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 observe the effectiveness and safety of different doses of esketamine combined with propofol for intravenous administration in the child patients undergoing enhanced computed tomography(CT)examination,and to clarify the optimal clinical dose of esketamine in combination with propofol for sedation.Methods:This study is a randomized,controlled,double-blind(blinded to subjects and evaluators),and single-center clinical trial.A total of 120 preschool children undergoing enhanced CT examination were randomly divided into propofol group(P group),propofol+0.3 mg·kg-1 esketamine group(P+K3 group),and propofol+0.5 mg·kg-1 esketamine group(P+K5 group),and there were 40 cases in each group.All the children were given 2mg·kg-1 propofol,and additional propofol was administered in increments of 1 mng·kg-1 until the sedation criteria for entering the CT room were met[Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score ≤3].The vital signs of the children were observed and recorded at four time points:before sedation(T0),when sedation was satisfactory(T1),during contrast agent injection(T2),and upon awakening(T3).The examination time,time to satisfactory sedation(from the start of sedation to MOAA/S score≤3),and awakening time(from the end of the examination to MOAA/S score＞4)of the children in various groups were recorded.The total dose of propofol and the proportion of cases requiring additional propofol were compared among various groups.Adverse reactions during induction,examination,and after awakening were also compared among various groups.Results:There were no significant differences in general conditions of the children in three groups(P＞0.05).Hemodynamic parameters:at T2,compared with P group,the SpO2 levels of the children in P+K3 group and P+K5 group were increased(P＜0.05);at T1,compared with P group,the SBP levels of the children in P+K3 group and P+K5 group were increased(P＜0.05).There were no significant differences in examination time of the children in three groups(P＞0.05).Compared with P group and P+K3 group,the time to satisfactory sedation of the children in P+K5 group was shorter(P＜0.05).Compared with P group,the awakening time of the children in P+K3 group and P+K5 group was shorter(P＜0.05).Compared with P group and P+K3 group,the total dose of propofol of the children in P+K5 group was decreased(P＜0.05),and the proportion of cases requiring additional propofol was lower(P＜0.05).Adverse reaction indicators:compared with P group,the incidence of respiratory depression of the children in P+K3 group and P+K5 group was lower(P＜0.05),and the incidence of nausea and vomiting was lower(P＜0.05).Compared with P group and P+K3 group,the incidence of movement during the examination of the children in P+K5 group was lower(P＜0.05),and the incidence of dizziness was higher(P＜0.05).There were no significant differences in the incidence of increased airway secretions of the children in three groups(P＞0.05).Conclusion:The use of 0.5 mg·kg-1 esketamine combined with 2 mg·kg-1 propofol for intravenous administration in the child patients for enhanced CT examination sedation can improve the efficiency of such examinations and offers high safety and effectiveness.

Knee osteoarthritis (KOA) is a common chronic degenerative disease that not only causes pain and reduces the quality of life for patients but also imposes a significant societal burden. Clinical pathways can be developed by referencing recommendations from clinical practice guidelines to localize guidelines within the context of integrated traditional Chinese and western medical systems. However, existing clinical pathways suffer from shortcomings such as deficiencies in integrated traditional Chinese and western medical diagnosis and treatment, inadequate shared decision-making between healthcare providers and patients, and suboptimal visualization of clinical pathways. This study aimed to address and optimize the clinical pathway of KOA by comprehensively organizing and localizing the recommended guidelines. The concept of integrated traditional Chinese and western medicine was reflected through the construction of a path of joint decision-making between doctors and patients, emphasizing the coexistence of diagnosis and screening, the combination of clinical and imaging staging, joint decision-making between doctors and patients, and treatment stages. This pathway emphasizes patient-centered approach, with pain relief and functional rehabilitation running parallel, achieving the implementation of evidence-based concepts in practical medical practice. It provides a concrete basis for joint decision-making between doctors and patients in the integrated treatment of KOA with traditional Chinese and western medicine, which helps to improve diagnosis and treatment efficiency and patient quality of life.

Objective To study the clinical effect of Shengjin Yiwei Decoction on chronic heart failure(CHF)complicated with gastrointestinal dysfunction in patients with deficiency of stomach Yin.Methods Totally 68 patients with stomach Yin deficiency syndrome CHF complicated with gastrointestinal dysfunction in our hospital were selected.On the basis of active treatment of heart failure,the control group was treated with omeprazole enteric-soluble capsule,domperidone tablet and pancrease enteric-soluble capsule,and the experimental group was treated with Shengjin Yiwei Decoction.The clinical efficacy of the two groups was compared.traditional Chinese medicine symptom quantification score,gastrointestinal function quantification score,serum gastrin(GAS),plasma motilin(MTL),interleukin(IL)-6 and tumor necrosis factor(TNF)-α levels.Results The effective rate of experimental group was significantly higher than that of control group(χ2=13.73,P<0.05).After treatment,the quantitative score of gastrointestinal dysfunction,quantitative score of TCM symptoms,serum IL-6 and serum TNF-α levels in 2 groups were significantly lower than before treatment,and the above indexes in test group were significantly lower than control group(P<0.05).The levels of serum GAS and plasma MTL in 2 groups were significantly higher than before treatment,and the above indexes in test group were significantly higher than those in control group(P<0.05).Conclusion Shengjin Yiwei Decoction has obvious curative effect on stomach and Yin deficiency syndrome CHF complicated with gastrointestinal dysfunction,can improve clinical manifestations,adjust the level of gastrointestinal hormones and inflammatory factors,and is worthy of clinical application.

