ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology， molecular docking， and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards， Online Mendelian Inheritance in Man （OMIM）， PharmGKB， Therapeutic Target Database （TTD）， Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0， the STRING database was used to analyze the protein-protein interactions， and Cytoscape was used for the core target analysis and visualization. Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG） were employed for enrichment analysis. Molecular docking was carried out in Autodock， and cell experiments were conducted to verify the prediction results. In the cell experiments， estradiol and progesterone （E₂+P） were used to intervene in human mammary epithelial/MCF-10A cells， and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 （CCK-8） was used to measure the cell proliferation， and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot， respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained， from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes， which may be related to protein kinase B （Akt）-related molecular functions， estrogen signaling pathway， prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 （ESR1）， serine/threonine kinase 1 （Akt1）， non-receptor tyrosine kinase （SRC）， and signal transducer and activator of transcription 3 （STAT3） all had strong binding activity with the nine active ingredients， suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway and the Janus kinase （JAK）/STAT3 signaling pathway. The results of cell experiments showed that E₂+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells （P<0.05）， while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E₂+P （P<0.05）. Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E₂+P （P<0.01）. The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K， Akt， JAK2， and STAT3 in MCF-10A cells treated with E₂+P （P<0.01）. The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K， p-Akt/Akt， p-JAK2/JAK2， and p-STAT3/STAT3 in MCF-10A cells treated with E₂+P （P<0.05）. ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells， which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.

AIM:To investigate the therapeutic effects of syringin(SY)on vascular cognitive impairment(VCI)in rats and its possible mechanisms.METHODS:The rats were allocated into three groups:sham group(n=15);model group(n=21);and SY treatment group(n=19).The VCI rat model was induced via a modified bilateral ligation of the common carotid artery.Three days after the model induction,the SY treatment group received intraperitoneal injec-tions of 50 mg/kg SY once daily for 28 d.In total,15 rats in the sham operation group,17 rats in the model group,and 17 rats in the SY treatment group were included for further investigation.The cognitive and learning functions of the rats were assessed using the Morris water maze test,Y-maze test,and novel object recognition experiment.Cerebral blood flow was monitored through laser speckle imaging,while Evans blue staining was used to assess damage to the blood-brain barrier.Nissl staining,microtubule-associated protein-2(MAP-2),and neuronal nuclear antigen(NeuN)co-localization immuno-fluorescence staining demonstrated the extent of hippocampal damage.ELISA was employed to measure the levels of inter-leukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)in the brain tissue.Microglial activation was observed via ionized calcium-binding adapter molecule 1(IBA1)immunofluorescence staining,and Western blot analysis detected the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88)and phosphorylated(p)-P65 pro-teins in the brain tissue.RESULTS:Compared with the sham group,rats in the model group exhibited reduced cognitive function and cerebral blood flow(P＜0.01),increased blood-brain barrier permeability and degree of hippocampal tissue damage(P＜0.01),upregulation of TLR4,MyD88,and p-P65 protein expression in the brain tissue(P＜0.01),elevated levels of IL-1β,IL-6 and TNF-α(P＜0.01),as well as microglia activation(P＜0.01).In contrast to the model group,rats in the SY group demonstrated enhanced cognitive function and cerebral blood flow(P＜0.01),decreased blood-brain barrier permeability and degree of hippocampal tissue damage(P＜0.01),downregulation of TLR4,MyD88 and p-P65 protein expression in the brain tissue(P＜0.01),reduced levels of IL-1β,IL-6 and TNF-α,and reduced microglia density(P＜0.01).CONCLUSION:SY enhances cognitive function in VCI rats by improving cerebral blood flow,safeguarding the integrity of the blood-brain barrier,attenuating neuroinflammation,mitigating neuronal damage within the hippocam-pus,and inhibiting TLR4/MyD88/NF-κB signaling pathways.

Objective:To investigate the construction effects of the graduate biochemistry technology courses based on the outcome-based education (OBE) concept, analyze the technical needs of graduate students, and further integrate and optimize the teaching methods.Methods:A self-compiled questionnaire with good reliability and validity was used to conduct an overall sampling survey on the graduate students who took the elective courses in Batch 2021 in a medical college in Shanghai. Excel and GraphPad Prism software were used for data analysis.Results:According to this survey, the courses gain good effects in terms of teaching framework, course facilities, teaching forms, teaching contents and comprehensive evaluation of teaching. A total of 112 students (95.2%) thought that the course was very helpful to the expansion of experimental technology and experimental operation ability. However, there were still some teaching needs, such as expanding the types of experiments and increasing experimental operations.Conclusions:Under the guidance of OBE concept, the construction of the graduate biochemistry technology courses has gradually achieved good results. Later, the online-offline hybrid teaching form will be further improved and the curriculum teaching arrangement will be optimized further.

