Objective:To investigate the clinical features,gene mutation profile,efficacy and prognostic factors of primary extranodal diffuse large B-cell lymphoma(EN-DLBCL).Methods:A retrospective analysis was performed for 382 patients with primary EN-DLBCL with complete clinical data who were treated in West China Hospital from January 2013 to January 2023,and their clinical characteristics,gene mutation profile,efficacy and prognostic factors were analyzed.Results:The median age of the 382 patients with EN-DLBCL was 56 (18-89 )years old.The male-to-female ratio was 1.12∶1,and the most common primary sites were gastrointestinal tract (31.7％),Wechsler ring (19. 1％)and breast gland (7.1％).A total of 51 gene mutations were fund,and the most common frequencies of gene mutations were TP53 (32.5％),MYD88 (32.5％),and CD79B (30.0％).The median follow-up was 63 months,and the 5-year progression-free survival (PFS)rate was 74.5％ and the 5-year overall survival (OS)rate was 89.6％. The adverse factors on PFS were as follows:>1 extranodal sites involvement (P<0.001),P53≥50％(P<0.001),hyper double expression(hDEL)of C-myc>50％/Bcl-2>70％(P<0.001).The adverse factors affecting the OS of patients were as follows:>1 extranodal sites involvement (P<0.001),P53≥50％(P<0.001),hDEL(P<0.001). Chemotherapy combined with local radiotherapy could improve PFS (P=0.041)and OS (P=0.003),while R-CHOP+X (molecule agents as BTKi、HDACi、Lenalidomide)failed to show a significant difference in PFS (P=0.075)and OS (P=0.767 ).Among the 40 patients who underwent next-generation sequencing at high risk,there was no significant in PFS (P=0.849)and OS (P=0.500)of patients with positive MYD88 and/or CD79B mutations (MCD subtype)treated with BTKi and patients with negative MYD88 and CD79B mutations.Conclusion:Primary EN-DLBCL can involve multiple organs or tissue sites.TP53,MYD88,and CD79B are the most common gene mutations.The efficacy of BTKi in patients with positive MCD subtypes at intermediate and high risk is not inferior to that in MCD-negative control patients.

Objective:To explore the diagnosis and treatment of acquired hemophilia A (AHA ) based on the analysis of clinical data.Methods:A retrospective analysis was conducted on the clinical manifestations,laboratory characteristics,treatment,and outcomes of 25 patients diagnosed with AHA who were admitted to the Second Hospital of Hebei Medical University. Results:Among all patients,11 cases had secondary factors,including 5 cases of autoimmune diseases,3 cases of pregnancy-related disease,1 case of pemphigoid,1 case of Graves'disease,and 1 case of monoclonal gammaglobulinemia of unknown significance (MGUS ).The bleeding sites include the skin,mucous membrane,muscle,joint cavity and brain tissue.Twenty-three patients were treated with prednisone combined with cyclophosphamide (CP regimen),one patient with rituximab combined with cyclophosphamide because of femoral head necrosis,and one case with rituximab monotherapy because of gastrointestinal bleeding after prednisone treatment. Among them,23 cases achieved complete remission (CR),2 cases were partial remission (PR),and 8 cases relapsed after CR.All of 10 patients including 2 cases with PR and 8 relapsed cases after CR were treated with rituximab.At last,8 patients achieved CR,and 2 patients (both were patients with recurrence after first CR)achieved PR.These two patients achieving PR were treated with low-dose rituximab combined with bortezomib (RB regimen ).One patient reached CR after 4 cycles and the other reached CR after 6 cycles of RB regimen.After CR,4 of the 10 patients treated with rituximab received maintenance therapy with rituximab monotherapy for 1.5 to 2 years,in which,none of them relapsed.Among the 6 patients who did not receive maintenance therapy,4 patients relapsed after CR,and the median time to relapse was 15 months.Eight patients treated with CP regimen developed common infections,and two patients treated with rituximab developed severe pneumonia.All 25 patients survived until the end of follow-up.Conclusion:Skin ecchymosis,mucous hemorrhage and muscle hematoma are the most common hemorrhagic manifestations in AHA,and joint hemorrhage and cerebral hemorrhage can also occur.CP regimen is the preferred option of first-line therapy for AHA.Rituximab can be used for patients with steroid contraindication or who failed to respond to the above therapy or relapsed after effective treatment,and maintenance therapy is recommended to reduce the risk of recurrence.Meanwhile,close attention should be paid to the occurrence of infection events during rituximab treatment.Rituximab in combination with bortezomib can also be used in patients with refractory or relapsing AHA.

