ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

Exportin 1 (XPO1) is aberrantly overexpressed in various malignant tumors and can lead to the loss of anti-tumor effects of important tumor suppressor proteins such as p53, RB1, and FOXO by mediating their nuclear export. Although XPO1 inhibitor Selinexor has entered clinical application, its single-agent anti-tumor activity remains suboptimal, which is closely related to the compensatory activation of multiple signaling pathways in response to XPO1 inhibition. Focusing on the core regulatory role of XPO1 in tumor cells, this article systematically summarizes the current landscape of combination therapies involving XPO1 inhibitors and various targeted agents, including inhibitors of CDK4/6, FLT3, BET, ATR, and BCL2/MDM2, aiming to provide some reference for the development of XPO1-centered combination therapy strategies.

AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

Objective To study the death status of pancreatic cancer among residents in Xuhui district, Shanghai, from 1992 to 2021, and analyze its trends of change, so as to provide evidence for the prevention and treatment of pancreatic cancer. Methods Based on the database of Shanghai death registration system from 1992 to 2021, the crude mortality rate, standardized mortality rate, age-specific mortality rate and other indicators of pancreatic cancer among registered residents in Xuhui district were calculated. The Joinpoint software was used to analyze the trends of average annual percent change (AAPC) of pancreatic cancer mortality rate, and the age-period-cohort model was used to analyze the age effect, period effect and birth cohort effect pairs significant changes in pancreatic cancer mortality. Results In 2021, the mortality rate of pancreatic cancer in Xuhui district, Shanghai, ranked fourth among malignant tumors, and the winning rate and world standard rate of the whole population, males and females were 8.34/100 000 (8.81/100 000, 7.98/100 000) and 7.28/100 000 (7.69/100 000, 6.96/100 000), respectively, with males higher than females. AAPC of crude mortality rate and the standardized (6) mortality rate were higher in males than that in females. The age-specific mortality rate increased with the increase of age, and the highest mortality rate was found in 60-84 years old group. The age-period-cohort model showed that from 1992 to 2021, the annual net shift of pancreatic cancer mortality among the whole population, male and female residents in Xuhui district, Shanghai, was 1.22%, 1.58%, 1.15% (P=0.20, 0.19, 0.45) respectively, and the time trend was not significant. From the perspective of age effect, the risk of death from pancreatic cancer in the whole population and with age deviation in males had an obvious trend with increasing age (P<0.05), while the age effect in females had no obvious trend. From the perspective of period effect, no period deviation was significant in the whole population, males and females (P>0.05). In terms of cohort effects, there were significant differences in the whole population and the male cohort deviations(P<0.05). No significant cohort effect was observed in the female population. Conclusions The mortality rate of pancreatic cancer among registered residents in Xuhui district, Shanghai from 1992 to 2021, was on the rise, especially in the 60-84 years old group and male. The prevention and control of pancreatic cancer needs to develop effective epidemic prevention measures for corresponding populations.

Objectives:To investigate the risk factors of acute myocardial infarction(AMI)patients with a family history of premature coronary heart disease(FHpCHD)in China and analyze the relationship between these risk factors and premature myocardial infarction.Methods:Using data form the Chinese Acute Myocardial Infarction(CAMI)Registry which enrolled a total of 28 070 patients with AMI from 108 hospitals between January 1,2013 to September 30,2014.We compared the demographic data,cardiovascular risk factors,clinical characteristics,and prognosis in AMI patients with and without FHpCHD.FHpCHD is defined as the history of myocardial infarction,angina,sudden cardiac death and/or revascularization(including coronary artery bypass grafting and percutaneous coronary intervention)among first-degree relatives(father,mother,brother and sister)aged≤55 years old for men or≤65 years old for women.The risk factors included obesity,hypertension,diabetes,hyperlipidemia,unhealthy diet,lack of physical activity,smoking,and frequent alcohol consumption.The correlation between family history and premature AMI was calculated by the multivariate Logistic regression analysis.The risk contribution values of the affected first-degree relatives were determined by applying the Shapley algorithm.Results:A total of 893 cases(4.12%)of AMI patients had FHpCHD.Among patients with premature AMI,467 cases(6.20%)had FHpCHD.AMI patients with FHpCHD were younger,and had a higher proportion of male,obesity/overweight,hypertension,hyperlipidemia,and stroke history,unhealthy lifestyle(such as frequent alcohol consumption and current smoking),and a higher proportion of multi-vessel lesions in coronary angiography compared to those without FHpCHD(all P<0.05).AMI patients with FHpCHD had a significantly higher proportion of risk factors(P<0.01).After adjusting for sociodemographic factors,lifestyle,and cardiovascular risk factors,multivariate Logistic analysis revealed that FHpCHD was significantly associated with premature AMI(OR=1.793,95%CI:1.553-2.070,P<0.0001).The calculation using the Shapley algorithm showed that the father had the highest risk contribution value(40.27%).Conclusions:AMI patients with FHpCHD exhibit a clustering of family unhealthy lifestyle and cardiovascular risk factors,with an earlier onset age and more severe coronary artery disease.FHpCHD is associated with AMI,independent of lifestyle and cardiovascular risk factors.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.