OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To observe the imaging features of extramacular retinoschisis (EMRS) and paravascular abnormalities (PVA) in myopic patients, and preliminary analyze the differences in age, best corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), and subfoveal choroidal thickness (SFCT).Methods:A cross-sectional clinical study. A total of 60 myopia patients with EMRS who were admitted to Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from January 2023 to June 2024 were included in the study. There were 18 male cases with 18 eyes and 42 female cases with 42 eyes. Age was (37.57±17.14) years; SE was (-10.76±4.66) D; AL was (28.36±1.87) mm. According to the characteristics of ultra-wide-angle optical coherence tomography images, PVA was divided into perivascular cysts (PC), perivascular microfolds (PM) and perivascular lamellar holes (PLH). According to the splitting level, EMRS can be divided into inner layer, middle layer and outer layer. According to SE, the affected eyes were divided into low myopia group, moderate myopia group and high myopia group. The occurrence of EMRS near optic disc, supratemporal, suprasal and subnasal, as well as the clinical characteristics of patients with EMRS at different locations, levels and forms of PVA were observed. Age, BCVA, SE, AL and SFCT of EMRS patients at different locations and levels were compared by independent sample t test. χ2 test or Fisher exact probability test were used to compare the categorical variables between groups. Results:In 60 eyes, EMRS were located in supratemporal, infratemporal, supranasal, subnasal, and paratopic discs in 36, 43, 15, 13, and 14 eyes, respectively. The EMRS in the inner and outer layers were 59 (98.3%, 59/60) and 35 (58.3%, 35/60) eyes, respectively. PVA was present in 47 eyes (78.3%, 47/60). Among them, PC, PM and PLH were 45, 39 and 18 eyes, respectively. The age of those with paratopic splitting was older than those without paratopic splitting ( t=2.720). Those with temporal splitting had worse BCVA and longer AL than those without splitting ( t=2.139, 2.119). Those with subnasal splitting had worse BCVA, higher myopia, longer AL and thinner SFCT than those without splitting. The differences were statistically significant ( t=2.926, -2.640, 2.635, -3.938; P<0.05). Compared with other types of EMRS, patients with inner EMRS had younger age ( t=-2.383), better BCVA ( t=-4.825), shorter AL ( t=-4.767), lower myopia ( t=4.791), and thicker SFCT ( t=4.791); patients with full-layer EMRS were older ( t=2.419), worse BCVA ( t=3.656), longer AL ( t=2.677), higher degree of myopia ( t=-2.755), and thinner SFCT ( t=-3.283), with statistical significance ( P<0.05). There was significant difference in SFCT among patients with or without PC ( t=-2.396, P<0.05). Compared with eyes without PM and PLH, eyes with PM had worse BCVA, longer AL, higher myopia, and thinner SFCT, and the differences were statistically significant (PM: t=2.514, 3.078, -2.811, -4.205; P<0.05; PLH: t=2.514, 2.992, -2.949, -1.773; P<0.05). Conclusions:EMRS primarily occurs in the temporal side, with the highest frequency in the inner layer. Patients with inner-layer EMRS are younger, have better BCVA, shorter AL, lower myopia, and thicker SFCT, whereas patients with full-layer EMRS exhibit the opposite characteristics.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

Aim To investigate the effect of triptolide(TP)on corticosterone(CORT)-induced depression-like behaviors in mice and explore the antidepressant mechanism of TP based on the CREB/BDNF/TrkB sig-naling pathway.Methods Sixty 8-week-old male C57BL/6J mice were randomly divided into five groups:control group,CORT group,TP groups of low and high doses(10,30 μg·kg-1),and fluoxetine(FLU)group(10 mg·kg-1).Except for the control group,the other groups received subcutaneous injec-tions of CORT for three consecutive weeks to establish the model of depression.During the last two weeks of modeling,normal saline,TP and FLU were adminis-tered via intraperitoneal injection respectively.After the administration,depression-like behaviors in mice were assessed using forced swimming test,tail suspen-sion test,and sucrose preference test.Biochemical methods were used to measure the levels of SOD and MDA in the hippocampus and prefrontal cortex(PFC).Cell apoptosis was detected by TUNEL meth-od.Immunohistochemistry,immunofluorescence,and Western blotting were employed to detect the expres-sion of apoptosis/autophagy-related proteins,synaptic structure markers,and proteins related to the CREB/BDNF/TrkB signaling pathway.Results TP signifi-cantly ameliorated CORT-induced depression-like be-haviors in mice,mainly manifested by reduced immo-bility time in the tail suspension test and forced swim-ming test,and increased sucrose preference rate.TP alleviated CORT-induced oxidative stress by increasing SOD levels and reducing MDA production in brain tis-sue.Additionally,TP also inhibited apoptosis and ex-cessive autophagy of neurons in the hippocampus and prefrontal cortex,maintained synaptic plasticity,and significantly upregulated the expression of p-CREB,BDNF,and TrkB.Conclusions TP exhibits potential antidepressant effect in mice by upregulating the CREB/BDNF/TrkB signaling pathway,reducing oxida-tive stress,inhibiting excessive neuronal apoptosis and autophagy,and improving synaptic plasticity.

