[Efficacy of Activated Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy of activated autologous bone marrow and peripheral blood hematopoietic stem cell transplantation (Auto-HSCT) and matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for the first complete remission of adult acute myeloid leukemia (AML-CR1). METHODS: For 86 adult patients with first complete remission of AML who underwent auto-HSCT (41 cases) and MSD-HSCT (45 cases) in our hospital from June 2012 to June 2020, the patients were treated with modified MAC ï¼»Malflane 160 mg/(m2·d), -3 days, Ara-C 2 g/(m2·2), -3 days 21∶00, -2 days 9∶00, CTX 60 mg/(kg·d),-3 d, -2 dï¼½, the stem cells were activated by IL-2 (1 000 U/ mL), IFN-α (100 U/ mL) and IFN-γ (100 U/ml). The overall survival (OS), leukemia free survival (LFS), cumulative incidence of recurrence (CIR) and non-recurrence mortality (NRM) of patients with different types of transplantation were compared. RESULTS: The 3-year OS rates of Auto-HSCT group and MSD-HSCT group were 75% and 69.5%, and the 3-year LFS rates were 70.6% and 82.4%, respectively. There was no statisticaly significant difference in the 3-year OS rates of low risk, medium risk and high risk patients in the Auto-HSCT and MSD-HSCT group (90.2% vs 87.5%, 68.4% vs 68.8%, 28.6% vs 53.3%), the LFS rates of low risk, medium risk and high risk patients in the auto-HSCT and MSD-HSCT group were 90.2% and 87.5%(P=0.838), 71.8% and 91.7%(P=0.184), 0 and 67.5%(P=0.027), respectively. The NRM of Auto-HSCT and MSD-HSCT group were 4.9% and 20% (P=0.036), and CIR were 24.4% and 13.3% (P=0.188). Univariate analysis showed that the survival time of patients was significantly correlated with the number of CR courses and disease risk stratification (P=0.005, P=0.000). Cox multivariate analysis showed that disease risk stratification was an independent risk factor affecting OS (P=0.001). CONCLUSION: For adult patients with primary AML-CR1, Auto-HSCT is safe and effective. In the absence of sibling donor, Auto-HSCT can be regarded as an effective post-remission treatment for patients with intermediate risk AML-CR1.

Analysis of reflux as the aetiology of laryngeal dysplasia progression through a matched case-control study.

OBJECTIVES: Laryngeal dysplasia (LD) is a precancerous lesion of the larynx. In this study, the laryngeal tissue of patients with laryngeal dysplasia was taken as the research object, and the aetiology of reflux was analysed. METHOD: Patients with laryngeal dysplasia after surgery were selected as our subjects. The levels of pepsin, enterokinase and bilirubin in laryngeal tissue samples of the two groups were detected by immunohistochemical method. RESULTS: The OR values (95% CI) of pepsin, enterokinase and bilirubin were 0.67 (0.19-2.36), 0.80 (0.22-2.98) and 1.33 (0.30-5.96), respectively, in the univariate analysis. Besides, in the multivariate analysis, the OR values (95% CI) of pepsin, enterokinase and bilirubin were 0.57 (0.14-2.30), 0.73 (0.18-2.92) and 1.40 (0.30-6.53), respectively. CONCLUSION: Larger sample size should be applied to prospective studies on whether reflux is a risk factor for laryngeal cancer.

Post-COVID-19 Epidemic: Allostatic Load among Medical and Nonmedical Workers in China.

BACKGROUND: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. OBJECTIVE: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. METHODS: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. RESULTS: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated. CONCLUSIONS: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.

Penicilindoles A-C, Cytotoxic Indole Diterpenes from the Mangrove-Derived Fungus Eupenicillium sp. HJ002.

Three new indole diterpenes, penicilindoles A-C (1-3), were isolated from the mangrove-derived fungus Eupenicillium sp. HJ002. Their planar structures and absolute configurations were determined by interpretation of NMR spectroscopic data, HR-ESIMS, and X-ray diffraction analysis using Cu Kα radiation. The cytotoxic and antibacterial activities were evaluated in vitro; penicilindole A (1) showed cytotoxic activity against human A549 and HepG2 cell lines with IC50 values of 5.5 and 1.5 µM, respectively.

