1.Simvastatin alleviates kidney ischemia reperfusion injury by inhibiting ferroptosis
Zhihui FU ; Zhongzhong LIU ; Qifa YE ; Qi XIAO ; Qin DENG ; Jiansheng XIAO ; Biqi FU
Acta Universitatis Medicinalis Anhui 2026;61(1):45-52
ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury (IRI) in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups: Sham operation group (Sham group), kidney IRI group (IR group), and simvastatin pretreatment+kidney IRI group (SIM group). Hematoxylin-eosin (HE) staining of kidney tissue and detection of serum creatinine (SCr) and lactate dehydrogenase (LDH) were used to evaluate kidney injury. The levels of superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) were detected to evaluate oxidative stress. The contents of ferrous iron (Fe2+) and ferric iron (Fe3+) in kidney tissue were detected, and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 (KLF2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-coa synthetase long chain family member 4 (ACSL4) protein in kidney tissue were detected. ResultsCompared with the IR group, the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum (P < 0.001). It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS (P < 0.01). Simvastatin pretreatment reduced the contents of Fe2+ and Fe3+ in the tissues (P < 0.01) and alleviated mitochondrial damage. It also promoted the expression of KLF2 (P < 0.01), up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11, and down-regulated the expression of ferroptosis-related damage protein ACSL4 (P < 0.05). ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.
2.Strategies for the diagnosis and treatment of pulmonary chronic graft-versus-host disease after hematopoietic stem cell transplantation
Chunrong JU ; Shunqing WANG ; Xi ZHANG ; Qifa LIU
Chinese Journal of Hematology 2025;46(8):771-778
Hematopoietic stem cell transplantation (HSCT) is currently an effective method to cure hematologic malignancies and bone marrow failure diseases, and can restore hematopoietic function destroyed by hematologic malignant diseases. In recent years, HSCT has developed rapidly in China, but pulmonary chronic graft-versus-host disease after transplantation has seriously affected the quality of life and long-term survival of patients. Therefore, this article aims to describe the risk factors, clinical classification, and early diagnosis and treatment strategies of pulmonary chronic graft-versus-host disease, and proposes that lung transplantation is the only effective therapeutic intervention when medical treatment proves ineffective for end-stage pulmonary cGVHD.
3.Strategies for the diagnosis and treatment of pulmonary chronic graft-versus-host disease after hematopoietic stem cell transplantation
Chunrong JU ; Shunqing WANG ; Xi ZHANG ; Qifa LIU
Chinese Journal of Hematology 2025;46(8):771-778
Hematopoietic stem cell transplantation (HSCT) is currently an effective method to cure hematologic malignancies and bone marrow failure diseases, and can restore hematopoietic function destroyed by hematologic malignant diseases. In recent years, HSCT has developed rapidly in China, but pulmonary chronic graft-versus-host disease after transplantation has seriously affected the quality of life and long-term survival of patients. Therefore, this article aims to describe the risk factors, clinical classification, and early diagnosis and treatment strategies of pulmonary chronic graft-versus-host disease, and proposes that lung transplantation is the only effective therapeutic intervention when medical treatment proves ineffective for end-stage pulmonary cGVHD.
4.Clinical characteristics and current status of organ donations and Organ Procurement Organizations in foreign countries
Fushun ZHONG ; Yongkang FANG ; Linjiong LIU ; Xiaoli FAN ; Qifa YE
Chinese Journal of Organ Transplantation 2024;45(1):47-56
Organ transplantation has been an important means of rescuing the lives of end-stage patients with organ failure. However, an acute shortage of donor organs has become a common dilemma for organ transplantation all over the world so as to seriously restrict the development of organ transplantation. Many foreign countries have established a relatively mature organ donation system to foster favorable conditions for alleviating a shortage of donor organs. This review summarized the global measures and current domestic efforts of facilitating organ donation to provide theoretical rationales for further optimizing organ donations and transplantation system in China.
5.Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation
Rong FU ; Ren LIN ; Zhiping FAN ; Fen HUANG ; Na XU ; Li XUAN ; Yifei HUANG ; Hui LIU ; Ke ZHAO ; Zhixiang WANG ; Ling JIANG ; Min DAI ; Jing SUN ; Qifa LIU
Chinese Journal of Hematology 2024;45(1):62-67
Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.
6.The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia
Shiyu DENG ; Jiawang OU ; Zicong HUANG ; Junjie CHEN ; Zihong CAI ; Qifa LIU ; Hongsheng ZHOU
Chinese Journal of Hematology 2024;45(3):257-263
Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.
7.A case report of reno-portal anastomosis liver transplantation for grade 4 portal vein thrombosis
Zhongzhong LIU ; Zibiao ZHONG ; Chenbiao XUE ; Wei ZHOU ; Shaojun YE ; Qifa YE
Chinese Journal of Organ Transplantation 2024;45(4):265-268
The relevant clinical data were reviewed for a recipient of grade 4 portal vein thrombus undergoing reno-portal anastomosis liver transplantation on May 19, 2022. Liver function transaminase and bilirubin gradually normalized within 2 weeks after operation. An elevation of creatinine showed mild functional impairment at Day 5-7 post-operation and then recovered quickly. No portal vein thrombosis, gastrointestinal hemorrhage, ascites and other complications occurred within 2 years post-operation. The survival was excellent during 2-year follow-ups.
