ObjectiveTo establish a mouse model of particulate matter 2.5 （PM_2.5）-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM_2.5-induced ocular surface damage by regulating the reactive oxygen species （ROS）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop （0.1 mL） of 5 g·L^-1 PM_2.5 suspension in both eyes， four times daily. Successfully modeled mice were randomized into four groups （n=10）： Model， p38 MAPK inhibitor， Chufeng Yisuntang， and combination （Chufeng Yisuntang at 7.3 g·kg^-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg^-1）. Chufeng Yisuntang was administered via gavage， and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion， tear film break-up time， and corneal fluorescein staining were assessed. After intervention for 4 weeks， hematoxylin and eosin （HE） staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum levels of ROS， malondialdehyde （MDA）， superoxide dismutase （SOD） 1， and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels， respectively， of p38 MAPK， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific proteinase-3 （Caspase-3） in the corneal tissue. ResultsCompared with the control group， the model group exhibited reduced tear secretion volume and tear film breakup time， along with increased corneal fluorescein staining scores （P<0.01）. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group demonstrated increased tear secretion volume and tear film breakup time， along with decreased corneal fluorescein staining scores （P<0.01）. HE staining revealed that compared with the control group， the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness， along with reduced meibomian gland acini and intensely stained， densely packed nuclei around the acini. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group showed intact corneal structure， improved cell morphology， and reduced damage severity. ELISA revealed elevated ROS and MDA levels （P<0.01） and decreased SOD1 and SOD2 levels （P<0.01） in the model group compared with the control group. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination lowered ROS and MDA levels （P<0.01）， while raising SOD1 and SOD2 levels （P<0.05， P<0.01）. Western blot revealed that compared with the control group， the model group exhibited increased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and reduced protein level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the protein level of Bcl-2 （P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and increased protein level of Bcl-2 （P<0.01）. Real-time PCR revealed that compared with the control group， the model group exhibited upregulated mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， and downregulated mRNA level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the mRNA level of Bcl-2 （P<0.05， P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased mRNA levels of p38 MAPK， Bax， and Caspase-3 expression （P<0.05， P<0.01） and increased mRNA level of Bcl-2 （P<0.01）. ConclusionChufeng Yisuntang may partially protect against PM_2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway， enhancing antioxidant defense， and reducing epithelial apoptosis.

AIM: To evaluate safety, efficacy, visual quality, and patient satisfaction after optimized monovision Q-value-customized femtosecond laser-assisted in situ keratomileusis(FS-LASIK)for myopia, astigmatism, and presbyopia. METHODS: This prospective study enrolled patients suffering myopia, astigmatism, and presbyopia. At 1 y post operation, uncorrected distance, intermediate and near visual acuity(UDVA, UIVA, UNVA), refraction, corneal higher order aberrations(HOAs), Q value, objective visual quality, and near stereoacuity were evaluated. The impact of surgery on patients' living quality and their satisfaction were evaluated based on National Eye Institute Refractive Error Quality of Life Instrument(NEI RQL)scores at 1-year follow-up.RESULTS:The study enrolled 36 patients(72 eyes)including 12 males(33%)and 24 females(67%)with an average age of 46.03±3.60(range 40-53)y. One year postoperatively, 97% of patients achieved binocular UDVA of 1.0 or better, 89% achieved UIVA of 0.63 or better, and 97% achieved UNVA of 1.0 or better. The spherical equivalent refraction(SE)in dominant eye within ±1.00 D was 100%. SE in non-dominant eyes was uncorrected compared with the preoperative target correction, with a mean difference of -0.27±0.34 D before and after surgery(P<0.001). while in the non-dominant eyes, the anterior corneal Q-value within the 5 mm zone increased negatively compared with the preoperative value(-0.33±0.24 vs -0.21±0.09, P<0.001). In the non-dominant eye, spherical aberration and longitudinal spherical aberration were lower than preoperative values(both P<0.001). Besides, there were no significant changes in objective scatter index(OSI), modulation transfer function cutoff frequency(MTF cut off)and Strehl ratio(SR)in both dominant and non-dominant eyes(all P>0.05), and the near stereoacuity was better after surgery(P=0.007). Additionally, the patient satisfaction rate with the surgery was 94%, the satisfaction rates for UDVA and UNVA were both 98%. The 11% of patients required to wear low-diopter glasses when driving at night.CONCLUSION:Optimized monovision Q-value-customised FS-LASIK is a safe and effective procedure for correcting myopia, astigmatism, and presbyopia. It provides favorable subjective and objective visual quality and high patient satisfaction. The under correction in non-dominant eyes is observed, indicating the further optimization of nomogram is needed.

