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 evaluate the clinical safety and effectiveness of intravascular stent combined with 125I seed strip implantation in the treatment of superior vena cava syndrome(SVCS)caused by malignant tumors.Methods The clinical data of 43 patients with SVCS,who were admitted to the Affiliated Hospital of Xuzhou Medical University of China from May 2017 to October 2022,were retrospective analyzed.Of the 43 patients,27 received intravascular stent combined with l25I seed strip implantation(observation group),and 16 received simple intravascular stent implantation(control group).The stent patency rate,clinical symptom relief rate,and survival time were compared between the two groups.Results Successful operation was accomplished in all the 43 patients.In the observation group,the postoperative 3-month stent patency rate and average survival time were 88.7％and 39.1 weeks respectively,which were significantly higher than 62.5％and 21.8 weeks respectively in the control group,the differences between the two groups were statistically significant(P=0.033 and P=0.035 respectively).After treatment,all the clinical symptoms were relieved.Conclusion For the treatment of SVCS,intravascular stent combined with 125I seed strip implantation is clinically safe and effective,it can be used as the preferred treatment option.(J Intervent Radiol,2024,33:632-635)

The gut microbiota is a vast microbial ecosystem,specifically present in the organism and plays an important regulatory role in the body's health or disease state together with its metabolites.After spinal cord injury,the complex pathophysiology at the site of trauma makes axonal regeneration difficult,and the autonomic motor dysfunction induced by spinal cord injury disrupts gastrointestinal function and causes gut microbiota imbalance.The previous clinical outcomes of neurorepair strategies after spinal cord injury have not been ideal.The dysregulated gut microbiota and neuroinflammation after spinal cord injury are closely associated with the prognosis of the patients.The potential mechanisms by which the gut microbiota may influence the neuroinflammation after spinal cord injury may include the activation of gut-associated lymphoid tissue and disruption of the intestinal barrier by the imbalanced microbiota,and gut microbiota and its metabolites such as lipopolysaccharides(LPS),short chain fatty acids(SCFAs),5-hydroxytryptamine(5-HT),and tryptophan,as well as immune cells,inflammatory factors,and neurotransmitters the local inflammatory response in the spinal cord through the circulatory system.This paper revews the studies on the changes in gut microbiota after spinal cord injury and their effects on the spinal cord neuroinflammation,providing new targets and new ideas for improving the neuroinflammation after spinal cord injury.

The article reviews the clinical and mechanism researches of acupuncture-moxibustion in treatment of rheumatoid arthritis (RA) in recent two decades at home and abroad. The results indicate that acupuncture-moxibustion is conductive to RA with fewer adverse reactions for the patients, and improves joint function and quality of life to a certain extent. The therapeutic results of acupuncture-moxibustion result from the multi-target, multi-level collaborative effect on RA. In mechanism, the overall regulation of the neuro-immuno-endocrine system is involved. RA is attenuated through inhibiting inflammatory responses, regulating relevant signaling pathways, maintaining the balance of osteoblasts and articular cartilage, and adjusting the gene expression. Although some achievements have been obtained in clinical and mechanism researches, it still needs to deepen the mechanism research so as to promote the clinical application of acupuncture-moxibustion and provide the new approaches to its innovation and development.
Humans ; Moxibustion ; Arthritis, Rheumatoid/therapy* ; Acupuncture Therapy ; Animals

Objective: To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on arrhythmia during acute myocardial ischemia-reperfusion and the expression of connexin 43 (Cx43) in rats. Methods: A total of 40 Sprague-Dawley male rats were used. Ten rats were randomly selected as the blank group, and the remaining 30 rats were randomly divided into a model group and an EA group, with 15 rats in each group. Before modeling, rats in the EA group received one session of EA intervention at bilateral Neiguan (PC6) for 30 min; the other groups were treated with the same grasping and anesthesia for 30 min without intervention. PowerLab physiological recorder was used to record electrocardiograph within 30 min of infarction. After the experiment, cardiac tissue and serum were collected from rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in the ventricular infarction area of rats in each group. The expression of Cx43 protein in the myocardium of each group was detected by Western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of Na+-K+-ATPase in myocardial tissue and the serum content of endogenous digitalis-like factor (EDLF) in rats. Results: There was no statistical difference in arrhythmia score between the EA group and the model group, but the total duration and average duration of arrhythmia in the EA group were decreased (P<0.01). HE staining showed that compared with the blank group, myocardial cells in the model group were disorganized and seriously damaged. The pathological changes in the EA group were similar to those in the model group, but the damage was relatively minor. The results of WB showed that compared with the blank group, the Cx43 expression in myocardial tissue of the model group was decreased (P<0.01); compared with the model group, the Cx43 expression in the EA group was increased (P<0.01); compared with the blank group, the Na+-K+-ATPase activity in myocardial tissue of the model group was significantly decreased (P<0.01); compared with the model group, the Na+-K+-ATPase activity in the EA group was increased (P<0.01). ELISA results showed that compared with the blank group, the serum EDLF content in the model group was significantly increased (P<0.01); compared with the model group, the EDLF content in the EA group was decreased (P<0.01). Conclusion: EA at Neiguan (PC6) can delay and reduce the onset of arrhythmia during myocardial infarction in the rat model of myocardial ischemia-reperfusion. Its mechanism of action may be related to the regulation of the Cx43 expression in myocardial tissue, improvement of the activity of Na+-K+-ATPase in myocardial tissue, and increase in the content of serum EDLF.

