[The clinical safety and efficacy of selinexor combined with venetoclax and azactitidine induction therapy in relapsed and refractory acute myeloid leukemia].

To determine the efficacy and safety of selinexor combined with venetoclax (VEN) and azactitidine (AZA) for patients with relapsed and/or refractory acute myeloid leukemia (R/R AML) . Twelve patients with R/R AML treated with selinexor plus VEN and AZA in the Affiliated Cancer Hospital of Zhengzhou University from May 2022 to May 2023 were included. Their clinical data were retrospectively analyzed. Among the 12 R/R AML patients, 5 (41.7%) achieved complete remission (CR) , 1 (8.3%) achieved CR with incomplete hematological recovery, and 5 (41.7%) achieved partial remission. The median time to reach CR was 28 (16-59) days. The median PFS was 61 (15-300) days. The main adverse event of the regimen was hematological toxicity. No chemotherapy-related deaths were observed. The combination of selinexor plus VEN and AZA is an effective treatment for R/R AML patients.

[Analysis of the clinicopathologic features as well as diagnosis and treatment of 59 patients with Castleman disease].

Objective: To investigate the clinicopathologic features, treatment, and prognosis in patients with Castleman disease (CD) . Methods: We retrospectively analyzed the clinicopathologic data of 59 patients for whom a diagnosis of Castleman disease was confirmed using pathological examination from October 2011 to October 2019 at the Henan Cancer Hospital. The patients were divided into the following two groups as per the following clinical classifications: unicentric CD (UCD, n=47) and multicentric CD (MCD, n=12) . Data on clinical manifestations, laboratory findings, treatment, and prognosis were analyzed. Results: There was no significant difference in the median age and the ratio of male to female between the UCD and MCD. UCD was characterized by asymptomatic enlargement of the single lymph node. The main pathological type was hyaline vascular histopathology (83.0%) . Of these, 44 patients chose surgical resection, and their prognosis was good. Treatment. MCD was characterized by multiple enlarged superficial and/or deep lymph nodes with B symptoms, weakness, and hepatosplenomegaly. Anemia, hypoproteinemia, and globulin level were increased on laboratory examinations. Plasmacyte histopathology was the main pathological type and was present in about 50.0% of the subjects. Only chemotherapy was performed for these MCD patients, followed by chemotherapy or chemotherapy followed by radiotherapy, and the efficient was 58.3% (7/12) . Conclusions: UCD, characterized by asymptomatic enlargement of the single lymph node, shows good postoperative prognosis. MCD has relatively complex clinical manifestations and poor prognosis, and optimal treatment is yet to be established.

[Epidemiology and molecular biology of respiratory syncytial virus among hospitalized children in Guangzhou from 2013 to 2017].

Objective: To understand the genetic variation and epidemiological characteristics of human respiratory syncytial virus (HRSV) in Guangzhou. Methods: Nasopharyngeal swabs specimens were collected from 0-6 year old children hospitalized with acute respiratory infection, then HRSV was tested and genotyped by RT-PCR. Phylogenetic tree was bulit using MEGA 6.0 software. NetNGlyc 1.0 server was used to predict the potential N-linked glycosylation sites. Results: A total of 1 225 nasopharyngeal specimens were collected, including 783 males and 442 females. The median (P(25), P(75)) age was 8 (3, 24) months. Among the 209 HRSV-positive cases (17.06%), 117 cases (55.98%) were HRSV-A and 92 cases (44.02%) were HRSV-B. The two distinct subgroups (HRSV-A and HRSV-B) alternately played dominant role to cause HRSV infection and exchange almost once every two years. The HRSV prevalence rate decreased with age. The HRSV-positive rate among children under 2 years old was 18.83% (196 cases), accounting for 93.78% of the total positive cases. There were 32 HRSV positive cases co-infected with at least one respiratory virus, with the co-infection rate of 15.31%. Phylogenetic tree analysis of the second hypervariable region (HVR2) of the G protein classified the HRSV-A specimens into ON1 (n=62) and NA1 (n=2) genotypes while all HRSV-B specimens belonged to BA genotype (n=53). The HVR2 of the G protein varied in using stop condon, amino acid substitutions, glycosylation sites. Conclusion: Children under 2 years old were the high risk population of HRSV infection in Guangzhou. ON1 genotype turned into a primary genetype of the HRSV-A subgroup while BA genotype dominated the HRSV-B subgroup. A greater diversification of amino acid substitutions, and some deletion and insertion of glycosylation sites embodied the polymorphism of G protein as main protective antigen.

