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Xin Yang,1 Xiaoguang Cui,1 Xiao Yang,2 Bincheng Ren,1 Xiaojing Cheng,1 Xinrui Zhao,1 Shanshan Liu,1 Tian Tian,1 Hui Zhao,1 Li Qu,1 Xueyi Li1 1Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China; 2Scientific Research Center and Precision Medical Institute, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Xueyi Li, Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China, Tel +86 13992891987, Fax +86 02987679832, Email li-xueyi@139.comPurpose: This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients.Patients and Methods: This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan–Meier method and Cox regression analysis.Results: Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin > 1030.0 ng/mL (p< 0.001), ALT > 103.0 U/l (p< 0.001), AST > 49.0 U/l (p< 0.001), γGT > 82.0 U/l (p< 0.001), ALP > 133.0 U/l (p< 0.001), lactate dehydrogenase (LDH)> 474.0 U/l (p< 0.001), plasma albumin (ALB) < 35.7 g/l (p< 0.001) and direct bilirubin (DBIL) > 2.80 μmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p< 0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p< 0.001) in anti-MDA5 positive DM patents.Conclusion: Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.Keywords: anti-melanoma differentiation-associated gene 5 antibody, liver involvement, ferritin, macrophage, interstitial lung disease, dermatomyositis

Guanming Shao,&ast; Yonghui Ma,&ast; Chao Qu, Ruiqian Gao, Chengzhan Zhu, Linlin Qu, Kui Liu, Na Li, Peng Sun, Jingyu Cao Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Sun; Jingyu Cao, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Email psun1@qdu.edu.cn; cjy7027@163.comBackground: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA).Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems.Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.Keywords: hepatocellular carcinoma, liver resection, recurrence, machine learning, neutrophil-to-eosinophil ratio

Shan Li,1,&ast; Fengdi Zhang,2,&ast; Ritian Lin,1 Qinjuan Sun,1 Lihong Qu,2 Lan Zhong1 1Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Infectious Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Zhong, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150, Jimo Road, Pudong New Area, Shanghai, 200120, People’s Republic of China, Email lanzhong@tongji.edu.cn Lihong Qu, Department of Infectious Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Email 18916510601@163.comPurpose: The rapid global spread of the SARS-CoV-2 Omicron variant introduces a novel complication: the emergence of IBD (inflammatory bowel disease)-like ulcers in certain patients. This research delves into this new challenge by juxtaposing the clinical manifestations and genetic expression patterns of individuals affected by the Omicron variant of COVID-19 with those diagnosed with IBD. It aims to decode the link between these conditions, potentially shedding light on previously unexplored facets of COVID-19 pathophysiology. This investigation emphasizes gene expression analysis as a key tool to identify wider disease correlations and innovative therapeutic avenues.Patients and Methods: From March to December 2022, patients with SARS-CoV-2 Omicron infection and inflammatory bowel disease and healthy controls were recruited in Shanghai East Hospital, Shanghai, China. The epidemiological and clinical characteristics of the patients were compared. Four RNA sequencing datasets (GSE205244, GSE201530, GSE174159, and GSE186507) were extracted from the Gene Expression Omnibus database to detect mutually differentially expressed genes and common pathways in patients with SARS-CoV-2 infection and inflammatory bowel disease.Results: Compared to patients with active inflammatory bowel disease, patients with SARS-CoV-2 infection were more likely to have elevated interferon-α levels and an increased lymphocyte count and less likely to have high interleukin-6, tumor necrosis factor-α, and C-reactive protein levels and an elevated neutrophil count. A total of 51 common differentially expressed genes were identified in the four RNA-sequencing datasets. Enrichment analysis suggested that these genes were related to inflammation and the immune response, especially the innate immune response and nucleotide oligomerization domain-like receptor signaling pathway.Conclusion: The inflammation and immune-response pathways in COVID-19 and inflammatory bowel disease have several similarities and some differences. The study identifies the NLR signaling pathway’s key role in both COVID-19 and IBD, suggesting its potential as a target for therapeutic intervention and vaccine development.Keywords: viral-induced inflammation, omicron infection, RNA sequencing, gene expression in infection, inflammatory bowel disease

