Chronic lung allograft dysfunction (CLAD) is a common complication after lung transplantation, which severely impairs the long-term survival of patients. At present, effective therapeutic approaches remain lacking. Dysregulation of the lung microbiome acts as a pathogenic factor for a variety of pulmonary diseases. Accumulating studies have demonstrated that the compositional characteristics of the lung microbiome after lung transplantation are closely associated with CLAD. Therefore, this article reviews the definition of CLAD, characteristics of the lung microbiome, the influence of the lung microbiome on the occurrence and progression of CLAD, the potential mechanisms underlying the lung microbiome in the pathogenesis of CLAD, and microbiome-based intervention strategies for CLAD. It aims to provide novel insights for the prevention and treatment of CLAD following lung transplantation and further improve the prognosis of lung transplant recipients.

Metabolic associated fatty liver disease （MAFLD） is a highly prevalent chronic liver disease worldwide， and the mechanism underlying its progression to metabolic associated steatohepatitis and liver fibrosis remain unclear. Endoplasmic reticulum stress （ERS） and ferroptosis （Fer） are deeply involved in the pathological evolution of MAFLD. This article systematically reviews the core regulatory mechanisms of ERS and its role in regulating lipid metabolism， inflammation response， and cell apoptosis in MAFLD. It also analyzes the core mechanism of Fer and discusses the predisposing factors for Fer in the pathological microenvironment of MAFLD， as well as the role of Fer in exacerbating hepatocyte death and activating the progression of liver fibrosis. This article proposes that the crosstalk between ERS and Fer is a key driver for the progression of MAFLD， which provides new references and ideas for the clinical intervention of MAFLD.

Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.

Post-stroke cognitive impairment （PSCI） is a highly prevalent severe complication after stroke. In traditional Chinese medicines （TCM）， its core pathogenesis is characterized by deficiency in origin and excess in superficiality： wind， phlegm and blood stasis accumulate， cloud the clear orifices and lead to loss of mental activity， and Xingnao kaiqiao is the targeted principal treatment. This review summarizes the research progress on the pharmacological mechanisms of representative Xingnao kaiqiao-type TCM including Acorus tatarinowii ， Curcumae Radix ， Polygala tenuifolia ， borneol and musk， as well as clinical applications of their related compound formulas and Chinese patent medicines in the treatment of PSCI. The results show that these TCM can improve cognitive function through multiple pathways： targeted regulation of blood-brain barrier permeability， inhibition of neuroinflammation mediated by Toll like receptor 4/nuclear factor-κB， high mobility group protein B1 in ischemic brain tissue and other pathways， and activation of brain-derived neurotrophic factor/tyrosine kinase receptor B， cyclic adenosine monophosphate （cAMP）/protein kinase A/cAMP response element-binding protein and other pathways to promote synaptic plasticity. In terms of clinical application， the evidence chains of formulas based on Acorus tatarinowii and Polygala tenuifolia are relatively complete， which are the core medications to improve cognitive function and activities of daily living； Curcumae Radix has protective potential in the prodromal stage with vascular risk factors； borneol enhances the curative effect of compound prescriptions by improving blood-brain barrier function； musk is mainly used in the acute severe stage. At present， most of the mechanism evidence comes from animal experiments， high-quality large-sample clinical studies directly targeting PSCI populations are still scarce. Subsequent large-sample multicenter studies are needed in the future， combined with multi-omics and multimodal imaging techniques to further clarify its deep-seated mechanism of action.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective To evaluate the diagnostic value of coiled-coil domain containing 83(CCDC83),carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)199 detection in patients with colorectal cancer(CRC).Methods A total of 168 patients with colorectal diseases and 80 healthy physical examination subjects admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from September 2022 to January 2025 were selected as the study objects.Participants were classified into three groups based on pathological diagnosis and colonoscopy findings:colorectal cancer group(n=80),colorectal benign disease group(n=88),and healthy control group(n=80).Serum samples from all three groups were collected for detection of CCDC83,CEA,and CA199 expression levels.The diagnostic value was analyzed using receiver operating characteristic(ROC)curves.Results Colorectal cancer group exhibited significantly higher expression levels of CCDC83,CEA,and CA199 compared to colorectal benign disease group and healthy control group,with statistically significant differences(P＜0.05).ROC curve analysis demonstrated diagnostic value for CCDC83,CEA,and CA199,with CCDC83 showed superior specificity compared to CEA and CA199.Conclusion CCDC83,CEA and CA199 showed good diagnostic efficacy for colorectal cancer.

