Cardamonin, a natural flavonoid compound, exhibits potential anti-aging properties, yet its precise mechanisms still remain unclear. In this study, we established cellular senescence models using bleomycin and H2O2 and treated the cells with varying concentrations of cardamonin to investigate its anti-senescence effects and underlying mechanisms. Senescence-associated β-galactosidase (SA-β-gal) staining was employed to assess senescent phenotypes, while immunofluorescence was used to detect DNA damage levels. Intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA probe, and Western blot was performed to analyze the expression of p53, p21, collagen, α-smooth muscle actin (α-SMA), mechanistic target of rapamycin (mTOR), and p-mTOR. To further validate the mechanistic target, MHY1485 was utilized to activate the mTOR pathway and evaluate its regulatory impact on senescence phenotypes. The results demonstrated that cardamonin significantly alleviated bleomycin- and H2O2-induced cellular senescence. Mechanistic studies revealed that cardamonin reduced ROS accumulation and suppressed mTOR phosphorylation. Notably, MHY1485-mediated activation of the mTOR pathway reversed senescence and fibrotic phenotypes, providing reciprocal validation of the target mechanism. In conclusion, cardamonin mitigates cellular senescence by targeting the mTOR-ROS axis, offering a promising therapeutic strategy for anti-aging interventions and the treatment of idiopathic pulmonary fibrosis (IPF).

Objective:To summarize and compare the clinical characteristics of immune checkpoint inhibitor-associated pneumonia(CIP)in elderly and non-elderly lung cancer patients treated with immune checkpoint inhibitors(ICIs).Methods:We conducted a retrospective analysis of the clinical data from 61 patients who developed CIP following ICIs treatment in the Respiratory and Critical Care Medicine Department and the Oncology Department of Beijing Hospital from May 2016 to April 2024.The clinical characteristics of patients aged 65 years and older were compared with those of patients younger than 65 years.Results:A total of 61 patients were included in the study, with 26 patients in the group aged <65 years[aged 39-64(56.3±5.6)years].Within this group, the clinical grades were distributed as follows: 5 patients in grade 1(G1), 12 in grade 2(G2), 7 in grade 3(G3), and 2 in grade 4(G4).Twelve patients underwent bronchoscopy, while 17 patients received corticosteroid therapy after developing CIP.Additionally, 20 patients permanently discontinued immunotherapy due to CIP.Notably, one patient showed improvement in CIP following treatment, which allowed for the continuation of ICIs.Importantly, no patients in this group experienced mortality due to CIP.In the group aged ≥65 years[aged 65-83(71.9±4.9)years], there were 35 patients, categorized as follows: 4 in G1, 22 in G2, 5 in G3, and 4 in G4.Twenty-one patients underwent bronchoscopy, 31 received corticosteroid therapy after developing CIP, and 30 patients permanently discontinued immunotherapy due to CIP.Similarly, one patient in this group demonstrated improvement in CIP following treatment, which permitted the continuation of ICIs.Importantly, no patients in this group experienced mortality due to CIP.Compared to patients aged <65 years, those aged ≥65 years experienced a shorter median time to the occurrence of CIP, with a median of 2(1, 4)months versus 5.5(2, 8)months for the younger group( Z=-3.231, P=0.001).Furthermore, a higher proportion of patients aged ≥65 years received corticosteroid therapy after developing CIP(88.57% or 31 cases)compared to 65.38%(17 cases)in the younger group( χ2=4.704, P=0.030).There were no statistically significant differences in the occurrence of CIP symptoms or chest imaging characteristics between the two age groups(both P>0.05). Conclusions:Patients aged 65 years and older experience a shorter median time to develop CIP following the use of ICIs.However, there is no significant difference in clinical outcomes when compared to the group aged under 65 years, provided that early identification and diagnosis are achieved.

