Clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns / 中华烧伤杂志

Objective: To explore the clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 11 patients with cervical cicatrix contracture deformity after burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 3 males and 8 females, aged 5 to 46 years, with a course of cervical cicatrix contracture deformity of 5 months to 8 years. The degree of cervical cicatrix contracture deformity was degree Ⅰ in one patient, degree Ⅱ in nine patients, and degree Ⅲ in one patient. In the first stage, according to the sizes of neck scars, one rectangular skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 200 to 600 mL was placed in the back. The expansion time was 4 to 12 months with the total normal saline injection volume being 3.0 to 3.5 times of the rated capacity of expander. In the second stage, free expanded thoracodorsal artery perforator flaps with areas of 10 cm×7 cm to 24 cm×13 cm were cut out to repair the wounds with areas of 9 cm×6 cm to 23 cm×12 cm which was formed after cervical cicatectomy. The main trunk of thoracodorsal artery and vein were selected for end-to-end anastomosis with facial artery and vein, and the donor sites were directly closed. The survival of flaps and healing of flap donor sites were observed on the 14th day post surgery. The appearances and cicatrix contracture deformity of the flaps, recovery of cervical function, and scar hyperplasia of donor sites were followed up. Results: On the 14th day post surgery, the flaps of ten patients survived, while ecchymosis and epidermal necrosis occurred in the center of flap of one patient and healed 2 weeks after dressing change. On the 14th day post surgery, the flap donor sites of 11 patients all healed well. During the follow-up of 6-12 months post surgery, the flaps of ten patients were similar to the skin around the recipient site in texture and color, while the flap of one patient was slightly swollen. All of the 11 patients had good recovery of cervical function and no obvious scar hyperplasia nor contracture in the flaps or at the donor sites. Conclusions: Application of expanded thoracodorsal artery perforator flaps can restore the appearance and function of the neck, and cause little damage to the donor site in reconstructing the cervical cicatrix contracture deformity after burns, which is worthy of clinical reference and application.

Prolactinic effects and molecular mechanisms of total sterone from Echinops latifolius Tausch on the milk deficient model rats / 中国临床药理学与治疗学

AIM: To investigate the effect of an effective component total sterone (TSR) of Echinops latifolius Tausch, the main component of a Chinese patent medicine Cuiru Keli (national drug standard WS3-413 (Z-085)-2003 (Z), on lactation and its possible mechanism. METHODS: After mating between male and female SD rats, 60 female rats were randomly divided into normal control group, model group, TSR low-dose and high-dose groups and prolactin granule positive control group, with 12 female rats in each group and 8 newborn rats in each nest. In addition to the normal control group, the rats in each group were intraperitoneally injected with levodopa 2 mg/kg once a day for 7 days from the second day of delivery. The rats in the normal control group were given normal saline by gavage once a day for 14 days. From the beginning of self-sufficiency, the single lactation of the female rats was measured every day until the 14th day, and then the female rats in each group were killed. Pathological HE staining was used to observe the morphological changes of mammary gland tissue in each group. ELISA was used to detect the levels of serum prolactin (PRL) and 5-hydroxytryptamine (5-HT). Immunohistochemistry was used to detect the distribution of PRL in mammary gland tissue of each group. Furthermore, Real-time qPCR was used to detect the expression of milk protein, milk fat related genes β-casein, FAS, ACC and the expression of canonical Wnt signaling pathway related genes β-catenin, c-Myc, CCND1, SFRP4, DNMT1, MeCP2 in mammary gland of each group. RESULTS: Both low and high dose TSR could significantly increase the single lactation volume, improve the pathological morphology of mammary gland, and increase the serum levels of PRL and 5-HT. TSR increased the distribution of PRL and up-regulated the expression of milk protein, milk fat related genes β-casein, FAS, ACC and canonical Wnt signaling pathway related genes β-catenin, c-Myc, CCND1, SFRP4, DNMT1, MeCP2.CONCLUSION: TSR can significantly promote lactation in lactation deficient rats, and its mechanism may be related to promoting the release of PRL and 5-HT in serum, increasing the distribution of PRL in mammary gland, up-regulating the milk protein and milk fat related genes and activating the canonical Wnt signal.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

A “Prime and Deploy” Strategy for Universal Influenza Vaccine Targeting Nucleoprotein Induces Lung-Resident Memory CD8 T cells

