Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective:To investigate whether caffeic acid phenethyl ester (CAPE) would improve peritoneal dialysis (PD)-associated peritoneal fibrosis by alleviating oxidative stress through activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into four groups by the random number table: control (CON) group (0.9% normal saline 20 ml/d intraperitoneal injection), CAPE group (0.9% normal saline 20 ml/d+CAPE 10 mg·kg -1·d -1 intraperitoneal injection), PD group [4.25% glucose peritoneal dialysis fluid (PDF) 20 ml/d intraperitoneal injection with lipopolysaccharide 0.6 mg/kg intraperitoneal injection at day 1, 3, 5 and 7], and PD+CAPE group (CAPE 10 mg·kg -1·d -1 intraperitoneal injection in addition to PD group), with 8 rats per group. On day 28, rats were euthanized after peritoneal equilibration test, and then the parietal peritoneum and omentum were collected for follow-up tests. To further investigate the mechanism, primary peritoneal mesothelial cells (PMCs) of rats were isolated and cultured. The PMCs were stimulated with 2.5% glucose PDF and added with 5 μmol/L CAPE intervention. The Nrf2 inhibitor (ML385) was used to identify whether CAPE protected PMCs from PDF by activating the Nrf2/HO-1 pathway. Histopathological staining was used to detect structural changes of the peritoneum, and immunohistochemical analysis was performed on cleaved caspase-3, Bax, α-smooth muscle actin (α-SMA), fibronectin (FN), and typeⅠ collagen (Col-Ⅰ) protein. Western blotting was used to detect the protein expression of α-SMA, FN, transforming growth factor-β1 (TGF-β1), HO-1 and nuclear Nrf2 (N-Nrf2). The apoptosis detection kit was used to detect apoptosis and flow cytometry was used to detect reactive oxygen species (ROS) in PMCs. The malondialdehyde (MDA) and superoxide dismutase (SOD) activity detection kit were used to detect MDA content and SOD activity. Cell immunofluorescence was used to analyze the protein expression of Nrf2 in PMCs. Results:Compared with the CON group, the PD group had thicker peritoneum, and the expression levels of cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰand MDA in peritoneum were significantly higher, while HO-1, N-Nrf2 protein expression and SOD activity were lower (all P<0.05). Compared with the PD group, the parietal peritoneum morphology of CAPE+PD group was improved, accompanied by reduced cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰ protein expression, and MDA content, while N-Nrf2, HO-1 protein expression, and SOD activity were higher (all P<0.05). Compared with the CON group, the PD group had significantly lower ultrafiltration volume and higher peritoneal permeability (both P<0.05). After CAPE intervention, the peritoneal transport function of the rats was significantly improved ( P<0.05). In cultured PMCs, PDF inhibited nuclear translocation of Nrf2 and protein expression of HO-1, and upregulated intracellular ROS level. In addition, PDF increased cell apoptosis and the protein expression levels of α-SMA, TGF-β1 and FN (all P<0.05). CAPE activated nuclear translocation of Nrf2, increased HO-1 protein expression, downregulated intracellular ROS level, and partially reversed PDF-induced cell apoptosis and epithelial- mesenchymal transition (all P<0.05). The protective effects of CAPE on PMCs were partially abolished by ML385 (all P<0.05). Conclusions:CAPE can reduce PD-induced PMCs apoptosis and epithelial-mesenchymal transition by attenuating oxidative stress, and significantly improve peritoneal fibrosis and ultrafiltration function. The beneficial effects of CAPE on peritoneum are related to activation of Nrf2/HO-1 pathway.

