Gastrointestinal graft versus host disease is one of the most severe complications after hematopoietic stem cell transplantation, which can occur in patients of any age groups. Its clinical manifestations include nausea, vomit, abdominal pain, diarrhea and the like. Severe gastrointestinal graft versus host disease could directly influence the patients' clinical prognosis and therapeutic efficacy of transplantation. Here we had a review of the research progress on nutritional support and diet management strategies for gastrointestinal graft versus host disease. It is of great clinical significance to form a step-wise nutritional support model to reduce the risk of malnutrition in patients with gastrointestinal graft versus host disease, which would contribute to improving patients' general condition, relieving digestive tract symptoms, and reducing the risk of complications.

Objective To explore the effects of proteasome 20S subunit beta 8(PSMB8)on the prolif-eration,migration,and invasion of clear cell renal cell carcinoma(ccRCC)cells and whether PSMB8 promotes tumor progression by activating the mitogen-activated protein kinase kinase(MEK)/extracellular signal-regula-ted kinase(ERK)signaling pathway.Methods The Cancer Genome Atlas was employed to analyze the mRNA levels of PSMB8 in ccRCC and normal tissue,and the expression levels of PSMB8 in ccRCC tissue and cells were determined by real-time quantitative PCR,Western blotting,and immunohistochemistry.Furthermore,the cell lines with stable overexpression and knockdown of PSMB8 were constructed.The CCK-8 assay and colony forma-tion assay were employed to examine the cell proliferation,and the wound healing assay and Transwell assay were employed to examine the invasion and migration of cells.Kyoto Encyclopedia of Genes and Genomes pathway enrich-ment was performed to analyze the co-expressed genes of PSMB8.Western blotting was used to measure the phospho-rylation levels of the proteins in the MEK/ERK signaling pathway.Finally,the rescue experiment was carried out with the ERK agonist C16-PAF.Results Compared with the normal tissue,the ccRCC tissue showed up-regulated mRNA and protein levels of PSMB8(both P＜0.001),which were associated with the TNM stage of patients with ccRCC(P＜0.001).Compared with the negative control group,overexpression of PSMB8 promoted the prolifera-tion(P=0.021,P=0.039),migration and invasion(all P＜0.001)of 786-O and ACHN cells,and the knock-down of PSMB8 inhibited the proliferation(P=0.022,P=0.005),migration and invasion(all P＜0.001)of 786-O and ACHN cells.The pathway enrichment analysis of co-expressed genes of PSMB8 predicted the mitogen-ac-tivated protein kinase signaling pathway(P＜0.001).After the knockdown of PSMB8,786-O and ACHN cells showed lowered phosphorylation levels of MEK1/2(P=0.017,P=0.016)and ERK1/2(P=0.010,P=0.040)and down-regulated transcription levels of ERK downstream factors c-Myc(P=0.043,P=0.038),c-Fos(P=0.025,P=0.008),and CyclinD1(P=0.006,P=0.047).Compared with the ERK agonist C16-PAF group,the PSMB8 knockdown+C16-PAF group showed inhibited proliferation(P=0.003,P=0.002),migration and invasion(all P＜0.001)of 786-O and ACHN cells.Conclusion PSMB8 may promote the proliferation,migration,and invasion of ccRCC cells by activating the MEK/ERK signaling pathway.

