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

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients. METHODS: The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed. RESULTS: Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively. CONCLUSION The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.
Child ; Cytomegalovirus Infections ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Parents ; Retrospective Studies ; Thalassemia/therapy* ; Transplantation Conditioning/methods* ; Treatment Outcome ; Viremia

OBJECTIVE: To investigate the expression of CD56 in multiple myeloma (MM) cells and its relationship between extramedullary disease and extramedullary relapse. METHODS: Clinical data of 99 patients with MM treated in our hospital from January 2015 to December 2019 was retrospectively analyzed. The patients were divided into positive group and negative group according to the expression of CD56. The relationship between CD56 and multiple myeloma extramedullary disease, extramedullary relapse was analyzed. RESULTS: Among 99 newly diagnosed patients with MM, the positive rate of CD56 was 65%, and the incidence of extramedullary disease of patients in the CD56 positive group was lower than that in the CD56 negative group (17.19% vs 48.57%) (P<0.01). Meanwhile, the incidence of extramedullary relapse of patients in the CD56 positive group was lower than that in the CD56 negative group (1.56% vs 34.29%) (P<0.01). CONCLUSION CD56 is highly expressed in MM, and its low expression is associated with the occurrence of extramedullary disease and extramedullary relapse, which suggests that CD56 may be an important indicator for predicting the occurrence of extramedullary disease and extramedullary relapse.
CD56 Antigen ; Humans ; Multiple Myeloma ; Neoplasm Recurrence, Local ; Retrospective Studies

Objective At present no deep investigation has been done on the relationship between handgrip strength and appendicular lean mass (ALM) in patients with chronic obstructive pulmonary disease (COPD). The study aimed to explore the present situation of handgrip strength in patients with stable COPD and relationship between handgrip strength and ALM.Methods A total of 93 patients with stable COPD who hospitalized in our department from August 2016 to July 2017 were selected for the study. All the patients underwent handgrip strength test, body composition analysis, as well as the analysis of the relationship between handgrip strength and ALM.Results Multivariate linear regression analysis showed age(X1), education(X2), smoking(X3), course of disease(X4) and lower limb lean mass(X5) could be taken as predictive factors for the variation degree of handgrip strength (R2=50.5%), and multiple linear regression equation was Y=9.959-4.315X1+1.397X2+2.679X3-1.526X4+1.538X5. The variation degree decreased to 48.1% when the course of disease was removed from the model, 28.3% when the limb lean mass was removed, 26.5% when two variables were removed. The correlation coefficients of ALM, upper limb, lower limb and torso lean mass (\[22.32±3.25\]kg, \[6.48±1.05\]kg, \[15.83±2.26\]kg, \[22.27±3.22\]kg) with handgrip strength (\[32.27±7.27\]kgf) were respectively 0.484, 0.436, 0.496 and 0.496 (P＜0.01).Conclusion The handgrip strength in patients with stable COPD is closely associated with ALM, and the course of disease and the lower limb lean mass greatly affect the handgrip strength. Clinical workers should pay extra attention to the relationship in order to give timely clinical intervention.

OBJECTIVETo study the dynamic changes of levels of hepatocyte growth factor (HGF) in tears and their association with corneal haze in rabbits early after epipolis laser in situ keratomileusis (Epi-LASIK).

METHODSTwenty-four New Zealand rabbits received Epi-LASIK with an ablation depth of 100 µm in one eye and of 150 µm in the other eye. Before and at 3, 7, 14, and 30 days after the surgery, the level of HGF in tears collected from the rabbits was measured using enzyme-linked immunosorbent assay (ELISA), and corneal haze was graded after surgery.

RESULTSIn all the rabbits, corneal epithelium healing occurred in 3 to 5 days after Epi-LASIK. Corneal haze appeared 3 days postoperatively in the rabbits accompanied by increased levels of HGF in tears. At 3, 7, 14, and 30 days after the surgery, the rabbits with an ablation depth of 150 µm showed more obvious corneal haze (P<0.05) and significantly higher levels of HGF in tears than those with an ablation depth of 100 µm (P<0.05).

CONCLUSIONIn rabbits receiving Epi-LASIK, HGF levels in tears and the grade of corneal haze show a positive correlation early after the surgery and are both related with the depth of ablation.

