Objective To sum up the clinical experience of the diagnosis and treatment of membranous glomerulopathy associated with chronic graft-versus-host disease(cGVHD) following allogeneic stem tell transplantation(alloSCT).Methods One case of acute acute lymphoblastic leukemia(received) HLA complete matched alloSCT and subjected to methopterin and Tacrolimus(FK506)postoperatively for prevention of GVHD.Nineteen days after operation,the patient suffered from(acute) GVHD and recovered by using methylprednisolone.On the day of 182 and 235 after transplantation,FK506 and prednisone were withdrawn.Five days later,cGVHD occurred,showing liver(dysfunction) and nephrotic syndrome.Membranous glomerulopathy(stage II) was pathologically (diagnosed) and treated with FK506 and prednisone.Results In membranous glomerulopathy,the(patient) got albuminuria(++++),leukocytes 75/?L,epicytes(359.5)/?L,pathological casts(+),24-h urine protein(4.28) g.Renal biopsy revealed that glomeruli were slightly enlarged,partial(capillary) compressed to be closed,glomerular basement membrane(GBM) was slightly thickened and mesangium slightly proliferate.Masson stain indicated the deposition of pink material along the glomerular capillary walls.And IgG(+++),C3(+++) and IgA(++) were detected at the GBM in a granular pattern by immunofluorescent stain.Electron microscopy showed numerous subepithelial(deposits).After treatment with prednisone and FK506 for 2 months,proteinuria was gradually(decreased).Conclusions GVHD associated membranous glomerulopathy should be considered when the patient got nephrotic syndrome or proteinuria after alloSCT.Renal biopsy is beneficial to the diagnosis of GVHD.Glucocorticoid and FK506 is effective in the treatment of GVHD.

Objective To explore the utility of cone-beam CT in the evaluation of prostatic arterial embolization (PAE). Methods In a retrospective study, images of DSA and cone-beam CT for PAE in 81 patients with moderate to severe grade benign prostatic hyperplasia were evaluated. In 162 cases of internal iliac arteries (ⅡAs) in 81 patients, images of 6 ⅡAs were excluded due to the technical problems. Therefore, images of 156ⅡAs were included for evaluation. We aim to evaluate the utility of cone-beam CT versus DSA in differentiating PAs and their origins, and demonstrating anastomoses with adjacent arteries. Statistical analyses were performed with Chi-square test to compare the rate of demonstrating vessels between cone-beam CT and DSA. Results One hundred and sixty-one PAs were demonstrated in 156ⅡAs by selective DSA and Cone-beam CT. Cone-beam CT and DSA images demonstrated 158 (98.1%, 158/161) and 130 (80.8%, 130/161) PAs, respectively. The statistical difference was significant (χ2=25.78, P<0.05). PAs were demonstrated by cone-beam CT images alone in 27ⅡAs (17.3%, 27/156) and were demonstrated by DSA images alone in 3ⅡAs (1.9%, 3/161).The statistical difference was significant (χ2=22.31, P<0.05). In 137 PAs that were initially defined by DSA alone, 7 of those (5.1%, 7/137) were eventually proven not to be PAs by further selective cone-beam CT acquisitions. Origins of PAs were shown by Cone-beam CT images alone in 11 ⅡAs. In the remaining 145 ⅡAs (92.9%, 145/156), origins of PAs were shown by both
cone-beam CT and DSA images. The percentage of PA anastomoses demonstrated by cone-beam CT was 42.3%(66/156), which was higher than DSA (31.4%, 49/156). The statistical difference was significant (χ2=3.98, P<0.05). Conclusions Cone-beam CT is useful in demonstrating PAs and their origins fromⅡAs, as well as anastomoses with adjacent arteries.

Humans ; Immunotherapy ; Leukemia, Myeloid, Acute ; therapy ; Receptors, Antigen, T-Cell ; T-Lymphocytes

Objective:To investigate the early predictive value of lupus anticoagulant (LA) ratio, D-dimer (D-D) and soluble endothelial protein C receptor (sEPCR) on deep vein thrombosis (DVT).Methods:Thirty hundred and fifty patients who performed surgery for lower extremity fracture and suspected DVT in Zhejiang Rongjun Hospital from October 2018 to October 2019 were enrolled. With deep vein contrast of the lower extremity as the gold standard, 82 patients with confirmed DVT were treated as the observation group and 268 patients without DVT as the control group. The levels of LA, D-D and sEPCR of two groups were detected by coagulation, immunoturbidimetry and enzyme linked immunosorbent assay—sandwich technique respectively. Indexes of the two groups were compared. Pearson correlation was used to analyze the relationship between plasma levels of LA, D-D and sEPCR, and the predictive value of plasma sEPCR, LA ratio and D-D level on DVT was evaluated by receiver operator characteristic (ROC) curve.Results:The plasma sEPCR, LA ratio and D-D levels in the observation group were significantly higher than those in the control group [(143.30 ± 11.28) μg/L vs.(112.56 ± 14.62) μg/L, 1.51 ± 0.24 vs. 1.22 ± 0.18, (1 013.00 ± 319.54) μg/L vs. (425.17 ± 100.36) μg/L] with statistically significant differences ( P < 0.05). There was no significant differences in activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) between the two groups ( P > 0.05). In the observation group, plasma sEPCR level was positively correlated with LA ratio and D-D level ( r = 0.280, P = 0.011; r = 0.563, P < 0.001), and LA ratio was positively correlated with D-D level( r = 0.741, P < 0.001). The area under curve (AUC) of D-D in diagnosis of DVT was 0.940, and the sensitivity and specificity were 87.80% and 87.69% when the cut-off value was 569.43 μg/L. The AUC of LA ratio in the diagnosis of DVT was the smallest, which was 0.912, the sensitivity and specificity were 87.80% and 91.25% when the cut-off value was 1.23. The sensitivity was 95.12% and specificity was 95.00% of sEPCR and LA ratio combined with DD in diagnosis of DVT. Conclusions:LA and D-D combined with sEPCR has high predictive value for DVT.

