Objective To investigate the effect of Qingchi Powder(composed of calamina,Halloysitum Rubrum,Phellodendri Chinensis Cortex,Sophorae Flavescentis Radix,Catechu,Indigo Naturalis,Rhizoma Bletillae,and Notoginseng Radix et Rhizoma powder)retention enema on intestinal flora and Toll-like receptor 4(TLR4)/NOD-like receptor thermoprotein domain-related protein 3(NLRP3)signaling pathway in peripheral blood mononuclear cell(PBMC)of children with ulcerative colitis(UC).Methods A total of 100 children with UC were randomly divided into control group and study group,with 50 cases in each group.The control group was treated with oral administration of Mesalazin Enteric-Coated Tablets,and the study group was treated with Qingchi Powder retention enema on the basis of treatment for the control group.The treatment for the two groups lasted for 8 consecutive weeks.Before and after treatment,the distribution of intestinal flora and the relative mRNA expression levels of TLR4 and NLRP3 in PBMC,serum contents of TLR4 and NLRP3 protein,and serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in the two groups were observed.After treatment,the clinical efficacy of the two groups was evaluated,and Spearman test was used to analyze the correlation of total effective rate with the relative mRNA expression levels of TLR4 and NLRP3 in PBMC and serum contents of TLR4 and NLRP3 protein.Results(1)After 8 weeks of treatment,the total effective rate of the study group was 94.00%(47/50),and that of the control group was 70.00%(35/50).The intergroup comparison(tested by chi-square test)showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the number of Enterococcus and Enterobacteriaceae in the two groups was significantly lowered(P＜0.05),and the number of Bifidobacterium and Lactobacillus was significantly increased compared with that before treatment(P＜0.05).After treatment,the number of Enterococcus and Enterobacteriaceae in the study group was significantly lower(P＜0.05)and the number of Bifidobacterium and Lactobacillus was significantly higher than that in the control group(P＜0.05).(3)After treatment,the mRNA relative expression levels of TLR4 and NLRP3 in PBMC of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(4)After treatment,the serum TLR4 and NLRP3 protein levels in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(5)After treatment,the levels of serum inflammatory factors of TNF-α,IL-1β and IL-6 in the two groups significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(6)Spearman correlation analysis showed that the mRNA relative expression levels of TLR4 and NLRP3 in PBMC and serum TLR4 and NLRP3 protein levels in children with UC were significantly negatively correlated with the total effective rate of curative effect(P＜0.001).Conclusion Qingchi Powder retention enema can down-regulate the expression levles of key signaling molecules of TLR4/NLRP3 pathway in PBMC of children with UC,regulate the intestinal flora of children,and improve the inflammatory response.It has significant curative effect and is worthy of expanding its application in clinic.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Objective:To evaluate the application effect of intelligent digital technology combined with quality control index system management mode in the management of large medical imaging equipment.Methods:Based on the composition and operation of medical imaging equipment,the intelligent digital technology and quality control parameter system architecture were integrated,and the joint management mechanism was used to manage large medical imaging equipment.A total of 26 medical imaging equipment in clinical use in Wuhan First Hospital from 2022-2023 were selected.According to different equipment management methods,conventional management method(13 units)and intelligent digital technology combined with the quality control index system mode(referred to as intelligent mode)(13 units)were adopted for management.The clinical effectiveness,management quality,management level and recognition scores of management personnel involved in the use of medical imaging equipment were compared between the two management methods.Results:The average start-up rate,operation rate,and turnover rate of the equipment managed by intelligent mode were(90.56±4.69)％,(12.36±2.45)％and(15.69±3.65)％,respectively,which were higher than those of conventional management method,the difference was statistically significant(t=13.366,15.637,9.082,P＜0.05).The average scores of clinical operation,information data,quality control and maintenance of the equipment managed by intelligent mode were(93.65±4.21)points,(94.65±4.36)points,(95.36±6.56)points and(94.26±5.63)points,respectively,which were higher than those of conventional management method,the difference was statistically significant(t=7.794,6.818,6.918,10.136,P＜0.05).The reasonable placement rate,standardized recording rate and equipment serviceability rate of equipment managed by intelligent mode were 76.92％(10/13),84.61％(11/13)and 84.61％(11/13),respectively,which were higher than those of conventional management method,the difference was statistically significant(x2=8.714,12.462,9.905,P＜0.05).The recognition scores of engineers,operators,medical staff and managers involved in the management and use of equipment were(93.54±3.65)points,(92.58±4.58)points,(90.78±3.14)points and(92.65±3.41)points,respectively,which were higher than those of conventional management method,the differences was statistically significant(t=3.333,4.142,6.424,7.278,P＜0.05).Conclusion:The application of intelligent digital technology combined with quality control index system management mode in the management of large medical imaging equipment can improve the quality of clinical use of equipment,enhance equipment technical support capabilities,and reduce equipment failure rate.

