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

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To discuss the clinical characteristics,intervention timing,diagnosis and treatment plan,and prognosis of one patient with immune thrombotic thrombocytopenic purpura(iTTP),and to provide more clinical evidences for the precise diagnosis and treatment of this rare disease.Methods:The clinical data of one patient with iTTP were collected,who had been previously misdiagnosed with acute infection after receiving a virus-inactivated vaccine.The data included clinical manifestations and ancillary examination informations.The relevant literatures were reviewed.Results:The patient,a 60-year-old male,was admitted with"fever for 6 d."The physical examination results showed scattered red maculopapules on the lower limbs,with only mild thrombocytopenia initially,and the admission PLASMIC score was 5 points.Initially diagnosed with acute infection,the patient was treated with anti-inflammatory,anti-infective,and corticosteroid therapies,but the response was poor.After one week,the re-evaluation results showed a significant decrease in the platelet count,progressing to severe thrombocytopenia,hematuria,dark-colored urine,and neurological and psychiatric symptoms as the disease progressed.The further examination results showed the PLASMIC score was increased to 7 points.After high suspicion of iTTP,therapeutic plasma exchange(TPE)was initiated immediately.The a disintegrin and metalloproteinase with thrombospondin type 1 motif member 13(ADATMS13)activity level was<1%during treatment,and the test for ADAMTS13 inhibitors was positive.The genetic testing results revealed a missense mutation in an iTTP-susceptible gene.After a confirmed diagnosis,the patient was treated regularly with intravenous rituximab,completing four treatment cycles,and followed up to the present;the treatment deemed effective.Conclusion:iTTP is often delayed in the diagnosis due to atypical initial clinical symptoms.Once suspected,the treatment based on TPE and glucocorticoids should be initiated immediately.New drugs like rituximab provide a multidisciplinary treatment strategy option for iTTP.

Objective:To evaluate modified extended trochanteric osteotomy (ETO) applied in the revision of Vancouver B2/B3 periprosthetic femoral fractures (PFF).Methods:A retrospective study was conducted to analyze the 35 patients with Vancouver B2/B3 PFF who had been treated at Joint Disease Department Ⅱ, Zhengzhou Orthopedic Hospital from January 2012 to November 2020. There were 10 males and 15 females with an age of (74.3±7.8) years. The time from their primary replacement to revision was (120.3±28.6) months. By the Vancouver classification, 26 cases were type B2 and 9 ones type B3. The modified ETO was used in the revision surgery for all patients. The clinical efficacy was evaluated using Harris hip score, imaging evaluation was performed using the Beals and Tower criteria at the last follow-up, and complications were recorded.Results:The operation time for this cohort was (148±32) min and intraoperative bleeding (800±150) mL. All patients were followed up for (45.2±15.3) months. The Harris score increased significantly from preoperative (21.3±11.2) points to (86.2±5.2) points at the last follow-up ( P < 0.001). By the Beals and Tower evaluation, 9 cases were rated as excellent, 24 cases as good, and 2 as poor. All the fractures and sites of trochanteric osteotomy got healed after (4.4±2.8) months except for 1 case of nonunion. Prosthesis subsidence occurred in 3 cases, in 2 of which the subsidence stopped 6 months later and in only 1 of which revision was needed due to the subsidence. Upward block displacement of the greater trochanteric fracture occurred in 2 cases, but did not exceed 1 cm. One case of postoperative dislocation responded to manual reduction. Conclusion:In the revision of Vancouver B2/B3 PFF, the modified ETO can improve fracture healing, and reduce postoperative dislocations and complications, leading to satisfactory clinical efficacy.

