AIM: To investigate the diagnostic and prognostic value of differential expression of Cyclin D1 and p53 in eyelid tumors.METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(rs=0.71, P<0.05)and TNM stage(rs=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(rs=0.76, P<0.05)and histological subtype(rs=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.

ObjectiveTo investigate the association between triglyceride-glucose (TyG) index and the risk of stroke in middle-aged and elderly individuals with hypertension, so as to provide more evidence for the prevention and treatment of stroke. MethodsMiddle-aged and elderly hypertensive individuals who took part in all four surveys in 2011, 2013, 2015, and 2018 were selected as the research subjects based on data from the China Health and Retirement Longitudinal Study (CHARLS). Participants were divided into four groups (≤Q1， >Q1~Q2， >Q2~Q3， and >Q3) based on TyG index quartiles, and the cumulative risk of stroke in different groups was analyzed using the Kaplan-Meier method. Different Cox proportional hazards regression models were constructed to analyze the relationship between the TyG index and stroke risk. Sensitivity analysis were performed to evaluate the robustness of the results. ResultsA total of 4 596 participants were included in the study. Among them, 338 individuals (7.35%) had a stroke during the 7-year follow-up period. The cumulative risk of stroke increased with higher TyG index levels. Results from the Cox regression models indicated that higher TyG levels were associated with an increased risk of stroke among middle-aged and elderly individuals with hypertension. Compared with the lowest TyG index quartile (≤Q1: TyG index ≤8.33) group, the highest quartile (>Q3: TyG index >9.17) group showed a 45.10% increased risk of stroke (HR=1.451, 95% CI:1.017‒2.072). ConclusionA higher TyG index is associated with an increased risk of stroke in middle-aged and elderly individuals with hypertension.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective To investigate the spatiotemporal expression pattern of metabotropic glutamate receptor 4(mGluR4)in the mouse cochlear basilar membrane and its dynamic changes during postnatal development until hair cell synaptic maturation.Methods Ten healthy 3-month-old C57BL/6L wild-type mice(5 males,5 females,25～35 g)were bred to obtain offspring.Cochlear samples from postnatal days 1～30(P1～P30)were analyzed.Frequency-specific auditory brainstem response(ABR)thresholds were measured at 45.2,32.0,22.6,16.0,11.3,8.0,5.6,and 4.0 kHz in P12,P14,P16,P21,and P30 mice.Immunofluorescence assay combined with confocal laser scanning microscopy was used to scan cochlear whole-mount preparations.Spatiotemporal co-localization profiling of mGluR4 and synaptic markers Ctbp2 and Snap25 was observed,and quantitative comparisons of fluorescent puncta density were performed.Results ABR testing revealed undifferentiated waveforms in all P12 mice,while 70%of P14 mice exhibited well-defined Wave I.In P14,P16,P21 and P30,mice undergoing ABR testing,50%failed to exhibit ABR waveforms when stimulated by 45.2 kHz tones,and 87.5%showed no response to 32.0 kHz stimuli.Auditory response thresholds for other frequencies progressively decreased with increasing postnatal age.Immunolocalization demonstrated stronger mGluR4 expression in inner hair cells(IHCs)versus outer hair cells(OHCs).Distinct mGluR4 puncta were observed at IHC presynaptic active zones(co-localized with Snap25)as early as P11,but showed minimal overlap with CtBP2-labeled ribbons.Quantitative analysis revealed significantly higher mGluR4 puncta density at P30 compared to P14 synapses(P<0.05).Conclusion Postnatal upregulation of mGluR4 at IHC synaptic regions correlates with functional maturation.These findings suggest mGluR4 may modulate vesicular exocytosis regulation and exert pharmacological inhibition on glutamate release,potentially influencing synaptic plasticity during auditory pathway refinement.

