ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Endothelial dysfunction induced by inflammation and oxidative stress represents a critical pathological mechanism in cardiovascular and cerebrovascular diseases, including sepsis and atherosclerosis. Although crebanine has been reported to possess antiinflammatory and analgesic properties, its effects on inflammation and oxidative stress in endothelial cells remain unknown. In this study, we assessed cell viability, apoptosis, and migration using the Cell Counting Kit-8 (CCK-8), flow cytometry, and a wound healing assay, respectively. The levels of reactive oxygen species (ROS) and the expression of inflammatory and oxidative stress markers were determined by qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and Western blotting analysis. Our results demonstrated that crebanine alleviated lipopolysaccharide (LPS)-induced apoptosis and dysfunction in human umbilical vein endothelial cells (HUVECs). Crebanine treatment inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and malondialdehyde (MDA), while it enhanced the activity of the antioxidant enzyme superoxide dismutase (SOD). Mechanistically, crebanine suppressed LPS-induced activation of the NF-κB signaling pathway in HUVECs. Furthermore, the improvement effect of crebanine on the inflammation and dysfunction in LPS-treated HUVECs was reversed by diprovocim, an NF-κB activator.These findings suggest that crebanine ameliorates LPS-induced inflammation and oxidative stress in HUVECs by inhibiting the NF-κB signaling pathway, indicating its potential therapeutic value for treating vascular endothelial dysfunction-related diseases.

Rheumatoid arthritis （RA） is an autoimmune disease characterized by chronic synovial inflammation and joint destruction， with a complex pathogenesis. Macrophage polarization plays a pivotal role in disease progression. Recent studies demonstrate that microRNA （miRNA）， as critical post-transcriptional regulators， can participate in the inflammatory response process by regulating the polarization state of macrophages， thereby aggravating RA joint damage. This review summarizes the mechanism of action of various miRNA in regulating macrophage polarization， and emphasizes their potential therapeutic value in RA.

Objective To explore the predictive value of artificial intelligence (AI)-based lung nodule CT quantitative analysis for the invasion degree of lung adenocarcinoma spectrum lesions. Methods According to the invasion degree of lung adenocarcinoma spectrum lesions, patients with surgically and pathologically confirmed lung adenocarcinoma spectrum lesions from January to June 2023 in Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University were retrospectively collected and divided into a non-invasive group and an invasive group, including atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma patients in the non-invasive group, and invasive adenocarcinoma patients in the invasive group. All enrolled patients underwent chest CT before surgery, and then the lung nodules were quantitatively analyzed using an AI-based computer-aided diagnosis system to compare the related quantitative parameters of lung nodules that have been surgically removed and pathologically confirmed as lung adenocarcinoma spectrum lesions between the two groups. The relationship between various CT quantitative features and the invasion degree of lung adenocarcinoma spectrum lesions was analyzed. Results A total of 149 patients (149 lesions) were included, including 42 males and 107 females, aged 29-81 (56.35±10.75) years. There were 72 patients in the non-invasive group and 77 patients in the invasive group. Statistical differences were observed between the two groups in long diameter, short diameter, volume, surface area, mass, maximum cross-sectional area, 3D long diameter, maximum CT value, minimum CT value, average CT value, entropy, kurtosis, skewness, malignancy probability and other indicators (P<0.05). Multivariate binary logistic regression analysis showed that long diameter [OR=1.687, 95%CI (1.364, 2.085), P<0.001], average CT value [OR=1.006, 95%CI (1.002, 1.009), P=0.002], and malignancy probability [OR=1.034, 95%CI (1.005, 1.063), P=0.020] were independent risk factors for the invasion degree of lung adenocarcinoma. The predictive model combining the above parameters demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.951, sensitivity of 0.818, and specificity of 0.972. Using a Nomogram to quantify the three independent risk factors, the cross-validation was performed to evaluate the stability of the model, and the average C-index of cross-validation was 0.950, with each fold C-index >0.75, indicating that the prediction performance of the model was stable, and the calibration curve and decision curve indicated good predictive performance. Conclusion The visualization prediction model constructed by AI-based quantitative analysis of lung nodules in CT demonstrates significant discriminative effectiveness in the assessment of invasiveness in lung adenocarcinoma spectrum lesions. This visualization prediction model can provide a quantitative decision-making basis for the preoperative identification of the degree of invasiveness in lung adenocarcinoma spectrum lesions.

Objective To investigate the effect of G9a histone methyltransferase inhibitor BIX01294 on the proliferation of vascular smooth muscle cell(VSMC)and its underlying mechanism.Methods Twelve SD rats were divided into the control group and the treatment group,with 6 rats in each group.The rats were anesthetized by intraperitoneal injection with sodium pentobarbital,then exposed the common carotid artery and the internal and external carotid artery after disinfection and skin preparation,ligated the distal end of the internal and external jugular veins,clamped the proximal end of the common carotid artery,cut the external carotid artery,inserted the balloon catheter,blocked the blood flow by compression,and ligated the proximal end of the external carotid artery after withdrawing the balloon.The common carotid artery clamping state of rats in the treatment group was maintained after withdrawing the balloon,then restored the blood flow after perfusion with 100 μmol/L BIX01294 solution for 30 seconds;rats in the control group were restored the blood flow after perfusion with PBS for 30 seconds.VSMC were divided into the normal group and the BIX01294 groups.Cells in the normal group were cultured in low glucose medium containing 2%fetal bovine serum,and cells in the BIX01294 groups were co-treated with 2.5,5.0,7.5 and 10.0 μmol/L BIX01294 on the basis of the normal group,respectively.CCK-8 assay and EDU assay were used to detect the cell activity and proliferative ability respectively,to screen appropriate concentration of BIX01294.The cell apoptosis was detected by TUNEL assay between the normal group and the BIX01294 group,and the control group and the treatment group.Western blot was used to detect the expression levels of autophagy-and apoptosis-related proteins in the normal group and BIX01294 group.Results Compared with 0 μmol/L,the activity and proliferative ability of VSMC decreased in a concentration-dependent manner after treatment with BIX01294 at different concentrations(P<0.05).Compared with the normal group,the apoptosis level of VSMC in the BIX01294 group was increased(P<0.05),the expression of VSMC autophagy-and apoptosis-related proteins of LC3Ⅰ/Ⅱ and Bax were up-regulated(P<0.05),and the expression of Bcl-2 and p62 proteins were down-regulated(P<0.05).In vivo test results showed that BIX01294 local perfusion aggravated the apoptosis of carotid VSMC.Conclusion BIX01294 activates VSMC autophagy and apoptosis and inhibits its proliferation.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Objective:Multi-drug resistant bacterial infection（MRSA） complications occurring in cochlear implant recipients is rare and of serious consequence. This paper aimed to summarize the treatment experience of a patient with MRSA infection after cochlear implantation. A patient with nasopharyngeal malignant tumor after radiotherapy developed to severe sensorineural deafness. She suffered MRSA infection nine days after cochlear implantation. Since the wound failed to heal after weeks of topical and systemic sensitive antibiotic therapy, the patient underwent surgery for wound debridement. The stimulator-receiver and the electrode of the implant was removed, negative pressure wound therapy was applied, and systemic anti-infection treatment with sensitive antibiotics for weeks, the patients recovered and was discharged from hospital 69 days after infection.
Humans ; Cochlear Implantation/adverse effects* ; Female ; Drug Resistance, Multiple, Bacterial ; Staphylococcal Infections/therapy* ; Methicillin-Resistant Staphylococcus aureus ; Cochlear Implants ; Anti-Bacterial Agents/therapeutic use* ; Postoperative Complications ; Middle Aged