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.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

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．

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

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.

Objective To analyze the changes in the expression levels of serum Dickkopf-related protein 1(DKK-1)and latent transforming growth factor binding protein 2(LTBP2)in patients with connective tissue disease(CTD)related interstitial pneumonia(IP)of different disease activity levels before and after treatment.Methods A total of 121 CTD patients who visited the First Affiliated Hospital of Hebei North University from January 2022 to October 2023 were collected and separated into an observation group(CTD-related IP patients,n=62)and a reference group(CTD without IP patients,n=59)based on the incidence of IP.The observation group was separated into a stable phase group(n=26)and an acute exacerbation phase group(n=36)based on disease activity.Enzyme-linked immunosorbent assay(ELISA)detected DKK-1 and LTBP2 levels.Pearson or Spearman were used to analyze correlations between DKK-1 and LTBP2 levels with clinical data.Logistic regression was applied to analyze influencing factors of acute exacerbation in CTD-related IP patients.Results The serum levels of DKK-1(14.98±3.32 ng/ml)and LTBP2(32.64±4.01 ng/ml)in the observation group were higher than those in the reference group(2.21±0.67 ng/ml,8.73±2.15 ng/ml),the differences were statistically significant(t=28.983,57.518,all P＜0.05).The proportions of patients with ground glass opacity(66.67%)and honeycomb opacity(52.78%),serum DKK-1(19.67±4.10 ng/ml),LTBP2(38.76±4.92 ng/ml)and C-reactive protein(CRP)(32.46±3.12 mg/L)in the acute exacerbation group were higher than those in the stable phase group(30.77%,23.08%,8.48±1.37 ng/ml,24.17±3.65 ng/ml,22.05±2.80 mg/L),the differences were statistically significant(t/x2=7.790,5.534,13.362,12.781,13.524,all P<0.05).The serum levels of DKK-1 and LTBP2 in patients with acute exacerbation of CTD-related IP after treatment were positively correlated with ground glass opacities,honeycomb opacities,CRP and different disease activity(r=0.526,0.518,0.513,0.548;0.499,0.514,0.520,0.561,all P<0.05).As the treatment time extended,the serum levels of DKK-1 and LTBP2 in CTD-related IP patients in the stable and acute exacerbation groups decreased,and the serum levels of DKK-1 and LTBP2 in the acute exacerbation group were higher than those in the stable group before treatment,1 month after treatment,and 3 months after treatment,the differences were statistically significant(t=13.355,13.206,15.913;12.781,12.263,11.161,all P<0.05).DKK-1[OR(95%CI):2.458(1.297～4.657)],LTBP2[OR(95%CI):2.739(1.567～4.789)]were independent risk factors for acute exacerbation of CTD related IP patients(all P<0.05).Conclusion The serum levels of DKK-1 and LTBP2 in CTD-related IP patients are increased,and closely related to disease activity.Both decrease after 3 months of treatment and can monitor the treatment efficacy of patients to a certain extent.

Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis