Objective To explore the mechanisms of mesenchymal stem cells (MSC) in the treatment of concanavalin A (ConA)-induced acute immune liver injury in mice.Methods MSC were isolated and cultured from bone of the four limbs of three-week-old C57BL/6 mice.The specific surface markers were identified and osteogenic,adipogenic differentiation ability were tested.A total of 15 six to seven-week old C57BL/6 mice were divided into control group,MSC treatment group and phosphate buffer saline (PBS) treatment group,five mice in each group.The mice of MSC treatment group was injected through tail firstly with ConA and then MSC,PBS treatment group was injected through tail firstly with ConA and then PBS,control group was injected through tail with PBS twice.The mice were sacrificed in 14 to 16 hours after injection.The level of alanine aminotransferase (ALT),aspartate transaminase (AST) in peripheral blood were detected and the pathological change in liver tissue was scored by Knodell score system.Activation rate of splenic CD4+ T cells and the proportion changes of T hepler cell (Th)1,Th2,Th17 and regulatory T cells (Treg) were detected by flow cytometry and the ratio of Th17/Treg was calculated.The levels of tumor necrosis factor α (TNF-α),interferon (IFN)-γ and interleukin (IL)-4 in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA).Independent-sample t test was used for comparison between groups of measurement data.Results ALT,AST and Knodell score of MSC treatment group was (174.2± 46.9) U/L,(185.6± 71.6) U/L and 3.4±1.3,respectively,which were better than those of PBS treatment group ((647.0± 118.0) U/L,(749.0± 104.0) U/L and 5.2 ±0.8,respectively),and the differences were statically significant (t =8.33,9.98 and 2.55,all P＜0.05).The activation rate of splenic CD4+ T cell of PBS treatment group was (26.10±2.17) ％,the proportion of Th1 and Th2 in CD4+ T cell was (5.81±0.79) ％ and (5.98± 1.22)％,the ratio of Th17/Treg was 0.29±0.03,the levels of TNF-α,IFN-γ and IL4 in peripheral blood were (1 281.95±88.61) U/L,(1 838.66±196.91) U/L and (1 192.36±163.94) U/L,which were higher than those of control group ((13.74±1.59)％,(1.35±0.17)％,(2.13±0.17)％,0.15± 0.05,(21.71±2.50) U/L,(11.84±1.28) U/L and (24.46±3.96) U/L),and the differences were statistically significant (t=10.26,12.37,7.02,5.30,31.79,15.93 and 20.75,all P＜0.01).There was no statistically significant difference in the activation rate of splenic CD4+T cell between MSC treatment group and PBS treatment group ((26.20±3.09)％ vs (26.10±2.17)％,P＞0.05).However,in MSC treatment group,the proportion of Th1 and Th2 in CD4+ T cell ((1.83±0.52) ％ and (2.75±1.06％)),the ratio of Th17/Treg (0.18±0.02) and the levels of TNF-α,IFN-γ and IL-4 in peripheral blood ((760.71± 73.19) U/L,(742.49±76.46) U/L and (825.76±101.74) U/L) significantly decreased compared with those of PBS treatment group,and the differences were statistically significant (t=9.45,4.48,6.41,10.14,5.56 and 10.22,all P＜0.01).There was no significant difference in the ratio of Th17/Treg between MSC treatment group and control group (P＞0.05).Conclusions The therapeutic effects of MSC on ConA induced acute immune liver injury were through influence splenic CD4+ T cell subsets by decreasing the proportion of Th1 and Th2 and then declining the levels of secreted cytokines such as TNF,IFN-γ and IL-4 in peripheral blood,increasing the proportion of Treg and decreasing the proportion of Th17 and keeping the balance of Th17/Treg.

Objective:To establish a comprehensive and detailed evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery, providing reference for promoting the construction of clinical practice bases for nursing graduate students majoring in midwifery in China.Methods:Based on the theoretical framework of international midwifery practice basic skills, an evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery was established through literature analysis and Delphi method. Analytic hierarchy process was used to calculate the weights of indicators at all levels.Results:This study conducted two rounds of consultation with 20 experts. In the two rounds of consultation, the positivity coefficients of experts were 84.38% and 74.07%, and the authority coefficients of the expert groups were 0.91 and 0.94, respectively. The total Cronbach's α coefficients of the index system were 0.930 and 0.965, respectively, and the Kendall harmony coefficients of the overall indicators were 0.230 and 0.297 ( P<0.01). The final evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery included five primary indicators, 14 secondary indicators, and 76 connotation indicators. Conclusions:Based on the service purpose of maternal and child health and the functional positioning of the base, this study constructs a scientific and reliable evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery.