Objective:To establish a medical equipment maintenance model based on the analytic hierarchy process(AHP),and to study its application effect in the management of orthopedic medical equipment in hospitals.Methods:Based on the analytic hierarchy process(AHP),the equipment maintenance model was constructed from the classification of the service life,failure mode,failure consequences and other indicators of orthopedic medical equipment.25 sets of medical equipment in clinical use in the Department of Orthopedics of The Second Affiliated Hospital of the Air Force Medical University from 2019 to 2022 were randomly selected,taking the time as the dividing point,the traditional orthopedic medical equipment management model(referred to as traditional management)was implemented during the equipment use period from 2019 to 2020,and the equipment maintenance model based on AHP was used to manage orthopedic medical equipment(referred to as model management)during the equipment use period from 2021 to 2022.A total of 1,000 equipment usage records were collected,500 for each mode,and the effect of equipment repair and maintenance,the satisfaction score of equipment usage management and the incidence of adverse events were compared under different management modes.Results:The cost-effectiveness of equipment using the model management mode was an average of CNY(34,500.00±4,700.00)per unit per year,which was higher than that of the traditional management mode,the difference was statistically significant(t=8.417,P<0.05),the maintenance costs and operating costs were CNY(15,381.95±13.67)per year and CNY(31,600.00±10,500.00)per year,respectively,which lower than those of the traditional management model,the difference was statistically significant(t=858.675,5.371,P<0.05).The scores of equipment management personnel on equipment performance,timeliness and cleanliness of the equipment using the model management mode,and the patients'satisfaction with convenience,effect and comfort of the equipment(9.65±1.14),(9.74±1.38),(9.53±1.09),(9.58±1.07),(9.62±1.14)and(9.81±1.28),respectively,which were all higher than those of the traditional management mode,the difference was statistically significant(t=5.629,5.687,4.736,8.085,5.330,7.680,P<0.05).The total incidence of adverse events in equipment using model management mode was 4.8%(24/500),which was lower than that of the traditional management mode,the difference was statistically significant(x2=12.515,P<0.05).Conclusion:The application of medical equipment maintenance model based on analytic hierarchy process to the management of orthopedic medical equipment can effectively reduce the equipment maintenance cost,improve the cost-effectiveness of the equipment,and improve the satisfaction of the equipment use management personnel.

Objective:To evaluate the effects of GSK484 on ventilator-induced lung injury (VILI) and neutrophil extracelluar traps (NETs) in mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 5-6 weeks, weighing 15-20 g, were divided into 4 groups ( n=12 each) by a random number table method: spontaneous breathing group (group S), spontaneous breathing+ GSK484 intervention group (group SG), VILI group (group V), and VILI + GSK484 intervention group (group VG). The animals kept spontaneous breathing for 4 h after tracheal intubation in S and SG groups. The animals were mechanically ventilated for 4 h (tidal volume 30 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, positive end-expiratory pressure 0 mmHg, fraction of inspired oxygen 21%) in V and VG groups. At 3 days before developing the VILI model, GSK484 4 mg/kg was intraperitoneally injected once a day in SG and VG groups, while the equal volume of normal saline was given instead in S and V groups. Blood samples were collected from the abdominal aorta for blood gas analysis at 4 h of spontaneous breathing or mechanical ventilation, and PaO 2 was recorded. The mice were then sacrificed and bronchoalveolar lavage fluid (BALF) was collected and lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope after HE staining) which were scored and for determination of wet to dry weight ratio (W/D ratio), concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) in BALF (by enzyme-linked immunosorbent assay), expression of peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), high mobility group box 1 (HMGB1) and citrullinated-histone 3 (Cit-H3) in lung tissues (by Western blot). Results:Compared with S and SG groups, the lung injury score and W/D ratio were significantly increased, PaO 2 was decreased, concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 in lung tissues was up-regulated in V and VG groups ( P<0.05). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 was increased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group VG ( P<0.05). Conclusions:GSK484 can alleviate VILI in mice, and the mechanism is associated with inhibition of PAD4, reduction of the production of NETs and attenuation of inflammatory responses in lung tissues.