OBJECTIVE To investigate the effects and potential mechanism of Panax notoginseng saponins （PNS） on gastric mucosal injury and inflammatory response in rats with chronic atrophic gastritis （CAG） via the stem cell factor（SCF）/cellular tyrosine kinase receptor（c-kit） signaling pathway. METHODS Male SD rats were used to establish a CAG rat model through intragastric administration of N -methyl- N ′-nitro- N -nitrosoguanidine combined with an irregular diet. Successfully modeled rats were randomly divided into a model group， positive control-vitacoenzyme group （Positive group， 250 mg/kg）， PNS low- and high-dose groups （PNS-L and PNS-H groups， 9， 18 mg/kg）， and high-dose PNS+SCF/c-kit inhibitor group （PNS-H+ISCK03 group， 18 mg/kg+47 mg/kg）， with 8 rats in each group. Additionally， 8 healthy rats were selected as a control group. After the final administration， the activities of serum gastrin （GAS）， motilin （MTL） and pancreatic polypeptide （PP）， as well as the levels of tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and IL-8 in gastric mucosal tissues， were measured in each group. Pathological changes of the gastric mucosal and ultrastructure of the epithelial cells were observed， and gastric mucosal atrophy was scored. Cell apoptosis in gastric mucosal tissues and the expressions of proliferating cell nuclear antigen （PCNA）， nuclear factor-κB p65 （NF-κB p65）， SCF and c-kit were detected. RESULTS Compared with the control group， the model group showed significantly increased inflammatory cell infiltration in the gastric mucosal， extensive epithelial cell detachment， severe ultrastructural damage， and significantly elevated or up-regulated gastric mucosal atrophy score， TNF-α and IL-8 levels in gastric mucosal， cell apoptosis rate， and NF-κB p65 protein expression. Meanwhile， serum levels of GAS and MTL， PP activity， the level of IL-10 in gastric mucosal tissue， and protein expressions of PCNA and SCF， as well as the phosphorylation level of c-kit， were significantly decreased or down-regulated （ P ＜0.05）. Compared with the model group， Positive， PNS-L and PNS-H groups exhibited markedly improved pathological changes in the gastric mucosal and significant amelioration of the quantitative indicators， with the PNS-H group showing significantly better improvement than the PNS-L group （ P ＜0.05）. However， ISCK03 significantly reversed the ameliorative effects of high-dose PNS on the above indicators in rats （ P ＜0.05）. CONCLUSIONS PNS improves gastric mucosal injury in CAG rats by reducing the inflammatory response and promoting gastric mucosal repair； these effects may be related to the activation of the SCF/c-kit signaling pathway.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

AIM:To evaluate the clinical efficacy of 0.05% cyclosporine eye drops(Ⅱ)combined with sodium hyaluronate eye drops in treating patients with type 2 diabetes mellitus(T2DM)and moderate-to-severe dry eye.METHODS:A total of 120 T2DM patients(120 eyes)with moderate-to-severe dry eye, treated at the endocrinology and ophthalmology departments at the Affiliated Hospital of Xuzhou Medical University from January 2024 to September 2024, were enrolled in the study. The patients were randomly divided into two groups: combination group [0.05% cyclosporine eye drops(Ⅱ)+ sodium hyaluronate eye drops] and control group(sodium hyaluronate eye drops alone), with 60 cases(60 eyes)in each group. Assessments were conducted at baseline and at 1, 2, and 3 mo post-treatment, including the ocular surface disease index(OSDI), non-contact tear meniscus height(NITMH), first non-invasive tear breakup time(NIBUTf), meibomian gland loss score, lipid layer thickness grade, conjunctival hyperemia grade, and corneal fluorescein staining(FL)score. At 3 mo after treatment, changes in tear inflammatory factors were observed, and corneal subbasal nerve plexus(SBN)morphology/density were analyzed using in vivo confocal microscopy(IVCM).RESULTS:At 1, 2, and 3 mo post-treatment, both groups showed statistically significant increases in NITMH and NIBUTf compared to baseline(all P<0.05), with greater improvement observed in the combination group(both P<0.05). OSDI and FL scores significantly decreased from baseline(all P<0.05), with more pronounced reductions in the combination group(both P<0.05). Meibomian gland loss scores showed no significant improvement in either group(all P>0.05). At 3 mo after treatment, tear levels of interleukin 6(IL-6)and matrix metalloproteinase-9(MMP-9)significantly decreased in both groups(all P<0.001), with a greater reduction noted in the combination group(both P<0.001). The combination group displayed increased corneal nerve branch density and nerve fiber density, along with decreased nerve tortuosity and dendritic cell(DC)density compared to baseline(all P<0.001), while the control group did not show significant changes(all P>0.05).CONCLUSION: The combination of 0.05% cyclosporine eye drops(Ⅱ)and sodium hyaluronate eye drops significantly improves clinical outcomes in T2DM patients with moderate-to-severe dry eye. This treatment effectively alleviates ocular surface inflammation, restores corneal nerve morphology and density, and demonstrates a favorable safety profile.

AIM: To explore the risk factors associated with diabetic retinopathy(DR)based on ultra-widefield swept-source optical coherence tomography angiography(UWF-SS-OCTA), and to establish a clinical prediction model.METHODS:A total of 235 patients(235 eyes)with type 2 diabetes mellitus who were treated in the Affiliated Hospital of Xuzhou Medical University from July to November 2024 were selected as the research objects. According to the presence or absence of DR, they were divided into 120 cases(120 eyes)in non-DR group(NDR group)and 115 cases(115 eyes)in non-proliferative DR group(NPDR group). Data on general characteristics, laboratory tests, and OCTA results were collected for both groups. Univariate analysis was employed to identify DR-related risk factors. Logistic regression analysis was conducted to analyze these risk factors and to establish a DR prediction model. The efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).RESULTS: The duration of diabetes, fasting blood glucose, blood urea nitrogen(BUN), history of hypertension, and the choroidal vascular index(CVI)were found to be statistically significant in the model(all P<0.05). Specifically, the duration of diabetes, fasting blood glucose, BUN, and history of hypertension were identified as risk factors for DR among diabetic patients, while CVI was recognized as a protective factor. The area under the curve for the model predicting the probability of DR was 0.898(0.859-0.938), with a diagnostic threshold of 0.438. The corresponding sensitivity and specificity were 87.8% and 78.3%, respectively, indicating that the model possesses high predictive value for the occurrence of DR.CONCLUSION: The duration of diabetes, fasting blood glucose, BUN, history of hypertension, and CVI are significantly correlated with DR. The established prediction model demonstrates a substantial screening capability for DR.

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL