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2022 ◽  
Vol 12 ◽  
Fanhua Kong ◽  
Shaojun Ye ◽  
Zibiao Zhong ◽  
Xin Zhou ◽  
Wei Zhou ◽  

Renal transplantation is currently the most effective treatment for end-stage renal disease. However, chronic antibody-mediated rejection (cABMR) remains a serious obstacle for the long-term survival of patients with renal transplantation and a problem to be solved. At present, the role and mechanism underlying immune factors such as T- and B- cell subsets in cABMR after renal transplantation remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood monocytes (PBMCs) from cABMR and control subjects was performed to define the transcriptomic landscape at single-cell resolution. A comprehensive scRNA-seq analysis was performed. The results indicated that most cell types in the cABMR patients exhibited an intense interferon response and release of proinflammatory cytokines. In addition, we found that the expression of MT-ND6, CXCL8, NFKBIA, NFKBIZ, and other genes were up-regulated in T- and B-cells and these genes were associated with pro-inflammatory response and immune regulation. Western blot and qRT-PCR experiments also confirmed the up-regulated expression of these genes in cABMR. GO and KEGG enrichment analyses indicated that the overexpressed genes in T- and B-cells were mainly enriched in inflammatory pathways, including the TNF, IL-17, and Toll-like receptor signaling pathways. Additionally, MAPK and NF-κB signaling pathways were also involved in the occurrence and development of cABMR. This is consistent with the experimental results of Western blot. Trajectory analysis assembled the T-cell subsets into three differentiation paths with distinctive phenotypic and functional prog rams. CD8 effector T cells and γδ T cells showed three different differentiation trajectories, while CD8_MAI T cells and naive T cells primarily had two differentiation trajectories. Cell-cell interaction analysis revealed strong T/B cells and neutrophils activation in cABMR. Thus, the study offers new insight into pathogenesis and may have implications for the identification of novel therapeutic targets for cABMR.

2022 ◽  
Vol 8 ◽  
Ga-Won Lee ◽  
Min-Hee Kang ◽  
Jin-Ha Jeon ◽  
Doo-Won Song ◽  
Woong-Bin Ro ◽  

A 7-year-old castrated male Poodle dog presented with chronic progressive lymphocytosis. Hematologic and peripheral blood smear findings included remarkable lymphocytosis with well-differentiated small lymphocytes. Cytology of bone marrow aspirate showed hypercellular integrity with infiltration of small mature lymphocytes, accounting for 45% of all nucleated cells. Flow cytometry of blood and marrow samples revealed neoplastic lymphocytes predominantly expressing the CD21 molecule. B-cell chronic lymphocytic leukemia (CLL) was diagnosed on an immunophenotypic analysis. Administrations of prednisolone and chlorambucil were initiated and the response was unremarkable. Therefore, additional treatment with imatinib was provided, which resolved the hematologic abnormalities associated with CLL. Flow cytometry after ~1 year of treatment showed normalization of the count of lymphocytes positive for CD21 and resolved hematologic lymphocytosis. The dog was followed-up for 2 years, and there were no severe adverse effects. This case indicates that imatinib may be a good option as an adjunctive therapy with prednisolone and chlorambucil treatment for CLL in dogs without treatment response.

2022 ◽  
Vol 23 (1) ◽  
Dandan Guo ◽  
Huifang Wang ◽  
Jun Liu ◽  
Hang Liu ◽  
Ming Zhang ◽  

Abstract Background We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT). Methods The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed. Results The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p < 0.001), preoperative hypertension (HR 1.670, 95% CI 0.962-2.898; p = 0.068), preoperative eGFR (HR 0.996, 95% CI 0.991-1.001; p = 0.143), uric acid at 3 months (HR 1.002, 95% CI 1.001-1.004; p = 0.028), haemoglobin at 3 months (HR 0.970, 95% CI 0.956-0.983; p < 0.001), and average concentration of cyclosporine A at 3 months (HR 1.002, 95% CI 1.001-1.003; p < 0.001). According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function. Conclusions With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.

