Objective To deplore the immunoregulatory function changes of mesenchymal stem cells(MSCs)from multiple myeloma(MM)patients and its effects on the pathogenesis of myeloma bone disease.Methods MSCs from MM patients and normal controls were isolated and the immunophenotype was detected.Real-time PCR was performed to detect the expressions of TGF-β1,TGF-β2,TGF-β3,IL-6,IL3,TNF-α,FasL and RANKL of MSCs.Transwell coculture systems were performed between MSCs and T cells.Lymphocyte proliferative assay was employed to detect the effect of MSCs on T cell proliferation.The effect of MSCs on T cell cycle and T cell activation markers CD25 and CD69 expression were analyzed by flow cytometry.Cleaved caspase 3 protein by western blot and hoechst 33258 staining were employed to detect the apotosis of T cells.Influence of T cells on the osteogenesis potential of MSCs were detected by Von kossa stain,real-time PCR and Western blot.Results MSCs from both MM patients and normal controls possessed similar morphology and immunophenotypes.MM derived MSCs exhibited increased expressions of TGF-β1,IL-6,IL-3,TNF-α and RANKL and decreased expression of TGF-β2,TGF-β3 and FasL.The inhibitory effect of MM derived MSCs on T cell proliferative ability was attenuated compared to control MSCs.MSCs from normal controls silence more T cells in Go/G1 phase than those from MM patients.The daupening effect of MM derived MSCs on activation-induced T apoptosis seemed to be enhanced.Expression of T cell activation markers were significantly inhibited by MSCs from normal controls.Both T cells cocultured with MM deprived MSCs and T cells directly from MM patients inhibited osteogenesis potential of MSCs from normal controls.Conclusion MSCs from MM patients showed impaired immunoregulatory capability on T cells.The activated T cells,in turn,inhibited the osteogenesis potential of MSCs.This may participate in the pathogenesis of myeloma bone disease.

Objective To explore the role of stem cell factor(SCF)-mediating fibroblasts and mast cells interaction in pathophysiology process of asthma.Methods We transfected NIH3T3 cells with SCF antisense oligonucleotide(SCF ASON) and detected SCF expression by immunochemistry and RT-PCR.Then,we isolated mast cells from mouse bone marrow and established NIH3T3 and mast cells cocultures.After SCF ASON intervention,histamine and eotaxin levels in culture supernatants were determined by ELISA and fluorometry.Growth curves of fibroblasts and mast cells were drawn.We also observed mast cells apoptosis by AO stain and flow cytometric analysis.Results SCF ASON strikingly down-regulated SCF protein and mRNA level of NIH3T3 cells.SCF ASON intervention inhibited the growth of NIH3T3,and induced mast cell apoptosis in cocultures(14.0%?0.81% at 96 hour).Both histamine[(3.08?0.38)?g/L vs(3.83?0.41)?g/L,P

Objective:To compare the prediction efficiency of traditional linear regression model and four machine learning models on the learning behavior of clinical medical postgraduates, and to explore the pros and cons and applicability of different prediction models.Methods:A total of 6,922 clinical medical postgraduates were surveyed, their comprehensive learning behavior scores were obtained through the learning behavior scale. In the training set, Lasso linear regression and artificial neural network, decision tree, Bootstrap random forest, and lifting tree were used to build prediction models respectively. The above models were used to predict the validation set data and compare the prediction efficiency.Results:The comprehensive learning behavior score of clinical medical postgraduates was (3.31±0.54) points, and the overall compliance rate was 74.02%. In the linear regression model, the influence of age, school level, degree type, learning interest, pressure and satisfaction on learning behavior were statistically significant. In the prediction of validation set, the sensitivity, specificity, and accuracy of the linear regression model were 0.484, 0.914, and 0.801, respectively. The indexes of the four machine learning models were higher than those of the traditional linear regression model, and the Bootstrap random forest had the highest elevation.Conclusion:The linear regression model has a good prediction effect on learning behavior, and machine learning is superior to linear regression model in terms of accuracy of prediction. However, traditional linear regression models are superior to machine learning models in computational efficiency and interpretability.

Objective:To investigate the characteristics of gene mutations in colorectal cancer(CRC)patients by using next-generation generation sequencing(NGS).Methods:Blood and tissue samples were collected from 90 CRC patients admitted to Beijing Hospital between August 5, 2016 and December 29, 2020.Analysis of driver gene mutations was performed by using a 1021-gene NGS panel.Results:There were 43 tissue samples and 83 blood samples.Also, 36 patients had both tissue and blood samples.The frequency rates of KRAS and BRAF mutations were 51.2%(22/43)and 20.9%(9/43)in tissue samples, and 3 rare concomitant KRAS/ BRAF mutations were detected.The frequency rates of KRAS and BRAF mutations were 26.5%(22/83)and 10.8%(9/83)in blood samples.In patients with tissue and blood samples, the rates of KRAS and BRAF mutations were 52.8%(19/36)and 10.8%(8/36). Conclusions:The rate of KRAS mutations in tissue samples from colorectal cancer patients is similar to rates reported in the literature, but the rate of BRAF mutation and the rate of rare KRAS and BRAF co-mutations are higher than those reported from other countries.

