OBJECTIVE: To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. METHODS: RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. RESULTS: 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. CONCLUSION 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism* ; Arthritis, Rheumatoid/metabolism* ; Animals ; Cell Movement/drug effects* ; Humans ; Catechols/therapeutic use* ; Fibroblasts/drug effects* ; Mice ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/cytology* ; Cells, Cultured ; Male ; Arthritis, Experimental ; Anti-Inflammatory Agents/pharmacology* ; NF-KappaB Inhibitor alpha ; Inflammation

Objective To investigate the predictive ability of cyst fluid characteristics for malignant intraductal papillary mucinous neoplasms (IPMNs). Methods We prospectively collected fresh cyst fluid from patients undergoing pancreatic resection at the Department of Hepatobiliary Pancreatic Spleen Surgery, Changhai Hospital, Shanghai, from September 2023 to December 2024, who were ultimately pathologically confirmed with IPMN. We assessed the characteristics of cyst fluid, including viscosity, clarity, and color, and explored its predictive performance for benign or malignant. Results A total of 40 patients with IPMN were included. The sensitivity of the string sign （+） for diagnosing high-grade dysplasia/ invasive carcinoma （HGD/IC） was 90.9%, specificity was 92.9%, and accuracy was 76.0%. The cyst fluid of intestinal-type IPMN often exhibited a gelatinous consistency, and there was no significant difference in the distribution of gelatinous consistency between the HGD/IC group and the low-grade dysplasia （LGD） group. There were no significant differences in CEA, glucose, and amylase levels in the cyst fluid between the HGD/IC group and the LGD group. Conclusions The characteristics of pancreatic cyst fluid, especially viscosity, can effectively predict the benign or malignant nature of IPMN.

Objective To conduct a bibliometric and visual analysis of global literature on cardi-ovascular immune-related adverse events(irAEs)induced by immune checkpoint inhibitors(ICIs)in cancer treatment,and to explore the research status,hotspots,and future trends in this field.Meth-ods The Web of Science Core Collection(WOSCC)database was utilized to retrieve and screen rel-evant literature.CiteSpace software was employed for visual analysis of countries,institutions,au-thors,and keywords.Results A total of 1,350 articles were retrieved,with an annual increase in publication volume.The United States dominated in terms of national,institutional,and author contri-butions,while European countries and institutions demonstrated close collaborative networks.Keyword analysis and cited reference mapping revealed an evolution of research hotspots:from initial mechanistic investigations to monoclonal antibody applications,and subsequently to safety concerns.Current lre-search focuses on ICI monoconal antibody combination therapy for malignancies and cardiovascular irAEs,particularly fatal myocarditis,which has emerged as a prominent topic.Conclusion ICIs mon-oclonal antibody therapies and their associated cardiovascular irAEs,especially combination therapies and life-threatening myocarditis,represent key research frontiers.Investigations into drug combination strategies and fatal myocarditis may guide future research directions.

Objective:To analyze the characteristics of pancreatic metastatic tumors and evaluate the clinical value of endoscopic ultrasound-guided fine-needle aspiration or biopsy (EUS-FNA/B) in their diagnosis.Methods:A retrospective analysis was conducted on clinical, radiological, and pathological data of 11 cases with pancreatic metastatic tumors diagnosed by EUS-FNA/B at the First Affiliated Hospital of Naval Medical University between January 2011 and December 2020. Tumor size, number of lesions, time interval between diagnosis of metastatic lesions and primary tumors, radiological and EUS findings and pathological types were recorded, and success rate and diagnostic rate of EUS-FNA/B were analyzed.Results:The 11 patients with pancreatic metastatic tumors had an age range of 43 to 76 years, including 7 males and 4 females. Eight cases presented with symptoms of abdominal pain and poor appetite, 1 case had cervical lymph node enlargement, and 2 cases were detected during routine physical examination. Five cases had abnormal serum tumor markers. All patients had a confirmed history of primary tumors, and the median time interval between diagnosis of pancreatic metastatic lesions and primary tumors was 24 months (-1-124 months). Seven cases had solitary lesions, and 4 cases had multiple nodules under EUS. Eight cases were initially diagnosed clinically as pancreatic lesions or tumor, while 3 cases were considered as pancreatic metastatic tumor. All of 11 cases underwent EUS-FNA/B and were histologically confirmed as pancreatic metastatic tumors. The most common pathological type was lung small cell neuroendocrine cancer ( n=4), followed by renal cell carcinoma ( n=3), and esophageal squamous cell carcinoma ( n=1), pulmonary squamous cell carcinoma( n=1), malignant melanoma ( n=1), and gastric adenocarcinoma ( n=1). Conclusions:The pancreas is not a common target site for tumor metastasis.EUS-FNA/B is a relatively safe minimally invasive method for the diagnosis of pancreatic metastatic tumors.