Lung-resident memory T cells (TRM ) play an essential role in protecting against pulmonary virus infection. Parenteral administration of DNA vaccine is generally not sufficient to induce lung CD8 T RM cells. This study investigates whether intramuscularly administered DNA vaccine expressing the nucleoprotein (NP) induces lung T RM cells and protects against the influenza B virus. The results show that DNA vaccination poorly generates lung TRM cells and massive secondary effector CD8 T cells entering the lungs after challenge infection do not offer sufficient protection. Nonetheless, intranasal administration of non-replicating adenovirus vector expressing no Ag following priming DNA vaccination deploys NP-specific CD8 TRM cells in the lungs, which subsequently offers complete protection. This novel ‘prime and deploy’ strategy could be a promising regimen for a universal influenza vaccine targeting the conserved NP Ag.

Adenovirus Vectors: Excellent Tools for Vaccine Development

Adenovirus was originally used as a vector for gene therapy. In recent years, with the development of the next-generation vectors with increased safety and high immunogenicity to transgene products, its utility as a vaccine vector has continued to increase. Adenovirusbased vaccines are currently being tested not only to prevent various infectious diseases but also to be applied as cancer vaccines. In this review, I discuss the innate and adaptive aspects of the immunological characteristics of adenovirus vectors and further examine the current status of advanced adenovirus-based vaccine development. Various methods that can overcome the limitations of currently used adenoviruses as vaccine vehicles are also discussed. Through this study, I hope that vaccine development using adenovirus vectors will be expedited and more successful.

Effects of dexmedetomidine on short-term prognosis of elderly patients with gastric cancer after laparoscopic radical gastrectomy / 肿瘤研究与临床

Objective:To investigate the effects of dexmedetomidine on short-term prognosis in elderly patients with gastric cancer after laparoscopic radical gastrectomy.Methods:A total of 60 elderly patients with gastric cancer admitted to Shanxi Provincial Cancer Hospital from June 2018 to September 2019 were selected as the research objects. The patients were randomly divided into the observation group and the control group according to random number method, 30 cases in each group. All patients underwent laparoscopic radical gastrectomy. The patients in the control group received routine intravenous anesthesia, and the patients in the observation group were assisted with intravenous infusion of dexmedetomidine on the basis of anesthesia in the control group. The general situation during and after surgery, hemodynamics and postoperative delirium of patients in the two groups were observed and compared.Results:The anal exhaust time and hospitalization time in the observation group was shorter than that in the control group [(72±10) h vs. (79±13) h, t = 8.384, P = 0.031; (11.0±1.7) d vs. (12.9±1.9) d, t = 7.404, P = 0.022]. While the time of abdominal drainage was (8.4±2.8) d and (8.6±1.6) d, respectively in the observation group and the control group, and the difference was not statistically significant ( t = 0.958, P = 1.092); the volume of abdominal drainage was (534±50) ml and (545± 55) ml, respectively, and the difference was not statistically significant ( t = 0.847, P = 1.202). Compared with the preoperative baseline, the mean arterial pressure (MAP) in the two groups was stable during the operation. At extubation, the MAP in the control group [(104±5) mmHg, 1 mmHg = 0.133 kPa] was higher than that in the observation group [(92±7) mmHg] ( t = 7.383, P < 0.01); in the control group, the MAP at extubation was also higher compared with the preoperative MAP [(92±9) mmHg] ( P < 0.05). The heart rate in the observation group was lower than that before surgery and the same period in the control group.The incidence rate of delirium and suspicious delirium was 3% (1/30) and 7% (2/30) in the observation group, 10% (3/30) and 13% (4/30) in the control group within 7 d after surgery, and there were statistically significant differences in delirium and suspicious delirium between the two groups ( χ2 = 9.394, 7.485, all P < 0.05). Conclusion:Dexmedetomidine can reduce the incidence of delirium in elderly patients with gastric cancer after laparoscopic radical gastrectomy, and make the hemodynamics more stable and recovery faster.

