Diabetic retinopathy （DR） is a microvascular complication of diabetes and one of its most common complications. Prolonged hyperglycemia induces oxidative stress， inflammatory responses， apoptosis， and pathological angiogenesis， ultimately disrupting the blood-retinal barrier（BRB） and leading to visual impairment or even blindness. Recent studies show that the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway plays an important role in the development of DR's pathological changes. Meanwhile， Chinese herbal monomers have been shown to modulate the Nrf2 signaling pathway， thereby intervening in the development of DR. In terms of inhibiting oxidative stress， saponin compounds such as platycodin-D and ginsenoside Rb1 downregulate the expression of malondialdehyde （MDA）， thereby ameliorating retinal oxidative stress. Flavonoids such as total flavonoids from Pueraria lobata flower and puerarin upregulate the expression of superoxide dismutase （SOD） and glutathione peroxidase （GPx）， effectively clearing lipid peroxides. Regarding the suppression of inflammation， phenolic compounds like resveratrol and chlorogenic acid inhibit the nuclear factor kappa B （NF-κB） pathway， reducing the release of tumor necrosis factor-alpha （TNF-α） and mitigating inflammatory responses. In the context of inhibiting apoptosis， polysaccharides such as Polygonatum sibiricum polysaccharide and Angelica sinensis polysaccharide downregulate the expression of the pro-apoptotic protein Bcl-2-associated X protein （Bax） and suppress the activity of the executioner Caspase-3， thereby reducing the apoptosis rate. As for the inhibition of neovascularization， compounds including bilobalide and physcion significantly decrease the protein expression of vascular endothelial growth factor （VEGF）， leading to a reduction in retinal pathological angiogenesis. Furthermore， Chinese herbal compound prescriptions such as Tongluo Zhujing pills， Yiqi Huoxue Yangyin decoction， Qiming granules， and Danlou tablets can also intervene in the onset and progression of DR through the mechanisms described above. In summary， both Chinese herbal monomers and Chinese herbal compound prescriptions can modulate the Nrf2 signaling pathway to inhibit oxidative stress， alleviate inflammation， and participate in maintaining BRB integrity， suppressing retinal neovascularization， and preventing neurodegeneration， thereby delaying the progression of DR. Therefore， this paper reviews and summarizes recent studies at home and abroad on how traditional Chinese medicine （TCM） works to treat DR， and the relationship between the Nrf2 pathway and DR. It aims to provide research ideas for preventing and treating DR.

ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective:To investigate the clinical and pathological significance of the DICER1 mutation in follicular thyroid carcinoma (FTC).Methods:Sixty-eight cases of primary FTC resected between 2009 and 2023 were retrieved from The Affiliated Hospital of Qingdao University, Qingdao, China. Sanger sequencing was performed to identify DICER1 and TERT promoter mutations in all cases. Cases with DICER1 or TERT promoter mutations were subject to additional examination of potential mutations in KRAS, HRAS, and NRAS. The clinical and pathological features of DICER1-mutant FTCs were then analyzed. The relationship between DICER1 mutations and TERT-promoter/RAS mutations was also assessed.Results:DICER1 mutations were detected in 16 of the 68 FTC cases (23.5%), with 11 near E1813 at exon 25, 6 near D1709 at exon 24, and 1 in the splice region of exon 25. Two cases harbored two (distinct) mutations. All patients with DICER1-mutant FTC were female. Compared with patients with DICER1-wild-type FTC, those with DICER1-mutant were much younger, and had a higher proportion of minimally invasive subtype. Nine FTCs with DICER1 mutations were subject to further sequencing on adjacent non-cancerous tissues or lymph node tissues, but no mutations were detected. TERT-promoter or RAS hotspot mutations were not identified in any of the DICER1-mutant cases. However, TERT-promoter mutation was found in 6 DICER1-wild-type cases (8.8%, 6/68), with 3 cases also having RAS hotspot mutations and exhibiting highly aggressive biological behaviors.Conclusion:DICER1 mutations may occur in FTCs and appear mutually exclusive with RAS and TERT-promoter mutations, warranting further study as RAS-like mutations.

