ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

OBJECTIVE: To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province, and to analyze the genotypes and hematological phenotypes. METHODS: Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province, whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations. The mutations of β-globin gene clusters were confirmed by polymerase chain reaction (PCR) and Sanger DNA sequencing technology. RESULTS: The 3.5 kb deletion in β-globin gene cluster (NC_000011.10: g. 5224302-5227791del3490bp) was detected in 4 patients' samples, of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation. These 2 patients displayed moderate anemia phenotype, while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype. CONCLUSION Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia, compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia. In areas with a high incidence of thalassemia, suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.
Humans ; beta-Globins/genetics* ; Multigene Family ; beta-Thalassemia/genetics* ; Mutation ; Genotype ; Sequence Deletion ; Phenotype ; Male ; Female

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Objective:To investigate the association between baseline hemoglobin level and early neurologic deterioration(END)after intravenous thrombolysis in patients with acute ischemic stroke(AIS).Methods:Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation(CASE-Ⅱ,NCT04487340).Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy,and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis.Results:A total of 8162 patients were included.Patients with END had lower baseline hemoglobin levels(136 and 140 g/L,P<0.01)and higher rates of anemia(24.2%and 16.9%,P<0.01)compared with non-END patients.Binary logistic regression analysis showed that baseline hemoglobin level(OR=0.995,95%CI:0.991-0.999,P<0.05)and anemia(OR=1.238,95%CI:1.055-1.454,P<0.01)were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients.Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients(P<0.01),although this relationship was only significant in male patients(P<0.05)and not in female patients(P>0.05).Conclusion:There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis,especially in male patients,in whom both lower and higher hemoglobin level may increase the risk of END.

Objective To analyze the cellular senescence pathways and their associated genes with bioinformatic analysis by screening differentially expressed genes(DEGs)during embryonic kidney development with aid of transcriptomics in order to explore the relationship between cellular senescence and embryonic kidney development.Methods After the kidney tissues from mice at embryonic age of 14.5 days(E14.5 group)and 18.5 days(E18.5 group)were collected,the kidney tissue structure was observed with periodic acid Schiff(PAS)staining,the expression profiles of the related genes during embryonic kidney development were analyzed by transcriptomics,and the changes in the genes related to cellular senescence were further analyzed with bioinformatics.The expression levels of target genes were verified by real-time quantitative fluorescence PCR and Western blotting.Results With the development of the embryonic kidney,the kidney structure gradually matured.The results of transcriptomic and bioinformatic analyses revealed that cellular senescence-related genes played an important role in the development of embryonic kidney.The mRNA and protein levels of Cdkn1a(P21),which was correlated with cellular senescence,were significantly higher(P＜0.05),while the mRNA levels of Skp2,Ccne1,Ccnd2,and Cdk4 were decreased in the E1 8.5 group than the E14.5 group(P＜0.05).Conclusion Obvious changes in the expression levels of cellular senescence-related genes are observed during embryonic kidney development,suggesting that cellular senescence plays an important role in the development.

Objective:To explore the application effects of scenario simulation combined with checklist-based teaching in clinical decision-making ability training of nursing interns in burn department.Methods:This study was a randomized controlled study. A total of 53 nursing interns who met the inclusion criteria and underwent internships at Institute of Burn Research of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), which was hereinafter referred to as the hospital, from July 2023 to March 2024 were randomly assigned to convention group ( n=25, 5 males and 20 females, aged (21.6±0.8) years) and joint group ( n=28, 6 males and 22 females, aged (21.2±1.3) years) using the envelope method. The nursing interns in convention group and joint group respectively received conventional teaching and scenario simulation combined with checklist-based teaching based on conventional teaching for clinical decision-making training. Before and after the training, the theoretical examination and skill assessment were performed on nursing interns, the clinical decision-making ability of nursing interns was evaluated with a clinical decision-making ability measurement questionnaire designed for undergraduate nursing students. After training, the satisfaction of the instructors on nursing interns' learning and the satisfaction of the nursing interns on the instructors' teaching were investigated by the instructors' satisfaction questionnaire and nursing interns' satisfaction questionnaire in the hospital, respectively. Results:After training, the theoretical examination and skill assessment scores of nursing interns in joint group were significantly higher than those in convention group (with Z values of -5.73 and -6.26, respectively, P<0.05). The theoretical examination (with Z values of -6.07 and -6.45, respectively, P<0.05) and skill assessment (with Z values of -6.08 and -6.48, respectively, P<0.05) scores of nursing interns in joint group and convention group after training were significantly higher than those before training. After training, the total scores of clinical decision-making ability and the scores of adaptability to clinical environment, clinical thinking, nurse-patient communication skills, and comprehensive basic quality of nursing interns in joint group (97.00 (95.42, 98.02), 18.00 (17.00, 19.00), 25.00 (24.10, 27.00), 19.00 (18.00, 20.75), and 20.00 (19.00, 21.75), respectively) were significantly higher than those in convention group (87.90 (86.30, 90.30), 16.00 (14.50, 17.00), 24.00 (22.35, 25.00), 17.00 (15.00, 18.00), and 17.50 (16.00, 20.00), with Z values of -6.24, -3.45, -2.90, -3.68, and -3.27, respectively, P<0.05). The total scores of clinical decision-making ability and the scores of adaptability to clinical environment, clinical thinking, knowledge structure, nurse-patient communication skills, and comprehensive basic quality of nursing interns in joint group after training were significantly higher than those before training (with Z values of -6.43, -5.21, -5.44, -4.31, -5.02, and -6.32, respectively, P<0.05). Except for the scores of nurse-patient communication skills, the total scores of clinical decision-making ability and the scores of adaptability to clinical environment, clinical thinking, knowledge structure, and comprehensive basic quality of nursing interns in convention group after training were significantly higher than those before training (with Z values of -6.06, -5.06, -5.71, -3.76, and -5.90, respectively, P<0.05). After training, the total scores of satisfaction of the instructors on nursing interns' learning and the scores of learning ability and professional competence in joint group were significantly higher than those in convention group (with Z values of -4.55, -5.45, and -3.21, respectively, P<0.05); the total scores of satisfaction of the nursing interns on the instructors' teaching and the scores of teaching ability and professional competence in joint group were significantly higher than those in convention group (with Z values of -5.95, -5.99, and -5.34, respectively, P<0.05). Conclusions:Scenario simulation combined with checklist-based teaching can effectively enhance the theoretical and skill levels, clinical thinking, and nurse-patient communication skills of nursing interns in burn department, as well as improve teaching and learning satisfaction.