Objective:To investigate the association between C-reactive protein (CRP)/albumin (ALB) ratio (CAR) and mortality in peritoneal dialysis (PD) patients.Methods:Clinical data of 791 PD patients in the Second Affiliated Hospital of Soochow University from January 1, 2004 to December 31, 2019 were retrospectively collected. According to the baseline quartiles of CAR, patients were divided into three groups: low-level CAR group (CAR≤0.161 mg/g, n=264), medium-level CAR group (CAR 0.162-0.214 mg/g, n=263) and high-level CAR group (CAR≥0.215 mg/g, n=264). The clinical data among the three groups were compared. Follow-up was ended on March 31, 2020, or when the patients stopped PD due to death, shift to hemodialysis, renal transplantation or recovery of renal function. Kaplan-Meier survival curve, multivariate Cox proportional hazard model and Fine-Gray competing risk model were used to assess the relationship between CAR and all-cause mortality and cardiovascular and cerebrovascular mortality. The association between CAR, CRP, ALB, neutrophil to lymphocyte ratio (NLR), or platelet to lymphocyte ratio (PLR) and mortality in PD patients was compared by receiver-operating characteristic curve (ROC curve) analysis. Results:The age of the patients was (59.8±15.7) years old, and 447(56.5%) patients were males. 714(90.3%) patients had hypertension. 233(29.5%) patients had diabetes. 182(23.0%) patients had cardiovascular diseases. The median follow-up time was 55(31, 88) months. By the end of the follow-up, 236 deaths (29.8%) happened, and 95 patients (12.0%) died from cardiovascular and cerebrovascular diseases. Kaplan-Meier survival analysis results showed that the overall survival rate of the high-level CAR group was lower than those of the low-level CAR group and medium-level CAR group (Log-rank test χ2=109.50, P<0.001). Multivariate Cox regression analysis and Fine-Gray competing risk model revealed that CAR was independently correlated with all-cause mortality and cardiovascular and cerebrovascular mortality after adjusting for confounding factors ( HR=2.891, 95% CI 1.921-4.351, P<0.001; SHR=1.297, 95% CI 1.128-1.490, P<0.001). ROC curve analysis results showed that the area under the curve ( AUC) of CAR for predicting the risk of all-cause mortality in PD patients was 0.737(95% CI 0.700-0.774), which was superior to those of CRP ( AUC=0.643, 95% CI 0.599-0.687), NLR( AUC=0.608, 95% CI 0.563-0.653) and PLR ( AUC=0.554, 95% CI 0.508-0.601), and slightly lower than ALB ( AUC=0.752, 95% CI 0.716-0.788). The optimal cutoff value of CAR for death was 0.19 mg/g, with the sensitivity and specificity of 70.8% and 68.3%, respectively. Conclusions:Increasing CAR level is an independent risk factor of all-cause mortality and cardiovascular and cerebrovascular mortality in PD patients, and its correlation with mortality is higher than those of inflammatory parameters such as CRP, NLR and PLR.

Objective To investigate the relationship of red cell distribution width (RDW) with all-cause mortality and cardiovascular disease (CVD) mortality in patients undergoing maintenance hemodialysis (MHD).Methods A retrospective analysis was performed in patients who initiated MHD from January 2008 to September 2017 in the hemodialysis center of the Second Affiliated Hospital of Soochow University.Basic data on demographic,dialysis and laboratory were collected,and echocardiography indicators and clinical outcomes were recorded.Patients were divided into four groups according to the quartile of RDW level.Kaplan-Meier survival analysis was used to compare the difference of survival rate among the groups.Cox regression analysis was used to analyze the risk factors of all-cause and CVD-related mortality,and predictive value of RDW for all-cause and CVD-related death in hemodialysis patients.Results A total of 268 MHD patients were enrolled in this study with age of (60.9± 15.8) years and dialysis duration of (58.1±9.1) months,including 159 males (59.3％).Kaplan-Meier survival analysis showed that the 1-year overall survival rates of Q1 group (RDW≤ 13.8％,n=61),Q2 group (RDW 13.9％-14.6％,n=66),Q3 group (RDW 14.7％-15.6％,n=73)and Q4 group (RDW≥15.7％,n=68) were 96.8％,95.1％,93.1％ and 85.7％ respectively;3-year overall survival rates were 88.5％,87.5％,59.2％ and 51.8％ respectively;5-year overall survival rates were 71.5％,65.4％,33.6％ and 17.7％ respectively;The difference between the groups was statistically significant (all P ＜ 0.01).The 1-year CVD survival rates were 98.4％,96.6％,95.8％ and 92.4％ respectively;3-year CVD survival rates were 94.8％,92.5％,84.4％ and 70.4％ respectively;5-year CVD survival rates were 86.9％,81.3％,65.6％ and 51.3％ respectively;The difference between the groups was statistically significant (all P ＜ 0.01).Multivariate Cox regression analysis showed that RDW≥15.7％ was an independent risk factor for all-cause and CVD-related mortality in MHD patients.The risk of all-cause mortality in Q4 group was 3.098 times higher than that in Q 1 group (95％ CI 1.072-8.950,P=0.037) and the risk of CVD-related mortality was 2.661 times (95％ CI 1.111-8.342,P=0.048).Receiver operating characteristic curve (ROC) showed that RDW=14.85％ was the best cut-off point for predicting the all-cause mortality in HD patients (P ＜ 0.01),RDW=15.45％was the best cut-off point for predicting the cardiovascular disease mortality (P ＜ 0.01),and RDW=14.45％ had a higher 5-year survival rate (P ＜ 0.01).Conclusion RDW can independently predict all-cause and CVD-related mortality risk in hemodialysis patients,and it has important value for prognosis.

