Objective To investigate the efficacy and safety of ultrafiltration therapy in elderly patients with congestive heart failure(CHF)and frailty.Methods A total of 88 hospitalized elderly patients with CHF and frailty were randomly assigned to the ultrafiltration group(n=44)and the control group(n=44).The control group treated with standard drug therapy.The ultrafiltration group treated with ultrafiltration,however,diuretics were not used during ultrafiltration treatment.Efficacy assessment was compared between the two groups,including patient body weight,N-terminal pro-brain natriuretic peptide(NT-proBNP)levels at 48 hours after treatment,dyspnea severity scores at 48 hours and 1 week after treatment,hospitalization duration and readmission rate within 3 months.Safety assessment parameters included serum creatinine,urea nitrogen,Na+and K+concentration at 48 hours after treatment and creatinine level 1 week after treatment.Results Efficacy assessment indicated that at 48 hours after treatment,both groups showed a significant reduction in patient body weight and NT-proBNP levels compared to pre-treatment levels(P＜0.05).However,there were no significant difference in body weight and NT-proBNP levels before and after treatment between the two groups(P＞0.05).Dyspnea severity scores for both groups increased at 48 hours after treatment,then decreased at 1 week after treatment.The ultrafiltration group exhibited higher dyspnea severity scores than that of the control group at 48 hours after treatment(P＜0.05).The length of hospital stay and the rate of re-hospitalization within 3 months were lower in the ultrafiltration group compared to those of the control group(P＜0.05).Safety assessment revealed that there were no significant differences in serum urea nitrogen and Na+levels before and 48 hours after treatment between the two groups(P＞0.05).However,serum K+levels were higher after 48-hours treatment in the ultrafiltration group than those of the control group(P＜0.05).There were no significant changes in creatinine levels before and after treatment in the control group(P＞0.05),while creatinine levels were lower 1 week after treatment in the ultrafiltration group compared to those of pre-treatment and 48 hours after treatment,and were lower than those of the control group(P＜0.05).Conclusion Ultrafiltration is a safe and effective method for elderly patients with CHF and frailty.

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

Objective:To investigate the diagnostic value of Chinese-thyroid imaging reporting and data system (C-TIRADS) combined with shear wave elastography (SWE) in thyroid microcarcinoma.Methods:The clinical data of 270 patients (367 nodules) who underwent thyroid ultrasound examination and confirmed by pathology from January 2019 to June 2021 in the Affiliated Hospital of Jining Medical University were analyzed retrospectively. All patients were assisted by SWE in preoperative ultrasound examination to measure the maximum elastic modulus (E max), the average elastic modulus (E mean) and the minimum elastic modulus (E min). The receiver operating characteristic (ROC) curve was drawn to get the optimal threshold of SWE according to the pathological results. The diagnostic value of C-TIRADS, SWE and their combined in different diameters thyroid micronodules was analyzed. Results:Among 367 thyroid nodules, 119 nodules were benign and 248 nodules were malignant. The area under the curve (AUC) of E max in diagnosing TMC was significantly larger than that of E mean and E min (0.883 vs. 0.822 and 0.706), and there was statistical difference ( P<0.05); the best cut-off value of E max was 29.5 kPa. The ROC curve analysis results showed that the AUC of C-TIRADS combined with SWE in diagnosis of TMC was significantly larger than that of C-TIRADS and SWE alone (0.884 vs. 0.800 and 0.853), and there was statistical difference ( P<0.05); the sensitivity, accuracy and negative predictive value of C-TIRADS combined with SWE in diagnosis of TMC were significantly higher than those of C-TIRADS alone (90.32% vs. 80.24%, 89.10% vs. 80.11% and 81.10% vs. 65.97%), and there were statistical differences ( P<0.05). Thyroid nodules were divided into ≤0.5 cm nodules (56 nodules) and 0.5 to 1.0 cm nodules (311 nodules) according to the maximum diameter, the sensitivity and accuracy of C-TIRADS combined with SWE in diagnosing TMC in 0.5 to 1.0 cm nodules were significantly higher than those in ≤0.5 cm nodules: 91.82% (202/220) vs. 78.57% (22/28) and 90.68% (282/311) vs. 80.36% (45/56), and there were statistical differences ( χ2 = 4.99 and 5.20, P<0.05), but there was no statistical difference in specificity between 2 groups ( P<0.05). Conclusions:C-TIRADS combined with SWE can further improve the diagnostic value of TMC, which is worth popularizing and applying in clinic.

