To investigate the effects of wogonoside on high glucose-induced dysfunction of human retinal microvascular endothelial cells (hRMECs) and streptozotocin (STZ)-induced diabetic retinopathy in rats and explore the underlying molecular mechanism.@*METHODS@#HRMECs in routine culture were treated with 25 mmol/L mannitol or exposed to high glucose (30 mmol/L glucose) and treatment with 10, 20, 30, 40 μmol/L wogonoside. CCK-8 assay and Transwell assay were used to examine cell proliferation and migration, and the changes in tube formation and monolayer cell membrane permeability were tested. ROS, NO and GSH-ST kits were used to evaluate oxidative stress levels in the cells. The expressions of IL-1β and IL-6 in the cells were examined with qRT-PCR and ELISA, and the protein expressions of VEGF, HIF-1α and SIRT1 were detected using Western blotting. We also tested the effect of wogonoside on retinal injury and expressions of HIF-1α, ROS, VEGF, TNF-α, IL-1β, IL-6 and SIRT1 proteins in rat models of STZ-induced diabetic retinopathy.@*RESULTS@#High glucose exposure caused abnormal proliferation and migration, promoted angiogenesis, increased membrane permeability (P < 0.05), and induced inflammation and oxidative stress in hRMECs (P < 0.05). Wogonoside treatment concentration-dependently inhibited high glucose-induced changes in hRMECs. High glucose exposure significantly lowered the expression of SIRT1 in hRMECs, which was partially reversed by wogonoside (30 μmol/L) treatment; interference of SIRT1 obviously attenuated the inhibitory effects of wogonoside against high glucose-induced changes in proliferation, migration, angiogenesis, membrane permeability, inflammation and oxidative stress in hRMECs. In rat models of STZ-induced diabetic retinopathy, wogonoside effectively suppressed retinal thickening (P < 0.05), alleviated STZ-induced retinal injury, and increased the expression of SIRT1 in the retinal tissues (P < 0.001).@*CONCLUSION@#Wogonoside alleviates retinal damage caused by diabetic retinopathy by up-regulating SIRT1 expression.

Establishment and functional in vitro characteristics of three-dimensional collagen HepaRG microsphere / 中国组织工程研究

BACKGROUND: Some recent studies have shown that the three-dimensional (3D) model of HepaRG cells can better mimic the in vivo microenvironment and show better liver differentiation and function compared with two-dimensional culture. OBJECTIVE: HepaRG was selected to prepare 3D collagen microspheres, and the adaptive culture and functional expression of cells in the collagen microspheres were evaluated. METHODS: Collagen hydrogel was used as the scaffold for 3D HepaRG and HepG2 microspheres. Stable cell spheres were formed. HepaRG microspheres, HepG2 microspheres, HepaRG two-dimensional culture and HepG2 two-dimensional culture were used as controls. At 1, 6, and 12 days of culture, cell survival was detected by the Live/Dead assay staining. After 1, 6, 12, and 16 days of culture, the urea synthesis and CYP3A4 secretion of the supernatant were detected in each group. After 12 days of culture, relative expression of CYP3A4, CYP1A2, UGT1A1, and CPS1 mRNA was detected by qPCR. The expression levels of hepatocyte marker albumin and CYP3A4 protein were determined using western blot assay. RESULTS AND CONCLUSION: (1) In 12 days of culture, Live/Dead assay staining showed that the cell viability in the 3D collagen microsphere was well-maintained and the amount of central necrotic cells was small, with high cell viability. In the 3D collagen microsphere, especially HepaRG cells, multiple cellular clusters formed and adjacent clusters were connected closely, which created a cross-linked structure. (2) After 1, 6, and 12 days of culture, the urea content of HepaRG 3D collagen microspheres was higher than that of HepaRG two-dimensional culture (P < 0.05). After 1, 6, 12, and 16 days of culture, the urea content of HepG2 3D collagen microspheres was higher than that of HepG2 two-dimensional culture (P < 0.05). After 1, 6, and 12 days of culture, the secretion of CYP3A4 in HepaRG 3D collagen microspheres was higher than that in HepaRG two-dimensional culture (P < 0.05). After 6 and 12 days of culture, the secretion of CYP3A4 in HepG2 3D collagen microspheres was higher than that in HepG2 two-dimensional culture (P < 0.05). (3) The relative expression of CYP3A4, CYP1A2, UGT1A1, and CPS1 mRNA in HepaRG 3D collagen microspheres was higher than that in HepaRG two-dimensional cells (P < 0.05), and the relative expression of CYP1A2 in HepG2 3D collagen microspheres was higher than that in HepG2 two-dimensional culture (P < 0.05). (4) The expression levels of albumin and CYP3A4 protein in HepaRG 3D collagen microspheres were higher than those of HepG2 3D collagen microspheres, ordinary microspheres, and two-dimensional culture (P < 0.05). (5) These results indicated the high-level expression of hepatocyte functions in 3D collagen HepaRG microsphere, which could be taken as a reference in drug metabolism evaluation in vitro and tissue engineering application.

Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study / 中华医学杂志(英文版)

BACKGROUND@#Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).@*METHODS@#The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.@*RESULTS@#The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.@*CONCLUSION@#Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Exploration and practice of teaching staff incentive development in the clinical teaching reform under the background of medical and educational collaboration / 中华医学教育探索杂志

The sustainable development of the teaching staff is crucial to the overall advancement of medical education reform under the background of medical and educational collaboration. With the support of the Shanghai Key Teachers' Teaching Incentive Program, Shanghai Jiao Tong University School of Medicine has established the interdisciplinary and inter-school teaching teams for undergraduate students and broken though the "last mile" of fully implementing the medical teaching reform of organ-system integrated curriculum in the country. Meanwhile, we also has reformed hourly remuneration system, formulated rules and regulations corresponding to each link, and improved the supervision mechanism, which has consolidated the mechanism of medical and educational collaboration, promoted the development of community for teachers and comprehensively improved the quality of medical education.

Panax notoginseng saponins prevent colitis-associated colorectal cancer development: the role of gut microbiota / 中国天然药物

Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.

Exploration and practice of teaching staff incentive development in the clinical teaching reform under the background of medical and educational collaboration / 中华医学教育探索杂志

The sustainable development of the teaching staff is crucial to the overall advancement of medical education reform under the background of medical and educational collaboration. With the support of the Shanghai Key Teachers' Teaching Incentive Program, Shanghai Jiao Tong University School of Medicine has established the interdisciplinary and inter-school teaching teams for undergraduate students and broken though the "last mile" of fully implementing the medical teaching reform of organ-system integrated curriculum in the country. Meanwhile, we also has reformed hourly remuneration system, formulated rules and regulations corresponding to each link, and improved the supervision mechanism, which has consolidated the mechanism of medical and educational collaboration, promoted the development of community for teachers and comprehensively improved the quality of medical education.

Study on the teaching supervision of online teaching based on the quality control concept of outcomes-based education / 中华医学教育探索杂志

Supervision of teaching is of great significance to the substantive equivalence of "online" and "offline" teaching. Compared with the conventional supervision of offline teaching, supervision of online teaching has its particularity. The School of Medicine of Shanghai Jiao Tong University has formulated the online teaching supervision program, relying on the constantly improving supervision system in long-term practice and based on the quality control concept of OBE (outcomes-based education) which aims to improve the learning effect of students. The supervision program of online teaching includes full coverage of expert supervision, smooth feedback channels for students, prompt communication and solutions by management supervision, etc. And the effect of online teaching supervision on students' learning effect can be tested in practice. The effect of the online teaching has been investigated by the questionnaire survey. The results show that online teaching expert supervision has higher satisfaction and students learning effect is better, which illustrates that the online supervision program has played a positive role in teaching.

Exploration and reflection on reconstruction of medical teaching team based on online teaching mode / 中华医学教育探索杂志

To overcome the impact of COVID-19 on medical education, School of Medicine of Shanghai Jiao Tong University reconstructed the medical teaching team under the mode of online medical education. Through the reconstruction of online teaching team and the implementation of full coverage of teaching incentives, the teaching pressure of teachers has been eased, students' autonomous learning and personalized training have been promoted, teachers' ability of information-based teaching and professional development level have been improved, and a new position of moral education has been opened up. The medical teaching team under the online teaching mode ensures the teaching quality, and also brings the possibility of multi-dimensional innovation and reform for the future development of education, which meets the actual needs of the current integration of curriculum teaching reform and development in medical colleges.