One new cytochalasin metabolite isolated from a mangrove-derived fungus Daldinia eschscholtzii HJ001.

One new cytochalasin metabolite [11]-cytochalasa-5(6),13-diene-1,21-dione-7,18-dihydroxy-16,18-dimethyl-10-phenyl-(7S*,13E,16S*,18R*) (1), together with three known compounds (2-4) were obtained from the EtOAc extract of the endophytic fungus Daldinia eschscholtzii HJ001 isolated from the mangrove Brguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Compounds 1 and 2 were evaluated for their antibacterial and cytotoxic activities.

Wuzi Yanzong pill, a Chinese polyherbal formula, alleviates testicular damage in mice induced by ionizing radiation.

BACKGROUND: Chinese medicine Wuzi Yanzong pill (WZYZP) was firstly documented in ancient Chinese medical works "She Sheng Zhong Miao Fang" by Shi-Che Zhang in 1550 AD. The traditional herbal formula is widely used in treating nephrasthenia lumbago, prospermia, erectile dysfunction and male sterility. The present study was to explore the effects of WZYZP on ionizing irradiation-induced testicular damage in mice. METHODS: The pelvic region of male mice was exposed to X-rays for inducing testicular damage. The effects of WZYZP on testicular damage were evaluated in terms of testes weight, sperm quantity and motility, testes oxidative status and serum hormone levels. The alterations in testicular structure were examined by hematoxylin-eosin staining. Additionally, changes in proliferating cell nuclear antigen (PCNA) expression of testes were explored by western blot. RESULTS: Pelvic exposure to x-ray induced reduction in testes weight and sperm quality, along with oxidative stress and abnormal testicular architecture in testes. Oral administration of WZYZP for 3 weeks markedly increased testes weight, sperm quantity and motility, and attenuated testicular architecture damage. Meanwhile, WZYZP treatment significantly reversed the reduction of serum testosterone, and decreased testes malondialdehyde (MDA) and Oxidative stress index (OSI) relative to the radiated mice. Additionally, WZYZP effectively prevented the downregulation of PCNA expression in testes induced by x-ray irradiation. CONCLUSION: These findings suggest WZYZP exhibits ameliorating effects against ionizing irradiation-induced testicular damage in mice, which may be related to its antioxidation.

Dihydroisocoumarins from the Mangrove-Derived Fungus Penicillium citrinum.

Three new dihydroisocoumarin penicimarins G-I (1-3), together with one known dihydroisocoumarin (4) and three known meroterpenoids (5-7), were obtained from a fungus Penicillium citrinum isolated from the mangrove Bruguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of spectroscopic data. The absolute configuration of 1 was determined by the X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of 2 and 3 were determined by comparison of their circular dichroism (CD) spectra with the literature. All compounds were evaluated for their antibacterial activities and cytotoxic activities.

[Effect of Scalp Penetration Acupuncture on the Expression of NGF in Brain Tissue around Hematoma of Intracerebral Hemorrhage Rats].

Objective To observe the effects of scalp penetration acupuncture on the expression of nerve growth factor (NGF) in brain tissue around hematoma of intracerebral hemorrhage rats. Methods To- tally 120 healthy male Wistar rats were divided into the sham-operation group, the model group, the acupunc- ture group by random digit table, 40 in each group. Rats in each group were further randomly divided into 4 time points, i.e., 6 h, 24 h, day 3, day 7. The intracerebral hemorrhage rat model was prepared by modified autologous arterial blood method, intervened by electroacupuncture (EA) at Baihui (DU20) through Taiyang (EX- HN5). Neuroethological assessment was conducted by Longa score. The expression of NGF positive cells in brain tissue around hematoma was detected using immunohistochemical method. The amount of NGF mRNA expression was measured by q-PCR. Results Compared with the sham-operation group, neurobehavioral scores increased, NGF positive cells increased, NGF mRNA expression increased in the model group at each time point, with statistical difference shown (P <0.05). Compared with the model group, 6 h neurobehavioral scores,NGF positive cells, mRNA expression of NGF did not change significantly in the acupuncture group, with no statistical difference shown (P > 0. 05). Neuroethological scores decreased, NGF positive cells increased, mRNA expression of NGF was up-regulated in the acupuncture group at 24 h, day 3 and 7, respec- tively, with statistical difference shown (P <0. 05). Conclusion scalp penetration acupuncture could up-regulate gene and protein expressions of NGF, and promote recovery of nerve function, showing favorable neuro-protective effects.