This study aims to establish a time-resolved fluorescence immunochromatography method for simultaneous determination of human papillomavirus (HPV) type 16 E6 and L1 protein concentrations. The amount of lanthanide microsphere-labeled antibodies, the concentration of coated antibodies, and the reaction time were optimized, and then a test strip for the simultaneous determination of the protein concentrations was prepared. The performance of the detection method was evaluated based on the concordance of the results from clinical practice. The optimal conditions were 8 μg and 10 μg of HPV16 L1 and E6-labeled antibodies, respectively, 1.5 mg/mL coated antibodies, and reaction for 10 min. The detection with the established method for L1 and E6 proteins showed the linear ranges of 5-320 ng/mL and 2-64 ng/mL and the lowest limits of detection of 1.78 ng/mL and 1.09 ng/mL, respectively. There was no cross reaction with human immunodeficiency virus (HIV), treponema pallidum (TP), or HPV18 E6 and L1 proteins. The average recovery rate of the established method was between 97% and 107%. The test strip prepared in this study showed the sensitivity, specificity, and diagnostic accuracy of 97.46%, 90.57%, and 95.32%, respectively, in distinguishing patients with cervical cancer and precancerous lesions from healthy subjects, with the area under the curve (AUC) of 0.980 1 and 95% Confidence Interval (CI) of 0.956 5 to 1.000 0. The time-resolved fluorescence immunochromatography combined with the test strips prepared in this study showed high sensitivity, high accuracy, simple operation, and rapid reaction in the quantitation of HPV16 E6 and L1 proteins. It thus can be used as an auxiliary method for the diagnosis and early screening of cervical cancer and precancerous lesions and the assessment of disease course.
Oncogene Proteins, Viral/immunology* ; Humans ; Chromatography, Affinity/methods* ; Female ; Human papillomavirus 16 ; Repressor Proteins/immunology* ; Capsid Proteins/immunology* ; Papillomavirus Infections/diagnosis* ; Fluorescence ; Uterine Cervical Neoplasms/virology*

The global pandemic of coronavirus disease 2019(COVID-19)poses a serious threat to human health,leading to a relatively high mortality in patients with severe or critical conditions in particular.Hyperglycemia is one of the high-risk factors for poor prognosis in these patients.Patients with COVID-19 are more likely to develop hyperglycemia,regardless of whether there is a previous history of diabetes mellitus.Glucocorticoid therapy is an important part of the anti-inflammatory regimen for COVID-19.However,the use of glucocorticoid significantly increases the occurrence of hyperglycemic events in COVID-19 patients,ultimately leading to poor prognosis.Timely monitoring of blood glucose and early intervention for hyperglycemia contribute to the improvement in the outcome of COVID-19 patients.In this paper,we comprehensively reviewed the potential mechanisms of COVID-19 and concomitant hyperglycemia.We reviewed the latest findings on the blood glucose management strategies for COVID-19 patients with concomitant hyperglycemia,aiming to optimize the management of hyperglycemia in COVID-19 patients and improve the outcome of the disease.

Hepatocellular carcinoma (HCC) is one of the malignant tumors of the digestive system with the highest morbidity and mortality. The vast majority of patients with intermdiate and advanced HCC have low response rates and poor long-term survival to a series of treatments mainly based on transcatheter arterial chemoembolization (TACE). In recent years, molecular targeted therapy, immunotherapy and their combination with TACE have developed rapidly. This article reviews the research progress of TACE combined with systemic drug therapy in HCC and looks forward to the future direction of precise treatment of HCC.

