Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Objective:To establish a green fluorescent protein(GFP)and firefly luciferase(Luc)double-labeled Epstein-Barr virus(EBV)infec-ted B lymphoblastoid cell lines(B-LCL)and apply them to mouse models,then compare the advantages and disadvantages of models inocu-lated by intravenous(IV)or subcutaneous(SC).Methods:B lymphoblastoid cell lines double-tagged with GFP/Luc(B-LCL-GL)were con-structed through lentivirus transduction,puromycin intervention.Subcutaneous xenograft and hematogenous metastasis models were re-spectively established by subcutaneous or intravenous injection of B-LCL-GL cells at three concentrations in(NOD)/Prkdcscid/IL-2Rγnull(NPG)mice for in vivo bioluminescence imaging.Results:In the B-LCL-GL group,the ratio of the GFP-positive cell population was 92.5%,and the average luminescence intensity was as high as 4.80E+08 Photons/s,which was considerably higher than that of untreated B-LCLs.In the hematogenous metastasis models,tumor bioluminescence was initially located in the peritoneal area and then spread throughout the en-tire body between 7 and 28 days.In the subcutaneous xenograft models,strong central and weak peripheral tumor-related biolumines-cence signal was detected on day 7 in the three groups,which then spread throughout the body on day 28 in the high-dose group.Taken to-gether,there was no significant difference in tumor progression between the two routes of administration when using the same dose of B-LCL-GL cells.However,the survival analysis indicated that the IV injection group,in which all the mice ultimately died,had a shorter time frame for testing than that of the SC injection group,in which the mice survived until day 100 in the low-dose and medium-dose groups,thus allowing for long-term testing.Conclusions:GFP and Luc dual-positive B-LCLs were successfully established to generate hematogenous metastasis and subcutaneous xenograft models,which allow the monitoring of the location and size of lymphomas in vivo.It provide plat-form for the study of tumor characteristics and selecting anti-tumor drugs.

Objective:To reduce the immunogenicity of vaccinia virus vector by replacing the D8L region, which is a neutralizing antibody epitope in vaccinia virus, with an exogenous gene.Methods:A gene fragment encoding influenza virus hemagglutinin (HA) was inserted into the D8L region to replace it using homologous recombination technique. Then, a recombinant vaccinia virus influenza vaccine was constricted. A recombinant vaccinia virus vaccine with the TK region expressing HA was used as a control. The expression of HA was validated by Western blot. BALB/c mice were immunized with the vaccines and the serum antibody titers two weeks after each immunization were evaluated by ELISA and hemagglutination inhibition assay. The protective efficacy of the recombinant vaccinia virus was assessed through a challenge experiment.Results:Western blot confirmed the successful expression of HAD8L protein in the constructed recombinant vaccines. ELISA and hemagglutination inhibition assay showed that after the primary immunization, the anti-HA antibody titer induced by the recombinant vaccinia virus with D8L region mutation was slightly higher than that induced by the vaccine with TK region mutation, and the difference was statistically significant with the increase of immunization times ( P<0.05). The recombinant vaccinia virus with D8L region mutation showed significantly lower immunogenicity than the recombinant virus with TK region mutation after the primary immunization, but there was no significant difference between them with the increase of immunization times ( P>0.05). After H1N1pdm challenge, no virus was detected in the mice immunized with the recombinant vaccinia virus with D8L region mutation and the mice showed mild lung inflammation and less tissue damage. Conclusions:This study indicated that inserting exogenous genes into the D8L region of the neutralizing antibody epitope in the vaccinia virus vector could help to reduce the immunogenicity of the vector itself and enhance the immunogenicity of the exogenous genes. This provided a reference for the use of the vaccinia virus vector as a delivery tool in the field of vaccines or gene therapy.

Objective:To investigate the clinical efficacy differences of stereotactic electroencephalogram (SEEG) electrode implantation in medically-refractory temporal lobe epilepsy (TLE) patients with different neuroimaging manifestations before surgery.Methods:A total of 59 patients with medically-refractory TLE who accepted SEEG electrode implantation in Department of Neurosurgery, First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2018 to December 2021 were enrolled. These were divided into groups according to neuroimaging manifestations before surgery, including MRI-positive group and MRI-negative group, PET-positive group and PET-negative group, or PET&MRI concordant group (concordant group) and PET&MRI discordant group (discordant group). Modified Engel classification was used to evaluate the clinical efficacy of these patients at 12-month follow-up after surgery, and efficacy differences among different patient groups were compared.Results:Significant differences were noted in distributions of modified Engel classification between the MRI positive and negative groups, as well as the concordant and discordant groups at 12-month follow-up after surgery ( P<0.05); patients in the MRI positive group had better outcomes than those in the MRI negative group (mean rank judgment: 27.00 and 34.08), while patients in concordant group had better outcomes than those in discordant group (mean rank judgment: 23.32 and 31.19). Significant differences were noted in distributions of modified Engel classification at 12-month follow-up after surgery between different signal abnormal regions in the MRI positive group ( P<0.05); patients with hippocampal sclerosis or amygdala abnormalities had better outcomes than those with simultaneous abnormalities in the temporal lobe internal and external regions (mean rank judgment: 14.50 and 16.50). Conclusion:When the preoperative MRI of patients with medically-refractory TLE is negative, especially when results of structural imaging and functional imaging are inconsistent, SEEG electrode implantation and path planning as well as later surgical plan should be considered more carefully.