Objective:To investigate the risk factors associated with one-year mortality following surgery for intertrochanteric fractures in elderly patients and develop a survival prediction model.Methods:A retrospective analysis was conducted on clinical data from 532 elderly patients with intertrochanteric fractures admitted to the People's Hospital of Xinjiang Uygur Autonomous Region and the People's Hospital of Xinyang between January 2020 and September 2022.Patient demographics, laboratory indicators, and surgical variables were documented.The primary outcome assessed was the one-year mortality rate.Risk factors were identified through univariate and multivariate Cox regression analyses, leading to the development of a prognostic model.The model's predictive performance was evaluated using the Concordance Index(C-Index), time-dependent receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).Results:Multivariate Cox regression analysis identified several key factors associated with one-year mortality after intertrochanteric fractures in elderly patients.These factors included the modified five-item frailty index( OR=1.338, 95% CI: 1.147-1.561, P<0.001), ICU admission( OR=1.694, 95% CI: 1.230-2.333, P=0.001), preoperative hemoglobin levels( OR=1.281, 95% CI: 1.016-1.616, P=0.036), surgical waiting time( OR=1.570, 95% CI: 1.063-2.319, P=0.023), and age( OR=2.196, 95% CI: 1.712-2.816, P<0.001).The prediction model showed good consistency with a C-Index of 0.769(95% CI: 0.723-0.818)in the modeling group and 0.715(95% CI: 0.612-0.750)in the validation group.Time-dependent ROC areas under the curve were 0.802(95% CI: 0.722-0.850)and 0.718(95% CI: 0.640-0.808)for the modeling and validation groups, respectively.Calibration curves for both groups indicated a good model fit, and decision curve analysis demonstrated a positive net benefit, highlighting the clinical applicability of the model. Conclusions:The modified five-item frailty index, ICU admission, preoperative hemoglobin, surgical waiting time, and age independently predict one-year mortality after surgery for intertrochanteric fractures in elderly patients.This prognostic model, utilizing these factors, shows high predictive accuracy, assisting clinicians in quick personalized assessments and setting informed expectations in clinical practice.

Objective To explore the expression and diagnostic value of circulating microRNA(miR)-126-3p in non-small cell lung cancer(NSCLC).Methods Multi-centred miR chips and sequencing data were col-lected to investigate the differential expression of circulating miR-126-3p in NSCLC.In order to evaluate the comprehensive expression level of circulating miR-126-3p in the cycle,the standardized mean difference(SMD)and summary receiver operating characteristic(sROC)curve were calculated,and the area under curve(AUC)of sROC curve was analyzed.Sensitivity,specificity,positive negative likelihood ratio were ex-plored,and the expression of circulating miR-126-3p was further comprehensively analyzed in combination with tissue.By using miRDB,starBase v2.0,and TargetScan 7.1,combined with up-regulated differentially expressed genes in NSCLC,potential target genes of circulating miR-126-3p were screened using complemen-tary sequence method.Results Based on six circulating miR datasets,the expression level of circulating miR-126-3p was higher than that of the control group,and the difference was statistically significant(P＜0.05).The receiver operating characteristic curves showed that circulating miR-126-3p had strong diagnostic efficacy(AUC＞0.5),and the comprehensive expression of circulating miR-126-3p was lower in 199 cases of NSCLC group than in the control group(SMD=-1.46).The sROC curve showed that circulating miR-126-3p distin-guished the NSCLC group from the control group with high accuracy(AUC=0.91),Egger's test showed no publication bias(P＞0.05),with sensitivity and specificity 0.80,and positive likelihood ratio and negative likelihood ratio were 5.37 and 0.18,respectively.In addition,a comprehensive analysis of the circulation and tissue of 1 320 NSCLC samples from 26 datasets showed that circulating miR-126-3p expression was lower in NSCLC group than in the control group(SMD=-2.07).The sROC curve showed that low-expression circu-lating miR-126-3p had high accuracy in distinguishing between the NSCLC group and the control group(AUC=0.97).In addition,potential target genes ADAM9 and SLC7A5 were screened for circulating miR-126-3p,and their expression in NSCLC group was higher than that in the control group.Conclusion Low ex-pression of circulating miR-126-3p in the circulation may be an important biomarker for high-precision screen-ing of NSCLC.

