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 analyze the risk factors and re-intervention strategies for mid- and long-term residual after arterial switch operation (ASO). Methods The clinical data of children with complex congenital heart disease who underwent ASO surgery in Shanghai Children’s Medical Center from January 2006 to June 2022 were retrospectively collected, and the risk factors for mid- and long-term residual after ASO were analyzed. Results A total of 952 children undergoing ASO were enrolled in this study, including 654 males and 298 females with an average age of (102.9±90.1) d and weight of (4.6±1.6) kg. There were 421 patients with D-transposition of the great arteries with intact ventricular septum (D-TGA/IVS), 357 patients with D-transposition of the great arteries with ventricular septal defect (D-TGA/VSD), and 174 patients with right ventricle double outlet combined with subpulmonary ventricular septal defect (Taussig-Bing malformation). Eighty-nine patients died early after the surgery, the mortality rate was 9.3%. The 746 surviving children were regularly followed up after the surgery (follow-up rate 86.4%), with a median follow-up time of 79.4 (12.0-188.0) months. During the follow-up, 53 children underwent surgical re-intervention due to residual, including 33 males and 20 females, with a median age of 62.5 (17.0-214.0) months. The median surgical weight was 19.0 (8.2-86.0) kg, and the mean time of re-intervention was 28.0-170.0 (77.5±45.4) months after the ASO. Residual problems included common trunk and branch stenosis of the pulmonary artery in 23 patients, right ventricular outflow tract (RVOT) obstruction in 11 patients, left ventricular outflow tract obstruction in 6 patients, aortic arch restenosis in 5 patients, aortic insufficiency in 5 patients, residual shunt of ventricular septal defect in 2 patients, and tricuspid valve insufficiency in 1 patient. The early postoperative mortality rate was 3.8% (2/53), with the causes of death being acute myocardial infarction due to coronary artery injury and acute left heart failure, respectively. The mean follow-up time of the surviving children was (52.4±28.6) months, and no mid- and long-term death occurred. Two patients underwent the third operations due to pulmonary restenosis. The multivariate analysis result showed that combined aortic arch surgery and early postoperative RVOT velocity>3 m/s were independent risk factors for mid- and long-term residual after ASO. Conclusion ASO is an ideal procedure for the treatment of D-TGA/IVS, D-TGA/VSD and Taussig-Bing malformations. Combined aortic arch surgery and early postoperative RVOT velocity>3 m/s are independent risk factors for mid- and long-term residual after ASO.

Objective To analyze the clinical efficacy of right midaxillary straight incision surgery in the treatment of doubly committed subarterial ventricular septal defect. Methods The clinical data of children with doubly committed subarterial ventricular septal defect who received surgeries in our hospital from August 2020 to July 2023 were analyzed retrospectively. All the children underwent surgical repair and were divided into two groups according to the incision position, including a right midaxillary straight incision group and a median incision group. The outcomes were compared between the two groups. Results A total of 187 patients were enrolled. There were 102 patients in the right midaxillary straight incision group, including 55 males and 47 females with a median age of 26.0 (5.0, 127.0) months and a median weight of 12.5 (5.1, 32.8) kg at surgery. There were 85 patients in the median incision group, including 37 males and 48 females with a median age of 4.0 (2.0, 168.0) months and a median weight of 6.7 (4.8, 53.9) kg at surgery. No mortality occurred in the study. There was no statistical difference between the two groups in the cardiopulmonary bypass time [(50.0±18.4) min vs. (46.1±15.7) min] or aortic cross-clamping time [(31.3±18.6) min vs. (26.3±17.5) min] (P>0.05). Compared to the median incision group, the time from the end of cardiopulmonary bypass to the closure of chest [(22.3±15.6) min vs. (37.1±13.4) min, P<0.001], postoperative hospital stay [(6.9±3.9) d vs. (8.6±3.6) d, P=0.002], the length of incision [(4.3±2.7) cm vs. (8.5±3.2) cm, P<0.001], drainage volume [(79.0±32.2) mL vs. (100.2±43.1) mL, P<0.001], and the pain score on the 2nd and the 3rd day after the operation were statistically better in the right midaxillary straight incision group (P<0.05). The medical experience and incision satisfaction scores at discharge of the right midaxillary straight incision group were higher (P<0.05). During the follow-up of 21.0 (1.0, 35.0) months, no residual shunt was detected and all patients in both groups had a normal cardiac function and mild or less valve regurgitation. Conclusion Compared to the median incision, minimally invasive right midaxillary straight incision for the repair of doubly committed subarterial ventricular septal defect offers comparable efficacy and reliability, with the added advantages of being minimally invasive, cosmetically superior, and promoting faster postoperative recovery.