Background and Objectives: Mesenchymal stem cells (MSCs) have the multipotent capacity to differentiate into multiple tissue lineages as well as to self-renew, which is the main origin of adipocytes. IL6/IL6R pathway exerts a significant role in tissue regeneration and cell differentiation. Whereas, the underlying mechanism between IL6/IL6R pathway and MSCs adipogenesis differentiation remains elusive. Methods: MSCs from healthy donors were cultured in adipogenesis differentiation medium for 0∼14 days, during which their adipogenesis differentiation degree was evaluated by Oil Red O staining. The expression of IL6R was detected in MSCs during adipogenesis differentiation. Knockdown and overexpression of IL6R were respectively performed using siRNA and lentivirus to investigate its effect on MSCs adipogenesis differentiation. The adipogenesis marker genes expression and MAPK pathway activation were detected by Western blotting. The role of P38 pathway in the adipogenesis differentiation of MSCs was determined using the specific inhibitor SB203580. Results: The expression of IL6 and IL6R increased during adipogenesis differentiation in MSCs, which were positively correlated with Oil Red O quantification result. Knockdown and overexpression experiments demonstrated a positive correlation between the expressions of IL6R and MSCs adipogenesis differentiation, accompanied by same trend of P38 phosphorylation. Besides, the specific P38 inhibitor SB203580 markedly inhibited the adipogenesis differentiation potential of MSCs. Conclusions This study reveals IL6R facilitates the adiogenesis differentiation of MSCs via activating P38 pathway.

Objective: To analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods: The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children′s Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results: The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ²=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ²=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ²=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ²=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05). Conclusions The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.

To analyze the clinical characteristics of newly treated high?risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high?risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children's Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan?Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow?up time was 36 months (1 day-138 months), and the 5?years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5?years OS between radiotherapy group and non?radiotherapy group (42.3% vs. 38.3%, χ2=3.671, P=0.055). The 5?years OS in transplantation group was significantly better than the non?transplantation group (44.3% vs. 35.5%, χ2=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5?years OS rate than the non?radiotherapy combined transplantation group (45.8% vs. 37.3%, χ2=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high?risk NB patients (χ2=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high?risk NB patients by Cox regression models ( HR=1.896, 1.100, 95%CI :1.113-3.231, 1.020-1.187, both P<0.05). Conclusions The prognosis is unfavorable in high?risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high?risk NB patients with bone marrow metastasis.

Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions. However, the properties of MSCs from AS patients in an inflammatory environment have never been explored. Lipopolysaccharide (LPS), a proinflammatory substance derived from the outer membrane of Gram-negative bacteria, can alter the status and function of MSCs. However, whether MSCs from AS patients exhibit abnormal responses to LPS stimulation has not been reported. Autophagy is a lysosome-mediated catabolic process that participates in many physiological and pathological processes. The link between autophagy and AS remains largely unknown. The level of autophagy in ASMSCs after LPS stimulation remains to be addressed. In this study, we demonstrated that although the basal level of autophagy did not differ between MSCs from healthy donors (HDMSCs) and ASMSCs, LPS-induced autophagy was weaker in ASMSCs than in HDMSCs. Specifically, increased TRAF4 expression in ASMSCs impaired LPS-induced autophagy, potentially by inhibiting the phosphorylation of Beclin-1. These data may provide further insight into ASMSC dysfunction and the precise mechanism underlying the pathogenesis of AS.
Autoimmune Diseases ; Autophagy* ; Bacteria ; Gram-Negative Bacteria ; Humans ; In Vitro Techniques ; Membranes ; Mesenchymal Stromal Cells* ; Pathologic Processes ; Phosphorylation ; Rheumatic Diseases ; Sacroiliac Joint ; Spine ; Spondylitis, Ankylosing* ; Tissue Donors ; TNF Receptor-Associated Factor 4*

Objective: To observe the impact of cardiac resynchronization therapy (CRT) on ventricular remodeling in patients with III°atrio-ventricular block (AVB) combining systolic dysfunction.
Methods: A total of 49 III °AVB patients received CRT in our hospital from 2009-01 to 2014-10 were studied. Echocardiography was conducted at pre-operation and 6, 12 months post-operation to measure left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and mitral regurgitation (MR) grade in order to observe the changes of cardiac structure and function in relevant patients.
Results: Compared with pre-operative condition, at 6 months post-operation, LVEF was increased (4.92±5.24)%and at 12 months post-operation, it was further increased (5.02±6.52)%, both P<0.05;at 6 months post-operation, LVESV reduced (25.02±17.95) ml and at 12 months post-operation, it was further reduced (24.79±22.49) ml, both P<0.05. Compared with pre-operative condition, at 6 months post-operation, LVEDV dropped (25.61±24.24) ml, LVEDD dropped (3.22±2.91) mm, LVESD dropped (4.43±2.86) mm and MR grade dropped 0.49±0.76, all P<0.05. Compared with 6 months post-operation, at 12 months post-operation, LVEDV declined (28.18±22.36) ml, LVEDD declined (4.17±3.14) mm, both P<0.05, LVESD declined (4.92±4.40) mm, P<0.01 and MR grade declined (0.22±0.55), P<0.05.
Conclusion:CRT may reverse ventricular remodeling and improve cardiac function in patients with III°AVB combining systolic dysfunction.

