Objective : To investigate the effects of astragalus mongholicus extract ( AME) on lung injury and the myeloid differentiation factor 88 ( MyD88 ) / Toll-like receptor 4 ( TLR4 ) / nuclear factor kappa B ( NF-κB) p65 pathway in rheumatoid arthritis induced interstitial lung disease (RA-ILD) rats． Methods : SD rats were randomly divided into a control group，RA-ILD group，low-dose AME group (5 g / L) ，high-dose AME group ( 10 g / L) ，and high-dose AME + lipopolysaccharide (LPS) group ( 10 g / L AME + 1 mg / L TLR4 activator LPS) ．Except for the control group，rats in all other groups were injected with bovine type Ⅱ collagen，Freund ’s complete adjuvant， and bleomycin to establish the RA-ILD model．The arthritis index and lung tissue wet-dry weight ratio of rats were tested．ELISA was applied to detect the levels of inflammatory factors interleukin (IL) -1 β , IL-6 and tumor necrosis factor-α ( TNF-α) in bronchoalveolar lavage fluid． Hematoxylin eosin staining was used to observe pathological changes of rat knee joint tissue and lung tissue．Western blot was applied to detect the expression of autophagy fac- tors Beclin 1，microtubule-associated protein 1A /1B-light chain 3 (LC3) Ⅱ / Ⅰ , and MyD88 /TLR4 /NF-κB p65 pathway related proteins in lung tissue． Results : Compared with control group，knee joint tissue and lung tissue of rats in RA-ILD group were damaged，the arthritis index，lung tissue wet-dry weight ratio，levels of IL-1 β , IL-6， and TNF-α , the expression levels of MyD88 and TLR4 proteins ，and p-NF-κB p65 /NF-κB p65 ratio increased (P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins decreased (P＜0. 01) ．Compared with RA-ILD group，the low-dose and high-dose AME groups showed reduced tissue damage in rats，the arthritis index，lung tis- sue wet-dry weight ratio，levels of IL-1 β , IL-6，and TNF-α , the expression levels of MyD88 and TLR4 proteins， and p-NF-κB p65 /NF-κB p65 ratio showed a dose-dependent decrease (P＜0. 05 or P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins showed a dose-dependent increase (P＜0. 05 or P＜0. 01) ．Compared with high- dose AME group，the tissue damage of rats in the high-dose AME + LPS group was worsened，the arthritis index， lung tissue wet-dry weight ratio，levels of IL-1 β , IL-6，and TNF-α , the expression levels of MyD88 and TLR4 pro- teins，and p-NF-κB p65 /NF-κB p65 ratio were higher (P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ pro- teins was lower (P ＜0. 01 ) ． Conclusion AME inhibits the MyD88 /TLR4 /NF-κB p65 pathway and alleviates lung injury in RA-ILD rats．

Objective:To investigate the expressions and prognostic value of lysyl oxidase like protein 2(LOXL2),chemo-kine c-c-motif ligand 18(CCL-18)and chitinase protein 40(YKL-40)in connective tissue disease with pulmonary interstitial lesions.Methods:A total of 308 patients with connective tissue disease who were treated in the First Affiliated Hospital of Hebei North Univer-sity from July 2021 to February 2022 were selected,including 108 patients with pulmonary interstitial disease(pathological group),200 patients without pulmonary interstitial disease(non pathological group),and another 35 healthy volunteers as the control group.Serum levels of LOXL2,CCL-18 and YKL-40 were detected by ELISA;Logistic regression analysis was applied to analyze the factors affecting the prognosis of patients with connective tissue disease and pulmonary interstitial disease;the predictive value of serum LOXL2,CCL-18 and YKL-40 levels on the prognosis of patients with connective tissue disease and pulmonary interstitial disease was analyzed by receiver operating characteristic(ROC)curve analysis.Results:Compared with control group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the non pathological group and the pathological group were obviously increased(P<0.05);the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the le-sion group were higher than those in the non lesion group(P<0.05);compared with the survival group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease in the death group were obviously higher(P<0.05);Logistic regression analysis showed that LOXL2,CCL-18 and YKL-40 were risk factors for the prognosis of patients with connective tissue disease and pulmonary interstitial disease(P<0.05);the area under the ROC curve(AUC)of the combined detection of serum LOXL2,CCL-18 and YKL-40 in predicting the prognosis of patients with connective tissue disease and pulmonary interstitial disease was 0.967,which was better than their respective independent prediction(Zcombined detection-LOXL2=1.735,P=0.041;Zcombined detection-CCL-18=2.481,P=0.007;Zcombined detection-YKL-40=2.008,P=0.022).Conclusion:The serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease are elevated,which has certain value in the prognosis evaluation of patients with connective tissue disease combined with pulmonary interstitial disease.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