ObjectiveTo analyze the clinical characteristics and imaging features of effectively treated pediatric Mycoplasma pneumoniae pneumonia （MPP） with pulmonary consolidation， follow up the volume changes of pulmonary consolidation on lung CT scans of the affected children， and investigate the resolution patterns of pulmonary consolidation， and predict the time required for complete resolution. MethodsWe enrolled children with MPP and pulmonary consolidation hospitalized in the Department of General Pediatrics at Children's Hospital of Chongqing Medical University between January 2018 and May 2024. Data collected included demographics， clinical symptoms， laboratory indicators， treatment status， imaging data during hospitalization， as well as follow-up lung CT data and reexamination intervals after discharge. Consolidation volumes were measured before and after the treatment to calculate the resolution rate and resolution velocity. Descriptive statistical analysis was performed on clinical characteristics， imaging features and consolidation resolution. ResultsAmong 238 children with MPP and lung consolidation， females slightly outnumbered males （the male to female ratio is 109 vs.129）， with a mean age of approximately 5 years. At admission， the median cough and fever durations were 7 （5-9） days and 6 （ 4-7） days， respectively. No significant increase was found in white blood cells count or lactate dehydrogenase（LDH）， and hypersensitive high-sensitivity C-reactive protein （CRP） slightly increased. Azithromycin was the first line of treatment in most cases， though second-line drugs increased in the recent two years due to the rising resistance. Bronchoalveolar lavage was performed in 66.8% （159/238） of children， and 33.2% （79/238） did not receive lavage. Consolidation was predominantly unilateral （206 unilateral vs. 32 bilateral） and right-sided （117 right-sided vs. 89 left-sided）. The ratio of consolidation volume to total lung volume was 4.48 （2.61-7.35） %， the consolidation resolution rate at follow-up was 96.08 （ 88.02-98.95） %， the reexamination interval was 17 （ 15-21） days， the resolution velocity was 2.15 （1.23-4.01） cm³/d， and the time to complete resolution was 18.96 （16.14-23.33） days . ConclusionsPulmonary consolidation in pediatric MPP achieves substantial resolution on CT within 2-3 weeks after effective clinical treatment. Initial consolidation volume and resolution velocity can predict the time required for complete resolution， thereby clinically guiding optimal CT follow-up scheduling.

Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

Objective To explore the clinical efficacy of the medicated stick massage at meridian knot points in treating Qi stagnation and blood stasis type lumbar disc herniation(LDH)based on the meridian theory.Methods The patients with LDH in the ward 5 of orthopedics department in this hospital from Sep-tember 2024 to April 2025 were selected as the research subjects.On the basis of routine treatment and care,the control group adopted the medicated stick massage at points,while the experimental group adopted the medicated stick massage at meridian knots.The visual analogue scale(VAS)scores,Japanese Orthopaedic So-ciety(JOA)score,TCM syndrome scores and TCM syndrome therapeutic effects before intervention and in two weeks after intervention were compared between the two groups.Results The VAS scores,each item score and total score of JOA,TCM syndrome scores and TCM therapeutic effects after 2-week intervention in the experimental group all were superior to those in the control group,and the differences were statistically significant(P＜0.05).Conclusion Selecting the medicated stick massage at the meridian knots under the guidance of meridian theory could significantly improve the pain symptoms,lumbar function,TCM syndrome scores,the therapeutic effects are definite,and is worthy of clinical promotion and application.

