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 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．

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

Objective:To investigate the effects of tranexamic acid on the drainage duration after primary unilateral total knee arthroplasty (TKA).Methods:From June 2017 to December 2018, a total of 182 patients (42 males and 140 females) who underwent primary TKA were included. The age of patients was 68.1±7.1 years (60-76 years). According to the random number table, the subjects were divided into four groups: 45 cases in tranexamic acid group 1 (TXA1), 46 cases in tranexamic acid group 2 (TXA2), 46 cases in tranexamic acid group 3 (TXA3) and others in none tranexamic acid group (NTXA). The patients in TXA1-3 groups received intravenous infusion combined with local application of tranexamic acid. The patients in NTXA group were locally perfused in the joint cavity with 100 ml normal saline after surgery. The drainage volume, total blood loss, invisible blood loss, degree of postoperative joint swelling, Hospital for Special Surgery (HSS) and visual analogue scale (VAS) of pain were compared among the four groups.Results:The postoperative drainage volume of TXA1-3 groups was 85.5±34.3 ml, 189.4±72.3 ml and 215.3±93.4 ml, respectively, which were less than that of the NTXA group (351.3±113.5 ml) with significant difference ( F=11.5, P=0.005). The postoperative drainage volume of TXA1 group was less than that of TXA2-3 groups. The total postoperative blood loss was 699.0±255.7 ml, 710.4±296.1 ml, and 715.8±248.2 ml in the TXA1-3 groups, respectively, which were less than that of the NTXA group (1 130.5±354.2 ml) with significant difference ( F=13.1, P=0.001). At the 4th day after TKA, the knee swelling degree of TXA1-3 groups was 1.25±0.07, 1.13±0.12, and 1.12±0.13, respectively, which were less severe than that of the NTXA group (1.43±0.22) with significant difference ( F=8.23, P=0.015). There were 2 cases with positive bacterial culture in NTXA group and TXA3, 3 cases with hematoma and 1 case with delayed wound healing in the NTXA group. Conclusion:The application of tranexamic acid after TKA can reduce postoperative drainage volume, latent blood loss and total blood loss. The removal of the drainage at 18 h after the operation can not only drain completely, relieve pain and promote knee joint function, but also effectively reduce the risk of infection associated drainage.

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.

BACKGROUND: Our previous findings indicate that inflammation-activated bone marrow mesenchymal stem cell conditioned medium (MSC-CM) contribute to repairing the structure and function of the small intestine after radiation-induced acute intestinal injury. However, it is unclear whether the repair effect can be achieved by regulating small intestinal stem cells. OBJECTIVE: To investigate the effects of inflammation-activated bone marrow MSC-CM on the small intestinal epithelial stem cells after acute radiation-induced intestinal injury and to further discuss the repairing mechanism. METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were separated, cultured and identified. Then, the bone marrow mesenchymal stem cells were co-cultured with normal or radiation-induced IEC-6 cell lines in the Transwell system for 24 hours. Inflammation-activated bone marrow mesenchymal stem cells were cultured alone for 48 hours. Non-activated MSC-CM (MSC-CMNOR) and MSC-CM under radiation-induced inflammatory condition (MSC-CMIR) were collected. Adult Sprague-Dawley rats (provided by the Experimental Center of Sun Yat-Sen University North Campus) were randomly divided into four groups with 20 rats in each group: control group, radiation group, radiation+MSC-CMNOR group and radiation+MSC-CMIR group. The rats in the latter three groups were exposed to one-off 14 Gy whole abdominal radiation to make a rat model of acute radiation-induced small intestinal injury. Three-day continuous administration beginning within 4 hours after successful modeling was given via the tail vein and intraperitoneal implantation of Alzet micro-osmotic pumps: EMEM-F12 (200 μL/d) for the radiation group, MSC-CMNOR for radiation+MSC-CMNOR group and MSC-CMIR for radiation+MSC-CMIR group. There was 2 mL of concentrated conditioned medium in the pump which was released at a constant rate of 10 μL/h into the abdominal cavity after implantation. Intestinal samples were collected at 1, 3, 5, 7 days after radiation for immunochemistry staining, western blot and qRT-PCR detection. RESULTS AND CONCLUSION: (1) On the 3rd day after radiation, Lgr5 positive cells, which were actively proliferating on the base of crypts, became significantly reduced compared with the normal control group, and there was nearly no existing Lgr5 positive cells. However, after infusion of MSC-CMIR, Lgr5 positive intestinal stem cells were significantly increased compared with the radiation group, while in the radiation+MSCNOR group, there was no significant increase in Lgr5 positive intestinal stem cells. (2) On the 3rd day after radiation injury, Bmi1 positive intestinal stem cells were almost invisible. After infusion of MSC-CMIR, Bmi1 positive intestinal stem cells increased significantly, and it was observed not only in the +4 cell position but also in the common position used to be Lgr5 stem cells, indicating that Bmi1 stem cells could differentiate into Lgr5 positive cells to act its repairing effect. (3) Western blot and qRT-PCR further confirmed that the radiation+MSC-CMIR group was significantly higher on the Lgr5 expression level than the radiation group and the radiation+MSC-CMNOR group, and it returned to the normal level on the 7th day after the continuous high expression level. The repair effect of radiation+MSC-CMNOR group was weaker, and only on the 7th day, the expression level of Lgr5 was statistically different from the radiation group. To conclude, inflammation-activated bone marrow MSC-CM exert a protective effect on the small intestinal epithelial stem cells after acute radiation-induced intestinal injury

Objective To discuss the treatment of periprosthetic femoral fractures (PFF) with unstable prosthesis by replacement of long-stem femoral prosthesis and internal fixation.Methods From December 2005 to December 2014,15 PFF patients with unstable prosthesis (15 hips) following were treated at our department.They were 10 men and 5 women,aged from 64 to 89 years (mean,76.2 years).Their primary surgeries included total hip arthroplasty in 13 cases and biological bi-polar replacement of femoral head in 2.Two prostheses were cement and 13 biological.By Vancouver classification,9 cases were type B2,and 6 type B3.The unstable prostheses in the 15 cases were replaced by long-stem femoral ones,followed by internal fixation.At the last follow-ups,clinical outcome were evaluated by Harris scoring and images of PFF by Beals & Tower criteria.Complications were documented.Results One died 4 months after operation.The other 14 patients were followed up for an average of 4.5 years (from 6 months to 9 years).Fracture union was achieved in 12 cases after an average of 3.9 months (from 3 to 9 months).Nonunion occurred in 2 cases.Imaging evaluation revealed 9 excellent cases,3 good ones and 2 poor ones.The Harris scores at the last follow-up averaged was 82.3 points (from 50 to 100 points).Deep vein thrombosis occurred preoperatively in one case and posterior tibial vein thrombosis occurred in 2 cases respectively on day 3 and day 10 postoperatively.No such complications occurred as malunion,fixation failure,dislocation or prosthesis loosening.Conclusion Satisfactory outcomes can be achieved by replacement of long-stem femoral prosthesis combined with appropriate fixation for treatment of PFF with unstabrosthesis.