Objective:To investigate mental health literacy and advance care planning(ACP)condition,their influencing fac-tors,and their correlation in elderly patients with coronary heart disease(CHD).Methods:General data of 500 elderly CHD patients admitted in the Second Affiliated Hospital of Chinese PLA Air Force Military Medical University between January 2020 and December 2021 were collected.Mental health literacy and ACP condition were assessed.Multivariate linear regres-sion was used to analyze their influencing factors,and Pearson method was used to analyze their association.Results:Total score of Multicomponent Mental Health Literacy(MHL)was(10.78±2.57)points,and total score of Advance Care Plan-ning Readiness Scale(ACPRS)was(71.41±4.84)points in the 500 elderly CHD patients.Multivariate linear regression a-nalysis indicated that level of disease uncertainty had negative impact on MHL score,presence of spouse and trust in medical care had positive impact on MHL score(P＜0.05 or＜0.01);number of complications had negative impact on ACPR score,while presence of spouse and family mean monthly income had positive impact on ACPRS score(P＜0.05 or＜0.01).Pearson correlation analysis indicated that MHL score was positively correlated with ACPRS score(r=0.476,P＜0.001).Conclusion:Both mental health literacy and ACP status need to be improved in elderly CHD patients.They are posi-tively correlated with each other.Presence of spouse,number of complications and trust in medical care are the important influencing factors.Therefore,medical staff can take targeted measures to improve ACP readiness and mental health quality.

Objective To investigate the role of CCCTC-binding factor(CTCF)in the development of oxaliplatin(OXA)-induced gastric cancer drug-tolerant cells(DTCs)and to preliminarily elucidate its underlying mechanisms.Methods The DTCs model of gastric cancer was established by treating MGC803 cells with OXA.Overexpression and knockdown of CTCF in MGC803 cells were performed to observe their effects on the formation of DTCs in gastric cancer.Additionally,Bcl2-like protein 1(BCL2L1)was knocked down in CTCF-overexpressing cells,and its impact on DTCs formation was evaluated.Flow cytometry was used to analyze the effects of varying CTCF/BCL2L1 expression levels on the apoptosis of gastric cancer cells under OXA treatment.Immunohistochemistry(IHC)was employed to detect the expression levels of CTCF/BCL2L1 in gastric cancer tissues,and the therapeutic outcomes of neoadjuvant chemotherapy in patients with different CTCF/BCL2L1 expression levels were assessed.Results Gastric cancer DTCs can be obtained following a regimen of continuous treatment of MGC803 cells with a specific concentration of oxaliplatin(OXA,1.5 μmol/L)for 5 days,followed by an additional 5-day culture period post-treatment cessation.The upregulation of CTCF has been shown to facilitate the formation of DTCs in gastric cancer,whereas its downregulation inhibits this process(P<0.05).In MGC803 gastric cancer cells,the expression level of BCL2L1 is positively correlated with that of CTCF.Knockdown of BCL2L1 in MGC803 cells overexpressing CTCF can reverse the pro-DTC formation effect of CTCF(P<0.05).Overexpression of CTCF confers resistance to OXA-induced apoptosis in gastric cancer cells,and this anti-apoptotic effect can be reversed by BCL2L1 knockdown in MGC803 cells overexpressing CTCF(P<0.05).In the tumor tissues of the majority of gastric cancer patients,the expression levels of BCL2L1 are positively correlated with those of CTCF,and the efficacy of neoadjuvant chemotherapy is notably reduced in patients with high expression of the CTCF/BCL2L1 axis compared to those with low expression(P<0.05).Conclusion CTCF promotes the formation of OXA-related gas-tric cancer DTCs by upregulating BCL2L1 expression and inhibiting apoptosis,making the CTCF/BCL2L1 axis a potential therapeutic target for DTCs in gastric cancer.

Objective:This study aims to explore the rehabilitation effect of continuous rehabilitation management based on Internet thinking on patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This randomized controlled study enrolled 100 CHD patients admitted in Second Affiliated Hospi-tal of Chinese PLA Air Force Military Medical University between October 2020 and December 2021.They were di-vided into control group(n=50)and intervention group(n=50).Patients in control group received routine reha-bilitation nursing mode,compared to those in intervention group applying"Internet+"continuous rehabilitation nursing intervention program,both groups were intervened for 3 months.Cardiac function,cardiopulmonary exer-cise test indexes,depression,medication compliance,quality of life and incidence of adverse cardiovascular events within 1-year follow-up were compared between two groups.Results:Compared with patients in control group after 3 months,those in intervention group had significant higher oxygen uptake at anaerobic threshold(VO2@AT)[(11.75±0.39)ml·kg-1·min-1 vs.(10.17±0.76)ml·kg-1·min-1],peak oxygen uptake(Peak VO2)[(17.87±0.72)ml·kg-1·min-1 vs.(16.66±0.24)ml·kg-1·min-1],left ventricular ejection fraction(LVEF)[(51.15±2.42)％vs.(44.09±1.94)％],scores of Morisky Medication Adherence Scale(MMAS-8)[(5.29±0.30)points vs.(4.11±0.27)points]and Seattle Angina Questionnaire(SAQ)[(85.50±4.37)points vs.(73.27±2.53)points],and significant lower left ventricular end-diastolic diameter(LVEDd)[(40.51±0.41)mm vs.(46.64±0.99)mm],score of Patient Health Questionnaire-9(PHQ-9)[(7.67±0.85)points vs.(9.66±1.43)points]and total incidence of adverse cardiovascular events within 1-year follow-up(4.00％vs.16.00％)(P＜0.05 or＜0.01).Conclusion:Internet continuous rehabilitation intervention could improve car-diopulmonary exercise capacity and cardiac function,help to improve their quality of life and relieve depression,and reduce the risk of adverse cardiovascular events in CHD patients after PCI.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal