This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.

This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

Objective:To explore the predictive value of MB isoenzyme of creatine kinase (CK-MB) and poisoning severity score (PSS) in the clinical prognosis of patients with wasp sting.Methods:A retrospective study was conducted. The clinical data of patients who were stung by wasps admitted to emergency department of the First Affiliated Hospital of Henan University of Science and Technology from July 2017 to November 2019 were collected. The 24-hour acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), CK-MB and PSS scores of the patients were collected after admission, and 28-day outcome was recorded. Spearman correlation analysis method was used to analyze the correlation between CK-MB and PSS score. Logistic regression model was used to construct joint predictors, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of various indicators for 28-day prognosis of patients with wasp stings.Results:Finally 90 patients were included in the analysis. There were 67 patients survived at 28 days, and 23 dead with the 28-day mortality of 25.6%. APACHEⅡ score, CK-MB and PSS score in the death group were significantly higher than those in the survival group [APACHEⅡscore: 19.7±2.7 vs. 13.7±2.3, CK-MB (U/L): 183 (151, 243) vs. 36 (21, 75), PSS score: 17.7±2.6 vs. 9.3±4.5, all P < 0.01]. The correlation analysis showed that CK-MB and PSS score were positively correlated ( r = 0.843, P < 0.01). Logistic regression model fitted CK-MB and PSS score, and Hosmer-Lemeshow test showed that the model fitted well. ROC curve analysis showed that the area under ROC curve (AUC) of CK-MB for predicting 28-day outcome was 0.957, the sensitivity was 91.3%, and the specificity was 88.1%; the AUC of PSS score was 0.908, the sensitivity was 91.3%, and the specificity was 90.8%. The AUC of CK-MB combined with PSS score was 0.964, the sensitivity was 100%, and the specificity was 79.4%, indicating that CK-MB combined with PSS score had higher predictive value and higher sensitivity for 28-day prognosis of patients with wasp sting. Conclusions:High CK-MB level and high PSS score in early stage of wasp sting injury indicate poor prognosis. Both CK-MB and PSS score can be used as predictors for predicting the prognosis of patients with wasp stings. In addition, CK-MB combined with PSS score have greater predictive value .

Objective:To explore the relationship between the reconstitution of immune cells in patients with hematological malignancies and the occurrence of chronic graft-versus-host disease (cGVHD) after treatment with unrelated cord blood transplantation (UCBT) and sibling peripheral blood stem cell transplantation (PBSCT) .Methods:A total of 124 patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) in the First Affiliated Hospital of University of Science and Technology of China from March 2018 to August 2019, including 96 patients with UCBT and 28 patients with PBSCT. Peripheral blood immune cells of patients with UCBT and PBSCT were detected at 1, 3, 6, 9, and 12 months after transplantation using flow cytometry, and both UCBT and PBSCT patients were divided into cGVHD and non-cGVHD groups based on whether cGVHD occurred to explore the correlation between the immune cells reconstitution of the two types of transplantation and cGVHD.Results:①The cumulative incidence of the moderate to severe cGVHD in the UCBT group was significantly lower than that in the PBSCT group[9.38% (95% CI 3.35%-15.02%) vs 28.57% (95% CI 9.72%-43.50%) , P=0.008]; the 2-year cumulative incidence of cGVHD and moderate to severe cGVHD in the UCBT group was lower than that in the PBSCT group[15.60% (95% CI 9.20%-23.60%) vs 32.10% (95% CI 15.80%-49.70%) , P=0.047; 10.40% (95% CI 5.30%-17.50%) vs 28.60% (95% CI 13.30%-46.00%) , P=0.014]. ②The absolute counts of CD4 +T cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[59.00 (36.70-89.65) ×10 7/L vs 31.40 (18.10-44.00) ×10 7/L, P<0.001; 71.30 (49.60-101.45) ×10 7/L vs 41.60 (25.82-56.27) ×10 7/L, P<0.001; 83.00 (50.17-121.55) ×10 7/L vs 44.85 (31.62-62.10) ×10 7/L, P<0.001]; the proportions of CD4 +T cells in the UCBT group were always higher than those in the PBSCT group ( P<0.05) . The absolute counts and proportions of B cells in the PBSCT group were higher than those in the UCBT group at the first month after transplantation[0.70 (0.30-1.70) ×10 7/L vs 0.10 (0-0.30) ×10 7/L, P<0.001; 0.45% (0.30%-2.20%) vs 0.20% (0.10%-0.40%) , P=0.002]; the absolute counts and proportions of B cells in the UCBT group were higher than those in the PBSCT group at 9 and 12 months after transplantation[53.80 (28.00-103.20) ×10 7/L vs 23.35 (5.07-35.00) ×10 7/L, P<0.001; 21.45 (11.80-30.45) % vs 9.00% (3.08%-16.73%) , P<0.001. 66.70 (36.97-98.72) ×10 7/L vs 20.85 (7.72-39.40) ×10 7/L, P<0.001; 22.20% (14.93%-29.68%) vs 8.75% (5.80%-18.93%) , P<0.001]. The absolute counts and proportions of regulatory B (Breg) cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[1.23 (0.38-3.52) ×10 7/L vs 0.05 (0-0.84) ×10 7/L, P<0.001; 5.35% (1.90%-12.20%) vs 1.45% (0-7.78%) , P=0.002. 2.25 (1.07-6.71) ×10 7/L vs 0.12 (0-0.77) ×10 7/L, P<0.001; 6.25% (2.00%-12.33%) vs 0.80% (0-5.25%) , P<0.001. 3.69 (0.83-8.66) ×10 7/L vs 0.46 (0-0.93) ×10 7/L, P<0.001; 6.15% (1.63%-11.75%) vs 1.40% (0.18%-5.85%) , P<0.001].The absolute counts and proportions of CD3 +T cells, CD8 +T cells, and Treg cells in the UCBT group were not significantly different from those in the PBSCT group. ③The absolute counts of B cells in the non-cGVHD group of UCBT patients were higher than those in the moderate to severe cGVHD group at 6 and 12 months after transplantation ( P=0.038, P=0.043) ; the proportions of B cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 6 months after transplantation ( P=0.049) . The absolute counts of Breg cells in the non-cGVHD group of patients with UCBT were higher than those in the moderate to severe cGVHD group at 6, 9, and 12 months after transplantation ( P=0.006, P=0.028, P=0.050) ; the proportions of Breg cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 9 months after transplantation ( P=0.038) . ④The absolute counts and proportions of B and Breg cells in the non-cGVHD group of patients with PBSCT were not statistically different than those in the moderate to severe cGVHD group. Conclusion:In the process of immune cell reconstitution, the Breg cells in the UCBT group were higher than those in the PBSCT group, and the Breg cells in the non-cGVHD group of the two types of transplantation were always higher than those in the moderate to severe cGVHD group, indicating that Breg cells can reduce the occurrence of cGVHD, revealing the possible reason for the lower incidence of cGVHD in the UCBT group.