AIM: To study the effect of Qingdaipowder Gel (QDPG) on mice specific dermatitis (AD) model and the antibacterial effect of the ethanol extract of Qingdaipowder. METHODS: AD model of mice was established by repeated skin induction with 2,4-dinitrochlorobenzene (DNCB). Fifty-six mice were randomly divided into blank group, model group, Hydrocortisone Butyrate Cream group (Hyd, 1.5 mg/cm

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

Objective:To explore the safety of cyclophosphamide combined with taxane chemotherapy in triple-negative breast cancer patients with chronic renal failure and the management strategy of complications.Methods:Data of 8 patients with triple-negative breast cancer and chronic renal failure admitted to our hospital from Jun 2016 to Dec 2019 were retrospectively analyzed.Results:Eight patients received standard cyclophosphamide combined with taxane (TC regimen) chemotherapy after operation, 5 of which received docetaxel 75 mg/m 2 + cyclophosphamide 600 mg/m 2, and 3 received albumin paclitaxel 260 mg/m 2+ cyclophosphamide 600 mg/m 2, during chemotherapy, only leukopenia, hair loss and gastrointestinal reactions occurred in grades 3 to 4, and the incidence was 25%, 25% and 12%, respectively. Four patients adjusted the dosage due to adverse reactions. One patient quit, the remaining patients successfully completed 4 cycles of chemotherapy. The average serum creatinine before chemotherapy was (498±63) μmol/L, and after chemotherapy, it was (518±61) μmol/L ( t=-2.335, P>0.05). Conclusions:Combined with chronic renal failure is not a contraindication to postoperative chemotherapy for patients with breast cancer. It is safe to choose standard TC regimen and adjust the dose of adjuvant chemotherapy for patients with triple-negative breast cancer.

To minimize the predatory harvest of Heterosmilax yunnanensis and maintain the sustainable utilization of its resources, a study on the tending technology of wild H. yunnanensis was carried out. The results showed that the tuber tending model had a higher seed emergence rate, shorter growth period and easier control of male and female ratios than other tending models; by removing shrubs, topping, bending pruning, controlling insects and pests and other effective technical measures, the growth period of H. yunnanensis was shortened; the average annual net income of the tending area was 1 086 yuan/mu (1 mu≈666.67 m²), which was 86.9% higher than before. This study was conducive to increasing the yield and quality of H. yunnanensis in Karst landform area, and instructive for the tending of other wild traditional Chinese medicinal herbs in this area.
Female ; Humans ; Male ; Smilacaceae

ObjectiveTo analyze the risk factors related to perforation of lateral wall by lower cervical pedicle screw instrumentation in the treatment of cervical spinal disorders. MethodsA retrospective review was made to analyze 214 cervical vertebral injury patients ( 1 024 pedicle screws were used) treated with pedicle screw instrumentation at C3-7 from July 2004 to July 2009. Lateral walls of 18 patients were perforated (a total of 28 pedicle screws). The surgeons assessed the position and the angle of the screw in the pedicle, and the relation and the distance between the screw and the pedicle walls by carefully probing intraoperative walls of cervical pedicles and studying postoperative thin-slice computed tomography (CT) scan of the fixed vertebral segments of the cervical spine. The data of patients with lateral wall perforation was recorded and analyzed statistically. ResultsPerforation of the lateral wall occurred in 18 patients (28 pedicle screws). Backward step by step Logistic regression analysis was used and two variables were selected in the end. ConclusionsRatio variance between inner and lateral wall is the risk factor of perforation in the lateral wall associated with lower cervical pedicle screw instrumentation, while the angle variance between implanted screws and CT measurements is the protection factor of perforation in the lateral wall.

Objective To analyze the complications of lower cervical pedicle screw fixation in treatment of the cervical spine disorders and discuss the operative technique. Methods A retrospective study was made in 104 patients with different cervical injuries treated by C3-7 pedicle screw fixation (total use of 624 screws) from July 2004 to March 2008. One stage posterior reduction and fixation using lower cervical pedicle screw-rod system or screw-plat system were performed in 66 traumatic patients and the nerve condition was evaluated by Frankel criteria system. For 46 non-traumatic patients, laminoplasty or laminectomy was performed for decompression, and cervical pedicle screw-rod system or screw-plat system were used in deformity correction and stability reconstruction. Based on exploration to quadric walls of vertebral pedicle during operation, postoperative thin-slice CT scan along operative vertebra segments' pedicle and bilateral oblique position X-ray of cervical spine in all patients, we evaluated screw location, screw angle as well as the distance and the relation between the screws and the internal pedicle wall or lateral wall. Results In this study, the lower cervical pedicles of 104 patients were fixated with 624 screws including 77 screws (12.34% ) for pedicle wall damage, 68 screws (10.8% ) for the lateral wall injury, 56 screws (8.97% ) for grade Ⅰ violation of pedicles, 12 screws (1.92% ) for grade II violation of pedicles Ⅱ violation of pedicles and 9 screws (1.44% ) for inferior wall injury of cervical pedicle. The follow-up lasted for 3-24 months (average 9. 8 months), which showed breakage of two screws (0.32% ) and loosening of one screw (0.16% ). Conclusions Lower cervical pedicle screw fixation has relatively low incidence of complications and is a safe operation. The complications can be minimized by sufficient preoperative imaging studies of the pedicles, familiar with the feature of opography and reasonable surgery technique.