Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

OBJECTIVES: To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC). METHODS: SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis. RESULTS: Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis. CONCLUSIONS MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Activating Transcription Factor 4/metabolism* ; Transcription Factor CHOP/metabolism* ; Rats ; Eukaryotic Initiation Factor-2/metabolism* ; Signal Transduction/drug effects* ; eIF-2 Kinase/metabolism* ; Cannabidiol/pharmacology* ; Neurons/metabolism* ; Brain Concussion/metabolism* ; Male ; Molecular Docking Simulation

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

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

OBJECTIVE To investigate the effect of Jianpi Yangzheng(JPYZ)formula regulating tumor-associated macrophage(TAM)exosomes on anoikis in gastric cancer and its mechanism.METHODS TAM model was established by inducing human mononuclear THP-1 cells in vitro;M0,TAM and TAM+JPYZ formula exosomes were extracted by ultracentrifugation and co-incuba-ted with gastric cancer cells.Flow cytometry was used to detect the effect of exosomes in each group on anoikis in gastric cancer cells.A BALB/c transplanted tumor mouse model was constructed,and the expression level of apoptotic proteins in transplanted tumors was detected by Western blot.Label-free mass spectrometry proteomics and bioinformatics were used to analyze the differential proteins in gastric cancer cells before and after intervention;Western blot and qPCR experiments were used to detect the expression level of dif-ferential protein isocitrate dehydrogenase 1(IDH1),and ubiquitination experiments were used to detect the ubiquitination level of IDH1;kits were used to detect the levels of α-ketoglutarate(α-KG),NADPH/NADP+,glutathione(GSH/GSSG)and reactive oxy-gen species(ROS)content.RESULTS The anoikis rate of gastric cancer cells was reduced after TAM exosomes intervention(P<0.05,P<0.01),while it was significantly increased after TAM+JPYZ exosomes intervention(P<0.05,P<0.01).In the in vivo mouse experiment,the ratio of Cleaved Caspase-3/Caspase-3 in the tumor of the TAM exosome group was reduced(P<0.05),while the ra-tio was significantly increased after TAM+JPYZ exosome intervention(P<0.05).Proteomic analysis showed that IDH1 was significant-ly different after intervention,and was related to tricarboxylic acid cycle metabolism.Compared with the M0 group,the IDH1 ubiquiti-nation level of gastric cancer cells in the TAM group with exosome intervention was increased,the levels of α-KG,NADPH/NADP+and GSH/GSSG were significantly increased,and the ROS content was reduced(P<0.05),while TAM+JPYZ exosomes could reverse the above phenomenon.CONCLUSION JPYZ Formula can regulate TAM exosomes to cause ubiquitin degradation of IDH1 in gas-tric cancer cells,reduce the level of tricarboxylic acid cycle metabolism in gastric cancer cells,promote ROS accumulation,induce anoikis in gastric cancer,and thus inhibit the development of gastric cancer.

Objective:To determine the safety and efficacy of sandwich surgery in minimally invasive orthopedic surgery.Methods:A retrospective analysis was performed on 79 pectus carinatum patients undergoing minimally invasive orthopedic surgery admitted to the Department of Thoracic Surgery, Beijing Children's Hospital from July 2016 to July 2018, including 53 cases in the Abramson surgery group and 26 cases in the sandwich surgery group.Results:79 cases successfully completed the operation, the difference in complication rate between the two groups was not statistically significant. All cases were followed up to two years after bar removal, and no recurrence during the follow-up period. The excellent rate of orthopedic effect in sandwich surgery group was higher than that in Abramson surgery group.Conclusion:Sandwich surgery is safe, feasible and can achieve satisfactory postoperative results. It can be used as a surgical option for the treatment of pectus carinatum with depression or depression after orthosis.

Objective To standardize nursing management on postoperative patients with a left ventricular assist-ant device(LVAD).Methods The first draft of the Consensus was formed on the basis of literature review.2 rounds of expert consultations and a round of online meeting discussion were held for adjustments and modifications the draft of the Consensus.Results The recovery rate of the inquiry questionnaire was 93.75%.The authority coefficients of the 2 rounds of inquiry experts were 0.927 and 0.920.The concentration degree of expert opinions for each indicator was greater than 3.5 score,and the coefficient of variation was less than 0.25.The Kendall harmony coefficients for 2 rounds of correspondence were 0.402 and 0.407(P<0.01).The final Consensus formed through expert consultations and meetings includes 7 themes:hemodynamic monitoring,LVAD function monitoring,coagulation function monitoring,percutaneous cable and wound care,exercise rehabilitation care,health education and guidance,and pre-discharge assessment.Conclusion The Consensus is scientific,rigorous,and authoritative.The Consensus covers all aspects of postoperative care for patients with LVAD,and it will benefit to clinical practice.