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation / 中华医学杂志(英文版)

BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

Anesthesia effect analysis of propofol closed-loop target-controlled infusion system in esophageal cancer surgery / 肿瘤研究与临床

Objective:To analyze the anesthesia effect of closed-loop target-controlled infusion system in esophageal cancer surgery.Methods:A total of 78 patients with esophageal cancer who underwent surgery in Shanxi Provincial Cancer Hospital from February to October 2019 were selected and divided into observation group and control group by random number table method, with 39 cases in each group. The patients in the observation group were anesthetized by closed-loop target-controlled infusion of propofol, while the propofol target-controlled infusion concentration of patients in the control group was manually controlled by anesthesiologists. The dosage of propofol, the time from drug discontinuation to recovery, the time of stay in post-anesthesia care unit (PACU), the incidence of hypoxemia after entering PACU and the incidence of anesthesia related complications were analyzed and compared between the two groups.Results:The dosage of propofol in the observation group was lower than that in the control group [(978±163) mg vs. (1 307±278) mg], and the difference was statistically significant ( t = 9.234, P = 0.028). The time from drug discontinuation to recovery in the observation group was shorter than that in the control group [(9.7±1.2) min vs. (13.2±2.6) min], and the difference was statistically significant ( t = 9.895, P = 0.025). The time of stay in PACU in the observation group was shorter than that in the control group [(15.6±2.4) min vs. (19.5±3.0) min], and the difference was statistically significant ( t = 9.536, P = 0.026). The incidence of hypoxemia after entering the PACU in the observation group was lower than that in the control group [7.69% (3/39) vs. 23.08% (9/39)], and the difference was statistically significant ( χ2 = 10.271, P = 0.016). The total incidence of postoperative anesthesia-related complications in the observation group was lower than that in the control group [10.26% (4/39) vs. 23.08% (9/39)], and the difference was statistically significant ( χ2 = 8.353, P = 0.021). Conclusion:The application of closed-loop target-controlled infusion system can effectively reduce the dosage of propofol, shorten the recovery time of patients and the time of stay in PACU, reduce the incidence of hypoxemia after entering PACU and the incidence of postoperative anesthesia related complications, which is worthy of clinical application.

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus

PURPOSE: Respiratory syncytial virus (RSV) can cause serious respiratory illnesses such as pneumonia, asthma, and bronchiolitis in infants and elderly or immunocompromised individuals. An RSV vaccine has yet to be developed; only prophylactic anti-RSV antibody is commercially available. So, we investigated whether our vaccine candidate is able to induce type 1 CD4+ T helper (Th1), CD8+ T-cell responses, and protective immunity without vaccine-enhanced disease (VED) against RSV. MATERIALS AND METHODS: We used RSV G protein fragment (Gcf A) with recombinant baculovirus capable of expressing the RSV M2 protein (Bac M2) as a vaccine candidate, and injected this vaccine (Gcf A/Bac M2) intramuscularly, and challenged with RSV intranasally into mice. Enzyme-linked immunosorbent assay, flow cytometry, plaque assay, and weight measurement were performed to confirm humoral immunity, cellular immunity, and protective immunity. RESULTS: The Gcf A/Bac M2 formulation induced a stronger IgG response to Gcf A than Gcf A inoculation alone, and the ratio of IgG1/IgG2a indicated that the responses shifted predominantly to Th1. In addition, both RSV G-specific Th1 responses and RSV M2-specific CD8+ T-cell responses were induced, and G protein-associated eosinophilic infiltration was suppressed compared to the control group. Moreover, the Gcf A/Bac M2 group showed effective protection after an RSV challenge. CONCLUSION: Bac M2 could serve as a vaccine with intrinsic adjuvant activity, and the Gcf A/Bac M2 shows promise as a vaccine candidate for inducing protective immunity without inciting VED.

Nucleoprotein vaccine induces cross-protective cytotoxic T lymphocytes against both lineages of influenza B virus

PURPOSE: The influenza B virus diverges into two antigenically distinct lineages: B/Yamagata and B/Victoria. Influenza B is the dominant circulating virus during some influenza seasons, and recent data demonstrated that influenza A and B infection similarly cause severe clinical symptoms in hospitalized patients. Nucleoprotein (NP) is a good target for a universal influenza vaccine. This study investigated whether NP epitope variation within two lineages affects the dominant cytotoxic T lymphocyte (CTL) responses induced by vaccination and the resultant protective immunity. MATERIALS AND METHODS: The NP of B/Yamagata/16/1988, the representative strain of the Yamagata lineage, includes a dominant CTL epitope, FSPIRITFL, while B/Shangdong/7/1997 from the Victoria lineage has one amino acid difference in this sequence, FSPIRVTFL. Two recombinant replication-deficient adenovirus (rAd)-vectored vaccines expressing either NP were prepared (rAd/B-NP(I) and rAd/B-NP(V), respectively) and administered to BALB/c mice intranasally. To examine the efficacy of vaccination, antibody responses, CTL responses, and morbidity/mortality after challenge were measured. RESULTS: Both vaccines induce similar antibody and CD8 T-cell responses cross-reacting to both epitopes, and also confer cross-protection against both lineages regardless of amino acid difference. CONCLUSION: The rAd-vectored vaccine expressing the NP could be developed as universal influenza B vaccine which provides broader protection.

Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Effect of cordycepin on apoptosis and autophagy of tongue cancer cells in vitro and the molecular mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of cordycepin on cell cycle, apoptosis and autophagy of human tongue cancer TCA-8113 cells and explore the mechanism of cordycepin for inhibiting the occurrence of tongue cancer.</p><p><b>METHODS</b>CCK-8 method was used to assess the inhibitory effect of cordycepin on TCA-8113 cell proliferation in vitro. The cell cycle and cell apoptosis of TCA-8113 cells treated with different concentrations of cordycepin were analyzed using flow cytometry. The expressions of apoptosis-related genes caspase-3, caspase-9, Bcl-2, and Bax were examined using quantitative real-time PCR and Western blotting, and immunohistochemistry was used to detect the expressions of autophagy-related proteins LC-3β, P62, p-mTOR, and AMPK.</p><p><b>RESULTS</b>CCK-8 assay showed that cordycepin significantly inhibited the proliferation of TCA-8113 cells in a concentration-dependent manner with an IC of 3.548 mg/mL at 24 h and an IC of 1.185 mg/mL at 48 h. Flow cytometric analysis showed that cordycepin caused cell cycle arrest at S phase and dose-dependently increased the apoptotic rate of TCA-8113 cells. Treatment of the cells with cordycepin enhanced the expressions of Bax, caspase-3 and caspase-9 at both the mRNA and protein levels and inhibited the expression of the antiapoptotic gene Bcl-2. Immunohistochemistry demonstrated that cordycepin promoted the expression of LC-3β and AMPK and inhibited the expression of P62 and p-mTOR.</p><p><b>CONCLUSION</b>Cordycepin inhibits the proliferation and induces apoptosis of HCT-116 cells through the mitochondrial pathway and induces autophagy via the AMPK/mTOR pathway.</p>

Relationship of Cell Compositions in Allografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of CD34 and CD14 Cell Doses / 中华医学杂志(英文版)

<p><b>Background</b>The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA).</p><p><b>Methods</b>A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis.</p><p><b>Results</b>A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14 (P = 0.018) and CD34 cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed.</p><p><b>Conclusions</b>These results provide evidence and explain that higher doses of CD34 and CD14 cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.</p>

Clinical implication of minimal residue disease monitoring by WT1 gene detection and flow cytometry in myelodysplastic syndrome with allogeneic stem cell transplantation / 中华血液学杂志

Objective: To investigate the clinical significance of minimal residual disease (MRD) monitoring by using WT1 gene and flow cytometry (FCM) in patients with myelodysplastic syndrome (MDS) who receiving allogeneic stem cell transplantation (allo-HSCT). Methods: WT1 gene and MDS-related abnormal immunophenotype were examined by real-time quantitative polymerase chain reaction (RQ-PCR) and FCM, respectively. The bone marrow samples were collected from patients with MDS who received allo-HSCT from Feb, 2011 to Oct, 2015 in Peking University People's Hospital before and after transplantation. Results: Among 92 MDS patients, 40 (48.2%) patients were positive for WT1 (WT1(+)) and 9 (10.8%) patients were positive for flow cytometry (FCM(+)). 27 patients (29.3%) met the criteria of our combinative standard, MRDco (MRDco(+)). Only FCM(+) post-transplant (P<0.001) and MRDco(+) (P=0.017) were associated with relapse. The cumulative incidence of relapse (CIR) at 2 years were 66.7% and 1.2% (P<0.001) in FCM(+) and FCM(-) groups. MRDco(+) group had a 2-year CIR of 23.0% while MRDco(-) group had a 2-year CIR of 1.6% (P=0.004). The specificity of post-transplant WT1, FCM and MRDco to predict relapse was 59.0%, 96.4% and 74.7%, respectively. The sensitivity of these three MRD parameters to predict relapse was 66.7%. Conclusion: Post-transplant FCM and MRDco are useful tools to monitor MRD for MDS after transplantation. The preemptive intervention based on MRDco is able to reduce the relapse rate.

