BACKGROUND:Disruption of biological rhythms(circadian rhythms)is a typical problem associated with aging.Maintaining the normal function of biological rhythms may be a promising anti-aging strategy.Expression of nuclear factor erthroid 2-related factor 2(Nrf2)is biologically regulated.The glycogen synthase kinase 3(GSK3)system represents a"regulatory valve"that controls subtle oscillations in Nrf2 levels.Circadian changes in the transcript levels of antioxidant genes can influence the response of organisms to oxidative stress.However,the specific molecular mechanism of GSK3/Nrf2 in regulating organismal aging is still puzzling. OBJECTIVE:To search for the general pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging by reviewing the literature in this field. METHODS:The bibliographic method was used to search,review and screen the relevant literature using the keywords of"glycogen synthase kinase 3,nuclear factor erthroid 2-related factor 2,biorhythms and aging"to lay a theoretical foundation for the analysis of the whole paper.Comparative analysis method,through reading and analyzing the obtained literature,was performed to compare the similarities and differences between the literature,thereby providing reasonable theoretical support for the argument.Further comparative analysis of the literature was conducted to clarify the relationship between the relevant indicators as well as the ideas for analysis throughout the text. RESULTS AND CONCLUSION:GSK3 can indirectly regulate Nrf2 expression through the regulation of rhythm genes.GSK3 and Nrf2 are components of anti-aging programs and are associated with biological rhythms.In addition,GSK3/Nrf2 is involved in several metabolic pathways,including those associated with age-related diseases(type 2 diabetes and cancer)and neurodegenerative diseases.

OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group （water）， model group （water）， Shengmai powder low-， medium-， and high-dose groups [2.61， 5.22 and 10.44 g/kg （based on crude drug dosage）] and positive control group （metoprolol， 30 mg/kg）， with 10 mice in each group. Except for the blank group， all other groups were subcutaneously injected with D-galactose， and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling， the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine （TCM） syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action， the percentage of immobility time， and the swimming exhaustion time of mice. The contents of aspartate transaminase （AST）， creatine kinase （CK） and lactate dehydrogenase （LDH） in the serum of mice were detected； cardiac function indexes [heart rate， left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， left ventricular mass index and whole heart mass index] were all detected； the histopathological morphology of mice myocardium was observed； the level of cardiomyocyte apoptosis in mice was detected； mRNA expression levels of B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Cleaved-caspase-3 in myocardial tissue of mice were detected； the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 （RyR2） and phospholamban （PLB）] in myocardial tissue of mice were detected. RESULTS Compared with the blank group， the body weight， total distance of open field action， swimming exhaustion time， LVEF， LVEDD， Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened （P＜0.05）； TCM syndrome score， the percentage of immobility time， heart rate， LVESD， left ventricular mass index， whole heart mass index， cardiomyocyte apoptosis rate， the contents of CK， LDH and AST in serum， mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased （P＜0.05）； there were inflammatory cell infiltration， disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder， most of the above quantitative indexes in mice were significantly reversed （P＜0.05）， the inflammatory cell infiltration in myocardial tissue was reduced， and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function， reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

OBJECTIVE: To quantitatively evaluate the accuracy of data obtained from liquid-interference surfaces using an intraoral 3D scanner (IOS) integrated with a compressed airflow system, so as to provide clinical proof of accuracy for the application of the compressed airflow system-based scanning head in improving data quality on liquid-interference surfaces. METHODS: The study selected a standard model as the scanning object, adhering to the "YY/T 1818-2022 Dental Science Intraoral Digital Impression Scanner" guidelines, a standard that defined parameters for intraoral scanning. To establish a baseline for accuracy, the ATOS Q 12M scanner, known for its high precision, was used to generate true reference values. These true values served as the benchmark for evaluating the IOS performance. Building on the design of an existing scanner, a new scanning head was developed to integrate with a compressed airflow system. This new design aimed to help the IOS capture high-precision data on surfaces where liquid-interference, such as saliva, might otherwise degrade scanning accuracy. The traditional scanning method, without airflow assistance, was employed as a control group for comparison. The study included five groups in total, one control group and four experimental groups, to investigate the effects of scanning lens obstruction, airflow presence, liquid media, and the use of the new scanning head on scanning process and accuracy. Each group underwent 15 scans, generating ample data for a robust statistical comparison. By evaluating trueness and precision in each group, the study assessed the impact of the compressed airflow system on the accuracy of IOS data collected from liquid-interference surfaces. Additionally, we selected Elite and Primescan scanners as references for numerical accuracy values. RESULTS: The scanning accuracy on liquid-interference surfaces was significantly reduced in terms of both trueness and precision [Trueness: 18.5 (6.5) vs. 38.0 (6.7), P < 0.05; Precision: 19.1 (8.5) vs. 31.7 (15.0), P < 0.05]. The use of the new scanning head assisted by the compressed airflow system significantly improved the scanning accuracy [Trueness: 22.3(7.6) vs. 38.0 (6.7), P < 0.05; Precision: 25.8 (9.6) vs. 31.7 (15.0), P < 0.05]. CONCLUSION The scanning head based on the compressed airflow system can assist in improving the accuracy of data obtained from liquid-interference surfaces by the IOS.
Imaging, Three-Dimensional/methods* ; Humans ; Dental Impression Technique/instrumentation*