Objective To summarize the application of double valve ring enlargement combined with mitral Chimney technique (Chimney Commando) in the secondary valve replacement and to analyze the efficacy in the near and medium term. Methods Patients who underwent the secondary aortic valve and mitral valve (double valve) replacement by Chimney Commando in Wuhan Asia Heart Hospital from 2019 to 2022 were included, and their clinical data were retrospectively collected to analyze the safety and feasibility of this procedure in secondary valve replacement of small aortic root patients. Results A total of 49 patients (44 females and 5 males) were included. The body surface area was 1.64±0.17 m2. The time from the first operation was 13.10±5.90 years. Except for 4 patients whose first operation was valvuloplasty, the remaining 45 patients were all patients after valve replacement, 41 patients of double valves replacement, including 39 patients with mechanical valve and 2 patients with biological valve. The majority of the aortic valves were St.Jude regent 19 mm or St.Jude regent 21 mm, accounting for 30.61% and 34.69%, respectively. The mitral valves were predominantly St.Jude 25 mm mechanical valves, making up 65.31%. All patients underwent Chimney Commando double valve ring enlargement, and the mean time of aortic occlusion was 154.00±45.40 min. The mean size of the aortic valve was 23.90±1.40 mm and that of the mitral valve was 28.20±1.20 mm, and the transvalvular pressure difference across the aortic valve was 20.16±5.76 mm Hg at 6 months postoperatively. There was one death during hospitalization due to multi-organ failure. The follow-up time ranged from 1 to 24 months with a median time of 8 months. Two patients were implanted with permanent pacemakers during the follow-up period and 1 patient died due to massive stroke and malignant arrhythmia. Conclusion Chimney Commando is safe and effective in patients with secondary double valve replacement, and the postoperative prosthetic valves have good hemodynamics, and can achieve good clinical results in the near and medium term.

The amount of data generated by the human experience in medical cases of classic formulas is large and the research value is high， but how to extract valuable information from these massive data is an important problem of researches on classical formulas. It is concluded that there are many problems in the current study of human experience in classical formulas， such as large amount of data， uneven quality， weak extrapolation and clinical application， which seriously affected the evidence strength of human experience in classical formulas and the contribution to experience accumulation and theoretical support. Therefore， from the structural perspective of the research questions， this paper proposed the research ideas of human experience in medical cases of classic formulas： firstly， according to the characteristics of traditional Chinese medicine （TCM） cases， based on the PICO model， which refers parti-cipants （P）， intervention （I）， comparisons （C）， and outcomes （O）， a TCM medical record evaluation tool in line with the evidence-based concept was constructed to evaluate the quality of medical cases； secondly， constructing a standardized database of human experience in classical formulas and using data mining algorithms to explore the deep relationship hidden in human experience； finally， the clinical value evaluation is carried out to verify the effectiveness of the diagnosis and treatment rules of classical formulas to achieve clinical transformation.

BACKGROUND:Clinical treatment for colon cancer mainly includes fluorouracil,irinotecan and oxaliplatin-based therapy.Studies have shown that membrane transport proteins such as ATP-binding cassette transport protein of G2(ABCG2)mediate the transport of these drugs.However,when patients develop resistance to these chemotherapeutic drugs,the high expression of ABCG2 leads to a significant decrease in the therapeutic effect and raises the problem of drug resistance in colon cancer.New drugs and treatments are urgently needed to improve the efficacy.Lycium barbarum polysaccharide has a wide range of biological activities.It can be used as anti-tumor drug to overcome the damage to normal cells in the process of chemotherapy and radiotherapy in tumor patients. OBJECTIVE:To explore the reversal effect of Lycium barbarum polysaccharide in combination with oxaliplatin on colon cancer drug-resistant cells through in vitro experiments to investigate the possible molecular mechanism of Lycium barbarum polysaccharide reversal on colon cancer drug-resistant cells. METHODS:Colon cancer cell line HCT116 and oxaliplatin-resistant cell line HCT116-OXR were selected for in vitro experiments.The optimal intervention concentration and intervention time of Lycium barbarum polysaccharide and oxaliplatin were determined by CCK8 assay of cell proliferation.Samples were further divided into the HCT116 control group,HCT116-OXR blank treatment group,Lycium barbarum polysaccharide group(2.5 mg/mL Lycium barbarum polysaccharide),and oxaliplatin group(10 μmol/L oxaliplatin),and Lycium barbarum polysaccharide + oxaliplatin group(2.5 mg/mL Lycium barbarum polysaccharide +10 μmol/L oxaliplatin).Cell apoptosis was detected by flow cytometry.The protein expression levels of phosphomannose isomerase(PMI)and ABCG2 were detected by immunofluorescence and western blot assay.Phosphatidylinositol3-kinase(PI3K),protein kinase B(AKT),B-cell lymphoma 2(Bcl-2)and BCL2-Associated X(Bax)were detected by western blot assay. RESULTS AND CONCLUSION:(1)HCT116-OXR was more sensitive to Lycium barbarum polysaccharide compared to HCT116(P<0.05).(2)Compared with the HCT116-OXR blank group,Lycium barbarum polysaccharide + oxaliplatin could promote apoptosis of HCT116-OXR cells(P<0.05).The protein expression of Bcl-2 was significantly down-regulated(P<0.05);the protein expression of Bax was significantly up-regulated(P<0.05);the protein expression of ABCG2,PMI,PI3K and AKT was significantly down-regulated(P<0.05).(3)These results indicate that Lycium barbarum polysaccharide reverses drug resistance in colon cancer by inhibiting PMI/PI3K/AKT signaling pathway,which lays the foundation for studying the molecular mechanism of Lycium barbarum polysaccharide's sensitizing chemotherapeutic effects.