The comparison of predicting clinical outcomes between immunolophenotype and hematological complete remission before human leukocyte antigen-matched sibling donor transplantation in acute myeloid leukemia / 中华血液学杂志

Objective: To assess the prognostic significance of immunophenotype complete remission (ICR) and hematological complete remission (HCR) before human-leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT) in acute myeloid leukemia (AML) patients. Methods: A cohort of 182 AML (non-APL) patients undergoing MSDT in HCR was retrospectively studied [including complete remission with ANC and PLT recovery (CR), CR with incomplete PLT recovery (CRp), CR with inconplete ANC and PLT recovery (CRi)]; ICR was determined as undetective minimal resudial disease (MRD) by multi-parameter flow cytometer. Results: ①Of the 182 patients, 97 were male, 85 female, and the median age was 41(4-62) years. ②The CR and CRi+CRp rates were 80.8% (147/182) and 19.2%(35/182), respectively; The 4-year cumulative incidence of relapse[CIR, (11.0±4.3)% vs (16.0±7.1)%, χ(2)=0.274, P=0.600], non-relapse mortality[NRM, (14.0±4.3)% vs (9.0±6.3)%, χ(2)=0.913, P=0.339], leukemia-free survival[LFS, (75.0±5.1)% vs (75.0±8.3)%, χ(2)=0.256, P=0.613], and overall survial [OS, (77.0±5.2)% vs (80.0±8.1)%, χ(2)=0.140, P=0.708] were comparable between the CRp+CRi and CR groups. ③Compared with the non-ICR group (n=35), the ICR group (n=147) showed lower 4-year CIR [(11.3±3.4) % vs (55.2±8.8) %, χ(2)=32.687, P<0.001], better 4-year LFS [(76.2±4.7)% vs (32.8±8.7)%, χ(2)=26.234, P<0.001] and OS[(79.0±4.7)% vs (39.0±9.1)%, χ(2)=25.253, P<0.001], and comparable NRM[(12.5±4.1)% vs (12.0±7.1)%, χ(2)=1.002, P=0.656]. ④Mulitvariate analysis confirmed the independent prognostic value of ICR in lower CIR [HR=11.026(95%CI 4.685-25.949), P<0.001], higher LFS [HR=5.785 (95% CI 2.974-11.254), P<0.001] and OS[HR=5.578 (95% CI 2.575-27.565), P<0.001]. Conclusion: The results indicated that ICR instead of HCR pre-transplantation had a significant prognostic value in AML patients undergoing MSDT.

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation / 中华医学杂志(英文版)

Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.

Experimental study on thermal insulation effect of insulation coatings of emergency treatment tent / 医疗卫生装备

Objective To explore the insulation effect of the coating so as to relieve the influence of solar overtemperature on the tent system.Methods The tent had an integrated structure with multi cavity and air column support,and the confined space was composed of the dual-layer tent body.There were 4 measuring points in the tent,of which,one was at the filter vent,two ones at the ceiling lamp and the remained one above the curtain in the buffer area.The tent was deployed in summer outdoor environment,four thermographs were used for real-time recording of intemal temperature changes in the tents with or without coating,and the recording began at 8:00 am and stopped at 5:00 pm.Comparison proved there was no significant differences between the measured values by the four thermographs (P＞0.05),and correlation analysis was executed based on numerical trend and variance analysis.Results The coating tent had the internal temperature lower than that in the non-coating tent,which had low mean temperature and low temperature range.The internal temperature in the coating tent was lower than ambient temperature at noon and afternoon,which meant the coating tent could lower the temperature effectively even in the duration at high temperature.Concusion Thermal insulation coating applied to the tent relieves the solar overtemperature effect effectively,and thus enhances the the tent's thermal environment adaptability.