Tiantian Xuan,1 Zhanmei Wang,1 Sibo Meng,1 Jiaxin Li,1 Jisheng Li,2 Fangli Cao,1,&ast; Linli Qu1,&ast; 1Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangli Cao; Linli Qu, Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +86-18561811936 ; +86-18561811457, Email caofangliqilu@163.com; qulinli2021@163.comPurpose: Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen.Patients and Methods: We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy.Results: Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8– 12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0– 7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed.Conclusion: MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.Keywords: colorectal cancer, maintenance therapy, cetuximab, RAS and RAF wild-type, targeted therapy

Oceanic absorption of heat generated by greenhouse gas emissions has resulted in warming of the dark ocean (>200 m) that contains a large refractory DOM (RDOM) pool. However, changes in microbially mediated production and degradation dynamics for RDOM components in response to warming of dark marginal basins remain unclear. Herein, we integrated data from the dark South China, Mediterranean and Japan Seas (temperature range: 0.09–15.1°C) to demonstrate that in situ production efficiency of two ubiquitous humic-like fluorophores increased at higher dark ocean temperature, whereas chromophores at a wavelength of 325 nm (aCDOM(325)) changed from production to degradation at higher temperature. Increased oxygen consumption and a reduction of labile substrates in future warmer dark ocean environments may initiate the final degradation of some semi-refractory components, thereby increasing the recalcitrance of RDOM, but decreasing the DOM inventory in dark basins and creating a positive feedback to rising atmospheric CO2.

Base-extracted particulate organic matter (BEPOM) collected in low (spring) and high (summer) runoff seasons in the Changjiang Estuary and adjacent nearshore/offshore shelf areas was examined using absorption and fluorescence spectroscopy. Parallel factor analysis (PARAFAC) identified two humic-like (C1p and C2p) biologically-refractory components and two protein-like (C3p and C4p) bioreactive components. Absorption coefficient a350p, C1p and C2p of BEPOM showed strong positive correlations with particulate organic carbon (POC), and were generally higher in spring than in summer. C4p correlated positively with Chl a, and was higher in summer than in spring. In the inner estuary, an anthropogenic POM signal from the highly polluted Huangpu River was effectively identified by the fluorescent component ratio (IT:IC)P. In the nearshore area during spring, resuspension within the well-developed turbidity maximum zone (TMZ) supplied large amounts of refractory POM into the water column. POM fractions from an autochthonous source (i.e., algal bloom) were dominant in the offshore area during the summer. A multivariate regression model inferred that POM export fluxes from the Changjiang River during spring had a higher percentage of labile POM fractions, which were subsequently retained by the TMZ. However, these labile fractions were discharged into the offshore shelf area contributing to hypoxia in the summer. The summer high runoff season also transported large amounts of refractory POM that was subsequently buried in the sediment. This study highlights the utilization of optical analyses to trace pollution sources and reveal POM fate and transport dynamics allowing better assessment of its ecological consequences in estuaries.

Integrated source apportionment and risk assessment of metals is of great importance for contamination source control and remediation at the regional watershed scale. To identify metal sources and source-specific ecological risks, sediments were collected in the Wen-Rui Tang urban watershed for metal analysis. Risk assessment showed considerable and extremely high risk for Cu and Cd with large spatial variation. Positive matrix factorization model extracted three main sources with reasonable prediction efficacy for metal concentrations. Due to different toxicity coefficients for various metals, the low concentration contribution of source factor 2 (27.2%) contributed 83.7% of total risk, while a high concentration loading for factor 3 (40.8%) only contributed 4.6% to total risk. Predicted source-specific risk was similar to determined risk level for Cr, Ni and Pb; however, Cu and Cd were predicted with decreased risk, while Zn had increased risk. Triangular fuzzy number (TFN) coupled with stochastic simulation showed elevated trend in risk simulation for Cd and Cu when compared with determined risk. The uncertainties for risk evaluation appear to result from spatial variations in metal concentrations. Source apportionment and specific-risk assessment results suggest that different strategies may be required to address mitigation of elevated metal concentrations versus ecological risk.