Objective:To evaluate the effective dose, efficacy and safety of remimazolam for induction of general anesthesia in super-elderly patients.Methods:Trial Ⅰ American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, aged ≥80 yr, with body mass index of 18-25 kg/m 2, undergoing elective surgery with general anesthesia in the Zhejiang Provincial People′s Hospital from January to March 2022, were selected. Remimazolam 0.12 mg/kg or propofol 0.8 mg/kg was intravenously injected in the first patient, and the dose of remimazolam or propofol in the next patient was determined by using the modified Dixon′s up-and-down method. The difference between the two successive doses was 0.01 mg/kg for remimazolam and 0.05 mg/kg for propofol. A positive response was defined as achieving an anesthesia depth (BIS value ≤ 65) within 5 min of administration. If the response was positive, the next patient received a lower dose, or conversely if negative, a higher dose was given in the next patient. The 50% effective dose (ED 50) and 90% effective dose (ED 90) of remifentanil and propofol and their 95% confidence intervals ( CIs) were calculated by Probit method. Trial Ⅱ One hundred and forty-six American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ elderly patients of either sex, aged ≥80 yr, with a body mass index of 18-25 mg/kg, scheduled for elective surgery with general anesthesia from April to October 2023 in Zhejiang Provincial People′s Hospital, were selected and divided into 2 groups ( n=73 each) by using a random number table method: remimazolam group (R group) and propofol group (P group). R group was induced with intravenous remimazolam ED 90 and P group was induced with intravenous propofol ED 90, and the injection time was both 30 s. If the BIS value was still greater than 65 at 5 min after administration, remimazolam 0.05 mg/kg was intravenously added each time in R group and propofol 0.5 mg/kg was intravenously added each time in P group until the patient′s BIS value ≤65. The success of anesthesia induction, time for successful induction of anesthesia and rescue sedation were recorded. The occurrence of intraoperative injection pain, hypertension, hypotension, bradycardia, hypoxemia, intraoperative awareness and postoperative delirium, nausea and vomiting was also recorded. Results:Trial Ⅰ The ED 50 (95% CI) of remimazolam was 0.148 (0.139-0.157) mg/kg, and the ED 90 (95% CI) was 0.160 (0.153-0.202) mg/kg; the ED 50 (95% CI) of propofol was 0.824 (0.726-0.983) mg/kg, and the ED 90 (95% CI) was 0.916 (0.860-2.472) mg/kg. Trial Ⅱ Compared with group P, the time for successful induction of anesthesia was significantly prolonged, the incidence of intraoperative injection pain and hypotension was decreased ( P<0.05), and no significant change was found in the success rate of anesthesia induction, rate of rescue sedation, intraoperative hypertension, bradycardia, hypoxemia, postoperative delirium, and nausea and vomiting in group R ( P>0.05). Conclusions:The ED 50 and ED 90 of remimazolam for induction of general anesthesia are 0.148 and 0.160 mg/kg, respectively, in super-elderly patients. Compared to propofol, remimazolam has a slightly longer onset time, but it is safer when used for induction of general anesthesia in super-elderly patients.

The report of the 20th National Congress of the Communist Party of China has made a major deployment to promote the expansion of high-quality medical resources and balanced regional layout, and the construction of national regional medical centers is an important measure to implement the landing. By analyzing the " three co-construction" mode of the National Children′s Regional Medical Center of Henan Children′s Hospital (Beijing Children′s Hospital Zhengzhou Hospital), this paper systematically introduced the internal and external decision-making, management and operation of the regional medical center from four aspects: management, talent, discipline and system. The practice and effectiveness in talent introduction and training, salary distribution, two-way communication, assessment and incentive, discipline construction, technology application, sharing and evaluation of scientific and technological innovation, institutional linkage and integration, as well as the construction of a hierarchical diagnosis and treatment system, were put forward. Suggestions such as construction according to local conditions, strengthening internal coordination, and optimizing external guarantee were put forward, so as to provide practical reference for the in-depth promotion of other national regional medical center construction projects.

