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.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

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.

Objective:To evaluate the effects of chlorinated organophosphate flame retardants (Cl-OPFRs) via respiratory and digestive tract exposure on multiple organs in mice.Methods:A short-term repeated exposure model of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP) in mice was established through intratracheal instillation and oral gavage administration. The exposure doses were 0.7, 1 and 2 mg·kg -1·day -1, respectively, with continuous administration for 14 days. The organs of the heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder and testis were collected and weighed to calculate the organ coefficients. The pathological and histological changes were observed by hematoxylin-eosin staining to quantitatively assess the effects of the three Cl-OPFRs on the various organs by using the pathology score. Results:Analysis of organ coefficients in tracheal drip-treated mice showed that the organ coefficients in the testes of the TCEP, TCIPP and TDCIPP groups were lower than those in the control group ( PTCEP-testis=0.045, PTCIPP-testis=0.012 and PTDCIPP-testis<0.001). The organ coefficients were lower in the lungs and small intestines of the TCEP group ( PTCEP-lung=0.006, PTCEP-small intestine=0.042). The organ coefficients for the stomach and large intestine were higher in the TDCIPP group ( PTDCIPP-stomach=0.014, PTDCIPP-large intestine=0.049). Analyses of gavage-contaminated mice showed that the organ coefficients for liver, stomach and small intestine in the TCEP and TDCIPP groups were higher than those in the control group ( PTCEP-liver=0.007, PTCEP-stomach=0.003, PTCEP-small intestine<0.001, PTDCIPP-liver=0.001, PTDCIPP-stomach=0.004, and PTDCIPP-small intestine<0.001). Histopathological analyses of the organs of tracheal drip dyed mice showed significant pathological damage in the lung tissue of the TCIPP group, mainly in the form of thickening of the interstitium, infiltration of inflammatory cells and alveolar collapse. The results of the analysis of gavage poisoned mice showed that TCIPP exposure could lead to blurring of the red and white medullary boundaries of spleen tissues, destruction of white medullary structures, etc., and induce small intestinal cryptitis. TDCIPP induced significant pathological damage to the liver tissues of mice, which mainly included cytoplasmic washout, infiltration of inflammatory cells, acute inflammation, and other injurious effects. Significant pathological damage to the intestinal tissues of mice was also observed. Conclusions:This study demonstrates that the toxic effects of Cl-OPFRs are significantly associated with exposure routes and compound specificity. Respiratory exposure predominantly induces TCIPP-mediated pulmonary injury, while digestive exposure causes TDCIPP-driven hepatointestinal toxicity. These findings provide preliminary evidence for the toxicity screening of Cl-OPFRs.

OBJECTIVE To investigate the epidemiological characteristics of respiratory human adenovirus(H AdV)infections in hospitalized children in Ningbo,and to provide data for formulating infection prevention and control strategies for HAdV.METHODS A total of 65 022 children hospitalized with respiratory infections at the Women and Children's Hospital of Ningbo University from Jul.2019 to Dec.2024 were selected as the study sub-jects.Multiple reverse transcription-polymerase chain reaction(RT-PCR)and capillary electrophoresis were used to detect 11 non-bacterial pathogens.Basic and clinical information of the children was collected for analysis.RESULTS A total of 65 022 specimens were tested,with 4 292 cases tested positive for HAdV positivity,yielding a positive rate of 6.60％.The lowest positive rate was observed in 2023(3.22％),while the highest was in 2024(13.97％).Compared to the years 2019-2023,the overall HAdV positive rate was high in 2024,peaking at 26.80％in Jun.,indicating an outbreak.The total HAdV positive rate was higher in boys(6.82％)than in girls(6.32％)(P=0.006).The highest HAdV positive rate was observed in the 2 to＜6 age group(9.00％),while the lowest was in the 0 to＜1 age group(2.33％).Among the HAdV-positive specimens,2 658 cases(61.93％)were single infections,and 1 634 cases(38.07％)were co-infections.The non-bacterial respiratory pathogens with the highest co-infection rates were human rhinovirus(34.09％),Mycoplasma pneumoniae(20.44％)and human parainfluenza virus(5.75％).CONCLUSIONS A n outbreak of HAdV infections is observed among hospitalized children in Ningbo in 2024.Higher positive rates are found in boys aged 2 to＜6 years,with a certain proportion of co-infections.

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 hep-atoprotective 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.