Objective To analyze the occurrence status and risk factors of frailty in elderly patients with heart failure (HF), and improve the prognosis of elderly patients with HF. Methods Totally 306 elderly patients with HF who received treatment in the hospital were selected from April 2021 to April 2024 as the study subjects. The occurrence of frailty was counted, and the patients were divided into frailty group and non-frailty group according to occurrence status of frailty. Univariate and logistic multivariate regression analyses were adopted to analyze the risk factors of frailty in elderly HF patients. Results Among the 306 patients, there were 92 cases of frailty, with an incidence rate of 30.07%. There were obvious differences in age, HF grading, nutritional status, negative emotions, left ventricular ejection fraction, hemoglobin and creatinine between groups (P<0.05). After logistic multivariate analysis, it was found that age≥70 years old, HF grading, malnutrition, negative emotions and creatinine were the high risk factors for frailty in elderly patients with HF, and left ventricular ejection fraction and hemoglobin level were the protective factors (OR: 1.662, 95%CI: 0.845-3.268; OR: 4.586, 95%CI: 2.318-9.071; OR: 3.971, 95%CI: 1.806-8.731; OR: 3.307, 95%CI: 1.457-7.503; OR: 0.456, 95%CI: 0.255-0.816; OR: 0.525, 95%CI: 1.156-0.967, P<0.05). Conclusion The risk of frailty is high in elderly patients with HF, and is affected by age, heart failure grading, nutritional status, negative emotions, left ventricular ejection fraction, hemoglobin and creatinine. Clinically, it is necessary to take prevention and intervention measures for such patients to reduce the occurrence of frailty.

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.

Objective: To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments. Methods : The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains. Results : A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05). Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.

Objective: To explore sex differences in 3D T1texture features in the progression of Alzheimer&#39;s disease (AD) and to predict the diagnosis of AD patients of different sex． Methods: Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. Results : In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male． Conclusion There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.

AIM: To study the clinical effects and safety of iontophoresis of xueshuantong injection combined with anti-vascular endothelial growth factor(VEGF)in the treatment of retinal vein occlusion(RVO)with macular edema(ME).

METHODS: Totally 106 patients(106 eyes)with RVO and ME in the hospital between June 2017 and June 2019 were divided into observation group and control group according to the random number table method with 53 cases(53 eyes)in each group, and they were all given intravitreal injection of conbercept, and observation group was additionally given iontophoresis of Xueshuantong injection for intervention, and they were treated for 3mo. Both groups were followed up for 1a and given supplementary therapy according to the condition of the disease. The best corrected visual acuity(BCVA), central retinal thickness(CRT)in macular area, supplementary therapy status, VEGF level in aqueous humor and adverse drug reactions were observed and compared between the two groups before and after treatment.

RESULTS: After treatment, the BCVA of the two groups was significantly improved(P<0.05)while the CRT in macular area was significantly thinned(P<0.05), and the BCVA on the 3, 6 and 12mo of treatment in observation group was better than that in control group while the CRT was thinner than that in control group(P<0.05). The macular volume and VEGF level in aqueous humor were significantly reduced in the two groups after treatment(P<0.05), and the macular volume and VEGF level on the 1, 3, 6 and 12mo of treatment in observation group were lower than those in control group(P<0.05). The injection frequencies of conbercept and triamcinolone acetonide and the proportion of patients with laser photocoagulation in observation group were lower than those in control group(P<0.05). During treatment, there was 1 eye of intraocular pressure increase and 3 eyes of subconjunctival hemorrhage in observation group, and there were 2 eyes of subconjunctival hemorrhage and 1 eye of endophthalmitis in control group(P>0.05).

CONCLUSION: Xueshuantong iontophoresis combined with intravitreal injection of conbercept for RVO with ME can effectively inhibit the expression of VEGF, reduce the ME and improve the visual acuity of the affected eyes. The efficacy and safety are worthy of recognition.

Aged-related macular degeneration(ARMD)is prone to occur in the people who aged 50a or older. The disease can lead to partial or even complete loss of sight in single or both eyes progressively. The pathogenesis of ARMD is still unclear, but the previous studies have shown that oxidative stress plays an important role. The mechanism of antioxidants on ARMD has gradually become a hotspot in recent years. In this paper, we briefly reviewed the mechanism of ARMD caused by oxidative stress and the application of antioxidants on ARMD.

Idiopathic macular hole(IMH)refers to the defect of retinal nerve epidermis in macular area with unknown pathogenesis. As present, pars plana vitrectomy combined with internal limiting membrane peeling has become a normal operation for the treatment of IMH, which enables most IMH patients to achieve anatomic healing, however, it is still unclear about the healing mechanism. The role of the glial cell activation in the pathological process of nervous system injury and disease has paid more and more attention. Nearly all the injuries and diseases of nervous system(including retina)are accompanied by the activation of glial cells; and Müller cells are the main type of glial cells in the human retina. In terms of anatomy and function, they are widely related to the cell bodies and processes of neurons in all layers of the retina, and play a supporting, nutritional and information transmission role in neurons. Numerous studies have shown that the activation and proliferation of Müller cells play a leading role in closed MH. It is reviewed in this paper that the role and its related mechanisms of Müller cells in the formation and healing of IMH.

AIM: To compare the changes of dry eye symptoms and signs after femtosecond-assisted laser in situ keratomileusis(LASIK)and conventional LASIK by Keratograph 5M.

METHODS: Sixty patients(120 eyes)who underwent corneal refractive surgery from June 2017 to November 2017 were enrolled. Thirty patients(60 eyes)underwent femtosecond-assisted laser LASIK and 30 patients(60 eyes)underwent conventional LASIK. All patients took examinations of Keratograph 5M dry eye related examinations,routine ophthalmological examinations and ocular surface disease index(OSDI)questionnaire before and 1wk, 1mo, 3mo and 6mo after surgery.

RESULTS: One week after operation, the OSDI scores of two groups were significantly higher than pre-operation(P<0.01), but 1mo after operation, the two groups recovered to the preoperative level(P>0.05). Noninvasive tear film break-up time(NI-BUT)in the conventional group was shorter 1wk, 1mo and 3mo after operation(P<0.01), while it was shorter in 1wk and 1mo after operation in femtosecond laser group(P<0.01). There was significant difference between conventional group and femtosecond laser group at 3mo after operation in NI-BUT(P<0.01). Tear meniscus hight(TMH)and the thickness of lipid layers of the two groups all decreased in 1wk and 1mo after operation(P<0.05).

CONCLUSION: Whether femtosecond-assisted or conventional LASIK will affect tear film stability and cause dry eye symptoms. The degree of influence decreases gradually with the time after operation, but femtosecond laser group can recover more quickly.