Objective To observe the changes in subfoveal choroidal thickness (SFCT) and peripapillary choroidal thickness (pCT) in nonarteritic anterior ischemic optic neuropathy (NAION). Methods Nineteen newly occurred NAION patients were included. The patients were divided into group A (20 affected eyes of 19 patients) and B (18 fellow eyes of 18 patients). Twenty eyes of 20 age, gender, intraocular pressure and axial length-matched healthy volunteers (group C) were enrolled in this study. The differences of age (t=1.58), gender ratios (χ2=0.107), intraocular pressure (t=0.092) and axial length (t=0.148) between 3 groups were not significant (P>0.05). SFCT, pCT were measured at first visit, 1 month and 3 months after treatment using enhanced deep imaging technique of spectral domain optical coherence tomography. The correlation of best corrected visual acuity (BCVA) and the choroidal thickness was investigated. Results At the first visit, the mean SFCT and pCT in group A were significant thicker than group C (t=2.957, 2.844; P=0.006, 0.009). There was no difference of SFCT and pCT between group B and C (t=2.019, 2.024; P=0.053, 0.057). There was no correlation between BCVA and SFCT, pCT (F=0.161, 0.033; P=0.695, 0.859). One month after treatment, SFCT in group A was still thicker than group C (t=2.803, P=0.009); while pCT was decreased in group A when compared to group C, but the difference was not significant (t=1.871, P=0.084). Three months after treatment, the differences of SFCT and pCT were not significant between group A and C (t=1.223, 1.105; P=0.236, 0.282). Conclusions At first visit, SFCT and pCT in NAION eyes showed a significant increase when compared to normal eyes. One month later, pCT in NAION eyes decreased to normal. Three months later, both SFCT and pCT decreased. These findings may suggest that a thickened choroid is a clinical characteristic at acute stage in NAION eyes.

Objective:To investigate the effects of early percutaneous coronary intervention (PCI) on myocardial perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction (STEMI) after thrombolysis.Methods:A total of 108 patients with STEMI treated in the Second Hospital of Hebei Medical University from January 2020 to December 2022 were divided into early PCI following thrombolysis group ( n=65) and primary PCI (pPCI) group ( n=43). The general clinical data, and the parameters of routine echocardiography at 1 day after PCI and before discharge were compared between the two groups. Myocardial contrast echocardiography (MCE) was used to evaluate myocardial perfusion at 1 day after PCI and before discharge. Results:There were no significant differences in general clinical data between the early PCI following thrombolysis group and the pPCI group (all P>0.05). The left ventricular ejection fraction (LVEF) in the early PCI following thrombolysis group and pPCI group before discharge was significantly higher than that on the 1st day after PCI(both P<0.05). The difference of LVEF was significant between the early PCI following thrombolysis group and the pPCI group before discharge and 1 day after PCI ( P<0.05). Compared with 1 day after PCI, the global longitudinal strain (LVGLS) of left ventricle increased in early PCI following thrombolysis group and pPCI group before discharge(both P<0.05). The difference of LVGLS between early PCI following thrombolysis group and pPCI group before discharge and 1 day after discharge was statistically significant( P<0.05). There were no significant differences in left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial volume (LAV), ratio of mitral early diastolic velocity to late diastolic velocity (E/A), mean early diastolic velocity of mitral annulus (Em) and E/Em 1 day after PCI and before discharge between early PCI following thrombolysis group and pPCI group (all P>0.05). MCE showed that the MCE score index of early PCI following thrombolysis group and pPCI group before discharge was significantly lower than that of 1 day after PCI(both P<0.001). Compared to the 1 day after PCI, the early PCI following thrombolysis group showed a significant increase in the proportion of normal microvascular perfusion (nMVP) and a decrease in the proportion of delayed microvascular perfusion (dMVP) and microvascular obstruction (MVO) before discharge (all P<0.05). In contrast, the pPCI group demonstrated a significant decrease in the proportion of both nMVP and dMVP before discharge compared to the first day after PCI (all P<0.05). However, the decrease in the proportion of MVO was not statistically significant ( P>0.05). Conclusions:Early PCI following thrombolysis and pPCI can enhance left ventricular systolic function and myocardial perfusion in patients with acute ST-elevation myocardial infarction. Early PCI following thrombolysis may offer additional advantages in improving left ventricular systolic function and myocardial perfusion.

Objective To investigate the efficacy of video-assisted teaching ward rounds for typical cases of oph-thalmology in clinical practice for medical undergraduates.Methods A total of 45 students from clinical medicine in Peking Union Medical College were enrolled.They were randomly divided into the experimental group(23 students)and control group(22 students).Primary angle closure glaucoma(PACG)was selected as the learning content,the experimental group was trained by video-assisted teaching ward rounds,while the control group was trained by internship in outpatient clinic.All students joined the test of typical case PACG and a ques-tionnaire survey was implemented for the experimental group.Results The average score of experimental group was higher than control group[(84.30±4.53)vs.(78.05±5.76),t＝4.05,P＜0.001].For video-assisted teaching ward rounds,in experimental group,86.9%(20/23)students believed it was more practical,95.6%(22/23)students thought it was very helpful and 91.3%(21/23)students considered it was conductive to im-prove interest of learning and clinical thinking ability.Conclusions Video-assisted teaching ward rounds improves students'understanding memory of ophthalmic typical cases,which is a potential supplement teaching method in clinical practice training of ophthalmology for medical undergraduates.

