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 analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

Objective:To compare the clinical outcomes of arthroscopic external tension band fixation versus open reduction and internal fixation in the treatment of greater tubercle fracture of the humerus.Methods:A retrospective cohort study was conducted on 55 patients with greater tubercle fracture of the humerus admitted to Taizhou Hospital of Zhejiang Province from September 2019 to June 2022, including 24 males and 31 females, aged 26-80 years [(61.7±10.5)years]. Out of them, 35 patients treated with open reduction and internal fixation (open reduction group), and 20 patients were treated with external anchor tension band under arthroscopy (arthroscopy group). The operation time, and the Visual Analogue Scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score and shoulder active range of motion (anterior flexion, abduction and posterior extension) before operation, at 1 month after operation and at the last follow-up were compared between the two groups. Bone healing was observed in both groups at the last follow-up. Postoperative complications were compared between the two groups.Results:All the patients were followed up for 12-29 months [(16.9±4.0)months]. There was no significant difference in operation time between the two groups ( P>0.05). There were no significant differences in the VAS score, ASES score, Constant-Murley score and shoulder active range of motion between the two groups before operation ( P>0.05). The VAS score of the arthroscopy group was 3(2, 3)points at 1 month after operation, which was significantly lower than that of the open reduction group [4(3, 4) points] ( P<0.01). No significant difference was found in the VAS score at the last follow-up between the two groups ( P>0.05).The ASES scores of the arthroscopy group were (70.6±4.2)points and (90.2±3.7)points at 1 month after operation and at the last follow-up respectively, which were significantly higher than those of the open reduction group [(64.7±6.4)points and (87.5±4.9)points respectively] ( P<0.05 or 0.01). There was no significant difference in the Constant-Murley score between the arthroscopy group [(71.8±4.3)points] and the open reduction group [(70.9±5.3)points] at 1 month after operation ( P>0.05), while the Constant-Murley score of the arthroscopy group was (94.1±3.1)points at the last follow-up, which was significantly higher than that of the open reduction group [(89.2±4.7)points] ( P<0.01). At 1 month after operation and at the last follow-up, ranges of motion of the anterior flexion, abduction and posterior extension were (52.7±12.3)° and (140.0±16.9)°, (57.4±8.6)° and (125.0±14.3)°, and 16(15, 19)° and 25(20, 30)° in the arthroscopy group respectively, which were significantly higher than those in the open reduction group [(42.2±5.2)° and (110.9±14.0)°, (52.8±6.0)° and (103.7±11.7)°, and 10(10, 20)° and 16(15, 25)° respectively] ( P<0.05 or 0.01). At the last follow-up, it was found that bony union was achieved in both groups. There were no obvious complications such as incision infection or joint stiffnessin both groups. In the open reduction group, 2 patients had internal fixation failure within 1-3 months after operation but was treated with revision operation; 6 patients developed shoulder stiffness at 3-6 months after operation but had outpatient rehabilitation. The incidence rate of postoperative complications in the arthroscopy group [0%(0/20)] was significantly lower than that in the open reduction group [23%(8/35)] ( P<0.05). Conclusion:Compared with open reduction and internal fixation with plates and screws, arthroscopic external anchor tension band fixation in the treatment of greater tuberosity fracture of the humerus has the advantages of earlier pain relief, better shoulder functional improvement, better recovery of shoulder mobility, and fewer complications.

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.