Adult ; Humans ; Retrospective Studies ; Pneumonia ; Community-Acquired Infections/epidemiology* ; Hospitalization

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To investigate the clinical outcomes and complication of posterior surgery for Scheuermann kyphosis fusing to different distal fusion levels.Methods:From January 2012 to December 2017, a consecutive cohort of 34 patients who were treated with posterior spinal instrumented correction and satisfied the inclusion criteria were retrospectively reviewed, including 29 males and 5 females, aged 17.1±4.3 years (range, 12-30 years). All of the patients had a minimum follow-up of 2 years. According to the distal fusion level, patients were divided into 2 groups. Group sagittal stable vertebra (SSV) (22 cases) included patients whose lowest instrumented vertebra (LIV) was SSV; Group SSV-1 (12 cases) included patients who had a LIV one level above the SSV. Radiographic parameters including global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured in the standing radiographs before and after operation and at the latest follow up. Intraoperative and postoperative complications were recorded. The Scoliosis Research Society-22 questionnaire (SRS-22) were conducted at pre-operation and the final follow up to evaluate the clinical outcomes. The sagittal radiographic parameters and the incidence of distal junctional kyphosis (DJK) were compared between the two groups.Results:There were no significant differences in terms of age, sex, radiographic measurements and scores of SRS-22 between two groups preoperatively ( P>0.05). The correction rates of GK in the SSV group and the SSV-1 group were 42.8%±7.6% and 43.2%±8.4% ( t=0.151, P=0.881) respectively. While the correction rates loss were 1.2%±5.2% and 3.9%±7.2% ( t=0.767, P=0.449) at the latest follow up. No significant difference was observed in terms of other radiographic parameters ( P>0.05). During the postoperative follow up period, 3 patients (16.7%) in SSV group and 2 patients (13.6%) in SSV-1 group developed DJK. The incidence of DJK did not show any significant difference between two groups ( χ2=0.057, P=0.812). At the final follow-up, the function scores of SRS-22 in SSV-1 group (4.1±0.6) was significantly higher than SSV group (3.7±0.5) ( t=2.300, P=0.028) and there was no significant difference in the rest of the domain ( P>0.05). Conclusion:Compared with stopping at SSV, fusion to SSV-1 could achieve comparable curve correction with the preservation of more lumbar motility. Moreover, it would not increase the risk of DJK. As a result, we recommend selecting SSV-1 as the ideal LIV for SK patients.

[摘 要] 目的：探讨表皮生长因子受体（epidermal growth factor receptor，EGFR）基因突变与非小细胞肺癌（non-small cell lung cancer，NSCLC）伴脑转移患者预后的相关性，为改善NSCLC合并脑转移患者预后、指导个体化治疗提供临床依据。方法：回顾性分析福建省立医院2013年1月1日至2018年9月30日期间收治的88例NSCLC合并脑转移患者的临床资料，随访取得患者的死亡时间，随访截止日期为2019年10月31日。收集和分析的临床资料包括性别、年龄、吸烟史、病理类型、基因检测、治疗情况、无进展生存期（progression free survival，PFS）、总生存期（overall survival，OS）等。运用生存分析（Kaplan-Meier生存时间曲线）评价EGFR突变型患者的预后，以单因素分析（log-rank检验）预测影响EGFR-TKI治疗效果的因素。结果：88例NSCLC脑转移患者有57例为EGFR突变型，其中位PFS（MPFS）为13.0个月（95%CI：11.951~14.049），明显高于EGFR野生型患者（P=0.003），患者中位生存期（median survival time，MST）为29.0个月（95%CI：20.531~37.468），明显高于EGFR野生型（P=0.001）。EGFR突变型中，Exon19-del突变组患者较Exon21 L858R突变组患者OS有延长趋势（P=0.05），Exon19-del+Exon20T790M突变组患者OS较Exon21 L858R突变组有延长趋势（P=0.077）。结论：EGFR突变组较野生型组NSCLC脑转移患者预后相对好些，且携带19外显子单一缺失突变的患者预后最好。

Objective:To investigate the prevalence of pre-diabetes mellitus (PDM) and the impact of occupation-related factors on PDM, among workers from a steel company in Tangshan city, Hebei province.Methods:Clustering sampling method was used to select a steel company and to carry out occupational health-related physical checkup programs for eligible workers who had working in this company for longer than one year. The study began in February and ended up in June, 2017. Workers who were with FPG level as ≤6.9 mmol/L, and free from diabetes, were selected as the subjects for this study. Questionnaires were used and physical examinations and FPG testing conducted.Results:The total number of subjects in this study was 4 173, of which 2 648 appeared as pre-diabetic, with the prevalence rate as 63.4 %. Increase of the PDM prevalence was in parallel with the length of service, among the workers. The risk for the pre-diabetes in those who worked more than 8 hours per day was 1.696 times higher than those who worked less than or equal to 8 h/d (95 %CI:1.517-1.937). Compared with those workers without exposures to heat, noise or carbon monoxides, the proportion of pre-diabetes appeared higher in workers exposed to heat, noise or CO with OR=1.782 (95 %CI: 1.205-2.636), 1.815 (95 %CI: 1.209-2.794) and 1.653 (95 %CI: 1.158-2.361), respectively. Risks for those who were exposed to heat or noise were higher than those who were free from exposure to any occupational hazards ( OR=2.098, 95 %CI: 1.296-3.397). Prevalence rates of pre-diabetes in those who were exposed to heat, noise or CO, were higher than that those who were not. Conclusion:Working hours and exposures to heat, noise or CO appeared as influential factors on PDM.