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.

OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

From the theoretical perspective of "body fluids and blood stasis mixing"， environmental microplastics （MPs） are conceptualized as a "novel turbid-toxin". This study aims to elucidate the complete pathogenic pathway through which MPs act as a key driving force （the "crucible" of pathogenesis） in the initiation and progression of atherosclerosis （AS）. By tracing the classical theories in the Chapter The Occurrence of All Diseases of Miraculous Pivot （Ling Shu）， this paper clarifies the core connotations of "body fluids"-it not only refers to endogenous pathological fluids and lipid turbidity but also provides a theoretical basis for incorporating "exogenous turbid fluids"， thereby laying a logical foundation for conceptualizing MPs as a "novel turbid-toxin". Meanwhile， the implications of "blood" （encompassing both blood quality abnormalities and blood stasis） and the dynamic process of "mixing" are elucidated. Drawing upon modern toxicological evidence， this paper demonstrates the high homology between MPs and "exogenous turbid-fluids" from three aspects： Morphology， toxicity， and invasion routes. The micro/nano-scale particle morphology of MPs enables mobility within the bloodstream. The multiple exposure pathways of MPs correspond to the traditional Chinese medicine understanding of pathogens invading through the mouth， nose， and skin. The characteristics of accumulating in vivo while inducing oxidative stress and inflammatory responses of MPs fully embody the pathogenic features-adhesion， binding， and vessel damage-of "turbid-toxin". On this basis， the dynamic pathogenesis of MP-induced AS is systematically interpreted. Initially， MPs with the "turbid-toxin" nature impair nutrient-defense harmony and cause endothelial dysfunction. Subsequently， as the core of "mixing"， they interact with blood lipids and immune cells， generating heat and phlegm to form a major pathological hub of chronic inflammation. Ultimately， this process drives the coalescence of phlegm， stasis， and turbid-toxin into tangible plaques， evolving from stable lesions to vulnerable masses and accumulations. By integrating classical pathogenic model with contemporary environmental medicine， this study establishes an analytical framework that bridges macro-theory and micro-mechanisms for understanding the cardiovascular risks of MPs through an integrative Chinese-Western medicine lens.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

Objective To establish and validate a multimodal MRI radiomics model based on intratumoral and peritumoral heterogeneity for prediction of spatial pattern of locally recurrent high-grade gliomas(HGGs).Methods A retrospective analysis was conducted on the clinical and imaging data of all HGGs patients who underwent maximum safe resection followed by postoperative radiotherapy combined with temozolomide treatment and experienced in local recurrence in Army Medical Center of PLA from 2012 to 2021.Two radiologists independently assessed the spatial patterns of locally recurrence HGGs through continuous follow-up MRI data,and primarily categorized the pattern into intra-resection cavity recurrence and extra-resection cavity recurrence.The subjected patients were randomly divided into a training set and a validation set in a 7∶3 ratio.In the training set,Pearson or Spearman correlation analysis and least absolute shrinkage and selection operator(LASSO)analysis were employed to screen radiomic features within the intratumoral and peritumoral regions,as well as to calculate radiomic scores.A radiomics model was established using logistic regression analysis.The performance of the model was assessed using calibration curves,Hosmer-Lemeshow goodness-of-fit test,and the area under the receiver operating characteristic curve(AUC).Validation of the model was performed in the validation set.Results A total of 121 patients with locally recurrent HGGs were enrolled in this study,including 54 in intra-resection cavity recurrence group and 67 in extra-resection cavity recurrence group.Among them,84 were assigned into the training set and 37 into the validation set.In the training set,the radiomics score for the extra-resection cavity recurrence group was 0.424(0.278,0.573),which was higher than that for the intra-resection cavity recurrence group[-0.030(-0.226,0.248),P<0.001].In the validation set,the radiomics score for the extra-resection cavity recurrence group was 0.369(0.258,0.487),which was higher than that for the intra-resection cavity recurrence group[0.277(0.103,0.322),P=0.033].The established radiomics model exhibited good calibration and performed well in predicting spatial recurrence patterns,with an AUC value of 0.844(95%CI:0.749～0.914)in the training set and 0.706(95%CI:0.534～0.844)in the validation set.Conclusion Our multimodal radiomics model combined with intratumoral and peritumoral heterogeneity can predict the spatial pattern of locally recurrent HGGs,providing a basis for individualized treatment of HGGs.

