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.

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 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 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.

The blood-brain barrier (BBB) constitutes a major obstacle to effective delivery of drugs to the brain. Recent technological advances have led to improvements in brain-targeted drug delivery. In this review, we summarize existing technologies for efficient drug delivery across the BBB. We discuss the mecha-nisms of current BBB-based drug delivery strategies and introduce prospects for application in brain-targeted delivery of traditional Chinese medicine. We highlight the use of physical techniques for brain-targeted drug delivery, including electroporation, ultrasound, magnetophoresis, microneedles, microwaves, and laser. The characteristics of these techniques and relevant studies employing these approaches are discussed. In general, microneedles, lasers, ultrasound, electroporation, magnetophoresis, and microwaves are effective for drug delivery across the BBB. Notably, the synergistic effects of multiple approaches are superior to the additive effects of each technique in isolation. Our review provides guidance for the practical application of brain-targeted drug delivery techniques in an efficient and safe manner.

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.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs,including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been proven to be effective in the treatment of wet age-related macular degeneration (wAMD).However,there are still some patients with poor efficacy,such as no response to initial treatment or poor response,and even relapse during the course of treatment.In view of the different targets and molecular characteristics of anti-VEGF drugs,the switch of anti-VEGF drugs and the adjustment of delivery pattern,dosages and intervals have been the strategies to cope with the poor efficacy in clinic.However,there are some differences in the results of current studies.Overall,the recovery of retinal anatomical outcome achieves more benefits,and it is relatively difficult to improve visual acuity.To determine which regimen would get the biggest benefits,a large number of randomized controlled clinical trials and long study period will be needed.

Objective To construct the connective tissue growth factor (CTGF) recombinant interference vector (shRNA) and observe its inhibitory effect on the expression of endogenous CTGF in retinal vascular endothelial cells.Methods The human CTGF shRNA was constructed and the high-titer CTGF shRNA lentivirus particles was acquired via three-plasmid lentivirus packaging system to infect retinal vascular endothelial cells.The optimal multiplicity and onset time of lentivirus infection were identified by tracing down the red florescent protein in interference vector.The cells were classified into three groups:blank control group,infection control group and CTGF knockdown group.The differences in cells migrating ability was observed through Transwell allay.The mRNA and protein expression of CTGF,fibronectin,a-smooth muscle actin (α-SMA) and collagen Ⅰ (Col Ⅰ) were quantified through real-time PCR testing and Western blot system.Data between the three groups were examined via one-way analysis of variance.Results The result showed that an optimal multiplicity of 20 and onset time of 72 hours were the requirements to optimize lentivirus infection.Transwell allay result showed a contrast in the number of migrated cells in the CTGF knockdown group and that in the blank control group and infection control group (F=20.64,P=0.002).Real-time PCR testing showed a contrast in related gene expression (CTGF,fibronectin,α-SMA and Col Ⅰ) in the CTGF knocked-down group and that in the blank control group and infection control group (F=128.83,124.44,144.76,1 374.44;P=0.000,0.000,0.000,0.000).Western blot system showed the statistical significance of the contrasted number of related protein expression (CTGF,fibronectin,α-SMA and Col Ⅰ) in the knockdown group and that in the blank control group (F=22.55,41.60,25.73,161.68;P=0.002,0.000,0.001,0.000).Conclusion The success in producing CTGF shRNA lentivirus particle suggests that CTGF shRNA lentivirus can effectively knock down CTGF expression.