Objective:To explore the clinical effect of antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap in the treatment of diabetic foot(DF).Methods:From April 2020 to July 2021, a total of 6 patients with DF were treated with antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap. The patients were 5 males and 1 female, aged from 45 to 67 years old with an average of 56.2 years old. The wounds were all located in dorsal foot, 4 in right foot and 2 in the left. The wound area was 2.4 cm×5.0 cm-6.5 cm×10.0 cm. The depth of wound were: 3 cases up to tendon layer, and 3 cases up to metatarsal bone. Two of the wound were complicated with metatarsal osteomyelitis. The wounds at Wagner grade 3 in 4 patients and grade 4 in 2 patients. The flap size was 3.0 cm×6.0 cm-8.0 cm×11.0 cm. All of the wounds were repaired with delayed supramolleolar perforator fascia flap after debridement, application of antibiotic bone cement and fumigation with Sanhuang decoction(a traditional Chinese medicine). The affected limbs were externally fixed with plaster and raised after surgery, and the colour, temperature, tension and capillary reaction of the flaps were closely observed. Stitches were removed 2 weeks after surgery and rehabilitation of the affected limb was performed. Regular follow-up was made postoperatively. The appearance of flaps and the scar of donor and recipient sites were observed. The foot and ankle function were evaluated by the American Orthopaedic Association foot and Ankle Surgery(AOFAS) score scale.Results:Six cases of DF had no recurrence of wound infection. All flaps survived well. The average follow-up time was 6(3-14) months. The postoperative follow-up revealed satisfactory appearance of the flap, only linear scars remained in the donor and recipient sites. The function of foot and ankle recovered well with full weight-bearing and normal walk. AOFAS scores ranged from 81 to 95.Conclusion:It is an effective method to treat DF by applying antibiotic bone cement combined with delayed superior lateral malleolus perforator fascial flap. The operation is simple, safe and can cut down the time of treatment, quickly control the wound infection. It deserves further trials.

Objective:To analyze the damage in hippocampal tissues of mice after whole-body irradiation with high- or low-dose ionizing radiation and to investigate the roles of microglia/macrophages polarization in the injury.Methods:C57BL/6 mice were randomly divided into three groups: sham irradiation group, low-dose group (0.05 Gy) and high-dose group (7 Gy). Low- and high-dose groups were respectively treated by whole-body irradiation with single dose of 60Co γ-rays. Hippocampal tissues of the mice were collected at 6 h, 1 d, 3 d and 7 d after irradiation. The morphology, structure and apoptosis of neurons were detected by HE staining, Nissl staining and Tunnel staining, respectively. RT-PCR and immunofluorescence assay were performed to detect the expression of M1 and M2 microglial markers at mRNA and protein levels in hippocampus tissues. The cognitive and emotional behaviors of mice were evaluated one month after the irradiation by Morris water maze, open field test, elevated plus maze and tail suspension test. Results:There were morphological and structural changes in the nerve cells in the hippocampus region of mice after irradiation, accompanied by apoptosis. Acute injuries occurred at 6 h after radiation, alleviated at 1 d and 3 d, and persisted at 7 d in a dose-dependent manner. The results of immunofluorescence staining and confocal imaging analysis showed that compared with the sham irradiation group, the high-dose group showed increased number of microglia, down-regulated expression of M1 microglial markers and up-regulated expression of M2 microglial markers in the hippocampus at 6 h and 1 d after radiation, while M2 microglial markers decreased at 3 d and 7 d after irradiation. PCR results showed that the expression of M1 and M2 microglial markers at mRNA level in the irradiation groups increased at 6 h after irradiation, but there was no statistical significance. The expression of related proinflammatory/anti-inflammatory factors was significantly up-regulated. The results of behavioral experiments showed that compared with the sham irradiation group, there was no statistical difference in cognitive or emotional behaviors at one month after irradiation.Conclusions:60Co γ-rays could damage mouse hippocampal tissues and result in the overexpression and different polarization patterns of microglia/macrophages in mice.

