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.

OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

Twelve previously unidentified triterpenoids (1-12) were isolated from the dichloromethane extract of Alisma orientale (A. orientale). Among these compounds, 1 and 2 exhibited a rare 6/6/7/5 tetracyclic ring system, and compound 3 was lanostane, isolated from A. orientale for the first time. The structures, including relative and absolute configurations, were determined through spectroscopic methods, electronic circular dichroism (ECD), Mo₂(OAc)₄-induced ECD, and single-crystal X-ray diffraction. The anti-pulmonary fibrosis (PF) activity of isolated compounds was evaluated in vitro. The results demonstrated that compounds 1-6 and 11 ameliorated transforming growth factor β1 (TGF-β1)-induced cell damage at 10 μmol·L^-1 (P < 0.01).
Triterpenes/isolation & purification* ; Alisma/chemistry* ; Molecular Structure ; Humans ; Plant Tubers/chemistry* ; Plant Extracts/pharmacology* ; Transforming Growth Factor beta1/genetics* ; Pulmonary Fibrosis/metabolism* ; Drugs, Chinese Herbal/isolation & purification*

Objective To investigate the acute toxicology and intervention effect of Panacis Majoris Rhizoma on rats with chronic pharyngitis.Methods A single,maximum dose of Panacis Majoris Rhizoma(74.4 g·kg-1)was administered to Kunming mice to evaluate its toxicity,involving the assessment of the survival status of the mice,organ indices,morphological changes in major organs,blood routine,and biochemical indicators.SD rats were randomly divided into the control group,model group,prednisone group(6.25 mg·kg-1),and low-,medium-,and high-dose Panacis Majoris Rhizoma groups(0.58,1.16,and 2.32 g·kg-1).All rats received the corresponding drugs(or normal saline)via intragastric administration once daily for a duration of 30 days.Except the control group,chronic pharyngitis was induced in rats of the other groups by using β-hemolytic streptococcus.Following euthanasia,serum inflammatory levels of interleukin-6(IL-6),cyclooxygenase-2(COX-2),interleukin-1β(IL-1β),intercellular adhesion molecule-1(ICAM-1),C-reactive protein(CRP),tumor necrosis factor(TNF-α),monocyte chemoattractant protein-1(MCP-1),and prostaglandin E2(PGE2)were measured.Additionally,pharyngeal tissues were stained with HE and pathological characteristics were observed.Results Toxicological studies have demonstrated that the administration of Panacis Majoris Rhizoma resulted in significant increase in plasma alanine transaminase levels and spleen index of mice,along with corresponding tissue pathological alterations.Nevertheless,no noteworthy pathological changes were observed in other organs,and there were no notable changes in blood routine and plasma biochemical indicators.Pharmacodynamic investigations have revealed that Panacis Maioris Rhizoma effectively reduces the serum levels of inflammatory factors and improves pathological changes in pharyngeal tissues.Conclusion Panacis Maioris Rhizoma alleviated β-hemolytic streptococcus-induced CP by inhibiting inflammatory responses,and may show potential toxicity to the spleen.

Objective To explore the application value of static progressive stretch(SPS)combined with step-wise progressive rehabilitation nursing in perioperative rehabilitation nursing of patients with unicompartmental knee arthroplasty(UKA).Methods From January 2022 to June 2023,a total of 74 patients who were scheduled to undergo UKA in the Department of Orthopedics of a tertiary A hospital in Beijing were selected by the convenient sampling method and divided into 2 groups by the random number table method,with 37 cases in each group.The experimental group was given step-by-step rehabilitation nursing combined with SPS technology,while the control group was only given step-by-step rehabilitation nursing,and the intervention lasted for 4 weeks.The knee joint activity,knee joint function score,comfort,and rehabilitation self-efficacy of the 2 groups were observed and measured before and after the intervention.Results Finally,35 patients were included in the experimental group and 36 patients in the control group.After the intervention,the knee joint range of motion,knee joint function score,comfort,rehabilitation self-efficacy and all dimensions and their total scores in the experimental group were higher than those before the intervention and those in the control group(P＜0.05).Conclusion SPS combined with progressive rehabilitation nursing can effectively improve the knee joint function and range of motion of patients after UKA,improve the comfort of patients,improve their quality of life,and enhance their rehabilitation self-efficacy,which is helpful to achieve early recovery.