Experimental study on thermal insulation effect of insulation coatings of emergency treatment tent / 医疗卫生装备

Objective To explore the insulation effect of the coating so as to relieve the influence of solar overtemperature on the tent system.Methods The tent had an integrated structure with multi cavity and air column support,and the confined space was composed of the dual-layer tent body.There were 4 measuring points in the tent,of which,one was at the filter vent,two ones at the ceiling lamp and the remained one above the curtain in the buffer area.The tent was deployed in summer outdoor environment,four thermographs were used for real-time recording of intemal temperature changes in the tents with or without coating,and the recording began at 8:00 am and stopped at 5:00 pm.Comparison proved there was no significant differences between the measured values by the four thermographs (P＞0.05),and correlation analysis was executed based on numerical trend and variance analysis.Results The coating tent had the internal temperature lower than that in the non-coating tent,which had low mean temperature and low temperature range.The internal temperature in the coating tent was lower than ambient temperature at noon and afternoon,which meant the coating tent could lower the temperature effectively even in the duration at high temperature.Concusion Thermal insulation coating applied to the tent relieves the solar overtemperature effect effectively,and thus enhances the the tent's thermal environment adaptability.

Challenges in the development of T-cell–based universal influenza vaccines

No abstract available.

Análisis de mortalidad debida a una infección del torrente sanguíneo por Enterococcus faecium en Taiwán central / Mortality analysis of Enterococcus faecium bloodstream infection in central Taiwan

Background: Bloodstream infections (BSIs) due to Enterococcus faecium (E. faecium), particularly those due to vancomycin-resistant enterococcus (VRE), are still a therapeutic challenge. Aim: To evaluate mortality from BSI due to E. faecium and VRE in central Taiwan. Materials and Methods: We retrospectively analyzed cases of significant E. faecium BSI in the Changhua Christian Hospital System between January 1, 2010 and December 31, 2013. Results: Of the 76 cases, 28 patients (36.8%) were admitted to intensive care units (ICUs) at the onset of BSI, 10 (13.2%) cases were associated with polymicrobial bacteremia, and 29 (38.2%) cases were associated with entry via the biliary tract. VRE was observed in 18 (23.7%) cases. The 30-day mortality rate was 13.1% (10/76). Multivariate logistic regression analysis showed that bacteremia of non-biliary tract origin (OR = 8.43, 95% confidence interval (95% CI) = 1.32-54.00, p = 0.002) and ICU admission (OR = 4.2, 95% CI = 1.7-10.0, p = 0.002) were significant risk factors for 30-day mortality, whereas appropriate antimicrobial therapy was a protective factor for 30-day mortality (OR = 0.33, 95% CI = 0.14-0.79, p = 0.013). Conclusions: Our results underscore the need to assist patients admitted to ICUs with E. faecium BSIs with a non-biliary tract origin. We emphasize the use of appropriate antimicrobial therapy for E. faecium BSI with the aim to rescue more patients with these infections.

Antecedentes: Las infecciones del torrente sanguíneo por Enterococcus faecium, particularmente aquellas causadas por enterococos resistentes a vancomicina (ERV), representan aún un desafío para los tratamientos. Este estudio está orientado a la evaluación de la mortalidad debido a la infección del torrente sanguíneo (ITS) por E. faecium y por enterococos resistentes a vancomicina (ERV) en Taiwán central. Materiales y Métodos: Analizamos de forma retrospectiva casos de ITS causadas por E. faecium genuinas en el Sistema del Hospital Changhua Christian, entre los días 1 de enero de 2010 y 31 de diciembre de 2013. Resultados: De los 76 casos analizados, 28 pacientes fueron ingresados a las Unidades de Cuidados Intensivos (UCI) al comienzo de una ITS (36,8%), 10 casos fueron asociados a bacteriemia polimicrobiana (13,2%), y 29 casos tuvieron como puerta de entrada la vía biliar. En 18 casos se pudieron observar ERV (23,7%). La mortalidad a 30 días fue de 13,1% (10/76). El análisis multivariado mediante regresión logística mostró que la bacteriemia de origen no biliar (OR = 8,43, 95% intervalo de confianza (95% CI) = 1,32-54,00; p = 0,002), y el ingreso a la UCI (OR = 4,2; 95% CI = 1,7-10,0; p = 0,002), fueron factores de riesgo significativos para el rango de mortalidad de 30 días, así como un tratamiento de antimicrobiano apropiado constituye un factor protector en contra la mortalidad (OR = 0,33; 95% CI = 0,14-0,79; p = 0,013). Conclusiones: Nuestros resultados destacan la necesidad de asistir a los pacientes ingresados a la UCI con ITS por E. faecium con origen no biliar. Hacemos énfasis a la aplicación de una antibioterapia adecuada para sacar adelante a un mayor número de pacientes con este tipo de infecciones.