[Prophylactic effect of TLR5 agonist flagellin on acute graft versus host disease after allogeneic hematopoietic stem cell transplantation and its mechanism].

This study was aimed to investigate the prophylactic effect of Toll like receptor (TLR)5 agonist flagellin on acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its possible mechanism. The animal model with allo-HSCT aGVHD was established by using purebred mice (male mouse C57BL/6 as donor, female mouse BALB/c as recipient) with complete-unidentical major histocompatibility antigen. The recipient mice were randomly divided into 3 groups: group 1 in which mice were injected with high purity (95%) flagellin before and after allo-HSCT respectively, group 2 in which mice received allo-HSCT without injection of flagellin, group 3 in which mice were radiated alone. The aGVHD features of mice in group 1 and 2 were observed and compared. The results showed that the typical symptoms of aGVHD appeared in transplanted mice. The death peak of mice in group 2 appeared at day 4-5 after transplantation. The aGVHD symptoms were obviously alleviated and the mean survival time was prolonged significantly in mice group 1 as compared with mice in group 2 (P < 0.05). The comparison of WBC count in peripheral blood of mice in 3 groups before transplantation showed no significant difference (P > 0.05), while WBC count of mice in group 1 and 2 showed the significant difference at days 14 and 21 after transplantation (P < 0.05). The pathological appearances of aGVHD in mice of group 1 were obviously reduced as compared with mice in group 2. The flow cytometric detection of Treg cell/CD4(+) T cell levels at different time before and after transplantation demonstrated that the Treg cell level in mice of group 1 at weeks 2-4 after transplantation significantly increased as compared with mice in group 2 (P < 0.05). It is concluded that flagellin can effectively prevent the aGVHD occurrence after allo-HSCT, reduce the symptoms and pathological changes of aGVHD, obviously prolong mean survival time of mice in group 1. The mechanism of flagellin effect may be associated to increase of Treg cell level in mice after allo-HSCT.

The short- and medium-term results of transcatheter closure of atrial septal defect with severe pulmonary arterial hypertension.

We investigated the short-term and medium-term results in patients with pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) undergoing transcatheter closure. Fifteen patients with severe PAH associated with ASD who underwent successful occluder implantation from 2007 to 2010 were included. Clinical, echocardiographic, and hemodynamic data were reviewed. Severe PAH was defined as pulmonary arterial systolic pressure measured by catheterization was ≥60 mmHg and pulmonary vascular resistance (PVR) ≥6 Wood Units (WU). Compared with baseline, the 6-minwalking distance significantly increased by 29.7 ± 26.3 m (P < 0.001) at 3 months (short-term) and 65.4 ± 63.6 m (P < 0.001) at 23.4 ± 9.7 months (medium-term), World Health Organization function class considerably improved after postclosure short-term and medium-term. Repeat cardiac catheterization (n = 7) showed that mean pulmonary arterial pressure decreased from 51.6 ± 9.4 mmHg at baseline to 21.0 ± 3.8 mmHg (P < 0.001) at follow-up of 12 months. The PVR decreased by 5.6 ± 1.1 WU (P < 0.001). Through carefully selected patients with severe PAH associated with ASD, transcatheter closure can be safely performed with a promising short-term and medium-term outcome. Trial occlusion is an effective way for deciding the reversibility of severe PAH in ASD patients. The role of aerosolized iloprost for pulmonary vasoreactivity testing in patients with severe PAH secondary to ASD requires further investigation.

