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.

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.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

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.

ObjectiveTo establish preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients and provide a basis for standardized diagnosis and treatment of ischemic stroke. MethodsRelevant literature on the diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients was retrieved， and data were mined and extracted to form an item pool. Based on the formation of the item pool， this study used the Delphi method to initiate two rounds of questionnaire surveys with selected experts to complete the initial screening of items and the discrimination of symptom importance. A prospective clinical investigation method was adopted to collect clinical information from patients， and statistical analysis methods and data mining techniques were comprehensively used to determine their primary and secondary symptoms. Based on the clear main and secondary symptoms identified， combined with expert group discussions， the study established preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients. ResultsA total of 25 relevant syndrome differentiation standards were included. After splitting， standardizing， and screening the items， the study established a pool of 48 items. The first round of questionnaire survey consulted 30 experts， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.359. According to the item screening criteria， 26 items were retained in this round of questionnaire survey. A total of 176 cases were collected through clinical information investigation， including 94 cases with spleen and kidney deficiency syndrome and 82 cases without spleen and kidney deficiency syndrome. The statistical results were as follows： ① Descriptive statistics： The main symptoms with a frequency of ≥ 30% included mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with a frequency of ≥ 10% and ≤ 30% were lassitude and disinclination to talk， shortness of breath， etc. ② Binary logistic regression analysis： The main symptoms with an odds ratio （OR） value of ≥ 3 were mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with an OR value of ≥ 1 and ≤ 3 were lassitude and disinclination to talk， shortness of breath， etc. Artificial neural network： The main symptoms with a weight value（W_ij）of ≥ 0.5 and < 1 were mental fatigue and lack of strength， lassitude and disinclination to talk， etc. The secondary symptoms with W_ij of ≥ 0.3 and < 0.5 were shortness of breath， flaccid limbs， etc. In the second round of questionnaire survey， a total of 37 experts were consulted， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.237. According to the criteria to determine primary and secondary symptoms based on the Delphi method， the main symptoms included in this round of the questionnaire were mental fatigue and lack of strength， lassitude and disinclination to talk， etc.， and the secondary symptoms were shortness of breath， dizziness， etc. ConclusionThe main symptoms of spleen and kidney deficiency syndrome in ischemic stroke patients are mental fatigue and lack of strength， weakness of the lower back and knees， loose stool， pale and edematous tongue texture possibly with tooth marks， and deep and thready pulse or weak pulse. The secondary symptoms include shortness of breath， dizziness， tinnitus and deafness， decreased appetite or postprandial abdominal distension， pale complexion， frequent micturition at night， dull tongue texture， and white and slippery tongue coating. The preliminarily established diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients can provide a standardized and objective basis， thereby better guiding clinical diagnosis and treatment of ischemic stroke.

[Purpose]To analyze the trends of incidence and age at onset of leukemia in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of leukemia from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province.All datasets were checked and evaluated based on data quality control criteria and were included in the analysis.Crude incidence rate(CIR),age-standardized incidence rate by Chinese standard population(ASIRC),the average annual percentage change(AAPC),the standardized average age at onset,the changes in the age structure of incidence and the changes in the birth cohort by year were calculated.[Results]The incidence rate of leukemia significantly increased from 5.22/105 in 2009 to 7.88/105 in 2019,with a significant upward trend(for CIR,AAPC=4.95％,95％CI:3.82％～6.09％;for ASIRC,AAPC=2.97％,95％CI:1.52％～4.43％).The incidence rates were in-creased in all age groups and increased with the birth cohort by years.There was a tendency of backward shift for the age composition of the population,with the increasing of composition for those over 60 years old.The mean age at onset increased from 48.62 years old in 2009 to 57.96 years old in 2019,with a backward shift in the mean age(β=0.773,P＜0.001),and the mean age at onset increased with the year only in rural areas after standardization(β=0.428,P=0.017).[Conclusion]Leukemia incidence rate in Jiangsu Province increased from 2009 to 2019,and the age at onset has shifted backwards.It's important to strengthen the early prevention and control of leukemia.