Objective To investigate the clinical efficacy of transjugular intrahepatic portosystemic shunt(TIPS)combined with indwelling catheter-directed thrombolysis for the treatment of portal vein thrombosis(PVT).Methods The clinical efficacy of 307 patients with portal hypertension complicated by PVT,who received successful TIPS combined with indwelling catheter-directed thrombolysis at the Affiliated Beijing Shijitan Hospital of Capital Medical University of China between January 2016 and December 2019,were retrospectively analyzed.Before and after TIPS,the inferior vena cava pressure(IVCP)and portal vein pressure(PVP)were measured,and the pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis portal pressure gradient(PPG,PPG=PVP-IVCP)was separately calculated.Reexamination of portal venography DSA was performed to determine the degree of PVT disappearance and whether the shunt was unobstructed.All patients were followed up for one year.Results The pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis mean PPG was(24.50±6.91)mmHg,(18.51±5.11)mmHg,and(10.17±3.97)mmHg,respectively.The post-thrombolysis mean PPG was strikingly lower than the pre-thrombolysis values,the differences were statistically significant(P＜0.001).Among the 307 patients,complete disappearance of PVT was observed in 221(72.3%),remarkable reduction of PVT in 86(27.7%),and no invalid result was seen.The patients having complete patency of the shunt flow accounted for 85.7%of the 307 patients(261/307),and the patients having partial patency of the shunt flow accounted for 14.3%of the 307 patients(46/307).Forty-two patients developed complications,and no death occurred.All patients were followed up for one year,and the main clinical symptoms were improved or completely disappeared.Among the 307 patients,an increase in thrombus volume was found in 17(5.5%)when compared to their postoperative values,which returned to the first-time postoperative level after local treatment of the thrombus via the TIPS shunt combined with catheter-directed thrombolysis.Within one year after TIPS and thrombolysis,overt hepatic encephalopathy(OHE)occurred in 54 patients(17.6%,54/307).One patient died of hepatic failure 9 months after TIPS,another patient died of cerebral hemorrhage 11 months after TIPS,and all the remaining patients were alive.Conclusion For patients with portal hypertension complicated by PVT,TIPS combined with indwelling catheter-directed thrombolysis is clinically safe and effective.The standardized,systematic management of the whole therapeutic process should be strengthened.(J Intervent Radiol,2024,32:22-27)

AIM:To investigate the effect of icari-in on renal fibrosis and injury in hypertension through Cx32-Nox4 signaling pathway.METHODS:Models of hypertensive nephropathy(HN)were es-tablished in spontaneously hypertensive rats(SHRs).The experiment was divided into 4 groups:normal control group(WKY rats),model group(SHR),icariin 10 mg·kg-1·d-1 group(icariin once dai-ly),icariin 30 mg·kg-1·d-1 group(icariin once daily),n=10.The expression of fibrosis-related proteins was detected in vivo.NRK-52E cells exposed to An-gⅡ were selected to observe the effects of icariin on kidney injury.Extracellular matrix(ECM)levels,including α-smooth muscle actin(α-SMA),collagenⅠ(Col-Ⅰ)and fibronectin(FN)expression were mea-sured by Western blot and immunohistochemistry.The expressions of oxidative stress markers includ-ing superoxide dismutase(SOD)and malondialde-hyde(MDA)were determined by the test kit.RE-SULTS:Icariin reduced renal fibrosis in SHR rats in vivo.Icariin down-regulated the expression of α-SMA,FN,and Col-Ⅰ and protected hypertension-damaged kidney tissue from progressive fibrosis(P＜0.05).Icariin increased the total SOD activity and decrease the MDA level in kidney and serum of SHR rats(P＜0.05).In addition,icariin increased the expression of Cx32 and decreased the expression of Nox4 in the kidneys of SHR rats(P＜0.05).Icariin had a protective effect on AngⅡ-mediated NRK-52E cell damage and fibrosis.CONCLUSION:Icariin can improve renal tubulointerstitial fibrosis and delay the progression of HN.Renal protection may be at-tributed to the regulation of oxidative stress medi-ated by the Cx32-Nox4 signaling pathway.