Objective:To observe the changes of follistatin-like protein 1 (FSTL1) in serum of patients with proliferative diabetic retinopathy (PDR).Methods:Twenty PDR patients confirmed by clinical examination and 20 normal people were included in the study. Human retinal vascular endothelial cells (HRCEC) were divided into HRCEC blank control group, 3 h hypoxia group, 6 h hypoxia group. Human umbilical vein endothelial cell (HUVEC) were divided into HUVEC blank control group, 3h hypoxia group, 6h hypoxia group. Real-time quantitative PCR (RT-PCR) and ELISA were used to determine the expression of FSTL1, TGF-β, VEGF, connective tissue growth factor (CTGF) mRNA and protein in peripheral blood and cells of all groups from all subjects.Results:The expressions of FSTL1, TGF-β1, CTGF, VEGF mRNA in blood samples of patients with PDR were 1.79±0.58, 0.97±0.21, 1.85±0.69 and 1.38±0.44. The expressions of FSTL1, TGF-β1 protein were 1.19±0.50, 0.71±0.24 ng/ml and 734.03±116.45, 649.36±44.23 ng/L. Compared with normal people, the differences were statistically significant ( tmRNA=0.90, 0.21, 2.85, 1.77; P=0.00, 0.00, 0.04, 0.02. tprotein=1.88, 7.68; P=0.00, 0.02). The cell viability of HRCEC cells in the 3 h hypoxia group and the 6 h hypoxia group were 0.66±0.05 and 0.64±0.04, respectively. Compared with the blank control group, the difference was statistically significant ( F=13.02, P=0.00). The cell viability of HUVEC cells in the 3 h hypoxia group and the 6 h hypoxia group were 0.63±0.06 and 0.68±0.06, respectively. Compared with the blank control group, the difference was statistically significant ( F=26.52, P=0.00). Comparison of FSTL1, TGF-β1, CTGF, and VEGF mRNA expression in HRCEC blank control group and 3 h hypoxia group, the differences were statistically significant ( F=14.75, 44.93, 85.54, 6.23; P=0.01, 0.00, 0.00, 0.03). Compared with the HRCEC blank control and 3 h hypoxia group, the expressions of FSTL1 and TGF-β1 protein were statistically significant ( P<0.05). There was a statistically significant difference in TGF-β1 protein expression in the hypoxic 6 h group ( P=0.03) and no significant difference in FSTL1 protein expression ( P=0.68). Comparison of FSTL1, TGF-β1, CTGF, and VEGF mRNA expression in HUVEC blank control group and 3h hypoxia group, the differences were statistically significant ( F=19.08, 25.12, 22.89, 13.07; P=0.00, 0.00, 0.00, 0.01). Immunofluorescence staining results showed that FSTL1, TGF-β1, CTGF, and VEGF proteins were positively expressed in cells in the 3h hypoxia and 6h hypoxia groups. Conclusion:The expression of FSTL1 gene and protein in serum of PDR patients was significantly higher than that of normal people.

Objective To observe RNA-Seq analysis of gene expression profiling in human retinal vascular endothelial cells after anti-vascular endothecial growth factor (VEGF) treatment.Methods Cultured the retinal vascular endothelial cells in vitro and logarithmic growth phase cells were used for experiments.The cells were divided into VEGF group and VEGF combined with anti-VEGF drugs group.The VEGF group cells were treated with 50 ng/ml VEGF for 72 h to simulate the high VEGF survival conditions of vascular endothelial cells in diabetic retinopathy.VEGF combined with anti-VEGF drug group cells was treated with 50 ng/ml VEGF and 2.5 μg/ml anti-VEGF drugs for 72 h to imitate the microenvironment of cells following the anti-VEGF drugs treatment,and whole transcriptome sequencing approach was applied to the above two groups of cells through RNA-Seq.Now with biological big data obtained as a basis,to analyze the differentially expressed genes (DEGs).And through enrichment analysis to explain the differential functions of DEGs and their signal pathways.Results The gene expression profiles of the two groups of cells were obtained.Through analysis,328 DEGs were found,including 194 upregulated and 133 downregulated ones.The functions of DEGs were influenced by regulations over molecular biological process,cellular energy metabolism and protein synthesis,etc.Among these genes,SI,PRX and HPGD were related to protein synthesis,BIRCT to cellular apoptosis,and ABLIM 1 and CRB2 to retinal development,and ABCG 1,ABCA9 and ABCA12 were associated with the cholesterol of macrophage and the transfer of phospholipid.GO enrichment analysis showed that DEGs mainly act in three ways:regulating biological behavior,organizing cellular component and performing molecular function.Pathway enrichment analysis showed that gene expressions of the two cell groups were differentiated in ECM receptor pathway,and Notch,mitogen-activated protein kinase,transforming growth factor (TGF)-β and Wnt signal pathways.Among them,the gene expression in TGF-β signal pathway attracts most attention,where the DEGs,such as CAMK2B,COL3A1,CYGB,PTGER2 and HS6ST2,among others,were closely related to fibrosis process.Conclusion The anti-VEGF drugs may enhance the expression ofCAMK2B,COL3A1,CYGB,PTGER2 and others genes related to TGF-β signal pathway and aggravate retinal fibrosis disease.