Objective:To preliminarily evaluate the immunogenicity and efficacy of two novel tuberculosis vaccine candidates (a fusion multicomponent protein EPDPA015f and a mixed multicomponent protein EPDPA015m) and to provide a new antigen combination for the development of tuberculosis vaccines.Methods:Recombinant plasmids for the expression of EPDPA015f and EPDPA015m proteins were constructed. Six-week-old BALB/c mice were immunized with EPDPA015f or EPDPA015m in combination with aluminium adjuvant (50 μg/mouse) for three times with an interval of 10 d. The mice were sacrificed 10 d after the last immunization to collect blood and spleen samples. Serum antibody titers and cytokine levels were measured by ELISA, Luminex technique and enzyme-linked immunospot assay (ELISPOT). Mycobacterial growth inhibition assay (MGIA) was used to detect the ability of mouse splenocytes to inhibit the growth of Mtb in vitro. One-way analysis of variance and t-test were used for statistical analysis. Results:Both EPDPA015f and EPDPA015m could induce the production of various cytokines and IgG antibodies at a high level. The levels of cytokines related to Th1 (IL-2, TNF-α, IFN-γ), Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) as well as other proinflammatory cytokines (GM-CSF, IL-12) were higher in the EPDPA015f group than in the adjuvant group ( P<0.05). The titer of IgG antibody induced by EPDPA015f was as high as 1∶4×10 6. The results of MGIA showed that the numbers of Mtb (lgCFU) in the PBS, adjuvant, EPDPA015f and EPDPA015m groups were 3.46±0.11, 3.51±0.06, 2.98±0.09 and 3.19±0.08, respectively. The number of colonies in the EPDPA015f group was the least as compared with that in the other three groups ( P<0.001, P<0.001, P<0.01). Conclusions:The vaccine candidate EPDPA015f could elicit more comprehensive and high-level cellular and humoral immune responses, and exhibited superior in vitro inhibitory activity against the growth of Mtb. EPDPA015f had the potential to be used as a preventive vaccine or a booster vaccine

Objective:To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB.Methods:Three full-length Mycobacterium ( M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M.tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results:Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance ( P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group ( P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group ( P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group ( P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group ( P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups ( P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant ( P>0.05). Conclusion:Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Objective: To evaluate the caries preventive effect and economic outcome of an oral health promotion model in rural primary schools in Guangxi Zhuang Autonomous Region. Methods: In November 2015, a baseline survey was conducted on the caries prevalence of rural first graders in program areas, and then a program intervention was carried out on the first graders of target primary schools. The intervention methods included the distribution of oral health care products, oral health education, teacher training, etc. In 2020, the method of cluster random sampling was adopted to include the sixth graders who received the program intervention as first graders and were still available in 2020 as the intervention group. During this period, the sixth graders transferred from foreign schools who failed to receive the program intervention as first graders were included in the non-intervention group. The caries preventive effect was evaluated by analyzing the caries epidemiological data of 2 652 children aged 11-13 years, comparing the intervention and non-intervention group. The cost of the program was estimated by the structural analysis method. A decision tree model was established by TreeAge pro2019 and incorporated into the effect parameters and cost parameters for cost-effectiveness analysis and sensitivity analysis. Results : The prevalence of caries in the intervention group was 54.8%, and the mean DMFT was 1.36 ± 1.64, both of which were lower than those in the non-intervention group. The difference in prevalence and mean DMFT between the two groups was statistically significant (P < 0.05). It costs CNY 319.83 per child to reduce suffering from caries. The number of patients with caries in the intervention group was the most sensitive indicator of an economic effect. The probability of a cost-effectiveness advantage for the program was 92.2%. Conclusion This oral health promotion model used in rural schools demonstrated a caries preventive effect that was very likely economically advantageous. It is of practical significance to improve and promote this model in the Guangxi Zhuang Autonomous Region.

Objective:To develop the modified medication regimen complexity index of Chinese version (mMRCI-C)and test its reliability and validity.Method:The Chinese version of MRCI was developed by modification,translation and back translation. The MRCI was interculturally adapted by 2-rounds of expert consultation and pilot study to ensure the semantics, content and conceptual equivalence. The validation of the mMRCI-C scale was tested among 420 community-dwelling elderly patients with type 2 diabetes mellitus(T2DM) in Shanghai Changfeng Community Health Service Center from October to December 2020. SPSS 23.0 was used to analyze the reliability and validity of the scale.Results:The mMRCI-C scale included 3 dimensions, namely drug dosage form (14 entries), medication frequency (5 entries), and additional instructions (6 entries), with a total of 25 entries. Among 420 valid questionnaires collected,the respondents were 212 males (50.4%) and 208 females (49.6%) with a mean age of (71.4±8.1) years. The test-retest reliability was 0.999 and internal consistency reliability was 0.849. The content validity exceeded 0.80,the convergent validity was 0.932; and discriminant validity P<0.001. Conclusion:The preliminary testing results show that the reliability and validity of the mMRCI-C scale are satisfactory.