Objective To investigate the prevalence of restless legs syndrome (RLS) in peritoneal dialysis patients and analyze the related risk factors.Methods This study was a cross-sectional study.The patients receiving maintenance peritoneal dialysis from January 2017 to December 2017 in the Peritoneal Dialysis Center of the Second Hospital Affiliated to Soochow University were selected as the study subjects.RLS was screened for peritoneal dialysis patients by epidemiological field investigation based on the RLS diagnostic criteria of the International Restless Leg Syndrome Research Group in 2014.Clinical data and laboratory examinations of selected patients were collected and the differences of clinical indicators between RLS and non-RLS patients were compared.The risk factors related to RLS were analyzed by logistic regression.Results Seventy-six cases of RLS were screened out from 396 PD patients.The prevalence of RLS was 19.2％.Compared with non-RLS group,RLS group patients had longer dialysis age,less 24 hours urine volume,and elevated blood intact Parathormone (iPTH) and alkaline phosphatase (AKP) (all P ＜ 0.05).There was no significant difference in primary disease ratio,sex,age,body mass index,blood pressure,hemoglobin,creatinine,urea nitrogen,uric acid,ferritin,serum iron,transferrin saturation,blood calcium,blood phosphorus,total cholesterol,triglyceride,low density lipoprotein,high density lipoprotein,eGFR,Kt/V,Ccr between RLS and non-RLS group patients (all P ＞ 0.05).Multivariate logistic regression analysis showed that long dialysis age (OR=1.010,95％CI 1.001-1.018,P=0.022) and high blood AKP (OR=1.005,95％CI 1.001-1.010,P=0.021) were independent risk factors for RLS in peritoneal dialysis patients (both P ＜ 0.05).Conclusions The prevalence of RLS is high in peritoneal dialysis patients.Long dialysis age and high blood AKP are independent risk factors for RLS.

Objective To analyze the therapeutic effect and prognosis of peritoneal dialysis in patients with end-stage polycystic kidney disease.Methods A retrospective analysis was performed on patients with polycystic kidney disease who were treated with peritoneal dialysis for more than 3 months between July 2007 and September 2016 in the Second Hospital Affiliated to Soochow University.A total of 45 patients were enrolled in this study.Another 45 patients of non-diabetic nephropathy were selected as the control group matched by gender,age,and time of PD initiation.The information of the two groups such as general data,dialysis related complications,incidence of peritonitis,prognosis was recorded.Survival analysis was performed using the Kaplan-Meier method and Log-rank test.The risk factors affecting patients' survival were analyzed with Cox regression model.Results There were no significant difference in pre-dialysis age,sex ratio,blood pressure,urine volume,body weight,eGFR,biochemical data,and the proportion of hypertension and diabetes mellitus in the polycystic kidney group and control group.24 h ultra-filtration volume,4 h D/Pcr,Kt/V and Ccr between the two groups showed no significant difference (all P ＞ 0.05).The incidence of peritonitis and the time of the first peritonitis in the two groups respectively as one episode per 82.4 months vs one episode per 81.5 months,(35.8±22.8) months vs (34.5±20.9) months had no statistical difference.The ratio of hernia (6.6％ vs 2.2％),thoracic and abdominal leakage (4.4％ vs 2.2％),dialysate leakage (0 vs 0),catheter dysfunction (4.4％ vs 6.6％),exit-site infections (11.1％ vs 6.6％),tunnel infections (4.4％ vs 2.2％) and non PD related infections (11.1％ vs 13.3％) had no significant difference.The 1-year,3-year,5-year patient survival of two groups respectively were 95.2％ vs 93.3％,78.9％ vs 75.0％,67.6％ vs 64.9％ (P=0.475),and 5-year technique survival was 78.7％ vs 76.7％ (P=0.623),demonstrating no obvious difference.Cox regression analysis showed that age and serum albumin were risk factors for the survival of patients.Conclusions The effect and prognosis of peritoneal dialysis in patients with polyeystic kidney and non polyeystic kidney were similar.Peritoneal dialysis is not the contraindication of polycystic kidney.Peritoneal dialysis can be used as a routine renal replacement therapy in patients with polycystic kidney disease.