Objective:To evaluate the degree of left atrial fibrosis in patients with persistent atrial fibrillation(AF) using four-dimensional automic left atrial quantitation(4D Auto LAQ).Methods:A total of 60 patients with persistent AF who underwent transcatheter radiofrequency ablation in the Second Hospital of Hebei Medical University from March 2022 to March 2023 were included. Patients were grouped according to the low-voltage area (mild<5%, moderate 5%-20%, severe>20%). General clinical data, conventional echocardiogram parameters, left atrial strain and related parameters of each group were compared. The relevant factors were obtained by Logistic regression analysis. The factor with the highest accuracy and its cut-off value was obtained by the ROC curve.Results:Sixty patients with persistent atrial fibrillation, were divided into mild low-voltage group(22 cases), moderate low-voltage group(20 cases), and severe low-voltage group(18 cases). There were statistical differences in gender, CHA2DS2-VASc score, peak value of early diastolic velocity of mitral inflow/average peak value of early diastolic tissue Doppler velocity of mitral annulus (E/e′), left atrial diameter (LAD), left atrial volume index (LAVI), left atrial maximal volume (LAVmax), left atrial minimal volume (LAVmin), left atrial total emptying fraction (LAEF), left atrial reservoir longitudinal strain (LASr), left atrial reservoir circumferential strain (LASr-c), left atrial myocardial work (LA MW, LA MW-c), left atrial stiffness (LA stiffness, LA stiffness-c) among the 3 groups(all P<0.05). The LASr had the highest correlation with low voltage area ( rs=-0.814, P<0.001). Logistic regression analysis showed that CHA2DS2-VASc, LAD, LAVI, LAVmax, LAVmin, LAEF, LASr, LASr-C, LA MW, LA MW-C, LA stiffness and LA stiffness-c could all predict the low voltage area(all P<0.05). The LA stiffness had the highest AUC (0.952). The cut-off value of severe low voltage was 1.15, the sensitivity was 94.4%, and the specificity was 83.3%. Conclusions:4D Auto LAQ can be used to evaluate the degree of left atrial fibrosis. The correlation between LA stiffness and substrate voltage mapping is the highest.

Objective This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis,as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions.Me-thods 1)The cancer genome atlas(TCGA)database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-check-point molecules that interfere with tumor immune escape.2)Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis.Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened.3)Immunohis-tochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on da-ta calculation in various stages of oral mucosal carcinogenesis.4)Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification.5)Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis.The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified.Results The expression of monocytes and neutro-phils increased during the process of oral mucosal carcinogenesis.The expression of eosinophils showed a single peak trend of up and down.The expression of mast cells decreased.In the process of oral mucosal carcinogenesis,the ex-pression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4(CTLA4)and programmed cell death-ligand(PD-L1)increased.The expression trends of monocytes,neutrophils,and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules.The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1.Monocytes,neutrophils,and eosinophils may pro-mote tumor immune escape mediated by CTLA4 and/or PD-L1,thereby accelerating the progression of oral mucosal carcinogenesis.Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1,delaying the progres-sion of oral mucosal carcinogenesis.Conclusion Therefore,interference with specific immune cells in innate immu-nity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent,inhibit tumor immune escape,and delay the progression of oral mucosal carcinogenesis.

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.
Saccharomyces cerevisiae/genetics* ; Sterols ; Phytosterols ; Biological Transport ; ATP-Binding Cassette Transporters/genetics*

【Objective】 To explore the expression of PCDH9 loss in regulating cell cycle and promoting tumor progression. 【Methods】 The clinical records of 127 cases of prostate cancer treated during 2018 and 2023 were collected, including 87 paraffin tissue samples from the G4-5 group and 40 from the G1-3 group. The expressions of PCDH9, p53, Rb and STAT3 were detected with immunohistochemical staining, and the relationship between their expressions and clinicopathological characteristics was analyzed. 【Results】 The expression deletion rate of PCDH9 in prostate cancer tissues in G4-5 group (44.8% vs.7.5%) was significantly higher than that in G1-3 group (P<0.001). The positive expression rates of p53 and STAT3 were 34.5% and 89.7%, respectively, and the expression loss rate of Rb was 27.6% in G4-5 group. The expression loss rates of PCDH9 and Rb were associated with neuroendocrine-like histological morphology, nerve invasion and vascular invasion (P<0.05). In G4-5 group of prostate cancer, PCDH9 expression was positively correlated with the expressions of p53 (r=0.345, P<0.05), Rb (r=0.503, P<0.05) and STAT3 (r=0.224, P<0.05). 【Conclusion】 PCDH9 is prone to loss of expression in high-group prostate cancer tissues, especially in cases with neuroendocrine-like histological morphology, which may regulate the cell cycle through the STAT3 signaling pathway, thereby promoting tumor progression.