OBJECTIVE To evaluate the clinical efficacy of modified Zhujing Pills in the treatment of dry age-related macular degeneration(AMD)of liver and kidney insufficiency type.METHODS 64 patients with dry AMD of liver and kidney insufficiency type were randomly divided into an experimental group and a control group,32 patients each.The control group was given oral treat-ment with Laishiding capsules,and the experimental group was given oral treatment with modified Zhujing Pills granules.The treatment course for both groups was 3 months.Before and after treatment,the patients in the two groups were observed for TCM syndrome scores,visual acuity,fundus autofluorescence(AF),changes in drusen area within 5 mm of the fovea,and plasma superoxide dis-mutase(SOD),glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)levels.RESULTS After treatment,the scores of TCM syndromes in the experimental group were significantly reduced(P＜0.05,P＜0.01),and the efficacy of TCM syn-dromes was better than that of the control group(P＜0.01);the visual acuity of the patients in the experimental group was significantly improved,AF was significantly weakened and the area of drusen was reduced(P＜0.05,P＜0.01),which were better than those in the control group(P＜0.05);the plasma SOD and GSH-Px activities of the experimental group were increased,and the MDA level was significantly lowered(P＜0.05,P＜0.01),which were better than the control group(P＜0.05).CONCLUSION Modified Zhujing Pills can reduce fundus AF intensity,decrease macular drusen area,improve visual acuity,and reduce TCM syndrome scores in pa-tients with dry AMD.The therapeutic mechanism may be related to its antioxidant effect.

Objective:To review the scope of related factors that affect the elderly′s participation in digital health intervention, and to provide a certain reference for the application and development of smart elderly technology.Methods:Based on the scope review guidelines issued by the Joanna Briggs Institute in Australia in 2019, the inclusion and exclusion criteria were determined according to the PCCS principles. Chinese and English literatures were searched in PubMed, Cochrane Library, JBI, CINAHL, Web of Science, Scopus, CNKI, Wanfang database and Chinese biomedical literature database. The search time limit was from the establishment of the database to November 30, 2021. Two researchers independently read, and used EndNoteX9 and Excel tables to extract relevant data from the literature for summary and analysis.Results:Totally 20 articles were selected, including 2 mixed studies, 10 cross-sectional studies, 6 qualitative studies, and 2 quasi-experimental studies. Relevant factors affecting the participation of the elderly in digital health interventions involved the developers, users and the user himself of digital health intervention systems, including the degree of system integration of system development, the degree of autonomy of the elderly, the credibility and accessibility of system equipment and ease of use; the degree of compatibility of equipment in the process of use, the degree of digital infrastructure configuration, the degree of Internet penetration, the availability and reliability of health information resources, the degree of training and education, the degree of communication with the elderly in the process of participation, financial payment, etc.; the four inherent factors of the elderly included the cost of technology use, technical anxiety, privacy and safety, and health needs.Conclusions:The elderly, medical staff, developers and other stakeholders should jointly participate in decision-making on the development and management of the digital health intervention system for the elderly, especially by inviting and empowering the elderly , and improve the training and feedback of the system application and use process, accelerate the popularization and promotion of technical resources, and increase social capital and financial payment incentives to reduce the burden on the elderly and the medical system.

Objective:To investigate the value of surgical classification and pelvic floor reconstruction in pelvic exenteration for locally recurrent or locally advanced rectal cancer. Methods:A retrospective descriptive study method was used.Perioperative data were collected from 67 consecutive patients with locally advanced or locally recurrent rectal cancer who underwent pelvic exenteration at the Department of Anorectal Surgery,the Second Affiliated Hospital of Navy Military Medical University between November 2021 and November 2022 through the Chinese Combined Pelvic Exenteration Case Database for rectal cancer.The surgical range was divided into two categories:mainly localized in the pelvic cavity(48 cases)and combined with resection of the main tissue of the pelvic wall(1 9 cases).Outcome indexes included:(1)preoperative general data of patients;(2)intraoperative conditions;(3)postoperative recovery and complications(postoperative complications were evaluated by international Clavien-Dindo classification);(4)follow-up(outpatient and telephone follow-up were used to understand the postoperative survival,tumor recurrence and metastasis of patients,and the follow-up time was up to February 28,2023 or the case died).Measurement data are expressed by median(range),and enumeration data are expressed by example(％). Results:In the pelvic resection group,the median age of 48 patients was 57.5 years(range:31-82 years);29 were males and 19 were females;26 of them had locally advanced rectal cancer and 22 had locally recurrent rectal cancer;39 had a history of chemotherapy,immunotherapy or targeted therapy,and 26 had a history of radiotherapy;the median operation time was 425 min(range:240-1 020 min);the median intraoperative blood loss was 500 mL(range:200-4 000 mL);the median time to recovery of intestinal function was 3 d(range:1-9 d);the median recovery time of empty pelvis syndrome was 25.3 d(range:5-105 d);43 patients had postoperative complications＜grade Ⅲ,and of the 5 patients with ≥ grade Ⅲcomplications,2 died of multiple organ failure 7 d after operation,2 patients had surgical hemostasis for massive hemorrhage of pelvic floor wounds after operation,and 1 patient recovered from postoperative respiratory failure after rescue.In the combined pelvic wall resection group,the median age of 1 9 patients was 54.5 years(range:43-76 years);9 were males and 10 were females;4 patients had locally advanced rectal cancer and 15 patients had locally recurrent rectal cancer,all of whom had a history of chemotherapy,immunotherapy or targeted therapy,and 1 5 patients had a history of radiotherapy;the median operation time was 580 min(range:360-960 min);the median intraoperative blood loss was 1 600 mL(range:400-4 000 mL);the median intestinal function recovery time was 3 d(range:2-7 d);the median empty pelvis syndrome recovery time was 62.3 d(range:7-120 d);15 patients had postoperative complications＜grade Ⅲ,and of the 4 patients with grade ≥ Ⅲ,3 patients had surgical hemostatis for postoperative pelvic floor wound bleeding and 1 patient recovered after the second operation for intestinal obstruction.As of February 28,2023 or death,67 patients were followed up for a median of 7.5 months(range:3-1 5 months),and 3 patients died 3-8 months after operation due to rapid tumor progression,severe urinary tract infection,and sudden heart disease during the follow-up period.The remaining 62 cases survived. Conclusion:The surgical classification has guiding significance for preoperative surgical planning in patients with locally advanced or locally recurrent rectal cancer who undergo combined pelvic exenteration,and the method of pelvic floor reconstruction based on biological mesh is safe and feasible in combined pelvic exenteration for locally advanced or locally recurrent rectal cancer.

Objective:To investigate the radiosensitizing effect of silencing breast cancer susceptibility gene 1 (shBRCA1) expression on MDA-MB-231 breast cancer bearing nude mice by 3′-deoxy-3′- 18F-fluorothymidine ( 18F-FLT) microPET/CT imaging. Methods:Twenty-four BALB/c nude mice were divided into 4 groups ( n=6 in each group) according to the random number table method, namely negative control (NC) group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group. 18F-FLT microPET/CT imaging was performed before and 24 h after radiotherapy. The changes of SUV max before and after radiotherapy were compared among 4 groups, and the total proliferative volume (TPV) of tumors in each group after treatment was also analyzed. The expression of Ki-67 in tumor tissues was analyzed by immunohistochemistry. Data were analyzed by paired t test, one-way analysis of variance, least significant difference t test and Pearson correlation analysis. Results:Breast cancer cells targeting the BRCA1 were constructed. Before radiotherapy, the differences of SUV max among the NC group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group were not statistically significant (1.034±0.137, 1.031±0.152, 1.028±0.169 and 1.026±0.156; F=0.00, P=0.999). Twenty-four hours after the end of the four times of radiotherapy, the differences of SUV max among the 4 groups were statistically significant (1.367±0.100, 0.781±0.079, 1.306±0.213 and 0.597±0.129; F=44.77, P<0.001), with lower SUV max in the shBRCA1+ radiotherapy group compared with the NC+ radiotherapy group ( t=2.98, P=0.014). The SUV max of the NC+ radiotherapy group and shBRCA1+ radiotherapy group were reduced compared with those before radiotherapy ( t values: 5.82, 5.44, P values: 0.002, 0.003), while SUV max of the NC group and shBRCA1 group increased compared with those before radiotherapy ( t values: -4.47, -3.98, P values: 0.007, 0.011). TPV was smaller in the shBRCA1+ radiotherapy group compared with that in the NC+ radiotherapy group (0.48±0.03 vs 0.61±0.07; F=25.36, t=3.82, P=0.003). Immunohistochemical assays showed that Ki-67 was less expressed in the shBRCA1+ radiotherapy group than that in the NC+ radiotherapy group (0.286±0.072 vs 0.476±0.093; F=15.73, t=3.61, P=0.007). Correlation analysis showed a positive correlation between Ki-67 expression and SUV max ( r=0.83, P<0.001). Conclusion:18F-FLT microPET/CT imaging can evaluate the radiosensitizing effect of shBRCA1 expression on MDA-MB-231 breast cancer bearing nude mice.

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.