Objective: To analyze the predictors of left ventricular reverse remodeling in patients with III? atrio-ventricular block (AVB) combining left ventricular systolic dysfunction after cardiac re-synchronization therapy (CRT). Methods: A total of 65 III? AVB patients received CRT in our hospital from 2009-01 to 2015-05 were enrolled. Clinical information before and after the operation were recorded. Left ventricular reverse remodeling was deifned by left ventricular end systolic volume (LVESV) decreased 15% or left ventricular ejection fraction (LVEF) increased≥5% at 12 months after CRT. The patients were divided into 2 groups: Reversal group,n=36 and No reversal group,n=29. Clinical condition was compared between 2 groups, predictors for CRT reversing left ventricular remodeling were evaluated by two classiifcation Logistic regression analysis. Results: The patients' average age was (62±14) years and 36/65 (55.4%) with reverse remodeling. In Reversal group, the ratios of female (P=0.011), baseline QRS width>120ms (P=0.001), inter-ventricular mechanical delay (IVMD)≥40 ms (P=0.027) and standard deviation of time-to-minimum systolic volume of 16 segments [Tmsv16-SD (%R-R)≥8.3%, (P=0.001)] were higher than those in No reversal group. Two classiifcation Logisitic regression analysis indicated that female (OR=6.228, 95%CI 1.561-24.842, P=0.01), QRS duration>120 ms (OR=7.778, 95% CI 1.996-30.769,P=0.003) and Tmsv16-SD (%R-R)≥8.3% (OR=8.134, 95% CI 2.064-32.057,P=0.003) were the independent predictors for ventricular reverse remodeling . Conclusion: Female, QRS>120ms and Tmsv16-SD (%R-R)≥8.3% could be used as the predictors for CRT reversing left ventricular remodeling in III? AVB patients combining left ventricular systolic dysfunction.

BACKGROUND:Ankylosing spondylitis is an autoimmune disease at high inflammatory state, and its pathogenesis is stil unclear. Besides, there is a lack of entirely satisfactory curative strategies. OBJECTIVE: To explore the immunoregulation capability of bone marrow mesenchymal stem cels from ankylosing spondylitis patients on macrophages and the potential therapeutic use of bone marrow mesenchymal stem cels from healthy donors on ankylosing spondylitis. METHODS: Bone marrow mesenchymal stem cels were extracted from 21 healthy donors and 25 ankylosing spondylitis patients respectively, and passage 4 cels were used in subsequent experiments. A human monocytic cel line was induced to differentiate into macrophages. The phenotypic markers of bone marrow mesenchymal stem cels and macrophages were detected by flow cytometry. Expressions of tumor necrosis factor-α and tumor necrosis factor-α-stimulated gene 6 (TSG-6) proteins in the supernatant of co-culture system were detected by ELISA. Quantitative real-time PCR was applied to detect the mRNA level of cytokines secreted by bone marrow mesenchymal stem cels and macrophages. RESULTS AND CONCLUSION:The typical mesenchymal stem cel surface markers were expressed in both bone marrow mesenchymal stem cels from healthy donors and patients with ankylosing spondylitis, and CD68 was detected positively in induced macrophages. The protein and mRNA levels of tumor necrosis factor-α secreted by macrophages co-cultured with bone marrow mesenchymal stem cels from patients with ankylosing spondylitis were obviously higher than those from healthy donors (P < 0.05). TSG-6 secreted by bone marrow mesenchymal stem cels from patients with ankylosing spondylitis was lower than that by bone marrow mesenchymal stem cels from healthy donors in both RNA transcriptional and protein levels (P < 0.05). Our study demonstrates that bone marrow mesenchymal stem cels from patients with ankylosing spondylitis shows abnormal immunoregulatory function on inhibiting the tumor necrosis factor-α secretion from macrophages, which reveals a mechanism of immune disorder in ankylosing spondylitis. The therapeutic mechanism of bone marrow mesenchymal stem cels from healthy donors may work by secreting enough TSG-6 to inhibit the activation of macrophages in patients with ankylosing spondylitis, and thereby to decrease the secretion of tumor necrosis factor-α. Cite this article:Sun SH, Wang P, Su CY, Xie ZY, Li YX, Li D, Wang S, Su HJ, Wu XH, Deng W, Wu YF, Shen HY. Bone marrow mesenchymal stem cels derived from patients with ankylosing spondylitis show abnormal immunoregulation capability on macrophages. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):13-19.