Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

OBJECTIVE To provide reference for rational clinical use of immune checkpoint inhibitor （ICI）. METHODS Electronic medical record information of patients who received ICI treatment from January 1st 2020 to December 31st 2023 at a certain hospital was collected. Patients were divided into thyroid immune-related adverse event （irAE） group （subdivided into clinical hypothyroidism， clinical hyperthyroidism， subclinical hypothyroidism， and subclinical hyperthyroidism subgroups） and non- thyroid irAE group based on whether they experienced immune-induced thyroid irAE. Univariate and multivariate Logistic regression analyses were employed to analyze the influencing factors of ICI-related thyroid adverse events. RESULTS A total of 382 patients who received ICI treatment were included， with 137 cases in the thyroid irAE group （accounting for 35.9%） and 245 cases in the non-thyroid irAE group （accounting for 64.1%）. Multivariate Logistic regression analysis， following univariate screening， revealed that ICI combined with radiotherapy was positively associated with the occurrence of thyroid irAE [odds ratio （OR）＝2.157， 95% confidence interval （CI） （1.144， 4.066）， P＜0.05]， while lung squamous cell carcinoma was negatively associated with the occurrence of thyroid irAE [OR＝0.600， 95%CI （0.369， 0.975）， P＜0.05]. Among various thyroid irAE， nasopharyngeal malignancy was positively associated with the occurrence of immune-related clinical hyperthyroidism [OR＝4.678， 95%CI （1.149， 19.042）， P＜0.05]； ICI combined with radiotherapy [OR＝2.622， 95%CI （1.227， 5.603）， P＜0.05] and lung adenocarcinoma [OR＝2.013， 95%CI （1.078， 3.759）， P＜0.05] were positively associated with the occurrence of immune-related subclinical hyperthyroidism. Age was negatively associated with the occurrence of immune-related clinical hypothyroidism [OR＝0.944， 95%CI （0.896， 0.995）， P＜0.05]； age [OR＝0.963， 95%CI （0.932， 0.994）， P＜0.05] and ICI combined with chemotherapy [OR＝0.332， 95%CI （0.137， 0.802）， P＜0.05] were negatively associated with the occurrence of immune-related subclinical hypothyroidism. CONCLUSIONS Among patients receiving ICI treatment， younger patients are more prone to thyroid irAE. Patients receiving ICI combined with chemotherapy are less likely to experience subclinical hypothyroidism， while ICI combined with radiotherapy significantly increases the risk of thyroid adverse events.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.

三级淋巴结构（TLS）是指非生理条件下由于长期发生炎症而形成的异位淋巴组织，是架构在成纤维细胞网络上的淋巴细胞聚集体，包含两个重要的结构区域——T细胞区和滤泡B细胞区。TLS在肿瘤中以不同的成熟状态存在，最终形成生发中心，其内含有T滤泡辅助细胞和滤泡树突状细胞，并且与B细胞紧密联系。近年研究明确了新生的 TLS的关键特征、相关的生物标志物及检测手段，进一步阐述了TLS通过刺激相关的肿瘤抗原调控淋巴细胞的浸润，以增强抗肿瘤免疫效应的作用机制。对TLS与肿瘤患者临床获益之间的相关性研究结果表明，TLS可作为包括免疫治疗在内的生物治疗的良好预后和预测因素。目前，研究者正在开发诱导TLS形成的技术，包括使用趋化因子、细胞因子、抗体、抗原提呈细胞或合成支架等。在“冷肿瘤”和“热肿瘤”中诱导TLS新生联合抑制炎性环境的治疗剂或免疫检查点抑制剂的方案，代表了肿瘤治疗的新希望。

ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

Objective To observe the regulating effect and mechanism of Yichang Sanjie Granules on intestinal flora and immune function in mice with colon cancer.Methods Sixty mice were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Yichang Sanjie Granules,and the overexpression of melanoma absent gene 2(AIM2)plasmid(pcDNA-AIM2)intervention group,with 10 mice in each group.Colorectal cancer model was prepared by oxidized azomethine(AOM)/dextran sulfate sodium(DSS)induction method in all groups except normal group.After drug administration,the survival curves of mice in each group were plotted and the tumor volume was calculated;serum levels of immunoglobulin(Ig)G,IgM,interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA);peripheral blood levels of CD3+,CD4+,CD8+ T cells were detected by flow cytometry;the splenic index was determined;Hematoxylin-eosin(HE)staining was used to observe the pathological changes in colon tissues;16S-rDNA intestinal flora sequencing was used to detect the α-diversity of intestinal flora and the structure of intestinal flora communities;and protein immunoblotting(Wetsern Blot)was used to detect the protein expressions of AIM2,apoptosis-associated speckled-like protein containing a CARD(ASC),and cystatinase-1(caspase-1)in colon tissues.Results Compared with the normal group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the model group were significantly decreased,and the tumor volume,serum levels of IL-1β and IL-18,peripheral blood level of CD8+,and splenic index were significantly increased(all P＜0.05),and the HE staining results showed the characteristic manifestations of colon cancer;compared with the model group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group were significantly increased,and the tumor volume,serum levels of IL-1β and IL-18,level of peripheral blood CD8+,and splenic index were significantly decreased(all P＜0.05),and the HE staining results showed the manifestations of colon cancer were improved.Compared with the normal group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group,and Ruminiclostridium in the model group were significantly decreased,while the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was increased in the model group(P＜0.05);compared with the model group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group and Ruminiclostridium were significantly increased,and the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was decreased in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group(all P＜0.05).Conclusion Yichang Sanjie Granules can increase autoimmunity and improve intestinal flora structure in mice with colon cancer,and its mechanism is related to the activation of AIM2 inflammatory vesicles.

Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147％and 155％,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Objective To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Methods We designed,developed,and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection.The precision of the liquid transfer and temperature control was tested.A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction(RT-PCR).The entire process,from SARS-CoV-2 nucleic acid extraction to amplification,was evaluated. Results The precision of the syringe transfer volume was 19.2±1.9 μL(set value was 20),32.2±1.6(set value was 30),and 57.2±3.5(set value was 60).Temperature control in the amplification tube was measured at 60.0±0.0 ℃(set value was 60)and 95.1±0.2 ℃(set value was 95)respectively.SARS-Cov-2 nucleic acid extraction yield through the device was 7.10×106 copies/mL,while a commercial kit yielded 2.98×106 copies/mL.The mean time to complete the entire assay,from SARS-CoV-2 nucleic acid extraction to amplification detection,was 36 min and 45 s.The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test(POCT).