Objective To evaluate the effect of pretransplant iron overload on the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). Methods Clinical data of 80 SAA recipients who underwent allo-HSCT for the first time were retrospectively analyzed. According to the incidence of iron overload, all recipients were divided into the iron overload group (n=20) and non-iron overload group (n=60). The engraftment rate, incidence of postoperative complications and clinical prognosis of the recipients afterallo-HSCT were statistically compared between two groups. The influencing factors of 2-year overall survival (OS) and 180 d transplantation related mortality (TRM) were analyzed by Cox proportional hazards regression model. Results The engraftment rate of neutrophils in the non-iron overload group was 98% (59/60), significantly higher than 75% (15/20) in the iron overload group (P < 0.05). The engraftment rate of platelet in the non-iron overload group was 90% (54/60), significantly higher than 65% (13/20) in the iron overload group (P < 0.05). The incidence rate of bloodstream infection in the non-iron overload group was 23% (14/60), remarkably lower than 40% (8/20) in the iron overload group (P < 0.05). The 180 d TRM of the recipients in the non-iron overload group was 17%, significantly lower than 45% in the iron overload group (P < 0.05). The 1- and 2-year OS of the recipients in the non-iron overload group were 82% and 80%, significantly higher than 50% and 44% in the iron overload group (both P < 0.05). Iron overload or not was an independent risk factor of the OS and TRM of the recipients (both P < 0.05). Conclusions Iron overload can affect the OS and TRM of SAA patients after allo-HSCT.