[Effect of bortezomib on the drug sensitivity of imatinib resistant K562/G01 cells].

OBJECTIVE: To explore the effect of bortezomib (BOR) on the drug sensitivity of imatinib-resistant chronic myeloid leukemia cell line K562/G01 cell and its mechanism. METHODS: MTT assay was used to detect the inhibition effect of cell growth, flow cytometry to cell cycle, and real time-PCR to the expression of COX-2 and mdr1 mRNA. RESULTS: Combination of 10 and 20 nmol/L BOR with imatinib could significantly enhance the sensitivity of K562/G01 to imatinib, the reverse factor was 1.83 and 2.72-fold respectively. Cell cycle arrested at G(2)/M phase could be observed by flow cytometry on BOR treatment. The over-expression of COX-2 and mdr1 could be down-regulated by BOR. CONCLUSIONS: BOR can enhance the imatinib sensitivity of imatinib resistant K562/G01 cell. The mechanism may be related to cell cycle phase arrested at G2/M and down-regulation of COX-2 and mdr1 expression.

[Diagnosis and treatment of laryngeal neuroendocrine carcinoma].

OBJECTIVE: To summarize the clinical features of laryngeal neuroendocrine carcinoma (LNEC). METHODS: The clinical data of all LNEC patients hospitalized during the period of June 1988 - December 2010 were analyzed retrospectively. RESULTS: Among all LNEC 12 patients as confirmed by pathological examination, there were typical carcinoid (n = 1), atypical carcinoid (n = 4) (2 with cervical metastasis, 1 with paraneoplastic syndrome), small cell neuroendocrine carcinoma (n = 7) (1 with adenocarcinoma). All patients with typical and atypical carcinoid underwent surgery. And postoperative radiotherapy was offered for those diagnosed with advanced stage or cervical metastasis. They were followed up for 1 - 12 years without local recurrence. All patients with laryngeal small cell neuroendocrine carcinoma received chemotherapy and radiotherapy. And the follow-up period was 0.5 - 6 years. One died of pulmonary metastasis within half a year while another died of liver metastasis within 3 years. CONCLUSION: It is important to classify the LNEC patients correctly since their clinical course, treatment and prognosis varies greatly with the diagnosis. For typical and atypical carcinoid of larynx, partial or total laryngectomy and neck dissection may be performed depending on the site and extent of primary tumor. However, for laryngeal small cell neuroendocrine carcinoma, the mainstay of treatment is made up of chemotherapy and radiotherapy. And the prognosis of this type remains very poor.

[Relationship between CD4(+)CD25(+) regulatory T cells, IL-2, TGF-beta and acute graft-versus host disease after allogeneic hematopoietic stem cell transplantation].

This study was aimed to investigate the relationship between CD4(+)CD25(+) regulatory T cells, IL-2, TGF-beta and acute graft-versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The percentage of peripheral blood CD4(+)CD25(+) Treg cells in CD4(+) T cells of 13 patients with hematological malignancies after allo-HSCT were detected by flow cytometry; serum levels IL-2 and TGF-beta in these patients were measured by ELISA. The results indicated that all the patients achieved engraftment. 5 patients developed aGVHD of grade I-II, 4 patients developed aGVHD of grade III-IV. The percentage of peripheral blood CD4(+)CD25(+) Treg cells out of CD4(+) T cells in patients without aGVHD was higher than that in patients with aGVHD (p < 0.05); the serum level of IL-2 in patients without aGVHD was lower than that of patients with aGVHD (p < 0.05); the serum level of TGF-beta in patients without aGVHD was higher than that of patients with aGVHD (p < 0.05). It is concluded that CD4(+)CD25(+) Treg cell level and the serum level of IL-2 and TGF-beta all are related to incidence and severity of aGVHD. These factors may be used as indicators for early evaluating and monitoring aGVHD after allo-HSCT.