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.

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.

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 effects of combined exposure to benzene series, dust and noise on occupational high-frequency hearing loss (HFHL) in the electronics manufacturing industry. Methods A total of 740 employees from an electronic manufacturing enterprise were selected as the study subjects. According to the detection of occupational hazard factors, they were divided into noise group, noise benzene group, and noise dust group, with 325, 167, and 248 people, respectively. Occupational health examinations were conducted on the study participants to analyze their HFHL detection status and influencing factors. Results Among all participants (n=740), 456 (61.62%) were male, 284 (38.38%) were female, and 123 (15.62%) were detected with HFHL. The detection rate of HFHL increased with age and length of service (P<0.01). According to the exposure factor grouping, the detection rates of HFHL in the noise group, noise benzene group, and noise dust group were 12.00%, 19.16%, and 20.97%, respectively (P<0.05). Multivariate logistic regression analysis showed that workers aged ≥ 40 years, with 10-20 years of work experience, ≥ 20 years of work experience, exposure to noise and benzene series, and exposure to noise and dust had an increased risk of developing HFHL to 1.734, 1.923, 3.071, 1.706, and 1.527, respectively (P<0.05). Conclusion Combined exposure to noise and benzene series, combined exposure to noise and dust, as well as age and extended length of service may increase the risk of HFHL among workers.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

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

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.