8.Allogeneic hematopoietic stem cell transplantation during the normalization stage of COVID-19 management
Chinese Journal of Hematology 2024;45(11):977-981
At present, the world has entered the normalization stage of coronavirus disease 2019 (COVID-19) management. COVID-19 continues to affect patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) for a long period. The author discussed the possible effect of COVID-19 on HSCT strategy and prognosis during this period based on literature reports. Transplantation should be deferred until clinical resolution and negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients infected with SARS-CoV-2 before transplantation. Donors infected with SARS-CoV-2 during the stem cell collection may not affect apheresis. Allo-HSCT recipients demonstrated a high rate of severe COVID-19 if COVID-19 occurred at the early stage of transplantation. Severe COVID-19 remains a risk factor for nonrelapse mortality and survival after transplantation. The association between COVID-19 and post-transplantation complications, such as other infections, endothelial injury-related complications, and relapse, needs to be further investigated in large samples.
9.Early cellular immune exhaustion in patients with Epstein-Barr virus activation following haploidentical hematopoietic stem cell transplantation
Yifei HUANG ; Shanyu ZHANG ; Jiabao HE ; Ya ZHOU ; Rongtao XUE ; Zhiping FAN ; Fen HUANG ; Na XU ; Jing SUN ; Qifa LIU ; Ren LIN
Chinese Journal of Hematology 2024;45(11):998-1004
Objective:This study aimed to investigate the association between early immune reconstitution and Epstein-Barr virus (EBV) reactivation by analyzing changes in natural killer (NK), B, and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods:This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation (HSCT). The immune reconstitution of NK cells, T cells, and B cells as well as the expression levels of NK and T cell exhaustion markers (PD-1, TIM-3, and CTLA-4) and cytotoxic function at 1, 2, and 3 months post-transplantation were compared between patients with EBV activation (EBV+ group) and those without activation (EBV- group) post- transplantation.Results:EBV activation occurred in nine patients post-transplantation (EBV+ group), whereas 14 patients demonstrated no activation (EBV- group). All patients with EBV activation exhibited EBV viremia, and no EBV-associated diseases occurred. No significant differences in the clinical characteristics were found between the two groups of patients. The median proportion of CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1 month post-transplantation ( P=0.033). The median proportion of the CD3 -CD16 negCD56 bri subset in the EBV+ group was significantly higher than that in the EBV- group at 2 months post-transplantation ( P=0.046). No significant differences in the median proportions of CD3 -CD19 + B cells were observed between the two groups at 1, 2, and 3 months post-transplantation. The expression of CTLA-4 on CD3 -CD16 briCD56 dim NK cells in the EBV+ group was significantly higher than that in the EBV- group at 1 month post-transplantation ( P=0.033). The expression of TIM-3 on CD3 +CD8 + T cells in the EBV+ group was significantly higher than that in the EBV- group ( P=0.009). The expression level of TIM-3 on CD3 -CD16 negCD56 dim NK cells in the EBV+ group was significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.023). The expression levels of TIM-3 on CD3 +CD4 + T cells in the EBV+ group than those in the EBV- group at 1 and 3 months post-transplantation ( P=0.002, P=0.043). The median positive rate of Granzyme B expression in CD3 +CD8 + T cells and CD3 +CD4 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1-month post-transplantation ( P=0.033, P=0.016). The median positive rate of Granzyme B expression in the CD3 -CD16 briCD56 neg cell subset in the EBV+ group was higher than that in the EBV- group at 2 months post-transplantation ( P=0.012). The median positive rate of Granzyme B expression in CD3 +CD4 + T cells in the EBV+ group remained significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.049). The median positive rate of perforin expression in the CD3 -CD16 briCD56 dim cell subset was significantly higher in the EBV+ group than in the EBV- group at 3 months post-transplantation ( P=0.003). The median positive rate of IFN-γ expression in CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 3 months post-transplantation ( P=0.036) . Conclusion:Delayed NK cell and T lymphocyte reconstitution, high exhaustion marker expression, and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.
10.Allogeneic hematopoietic stem cell transplantation during the normalization stage of COVID-19 management
Chinese Journal of Hematology 2024;45(11):977-981
At present, the world has entered the normalization stage of coronavirus disease 2019 (COVID-19) management. COVID-19 continues to affect patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) for a long period. The author discussed the possible effect of COVID-19 on HSCT strategy and prognosis during this period based on literature reports. Transplantation should be deferred until clinical resolution and negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients infected with SARS-CoV-2 before transplantation. Donors infected with SARS-CoV-2 during the stem cell collection may not affect apheresis. Allo-HSCT recipients demonstrated a high rate of severe COVID-19 if COVID-19 occurred at the early stage of transplantation. Severe COVID-19 remains a risk factor for nonrelapse mortality and survival after transplantation. The association between COVID-19 and post-transplantation complications, such as other infections, endothelial injury-related complications, and relapse, needs to be further investigated in large samples.

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