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

OBJECTIVE: Left ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of Compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism. METHODS: The left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson's trichrome staining, and hematoxylin-eosin (HE) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting. RESULTS: CDT attenuated the cardiac dysfunction, structural changes, histopathological changes and fibrosis induced by MI/RI. CDT significantly enhanced the level of Beclin1 and microtubule-associated protein 1 light chain 3 beta (LC3β), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation. CONCLUSION CDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.

OBJECTIVE To evaluate cerebrospinal fluid(CSF)flow dynamics and volume changes of pulsatile tinnitus(PT)patients caused by sigmoid sinus wall dehiscence(SSWD)with different intracranial pressure via MRI.METHODS Prospective enrolled 35 SSWD-PT patients with intracranial hypertension,25 SSWD-PT patients with normal intracranial pressure and 35 age-,sex-matched healthy controls.Demographic characteristics were recorded.Intracranial pressure was assessed by the index of transverse sinus stenosis(ITSS)and morphology changes.CSF flow dynamics were evaluated via phase-contrast magnetic resonance imaging(PC-MRI)and CSF volume were evaluated via three-dimensional T1-weighted turbo field echo(3D T1-TFE)sequence and ITK-SNAP software.Compared the differences of each index between three groups.RESULTS The mean flux and regurgitant fraction were significantly different among the three groups(P<0.05).The intracranial hypertension group presented significantly decreased mean flux(MF)and significantly increased regurgitant fraction(RF)compared to controls(P<0.017).There were no significant differences in MF and RF of normal intracranial pressure group compared with intracranial hypertension group and control group(P>0.017).There were no statistical differences in age,sex,body mass index,forward flow volume,backward flow volume,mean velocity,peak velocity,stroke volume and CSF volume(P>0.05).CONCLUSION SSW D-PT patients have abnormal changes in CSF,and those with increased intracranial pressure are more obvious.These changes may be associated with abnormal hemodynamics in the sigmoid sinus and the occurrence of PT.

Objective:To investigate whether dual-energy computed tomography(DECT) measurement of monosodium urate(MSU) crystal loading can predict the risk of gout flares.Methods:A single-center, prospective, observational study included 229 gout patients initially diagnosed at the Gout Clinic of Qingdao University from August 2021 to February 2022. The patients underwent MSU assessment of the bilateral feet using DECT. Following enrolment, all patients commenced uric acid-lowering therapy(ULT) and were followed up at 3 and 6 months. Patients who experienced at least one flare within 6 months were compared with those who did not, and the odds ratio( OR) for the risk of gout flares was calculated. Results:Patients who experienced gout flare had a significantly longer disease duration[(6.69±5.42) vs(4.14±4.86) years, P<0.01], a higher number of flares in the past year(4.80±1.73 vs 2.02±1. 23, P<0.01), a higher proportion of fatty livers(11.0% vs 1.4%, P<0.05), and a greater volume of MSU crystals in the feet[(3.52±9.74) vs(0.29±0.98)cm 3,P<0.05] compared to patients without gout flare. The results of the multifactorial logistic regression analysis indicated that the number of flares in the past year( OR=1.295, 95% CI 1.032-1.613, P<0.05) and feet MSU crystal volume( OR=3.245, 95% CI 1.164-9.064, P<0.05) were independent risk factors for gout flares. The receiver operating characteristic(ROC) curve indicated the integration of the MSU prediction model into the clinical prediction model resulted in a comprehensive prediction model with an area under curve(AUC) value of 0.780(95% CI 0.710-0.840), sensitivity of 0.83, and specificity of 0.62. Internal validation of the comprehensive prediction model using the Bootstrap method yielded a C-index of 0.770(95% CI 0.701-0.833) for predicting flares. The calibration curve of the model demonstrated a good fit between the predicted probability of flares and the actual probability, indicating high calibration accuracy. Conclusion:The volume of MSU crystals in the feet is an independent risk factor for flares following ULT. A larger volume of MSU crystals in the foot increases the likelihood of a flare. This study provides a basis for early prediction of flare and a reference for early preventive treatment.

