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Human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte (CTL) immune response must be reconstituted for long-term protection against CMV relapse and disease in hematopoietic stem cell transplantation (HSCT) recipients. We phenotypically quantitated absolute numbers of CMV-pp65 peptide-specific CTLs (CTLCMV) in 50 related donor unmanipulated allografts infused into HLA-matched or -mismatched recipients and examined the incidence of CMV reactivation. High CTLCMV with terminally differentiated effector CD45RO-CD62L- cell (TEMRA) phenotype in the allografts were associated with reduced risk of CMV reactivation, in the presence of sufficient CD45RO+CD62L- cell (TEM) infusion (≥0.208 × 106/kg). Early after transplantation, there was significant expansion of CTLCMV with the central memory CD45RO+CD62L+ cell (TCM) phenotype when CMV was reactivated. The frequencies of CTLCMV TNaive (CD45RO-CD62L+), TCM, and TEM at day 90 posttransplantation and of CTLCMV TEMRA at day 60 posttransplantation were greater in recipients with higher infusions of CTLCMV TEMRA, suggesting protective immunity transferred by infusion of CTLCMV within allografts. Moreover, the majority of the CTLCMV identified in the recipients early after HSCT was of donor origin. Our findings support that measuring levels of CTLCMV and its subsets in the donor grafts and manipulating these cells early after transplantation may help control CMV reactivation, which is closely correlated with immune reconstitution and differentiation of CTLCMV subsets. [Copyright &y& Elsevier]

To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival., Methods: The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed., Results: The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old ( P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine ( P =0.002), albumin≤30 g/L on d30 after transplantation ( P =0.007), CMV-DNA positive ( P =0.028), fungal infection before transplantation ( P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD ( P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation ( P =0.008) and albumin≤30 g/L on d30 after transplantation ( P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC ( P =0.041)., Conclusion: For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.

Objective: To investigate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of young patients with multiple myeloma (MM)., Methods: The clinical data of 8 young patients (median age：46 years) with MM who underwent allo-HSCT from HLA-indentical sibling donors in the First Affiliated Hospital of Chongqing Medical University from June 2013 to September 2021 were collected, and their survival and prognosis were retrospectively analyzed., Results: All the patients were successfully transplanted, and 7 patients could be evaluated the efficacy after transplantation. The median follow-up time was 35.2 (2.5-84.70) months. The complete response (CR) rate was 2/8 before transplantation and 6/7 after transplantation. Acute GVHD developed in 2 cases and extensive chronic GVHD developed in 1 case. Within 100 days, 1 case died of non-recurrent events, and 1-year and 2-year disease-free survival were 6 and 5 cases, respectively. At the end of follow-up, all the 5 patients who survived for more than 2 years survived, and the longest disease-free survival time has reached 84 months., Conclusion: With the development of new drugs, HLA-matched sibling donor allo-HSCT may be a curable treatment for young patients with MM.

Patterns of hepatitis B virus reactivation (HBV-R) in HBsAg (-)/HBcAb (+) patients with B-cell non-Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (-)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV-R in HBsAg (-)/HBcAb (+) B-cell NHL patients was 6.3% (14/222), of which that in HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV-R in B-cell lymphoma patients (training phase hazard ratio [HR], 10.123; 95% confidence interval [CI], 3.389-30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684-205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529-33.207; p < 0.001). In the training cohort, the mortality rate of HBsAg (-)/HBcAb (+) B-cell NHL caused by HBV-R was 14.3% (2/14) while that for HBV reactivated HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV-R and high mortality after HBV-R was found in HBsAg (-)/HBsAb (-)/HBcAb (+)/HBeAg (-)/HBeAb (+) patients with B-cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients., (© 2023 Wiley Periodicals LLC.)