Objective:To summarize and compare the clinical characteristics of immune checkpoint inhibitor-associated pneumonia(CIP)in elderly and non-elderly lung cancer patients treated with immune checkpoint inhibitors(ICIs).Methods:We conducted a retrospective analysis of the clinical data from 61 patients who developed CIP following ICIs treatment in the Respiratory and Critical Care Medicine Department and the Oncology Department of Beijing Hospital from May 2016 to April 2024.The clinical characteristics of patients aged 65 years and older were compared with those of patients younger than 65 years.Results:A total of 61 patients were included in the study, with 26 patients in the group aged <65 years[aged 39-64(56.3±5.6)years].Within this group, the clinical grades were distributed as follows: 5 patients in grade 1(G1), 12 in grade 2(G2), 7 in grade 3(G3), and 2 in grade 4(G4).Twelve patients underwent bronchoscopy, while 17 patients received corticosteroid therapy after developing CIP.Additionally, 20 patients permanently discontinued immunotherapy due to CIP.Notably, one patient showed improvement in CIP following treatment, which allowed for the continuation of ICIs.Importantly, no patients in this group experienced mortality due to CIP.In the group aged ≥65 years[aged 65-83(71.9±4.9)years], there were 35 patients, categorized as follows: 4 in G1, 22 in G2, 5 in G3, and 4 in G4.Twenty-one patients underwent bronchoscopy, 31 received corticosteroid therapy after developing CIP, and 30 patients permanently discontinued immunotherapy due to CIP.Similarly, one patient in this group demonstrated improvement in CIP following treatment, which permitted the continuation of ICIs.Importantly, no patients in this group experienced mortality due to CIP.Compared to patients aged <65 years, those aged ≥65 years experienced a shorter median time to the occurrence of CIP, with a median of 2(1, 4)months versus 5.5(2, 8)months for the younger group( Z=-3.231, P=0.001).Furthermore, a higher proportion of patients aged ≥65 years received corticosteroid therapy after developing CIP(88.57% or 31 cases)compared to 65.38%(17 cases)in the younger group( χ2=4.704, P=0.030).There were no statistically significant differences in the occurrence of CIP symptoms or chest imaging characteristics between the two age groups(both P>0.05). Conclusions:Patients aged 65 years and older experience a shorter median time to develop CIP following the use of ICIs.However, there is no significant difference in clinical outcomes when compared to the group aged under 65 years, provided that early identification and diagnosis are achieved.

Chronic obstructive pulmonary disease(COPD),as a global health challenge,brings heavy economic and psychological burdens to patients and their families.Accurately identifying the risk factors for COPD and excluding false associations are crucial for understanding its pathogenesis and formulating prevention strategies.Mendelian randomization(MR),as a supplementary method,has shown great potential in reducing the interference of confounding factors,lowering the cost of experimental research,and avoiding experimental ethical issues.This article focuses on MR and its main derivative methods,discusses their basic principles and applicable conditions,and analyzes their application effects and limitations in COPD research in combination with specific cases,enabling MR to be more widely applied in the study of influencing factors of COPD.

Chronic obstructive pulmonary disease(COPD),as a global health challenge,brings heavy economic and psychological burdens to patients and their families.Accurately identifying the risk factors for COPD and excluding false associations are crucial for understanding its pathogenesis and formulating prevention strategies.Mendelian randomization(MR),as a supplementary method,has shown great potential in reducing the interference of confounding factors,lowering the cost of experimental research,and avoiding experimental ethical issues.This article focuses on MR and its main derivative methods,discusses their basic principles and applicable conditions,and analyzes their application effects and limitations in COPD research in combination with specific cases,enabling MR to be more widely applied in the study of influencing factors of COPD.

【Objective】 To investigate the protective effects of aflexible sleeve penile protection device on reducing postoperative pain and wound edema in patients after circumcision. 【Methods】 A total of 54 patients who underwent circumcision at Yan’an Branch of Peking University Third Hospital during Feb.1 and May 31, 2023 were enrolled.The patients were randomly divided into the experimental group and control group, with 27 patients in either groups.Patients in the experimental group were treated with a flexible sleeve penis protection device after surgery, and patients in the control group were treated with traditional gauze bandage after surgery.Postoperative pain, wound edema and complications were compared between the two groups. 【Results】 In terms of pain, the visual analogue scale of the experimental group was significantly lower at 6 hours [(1.7±0.9) vs.(3.3±1.9), P<0.001] and 2 days [(2.0±1.3) vs.(3.3±1.3), P<0.001] after surgery than that of the control group, but there were no statistically significant differences between the two groups on the 4th and 7th postoperative days (P>0.05).In terms of edema, the edema score of the experimental group was significantly lower than that of the control group on the 2nd postoperative day [(2.0±1.0) vs.(4.0±0.8), P<0.001] , the 4th postoperative day [(1.5±1.2) vs.(2.6±0.9), P<0.001] , and the 7th postoperative day [(0.9±1.3) vs.(2.3±1.5), P<0.001] .There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). 【Conclusion】 The flexible sleeve penile protection device has significant effects of reducing early postoperative pain and reducing edema in patients undergoing circumcision.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.

Objective:To identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.