Objective:To investigate the prevalence of sarcopenia and potential influencing factors in middle-aged and elderly populations in Zhejiang Province.Methods:Data were obtained from Zhejiang Provincial Household Economic Status Survey, a cross-sectional survey was condcuted in middle-aged and olde adults selected through multi-stage sampling in three cities in Zhejiang (Huzhou, Jiaxing and Shaoxing) in July 2023. A total of 3 019 study participants, average age 62.3 years old, 53.5% men, were included according to the inclusion and exclusion criteria. Sarcopenia screening was conducted by using the questionnaire with five sarcopenia related-items. Univariable and multivariable logistic regression analysis was used to identify the factors associated with sarcopenia.Results:The prevalence of sarcopenia in the middle-aged and old study participants was 4.47%. Significant differences were observed between the participants with or without sarcopenia in terms of age, educational level, BMI, alcohol consumption status, diet habit, physical activity level, sleep quality, number of chronic diseases, childhood socioeconomic status, adulthood community socioeconomic status, muscle strength, walking assistance, ability to stand from seat, ability to climb stairs, and fall frequency ( P<0.05). Multivariable logistic regression analysis revealed that old age (≥75 years: OR=2.82, 95% CI: 1.60-4.97), low body weight ( OR=1.96, 95% CI: 1.06-3.62), unhealthy diet habit ( OR=1.57, 95% CI: 1.01-2.46), physical inactivity ( OR=5.80, 95% CI: 3.09-10.88), poor or very poor sleep quality ( OR=1.65, 95% CI:1.23-2.41), number of chronic diseases (1 chronic disease: OR=1.84, 95% CI: 1.08-3.14; 2 chronic diseases: OR=3.22, 95% CI: 1.81-5.71; 3 or more chronic diseases: OR=3.74, 95% CI: 2.11-6.65), poor childhood socioeconomic status ( OR=2.98, 95% CI: 1.23-7.20), and poor adulthood community socioeconomic status ( OR=3.87, 95% CI: 1.63-9.17) were significant risk factors for sarcopenia. Conclusions:The prevalence of sarcopenia was relatively low in middle-aged and old population in Zhejiang. Age, BMI, unhealthy diet, physical activity level, sleep quality, number of chronic diseases, childhood socioeconomic status, and adulthood community socioeconomic status were identified as significant influencing factors.

Objective:To investigate the association between blood pressure variability (BPV) and all-cause mortality and cardiovascular events in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and provide reference for clinical management in CAPD patients.Methods:This retrospective cohort study included patients who received CAPD at Guangdong Provincial People's Hospital between May 1, 2010, and July 31, 2023. Baseline and clinical data of the patients were collected. Coefficient of variation of systolic blood pressure (CVSBP) was used to assess BPV. The patients were divided into CVSBP T1, CVSBP T2 and CVSBP T3 groups based on CVSBP tertiles, and the differences among the three groups were compared. Diastolic blood pressure and mean arterial pressure were used to further assess BPV and sensitivity analysis was conducted. The primary endpoint was the composite outcome of all-cause mortality and cardiovascular events. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the association between CVSBP and the primary endpoint.Results:A total of 358 CAPD patients were included, with age of (43.6±13.3) years, and 197 males (55.0%). The proportion of males, proportion of smoking, baseline blood urea nitrogen, serum creatinine and serum albumin in CVSBP T2 (9.08%≤CVSBP<12.55%, n=120) group and CVSBP T3 (CVSBP≥12.55%, n=119) group were lower than those in CVSBP T1 group (CVSBP<9.08%, n=119), and baseline systolic blood pressure, residual kidney Kt/V and total Kt/V were higher than those in CVSBP T1 group, with statistically significant difference among the three groups (all P<0.05). During follow-up of 37(23, 76) months, 49 patients (13.7%) experienced the composite endpoint events, including 12 patients (3.4%) of all-cause deaths and 42 patients (11.7%) of cardiovascular events. Kaplan-Meier survival analysis showed that the incidence of composite endpoint events in CVSBP T3 group was higher than that in CVSBP T1 group and CVSBP T2 group, but the difference was not statistically significant (Log-rank χ2=3.795, P=0.150). Multivariate Cox regression analysis showed that, after adjusting for age, sex, diabetes, baseline systolic blood pressure, residual renal function, and serum albumin, as a continuous variable, CVSBP was not associated with the risk of composite outcome in CAPD patients ( HR=1.058, 95% CI 0.985?1.135, P=0.122); as a categorical variable, with CVSBP T1 group as reference, CVSBP T2 group and CVSBP T3 group were not associated with the risk of composite outcome ( HR=1.222, 95% CI 0.471?3.167, P=0.681; HR=1.827, 95% CI 0.737?4.530, P=0.193). The sensitivity analysis showed that increased variability of diastolic blood pressure ( HR=1.162, 95% CI 1.063?1.270, P=0.021) and increased variability of mean arterial pressure ( HR=1.114, 95% CI 1.030?1.204, P=0.007) were correlated with higher risk of composite outcome in CPAD patients. Conclusions:Systolic blood pressure variability during follow-up is not associated with risk of composite outcome of all-cause mortality and cardiovascular events in CAPD patients. Increased variability of diastolic blood pressure and increased variability of mean arterial pressure are associated with a higher risk of composite outcome in CPAD patients. Interventions to reduce BPV may be helpful to improve the long-term prognosis of CAPD patients.

Objective:To investigate the effects of Shenfu Xiongze Prescription on myocardial fibrosis induced by isoproterenol (ISO) in rats.Methods:SD rats were divided into blank control group, model group, and Shenfu Xiongze Prescription low-, medium-, and high-dosage groups according to random number table method. with 7 rats in each group. Except for the blank control group, the other groups were induced to form myocardial fibrosis in rats by intraperitoneal injection of isoprenaline. Shenfu Xiongze Prescription low-, medium-, and high-dosage groups were administered Shenfu Xiongze Prescription solution at dosages of 8.4, 16.8, and 33.6 g/kg, respectively, while the blank control group and the model group were given the same volume of normal saline for gavage, once a day, for consecutive 3 weeks. The heart structure and function were observed by echocardiography, the levels of BNP and IL-6 in serum were detected by ELISA, the pathological changes of myocardial tissue were observed by HE and Masson staining, and the expressions of TGF-β1 and α-SMA proteins in myocardial tissue were detected by Western blot.Results:Compared with the model group, the EF and FS values of Shenfu Xiongze Prescription in all dosage groups decreased ( P<0.01), the LVIDd and LVIDs increased ( P<0.05 or P<0.01), and the expressions of TGF-β1 and α-SMA proteins in myocardial tissue decreased ( P<0.01 or P<0.05); the levels of BNP and IL-6 in serum of the Shenfu Xiongze Prescription medium and high-dosage groups decreased ( P<0.05 or P<0.01), while the level of IL-6 in the low-dosage group decreased ( P<0.01). Conclusion:Shenfu Xiongze Prescription can inhibit rat myocardial fibrosis induced by isoprenaline, improve rat cardiac function, and its mechanism may be related to reducing inflammation in the heart and down-regulating the expressions of TGF-β1 and α-SMA proteins.