The 2015/2016 super El Niño event resulted in a positive precipitation anomaly during dry seasons in the Jiulong River watershed, southeast China. Four years (2014–2017) of high frequency, in situ humic-like fluorescent DOM (FDOMH) data in the Jiulong Estuary were coupled with extrapolation to a freshwater end-member FDOMH concentration and river discharge data to estimate riverine FDOMH export. The wetter El Niño dry season was followed by lower FDOMH export during the subsequent wet season. Furthermore, in the dry season after El Niño reached its strongest phase, a 90–187% increase in FDOMH export occurred. If widespread, this pattern suggests El Niño events may enhance export of FDOMH from south China rivers in dry seasons resulting in seasonal and annual shunting of the terrestrial DOM export, modulating coastal carbon cycling. This study highlights the need to incorporate climate-driven regulation patterns on DOM transport across the land-ocean interface.

Yin Yin,1 Lin Qu,1 Bai Jin,1 Zhengqiang Yang,2 Jinguo Xia,2 Lizhou Sun,1 Xin Zhou1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University Hospital, Nanjing, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University Hospital, Nanjing, People’s Republic of ChinaCorrespondence: Xin Zhou, Department of Obstetrics & Gynecology, The First Affiliated Hospital of Nanjing Medical University Hospital, Nanjing, People’s Republic of China, Tel +86 25 8620 0133, Fax +86-25-8371-6602, Email zhouxin101@sina.comPurpose: We aimed to investigate the combined effect of spiral suture of the lower uterine segment with intraoperative aortic balloon occlusion in morbidly adherent placenta previa cases.Patient and Methods: This retrospective, single-center study involved patients from 2017 to 2020. The study considered 68 cases of morbidly adherent placenta previa cases from medical records retrospectively with age ranging from 23 to 42 years. Bilateral uterine artery embolization was performed, to control excessive bleeding. Perioperative blood loss, hysterectomy rate, amount of blood transfusion, balloon occlusion time, fetal and maternal radiation dose, and postpartum complications were assessed.Results: A total of 68 patients underwent surgery. Hysterectomy was performed in three patients and uterine artery embolization in 21 patients. Of 53 patients who required blood transfusions, the amount of packed red blood cells given was 800 mL and the amount of plasma given was 400 mL. Median abdominal aortic balloon occlusion time was 17 minutes. Fetal and maternal radiation doses were 5 mGy and 12 mGy, respectively. One patient experienced surgery-related complications, a bladder injury. No major catheterization-related and postpartum complications were observed.Conclusion: Fertility-sparing surgery for women with morbidly adherent placenta could include abdominal aortic balloon occlusion and spiral suture of lower uterine segment.Keywords: morbidly adherent placenta previa, spiral suture, lower uterus, aortic balloon occlusion

IntroductionThere is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C.MethodsTen single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger.ResultsBased on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7).DiscussionOur study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD.

Chinese medicine plays a crucial role in maintaining the equilibrium of the intestinal microbiome, and this microbiome, in turn, plays a pivotal role in mediating the pharmacological effects of Chinese medicine on the host. Despite the significance of this interplay, there is a paucity of studies investigating the impact of orally administered Traditional Chinese Medicine (TCM) on the co-occurrence patterns of intestinal gut bacteria. In the present study, we incorporated Coix seed, Chinese yam, Semen euryales, and their combination into the diet of mice. Subsequently, we assessed the effects of these TCM on the diversity, community composition, and co-occurrence networks of gut bacteria by oral administration. Our findings underscored the substantial influence of the three TCM varieties and their mixture on the diversity and community composition of gut bacteria. Notably, all TCM utilized in our study exhibited the ability to enrich beneficial gut bacteria and inhibit pathogenic bacteria within the intestinal microbiome. Furthermore, oral administration of Coix seed, Chinese yam, Semen euryales, or their combinations resulted in increased thymus and spleen indices. Examination of network topological features revealed marked dissimilarities between the control group and the TCM oral administration groups. The co-occurrence pattern of bacteria in the TCM oral administration groups exhibited less complexity but greater stability compared to that in the control groups. These observations suggest that the bacterial community in TCM oral administration groups is more resilient to disturbances than in the control groups. [ABSTRACT FROM AUTHOR]