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Objective:To explore the targets and mechanisms of aerobic exercise on Alzheimer's disease(AD).Method:Thirty-two male clean-grade Wistar rats were randomly assigned to one of four groups:control,mod-el,positive drug and aerobic exercise.After intervention,the Morris water maze was employed to assess the learning and memory capabilities of the rats,and hematoxylin and eosin staining was utilized to observe patho-logical changes in hippocampal tissue.Transcriptomic and metabolomic analyses were conducted to identify dif-ferential metabolites and key genes associated with disease progression,with a focus on the expression of key genes through integrated analysis.Result:The water maze experiment showed that the aerobic exercise group significantly improved the learning and cognitive abilities of D-galactose-induced Alzheimer's disease model rats.Pathological staining showed a de-crease in the number of cells in the hippocampal CA1 region of the model group rats,characterized by deep staining of the nucleus and cytoplasm,cell shrinkage,loose and disordered arrangement,blurred boundaries be-tween the nucleus and cytoplasm,and increased gaps.The cell structure of hippocampal neurons in the aero-bic exercise group of rats was relatively clear and tends to be complete,with a decreasing trend in intercellu-lar gaps.No large-scale neuronal shrinkage was observed in the field of view,and the cell volume appeared normal.Transcriptomics screened out key genes mainly including four genes:indoleamine 2,3-dioxygenase 1(IDO1),tryptophan 2,3-dioxygenase 2(TDO2),plexin B1(PLXNB1),and tripartite motif protein 11(TRIM 11).Metabolomics screening identified ten differential metabolites,including N-formylcarnitine,trypto-phan,Kynurenine,5-hydroxytryptamine,5-hydroxytryptophan,creatine,N-acetylaspartate glutamate,histidine,Hydroxyprolyl-Isoleucine,and pyridoxine.This study showed that aerobic exercise significantly improved the learning and memory abilities of D-galactose-induced AD model rats,alleviated the damage and reduction of hippocampal CA1 neurons.Integrated analysis found that the content of tryptophan,kynurenine,5-hydroxytryp-tamine,and 5-hydroxytryptophan was directly regulated by IDO1 and TDO2.Conclusion:IDO1 and TDO2 are important targets for aerobic exercise in the treatment of AD.The neuropro-tective effects and reduction of oxidative stress and inflammation are the key therapeutic mechanisms of aero-bic exercise in AD.

Objective:To investigate the impact of high-dose fractionated irradiation on NK cell function and immune checkpoint expression.Methods:A total of 10 female C57BL/6N mice aged 6-8 weeks were subcutaneously injected with Lewis lung carcinoma (LLC) cells on the right shoulder to establish a subcutaneous tumor model. Mice were randomly divided into two groups: the control (Ctrl) group and the radiation (RT) group, with five mice in each group. The RT group received fractionated irradiation of 8 Gy × 3 fractions, while the Ctrl group was not irradiated. Three days later, flow cytometry was performed to compare the numbers of NK cells and the expressions of immune checkpoints, including programmed death-1 (PD-1) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), in the spleen, draining lymph nodes, and tumor tissue between the two groups. The activation state and cytotoxicity of NK cells were assessed by the expression of lysosomal-associated membrane protein 1 (CD107a) on the NK cell surface. Additionally, a second experiment was conducted with 20 tumor-bearing mice divided into four groups: Ctrl, RT, anti-TIGIT (αTIGIT) treatment, and RT combined with αTIGIT treatment (RT+ αTIGIT), with five mice per group. The RT and RT+ αTIGIT groups received fractionated RT, while the αTIGIT and RT+ αTIGIT groups were treated with blocking antibody αTIGIT at 0.5 mg/kg every 3 days and the Ctrl group was treated with isotype control IgG. Tumor size was monitored during the experiment. On day 20, mice were euthanized, Ki67 immunohistochemistry and TUNEL immunofluorescence staining were used to evaluate tumor cell proliferation and apoptosis.Results:Compared with the Ctrl group, fractionated high-dose RT resulted in a decrease in NK cell numbers in the spleen, tumor-draining lymph nodes, and tumor microenvironment in the RT group ( t=6.79-7.54, P<0.05), together with a significant upregulation of the mean fluorescence intensity of PD-1 and TIGIT ( t=4.16-5.65, P<0.05; t=6.12-21.13, P<0.05), and a decrease in CD107a+ expression ( t=5.64-8.99, P<0.05). Compared with the RT group, the RT+ αTIGIT group showed reduced tumor weight ( t=2.50, 9.12, P<0.05), decreased Ki67 expression ( t=12.10, P<0.05), and increased TUNEL expression ( t=5.42, P<0.05). Conclusions:The fractioned high-dose RT can impair NK cell function and upregulate immune checkpoint expression, thereby limiting the immune response. The combination of irradiation with anti-TIGIT antibody treatment can partially reverse this trend and improve tumor treatment efficacy.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.