Objective: To evaluate the role of neuroligin 1 (NL-1) in trafficking of GluR1-containing AMPA receptor to cell membrane in spinal cord dorsal horns during remifentanil-induced hyperalgesia in mice with incisional pain. Methods: Forty SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 5 groups (n=8 each) using a random number table method: control group (group C), NL1-shRNA plasmid group (group NL), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus blank vector group (group I+ R+ B), and incisional pain plus remifentanil plus NL-1-shRNA plasmid group (group I+ R+ NL). Negative lentivirus was intrathecally injected in group I+ R+ B.In NL and I+ R+ NL groups, 10 μl NL-1-shRNA lentivirus at 1×10⁸ IFU/ml was intrathecally injected once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected at the same time point in C and I+ R groups.After transfection was stable, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at 15 min intervals in C and NL groups.In I+ R, I+ R+ B and I+ R+ NL groups, 0.1 ml remifentanil 10 μg/kg was injected via the caudal vein for 4 consecutive times at 15 min intervals, and the model of incisional pain was established after the first administration.The mechanical paw withdrawal threshold (MWT) and tail-flick latency (TFL) were measured at 24 h before normal saline or remifentanil administration (T₀) and at 3, 6, 24 and 48 h after the end of administration (T_1-4). The animals were sacrificed after measurement of pain threshold at T₄, and L_4-6 segments of the spinal dorsal horn were then collected for determination of the expression of NL-1 protein and mRNA and AMPA receptors, and the ratio of AMPA receptor expression in the membrane protein to that in the total protein (m/t ratio) was calculated. Results: Compared with group C, the MWT was significantly decreased, and TFL was shortened at T_1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was up-regulated, and m/t ratio was increased in I+ R and I+ R+ B groups (P<0.05). Compared with I+ R and I+ R+ B groups, the MWT was significantly increased and TFL was prolonged at T_1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was down-regulated, and m/t ratio was decreased in group I+ R+ NL (P<0.05). Conclusion NL-1 in spinal cord dorsal horns can promote the trafficking of GluR1-containing AMPA receptors to cell membrane, which is involved in the development and maintenance of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective: To evaluate the role of spinal COX-1 and COX-2 in remifentanil-induced hyperalgesia in mice with incisional pain. Methods: Thirty-two male C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), incisional pain plus remifentanil group (group IR), incisional pain plus remifentanil plus selective COX-1 inhibitor group (group IR+ SC560), and incisional pain plus remifentanil plus selective COX-2 inhibitor group (group IR+ SC236). In IR, IR+ SC560 and IR+ SC236 groups, normal saline 10 μl, SC560 25 μg and SC236 25 μg were intrathecally injected, respectively, 15 min later remifentanil 10 μg/kg was injected via the tail vein for 4 times at 15 min intervals.An incisional pain model was established after the first injection of remifentanil.The mechanical paw withdrawal threshold (MWT) was measured at 24 h before normal saline or remifentanil injection and 3, 6, 24 and 48 h after the last injection (T₀-T₄). The mice were sacrificed after the last measurement of pain threshold, and the L_4-6 segments of the spinal cord were removed for determination of the expression of COX-1 and COX-2 (by Western blot) and expression of COX-1 and COX-2 mRNA (by quantitative real-time polymerase chain reaction). Results: Compared with group C, the MWT was significantly decreased, and the expression of COX-2 protein and mRNA was up-regulated in IR, IR+ SC560 and IR+ SC236 groups (P<0.05). Compared with group IR, the MWT was significantly increased in IR+ SC560 and IR+ SC236 groups (P<0.05). There was no significant difference in the MWT at each time point between IR+ SC560 and IR+ SC236 (P>0.05) .There was no significant difference in the expression of COX-2 protein and mRNA among group IR, group IR+ SC560 and group IR+ SC236 (P>0.05). There was no significant difference in the expression of COX-1 protein and mRNA among the four groups (P>0.05). Conclusion Compared with COX-1, spinal COX-2 plays a major role in the pathophysiological mechanism of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective:To evaluate the role of secreted protein acidic and rich in cysteine like protein 1 (SPARCL1) in spinal dorsal horns in the development of remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Forty-eight healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 6 groups ( n=8 each) using a random number table method: control group (group C), incisional pain group (group I), remifentanil group (group R), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus negative control group (group I+ R+ N), and incisional pain plus remifentanil plus SPARCL1-siRNA group (group I+ R+ S). In I+ R+ N and I+ R+ S groups, 1×10 8 IFU/ml negative control siRNA and SPARCL1-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C, I, R and I+ R groups.After transfection was stable, normal saline 0.1 ml was intravenously injected through the tail vein for 4 consecutive times at 15 min interval in C and I groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was intravenously injected via the tail vein for 4 consecutive times at 15 min interval in R, I+ R, I+ R+ N and I+ R+ S groups.The incisional pain model was established after the first administration via the tail vein in R, I+ R, I+ R+ N and I+ R+ S groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusing normal saline or remifentanil (T 0) and 3, 6, 24 and 48 h after stopping infusion (T 1-4). Animals were sacrificed after measuring pain threshold at T 4, and L 4-6 segments of the spinal cord were removed for determination of the expression of SPARCL1 protein and mRNA by Western blot and quantitative real-time polymerase chain reaction, respectively. Results:Compared with group C, MWT was significantly decreased and TWL was shortened at T 1-4 in I+ R and I+ R+ N groups and at T 2-4 in I, R and I+ R+ S groups, and the expression of SPARCL1 protein and mRNA was significantly up-regulated in R, I+ R and I+ R+ C groups ( P<0.05 or 0.01). Compared with group I and group R, MWT was significantly decreased, TWL was shortened, and the expression of SPARCL1 protein and mRNA was up-regulated in group I+ R ( P<0.01). Compared with group I+ R, MWT was significantly increased and TWL was prolonged at T 1-4, and the expression of SPARCL1 protein and mRNA was down-regulated in group I+ R+ S ( P<0.05 or 0.01). Conclusion:Enhanced activity of SPARCL1 in the spinal dorsal horns is involved in the development of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective:To investigate the value of bone marrow plasma cell morphology in the diagnosis and prognosis of plasma cell myeloma (PCM).Method:Observational study.Collect the bone marrow morphology image reports and corresponding monoclonal protein (M protein) identification results of 1071 patients [629 males and 442 females, Median age 62 (29, 93) years] diagnosed with PCM in the outpatient and inpatient departments of Beijing Chaoyang Hospital affiliated to Capital Medical University from January 1, 2017 to February 28, 2022. Combined with Durie‐Salmon(DS) and International Staging System (ISS) of 427 patients diagnosed with PCM and overall survival time (OS) of 436, summarize the relevant plasma cell morphological characteristics. Statistical methods include chi-square test, Kruskal-Walls test, Spearman correlation analysis and Kaplan-Meier survival analysis.Result:The bone marrow morphology reports showed that the typical morphological features of peripheral blood in 573 patients with PCM included plasma cells (40.84%), immature granulocytes (30.89%), rouleaux formation in erythrocytes (68.94%) and nucleated red blood cells (8.55%). The types of bone marrow plasma cells in 1 071 patients diagnosed with PCM included 372 (34.73%) plasmablasts, 674 (62.93%)immature plasma cells, and 25 (2.34%) mature plasma cells. There is a significant positive correlation between the number of bone marrow plasma cells (proportion of nuclear cells) and the concentration of IgG and IgA type, from M protein identification( r=0.55, r=0.60, P<0.01). The proportions of M protein types in 1 071 patients with PCM from high to low were IgG (45.75%), IgA (23.53%), light chain (19.61%), IgD (4.76%), non-secretory (4.3%), biclonal (1.78%), IgE (0.19%), IgM (0.08%). The typical characteristics of the bone marrow plasma cells in various M protein types included clustered distribution, different cell body sizes, inclusions in the cytoplasm, binuclear, polynuclear, and abnormal nuclear. The proportion of plasmablasts in DSⅢ stage was 44.81% (164/366), higher than 21.57% (11/51) in DSⅡstage, and the difference was statistically significant(χ 2=10.2, P<0.05). There was a significant positive correlation between the number of bone marrow plasma cells and DS and ISS stages( r=0. 0.23, r=0.30, P<0.01). The median OS of the PCM patients in the plasmablasts group was significantly shorter than that in the immature plasma cells group [56.0 (23.0, 101.8) months vs 75.9(31.6, 121.5) months, HR=1.42,95% CI 1.05-1.91, P=0.02]. The median OS of the PCM patients in the group of tumor plasma cells burden≥37.5% was shorter than that of the tumor plasma cells burden<37.5% [75.9 (21.4, 122.6)months vs 81.3 (36.6, 108) months, HR=1.54,95% CI 1.14-2.07, P<0.05]. Conclusion:The morphology and tumor burden of bone marrow plasma cells provide an important basis for the diagnosis of PCM and can be used as a prognostic indicator for patients with PCM.