ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

BACKGROUND:Luteolin has a variety of pharmacological activities such as antibacterial,anti-inflammatory,antioxidant,etc.,which can inhibit the release of cellular inflammatory factors,promote cell proliferation,and improve the cellular microenvironment.OBJECTIVE:To explore the potential roles and mechanisms of luteolin in promoting diabetic chronic wound healing using network pharmacology and in vivo experiments.METHODS:Potential targets of luteolin were screened using multiple databases,systemic pharmacology of Chinese medicines database,PubChem and UniProt databases.Genes related to wound healing were identified through the GeneCards database.A protein-protein interaction network was constructed to screen core targets,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the biological pathways that luteolin may affect.In vivo experiments in mice were conducted to observe the effects of luteolin on wound healing.Eighteen C57BL/6 mice were randomly divided into three groups.A 1 cm diameter full skin defect wound was made on the back of the control group(n=6),and a 1 cm diameter full skin defect wound was made on the back of the model group(n=6)and the treatment group(n=6)after the establishment of the diabetes model.The treatment group was given 200 mg/kg luteolin by gavage once a day for 9 consecutive days after the operation,and the wound healing was observed.At the end of drug administration,the samples were taken for hematoxylin-eosin and Masson staining.qRT-PCR was used to detect the mRNA expression of interleukin 6 and tumor necrosis factor α,and western blot was used to detect the protein expression of phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.RESULTS AND CONCLUSION:(1)Network pharmacological analysis identified 56 potential target genes associated with luteolin for the treatment of chronic wounds,of which the AKT gene was most closely linked to other target genes.Gene Ontology analysis indicated that luteolin could have antioxidant and anti-stress effects and have the potential to act as a multi-targeted drug.Kyoto Encyclopedia of Genes and Genomes analysis indicated that the target genes of luteolin were mainly enriched in the PI3K/AKT signaling pathway.(2)On the 9th day of drug administration,the remaining wound area of mice in the control and treatment groups was smaller than that of the model group(P＜0.05).Hematoxylin-eosin and Masson staining results showed that compared with the model group,the number of trabecular granulation tissues and collagen deposition were increased in the treatment group,and the degree of epithelialization was higher and close to that of the control group.The mRNA expression of interleukin 6 and tumor necrosis factor α on the wound surface was lower in the treatment group than the model group(P＜0.05),while the protein expression of p-PI3K and p-AKT was higher in the treatment group than the model group(P＜0.05).To conclude,luteolin inhibits wound inflammatory response and promotes healing of diabetic wounds by modulating the PI3K/AKT signaling pathway.

BACKGROUND:Luteolin has a variety of pharmacological activities such as antibacterial,anti-inflammatory,antioxidant,etc.,which can inhibit the release of cellular inflammatory factors,promote cell proliferation,and improve the cellular microenvironment.OBJECTIVE:To explore the potential roles and mechanisms of luteolin in promoting diabetic chronic wound healing using network pharmacology and in vivo experiments.METHODS:Potential targets of luteolin were screened using multiple databases,systemic pharmacology of Chinese medicines database,PubChem and UniProt databases.Genes related to wound healing were identified through the GeneCards database.A protein-protein interaction network was constructed to screen core targets,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the biological pathways that luteolin may affect.In vivo experiments in mice were conducted to observe the effects of luteolin on wound healing.Eighteen C57BL/6 mice were randomly divided into three groups.A 1 cm diameter full skin defect wound was made on the back of the control group(n=6),and a 1 cm diameter full skin defect wound was made on the back of the model group(n=6)and the treatment group(n=6)after the establishment of the diabetes model.The treatment group was given 200 mg/kg luteolin by gavage once a day for 9 consecutive days after the operation,and the wound healing was observed.At the end of drug administration,the samples were taken for hematoxylin-eosin and Masson staining.qRT-PCR was used to detect the mRNA expression of interleukin 6 and tumor necrosis factor α,and western blot was used to detect the protein expression of phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.RESULTS AND CONCLUSION:(1)Network pharmacological analysis identified 56 potential target genes associated with luteolin for the treatment of chronic wounds,of which the AKT gene was most closely linked to other target genes.Gene Ontology analysis indicated that luteolin could have antioxidant and anti-stress effects and have the potential to act as a multi-targeted drug.Kyoto Encyclopedia of Genes and Genomes analysis indicated that the target genes of luteolin were mainly enriched in the PI3K/AKT signaling pathway.(2)On the 9th day of drug administration,the remaining wound area of mice in the control and treatment groups was smaller than that of the model group(P＜0.05).Hematoxylin-eosin and Masson staining results showed that compared with the model group,the number of trabecular granulation tissues and collagen deposition were increased in the treatment group,and the degree of epithelialization was higher and close to that of the control group.The mRNA expression of interleukin 6 and tumor necrosis factor α on the wound surface was lower in the treatment group than the model group(P＜0.05),while the protein expression of p-PI3K and p-AKT was higher in the treatment group than the model group(P＜0.05).To conclude,luteolin inhibits wound inflammatory response and promotes healing of diabetic wounds by modulating the PI3K/AKT signaling pathway.

When inflammation is continuously activated or dysregulated， it can induce chronic tissue injury and organ dysfunction， and participate in the occurrence and development of various inflammatory diseases such as atherosclerosis and inflammatory bowel disease. Owing to high targeting， long-acting efficacy and programmability， nucleic acid drugs provide a new direction for the treatment of inflammatory diseases. This article reviews the classification， mechanism of action and application progress of nucleic acid drugs in inflammatory diseases. It is found that small interfering RNA （siRNA） can specifically cut target mRNA through RNA interference to achieve inhibiting the expression of the target protein； antisense oligonucleotide （ASO） can inhibit target protein expression by inducing microRNA （miRNA） degradation or regulating splicing processes； miRNA can achieve network intervention by regulating multiple inflammatory target genes. At present， important breakthroughs have been made in the field of inflammatory diseases with siRNA drugs including Lumasiran， Nedosiran （for primary hyperoxaluria 1） and Inclisiran （for atherosclerosis）， ASO drugs including Donidalorsen （for hereditary angioedema）， Volanesorsen and Olezarsen （for familial chylomicronemia syndrome） and Lademirsen （for Alport syndrome）， as well as miRNA drugs including Obefazimod （for inflammatory bowel disease） and Remlarsen （for pathological fibrosis）. These drugs are expected to become a new generation of anti-inflammatory therapeutic strategies and bring more precise and efficient treatment options for patients with chronic inflammation and fibrotic diseases.

BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

Chronic obstructive pulmonary disease (COPD), which predominantly affects middle-aged and elderly individuals, is associated with a significantly reduced quality of life and often triggers various other pulmonary conditions. Lung cancer, as one of the most prevalent and deadly pulmonary malignancies worldwide, poses a severe threat to global public health. The risk of developing lung cancer is markedly higher in COPD patients compared to the general population, indicating numerous associations between the two conditions that warrant in-depth investigation. Although a substantial body of research has explored the relationship between COPD and lung cancer, studies focusing on the molecular mechanisms underlying their connection remain limited. This article reviews the latest research progress on the mechanisms of COPD complicated by lung cancer from four perspectives: the role of chronic pulmonary inflammation, programmed cell death, genetic and molecular interactions, and dysbiosis of the pulmonary microbiome. The aim of this article is to provide new insights and references for the prevention and therapeutic strategies of COPD complicated with lung cancer.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

In January 2025， the European Society for Medical Oncology （ESMO） released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer： ESMO clinical practice guideline for diagnosis， treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines， and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.