The disease of critically ill patients was with rapid changes, and at any time faced the risk of emergency. The current commonly used rescue vehicles were larger and bulky implementation, which were not conducive to the operation, therefore the design of a portable rescue vehicle was needed. This new type of rescue vehicle is multi-layer folding structure, with small footprint, large storage space, so a variety of first aid things can be classified and put, easy to be cleaned and disinfected. In the rescue process, the portable rescue vehicles can be placed in the required position; box of various emergency items can be found at a glance with easy access; the height of the infusion stand can adjust freely according to the user height; the rescue vehicle handle can be easy to pull and adjust accord with human body mechanics principle. The portable rescue vehicle facilitates the operation of medical staff, and is worthy of clinical application.

Objective To reproduce a stable animal model of brain death in pigs, observe the change regularity of cerebral oxygen metabolism during the process of brain death, and to evaluate the significance and value of cerebral oxygen metabolism parameters for the diagnosis of brain death. Methods Twelve landrace pigs were used to create the brain death models using modified method of increasing epidural intracranial pressure (ICP). The mean arterial pressure (MAP) and ICP were monitored continuously during the process. The pigs were divided into four groups according to cerebral perfusion pressure (CPP) decreasing degree during brain death, namely CPP normal group and CPP decreasing 0%-30%, 30%-70%, and 70%-100% groups. Blood gas analysis of the external carotid artery and internal jugular vein were monitored discontinuously. The changes in cerebral oxygen metabolism parameters, including external carotid artery-internal jugular vein bulb oxygen content difference (AJDO2), internal jugular bulb-external carotid artery carbon dioxide partial pressure difference (DPCO2) and DPCO2/AJDO2 ratio, were observed. Results Brain death model were successfully reproduced in 12 experimental pigs. With MAP and ICP monitoring, the models at different stages of CPP could be repeatedly induced. The levels of AJDO2 and DPCO2 were increased gradually and then decreased, while the ratio of DPCO2/AJDO2 was constantly increased with the decrease of CPP. The level of AJDO2 in CPP decreasing 0%-30%group was significantly higher than that in CPP normal group [(5.86±1.21)% vs. (3.92±0.64)%], the levels of DPCO2 in CPP decreasing 0%-30% and CPP decreasing 30%-70% groups were significantly higher than those in CPP normal group [mmHg (1 mmHg = 0.133 kPa): 10.33±1.83, 11.48±2.32 vs. 6.11±1.43], and the ratios of DPCO2/AJDO2 in CPP decreasing 30%-70% and CPP decreasing 70%-100% groups were significantly higher than those in CPP normal group and CPP decreasing 0%-30% group (2.81±0.53, 4.12±1.07 vs. 1.57±0.64, 1.62±0.81). All the differences above were statistically significant (all P < 0.05). Conclusions With the decrease of CPP, cerebral oxygen metabolism showed a regular change during brain death. DPCO2 combined with DPCO2/AJDO2 is a reliable blood gas analysis index indicating intracranial hypoperfusion, which has certain reference value for the determination of brain death.

Objective To evaluate the diagnostic value of 18F-FDG PET-CT in looking for tumor primary lesion with multiple bone metastasis.Methods 84 patients with suspected bone metastases were detected by routine imaging (X -ray,CT,MRI)in our hospital from May 2012 to September 2014 were selected,18F -FDG PET/CT were used to find the primary lesion.The final diagnosis were confirmed by tissue pathology or by clinical imaging follow -up.The diagnostic sensitivity,specificity and accuracy on tumor bone metastasis of 18F -FDG PET/CT were recorded.Results In 84 patients,primary tumor was found in 49 cases,of which 46 cases (54.8%)confirmed pri-mary tumor by operation or pathology,the other 3 cases were false positive;35 patients were diagnosed as non meta-static bone tumor by PET/CT,in which 34 cases were finally confirmed as non metastatic bone tumor by pathology and follow -up;accuracy,sensitivity,specificity of 18F -FDG PET/CT were 54.8%(46 /84),93.9% (46 /49)and 95.2%(80 /84);18 cases of lung cancer,9 cases of prostate cancer,7 cases of breast cancer,5 cases of lymphoma, 4 cases of renal cell carcinoma,2 cases of liver cancer,1 cases of Uterine sarcoma were included in 46 primary tumors.Conclusion 18F -FDG PET/CT has a higher specificity,accuracy as well as higher detection rate in search of multiple bone metastases,thus it is beneficial to the clinical therapy.