Objective To investigate the value of derived neutrophil to lymphocyte ratio(dNLR)as a pre-dictive biomarker for immunotherapy response in advanced non-small cell lung cancer(NSCLC).Methods A total of 92 patients with advanced NSCLC who received anti-programmed cell death receptor(PD-1)combined therapy in the hospital from August 2018 to December 2019 were selected as the research objects.Peripheral blood samples were collected within 24 h before immunotherapy,complete blood cell count was measured,and dNLR was calculated.Patients with advanced NSCLC were treated with PD-1 inhibitors or combination regi-mens,and the response to immunotherapy was evaluated by objective response rate(ORR)and disease control rate(DCR).The receiver operating characteristic(ROC)curve was used to analyze the predictive value of dN-LR for the diagnosis and response to immunotherapy in advanced NSCLC.Multivariate Logistic regression model was used to analyze the relationship between dNLR and immunotherapy response in advanced NSCLC.Kaplan-Meier survival curve and Log-Rank test were used to analyze the overall survival(OS),progression-free survival(PFS)and disease-specific survival(DSS)of the low dNLR group and the high dNLR group.Re-sults The ORR and DCR of advanced NSCLC patients after immunotherapy were 32.61％and 65.22％,re-spectively,and the PFS and OS were 17.0(8.5,25.5)and 24.0(12.7,36.1)months,respectively.The dNLR of DCR group was lower than that of non-DCR group(P＜0.001).The dNLR of ORR group was lower than that of non-ORR group(P＜0.001).The area under the curve of dNLR for predicting DCR or ORR was 0.897(95％CI 0.829-0.965)and 0.874(95％CI 0.795-0.953),respectively.Multivariate Logistic regres-sion analysis showed that dNLR≥2.28 increased the risk of non-response to immunotherapy,and this inde-pendent relationship still existed after further adjustment for objective confounding factors(P＜0.05).Sur-vival curve results showed that patients with high dNLR had significantly shorter PFS,OS,and DSS(P＜0.05).Multivariate Cox regression analysis showed that high dNLR was an independent factor affecting the poor prognosis of patients with advanced NSCLC(P＜0.05).Conclusion High dNLR advanced NSCLC pa-tients are more difficult to benefit from immune therapy,and prognosis is worse.dNLR is promising as a pre-dictive biomarker for immunotherapy response in advanced NSCLC.

Objective:To evaluate the value of endoclip-assisted and submucosal injection-assisted cannulation techniques for difficult cannulation during endoscopic retrograde cholangiopancreatography (ERCP).Methods:Data of 12 458 patients treated with ERCP for the first time in the First Affilated Hospital of Naval Medical University from June 2015 to September 2020 were retrospectively analyzed. Twenty eight (0.22%) were identified as difficult cannulation where metal clip- or submucosal injection-assisted cannulation was used. The selective cannulation success rate, intubation time and complication incidence of the two techniques in difficult cannulation patients were analyzed.Results:Difficult cannulation was performed in 18 males (64.3%) and 10 females (35.7%) with an age of 69.6±14.1 years assisted by metal clips or submucosal injection. Five cases (17.9%) were type Ⅱ, 5 cases (17.9%) type Ⅲ, and 18 cases (64.3%) type Ⅴ according to papilla classification. Sixteen patients (57.1%) received metal clip-assisted cannulation, and 12 cases (42.9%) submucosal injection-assisted cannulation. Twenty-five (89.3%) patients successfully underwent selective cannulation with the cannulation time of 9.9±4.3 min. One case (3.6%) of mild post-ERCP pancreatitis and 3 cases (10.7%) of post-ERCP hyperamylasemia occurred. No postoperative bleeding or perforation occurred. All patients were cured and discharged after conservative treatment.Conclusion:When selective cannulation is difficult due to poor papilla exposure or deflection, endoclip- or submucosal injection-assisted cannulation can effectively improve the successful selective cannulation rate during ERCP with low complication incidence, which is worth of clinical promotion.

Objective:intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS).Methods:A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ2 test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results:PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt ( t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt ( t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion:TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.

Objective:By using balloon occlusive hepatic angiography in cirrhotic portal hypertension to evaluate contrast doses on the detection rate of intrahepatic venous-lateral branch shunt (HVVC), and the effect on hepatic venous pressure gradient (HVPG) and portal vein pressure gradient (PPG).Methods:From Jan 2018 to Jun 2021, 131 patients received transjugular intrahepatic portosystemic shunt (TIPS) at Beijing Shijitan Hospital.Results:A positive correlation between PVP and weged hepatic venous pressure (WHVP) ( r=0.241, P=0.001) was found when only by right hepatic vein approach. Ten ml of iodine contrast medium when compared to 5ml doses found more cases of intrahepatic venous-venous lateral branch shunt. The mean PPG of patients with HVVC was significantly higher than the mean of HVPG( P<0.05).The right hepatic vein was the only reliable vein by which WHVP was measured. Conclusions:Right hepatic vein manometry,adequate ballon occlusion and using 10ml of iodine contrast help get reliable WHVP and found HVVC; HVVC can affect the consistency of HVPG and PPG.