BACKGROUND: Parental myopia is an important risk factor for myopia in Chinese children and adolescents. This study aimed to assess the influence of parental myopia and the severity of myopia on offspring and to evaluate whether adopting healthy lifestyles can mitigate the effects of parental myopia on offspring. METHODS: This cross-sectional study analyzed data from children and adolescents aged 6-17 years with complete vision assessments and parental history of myopia from six provinces in China during 2013-2014. Parental demographic information, children's outdoor activity time, sleep time, and sedentary time were collected via questionnaire. Parental myopia was classified as no myopia, paternal myopia, maternal myopia, and both. The offspring were categorized into 10 groups based on parental myopia prescription. Associations of the above factors with myopia in children and adolescents were evaluated by logistic regression analysis. RESULTS: Among 40,864 children and adolescents (50.3% boys and 49.7% girls), 22,537 (55.2%) were diagnosed with myopia. In comparison to offspring devoid of parental myopia, children with one parent affected by myopia exhibited odds ratio (OR) of 1.75 (95% confidence interval [CI]: 1.62-1.88) for myopia, while those with both parents affected showed OR of 2.27 (95% CI: 2.02-2.55) after adjusted for lifestyle factors. The likelihood of myopia in offspring increased with increasing severity of parental myopia, with a 3.08-fold increase in risk observed when both parents presented high myopia. Nonetheless, children adhering to two or more healthy lifestyle factors demonstrated a diminished risk of myopia compared with those with fewer than two lifestyle factors, especially among offspring of non-myopic or mildly myopic parents. CONCLUSIONS Parental myopia has a dose-dependent association with their offspring. Healthy lifestyles may reduce the impact of parental factors on myopia in offspring. The observed associations suggest that although the genetic burden of parental myopia cannot be ignored, healthy lifestyles and nurturing are also very important.
Humans ; Myopia/epidemiology* ; Child ; Male ; Female ; Adolescent ; Cross-Sectional Studies ; China/epidemiology* ; Parents ; Surveys and Questionnaires ; Risk Factors

Histone deacetylase 3 (HDAC3) is an epigenetic modification enzyme that plays a crucial role in the development and progression of diabetes and its complications. Studies have reported that increased HDAC3 activity is associated with pancreatic β-cell dysfunction in type 1 diabetes, while in type 2 diabetes, HDAC3 affects insulin resistance and signaling by regulating the metabolism of the liver, adipose tissue, and muscle. Additionally, HDAC3 plays a key role in diabetic complications such as cardiomyopathy, retinopathy, and nephropathy. Selective inhibition of HDAC3 has the potential to improve insulin sensitivity, reduce chronic inflammation, and enhance pancreatic cell function, offering a promising new therapeutic strategy for diabetes and its complications.