Objective:To explore role of miR-146a in regulating TLR4/NF-κB pathway on inflammatory injury and neuropro-tection in intracerebral hemorrhage model rats and its possible mechanism.Methods:A total of 40 rats were selected and randomly divided into sham,model,over-expressing miR-146a adenovirus and negative virus injection groups,with 10 rats in each group.Garcia score was used for neurological function;HE staining was used to observe changes of brain tissues.ELISA was used to detect inflammatory factors levels.TLR4,NF-κB protein and gene expressions in brain tissues were detected by Western blot and RT-PCR.Results:Compared with model group,neural function score of overexpressed miR-146a adenovirus injection group was increased(P<0.05).Model group had abnormal cell morphology,edema and inflammation.Cell morphology,edema and inflammation were alleviated in overexpressed miR-146a adenovirus injection group.Inflammatory factors levels in model group were higher than sham group(P<0.05).Inflammatory factors levels in overexpressed miR-146a adenovirus injection group were lower than model group(P<0.05).TLR4,NF-κB protein and mRNA expressions in model group were increased than sham group(P<0.05).TLR4,NF-κB protein and mRNA expressions in overexpressed miR-146a adenovirus injection group were decreased than model group(P<0.05).Conclusion:miR-146a can improve neural function and reduce inflammatory injury in rats with intracerebral hemorrhage,possibly by inhibiting activation of TLR4/NF-κB signaling pathway and reducing inflammatory factors levels of brain tissues.

Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.

A simple, fast, and visual method for detecting antibodies against peste des petits ruminants virus (PPRV) using colloidal gold strips was developed. In this study, the pET-32a-N was transformed into Escherichia coli Rosetta (DE3) for expression. Hybridoma cell lines were generated by fusing SP2/0 myeloma cells with splenocytes from immunized mice with the expressed and purified N protein of PPRV. The PPRV N protein was labeled with colloidal gold particles as the gold-labeled antigen. The N protein served as the gold standard antigen and as the test (T) line-coated antigen, while the monoclonal antibody served as the quality control (C) line-coated antibody to assemble the colloidal gold immunochromatographic test strips for detecting antibodies against the N protein of PPRV. Hybridoma cell line designated as 1F1 was able to stably secrete the monoclonal antibody against the N protein of PPRV. The titer of 1F1 monoclonal antibody in ascites was 1:128 000 determined by indirect enzyme-linked immunosorbent assays (ELISA), and the immunoglobulin subtype of the monoclonal antibody was IgG1, with kappa chain. The obtained monoclonal antibody was able to specifically recognize the N protein of PPRV, as shown by Western blotting and indirect immunofluorescent assay (IFA). The developed colloidal gold test strip method was able to detect PPRV antibodies specifically, and there was no difference between different batches of the test strips. Testing of a total of 122 clinical sera showed that the compliance rate of the test strip with ELISA test was 97.6%.The test strip assay developed in this study has good specificity, reproducibility, and sensitivity, and it can be used for the rapid detection of PPRV antibodies.
Animals ; Mice ; Peste-des-Petits-Ruminants/prevention & control* ; Antibodies, Monoclonal ; Reproducibility of Results ; Peste-des-petits-ruminants virus ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Goats

Objective : o explore the effects of long non⁃coding RNA LINC00092 on the proliferation , migration and invasion of glioma. Methods : Using the cancer genome atlas(TCGA) and genotype⁃tissue expression (GTEx) databases , this study analyzed the expression of LINC00092 in pan⁃carcinoma and its effect on the prognosis of glioma. In addition , LINC00092 overexpression plasmid was constructed to detect the effects of LINC00092 on proliferation , migration , invasion and apoptosis of glioma cells by cell function experiments , including CCK⁃8 assay , Transwell assay and flow cytometry. Finally , qRT⁃PCR and Western blot were used to detect the effect of overexpression of LINC00092 on the expression level of IGF2BP1 . Results : The analysis of public databases revealed a widespread downregulation of LINC00092 in tumors , and its association with the development of glioblastoma multiforme (GBM) and low⁃grade glioma (LGG) . In vitro experiments demonstrated that overexpression of LINC00092 significantly reduced the proliferation , migration and invasion of glioma cells , while promoting apoptosis. Moreover, overexpression of LINC00092 led to a decrease in the expression levels of IGF2BP1 . Conclusion LINC00092 may inhibit glioma proliferation , migration and invasion by targeting IGF2BP1 , and promote glioma cell apoptosis.