[Therapeutic effect of combined use of interferon alpha-1b, interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia].

Objective: To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive. Methods: Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored. Results: Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively. Conclusion: The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.

[Clinical outcome of allogeneic hematopoietic stem cell transplantation in the treatment of 9 myeloid leukemia patients with granulocytic sarcoma].

To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS). Clinical outcome including hematopoietic reconstitution, transplant-related complications, survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT. Hematopoiesis reconstitution was achieved in all the 9 recipients. Four cases developed acute graft-versus-host disease (GVHD), and 1 with chronic GVHD. The median follow-up time after transplantation was 10(4-81) months. Only 2 cases survived, the other 7 died of relapse. The median time of relapse after transplantation was 5(3-19) months. Allo-HSCT is relatively effective treatment for patients with myeloid leukemia and GS. Relapse after transplantation remains the major factor of mortality.

[The significance of circulating tumor cells in head and neck squamous cell carcinoma: a preliminary study].

Objective: To investigate the significance of circulating tumor cells (CTC) in squamous cell carcinoma of the head and neck (HNSCC). Methods: Twenty-four patients with HNSCC treated between October 2016 and July 2017 in our department were selected (experimental group), including 23 males and 1 females, aged 47-81 years. There were 14 cases of squamous cell carcinoma of larynx and 10 cases of hypopharynx, including I-Ⅱ stage (5 cases) and Ⅲ- Ⅳ stage (19 cases). All patients were primary and/or relapsed after treatment. Nine healthy volunteers were selected as control group. A novel in vivo capture technique (CellCellector system) was used to detect CTC. SPSS23.0 was used for statistical analysis. Results: The total capture rate of CTC in patients with HNSCC before treatment was 70.8% (17/24), with 40% (2/5) for patients at I-Ⅱ stage, and 78.9% (15/19) for patients at Ⅲ- Ⅳ stage, and was 0 in patients of control group. The total capture rate of CTC in patients with HNSCC after treatment was 50% (8/16). There was no significant correlation between CTC and age, sex, location of tumor or lymph node metastasis (P>0.05). CTC was related to tumor staging and tumor differentiation (P<0.05). The positive rate of EGFRVⅢ in CTC was 26.3% (5/19). Conclusions: The CellCollector system is a very efficient way of detecting CTC, and CTC plays an important role in the occurrence, progression and metastasis of HNSCC.

[Establishment of Automation System for Detection of Alcohol in Blood].

OBJECTIVES: To establish an automation system for detection of alcohol content in blood. METHODS: The determination was performed by automated workstation of extraction-headspace gas chromatography （HS-GC）. The blood collection with negative pressure, sealing time of headspace bottle and sample needle were checked and optimized in the abstraction of automation system. The automatic sampling was compared with the manual sampling. RESULTS: The quantitative data obtained by the automated workstation of extraction-HS-GC for alcohol was stable. The relative differences of two parallel samples were less than 5%. The automated extraction was superior to the manual extraction. A good linear relationship was obtained at the alcohol concentration range of 0.1-3.0 mg/mL （r≥0.999） with good repeatability. CONCLUSIONS: The method is simple and quick, with more standard experiment process and accurate experimental data. It eliminates the error from the experimenter and has good repeatability, which can be applied to the qualitative and quantitative detections of alcohol in blood.

Anatomical versus non-anatomical liver resection for hepatocellular carcinoma exceeding Milan criteria.