Objective: To evaluate the clinical effect of haploid allogeneic hematopoietic stem cell transplantation(haplo-HSCT) in the treatment of severe aplastic anemia (SAA), and to explore the efficacy different between post-transplant cyclophosphamide (PT/Cy) and standard-dose ATG., Methods: The clinical data of 38 patients with SAA in our hospital from January 2012 to December 2019 were collected and retrospectively analyzed. The efficacy was evaluated. The patients with haplo-HSCT were divided into low-dose ATG combined with PT/Cy group and standard-dose ATG group, and the blood cell hematopoietic reconstruction time, GVHD incidence, mortality and survival time of the patients in the two groups was compared., Results: Among the 32 patients, hematopoietic reconstitution were detected in 9375%(30/32) recipients. The median time of neutrophil and platelet engraftment was 15(10-22) days and 13(7-30) days, respectively. The incidence of GVHD was 21.89%, the incidence of infection was 93.75%, and the 2-year overall survival rate was 84.38%. The hematopoietic reconstitution time, incidence of GVHD, mortality rate and survival time were no statistical differences between the patients in the two groups(all P>0.05)., Conclusion: Haplo-HSCT is an effective method for the treatment of SAA，low-dose ATG combined with PT/Cy can lighten the economic burden on patients, it would be a feasible treatment plan for SAA with light side effect.

Keloid, characterized by exuberant collagen deposition and invasive growth beyond original wound margins, results from abnormal wound healing. A recent microarray analysis identified homeobox (HOX) A11 antisense (HOXA11-AS) as a keloid-specific long non-coding RNA, although its potential role in keloid formation remains elusive. In this study, hematoxylin-eosin, Masson, and immunohistochemical staining of type I collagen (ColI) revealed abnormal arrangement and hyperplasia of fibers in keloid tissues along with increased ColI level. qRT-PCR and Western blot showed that HOXA11-AS and ColI were significantly upregulated, while miR-124-3p was decreased in both keloid tissues and human keloid fibroblasts (HKFs). Knockdown of HOXA11-AS inhibited cell proliferation (by CCK-8 and immunofluorescence staining of Ki67) and cell migration (by wound healing and transwell assays). Mechanistic experiments verified that HOXA11-AS acted as a sponge of micro-RNA (miR)-124-3p and Smad5 was a target of miR-124-3p. miR-124-3p sufficiently reversed the regulatory effects of HOXA11-AS, and Smad5 was involved in miR-124-3p-mediated biological functions. Furthermore, HOXA11-AS induced ColI synthesis via sponging miR-124-3p-mediated Smad5 signaling, thus promoting keloid formation. Overall, our study implied that HOXA11-AS induces ColI synthesis to promoted keloid formation via sponging miR-124-3p-mediated Smad5 signaling, which might offer a novel target for developing the therapy of keloid formation.

Objective: To detect whether the murine T-cell lymphoma cell line EL4 could be infected by murine cytomegalovirus (MCMV), and to observe the morphological changes and apoptosis of El4 cells before and after infection., Methods: EL4 cells were infected with MCMV smith strain with 1, 10 and 100 multiplicity of infection (MOI) respectively. The morphology of the cells was observed by light microscopy and Wright's-Giemsa staining. The survival rate was calculated by trypan blue staining. RT-PCR-based assay was used to detect the copy number of MCMV-DNA in the infected ELA cells. Flow cytometry was used to detect apoptosis. RT-qPCR was used to detect the mRNA expression levels of P53, P21, cFlip and Caspase 8. The protein expression levels of Caspase8, P53, BAX, BCL-2 and Cleaved Caspase3 proteins were detected by Western blot., Results: After Wright-Giemsa staining, it was found that the infected EL4 cells displayed larger volume, irregular nuclei and the folded twist under light microscopy. Compared with the normal control group, the survival rate of EL4 cells decreased, and the apoptosis rate statistically significantly (P<0.05) increased with the increasing MOI and the infected time in each group. While, the level of apoptosis protein P53, BAX/BCL-2, Cleaved-caspase3 and Caspase8 were up-regulated. And the survival rate, apoptosis rate and the apoptosis protein level of infected EL4 cells with MOI=10 were the most obvious at the 5 th day. Compared with MCMV infection group (MOI=60), the content of MCMV DNA in EL4 cells was decreased in MCMV+GGV group ［MOI=60, GCV 25 (g/ml)］, and the cell apoptosis rate and apoptosis protein expression of P53, Caspase8, BAX/BCL-2 were decreased (P<0.05)., Conclusion: Murine T-cell lymphoma cell line EL4 can be infected by MCMV and displayes an obvious apoptosis phenomenon. MCMV may up-regulate the expression levels of apoptosis protein P53, BAX-BCL-2, Cleaved-caspase3 and Caspase8 in EL4 cells. The drug ganciclovir reduces the copy mumber of MCMV DNA in infected EL4 cells and inhibited the killing effect of MCMV on EL4 cells.

