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 screen and identify specific monoclonal antibodies targeting the surface envelope protein E8L of the monkeypox intracellular mature virus based on mRNA immunization and single-cell sequencing.Methods E8L-mRNA was synthesized in vitro and encapsulated into lipid nanoparticles(LNPs)for immunization to induce immune responses.The antibody level in blood serum was detected to find out when the mice had produced sufficient antibodies.B cells in the spleen of the mice were isolated by flow cytometry sorting,followed by library construction and sequencing.Based on the analysis of light and heavy chain sequences of the antibodies from the sequencing data,E8L candidate monoclonal antibodies were screened according to the abundance ranking and expressed.The affinity of these monoclonal antibodies was detected by enzyme-linked immunosorbent assay(ELISA).Candidate antibodies with high affinity for E8L were applied to immunochromatographic assays to detect the monkeypox virus(MPXV)E8L protein.Results Mice were immunized by lipid nanoparticles encapsulating E8L-mRNA.Approximately 1.5 million B cells were selected by flow cytometry.After single-cell sequencing,17 candidate monoclonal antibodies for E8L were identified and expressed.Two high affinity monoclonal antibodies were obtained for monkeypox virus E8L protein by ELISA.These two antibodies were used as the basis for immunochromatographic assays to detect E8L protein,with a sensitivity of 0.5 ng/mL.Conclusion Two monoclonal antibodies with high affinity for the MPXV E8L protein are obtained,which can be potentially used for detecting monkeypox virus.

Objective:To develop and validate a clinical prediction model for assessing the risk of postoperative pulmonary complications (PPCs) in elderly patients undergoing surgery with general anesthesia.Methods:This prospective observational study enrolled patients aged ≥65 years who underwent general anesthesia with mechanical ventilation duration >3 hours across six tertiary hospitals between December 2022 and August 2023. Based on follow-up outcomes (until discharge or postoperative day 7), patients were categorized into a non-PPCs group and a PPCs group. Detailed records included baseline patient characteristics, preoperative comorbidities, surgical information (type, duration), and bedside lung ultrasound scores (LUS) assessed within 24 hours postoperatively using a standardized 12-zone protocol. Predictor selection was performed using LASSO regression. Significant predictors identified were incorporated into a multivariate logistic regression analysis to build the prediction model, visualized as a nomogram. Internal validation was conducted via bootstrap resampling (1 000 repetitions). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) for discrimination, calibration curves for calibration accuracy, and decision curve analysis (DCA) for clinical utility.Results:A total of 130 eligible elderly surgical patients were included. PPCs occurred in 17 patients (incidence rate: 13.1%). Multivariate analysis identified LUS ( OR=1.248, 95% CI: 1.099-1.417, P=0.001) and elective surgery type ( OR=0.206, 95% CI: 0.043-0.988, P=0.048) as independent predictors of PPCs. The nomogram model demonstrated an AUC of 0.867 (95% CI: 0.775-0.959) upon initial testing. Internal validation confirmed good discrimination (AUC=0.863, 95% CI: 0.778-0.972). Calibration curves indicated excellent agreement between predicted probabilities and observed outcomes. Decision curve analysis demonstrated significant clinical net benefit across a wide range of threshold probabilities (0.03-0.89). Conclusions:The clinical prediction model, developed using early postoperative LUS scores and surgical type, effectively predicts the risk of postoperative pulmonary complications in elderly patients following surgery under general anesthesia. The model exhibits strong discrimination, calibration, and clinical utility, providing clinicians with a reliable tool for individualized risk assessment to support clinical decision-making and potentially reduce PPC incidence.

Although the incidence of each type of rare tumor is extremely low, the cumulative patient population is large due to the wide variety of such tumors. The diagnosis and treatment of rare tumors in China are currently faced with numerous challenges, such as diagnostic difficulties and limited therapeutic options: traditional histopathological diagnosis has certain limitations, and most treatment regimens still rely on conventional approaches including surgery, radiotherapy and chemotherapy. With the advancement of molecular diagnostic technologies and precision medicine, especially the application of next-generation sequencing, liquid biopsy and artificial intelligence technologies, the diagnostic accuracy of rare tumors has been significantly improved. Meanwhile, innovative therapies such as bispecific antibodies, antibody-drug conjugates, and gene and cell therapies have brought new hope for patients. In the future, China needs to establish a hierarchical diagnosis and treatment network for rare tumors, strengthen drug development and clinical trial exploration, improve relevant medical insurance policies, and build a prevention, diagnosis and treatment system with Chinese characteristics for rare tumors, so as to provide better diagnosis and treatment services for patients.