Objective To systematically evaluate the diagnostic accuracy and clinical applicability of recognition of stroke in the emergency room (ROSIER) scale by systematic review and Meta-analysis. Methods The Chinese and English literatures concerning the diagnostic accuracy of ROSIER published from January 1st 2005 to December 31st 2018 by PubMed, Embase, Wanfang, VIP and CNKI databases were searched comprehensively and systematically. The sensitivity, specificity, and diagnostic odds ratio (DOR) of ROSIER in total population and subgroup analysis were pooled by using bivariate mixed effects model. Sensitivity analysis was used to evaluate the stability of the results. Deek funnel plot was utilized to evaluate publication bias. The clinical applicability of ROSIER was evaluated by Fagan Nomogram. Results A total of 28 studies incorporating 7 579 subjects were enrolled in this Meta-analysis. Meta-analysis in total population showed that the pooled sensitivity, specificity and DOR of ROSIER was 0.89 [95% confidence interval (95%CI) = 0.86-0.91, P = 0.00], 0.74 (95%CI = 0.67-0.80, P = 0.00) and 22.09 (95%CI =14.86-32.82, P = 0.00), respectively. Subgroup analysis of pooled sensitivity of ROSIER showed that Asian patients was significantly higher than European patients [0.89 (95%CI = 0.86-0.92) vs. 0.74 (95%CI = 0.66-0.82), P < 0.01], prospective study was significantly higher than retrospective study [0.89 (95%CI = 0.87-0.92) vs. 0.74 (95%CI = 0.61-0.88), P < 0.05], pre-hospital emergency was significantly higher than emergency department [0.87 (95%CI = 0.80-0.94) vs. 0.85 (95%CI = 0.81-0.90), P < 0.01], study with sample size ≤ 200 was significantly higher than study with sample size > 200 [0.88 (95%CI = 0.83-0.93) vs. 0.82 (95%CI = 0.76-0.88), P < 0.05], but there was no significant difference between different evaluators or different male to female ratio subgroups. Subgroup analysis of pooled specificity of ROSIER showed that European patients was significantly higher than Asian patients [0.81 (95%CI = 0.73-0.89) vs. 0.79 (95%CI = 0.73-0.85), P < 0.05], retrospective study was significantly higher than prospective study [0.88 (95%CI =0.78-0.97) vs. 0.79 (95%CI = 0.73-0.84), P < 0.05], pre-hospital emergency was significantly higher than emergency department [0.82 (95%CI = 0.73-0.91) vs. 0.79 (95%CI = 0.73-0.85), P < 0.01], emergency physicians was significantly higher than other medical workers [0.80 (95%CI = 0.74-0.86) vs. 0.79 (95%CI = 0.69-0.90), P < 0.05], study with sample size ≤ 200 was significantly higher than study with sample size > 200 [0.82 (95%CI = 0.76-0.89) vs. 0.78 (95%CI = 0.71-0.85), P < 0.05], but there was no significant difference between different male or female ratio subgroups. Sensitivity analysis showed that there was no significant change in pooled DOR before and after excluding each study, indicating that the results were stable. Funnel plot showed that there was a significant publication bias in the total population (P = 0.04), but there was no publication bias in the European population (P = 0.57) or the Asian population (P = 0.08). According to the results of the Fagan Nomogram, with the pretest probability of 50%, when ROSIER was positive, the probability of being diagnosed with stroke increased to 77%, and when ROSIER was negative, the probability of being diagnosed with non-stroke decreased to 13%. It was suggested that ROSIER had good applicability and high clinical diagnostic value. Conclusions ROSIER has high diagnostic sensitivity and specificity, and has high clinical diagnostic value. It is a valid stroke identification tool which can be widely used in Asian population, pre-hospital emergency and be utilized by trained medical worker.

Objective To explore the imaging biomarker for early diagnosis and disease course monitoring of Parkinson disease (PD) in arterial spin labeling (ASL) technique. Methods Between July, 2014 and May, 2017, 23 patients with PD underwent magnetic resonance imaging (MRI) and ASL examinations in our hospital, including 13 in the early stage and 10 in advanced stages. Voxel-based analysis (VBA) was used to observe the regional cerebral blood flow (rCBF) characteristics in PD patients in different stages and three-dimensional continuous arterial spin labeling (3D CASL) was used to analyze the mean cerebral blood flow (mCBF). Results No significant difference was found in mCBF among PD patients in the early stage, patients in advanced stages and normal control subjects (P=0.30). Compared with the normal control group, the patients with early-stage PD had decreased rCBF in resting state mainly in the right superior occipital gyrus and the right superior frontal gyrus as revealed by VBA (P<0.001);the patients with advanced PD showed decreased rCBF mainly in the left precentral gyrus and the postcentral gyrus (P<0.001). The patients with advanced PD exhibited lowered rCBF in the right substantia nigra and the bilateral corpus callosum as compared with the early-stage patients (P<0.001). Conclusions VBA of ASL reveals rCBF alterations in association with the disease progression in PD patients, suggesting that this technique might provide assistance in identification of potential markers for early PD diagnosis and for monitoring the disease course.

Objective To explore the imaging biomarker for early diagnosis and disease course monitoring of Parkinson disease (PD) in arterial spin labeling (ASL) technique. Methods Between July, 2014 and May, 2017, 23 patients with PD underwent magnetic resonance imaging (MRI) and ASL examinations in our hospital, including 13 in the early stage and 10 in advanced stages. Voxel-based analysis (VBA) was used to observe the regional cerebral blood flow (rCBF) characteristics in PD patients in different stages and three-dimensional continuous arterial spin labeling (3D CASL) was used to analyze the mean cerebral blood flow (mCBF). Results No significant difference was found in mCBF among PD patients in the early stage, patients in advanced stages and normal control subjects (P=0.30). Compared with the normal control group, the patients with early-stage PD had decreased rCBF in resting state mainly in the right superior occipital gyrus and the right superior frontal gyrus as revealed by VBA (P<0.001);the patients with advanced PD showed decreased rCBF mainly in the left precentral gyrus and the postcentral gyrus (P<0.001). The patients with advanced PD exhibited lowered rCBF in the right substantia nigra and the bilateral corpus callosum as compared with the early-stage patients (P<0.001). Conclusions VBA of ASL reveals rCBF alterations in association with the disease progression in PD patients, suggesting that this technique might provide assistance in identification of potential markers for early PD diagnosis and for monitoring the disease course.