Objective:To evaluate the safety and efficacy of hydroxyapatite-magnesium (HA-Mg) glaucoma drainage plate after implantation in rabbit eyes.Methods:Twelve New Zealand white rabbits were randomly assigned to HA-Mg drainage implant group and trabeculectomy group using the paired comparison method, with 6 rabbits in each group.The right eyes of rabbits were taken as the experimental eyes, and the left eyes of rabbits were taken as a normal control group.HA-Mg drainage implant group underwent implantation of the HA-Mg drainage plate and the trabeculectomy group underwent trabeculectomy.At 1, 3, and 5 months after surgery, the ocular condition was observed by slit-lamp examination with auxiliary lenses and the fixation of the drainage plate in the anterior chamber and subconjunctiva was measured by ultrasound biomicroscopy.At 5 months after surgery, corneal endothelial cell counts were performed with a corneal endothelial cell counter.The intraocular pressure (IOP) was continuously measured weekly for 21 weeks preoperatively and postoperatively.The flow patency of aqueous humor drainage channel was identified by the injection of trypan blue in anterior chamber.The aqueous humor drainage channels and surrounding tissues were evaluated by hematoxylin-eosin (HE) staining after HA-Mg drainage plate was completely degraded.This study was in accordance with China Animal Welfare Law and the ARVO Statement on the use of animals for ophthalmic research, and animal experiments were conducted in accordance with the Regulations on the Administration of Experimental Animals issued by the National Science Council.The study protocol was reviewed and approved by the Ethics Committee of The Third Affiliated Hospital of Chongqing Medical University (No.Kelun Pre-Examination [2021]14).Results:No systemic or ocular side effects were observed in the experimental animals after surgery.All 6 HA-Mg drainage plates were completely degraded about 4 months postoperatively, among which 4 plates were well-fixed and 2 plates had a minimal rotation, and no plate moved into the anterior chamber.At 5 months after surgery, the number of corneal endothelial cells in the HA-Mg drainage implant group and normal control group was 2 535.2±274.4 and 2 521.0±175.8, respectively, and there was no statistical significance between them ( t=0.073, P=0.857).There were statistically significant differences in IOP among the three groups at different time points before and after surgery ( Fgroup=26.409, P<0.001; Ftime=7.843, P<0.001), in which the IOP in trabeculectomy group and normal control group at different time points after surgery was higher than that in HA-Mg drainage implant group, and the IOP in HA-Mg drainage implant group at different time points after surgery was lower than that before surgery (all at P<0.05).The patency test revealed that the trypan blue could still drain from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation.The scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded 6 months postoperatively, and no obvious inflammatory cell infiltration was seen. Conclusions:After implantation of HA-Mg drainage plate in rabbit eyes, the intraocular pressure can be effectively lowered and the safety is good.

Objective To investigate the effect of Cyclocarya paliurus(Batal.)lljinskaja polysaccharides on insulin resistance in type 2 diabetic rats by regulating glucose transporter 4(GLUT4)translocation in islet and liver.Methods High-fat diet combined with low-dose streptozotocin(35 mg·kg-1)to induce type 2 diabetes model,all the rats were randomly divided into model control group,Cyclocarya paliurus polysaccharides groups(5,10 g·kg-1)and metformin group(0.25 g·kg-1),and treated for eight weeks(n=9 in each group).Fasting glucose and lipid were determined.Histopathology of rat islet and liver were observed by hematoxylin and eosin staining.Protein expressions of phosphorylated phosphoinositide-3-kinase(p-PI3K),phosphorylated serine-threonine kinase 1(p-Akt1),and GLUT4 in islet were measured by immunohistochemistry staining.GLUT4 translocation in the islet and liver was detected by immunofluorescence.Results Compared with the model control group,the Cyclocarya paliurus polysaccharides group and metformin group had declined fasting glucose levels and increased high-density lipoprotein(P＜0.05).The structure of the islets and liver was relatively complete.The content of p-PI3K,p-Akt1 and GLUT4 in the islet increased(P＜0.05).GLUT4 translocation in the liver and islet enhanced(P＜0.05).Conclusions Cyclocarya paliurus polysaccharides alleviate glucose and lipid metabolism disorders.The mechanism may lay in it activating protein expressions of p-PI3K,p-Akt1,and GLUT4 in islet cells.GLUT4 translocation to the islet and liver cell membrane are increased to regulate peripheral islet resistance.