Objective To evaluate the reliability and validity and perform cost-consequence analysis of the brief version of the Montreal cognitive assessment(MoCA)for identifying cognitive impairment in a community-based population ≥50 years of age.Methods The internal consistency and retest reliability of the brief version of the MoCA were analyzed,and the area under the curve(AUC),sensitivity,and specificity were determined to discriminate mild cognitive impairment(MCI)and dementia with the clinical dementia rating(CDR)as the diagnostic criterion.The consistency between the brief version and the full version was analyzed by the Kappa test and the Bland-Altman method,and the number of individuals entering the diagnostic assessment and the overall assessment time were estimated and compared between the two versions.Results A total of 303 individuals were included in this study,of whom 192,94,and 17 had normal cognitive function,MCI,and dementia,respectively.The Cronbach's α and re-test coefficients of the brief version of MoCA were 0.754 and 0.711(P<0.001),respectively.The brief version showed the AUC,sensitivity,and specificity of 0.889,74.5%,and 93.8% for identifying MCI,and 0.994,100%,and 93.8% for identifying dementia,respectively.When the brief version of MoCA was used to identify 94 patients with MCI in 303 individuals,107 individuals required additional diagnostic assessment,with an overall assessment time of 142.4 h,which represented decreases of 21.3% and 32.7%,respectively,compared with those of the full version.When the brief version of MoCA was used to identify 17 patients with dementia in 303 individuals,35 individuals required additional diagnostic assessment,with an overall assessment time of 70.4 h,a decrease of 29.5% in the time cost compared with the full version.Conclusions The brief version of MoCA can identify cognitively impaired individuals in a community-based middle-aged and elderly population,with diagnostic validity comparable to that of the full version but less time cost and fewer individuals needing additional diagnostic assessment to detect true-positive cases.It could be expanded for use in the community-based primary screening setting.
Humans ; Aged ; Middle Aged ; Cognitive Dysfunction/diagnosis* ; Male ; Female ; Mental Status and Dementia Tests ; Reproducibility of Results ; Dementia/diagnosis* ; Sensitivity and Specificity ; Aged, 80 and over ; Cost-Benefit Analysis

Aim To study the protective effect of a combination of IDO-1 inhibitor(3-047)with Icartin(Y003)at a mass ratio of 1∶1.6 on diabetic nephrop-athy in db/db mice and its mechanism of action.Methods After 24 weeks of treatment in db/db mice,on the basis of pharmacodynamic evaluation,16S rD-NA gene sequencing combined with untargeted metabo-lomics was used to further investigate the mechanism of improvement of diabetic nephropathy from the perspec-tive of the"microbial-intestinal-nephrotic"axis by the combination of 3-047 and Y003.Results Compared with the control group,mice in the model group showed significantly higher levels of FBG,Scr,BUN,TC,TG,LDL-C,lower levels of HDL-C(P＜0.05),significantly increased urinary albumin excretion rate,thickening of the glomerular basement membrane and dilatation of the tunica albuginea,aggravation of oxida-tive stress damage,lower abundance,structural and functional disorders of the intestinal flora.The combi-nation of 3-047 and Y003 could improve the above conditions to different degrees,significantly increase the relative abundance of Alloprevotella,Alistipes and Dubosiella,and decrease the relative abundance of Ligilactobacillus,Dubosiella and Lactococcus.A total of 11 biomarkers with significant differences were screened by metabolomics and enriched to the pathways of alanine,tyrosine and tryptophan biosynthesis,and unsaturated fatty acid biosynthesis.Conclusions The combination of 3-047 and Y003 could improve the dis-orders of glucose-lipid metabolism,reduce the structur-al and functional damage of renal tissues,and alleviate oxidative stress by regulating the intestinal flora and re-lated amino acid metabolism,and thus achieve a pro-tective effect on mice with diabetic nephropathy,dem-onstrating that the intestinal flora and the related me-tabolites are potential targets for the treatment of dia-betic nephropathy.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Objective:To investigate the early diagnostic value of contrast-enhanced ultrasound(CEUS)combined with serum creatinine(Scr)and urea nitrogen(BUN)in children with renal parenchymal injury caused by urinary tract infections(UTIs).Methods:A total of 120 children with UTIs admitted from January 2020 to January 2025 were selected and divided into a renal parenchymal injury group(n=65)and a non-injury group(n=55)based on the results of 99mTc-DMSA renal static imaging.All children underwent CEUS examination within 24 hours of admission to obtain hemodynamic parameters of the renal cortex and medulla(time-to-peak[TTP],peak intensity[PI],and area under the curve[AUC]),and Scr and BUN levels were measured.Multivariate logistic regression analysis was used to identify independent risk factors,and the diagnostic efficacy was evaluated using receiver operating characteristic(ROC)curves.Results:In the renal parenchymal injury group,Scr(0.82±0.25 vs 0.53±0.15 mg/dL),BUN(16.23±4.82 vs 12.42±3.27 mg/dL),and cortical TTP(51.47±12.38 vs 43.45±12.55 s)were significantly elevated,while cortical PI(32.63±6.37 vs 39.23±7.31 dB)and AUC(2915.36±536.37 vs 3415.35±681.5 dB·s)were significantly decreased(all P＜0.05).Multivariate analysis showed that Scr(OR=6.17),BUN(OR=2.58),cortical TTP(OR=1.98),and PI(OR=0.60)were independent predictors.In the ROC curve analysis,the combination of CEUS parameters(cortical TTP,PI,AUC)with Scr and BUN demonstrated the best diagnostic efficacy(AUC=0.953,sensitivity 87.3％,specificity 90.3％).Conclusion:CEUS can sensitively identify renal parenchymal injury associated with UTIs by dynamically assessing abnormal renal cortical blood perfusion.When combined with Scr and BUN,it significantly improves diagnostic accuracy,providing an important basis for early intervention and renal function protection in children with UTIs.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.