Objective To acquire,evaluate and integrate the best evidence of perioperative exercise interventions in patients with liver cancer and provide evidence-based references for clinical medical staff.Methods Following the"6S"Evidence Resource Pyramid model,literatures in perioperative exercise interventions published between January 2010 and June 2022 were retrieved from various databases,including BMJ Best Practice,UpToDate,Guidelines International Network,National Guideline Clearinghouse,National Institute for Health and Clinical Excellence,Scottish Intercollegiate Guidelines Network,Medlive,Cochrane Library,JBI,Web of Science,PubMed,Embase,CINAHL,CNKI,SinoMed,Wanfang Data,American Cancer Society,American College of Sports Medicine and International Liver Cancer Association from January 2010 to June 2022.Two researchers evaluated the quality of the retrieved literatures and extracted evidences that met the inclusion criteria.Results A total of 22 articles were included,yielding 26 pieces of evidence across seven themes:the necessity of exercise,evaluation before exercise,preoperative exercise program,postoperative exercise program,exercise monitoring,health education and effect evaluation.Conclusions This study provides a summary of the best evidence regarding perioperative exercise interventions in the patients with liver cancer.The findings offer valuable references for clinical healthcare providers to deliver evidence-based care for the patients with liver cancer.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

ObjectiveTo analyze the characteristics of HIV-1 molecular network and pretreatment drug resistance genes in the middle-aged and elderly people aged ≥50 years in Huzhou City, Zhejiang Province, and to provide an evidence for the prevention and control of AIDS epidemic. MethodsA total of 332 samples from the newly reported and untreated AIDS patients aged ≥50 years in Huzhou City from January 2020 to December 2023 were collected, pol genes were amplified by reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (nest⁃PCR). Phylogenetic trees analyzing the subtypes were constructed, and a molecular network with a gene distance threshold of 1.0% were constructed at the same time. Mutation sites of drug resistance-related genes were identified through the Data Analysis and Detection System of HIV-1 Resistance Gene Detection of Stanford University, USA. ResultsSequence samples of 308 patients were obtained, and9 genotypes were identified, including CRF07_BC in 172 cases (55.8%), CRF01_AE in 61 cases (19.8%), CRF08_BC in 43 cases (14.0%), CRF85_BC in 9 cases (2.9%), and CRF55_01B in 8 cases (2.6%), subtype B in 5 cases (1.6%), subtype C in 4 cases (1.3%), CRF67_01B in3 cases (1.0%), and unique recombination URF01_AE/07_BC in 3 cases (1.0%). When the gene distance threshold was 1.0%, 28 molecular clusters were formed, and 139 cases were connected to the network, with an access rate of 45.0%. The largest transmission cluster C1 contained 44 cases infected with CRF07_BC subtype, all of whom were heterosexually transmitted, and predominantly by males. A total of 30 patients were found to have low-grade or higher drug resistance mutations, and the pretreatment drug resistance rate was 9.7% (30/308). Among them, there were 5 cases (16.7%) of protease inhibitor (PI) related drug resistance mutations, and 26 cases (86.7%) of non-nucleoside reverse transcriptase inhibitors (NNRTI) related drug resistance mutations. ConclusionCRF07_BC is the subtype with the most clusters among the middle-aged and elderly infected patients aged ≥50 years in Huzhou City. Middle-aged and elderly transmission clusters are formed within the three counties of WX, NX and CX through related activities. Molecular network monitoring on newly reported cases aged ≥50 years in Huzhou City should be strengthened so that the new characteristics of epidemic changes can be detected in time, providing a scientific basis for adjusting AIDS prevention and control measures for the elderly.