Colorectal cancer is one of the most prevalent malignant tumors in the digestive system globally,with both its incidence and mortality showing an upward trend.In recent years,immunother-apy has become a research focus in the prognosis of CRC.Different states of tumor-infiltrating lym-phocytes(TILs)in patients have distinct impacts on tumor progression.The diversity of TILs and their interactions among cells reflect the complex relationship between tumors and the immune system.Patients with mismatch repair-deficient and microsatellite instability-high(dMMR/MSI-H)molecular phenotypes exhibit higher levels of TILs.Moreover,immune checkpoint inhibitors(ICIs),which are relevant targeted drugs for immune checkpoint blockade,also demonstrate a higher response rate in colorectal cancer patients with dMMR/MSI-H molecular phenotypes.This article reviewed the basic characteristics and prognostic value of TILs,as well as the relationship between dMMR/MSI-H and the immunological characteristics of colorectal cancer patients.

Objective:To investigate the role of Platycoside E(PE)in a mouse model of bleomycin(BLM)-induced pulmonary fibrosis by targeting the JAK/STAT signaling pathway to suppress macrophage M2 polarization.Methods:Forty BALB/c mice were randomly assigned to five experimental groups:blank control group,model group,pirfenidone(PDF)experimental group,PE high-dose group and PE low-dose experimental group,each with eight mice.After adaptive feeding,except for blank control group,all mice were used in the model of BLM nasal drip-induced pulmonary fibrosis.HE and Masson staining were employed to examine pathological alterations of lung tissue in mice;ELISA to detect concentrations of IL-10,IL-4,IL-17A and TNF-α in mice serum;expressions of CD206 and CD11b in lung tissue were detected by immunofluorescence.Western blot to detect protein expressions of JAK1,p-JAK1,STAT6 and p-STAT6 in lung tissues.Results:Compared with blank control group,tissues in model group showed distorted structure and thickened alveolar walls,fibrotic foci were formed,and alveolar inflammatory fraction and collagen volume fraction were significantly increased(P<0.01).ELISA showed that concentrations of IL-4,IL-10,IL-6 and TNF-α in serum were significantly reduced compared to those of model group.Immunofluorescence showed that fluorescence intensity of CD11b and CD206 treated by PE were decreased significantly.Western blot showed that expressions of JAK1,p-JAK,STAT6 and p-STAT6 proteins were significantly elevated in lung tissues of model mice.Following PE treatment,levels of the above proteins were diminished.Conclusion:PE can effectively improve lung fibrosis induced by BLM in mice,the mechanism may be related to the inhibition of JAK/STAT pathway to block macrophage M2 polarization.

Objective:To investigate the role of Platycoside E(PE)in a mouse model of bleomycin(BLM)-induced pulmonary fibrosis by targeting the JAK/STAT signaling pathway to suppress macrophage M2 polarization.Methods:Forty BALB/c mice were randomly assigned to five experimental groups:blank control group,model group,pirfenidone(PDF)experimental group,PE high-dose group and PE low-dose experimental group,each with eight mice.After adaptive feeding,except for blank control group,all mice were used in the model of BLM nasal drip-induced pulmonary fibrosis.HE and Masson staining were employed to examine pathological alterations of lung tissue in mice;ELISA to detect concentrations of IL-10,IL-4,IL-17A and TNF-α in mice serum;expressions of CD206 and CD11b in lung tissue were detected by immunofluorescence.Western blot to detect protein expressions of JAK1,p-JAK1,STAT6 and p-STAT6 in lung tissues.Results:Compared with blank control group,tissues in model group showed distorted structure and thickened alveolar walls,fibrotic foci were formed,and alveolar inflammatory fraction and collagen volume fraction were significantly increased(P<0.01).ELISA showed that concentrations of IL-4,IL-10,IL-6 and TNF-α in serum were significantly reduced compared to those of model group.Immunofluorescence showed that fluorescence intensity of CD11b and CD206 treated by PE were decreased significantly.Western blot showed that expressions of JAK1,p-JAK,STAT6 and p-STAT6 proteins were significantly elevated in lung tissues of model mice.Following PE treatment,levels of the above proteins were diminished.Conclusion:PE can effectively improve lung fibrosis induced by BLM in mice,the mechanism may be related to the inhibition of JAK/STAT pathway to block macrophage M2 polarization.

Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

Objective To investigate the the treatment of class Ⅲ malocclusion by orthognathic surgery combined with postoperative orthodontics.Methods Nine patients with skeletal class Ⅲ malocclusion were treated by surgery-first approach without pre-surgical orthodontic from January 2012 to August 2014.The studied sample consisted of 7 women and 2 men (aged 15-28 years old, mean age 19.7 years), who had obvious mandibular protrusion.2 to 3 days after surgery, intermaxillary traction was used to made the maxilla and mandible together by board;we replaced a rubber band every 2 to 3 days and lasted for four weeks.We would dismantle board and performed conventional orthodontic treatment after patient's facial swelling subsided, and the positional relationship between the jaw stabilized.Results The face type of 9 patients were greatly improved after orthodontic treatment for 6.5 to 19.5 months.Patients and their family members felt satisfied, and their occlusal function returned to normal.At 3 to 32 months follow-up, the postoperative appearance and occlusion were becoming good without obvious signs of recurrence.Conclusions The surgery-first approach is an effective method to treat skeletal class Ⅲ malocclusion.

Objective To construct bone marrow stem cell sheets and to investigate its effects in the process of osteogenesis.Methods BMSCs were differentiated into osteoblasts and then seeded into a temperature responsive culture dish to construct BMSC sheets.PLGA scaffolds in which both BMSC suspension and BMSC sheets were added,were implanted into the left side of the dogs' mandible.In the other side,PLGA scaffolds that were not wapped with BMSC sheets were implanted as control.At 16 weeks,the samples were processed for radiological analysis and histological examination.Results Cells in the BMSC sheets grew well.In the experimental side,the optical density of the samples was higher than that of the control side (P＜0.05) and plenty of lamellar bones and Haversian system were observed.Conclusions The formation of lamellar bones can be promoted by PLGA scaffolds and BMSC sheets in the process of tissue engineering bone reconstrution.

Objective To investigate the inhibition effects of an hTERT-promoter-dependent oncolytic adenovirus Ad-VT that expresses apoptin on human prostatic carcinoma cell PC-3. Methods MTT assay was used to measure viability of PC-3 cell which was infected by recombinant adenovirus.The viability was measured at time points of 12,24,36,48,60,72,84 and 96 h after infection.AO/EB staining,DAPI staining,Annexin V assay were used to investigate the lethal effect and style of Ad-VT on PC-3 cell in vitro.The Caspases were measured by whole cell extraction of PC-3 cells 48hrs after infection. Results Ad-VT,Ad-VP3 and Ad-GT inhibited the proliferation of PC-3 cell in vitro.Ad-VT and Ad-GT were more effective than Ad-VP3 on cell growth,P ＜ 0.05.At 48,72,96 h time points,the inhibition effect of Ad-VT on PC-3 cell exhibited a dose related manner.When infection at MOI 100,the inhibition effect of Ad-VT on PC-3 cells exhibited time related manner.The AO/EB staining,DAPI staining,Annexin V assay,Annexin V assays and Caspase assays showed that Ad-VT inhibited the proliferation of PC-3 cells by inducing apoptosis of prostate cancer cells,Loss of cytoplasmic membrane integrity. Conclusions The hTERT-promoterdependent oncolytic adenovirus Ad-VT could effectively suppress prostate cancer cells PC-3 growth.