Objective:To construct a reasonable and efficient clinical nursing pathway for elderly patients with acute chest pain in the emergency department, and to provide a standardized and rapid treatment process for such patients.Methods:Through literature review and theoretical analysis, the basic framework of clinical nursing pathway was preliminarily drawn up. Twenty one clinical medical and nursing experts from all over the country were selected to conduct two rounds of expert consultation with Delphi method, and the clinical nursing path was finally determined.Results:The recovery rates of the two rounds of questionnaires were 100.00% and 95.24%, and the rates of submission expert suggestions were 61.90% and 45.00%, the authority coefficients of experts were 0.85 and 0.88, and the coordination coefficients were 0.23 and 0.30. Finally, the clinical nursing pathway was constructed after two rounds of consultation.Conclusion:The positive coefficient and authority coefficient of the two rounds of experts were both high, and the variable coefficient and coordination coefficient were in line with the statistical requirements, so the clinical nursing path of the elderly patients with acute chest pain had high scientificity and reliability.

Objective:To evaluate the effect of portal vein restriction combined with hepatic artery ligation on Sprague Dawley(SD) rats liver regeneration and injury.Methods:Twenty-four healthy and clean SD male rats, 250-280 g, 7-8 weeks old, were randomly divided into portal vein ligation (PVL) group, mild restriction group and moderate restriction group with 8 rats in each group. In PVL group, the right, caudal and left branches of portal vein were ligated, and only the right branches of portal vein were preserved. The operation of mild and moderate restriction group was the same as PVL, however, the left branch of the portal vein was slightly and moderately restricted, and the left branch of the hepatic artery was ligated at the same time. At 72 hours after the operation, the left middle lobe was stained with hematoxylin-eosin and the total necrosis score was calculated. The right middle lobe was immunostained for Ki-67 and the number of positive cells was counted. The liver regeneration rate of the right middle lobe was calculated and the serum liver function indexes were measured.Results:The hepatic regeneration rate of right middle lobe in PVL group was (109.1±10.9)%, while that in moderate restriction group was (105.0±12.3)%, which was significantly higher than that in the mild restriction group (67.1±6.4)%, the differences were statistically significant ( P<0.05). The Ki-67 result was also higher in the PVL group than the mild restriction group. The total necrosis score was 4.50(3.25, 6.00) in moderate restriction group, 2.00(1.25, 3.00) in PVL group and 0(0, 0.75) in mild restriction group. The three groups showed a decreasing trend and the differences were statistically significant ( P<0.05). Alanine aminotransferase in mild restriction group was (48.4±11.4) U/L, was significantly lower than that in PVL group (67.2±12.2) U/L and moderate restriction group (74.3±14.2) U/L, the difference was statistically significant ( P<0.05). There were no significant differences in serum levels of aspartate aminotransferase, albumin and total bilirubin among the three groups ( P>0.05). Conclusion:Appropriate portal vein restriction combined with hepatic artery ligation can effectively induce the regeneration of liver tissue on the reserved lobe and control the damage of liver tissue on the occluded lobe.

BACKGROUND: Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo . This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. METHODS: Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment. RESULTS: Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t = 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). CONCLUSIONS Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.
Humans ; Cicatrix/diagnostic imaging* ; Skin/pathology* ; Collagen ; Imaging, Three-Dimensional/methods*

The aqueous two-phase system (ATPS) is an all-aqueous system fabricated from two immiscible aqueous phases. It is spontaneously assembled through physical liquid-liquid phase separation (LLPS) and can create suitable templates like the multicompartment of the intracellular environment. Delicate structures containing multiple compartments make it possible to endow materials with advanced functions. Due to the properties of ATPSs, ATPS-based drug delivery systems exhibit excellent biocompatibility, extraordinary loading efficiency, and intelligently controlled content release, which are particularly advantageous for delivering drugs in vivo. Therefore, we will systematically review and evaluate ATPSs as an ideal drug delivery system. Based on the basic mechanisms and influencing factors in forming ATPSs, the transformation of ATPSs into valuable biomaterials is described. Afterward, we concentrate on the most recent cutting-edge research on ATPS-based delivery systems. Finally, the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.

Chinese materia medica has a wide range of clinical applications， but it has many active ingredients with different physicochemical properties， and the target organs， action pathways and mechanisms for different ingredients to exert their efficacy are not the same. Therefore， it is difficult to design and develop a co-delivery system loading multiple components of Chinese materia medica to maximize the synergistic therapeutic efficiency. Based on the characteristics of effectiveness and functionality of active ingredients， the strategies for multi-component co-delivery of Chinese materia medica can be categorized into two types：firstly， based on the effectiveness of active ingredients， new carriers such as liposomes， nanoparticles can be constructed to load multi-components of Chinese materia medica. secondly， based on the functionality of some active ingredients of Chinese materia medica， they are employed in the construction of co-delivery system， which can give play to the dual characteristics of their own efficacy and preparation functions. In this paper， we summarized the relevant research progress of the above two types of multi-component co-delivery strategies， and mainly discussed the pharmaceutical functions of the active ingredients in co-delivery systems， in order to find a more suitable multi-component co-delivery strategy， promoting the design and development of new delivery systems of Chinese materia medica.