Jin Man,1 Jiajia Dong,2 Yilin Wang,1 Leiliang He,1 Songcheng Yu,1 Fei Yu,1 Jia Wang,1 Yongmei Tian,1 Lie Liu,1 Runping Han,2 Hongchao Guo,1 Yongjun Wu,1,3 Lingbo Qu2,4 1College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, People’s Republic of China; 2College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, People’s Republic of China; 3The Key Laboratory of Nanomedicine and Health Inspection of Zhengzhou, Zhengzhou, Henan 450001, People’s Republic of China; 4Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou, Henan 450001, People’s Republic of ChinaCorrespondence: Yongjun WuCollege of Public Health, Zhengzhou University, No.100 Science Avenue, Zhengzhou City 450001, People’s Republic of ChinaTel/Fax +86-371-67781450Email wuyongjun135@126.comLingbo QuCollege of Chemistry, Zhengzhou University, No. 100 Science Avenue, Zhengzhou City 450001, People’s Republic of ChinaTel/Fax +86-371-67781450Email qulingbo@zzu.edu.cnBackground: As two important tumor markers, vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) have a great value for clinical application in the early diagnosis of cancer. Due to the complex composition of biological samples, the results from combined detection of CEA and VEGF are often taken as a comprehensive indicator in order to make an accurate judgment on a disease. However, most of the current methods can only be used to detect the content of one biomarker. Therefore, it is necessary to explore a simple, rapid, low-cost, and highly sensitive method for the simultaneous detection of CEA and VEGF.Methods: Based on specific aptamers and magnetic separation, a time-resolved chemiluminescence enzyme-linked aptamer assay was developed for the simultaneous detections of CEA and VEGF in serum samples.Results: Under the optimal conditions, the linear range of the calibration curve for VEGF was from 0.5 to 80 ng mL− 1, and the limit of detection was 0.1 ng mL− 1. The linear range of the calibration curve for CEA was 0.5 to 160 ng mL− 1, and the limit of detection was 0.1 ng mL− 1. The established method was applied to detect VEGF and CEA in serum samples. The results were consistent with those of commercial kits.Conclusion: The method has high sensitivity and can quickly obtain accurate results, which could greatly improve the measurement efficiency, reduce the cost, and also reduce the volume of sample consumed. It can be seen that the method established in this study has important application value and broad application prospect in clinical diagnosis.Keywords: chemiluminescence assay, simultaneous detection, vascular endothelial growth factor, time-resolved, carcinoembryonic antigen

The internal heat exchange between each phase and the local thermal equilibrium scenarios in multi-phase fibrous materials are considered in this paper. Based on the two-phase heat transfer model, a criterion is proposed to evaluate the local thermal equilibrium condition, using derived characteristic parameters. Furthermore, the local thermal equilibrium situations in isothermal/adiabatic boundary cases with two different heat sources (constant heat flux and constant temperature) are assessed as special transient cases to test the proposed criterion system, and the influence of such different cases on their local thermal equilibrium status are elucidated. In addition, it is demonstrated that even the convective boundary problems can be generally estimated using this approach. Finally, effects on local thermal equilibrium of the material properties (thermal conductivity, volumetric heat capacity of each phase, sample porosity, and pore hydraulic radius) are investigated, illustrated, and discussed in our study.