BACKGROUND:The angiogenesis may be related to the proliferation of neural stem ceils,but there is still no unified view.OBJECTIVE:To observe the influence of angiogenesis on neural stem cell proliferation in the subventricular zone of rats after focal cerebral ischemia/reperfusion.METHODS:Male Sprague-Dawley rats were randomly divided into normal group,sham group,vascular endothelial growth factor (VEGF)+cerebral ischemia/reperfusion group,normal saline (NS)+cerebral ischemia/reperfusion group.The injection was done via the lateral cerebral ventricle.Then,each group was subdivided into four groups (1,2,7,14 days after ischemia/reperfusion).Focal cerebral ischemia/reperfusion models were made by the thread method.After modeling,the corresponding intervention was given in each group.The expression changes of Nestin and vWF mRNA in the subventricular zone were detected in all groups by immunohistochemical staining and real-time PCR,respectively.RESULTS AND CONCLUSION:There was a certain increase in vWF and Nestin positive expression in the subventricular zone after cerebral ischemia/reperfusion.At 7 days after ischemia,the expression of vWF mRNA and Nestin reached the peak,indicating the proliferation of neural stem cells in the subventricular zone after cerebral ischemia/reperfusion is associated with the time of angiogenesis.In addition,the expression of vWF mRNA and Nestin was significantly higher in the VEGF+cerebral ischemia/reperfusion group than the other two groups,indicating angiogenesis could promote the proliferation of neural stem ceils in the subventricular zone of rats after cerebral ischemia/reperfusion.

ObjectiveTo investigate sexual satisfaction (SS) and the factors associated with decreased SS among individuals with hearing disability.

METHODSWe conducted an investigation on SS among 439 individuals (268 males and 171 females, aged ≥18 yr) with hearing disability using a general information questionnaire, Center for Epidemiologic Studies Depression Scale, Social Support Rating Scale, and a self-report on SS. We identified the factors of decreased SS by multivariate ordinal logistic regression analysis.

RESULTSTotally 76 (17.3%) of the hearing-disability individuals investigated were dissatisfied with their sexual life. SS reduction was significantly correlated with the status of being single (OR=1.72), grade-1 or -2 disability (OR=1.78), physical diseases (OR=2.46), depression (OR=6.61), or inadequate subjective social support (OR=3.28).

CONCLUSIONSSS of hearing-disability persons is relatively low, which can be improved by treating physical diseases, promoting mental health, and providing psycho-social support.

OBJECTIVETo perform theory construction and empirical study of the competency model of rural general practitioners.

METHODSThrough literature study, job analysis, interviews, and expert team discussion, the questionnaire of rural general practitioners competency was constructed. A total of 1458 rural general practitioners were surveyed by the questionnaire in 6 central provinces. The common factors were constructed using the principal component method of exploratory factor analysis and confirmatory factor analysis. The influence of the competency characteristics on the working performance was analyzed using regression equation analysis.

RESULTSThe Cronbach 's alpha coefficient of the questionnaire was 0.974. The model consisted of 9 dimensions and 59 items. The 9 competency dimensions included basic public health service ability, basic clinical skills, system analysis capability, information management capability, communication and cooperation ability, occupational moral ability, non-medical professional knowledge, personal traits and psychological adaptability. The rate of explained cumulative total variance was 76.855%. The model fitting index were Χ(2)/df 1.88, GFI=0.94, NFI=0.96, NNFI=0.98, PNFI=0.91, RMSEA=0.068, CFI=0.97, IFI=0.97, RFI=0.96, suggesting good model fitting. Regression analysis showed that the competency characteristics had a significant effect on job performance.

CONCLUSIONSThe rural general practitioners competency model provides reference for rural doctor training, rural order directional cultivation of medical students, and competency performance management of the rural general practitioners.

This study was purposed to explore the anti-leukemic mechanism of quercetin (Que) in vivo and it enhancing chemotherapeutic effect of adriamycin (ADR) by establishing the quercetin-treated P388 transplanted nude mouse model. The P388 leukemic cells in logarithmic growth phase were taken and injected subcutaneously into BALB/c nude mice so as to establish the leukemia-transplanted nude mouse model. The model mice were treated by quercetin, ADR and their combination, and the survival changes of model mice were observed, the hemogram and peripheral blood cell count examination were performed regularly; the cell cycle was detected and the influence of quercetin on cell proliferation was analyzed by flow cytometry; the caspase-3 protein expression level was detected by ELISA; the mRNA and protein changes of NF-κB, BCL-2, BAX were measured by real-time quantitative flourascence PCR and Western blot respectively. The results indicated that the quercetin and adriamycin could significantly prolong the survival of P388 leukemia nude mice, and their combination displayed significantly prolonged effect. Quercetin and adriamycin alone or in their combination could reduce the ratio of G0/G1 phase in mice, the cell ratio in S phase and G2/M phase increased, and the effects of the combination group were more significant than that of the single agent groups. Quercetin could activate caspase-3 and promote leukemic cell apoptosis. Meanwhile, quercetin could down-regulate the expression of BCL-2 and NF-κB gene, and up-regulate the expression of BAX gene. It is concluded that through modulating the expression of apoptosis-related genes, the quercetin can inhibit leukemia cell proliferation, promote apoptosis, and enhance the chemotherapeutic effects of adriamycin. These results provide some valuable data for further research and development of quercetin as a new and effective anti-leukemic drug.
Animals ; Apoptosis ; Caspase 3 ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Doxorubicin ; pharmacology ; Drug Synergism ; Leukemia ; drug therapy ; pathology ; Mice ; NF-kappa B ; Quercetin ; pharmacology