Objective:To investigate the expressions and prognostic value of lysyl oxidase like protein 2(LOXL2),chemo-kine c-c-motif ligand 18(CCL-18)and chitinase protein 40(YKL-40)in connective tissue disease with pulmonary interstitial lesions.Methods:A total of 308 patients with connective tissue disease who were treated in the First Affiliated Hospital of Hebei North Univer-sity from July 2021 to February 2022 were selected,including 108 patients with pulmonary interstitial disease(pathological group),200 patients without pulmonary interstitial disease(non pathological group),and another 35 healthy volunteers as the control group.Serum levels of LOXL2,CCL-18 and YKL-40 were detected by ELISA;Logistic regression analysis was applied to analyze the factors affecting the prognosis of patients with connective tissue disease and pulmonary interstitial disease;the predictive value of serum LOXL2,CCL-18 and YKL-40 levels on the prognosis of patients with connective tissue disease and pulmonary interstitial disease was analyzed by receiver operating characteristic(ROC)curve analysis.Results:Compared with control group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the non pathological group and the pathological group were obviously increased(P<0.05);the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the le-sion group were higher than those in the non lesion group(P<0.05);compared with the survival group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease in the death group were obviously higher(P<0.05);Logistic regression analysis showed that LOXL2,CCL-18 and YKL-40 were risk factors for the prognosis of patients with connective tissue disease and pulmonary interstitial disease(P<0.05);the area under the ROC curve(AUC)of the combined detection of serum LOXL2,CCL-18 and YKL-40 in predicting the prognosis of patients with connective tissue disease and pulmonary interstitial disease was 0.967,which was better than their respective independent prediction(Zcombined detection-LOXL2=1.735,P=0.041;Zcombined detection-CCL-18=2.481,P=0.007;Zcombined detection-YKL-40=2.008,P=0.022).Conclusion:The serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease are elevated,which has certain value in the prognosis evaluation of patients with connective tissue disease combined with pulmonary interstitial disease.

To investigate the expression of miR-133a and miR-424 in the serum of patients with connective tissue disease(CTD)and interstitial lung disease(ILD)and their relationship with T lymphocyte subpopulations,total of 96 CTD-ILD patients treated in our hospital from December 2019 to December 2022 were selected as CTD-ILD group,while 96 CTD patients without ILD were as the control group.The real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect serum levels of miR-133a and miR-424;flow cytometry was applied to detect the levels of T lymphocyte subpopulations.Pearson method was applied to analyze the relationship of miR-133a and miR-424 with T lymphocyte subpopulations.Compared with the control group,the level of serum miR-133a in the CTD-ILD group was obviously reduced,while the expression level of miR-424 was obviously increased(P＜0.05).Under different degrees of pulmonary ventilation disorders,the expression level of miR-133a in the serum of mild,moderate,and severe patients decreased obviously,while the expression level of miR-424 increased obviously(P＜0.05).Under different grades of pulmonary diffusion dysfunction,the expression level of miR-133a in the serum of mild,moderate,and severe patients reduced obviously,while the expression level of miR-424 increased obviously(P＜0.05).Furthermore,the levels of CD4+and CD4+/CD8+in the CTD-ILD group were obviously increased,as compared to the control group,while the levels of CD8+and CD3+were obviously reduced(P＜0.05).In addition,miR-133a was negatively correlated with CD4+,and positively correlated with CD8+and CD3+;miR-424 was positively correlated with CD4+,and negatively correlated with CD8+and CD3+(P＜0.05).In conclusion,the expression level of miR-133a in serum of CTD-ILD patients is decreased,while the expression level of miR-424 is increased,and both of them are related to the T lymphocyte subpopulations.

Background::Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients.Methods::The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes.Results::The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07–2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09–2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively).Conclusions::Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.