Objective To investigate the neuroprotective effect and mechanism of salvia polyphenolic acid for injection (SAFI) on cerebral ischemia-reperfusion injury in rats. Methods A total of 100 SD rats were randomly divided into sham surgery group,model group,low-,medium-and high-dose (5,10,20 mg·kg-1) salvia polyphenolic acid groups,with 20 rats in each group. After being continuously administrated by intraperitoneal injection of SAFI once daily for three days,the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established using the thread embolization method at 1 hour after the last administration. The neurological deficit of rats was evaluated by Zea Longa score. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride(TTC) staining. The levels of serum NADPH oxidase(NOX),4-hydroxynonanal(4-HNE),8-hydroxydeoxyguanosine (8-OHdG),monocyte chemoattractant protein-1 (MCP-1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-18(IL-18),interleukin-6(IL-6),and intercellular adhesion molecule-1 (ICAM-1) were detected by ELISA kits. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the pathological changes of brain tissue and the morphology of neurons. The apoptosis of neuronal cells in brain tissue was detected by TUNEL. Immunofluorescence staining was used to detect the expression level of glial fibrillary acidic protein (GFAP) in brain tissue. Western Blot was used to detect the protein expression of NLRP3 and Caspase1 in brain tissue. Results Compared with the sham surgery group,neurological deficit scores in model group increased remarkably (P<0.01). The cerebral infarction volume increased significantly (P<0.01). Serious pathological damage of brain was observed,and neuronal density decreased significantly(P<0.01). The apoptosis rate of cortical cells increased obviously (P<0.01). The levels of serum NOX,4-HNE,8-OHdG,MCP-1,TNF-α,IL-1β,IL-18,IL-6 and ICAM-1 increased significantly (P<0.05,P<0.01). The protein expression of GFAP,NLRP3 and Caspase1 in brain significantly upregulated (P<0.01). Compared with the model group,neurological deficit scores in medium-and high-dose SAFI groups decreased remarkably (P<0.01). The cerebral infarction volume decreased significantly (P<0.01). Neuronal damage was ameliorated to varying degrees,and neuronal density increased significantly(P<0.05,P<0.01). The apoptosis rate of cortical cells decreased obviously (P<0.01). The levels of serum NOX,4-HNE,8-OHdG,MCP-1,TNF-α,IL-1β,IL-18,IL-6 and ICAM-1 decreased significantly (P<0.05,P<0.01). The protein expression of GFAP,NLRP3 and Caspase1 in brain significantly downregulated(P<0.01). Conclusion SAFI has a protective effect on MCAO/R rats,which can significantly reduce oxidative stress and inflammatory responses,thereby reducing pathological damage and apoptosis of brain tissue. Its mechanism may be related to the inhibition of NLRP3/Caspase-1 signaling pathway and astrocyte activation.

Objective To observe the clinical efficacy of Redo-Bentall surgery in the reoperation of aortic root lesions.Methods A retrospective analysis was performed on 46 patients who underwent Redo-Bentall surgery for aortic root lesions in our department from June 2010 to April 2022.They were 35 males and 11 females,at a mean age of 43.37±12.79 years,in 4.96±6.76 years since the last operation.General clinical data in perioperative period and during follow-up were collected and analyzed.Kaplan-Meier survival analysis was used to compare the survival rates of each etiological group.Results There were 9 cases of central end otitis,12 cases of Behset's disease,and 25 cases of other causes.After operation,4 cases(8.70％)experienced cardiac arrest,4 cases(8.70％)renal failure,2 cases(4.35％)gastrointestinal bleeding,2 cases(4.35％)new third-degree atrioventricular block and 2 cases(4.35％)permanent pacemaker placement.In perioperative period,3 cases(6.52％)died in hospital.During a mean follow-up of 5.03±3.27 years after discharge,5 cases(11.63％)were lost to follow-up,1 case died(2.33％),1 case had lacunar infarction(2.33％),and no severe bleeding or embolism complications was observed in the rest patients.The long-term survival rate was significantly lower in the endocarditis group(62.3％)and the Behcet's disease group(70％)than the other etiological groups(80％,P＜0.05).Conclusion The application of Redo-Bentall in the reoperation of aortic root lesions is safe and effective,but the survival rate is quite lower in the patients with infective endocarditis and Behcet's disease.