Abstract Background Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection among solid organ transplantation. The occurrence of PJP is dangerous and fatal if there is no early identification and sufficient treatment. Objective The aim of this study was to evaluate the risk factors and provide appropriate strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre. Patients/Methods From January 2009 to December 2018, a total of 167 kidney transplantation recipients with pneumonia were enrolled, including 47 PJP patients as PJP group and 120 non‐PJP patients as control group. The clinical characteristics of the two groups were analysed retrospectively. Results Multivariate analysis showed that high total dosage of ATG [OR, 2.03; 95% CI, 1.12–3.68] and cytomegalovirus (CMV) infection were independent risk factors for PJP. Trimethoprim‐sulfamethoxazole (TMP‐SMX) (1.44 g q6h)–based treatment was used for 2 weeks, and its dosage and course were adjusted according to the therapeutic effect and side effects. Forty‐five cases were recovered after 3 months of follow‐up, and two patients died of respiratory failure. TMP‐SMX (0.48 g/day) prophylaxis was used for 3–6 months and prolonged to 7–8 months after treatment for acute rejection, which reduced the incidence of PJP compared with those without prophylaxis. Conclusion Our study suggests that the high total dosage of ATG and CMV infection indicate the increased risk of PJP. The strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre were effective.
To explore the role and significance of blood group genotyping and gene sequencing technology in the identification of blood group subtypes.Blood type of the proband and his son were identified by blood type serology, and ABO genotyping and DNA sequencing were performed according to the results of serological expression pattern.The weak B antigen expression was found in the proband and his son by serological test, and was preliminarily identified as B3 subtype. The ABO blood group genotyping confirmed that the genotype of the proband and his son was B/O1 and B/O2, respectively. Finally, through gene sequencing, it was confirmed that the B101 allele of the proband and his son showed a heterozygous mutation of 5873CT.The combination of serology, genotyping and sequencing showed find new blood group gene mutation sites, which is important strategic significance for accurate blood group identification, personalized blood use and trasfusion safety, which is beneficial to clarify the molecular biological basis of ABO blood group subtypes.基于测序技术鉴定血型基因5873CT突变引起B抗原弱表达.探讨血型基因分型和基因测序技术在鉴定血型亚型中的作用和意义.利用血型血清学方法对先证者及其儿子进行初步血型鉴定，根据血清学表达格局结果选择疑难血型的补充实验，并进行ABO基因分型及测序.血清学实验发现，先证者及其儿子有弱B抗原的表达，血型血清学方法初步鉴定为B3亚型。ABO基因分型明确了先证者的基因型为B/O1，其儿子的基因型为B/O2。最终通过基因测序，证实先证者及其儿子的B101等位基因上intron1内均存在5873C>T杂合突变.采用血清学、基因分型和测序相结合的方法，可发现血型基因新突变位点，有益于阐明ABO亚型的分子生物学基础，对精准血型鉴定、个体化用血及输血安全有着重要战略意义.
Background Brain lymphatic drainage impairment is a prevalent characteristic in both aging and neurodegeneration. Surgery is more likely to induce excessive neuroinflammation and postoperative neurocognitive disorder (PND) among patients with aging and neurodegeneration. We hypothesized that surgical trauma may aggravate PND through preexisting cerebral lymphatic drainage impairment. However, there remains limited understanding about the role of surgery in changes of neurocognitive function in the populations with preoperative brain lymphatic drainage impairment. This study aims to expand our insight into surgery-induced glymphatic dysfunction, neuroinflammation and PND in middle-aged mice with preoperative brain lymphatic drainage impairment. Materials and methods Deep cervical lymph nodes ligation (LdcLNs) was performed on middle-aged mice to establish preoperative brain lymphatic drainage impairment. A month later, laparotomy was performed on these mice with or without LdcLNs followed by analysis of brain neuroinflammation, glymphatic function, neuronal damage, and behavioral test. Results LdcLNs disrupted meningeal lymphatic drainage. In middle-aged mice with LdcLNs, surgery exacerbated more serious glymphatic dysfunction accompanied by aggravation of A1 astrocytes activation and AQP4 depolarization. Furthermore, surgery caused neuronal damage via reducing expression of neuronal nuclei (NeuN), post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), as well as impairment in exploratory behavior and spatial working memory in middle-aged mice with LdcLNs. Additionally, surgery induced neuroinflammation with elevated microglia activation and increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as activated more expression of HMGB1/TLR-4/NF-κB pathway in middle-aged mice with LdcLNs. Conclusion Surgery exacerbates neuroinflammation and glymphatic dysfunction, ultimately resulting in neuronal damage and neurocognitive disorder in middle-aged mice with preoperative brain lymphatic drainage impairment. These results suggest that brain lymphatic drainage impairment may be a deteriorating factor in the progression of PND, and restoring its function may serve as a potential strategy against PND.