Objective:To explore the talent cultivation model of nursing professional group under the 1+X certificate system, to build a talent cultivation system for nursing professional groups with "three progressions, four integrations, and five cocultivation"Methods:From 1 July 2021 to 31 December 2023, built a professional group course system of "mutual sharing of foundations, mutual generation of majors, mutual selection of positions, and progressive improvement of abilities". Aligned course content with X certificate content. Deepen the reform of the three education systems, create a "dual teacher" teaching team that combines full-time and part-time work, and build teaching resources that connect the cloud and the ground. The application effect of this model was evaluated in 2021 nursing majors in Cangzhou Medical College by cluster sampling.Results:There were 748 students majoring in nursing in class of 2021, 150 boys aged 19-22(20.00 ± 1.23), 598 girls, aged 19-21(19.00 ± 2.57). There were 118 students majoring in midwifery in class of 2021, all of them were girls, aged 18-20(18.00 ± 2.11). There were 128 students majoring in rehabilitation therapy technology in class of 2021, 66 boys aged 19-21(19.00 ± 2.11), 62 girls aged 19-21(19.00 ± 2.54). Nursing professional group completed the "Basic Nursing Technology Training Guidance", "Elderly Care" and other 5 self-compiled textbooks, 730 students had participated in the X certificate assessment, 729 students e passed the assessment, the passing rate was 99.9%.Conclusions:The talent cultivation model of "three progressions, four integrations, and five co cultivation" in the nursing professional group can cultivate students′ professional abilities, and cultivate a composite technical and skilled talent with multiple abilities and interconnections in one job.

Objective To observe the clinical effect of automated peritoneal dialysis(APD)in urgent-start peritoneal dialysis patients with stage 5 chronic kidney disease(CKD).Methods A total of 60 patients with end-stage renal disease who underwent urgent-start peritoneal dialysis in Shenyang Red Cross Hospital from June 2021 to December 2023 were selected as study objects.According to peritoneal dialysis,patients were divided into APD group and intermittent peritoneal dialysis(IPD)group,with 30 patients in each group.Renal function,electrolyte,parathyroid hormone,inflammatory factors,nutritional indexes,brain natriuretic peptide,blood pressure,urine volume,ultrafiltration volume and adverse reactions were compared between two groups.Results After treatment,serum creatinine,urea nitrogen,uric acid,potassium,phosphorus,parathyroid hormone,C-reactive protein,interleukin-6,brain natriuretic peptide,systolic blood pressure and diastolic blood pressure in two groups were significantly lower than before treatment,and urine volume was significantly higher than before treatment(P＜0.05).Serum creatinine,urea nitrogen,uric acid,potassium,phosphorus,parathyroid hormone,C-reactive protein,interleukin-6,brain natriuretic peptide,systolic blood pressure and diastolic blood pressure in APD group were significantly lower than those in IPD group,and ultrafiltration volume in APD group was significantly higher than that in IPD group(P＜0.05).After treatment,there was no significant difference in urine volume between two groups(P＜0.05).No serious complications and death were observed during treatment.Conclusion APD is safe and effective,and is a good choice for urgent-start peritoneal dialysis in stage 5 CKD patients.

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.
Animals ; Receptors, Chimeric Antigen/metabolism* ; Multiple Myeloma/metabolism* ; Killer Cells, Natural/metabolism* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment

Background Occupational aluminum exposure may associate with cognitive impairment in workers. At present, brain functional imaging data are not available for evaluating cognitive dysfunction in workers with occupational exposure to aluminum. The role of brain functional connectivity in cognitive decline associated with occupational aluminum exposure is not clear yet. Objective To explore potential mediating effect of brain functional connectivity value on cognitive decline induced by occupational aluminum exposure, to assess the relationship between cognitive impairment and brain functional connectivity, and to identify appropriate imaging evidence of early cognitive changes induced by occupational aluminum exposure. Methods This study used a subset data from a previous cross-sectional survey. Based on the data of aluminum-exposed workers, over 40 years old, aluminum-exposed working years >1 year, Montreal International Cognitive Assessment (MoCA) (Beijing version) score <26 points, 20 workers were selected as the case group, and 40 healthy workers with the same basic conditions (age, smoking, drinking, etc.) in non-aluminum production were selected as the control group with a 1∶2 matching ratio. The basic information of the subjects was collected, plasma aluminum level and cognitive function level were evaluated, and different brain functional connectivity values of default mode network (DMN) were measured by magnetic resonance imaging. The mediating effect analysis was conducted to examine the role of brain functional connectivity in the relationship between aluminum exposure and cognitive function. Results The plasma aluminum concentration of the case group was 1.76 times higher than that of the control group [(33.04±12.02) µg·L⁻¹ vs (18.74±8.95) µg·L⁻¹, P<0.05]; the MoCA score was 9.5 points lower [(18.35±2.64) vs (27.85±0.92), P<0.05]. The mean functional connection values of DMN1 and DMN2 in the case group were lower than those in the control group (P<0.05). The mean functional connection values of the left precuneus, left middle cingulate cortex, left superior medial gyrus, left precentral gyrus, and left cerebellum also decreased in the case group compared with the control group (P<0.05). Plasma aluminum concentration was negatively correlated with DMN1 functional connectivity value and MoCA scores (b=−0.004, 95%CI: −0.008–−0.001; b=−0.15, 95%CI: −0.233–−0.067; P<0.05). The mean functional connection values of DMN1 and DMN2 were positively correlated with MoCA scores (b=10.945, 95%CI: 5.574–16.316; b=10.107, 95%CI: 2.457–17.758; P<0.05). With the increase of plasma aluminum concentration, MoCA score decreased, but when the plasma aluminum concentration exceeded 19.50 µg·L⁻¹, MoCA score decreased slowly. With the increase of the mean functional connectivity value of DMN1, MoCA score increased, but when the mean functional connectivity value of DMN1 exceeded 1.05 and continued to increase, the increase of MoCA score slowed down. The results of mediating effect analysis showed that the functional connectivity value of DMN1 partially mediated the relationship between plasma aluminum concentration and MoCA score, and the mediating effect was 25.80%. Conclusion Cognitive impairment in occupational aluminum-exposed workers is closely related to brain resting-state functional connectivity. There is a dose-response relationship of plasma aluminum concentration with DMN1 functional connectivity value and MoCA scores, and DMN1 functional connectivity value partially mediates the relationship between plasma aluminum concentration and MoCA scores. The brain functional connectivity value can be used as meaningful imaging data to study the cognitive decline induced by chronic aluminum exposure.

Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)₃]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)₃ exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L⁻¹ Al(mal)₃ respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L⁻¹ C188-9 +160 μmol·L⁻¹ Al(mal)₃]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)₃ dose. Compared with the control group, the cell viability of the Al(mal)₃ high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)₃ high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)₃ low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)₃ high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)₃ high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)₃ high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)₃ high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)₃ high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)₃ medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)₃ low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)₃ high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)₃ medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)₃ high-dose group increased by 10% (P<0.05). Compared with the Al(mal)₃ high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

Objective:To evaluate the diagnostic evaluation process and the effectiveness and safety of intracavitary therapy for pelvic congestion syndrome (PCS).Methods:A retrospective analysis was conducted on 38 patients admitted to Beijing Shijitan Hospital affiliated to Capital Medical University from March 2019 to February 2022. Combined with the patient′s symptoms, PCS was diagnosed by color Doppler ultrasound, computed tomography venography (CTV), and venography. The ovarian vein was embolized with controllable spring coil and polydocanol foam sclerosing agent. The patients were followed up 1, 3 and 6 months after operation.Results:The total surgical success rate of 38 patients was 100%, and the incidence of complications was 5.3%(2/38); Spring coils (2.8±0.3)per person; The dosage of hardener was (7.0±2.1)ml/person. The improvement rate of patient symptoms was 97.4%(37/38); After 1, 3, and 6 months of surgery, color Doppler ultrasound was reexamined and no recanalization was observed in the embolized ovarian veins; The diameter of the parauterine vein was (2.8±0.5)mm, which was significantly lower than the preoperative (7.5±1.9)mm ( P<0.05); The Visual Analogue Scale (VAS) score was significantly lower than the preoperative score [(2.12±1.87)points vs (7.58±0.82)points, P<0.001]. Conclusions:Process based assessment is helpful in identifying and diagnosing PCS patients who urgently need treatment; Endovascular treatment based on embolization of ovarian vein with controllable spring coil and foam sclerosing agent is minimally invasive, safe and effective.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Objective:To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins.Methods:A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ2 tests, and linear regression analysis. Results:One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group( M(IQR),3.0(4.3) vs.4.0(5.8), Z=-2.038, P=0.040).Additionally, the chronic venous insufficiency patients′ quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs.82.5(17.0), Z=-2.627, P=0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs.12.0(7.0) weeks, Z=-3.217, P<0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference ( χ2=0.453, P=0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference ( χ2=4.800, P=0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions:CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.