© 2014 Zhao et al.Antibodies are ubiquitous and essential reagents for biomedical research. Uses of antibodies include quantifying proteins, identifying the temporal and spatial pattern of expression in cells and tissue, and determining how proteins functi

OBJECTIVE: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. PATIENTS AND METHODS: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). CONCLUSIONS: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT), a naturally occurring alkaloid derived from the Camptotheca acuminate plant, exerts anti-tumor properties. However, its specific impact on head and neck squamous cell carcinoma (HNSCC) remains uncertain. The study was to explore the action and mechanism of CPT on HNSCC cells. First, two HNSCC cell lines (FaDu and TU686) and a normal immortalized keratinocyte (HEK001) cell line, were exposed to a spectrum of CPT concentrations (ranging from 10 to 50 µM) for durations of 24 h and 48 h. Cell viability, proliferation, migration, and invasion were assessed by CCK-8 assay, EdU incorporation assay, wound healing assay and transwell assay. Subsequently, si-RAB27A or negative control (NC) was introduced into FaDu and TU686 cells through transfection, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was manipulated with L740Y-P, an activator of this pathway. The expression of proliferating cell nuclear antigen (PCNA), E-cadherin, PI3K/AKT signaling factors and RAB27A were determined by Western blot analysis. RAB27A was detected by immunofluorescence assay. It was found that CPT significantly hindered the viability, proliferation (p<0.01), migration (p<0.001), and invasion (p<0.001) of FaDu and TU686 cells. At the molecular level, administration of CPT caused a decline in the expression of PCNA, P-PI3K, P-AKT, and RAB27A, alongside an elevation in E-cadherin levels within HNSCC cells (p<0.05, p<0.01 and p<0.001). Reducing RAB27A expression enhanced the suppressive impacts of CPT on HNSCC cell viability (p<0.05 and p<0.01), migration (p<0.001) and invasion (p<0.01), these effects that were reversed upon treatment with L740Y-P in HNSCC cells (p<0.001). In summary, our study highlights the efficacy of CPT in HNSCC, demonstrating its influence on cell processes via the RAB27A-mediated PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Qing Sun, Chao Wang, Bin Yan, Xiaohu Shi, Yue Shi, Ling Qu, Xiaochun Liang Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People’s Republic of ChinaCorrespondence: Xiaochun LiangPeking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, People’s Republic of ChinaTel +86 10 6915 5344Fax +86 10 6915 5344Email xcliang@vip.sina.comBackground: Jinmaitong (JMT) has been used to prevent and treat diabetic peripheral neuropathy (DPN) for decades. The present study aimed to elucidate the effects of JMT on thioredoxin-interacting protein (TXNIP) and Nod-like receptor protein 3 (NLRP3) inflammasome activation in the streptozotocin (STZ)-induced rat model.Methods: The diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg STZ. The rats were divided into 3 groups (n = 8–10 per group): diabetic control, JMT (0.876 g/kg/d), and alpha-lipoic acid (ALA; 100 mg/kg/d). Body weight and blood glucose levels were monitored every 4 weeks for 12 weeks. Mechanical allodynia and myelin sheath injury of sciatic nerves (SNs) were assessed using the mechanical withdrawal threshold (MWT) test and Luxol fast blue staining. Serum T-superoxide dismutase (T-SOD), malondialdehyde (MDA), and catalase (CAT) levels were measured using commercially available kits. TXNIP/NLRP3 inflammasome proteins, including TXNIP, NLRP3, pro-caspase-1, and cleaved -caspase-1, and the downstream protein interleukin (IL)-1β, were measured using immunohistochemistry and Western blot. Gasdermin D (GSDMDC1) protein expression was analyzed using Western blot, and serum IL-1β and IL-18 levels were detected using ELISA.Results: JMT did not significantly affect body weight or level of fasting blood glucose but improved mechanical allodynia and myelin sheath injury of SNs at 12 weeks following treatment. Moreover, JMT increased serum levels of the anti-oxidative enzymes CAT and T-SOD, and decreased MDA levels. Both JMT and ALA decreased expression of TXNIP, NLRP3, and cleaved-caspase-1 protein. JMT and ALA also decreased IL-1β, IL-18, and GSDMDC1 protein expression.Conclusion: The current study demonstrated that TXNIP/NLRP3 inflammasome activation is involved in the molecular mechanisms underlying JMT’s protective effects in the STZ-induced diabetic rat model, which provides novel evidence to support the future clinical use of JMT.Keywords: Jinmaitong, diabetic peripheral neuropathy, TXNIP/NLRP3 inflammasome, diabetic rat model, alpha lipoic acid