Objective:To investigate whether IL-6 using in early pregnancy can improve the pregnancy outcome of recurrent spontaneous abortion(RSA)mice and its relevant mechanism,providing new ideas for RSA clinical treatment.Methods:CBA/J×DBA/2 RSA model mice were constructed,and randomly divided the pregnant mice into five groups:control group,0.1 ng/ml IL-6 group,1 ng/ml IL-6 group,10 ng/ml IL-6 group and 100 ng/ml IL-6 group.IL-6 was not injected in control group,while different concentra-tions of IL-6 were respectively injected into other groups on the 0.5 day of pregnancy.Pregnant rats were killed at 13.5 d and the embryo loss rate was calculated,the placental tissue was taked out,and expressions of IL-6 and indoleamine 2,3-dioxygenase(IDO)in tissues were detected by Western blot.Results:Embryo absorption rates of 0.1 ng/ml IL-6 group,1 ng/ml IL-6 group,10 ng/ml IL-6 group and 100 ng/ml IL-6 group were obviously lower than that in control group(P=0.002 4,P=0.007 0,P=0.027 0,P=0.031 0).IL-6 of exogenous injection was positive correlated with that expressed in mice placental tissue(r=0.791,P=0.000 052).IL-6 concentration of exogenous injection was between 0～1 ng/ml,which was positively correlated with IDO expression in placental tissue(r=0.868,P<0.000 1),IL-6 was positively correlated with IDO expressed in placental tissue(r=0.982,P<0.000 1).IL-6 concentration of exogenous injection was between 1～100 ng/ml,which was inversely correlated with IDO expression(r=-0.725,P=0.002),and IL-6 was inversely correlated with IDO expressed in placental tissue(r=-0.972,P<0.000 1).Conclusion:A single intraperitoneal injection of specific concentration of exogenous IL-6 to RSA mice can reduce embryo absorption rate of mice and modify their pregnancy outcome,which possible mecha-nism is the exogenous IL-6 induces expressions of IL-6 and IDO for a long term.Whether the IDO expression in placental tissue in-crease or not can be regarded as a mark for whether the specific concentration IL-6 can protect the pregnancy or not.

Objective To explore the efficacy and safety of fluoroscopy-guided balloon dilation for esophageal strictures in patients with epidermolysis bullosa(EB).Methods The clinical data and follow-up results of EB patients,who received fluoroscopy-guided balloon dilation due to esophageal stricture at Shanghai Xinhua Hospital from May 2020 to May 2023,were retrospectively collected.The therapeutic efficacy and the prognosis of this treatment method were analyzed.Results A total of 17 EB patients received fluoroscopy-guided balloon dilation treatment due to dysphagia caused by esophageal stricture.Most esophageal strictures were single-site stenosis(13/17,76.5％)and it commonly occurred in the esophageal cervical segment(12/17,70.6％)and the upper thoracic segment(8/17,47.1％)of esophagus.Two patients developed esophageal bleeding after dilatation and no special treatment is required.No other post-treatment complications were observed.In most of the patients(15/17,88.2％)a long-term improvement of the dysphagia symptoms could be obtained after receiving a single balloon dilation treatment.By the last follow-up visit,most of the patients(15/17,88.2％)gained more weight when compared with their pre-treatment body weight,with an average increased weight of 2.97 kg.Conclusion Clinically,EB is a rare etiology that can cause an esophageal stricture.This esophageal stenosis is characterized by a single stenosis mostly located in the upper segment of the esophagus.Fluoroscopy-guided balloon dilation is an effective and safe treatment for this type of esophageal strictures.

Objective:To explore the impact of scutellarin on the levels of phosphatidylinositol 3-kinase(P13K)and phosphorylated P13K(p-PI3K)in activated microglia.Methods:A rat cerebral ischemia model was made by middle cerebral artery occlusion(MCAO)method.SD rats were randomly divided into three groups:sham operation group(Sham),cerebral ischemia group(MCAO),and cerebral ischemia with scutellarin group(MCAO+S).A model of ischemia-hypoxia injury of BV2 microglia was established by glucose-oxygen deprivation(OGD)and randomly assigned as control group(Control),OGD group and OGD+scutellarin group(OGD+S).Changes in PI3K and p-PI3K expres-sion in microglia were assessed using double immunofluorescence staining and Western Blot.Results:Immunofluores-cence staining and Western Blot analyses revealed a significant increase in p-PI3K levels in activated microglia both in vivo and in vitro(P＜0.05).Furthermore,treatment with scutellarin led to a further elevation in p-PI3K(P＜0.05).However,there were no significant alterations observed in PI3 K expression among the groups(P＞0.05).Conclusion:Scutellarin may play a positive role in the treatment of cerebral ischemia by up-regulating the phosphorylation level of P13K in activated microglia.