Objective:To explore the new generation of intelligent ICU Unit based on 5G and artificial intelligence technology.Methods:This study was conducted at the Second Affiliated Hospital, Zhejiang University School of Medicine from May 2019 to August 2020. Based on a multidisciplinary team including medical, nursing, hospital management, clinical medical engineering, 5G technology, information technology, artificial intelligence technology, logistics service, etc, was assembled to intelligently design and reconstruct an intelligent ICU Unit of Emergency ICU.Results:Based on 5G technology, a new intelligent ICU unit environment was constructed to realize remote and high-speed interaction of multi-dimensional information in ICU, including intelligent assistance of remote monitoring, remote ward rounds, remote consultation and family visits. An intelligent hospital infection prevention and control system was established including automatic identification and alarm of hand hygiene and personal protection.Conclusions:The new generation of intelligent ICU unit combined with 5G and artificial intelligence technology has changed the mode of medical service for critically ill patients and improved the service level, which is worthy of further exploration and application.

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

Objective:To explore the efficacy of remote programming after vagus nerve stimulation (VNS) in patients with refractory epilepsy.Methods:Thirty-four patients who received VNS in our hospital from October 2019 to October 2020 were chosen in our study. Among them, 19 patients accepted remote programming (remote programming group) and 15 patients regularly came to the outpatient clinic for regulation (outpatient regulation group). The seizure frequency, response rate (seizure frequency decreased by≥50%), McHugh grading, and incidence of postoperative complications between the 2 groups were compared 6 months after VNS.Results:The seizure frequency in the remote programming group and outpatient regulation group was 2 (0, 4) times/month and 4(1, 24) times/month, without significant difference ( Z=-1.602, P=0.105). The proportion of patients enjoying effective treatment in the two groups was 13/19 and 8/15, without significant difference ( P=0.781). Results of McHugh grading showed no significant difference between the two groups ( Z=-0.728, P=0.467). The proportion of patients with postoperative complications in the two groups was 3/19 and 2/15, without significant difference ( P=0.625). Conclusion:The remote programming after VNS is safe and effective, which can become an important complementary approach for outpatient regulation.

This study aimed to investigate whether β-elemene could improve the dysfunction of vascular endothelial cells induced by low shear force (LSS), and the proliferation and migration of vascular smooth muscle cells induced by oxidized low-density lipoprotein (ox-LDL). Parallel plate flow chambers and ox-LDL were used to establish vascular endothelial cells (ECs) dysfunction model and vascular smooth muscle cell (VSMCs) proliferation and migration model, respectively, and the effects of β-elemene on ECs dysfunction and VSMCs proliferation and migration were examined. The activity of ROS in ECs was measured by DHE and the activity of NO in ECs was tested by DAF-FM DA. The protein phosphorylation of Akt and ERK in ECs were detected by Western blot. The proliferation of VSMCs was measured by MTT. The migration of VSMCs was examined by cell scratch test and Transwell assay. The gene expression of MMP-2 and MMP-9 in VSMCs was measured by RT-qPCR. In ECs, β-elemene could significantly reduce the LSS-induced increase in ROS, significantly increase the LSS-induced decrease in NO, decrease the phosphorylation of ERK, and increase the phosphorylation of Akt. In VSMCs, β-elemene could significantly reduce the proliferation and migration of VSMCs induced by ox-LDL, and reduce the gene expression of MMP-2 and MMP-9. To conclude, β-elemene can improve the LSS-induced ECs dysfunction and ox-LDL-induced VSMCs proliferation and migration.

Objective To explore the efficacy and safety of apatinib combined with S-1 in patients with advanced NSCLC without sensitive gene mutation or unknown mutation status.Methods One hundred and four patients with advanced NSCLC without sensitive gene mutation or unknown mutation status were selected from the oncology department of the First Hospital of Qinhuangdao City,Hebei Province from April 2015 to April 2017.All patients refused intravenous chemotherapy.One hundred and four patients were randomly divided into treatment group (apatinib combined with S-1 group) and control group (S-1 alone group) by 1:1 digital method.However,two patients in the treatment group transferred to the control group for personal reasons.There is 50 cases in apatinib combined with S-1 group and 54 cases in S-1 group.The efficacy and adverse reactions of the two groups were evaluated.Results The objective remission rate was 48.0％ (24/50) and 27.8％ (15/54) (x2=4.530,P =0.033),the disease control rate was 82.0％ (41/50) and 74.1％ (40/54) (x2=0.947,P=0.331),the median PFS was 6.6 months and 3.4 months (t=25.555,P =0.000),the median OS was 16.0 months and 10.5 months (t =59.439,P =0.000),respectively.The overall incidence of adverse reactions was 82.0％ (41/50) and 70.4％ (38/54) respectively (x2 =1.923,P=0.166),of which 18.0％ (9/50) and 13.0％ (7/54) were more than grade 3 respectively (x2 =0.506,P =0.477).There was no death caused by treatment-related adverse reactions in both groups.Conclusion Appatinib combined with S-1 capsule has good short-term and long-term efficacy in the treatment of advanced non-small cell lung cancer without gene mutation or unknown mutation.The adverse reactions are tolerable and can be used as first-line treatment for patients unwilling to receive intravenous chemotherapy.