AIM:To automatically identify and quantitatively assess myopia-related fundus structural changes by combining non-mydriatic color fundus photography with an artificial intelligence(AI)-powered quantitative fundus analysis system and to further analyze the correlations between these fundus parameters and spherical equivalent(SE), axial length(AL), and age, providing the objective basis for monitoring myopia progression and supporting the formulation of personalized myopia prevention and control strategies. METHODS:A cross-sectional study was conducted enrolling myopic patients aged 18-50 y who underwent myopia screening from March 2023 to December 2023. Patients were stratified into three groups based on SE: the -3.00 D

Objective::To systematically study the mechanisms by which Yinzhihuang (YZH), a traditional Chinese medicine, ameliorates intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with significant maternal and fetal complications.Methods::This experimental study was conducted from January 2024 to August 2024, utilizing data from public databases (Traditional Chinese Medicine Systems Pharmacology, GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Proteome Xchange) alongside in vitro cell culture experiments. Network pharmacology identified active components of YZH and potential therapeutic targets for ICP. Ultra-performance liquid chromatography–mass spectrometry characterized YZH oral liquid, and its effective doses were evaluated in taurocholic acid (TCA)-induced HTR-8/SVneo cells, an in vitro ICP model. ICP-related targets were gathered from multiple databases, and hub genes were selected through bioinformatics and previously identified differentially expressed proteins. Functional annotation and pathway enrichment analyses were conducted, with validation in TCA-induced cells treated with various YZH concentrations (0.1%–5.0%) compared to controls. Molecular docking confirmed predicted interactions.Results::Using network pharmacology, 104 active compounds and 241 potential targets of YZH were identified. Integration of multiple databases yielded 1897 YZH-related therapeutic targets and 3783 ICP-associated genes. Proteomic analysis identified 227 differentially expressed proteins, from which 10 hub genes were selected; among these, APOA2, COL1A1, and ADIPOQ were significantly upregulated in ICP samples. UPLC-ESI-MS/MS detected 2022 compounds, predominantly flavonoids (25.07%, 507/2022) and phenolic acids (14.44%, 292/2022). Molecular docking demonstrated strong binding affinities between several active compounds and the hub genes. In TCA-induced HTR-8/SVneo cells, 0.5% YZH treatment significantly enhanced cell viability and modulated hub gene expression, supporting a potential multi-target mechanism.Conclusion::This study systematically explored the active components and potential targets of YZH in ICP through network pharmacology, proteomics, and in vitro validation. The findings suggest that YZH may act via the PPAR signaling pathway by modulating genes such as PPARA, PPARG, ADIPOQ, and APOA2.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals ; NF-kappa B/metabolism* ; Temporomandibular Joint Disorders/pathology* ; Temporomandibular Joint Disc/metabolism* ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Collagen/metabolism* ; Cells, Cultured ; Joint Dislocations/pathology* ; Interleukin-1beta ; Arthritis, Experimental

AIM: To investigate the efficacy of pars plana vitrectomy(PPV)with or without inner limiting membrane(ILM)peeling in refractory diabetic macular edema.METHODS:Totally 80 patients with refractory diabetic macular edema were retrospectively selected and assigned into groups according to the treatment method. Among them, 38 patients treated with PPV were included as group A, and 42 patients treated with PPV combined with ILM peeling were included as group B. The relevant data of patients in the two groups were collected, and the efficacy of the two groups was compared.RESULTS: At 1, 3, and 6 mo after surgery, the best corrected visual acuity(BCVA), central macular thickness(CMT), and severity of macular edema in the group B were all superior to those in the group A(all P<0.05). At 6 mo after the surgery, the incidence of complications in the group B was 12%, with no prominent difference compared to 18% of the group A(P>0.05).CONCLUSION:PPV combined with or without ILM peeling can improve visual function and relieve macular edema in patients with refractory diabetic macular edema. However, the combination of PPV and ILM peeling is superior to PPV alone in improving vision and relieving macular edema, and does not increase postoperative complications.

Objective To investigate the relationship between the serum red blood cell distribution width(RDW)to albumin(ALB)ratio,the expression of family with sequence similarity 19 member A5(FAM19A5)and leukocyte cell-derived chemotaxin 2(LECT2)with the glucose and lipid metabolism indexes in type 2 diabetes mellitus(T2DM)patients with metabolic syndrome(MS).Methods A total of 119 patients with T2DM were selected as the study group,and patients were divided into the MS group(67 cases)and the non-MS group(52 cases)based on whether they were complicated with MS.Meanwhile,93 healthy individuals who underwent physical examinations in our hospital during the same period were selected as the control group.RDW was detected by an automatic blood cell analyzer,and ALB was detected by an automatic biochemical analyzer.The ratio of RDW to ALB(RAR)was calculated.The serum levels of FAM19A5 and LECT2 were detected by enzyme-linked immunosorbent assay(ELISA).The correlation between serum and glycolipid metabolism indicators was analyzed by Pearson's method.The diagnostic value of serum RAR,FAM19A5 and LECT2 for MS in T2DM patients was analyzed by receiver operating characteristic(ROC)curve.Results Compared with the control group,the study group exhibited significantly higher levels of total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),serum RAR,FAM19A5 and LECT2,while high-density lipoprotein cholesterol(HDL-C)was significantly lower(P＜0.05).Compared to the non-MS group,body mass index(BMI),duration of T2DM,history of hypertension,blood pressure,waist circumference,TG,fasting insulin(FINS),FBG,glycated hemoglobin(HbA1c),homeostasis model assessment-insulin resistance(HOMA-IR),serum RAR,FAM19A5 and LECT2 were significantly increased,and HDL-C was decreased in the MS group(P＜0.05).Serum RAR,FAM19A5 and LECT2 were positively correlated with TG,FINS,FBG,HbA1c and HOMA-IR,and which was negatively correlated with HDL-C(P＜0.05).The area under the curve(AUC)for the diagnosis of T2DM patients with MS using RAR,FAM19A5 and LECT2 individually were 0.821,0.807 and 0.793,respectively,and the combined AUC was 0.952,indicating that the combined diagnostic efficacy of RAR,FAM19A5 and LECT2 was superior to their individual efficacies(P＜0.05).Conclusion Serum levels of RAR,FAM19A5 and LECT2 are elevated in T2DM patients with MS.These biomarkers exhibit a strong association with indices of glucose and lipid metabolism.The combination of these three markers has significant clinical diagnostic value for T2DM patients with MS.

The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.

Objective To summarize the potential risk factors that may arise in the national drug sampling and testing inspection process in recent years,to focuse on the operation of the quality management system,and to put forward proposals on how to do a good job under the new drug regulatory model of sampling and testing work.Methods Focusing on the investigation of data integrity and authenticity,the analysis focuses on the analysis of risk points such as reagent management,standard substance management,instrument,and facility management,electronic data management and other issues,and carries out a comprehensive verification of the effectiveness of the operation of the quality management system and so on.Results National drug sampling and testing institutes should strengthen the overall quality management,according to the operation of the laboratory,combined with their respective risk characteristics,reagent management,standard substance management,instrument and facility management,electronic data management and other aspects of the risk of systematic sorting and the establishment of the risk alert function,the development of risk warning lists,and the implementation of the corresponding risk control strategy.Conclusion National drug sampling and testing institutes must strengthen the operation of the process of influencing factors in the effective control of the emphasis on the testing of the work of the key control points and continue to standardize and improve the inspection process of the quality system to ensure that the quality of the various activities in a controlled state.