Objective To investigate the effects of Aurora kinase A(AURKA)on the tumor microenvironment of colorectal cancer(CRC)and to predict the active compounds in Chinese herbs that can target AURKA.Methods Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas(TCGA)database,the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.Results The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues(P＜0.05),and CRC patients with high AURKA expression had shorter overall survival.Compared with the AURKA low-expression group,the abundance of macrophages,monocytes,and effector memory CD4+and CD8+T cells was significantly downregulated in the AURKA high-expression group(P＜0.05).In addition,the cytotoxicity of T cells was significantly reduced(P＜0.05).Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells(MDSCs)and the expression levels of their chemokines CXCL2 and CXCL5(P＜0.05).Genes that were differentially expressed between the AURKA high-and low-expression groups were mainly enriched in monocyte migration,chemokine-induced cellular responses,and other related processes.Chinese herbal compounds,including hesperidin,aristololactam A Ⅱ a,anacardic acid,coumestrol,and 17β-estradiol,all showed binding energies to AURKA lower than-1.2 kcal/mol,indicating a certain level of binding stability.Among these Chinese herbal compounds,17β-estradiol exhibited the best binding stability to AURKA-3UOL.Conclusion The high expression of AURKA in CRC tissues suggests a poor clinical prognosis.AURKA can promote the development of a suppressive immune microenvironment in CRC,and 17β-estradiol,an active compound from Chinese herbs,is a potential therapeutic agent targeting AURKA.

The receptors of Newcastle disease virus(NDV)are sialic acid receptors that mainly in-clude neu5ac-α-2,3gal-β-1,4Glc(SAα2,3Gal)and neu5ac-2-s-α-2,6Gal10Me(SAα2,6Gal).The distribution and abundance of the two receptors in host cells have important effects on virus sus-ceptibility and intracellular proliferation.In order to further explore the effects of sialic acid recep-tors on susceptibility and proliferation characteristics of NDV different strains,the expression lev-els of SAα2,3Gal and SAα2,6Gal receptors on BHK-21 cell membrane were adjusted by overex-pression and RNAi assays,and the TCID50 values were determined after different BHK-21 cells were inoculated with NDV strains Ⅰ and LaSota.The results suggested that NDV strain LaSota preferentially binds to SAα2,6Gal and strain Ⅰ selectively binds to SAα2,3Gal receptor.Further-more,the viral titers of NDV strains LaSota and Ⅰ in cell culture were positively correlated with the expression levels of SAα2,6Gal and SAα2,3Gal receptors on host cell membrane respectively.In conclusion,our studies provide an understanding of the relationship between infectivity of NDV different strains and receptor types of host cell,and provide a method to increase viral titer of NDV for cell-based vaccine production.

This study aimed to identify,characterize,and functionally analyze the CYP450 gene fam-ily within Hyalomma asiaticum unfed nymphs(HasiUN)under regular physiological conditions,laying the groundwork for further study into the biosynthesis and metabolism of exogenous sub-stances associated with the CYP450 gene in HasiUN.Through our methods,we identified and characterized HasiUNCYP450 genes.We then annotated them using the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG).This was achieved with the help of bioinforma-tics,based on the transcriptome of 2-week-old HasiUN.Further on,we conducted a preliminary a-nalysis of tissue expression,distribution,and potential function with qRT-PCR and network inter-action predictions.Our analyses showed that 87 HasiUN CYP450 genes,ranging in size from 1089 to 1692 bp,encoded predominantly basic,hydrophilic,and unstable protein sequences.These se-quences had nearly identical numbers of transmembrane regions,both with and without a signal peptide.Phylogenetic and domain analyses indicated that HasiUN CYP450,having a complete CYP450 domain,were distributed among various clans,with most members found in clan 3.CYP20 clans,present in 13 species from 2 families and 7 genera,required either one-host or three-hosts to undergo their full life cycle.MEME analysis results hint at different clans having variations in the amount and combination of motifs.Expression level analysis showed that HasiUN CYP450 was expressed at different levels,with the highest distribution of normally expressed genes in clan 3 and low expression of all mito clan genes.Functional annotation revealed HasiUN CYP450 key as-sociation with biological processes,metabolism,and organismal systems according to the GO and KEGG annotations.Distribution results showed that HasiUN CYP20a1 was expressed in specific tissues,including salivary glands and ovaries.Functional analysis points to CYP20a1's role in UV-induced toxic metabolism,endocrine disruptor metabolism,and hazardous substance metabolism in the nervous system.Our research presents the first analysis of HasiUN CYP450 gene's biological characteristics and expression pattern under normal physiological conditions.Additionally,investi-gations into the distribution and function of a new category,HasiUN CYP20a1,were embarked upon.These findings establish a theoretical foundation for continued functional study of HasiUN CYP45 gene.