AIM:To investigate the therapeutic effects of syringin(SY)on vascular cognitive impairment(VCI)in rats and its possible mechanisms.METHODS:The rats were allocated into three groups:sham group(n=15);model group(n=21);and SY treatment group(n=19).The VCI rat model was induced via a modified bilateral ligation of the common carotid artery.Three days after the model induction,the SY treatment group received intraperitoneal injec-tions of 50 mg/kg SY once daily for 28 d.In total,15 rats in the sham operation group,17 rats in the model group,and 17 rats in the SY treatment group were included for further investigation.The cognitive and learning functions of the rats were assessed using the Morris water maze test,Y-maze test,and novel object recognition experiment.Cerebral blood flow was monitored through laser speckle imaging,while Evans blue staining was used to assess damage to the blood-brain barrier.Nissl staining,microtubule-associated protein-2(MAP-2),and neuronal nuclear antigen(NeuN)co-localization immuno-fluorescence staining demonstrated the extent of hippocampal damage.ELISA was employed to measure the levels of inter-leukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)in the brain tissue.Microglial activation was observed via ionized calcium-binding adapter molecule 1(IBA1)immunofluorescence staining,and Western blot analysis detected the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88)and phosphorylated(p)-P65 pro-teins in the brain tissue.RESULTS:Compared with the sham group,rats in the model group exhibited reduced cognitive function and cerebral blood flow(P＜0.01),increased blood-brain barrier permeability and degree of hippocampal tissue damage(P＜0.01),upregulation of TLR4,MyD88,and p-P65 protein expression in the brain tissue(P＜0.01),elevated levels of IL-1β,IL-6 and TNF-α(P＜0.01),as well as microglia activation(P＜0.01).In contrast to the model group,rats in the SY group demonstrated enhanced cognitive function and cerebral blood flow(P＜0.01),decreased blood-brain barrier permeability and degree of hippocampal tissue damage(P＜0.01),downregulation of TLR4,MyD88 and p-P65 protein expression in the brain tissue(P＜0.01),reduced levels of IL-1β,IL-6 and TNF-α,and reduced microglia density(P＜0.01).CONCLUSION:SY enhances cognitive function in VCI rats by improving cerebral blood flow,safeguarding the integrity of the blood-brain barrier,attenuating neuroinflammation,mitigating neuronal damage within the hippocam-pus,and inhibiting TLR4/MyD88/NF-κB signaling pathways.

【Objective】 To establish and verify a nomogram model of overall survival (OS) of prostate cancer patients based on the SEER data. 【Methods】 A total of 12 642 patients diagnosed with prostate cancer during 2010 and 2015 were extracted from the SEER database. Patients were randomly divided into the model group (n=8 850) and validation group (n=3 792). The independent risk factors for OS were analyzed with univariate Cox proportional risk regression, lasso regression and multivariate Cox proportional risk regression. A nomogram was constructed to predict the 1-year, 3-year and 5-year OS. The prediction potential of the model was evaluated with the consistency index (C-index), calibration curve and receiver operating characteristic (ROC) curve. 【Results】 Multivariate Cox regression analysis showed that age, T stage, N stage, M stage, bone metastasis, liver metastasis and regional lymphadenectomy were independent risk factors for OS (P<0.05). The seven factors were used to construct an OS nomogram model. The C-index of the modeling set was 0.750, and the area under the ROC curve (AUC) at 1, 3 and 5 years were 0.77, 0.77 and 0.76, respectively;the C-index of the validation set was 0.765, and the AUC at 1, 3 and 5 years were 0.83, 0.79 and 0.76, respectively. The calibration curves of the modelling set and validation set showed a good agreement with the actual survival prediction rate. Risk stratification of patients based on the nomogram model showed that the OS of patients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). 【Conclusion】 The nomogram can be used to predict the prognosis of prostate cancer patients, and is important for individualized treatment plans.

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

This paper introduces the clinical skill competition organized by the faculty of Otolaryngology Department of Shanghai Jiao Tong University School of Medicine, and analyzes the main problems in implementing items of basic life support, single ear compression bandage, debridement and suturing, foreign body removal from pharynx and larynx area, nasal packing and hemostasis and comprehensive skills. According to contestants' performances, their abilities in clinical analysis and operating skills have been tested, and their professional humanities have been cultivated. Thus, the aim of "promoting learning through examination and substituting competition for practice" is achieved through the competition. Clinical skill competitions can be used widely as supplement form of medical education for its practicability, entertainment, innovation and interaction.

COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Genetic Linkage ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide ; SARS-CoV-2/isolation & purification*

The residents and low-grade resident trainees of the Department of Otorhinolaryngology Head and Neck Surgery of the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine were selected as subjects. In the multi-touch virtual anatomy system, the lecturers made the anatomical signs of otolaryngology head and neck surgery, and applied them through the training method. Then the teachers explained the three sub-specialties of the nose, throat, neck and ear in the multi-touch virtual dissection table. The teaching method can stimulate the learning interest because of its vivid three-dimensional sense. The characteristics of teaching and learning are beneficial to the cultivation of medical education teachers. In addition, the one-time investment of equipment breaks through the supply bottleneck of traditional anatomical consumables and promotes active learning among medical students. The multi-touch virtual anatomy system can effectively improve the teaching methods, facilitate the interesting teaching, and has broad application prospects in medical teaching.

Objective: To investigate the effects of real-time anatomical demonstration and traditional teaching in otorhinolaryngology-head and neck surgery. Methods: Students who studied this course from Shanghai Jiao Tong University School of Medicine were divided into two groups: clinical students in 5-year program (n=22) were assigned to the experimental group and students from"5+3" stomatology major (n=35) were assigned to control group. Both groups had two class hours, with the same teacher teaching at the same day. Students in the experimental group were taught with theoretical teaching combined with real-time anatomical demonstration, while students in the control group was taught with traditional theoretical teaching with multimedia content. Students in the two groups completed the questionnaire and received quiz; SPSS 19.0 was used to perform the independent-samples T test of between-group data. Results: According to the questionnaire, scores for different items of the teaching method in the experimental group were higher than those in the control group. But according to the examination scores, average scores of the theoretical examination in the control group was (85.143±8.268), which was obviously higher than that of (64.545±11.434) in the experimental group, with statistically significant differences (t=7.885, P=0.000). Conclusion Teaching effect combined with real-time anatomical demonstration is not obvious to short-term examination, which may be related to the short-term understanding and absorption of knowledge for students in different majors, but it is coherent with the difference of entrance-examination scores of students from the two groups. This teaching model can stimulate students' interest in learning, and help them choose their professions, which may have certain advantages in the future long-term teaching effect.