Objective To explore the correlation between serum inflammatory indicators and short-term prognosis in patients with single-segment lumbar intervertebral disc protrusion(LDH)treated by transforaminal endoscopic discectomy(TELD).Methods From January 2015 to June 2022,137 patients with single-segment LDH received TELD treatment.The levels of serum inflammatory factors such as C-reactive protein(CRP),white blood cell count(WBC),erythrocyte sedimentation rate(ESR),and procalcitonin(PCT)of the patients before the operation and 3 days after the operation,as well as surgical data such as anesthesia methods,operation time,and blood loss were collected.The time for patients to resume work was collected,and the pain relief and functional recovery of the patients were evaluated by using the Visual Analogue Scale(VAS)and the Oswestry Disability Index(ODI).Pearson or Spearman rank correlation analysis was used to explore the correlations between demographic characteristics,inflammatory indicators,surgical data and short-term prognosis.Results The average time for patients to return to work was(3.55±2.13)months.There were statistically significant differences in the pain and functional scores at each time point compared with those at the previous time point(P＜0.05).The CRP,WBC and PCT of the patients after the operation were significantly increased compared with those before the operation,and the difference was statistically significant(P＜0.05).The levels of CRP and PCT in patients 3 days after surgery were significantly positively correlated with VAS 6 months after surgery.The duration of symptoms and the CRP level 3 days after surgery were significantly positively correlated with ODI 6 months after surgery.BMI was significantly positively correlated with the time to return to work(P＜0.05).Conclusion There is a certain correlation between the levels of serum inflammatory indicators in patients with single-segment LDH treated with TELD and the short-term prognosis.The increase of CRP and PCT 3 days after the operation may affect the rehabilitation process of the patients.

Objective To explore the correlation between serum inflammatory indicators and short-term prognosis in patients with single-segment lumbar intervertebral disc protrusion(LDH)treated by transforaminal endoscopic discectomy(TELD).Methods From January 2015 to June 2022,137 patients with single-segment LDH received TELD treatment.The levels of serum inflammatory factors such as C-reactive protein(CRP),white blood cell count(WBC),erythrocyte sedimentation rate(ESR),and procalcitonin(PCT)of the patients before the operation and 3 days after the operation,as well as surgical data such as anesthesia methods,operation time,and blood loss were collected.The time for patients to resume work was collected,and the pain relief and functional recovery of the patients were evaluated by using the Visual Analogue Scale(VAS)and the Oswestry Disability Index(ODI).Pearson or Spearman rank correlation analysis was used to explore the correlations between demographic characteristics,inflammatory indicators,surgical data and short-term prognosis.Results The average time for patients to return to work was(3.55±2.13)months.There were statistically significant differences in the pain and functional scores at each time point compared with those at the previous time point(P＜0.05).The CRP,WBC and PCT of the patients after the operation were significantly increased compared with those before the operation,and the difference was statistically significant(P＜0.05).The levels of CRP and PCT in patients 3 days after surgery were significantly positively correlated with VAS 6 months after surgery.The duration of symptoms and the CRP level 3 days after surgery were significantly positively correlated with ODI 6 months after surgery.BMI was significantly positively correlated with the time to return to work(P＜0.05).Conclusion There is a certain correlation between the levels of serum inflammatory indicators in patients with single-segment LDH treated with TELD and the short-term prognosis.The increase of CRP and PCT 3 days after the operation may affect the rehabilitation process of the patients.