AIM: To investigate the correlation between the expression of serum lipocalin 2(LCN2), chemokine like receptor 1(CMKLR1), and C-C motif chemokine ligand 11(CCL11)and the severity of disease in patients with type 2 diabetes mellitus(T2DM)and dry eye(DE).METHODS:A prospective selection of 97 patients(194 eyes)diagnosed with T2DM and DE at our hospital from May 2022 to May 2024 was made as the DE group, which was further divided into mild(47 cases, 94 eyes), moderate(34 cases, 68 eyes), and severe(16 cases, 32 eyes)subgroups based on the severity of dry eye. Additionally, 97 patients(194 eyes)of T2DM without DE were selected as non-DE group, and 97 healthy volunteers(194 eyes)who underwent physical examination during the same period were chosen as control group. Serum levels of LCN2, CMKLR1, and CCL11 were measured in all participants. Spearman correlation analysis was used to assess the relationship between serum levels of LCN2, CMKLR1, and CCL11 and the severity of DE in T2DM patients; multivariate Logistic analysis was used to analyze the factors affecting the severity of T2DM patients with DE. The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum LCN2, CMKLR1 and CCL11 levels for moderate to severe dry eye in T2DM patients.RESULTS: Serum levels of LCN2, CMKLR1, and CCL11 increased progressively from the control group to the non-DE group and then to the DE group(all P<0.05). Within the DE group, these levels also increased progressively from the mild to moderate and then to the severe subgroups(all P<0.05). Spearman correlation analysis showed that serum levels of LCN2, CMKLR1, and CCL11 were positively correlated with the severity of disease(rs=0.604, 0.591, 0.559, respectively; all P<0.05). Stepwise forward multivariate Logistic analysis showed that Schirmer's test(SⅠt), tear break-up time(BUT), serum levels of LCN2, CMKLR1 and CCL11 were the factors affecting the severity of T2DM patients with DE; ROC curve analysis indicated that the combined diagnosis of serum LCN2, CMKLR1, and CCL11 for the progression of T2DM with DE to moderate-to-severe stages had an area under curve(AUC)value of 0.896, which was significantly higher than that of individual diagnoses of LCN2, CMKLR1, and CCL11(Z=2.925, 2.704, 3.483, respectively; P=0.003, 0.007, <0.001).CONCLUSION: Serum LCN2, CMKLR1 and CCL11 levels are increased in T2DM patients with DE, and are positively correlated with the severity of DE. The combination of the three has a high diagnostic value for moderate to severe DE.

AIM: To investigate the expression and clinical diagnostic value of toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: From January 2023 to June 2024, 104 dry eye patients(104 eyes, disease group)who visited our hospital and 100 healthy individuals(100 eyes, control group)who underwent physical examination were selected. The changes of TLR4 and NF-κB in conjunctival epithelial cells and tears were analyzed. Pearson analysis was applied to analyze the correlation between TLR4 and NF-κB expression in conjunctival epithelial cells and tears. Logistic analysis was applied to analyze the factors that affected dry eye. ROC was applied to analyze the diagnostic value of TLR4 and NF-κB expression in conjunctival epithelial cells and tears for dry eye.RESULTS: The differences in the use of eye drops, tear film break-up time(BUT), Schirmer's test(SⅠt), tear film thickness(TFT), and corneal fluorescein staining(CFS)scores between the disease group and the control group were statistically significant(all P<0.01). The expression levels of TLR4 and NF-κB in conjunctival epithelial cells and tears in the disease group were significantly higher than those in the control group(all P<0.01). There was a positive correlation between TLR4 and NF-κB in conjunctival epithelial cells and tears(r=0.392, 0.348, all P<0.05). Frequent use of eye drops, CFS score, TLR4, and NF-κB were risk factors for dry eye(OR=2.153, 3.183, 1.578, 2.452, all P<0.05), while BUT, SⅠt, and TFT were protective factors for dry eye(OR=0.654, 0.755, 0.276, all P<0.05). The sensitivity, specificity, and AUC of TLR4 combined with NF-κB in conjunctival epithelial cells in the diagnosis of dry eye were 86.54%, 81.00%, and 0.889, respectively. The combination of TLR4 and NF-κB had higher diagnostic value for dry eye than uncombined diagnosis(Zcombination-TLR4=3.506, P=0.001; Zcombination-NF-κB=3.165, P=0.002). The sensitivity, specificity, and AUC of TLR4 combined with NF-κB in tears for diagnosing dry eye were 82.69%, 70.00%, and 0.818, respectively. The combination of TLR4 and NF-κB in tears had higher diagnostic value for dry eye than uncombined diagnosis(Zcombination-TLR4=3.117, P=0.002; Zcombination-NF-κB=2.363, P=0.018).CONCLUSION: The expression levels of TLR4 and NF-κB in conjunctival epithelial cells and tears of patients with dry eye are elevated. TLR4 and NF-κB are related to the development of dry eye, and that elevated levels of both are associated with an increased risk of dry eye disease. The combination of TLR4 and NF-κB has a certain diagnostic significance for dry eye.