Tim-3 expression in glioma cells is associated with drug resistance

Objective: T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) has been widely recognized as a negative regulator of antitumor immunity. However, the mechanism by which Tim-3 suppresses antitumor treatment in gliomas remains unclear. This study aims to explore whether Tim-3 is expressed and to evaluate its effect in drug-fasted glioma cells. Subjects and Methods: U87 and U251 glioma cell lines were tested. Cell proliferation activity, cell viability, and the protein and mRNA levels of Tim-3 were detected using CCK-8, flow cytometry, Western blotting, and reverse transcription-quantitative polymerase chain reaction, respectively. Enhancement of the sensitivity of glioma cells to chemotherapeutic agents was tested after inhibiting Tim-3 expression using Tim-3 small interfering RNAs (siRNA). Results: As temozolomide (TMZ) concentration increased, the ratio of apoptotic cells also increased accordingly. However, the level of Tim-3 expression in living cells from the high-dose group was higher than in the low- and middle-dose groups. After interfering with the expression of Tim-3 using siRNA against Tim-3, the killing effect of TMZ rose through an increase in apoptosis. Conclusions: The presence of Tim-3 mRNA and protein in glioma cells was detected. Significantly, knocking down Tim-3 expression improved the potential of TMZ treatment.

Quantification of Panax notoginseng saponins metabolites in rat plasma with in vivo gut microbiota-mediated biotransformation by HPLC-MS/MS / 中国天然药物

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.

Expression of EGR1 gene and location of EGR1 protein in differentiation of bovine skeletal muscle-derived satellite cells / 中国应用生理学杂志

OBJECTIVE@#To investigate the expression of EGR1 gene and the localization of EGR1 protein in bovine skeletal muscle-derived satellite cells (MDSCs), as well as to investigate the mechanism that EGR1 protein enters the nucleus.@*METHODS@#Bovine MDSCs were cultured in differentiation medium for 1 day, 3 days and 5 days, respectively, and each group was triplicate. The expression of EGR1 gene and the localization of EGR1 protein were studied at different differentiation period in MDSCs by qRT-PC and Western blot. Moreover, the changes on the expression of endogenous EGR1 gene and EGR1 proteins were explored by CRISPRi, site-directed mutagenesis and laser confocal method.@*RESULTS@#The results from the qRT-PCR and Western blot showed that the expressions of EGR1 gene on transcription level and translation level were significantly higher in differentiated cells than those in undifferentiated cells. The highest expression was found on the third day after the differentiation, and then began to decline. Immunofluorescence assays showed that EGR1 proteins were preferentially expressed in differentiated MDSCs, and increased along with the increase of number of myotubes. Confocal observation revealed that some EGR1 proteins were transferred into the nucleus in the differentiation of cells, however, the EGR1 proteins would not be detected in the differentiated MDSCs nuclei if a site directed mutagenesis (serine) on EGR1 protein occurred.@*CONCLUSION@#During the differentiation of bovine skeletal muscle satellite cells, the transcriptional level of EGR1 gene is increased, and some EGR1 proteins are transferred into the nucleus. The serine phosphorylation at position 533 of the C terminal of EGR1 protein is necessary for the nucleus transfer.

Introduction and reflection on the curriculum "society, the individual & medicine" in university of Ottawa faculty of medicine / 中华医学教育探索杂志

Taking the curriculum "society, the individual & medicine" in university of Ottawa faculty of medicine as an example, the cultivation models for comprehensive quality of medical students in China and Canada was compared. In University of Ottawa faculty of medicine, the curriculum "society, the individual & medicine" is throughout the whole medical education, including three themes of statistics and epidemiology related knowledge, health related issues and professional development. The varied teaching modes are combined with electronic teaching equipment and students' subjectivity in learning is emphasized. Drawing insights from the medical education in Canada, we should focus on promoting early contact and lifelong study of medical humanities curriculum for medical students, enriching the curriculum content, enhancing the curriculum practicality, diversifying the teaching methods, strengthening the teachers' training, improving the assessment system and establishing the long-term mechanism.