Abstract Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The breakdown of immune tolerance (regulatory T [Treg] cells and suppressor cytokines) plays an important role in ITP pathophysiology, especially in refractory ITP. Bone marrow–derived mesenchymal stem cells (BM‐MSCs) show immunomodulatory properties and have been extensively utilized for autoimmune diseases. However, it has not been fully elucidated how BM‐MSCs affect ITP. In this study, we explore the therapeutic mechanism of BM‐MSCs on ITP in mice. Dose‐escalation passive ITP mice were inducted by injection of MWReg30. BALB/c mice were randomly divided into two groups: ITP with BM‐MSC transplantation and ITP controls. The serum levels of cytokines (interleukin 10 [IL‐10] and transforming growth factor‐β1 [TGF‐β1]) were examined by enzyme‐linked immunosorbent assays. The frequency of Treg cells in both peripheral blood and spleen mononuclear cells was analyzed by flow cytometry, and the forkhead box P3 (Foxp3) messenger RNA (mRNA) level was measured by real‐time polymerase chain reaction. After BM‐MSC treatment, the platelet (PLT) counts were significantly elevated. Meanwhile, cytokines (TGF‐β1 and IL‐10), the ratios of Treg cells, and the Foxp3 mRNA expression level were significantly higher in the BM‐MSC group. Our results show that BM‐MSCs can improve PLT counts mainly by secreting suppressive cytokines and upregulating Tregs, which may provide new therapeutic potential for human ITP.
To investigate the expression and clinical significance of high mobility group box 1(HMGB1) in spleen of adult patients with chronic and refractory immune thrombocytopenia(ITP).Twenty chronic and refactory ITP patients received splenectomy were enrolled in ITP group and 20 cases of traumatic spleen rupture were enrolled in control group. The splenectomy efficacy in ITP patients was analyzed retrospectively. The HMGB1 expression in spleen tissue was detected by immunohistochemistry, and the correlation between different expression levels of HMGB1 and splenectomy efficacy were analysed. Meanwhile, the protein expression levels of HMGB1 in peripheral blood serum and mononuclear cells(PBMNC) of 25 patients with chronic and refractory ITP were detected by ELISA and Western blot.The median platelet count before splenectomy was 7.5 (0-20) ×109/L; all the patients showed that the initial response to splenectomy within the first month after operation was 100%, the median time of response was 1 day (1-6 days). The median peak platelet count post splenectomy was 448.5 (161-1272)×109/L. In the median time of 10(3-30) months, the platelets count in 8 patients was reduced to varying degrees. After a median follow-up of 69.5 months (22-195), complete response was found in 12 patients, 4 cases showed response and 4 did not. The HMGB1 expression positive rate in spleen of ITP patients was significantly higher than that in control group (85.0% vs 15.0%)(P<0.001). There were a negative correlation between the HMGB1 expression in ITP and therapeutic outcome after splenectomy (r=-0.791, P<0.01). In addition, HMGB1 expression levels in serum and PBMNC of the patients with chronic refractory ITP were also significantly higher than that in healthy controls (P<0.01).The splenectomy has been found to be effective therapeutic method for patients with ITP, the HMGB1 highly express in the spleen of the patients with chronic refractory ITP, but negatively correlats with the therapeutic outcome after splenectomy.
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