Objective: To investigate the regular pattern of Cytomegalovirus (CMV)-specific T cells (CTL) immune reconstitution after human leukocyte antigen (HLA) matched sibling donor allogeneic bone marrow(BM) plus peripheral blood hematopoietic stem cell (PBSC) transplantation., Methods: CTL from seventeen patients after transplantation was detected by flow cytometry, the IFN-γ secretion ability of CTL by enzyme-linked immunospot (ELISPOT) assay, and clonal analysis of TCR Vβ subfamily by gene scan assays. The relationship between CTL reconstitution and CMV infection was studied., Results: Both number and function of recipients CTL reached to normal control level at 30 d post-transplantation. The recipients achieved a high frequency CTL with IFN-γ response and restoration of T-cell receptor β (TCR Vβ) repertoire at one year post-transplantation. CTL with the central memory CD45RO(+)CD62L(+) cell phenotype expanded in PB when CMV was reactivated. The incidence of CMV reactivation was 35.83% (17.91% - 63.10%) after transplantation, and none of them developed CMV disease., Conclusion: After HLA matched related donor transplantation using mixed grafts, immune recovery to CMV seems to be early and fast. The incidence of CMV infection and disease are low.

Objective: To investigate the prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province., Methods: Data from 169 218 pregnant women in different regions of Guangdong province from January 2005 to June 2010 were analyzed retrospectively. The prevalence and epidemiological characteristics of thromboembolic disease during pregnancy or puerperium were investigated., Results: Of the studied population, (1) 201 cases (1.3‰) suffered from thromboembolic disease during pregnancy or puerperium including 128 cases of deep vein thrombosis (DVT), 68 cases of cerebral venous thrombosis (CVT) and 5 pulmonary embolism, the prevalence rates were 0.8‰, 0.4‰, and 0.02‰ respectively. (2) Risk factors in different regions showed that, in the Pearl River Delta area, the major risk factors for DVT would include previous or family history of thrombosis, pregnancy complications, with medically involved diseases, prolonged bed rest and pregnancy weight gain>15 kg etc. While in eastern, western, northern parts of Guangdong, the major risk factors for DVT would include pregnancy weight gain>15 kg, prolonged bed rest, preeclampsia, cesarean section and complications during pregnancy. In Pearl River Delta region, the major risk factors for CVT would include eclampsia, preeclampsia, pregnancy complications, prolonged bed rest>3 days, past history or family history of thrombosis. While eclampsia, preeclampsia, advanced age or younger age, pregnancy weight gain>15 kg, complications during pregnancy were the major risk factors for CVT in the eastern, western or northern parts of Guangdong., Conclusion: Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong were different. It was crucial to take effective measures in pregnant women with different epidemiological characteristics and risk factors to prevent and reduce the incidence of peripartum thromboembolic disease.

The aim of study was to investigate the modulation effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on adhesion molecule expression of memory T lymphocyte in the bone marrow grafts. rhG-CSF was administered in 41 donors by subcutaneous injection for 5 consecutive days. Bone marrow grafts were collected on day 4. The percentages of CD4+ and CD8+, and the expressions of CD49d, CD54, CD62L and CD11a on donor T cells of steady state-bone marrow grafts (SS-BM, n=11) and rhG-CSF primed bone marrow (G-BM, n=30) were analyzed by using multi-color flow cytometry. The results indicated that the percentages of CD4+ and CD8+ T cells were significantly lower in G-BM than those in SS-BM (p<0.05). There were no significant differences in the percentages of memory CD4+ and CD8+ T cells between SS-BM and G-BM (p>0.05). The expressions of CD49d on CD4+ and CD8+T cells were significantly lower in G-BM than that in SS-BM (p<0.05). Compared with SS-BM, the expressions of CD54 on CD4+, memory CD4+ T cells and CD8+ T cells were significantly lower in G-BM (p<0.05). The expressions of CD62L on CD4+ and CD8+ T cells and memory T cells were all significantly lower in G-BM (p values were all less than 0.001). The expressions of CD11a on CD4+, memory CD4+ T cells were significantly lower in G-BM than that in SS-BM (p<0.05). There were no significant differences in the expression of CD11a on CD8+, memory CD8+ T cells between SS-BM and G-BM (p>0.05). It is concluded that the expression of cell adhesion molecules on the CD4+ and CD8+ T cells in G-BM is down-regulated after rhG-CSF treatment of healthy donors.