Objective:To evaluate the efficacy and safety of radiotherapy as a combined mode with in-situ vaccine for patients with advanced soft tissue sarcoma(STS).Methods:The clinical data of 12 patients with advanced STS who received combination therapy mode at the Cancer Center of Gulou Hospital Affiliated to the School of Medicine of Nanjing University between December 2020 and September 2024 were retrospectively analyzed.All 12 patients received combined therapy.The main radiotherapeutic approach was hypofractionated radiotherapy.The targeted therapy mainly involved Anlotinib(in 10 cases)or Apatinib(in 2 cases).Immunotherapy mainly involved PD-1 antibodies.The primary endpoint was disease control rate(DCR),and the secondary endpoints were objective response rate(ORR)and safety.Results:Among the 12 STS patients who received combined treatment,0 cases achieved CR,4 cases achieved PR;7 cases had SD,and 1 case had PD.The ORR was 33%,and the DCR was 91.7%,among which the DCR of the target lesions was 100%.Among the 12 patients,9 patients experienced grade Ⅰ to grade Ⅱ adverse reactions.The most frequently occurring hematological adverse reactions were anemia(6 cases)and abnormal results of liver function tests(3 cases).The most frequently occurring non-hematological adverse reactions were proteinuria(5 cases),hypertension(4 cases),abnormal thyroid function(3 cases),anorexia(3 cases),and nausea and vomiting(2 cases).Only 2 cases had grade Ⅲ hematological toxicity,and 1 case had grade Ⅲpneumothorax.Conclusion:Radiotherapy as a combined therapy mode with in situ vaccine can achieve a higher DCR in advanced soft tissue sarcomas without serious adverse reactions.This combined treatment modality demonstrates good efficacy and safety.

Objective To evaluate the value of a machine learning-based biparametric magnetic resonance imaging(bpMRI)radiomics model in predicting clinically significant prostate cancer(csPCa)in the transitional zone.Methods A retrospective analysis was con-ducted on 507 cases in two medical centers.All patients underwent prostate MRI examinations before surgery,with complete patho-logical data.The case distribution was as follows:256 cases of csPCa,97 cases of clinically insignificant prostate cancer(ciPCa),and 154 cases of benign prostatic hyperplasia(BPH).Using the R language,the data from Center One was randomly divided into training and test groups at a ratio of 7∶3,and the data from Center Two as an independent external validation group.The image features from T2 WI and diffusion weighted imaging(DWI)were extracted,and the least absolute shrinkage and selection operator(LASSO)was used to reduce dimensionality and filter features.Two datasets were constructed based on T2 WI features alone and combined T2 WI and DWI features.Six prediction models were established using random forest(RF),logistic regression(LR),and support vector machine(SVM).The efficacy of six models of T2 WI features and combined T2 WI and DWI features in the diagnosis of prostate dis-eases through receiver operating characteristic(ROC)curve,area under the curve(AUC),and decision curve analysis(DCA)were compared and evaluated.Results In the training group,feature screening identified 7 and 8 features from the T2WI single sequence and the T2WI with DWI dual sequence for csPCa prediction in the transitional zone.The results showed that the T2WI with DWI dual sequence RF model had the highest AUC performance.The AUC of the training,test,and validation groups were 0.950,0.866,and 0.818,respectively.The test group accuracy was 0.805,sensitivity was 0.690,and specificity was 0.920;the validation group accu-racy was 0.726,sensitivity was 0.661,and specificity was 0.793.DCA showed that within a wide probability threshold range,the T2 WI with DWI dual sequence RF model had the greatest net benefit.Conclusion Based on the bpMRI radiomics model,non-invasive prediction of csPCa in the transitional zone can be achieved before surgery,which helps to make clinical diagnosis and treatment decisions.

Shear thinning is an ideal feature of bioink because it can reduce the chance of blocking. For extrusion based biological printing, bioink will experience shear force when passing through the biological printer. The shear rate will increase with the increase of extrusion rate, and the apparent viscosity of shear-thinning bioink will decrease, which makes it easier to block, thus achieving the structural fidelity of 3D printing tissue. The manufacturing of complex functional structures in tissue trachea requires the precise placement and coagulation of bioink layer by layer, and the shear-thinning bioink may well meet this requirement. This review focuses on the importance of mechanical properties, classification and preparation methods of shear-thinning bioink, and lists its current application status in 3D printing tissue trachea to discuss the more possibilities and prospects of this biological material in tissue trachea.