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.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective : To study the effect of EFHD2 protein deletion in Sertoli cells on Occludin，a component of tight junction protein and the localization and expression of EF-hand domain family member D2 (EFHD2) in mouse testis． Methods : Total RNA and protein were extracted from adult mice's heart ，liver ，spleen ，lung ，kidney， brain and testis tissues．The mRNA and protein levels of EFHD2 in each organ tissue were detected by qRT-PCR and Western blot．Immunofluorescence and immunohistochemistry detected the localization and expression of EF- HD2 in testicular tissues．SiRNA interference was used to reduce EFHD2 in Sertoli cells to detect Occludin protein expression. Results : qRT-PCR showed that the expression of EFHD2 was the highest in the testis．Western blot results showed that the expression level increased in testis tissue．Indirect immunofluorescence and immunohisto- chemistry results showed that the protein was mainly distributed in Sertoli cells and co-localized with cytoskeletal Vimentin，indicating that the protein was expressed in Sertoli cells．After the decrease of EFHD2 protein expres- sion，Occludin protein expression also decreased． Conclusion The expression of EFHD2 protein in the testis is relatively high，mainly distributed in Sertoli cells of the testis，co-localized with Vimentin，and can affect the nor- mal expression of tight junction protein Occludin．It is suggested that EFHD2 can promote and maintain the junction structure of Sertoli cells and provide a stable microenvironment for spermatogenesis.

Objective: To establish a microwave digestion-inductively coupled plasma mass spectrometry assay for simultaneous determination of multiple elements in placenta. Methods: Fresh placental tissues were dried at 60 ℃ for 15 h and ground into power. Then, 0.3 g homogenized samples were digested in a microwave digestion system. The interference from mass spectrometry was removed using the kinetic energy discrimination model in the inductively coupled plasma mass spectrometry, and the baseline interference was removed by online internal standards. The contents of 17 elements were determined in placental specimens using the established microwave digestion -inductively coupled plasma mass spectrometry assay, including V, Ni, Co, Fe, Cr, Cu, Zn, Mn, As, Sn, Sb, Ba, Se, Cd, Pb, Hg and Tl. Results: Good linearity was shown for V, Ni, Co, Cr, As, Se, Cd, Pb and Tl at 1 to 50 µg/L, Fe at 100 to 5 000 µg/L, Zn, Cu, Mn and Ba at 10 to 500 µg/L, Sn and Sb at 0.1 to 5 µg/L, and Hg at 0.2 to 2 µg/L, with all correlation coefficients of 0.999 8 and higher. The detection limits of these 17 elements ranged from 0.5 to 100 μg/kg, with relative standard deviations of 2.1% to 6.5%, and recovery rates of 83.3% to 110.0%. The determination results of 17 elements were all within the normal reference range defined in the certified reference materials of chicken (GBW10018). Conclusions The microwave digestion-inductively coupled plasma mass spectrometry established based on optimized pretreatments and mass spectrometry detection conditions, is feasible for simultaneous determination of multiple elements in placenta.

Grey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Objective:To investigate the situation related to HIV infection and influencing factors of traceability efficiency among sex partners of HIV positive men who have sex with men (MSM).Methods:A cross-sectional survey was conducted to investigate the traceability among sex partners of HIV-positive MSM in Ningbo from 2018 to 2020. Limiting-antigen avidity enzyme immunoassay determined recent HIV infection. The classified data was evaluated by chi-square test, and factors of traceability efficiency were analyzed by multivariate logistic regression.Results:A total of 374 newly confirmed HIV-positive MSM were recruited to participate in the HIV test in Ningbo from 2018 to 2020.HIV positive rate of sex partner was 15.7% (75/479,95% CI:12.4%-18.9%). HIV positive rates of sex partner of recent HIV infection MSM was 31.8% (21/66,95% CI:20.3%-43.4%). The proportion of newly confirmed HIV-positive sex partners of recent HIV infection MSM (76.2%) was higher than that of long-term HIV infection MSM (48.1%). The difference was statistically significant ( P=0.028). Results from the multivariate logistic regression analysis showed that HIV traceability efficiency was higher in the following subpopulations as; HIV positive MSM who were 36-45 years old (compared with 18-25 years old, OR=3.973,95% CI:1.364-11.569), HIV active detection (compared with HIV passive detection, OR=1.896, 95% CI:1.083-3.319), recent HIV infection MSM (compared with long-term HIV infection MSM, OR=3.733, 95% CI:1.844-7.556). Conclusions:HIV positive rate among partners of HIV positive MSM was very high. The traceability efficiency, which was recent HIV infection MSM and HIV active detection, was high. It is suggested to strengthen the traceability and focus on the newly confirmed HIV-positive MSM in VCT clinics.