Objective:To investigate the effect of blocking P21 activated kinase 1 (PAK1) activity on the proliferation, differentiation, and apoptosis of acute megakaryocytic leukemia (AMKL) cell lines (CHRF and CMK) .Methods:Cell counts were used to detect the effects of PAK1 inhibitors (IPA-3 and G5555) on AMKL cell proliferation inhibition and colony formation, and flow cytometry was used to detect its effects on AMKL cell cycle. The effect of PAK1 inhibitor on the expression of cyclin D1 and apoptosis-related protein Cleaved caspase 3 was detected using Western blot, while interference with the protein expression level of PAK1 in AMKL cells was assessed using lentivirus-mediated shRNA transfection technology. Flow cytometry was used to detect the effects of knockdown of PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in AMKL cells.Results:PAK1 inhibitors inhibited the proliferation of AMKL cells in a dose-dependent manner and reduced the ability of cell colony formation, and the difference was statistically significant when compared with the control group ( P<0.05) . Moreover, they also reduced the percentage of AMKL cells in S phase, and Western blot detection showed that the expression levels of phosphorylated PAK1 and cyclin D1 decreased significantly. Finally, PAK1 inhibitors induced AMKL cell apoptosis by up-regulating Cleaved caspase 3 and showed different abilities to increase the content of polyploid DNA in megakaryocytes. Only high concentrations of IPA-3 and low doses of G5555 increased the number of polyploid megakaryocytes, while knockdown of PAK1 kinase activity promoted AMKL cell differentiation and increased the apoptosis rate. Conclusion:PAK1 inhibitor significantly arrests AMKL cell growth and promotes cell apoptosis. Knocking down the expression of PAK1 promotes the formation of polyploid DNA and induces AMKL cell apoptosis. The above findings indicate that inhibiting the activity of PAK1 may control AMKL effectively.

Objective:To evaluate the efficiency of ResNet50-OC model based on deep learning for multiple classification of color fundus photographs.Methods:The proprietary dataset (PD) collected in July 2018 in BenQ Hospital of Nanjing Medical University and EyePACS dataset were included.The included images were classified into five types of high quality, underexposure, overexposure, blurred edges and lens flare according to clinical ophthalmologists.There were 1 000 images (800 from EyePACS and 200 from PD) for each type in the training dataset and 500 images (400 from EyePACS and 100 from PD) for each type in the testing dataset.There were 5 000 images in the training dataset and 2 500 images in the testing dataset.All images were normalized and augmented.The transfer learning method was used to initialize the parameters of the network model, on the basis of which the current mainstream deep learning classification networks (VGG, Inception-resnet-v2, ResNet, DenseNet) were compared.The optimal network ResNet50 with best accuracy and Micro F1 value was selected as the main network of the classification model in this study.In the training process, the One-Cycle strategy was introduced to accelerate the model convergence speed to obtain the optimal model ResNet50-OC.ResNet50-OC was applied to multi-class classification of fundus image quality.The accuracy and Micro F1 value of multi-classification of color fundus photographs by ResNet50 and ResNet50-OC were evaluated.Results:The multi-classification accuracy and Micro F1 values of color fundus photographs of ResNet50 were significantly higher than those of VGG, Inception-resnet-v2, ResNet34 and DenseNet.The accuracy of multi-classification of fundus photographs in the ResNet50-OC model was 98.77% after 15 rounds of training, which was higher than 98.76% of the ResNet50 model after 50 rounds of training.The Micro F1 value of multi-classification of retinal images in ResNet50-OC model was 98.78% after 15 rounds of training, which was the same as that of ResNet50 model after 50 rounds of training.Conclusions:The proposed ResNet50-OC model can be accurate and effective in the multi-classification of color fundus photograph quality.One-Cycle strategy can reduce the frequency of training and improve the classification efficiency.