Objective:To evaluate the effect of an electronic balance aid in balance rehabilitation training for patients with acute peripheral vestibular injury by comparing the outcomes of medication-only treatment and medication combined with vestibular rehabilitation using an electronic balance aid.Methods:This was a randomized controlled trial. The study subjects included 98 patients (40 males and 58 females, aged 25-69 years) diagnosed with idiopathic sudden sensorineural hearing loss (ISSNHL) with vertigo or vestibular neuritis, who were treated in the Department of Otorhinolaryngology-Head and Neck Surgery of Tianjin First Central Hospital from November 2022 to November 2023. All patients were randomly divided into the experimental group and the control group at a 1∶1 ratio using the sealed envelope method. Control group (conventional drug treatment): Patients received medication treatment for 2 weeks, including betahistine mesilate tablets, vitamin B1 tablets, methylcobalamin tablets, ginkgo biloba tablets, diphenhydramine hydrochloride injection (within 3 days of onset), metoclopramide hydrochloride injection, and glucocorticoids. Experimental group (conventional drug treatment+device training): On the basis of the same medication treatment as the control group, patients received vestibular rehabilitation training using an electronic balance aid (20 minutes per session, once a day,≥5 days per week, for a total of 2 weeks). SPSS software was used to compare the total scores of the Dizziness Handicap Inventory (DHI), the total scores of the Sensory Organization Test (SOT), and sensory analysis indicators between the two groups before and after treatment.Results:After treatment, vertigo symptoms significantly improved in both groups. DHI: The total DHI score in the control group decreased from 77.9±1.8 before treatment to 20.2±2.3 after treatment ( P<0.001). In the experimental group, the total DHI score decreased from 73.5±2.1 before treatment to 8.6±0.9 after treatment ( P<0.001). The difference in total DHI scores between the two groups after treatment was statistically significant, with the experimental group showing a lower score ( t=-4.616, P<0.001). The improvement in DHI scores was also more pronounced in the experimental group compared to the control group ( t=2.004, P=0.048). SOT: The total SOT score in the control group increased from 52.90±0.95 before treatment to 73.3±1.1 after treatment ( P<0.001). In the experimental group, the total SOT score increased from 54.9±0.8 before treatment to 83.5±0.9 after treatment ( P<0.001). The difference in total SOT scores between the two groups after treatment was statistically significant, with the experimental group showing a higher score ( t=7.104, P<0.001). The improvement in SOT scores was also more pronounced in the experimental group compared to the control group ( t=6.532, P<0.001). Sensory Analysis Indicators Proprioception (SOM): In the experimental group, the proprioception score significantly increased after treatment compared with before treatment ( t=-2.338, P=0.029), while, there was no statistically significant difference in the proprioception score of the control group before and after treatment ( P=0.537). Before treatment, there were no statistically significant differences in visual, vestibular, or visual dependence scores between the two groups (all P>0.05). After treatment, the visual, vestibular, and visual dependence scores of both groups significantly increased compared with those before treatment (all P<0.05); moreover, the post-treatment visual, vestibular, and visual dependence scores of the experimental group were significantly higher than those of the control group (all P<0.05). Conclusion:Compared with medication-only treatment, the combination of an electronic balance aid and medication for the treatment and rehabilitation training of patients with acute peripheral vestibular injury can significantly improve the therapeutic effect in the short term.