Objective:To explore the outcome of extended internal limiting membrane (ILM) peeling combined with releasing the edge technique for primary failed idiopathic macular hole (IMH) surgery.Methods:A retrospective analysis was performed. The data of 18 eyes of 18 IMH patients who were failed in primary surgery from August 2013 to June 2019 in Peking University People’s Hospital were enrolled in the study. Among them, 5 patients were males and 13 patients were females. The average age was 66.2±6.4 years. The BCVA were measured by ETDRS charts. The minimum macular hole size was measured on OCT B-scan image. The average preoperative BCVA and minimum macular hole size of primary surgery was 32.6±13.1 letters and 621.1±161.8 μm. The average preoperative BCVA and minimum macular hole size of second surgery was 34.4±12.3 letters and 499.0±148.6 μm. Average interval period of first and second surgery was 3.4±1.3 weeks. The surgical technique used in the reoperation included the extended ILM peeling combined with releasing the MH edges. The extended ILM peeling area ranged from 4 DD diameter to vascular arcades. The technique of releasing the macular hole edges was performed by using a silicone soft-tip extrusion cannula, with which tapping the edges softly or aspirated vacuum the edges concentricly. The average follow-up was 9.3±5.2 months. The clear OCT image can be obtained for confirming MH closure which was considered as the closure time in the first time. The comparison of preoperative and postoperative was performed by paired t-test. Results:The closure rate of second surgery was 94.4% (17/18), and average closure time was 2.1±1.0 weeks. Only 1 eye experienced the second surgical failure and received the third surgery to achieved macular hole closure. Average final follow-up BCVA was 51.5±13.0 ETDRS letters, with average improvement of 18.9 ETDRS letters (>3 lines) compared with preoperative BCVA of primary surgery. There was significantly statistical difference between the final BCVA and preoperative BCVA ( t=5.412, P <0.001). Eleven patients (61.1%) had 3 lines BCVA improvement, 15 patients (83.3%) had more than 1 line improvement, and 3 patients (16.7%) had on improvement. The final BCVA of patients significantly improved compared with preoperative BCVA of the second surgery ( t=7.595, P<0.001), with average improvement of 17.1±9.5 letters. Conclusion:The extended ILM peeling combined with releasing macular hole edges technique is effective to improve the closure rate and BCVA of primary failed IMH eyes.

Objective Proteus syndrome is a rare disease. The aim of the present study was to analyze the clinical characteristics and gene mutations of Proteus syndrome with a case report and relevant literature review. Methods Clinical data of the patient with Proteus syndrome were collected in detail and biochemical measurements and radiological examinations were conducted. Tissues from phalanges with lesions were obtained to extract DNA, and Sanger sequencing of AKT1 gene was carried on. The pathogenic mutation was further tested in peripheral blood samples of the patient, his parents and 250 healthy volunteers. Orthopaedic surgery was performed on the affected limbs of the patient. Results The patient was presented with progressive overgrowth of the right extremity, scoliosis, cerebral connective tissue nevus and lower extremity venous. A heterozygous mutation of AKT1 gene (c. 49G>A) was identified in DNA extracted from the affected bone tissue of the patient, but not be found in genomic DNA of peripheral blood samples from the patient, his parents and 250 healthy volunteers. Movement function of the affected limb improved significantly after the operations. Conclusions The prominent features of Proteus syndrome are overgrowth of one extremity and cerebral connective tissue nevus. A mosaic somatic mutation of AKT1 gene is one of the pathogenic mutations for Proteus syndrome, and orthopedic surgery may be a good way to improve symptoms of the disease.

Objective To investigate nursing intervention on prevention of deep venous thrombosis of lower extremity in total hip arthroplasty (DVT).Methods A total of 66 patients with orthopedic replacement surgery in our hospital were randomly divided into control group and treatment group,with 33 cases in each group,given conventional care and comprehensive nursing intervention,respectively.The incidences of deep vein thrombosis were compared.Results Pulmonary embolism occurred in three patients during surgery in the control group,and one patient in the treatment group.And 5 cases occurred DVT after one month in the control group,one patient with DVT in treatment group,and there was significantly difference in two groups (P ＜ 0.05).Conclusion Comprehensive nursing intervention for patients undergoing hip replacement surgery can effectively reduce the incidence of deep venous thrombosis,reduce the risk of rehabilitation,and improve the prognosis of patients.