2022 ◽  
Vol 11 ◽  
Alejandra Wu Chuang ◽  
Oliver Kepp ◽  
Guido Kroemer ◽  
Lucillia Bezu

Local anesthetics are frequently employed during surgery in order to control peri- and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.

2022 ◽  
Vol 8 ◽  
Antonio Carlos Lopes Câmara ◽  
Verônica Lourença de Sousa Argenta ◽  
Daniella Dianese Alves de Moraes ◽  
Eduardo Ferreira Fonseca ◽  
Tayná Cardim Moraes Fino ◽  

Determining the prognosis of poisoning by plants containing pyrrolizidine alkaloids is usually challenging. This study aimed to identify important prognostic parameters that can determine the severity of spontaneous poisoning by Crotalaria spectabilis in horses. Blood samples from 42 horses spontaneously poisoned by oats contaminated with C. spectabilis seeds were evaluated. Complete blood counts (CBC) and serum biochemical tests [urea, creatinine, total protein, albumin, total and direct bilirubin concentrations, aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and creatine kinase (CK) activities] were performed. Horses were followed up for 12 months to determine the long-term survival rate; after 12 months, they were divided into two groups: survivors (n = 30) and non-survivors (n = 12). Horses spontaneously poisoned with C. spectabilis had higher levels of urea, globulin, bilirubin (total, direct, and indirect), AST, GGT, and CK than the reference values. Non-survivor horses showed significantly higher (p &lt; 0.05) values of hemoglobin, GGT, and direct bilirubin than the survivor horses. Horses with serum GGT activity higher than 95 U/l had 14.0 times the risk of death compared to animals showing activities equal to or lower than this value, whereas horses with serum direct bilirubin concentration higher than 0.6 mg/dl (10.26 μmol/L) had 5.78 times the risk of death compared to the others. In summary, serum GGT activity and direct bilirubin concentration may be useful prognostic indicators for assessing the severity of C. spectabilis-poisoned horses.

2022 ◽  
Li-li Shen ◽  
Jun Lu ◽  
Jia Lin ◽  
Bin-bin Xu ◽  
Zhen Xue ◽  

Abstract Purpose The potential additive influence of adjuvant chemotherapy (AC) on prognosis of patients with stage II/III gastric cancer (GC) who experienced complications after radical surgery is unclear.Methods The whole group was divided into a postoperative complication (PC) group and a postoperative non-complication (NPC) group, and the overall survival (OS) rate, recurrence-free survival (RFS) rate and recurrence rate were compared between the two groups of patients. Results A total of 1563 patients between January 2010 and December 2015 in our center were included in this analysis. There were 268 patients (17.14%) in the PC group and 1295 patients (82.86%) in the NPC group. The 5-year OS rate of the PC group was 55.2%, the NPC group was 63.3%; and the 5-year RFS rate of the PC group was 53.7%, the non-PC group was 58.8%. Recurrence patterns showed no significant difference between the two group (all p>0.05). Adjuvant chemotherapy (AC) significantly improved the OS and RFS rates of patients with and without PCs (both p<0.05), and it showed no significant difference between the PC group and the NPC group who received AC (both p> 0.05). Stratified analysis showed that AC only improve the OS or RFS rates of stage III patients (both p<0.05). Further stratified analysis of the time interval (TI) from operation to initiation of AC in the PC group showed that a TI after 6 weeks (≥6eeks) improved only the OS and RFS rates of stage III patients, while when a TI within 6 weeks (<6weeks), a benefit was observed in stage II and III patients (both p<0.05).Conclusion AC can abolish the negative effect of PCs on the long-term survival of patients with stage III GC; for stage II patients, the above offset effect is affected by the TI. Delaying AC initiation after 6 weeks may not improve the survival of patients experienced stage II GC with complications.

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