AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.

ObjectiveAutoimmune thyroiditis （AIT） is a complex and immune-mediated disorder， with no established treatment protocol. Both Western and traditional Chinese medicine （TCM） focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM， using a novel evaluation method. Additionally， it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models， using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM， and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization， iodine induction， heterologous thyroid antigen immunization， and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%， 60%， 54%， and 63%， with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common， with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory， meeting the surface and structural effectiveness criteria of Western medicine. However， there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine， with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine， creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM， providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female

Objective:To investigate the repair effect of bone marrow mesenchymal stem cells(BMSCs)on interferon gamma(IFN-γ)induced ovarian granulosa cell immune injury.Methods:A model of IFN-γ-induced ovarian granulosa cell immune injury was estab-lished.KGN cells after modeling were co-cultured with human BMSCs(hBMSCs)and divided into three groups:negative control(NC)group,IFN-γ group,and BMSC group.After co-culture,cell proliferation was determined by a cell counting kit 8 assay for 3 consecu-tive days.Cell apoptosis was determined using an Annexin V-FITC apoptosis detection kit and a CytoFLEX flow cytometer.The estra-diol level and the mRNA expression levels of aromatase CYP19A1 and FSHR were measured to evaluate the hormone synthesis ability.The level of lactate dehydrogenase(LDH),mRNA expression levels of NLRP3,caspase-1(CASP1),and interleukin-1β,and protein expression levels of NLRP3,CASP1,and gasdermin-D were determined to evaluate cell pyroptosis.Results:The proliferation rate of granulosa cells in the IFN-γ group and the BMSC group was lower than that in the NC group at 24 h,48 h and 72 h,and that in the IFN-γ group was lower than that in the BMSC group(P<0.001).The number of apoptotic granulosa cells in the INF-γ group and the BMSC group was higher than that in the NC group,and that in the INF-γ group was higher than that in the BMSC group(P<0.001).The estradiol level in the INF-γ group and the BMSC group was lower than that in the NC group,and that in the INF-γ group was lower than that in the BMSC group(P<0.001).Compared with the IFN-γ group,the mRNA expression of CYP19A1 and FSHR in the BMSC group decreased(P<0.001).Compared with the IFN-γ group,the BMSC group had significantly decreased LDH level,mRNA expression levels of NLRP3 and CASP1,and protein expres-sion level of CASP1.Conclusion:hBMSCs repair the immune in-jury of KGN cells induced by IFN-γ by restoring cell proliferation,inhibiting cell apoptosis,repairing endocrine function,and reducing pyroptosis.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Objective To investigate the effect and molecular mechanism of safflower yellow(SY)on wound healing of diabetic foot ulcer(DFU)in mice.Methods Forty-five C57BL/6 mice were injected intraperitoneally with streptozotocin to establish diabetic models.The diabetic mice were randomly divided into the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with insulin-like growth factor-1(IGF-1)group,with 9 mice in each group.Before modelling,mice in the model group were not given any intervention,mice in the low-dose SY intervention group and high-dose SY intervention group were injected intraperitoneally with 5 and 20 mg·kg-1 SY,respectively,and mice in the high-dose SY combined with IGF-1 group were injected intraperitoneally with 20 mg·kg-1 SY and 0.03 mg·kg-1 IGF-1.Except for the sham operation group,the DFU model was established by incising the dorsal skin of the foot in the remaining four groups of mice.No wound on the dorsal skin of the foot was made in the sham operation group,and the remaining surgical steps were the same as those in the model group.The body mass of mice in each group was measured on day 14 after modelling using an electronic scale,tail vein blood was collected for fasting blood glucose measurement,and the wound width was measured using a small vernier caliper.Then,the mice were executed to collect the wound tissues.Hematoxylin-eosin staining was used to detect the histopathological changes in the wound tissues of mice in each group.Reverse transcription-quantitative real-time polymerase chain reaction was used to measure the relative expression levels of platelet-derived growth factor(PDGF),vascular endothelial growth factor(VEGF),alpha-smooth muscle actin(α-SMA),type Ⅰ collagen(collagen Ⅰ),protein tyrosine phosphatase 1B(PTP1B)and advanced glycation end products(AGEs)mRNA in the wound tissues of mice in each group.Western blot was used to detect the relative expression levels of proliferation marker Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-associated proteins(caspase-3,caspase-6,and caspase-7),p85 phosphatidylinositol-3-kinase(PI3K)and phosphorylated protein kinase B(p-AKT)protein in the wound tissues of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the wound tissues of mice in each group.Results The differences in blood glucose and body mass of mice among the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with IGF-1 group were not statistically significant(P＞0.05).The healing rate of wound tissues in the high-dose SY intervention group was significantly greater than that in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the healing rate of wound tissues among the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＞0.05).In the high-dose SY intervention group,a large number of collagen fibers were densely and orderly arranged in the wound tissues,accompanied by a large number of neovessels;in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group,the wound tissues were sparsely populated with collagen fibers,accompanied by a small number of neovessels.The relative expression levels of PDGF,VEGF,α-SMA and collagen Ⅰ mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expression levels of PTP1B and AGEs mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).The relative expression levels of PDGF,VEGF,α-SMA,collagen Ⅰ,PTP1B and AGEs mRNA showed no statistically significant difference among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The relative expression levels of Ki-67 and PCNA protein in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expre-ssion levels of caspase-3,caspase-6,caspase-7,p85 PI3K,and p-AKT protein were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the relative expression levels of Ki-67,PCNA,caspase-3,caspase-6,caspase-7,p85 PI3K and p-AKT protein among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＜0.01).There was no statistically significant difference in the levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the model,low-dose SY intervention and high-dose SY combined with IGF-1 groups(P＞0.05).Conclusion High-dose SY intervention promotes DFU wound healing in mice by increasing angiogenesis,collagen formation and cell proliferation and reducing insulin resistance,inflammatory response and cell apoptosis,which may be related to the inhibition of the PI3K/AKT pathway.