Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

Objective: To explore the associations between caregivers nutrition literacy and pediatric nonalcoholic fatty liver disease (NAFLD), so as to provide scientific evidence for the key contents of family intervention measures. Methods: In September 2022, a study involving 1 609 thirdgrade students and their caregivers from six schools in Yinzhou, Haishu, and Zhenhai Districts of Ningbo City, Zhejiang Province, was conducted. Venous blood samples were collected to measure lipid profiles and investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) among the children. Family Food Environment Questionnaire was used to assess the nutrition literacy levels of the caregivers. Generalized linear regression analysis was employed to explore the correlation between caregivers nutrition literacy levels and the prevalence of NAFLD in children. Results: Among the surveyed students, 191 were in the NAFLD group, whereas 1 418 were in the nonNAFLD group. The median nutrition literacy score of caregivers in the NAFLD group and nonNAFLD group all were 11.00 (9.00,12.00), which was not significantly different (Z=-0.40, P=0.71). The generalized linear regression results revealed that the level of nutrition literacy of caregivers had no significant effect on childrens Triglyceride-glucose (TyG) index and Triglyceride-glucose-Waisttoheight ratio (TyG-WHtR) [β(95%CI) were 0.001(-0.005-0.006) and 0.000(-0.014-0.014), P>0.05]. Conclusions The nutrition literacy level of caregivers has no significant correlation with the direct incidence of NAFLD in children. As for family intervention measures, it is necessary not only to improve the nutrition literacy level of caregivers but also to effectively apply nutritional knowledge in practice to optimize health management.

Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

AIM: To explore the effects of preoperative anterior segment parameters on the rotational stability of Toric intraocular lens(Toric IOL).METHODS:Prospective study. A total of 41 cataract patients(54 eyes)with combined corneal regular astigmatism from March to December 2023 were included and treated with cataract phacoemulsification combined with plate loop Toric IOL implantation in the Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University. The rotation degree of Toric IOL and uncorrected distance visual acuity(UCDVA)were evaluated at 1 d, 2 wk, and 1 mo postoperatively, the corrected distance visual acuity(CDVA)was evaluated at 2 wk and 1 mo after surgery, and the decentration and tilt of the Toric IOL were assessed at 2 wk postoperatively.RESULTS:A total of 33 patients(40 eyes)were included in this study. The UCDVA(LogMAR)of 1 d, 2 wk and 1 mo postoperatively were 0.10(0.10, 0.30), 0.05(0, 0.10)and 0(0, 0.10), respectively, which was improved compared with the preoperative levels of [0.80(0.49, 1.00)](P<0.001). The CDVA(LogMAR)of 2 wk and 1 mo postoperatively were 0.05(0, 0.15)and 0(0, 0.138), respectively, which was improved compared with preoperative levels of [0.52(0.40, 0.80)](P<0.001). The residual astigmatism of 2 wk and 1 mo postoperatively were 0.625(0.25, 0.75)D and 0.50(0.25, 0.75)D, respectively, which was significantly reduced compared with preoperative astigmatism of [1.82(1.31, 2.59)D](P<0.001). The preoperative anterior segment length(ASL), and lens thickness(LT)were positively correlated with Toric IOL rotation degree at 1 d(rs=0.463, P=0.003; rs=0.340, P=0.032)and 2 wk(rs=0.520, P=0.001; rs=0.409, P=0.009)postoperatively. At 1 mo postoperatively, only ASL was positively correlated with Toric IOL rotation degree(rs=0.463, P=0.003). The results of linear regression analysis showed that preoperative ASL was a predictor of rotation degree at 1 d, 2 wk and 1 mo after surgery(F1 d=10.098, P1 d=0.003; F2 wk=16.915, P2 wk<0.001; F1 mo=10.957, P1 mo=0.002). The rotation degree of Toric IOL was positively correlated with lens decentration(rs=0.360, P=0.043).CONCLUSION:The early postoperative rotation of Toric IOL is positively correlated with ASL, and the rotation is also positively correlated with lens decentration.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Objective: To understand the latent categories of sleep disturbances among children and adolescents with neurodevelopmental disorders (NDDs) in Tianjin and their relationship with behavioral and social issues, so as to provide a basis for preventing and improving sleep disturbances in the population. Methods: From September 2021 to June 2024, 272 children and adolescents aged 2-23 years with neurodevelopmental disorders were recruited from special education schools and designated rehabilitation institutions in Tianjin. Sleep disturbances were assessed using the Children s Sleep Habits Questionnaire (CSHQ). Behavioral and social issues and severity were evaluated using the Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS). Latent class analysis (LCA) was employed to categorize the subjects into different sleep disturbances categories. Cochran- Armitage test was used to analyze the trend of detection rate of sleep disturbances in different age groups. Spearman rank correlation was used to analyze the correlation between the scores of each scale. The generalized linear model was used to analyze the influence of CARS and ABC scale scores. Covariance analysis was used to examine differences in behavioral and social issues among the different categories. Results: Among 272 survey respondents, a total of 197(72.4%) children and adolescents with NDDs were identified with sleep disturbances. The detection rates of sleep disturbances were 88.9% for those aged 2-6 years, 70.6% for aged 7-12, 66.7% for aged 13-18 and 50.0% for 19-23 years old, which was decreased across age group ( Z =3.58, P <0.01). There was a positive correlation between the total CSHQ score and the total ABC score ( r=0.16, P =0.01). The generalized linear model analysis showed that after adjusting age, gender, parents education level and family monthly income, bedtime habit ( β =3.60) and sleeping latency disorder ( β =3.36) were positively correlated with CARS scores, while the bedtime habit ( β =16.73) and waking up at night ( β =17.46) were positively correlated with ABC scores ( P <0.05). LCA revealed that sleep disturbances in children and adolescents with NDDs could be classified into four categories. The covariance analysis results showed that there were statistically significant differences in the average scores of CSHQ (70.84±9.05, 50.96±6.64, 50.33±5.82, 43.84±5.44) and ABC (49.44± 39.34 , 53.04±39.75, 63.51±40.31, 38.14±34.23) among different categories of all partipants ( F=92.09, 3.95, P <0.05). Conclusion Sleep disturbances in children and adolescents with NDDs are severe and exhibit distinct categorical characteristics.

ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.