BACKGROUND: Liver resection is effective for hepatocellular carcinoma (HCC) exceeding the Milan criteria in selected patients. However, the benefit of anatomical resection (AR) versus non-anatomical resection (NAR) has not been clarified in this patient subgroup. This study aimed to compare outcomes between AR and NAR for HCC exceeding the Milan criteria. METHODS: Data on consecutive patients with HCC exceeding the Milan criteria who underwent liver resection with curative intent over a recent 6-year interval were extracted from a prospective single-centre HCC database and examined retrospectively. The postoperative outcomes of patients were compared before and after propensity score matching. RESULTS: Some 546 patients were included: 264 in the AR and 282 in the NAR group. In the original cohort, the AR group contained more patients with larger tumours, multiple tumours, macroscopic portal vein tumour thrombi, incomplete tumour capsules and microscopic vascular invasion. After propensity score matching, 177 pairs of patients were selected. The baseline data, including liver function and tumour burden, were similar in the matched groups. The 3-year recurrence-free survival rate was comparable between the matched NAR and AR groups (36·5 versus 28·5 per cent; P = 0·448). Similar results were observed for 3-year overall survival (57·5 versus 50·3 per cent; P = 0·385), recurrence patterns and early recurrence rates (57·6 per cent versus 59·9 per cent; P = 0·712). CONCLUSION: AR and NAR achieved favourable and similar outcomes for HCC exceeding the Milan criteria in selected patients.

[A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P=0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P=0.288; 35.7%(5/14) vs 5.3%(1/19), P=0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P=0.766, P=0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

[Outcome analysis of allogeneic hematopoietic stem cell transplantation for 41 patients with severe aplastic anemia].

OBJECTIVE: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo- HSCT) for patients with severe aplastic anemia (SAA). METHODS: A retrospective study was conducted in 41 SAA patients received allo-HSCT from Oct. 2001 to May 2015. There were 27 males and 14 females with median age of 17(2-43) years old. Of them, 24 received matched sibling donor HSCT, 17 received unrelated donor transplantation. RESULTS: Hematopoiesis reconstitution was achieved in 38 patients (92.68%). Median time of neutrophils and platelets implantation was 16(10-57) d and 20(9-83) d in evaluable patients, respectively. Acute GVHD occurred in 13 cases, chronic GVHD in 8 cases, and graft rejection in 5 cases. Median follow-up time was 27(3- 154) months. The prospective OS for 3 years was (75.1±8.3)%. Transplantation related mortality was 24.39% (10 cases). Multivariate analysis revealed that grade Ⅱ -Ⅳ aGVHD [P=0.018, OR=27.481 (95% CI 2.377-392.636) ] and invasive fungal disease [P=0.021, OR=21.364 (95% CI 1.732- 354.185) ] were independent risk factors of OS for SAA patients after allo- HSCT. CONCLUSION: Allo- HSCT is an efficient and safe therapy for the patients with SAA, not only for patients with HLA matched sibling donor, but also for those with only HLA matched unrelated donor available. Grade Ⅱ- Ⅳ aGVHD and invasive fungal disease were associated with lower OS rate.

Polluted dust derived from long-range transport as a major end member of urban aerosols and its implication of non-point pollution in northern China.

The contribution of polluted dust transported from local and distal sources remains poorly constrained due to their similar geophysical and geochemical properties. We sampled aerosols in three cities in northern China (Xi'an, Beijing, Xifeng) during the spring of 2009 to determine dust flux, magnetic susceptibility and elemental concentrations. Combining dust fluxes with wind speed and regional visibility records enabled to differentiate between dust transported from long range and derived from local sources, while the combination of magnetic susceptibility and enrichment factors (EF) of heavy metals (Pb, Zn) allowed to distinguish natural aerosols from polluted ones. Our results indicate that polluted dust from long-range transport became a major end member of urban dust aerosols. Human settlements as its potential sources were confirmed by a pollutant enriched regional dust event originating from populated areas to the south as inferred by back trajectory modeling, implying their non-point source nature of dust pollution.

Dendritic cells transfected with hepatocellular carcinoma (HCC) total RNA induce specific immune responses against HCC in vitro and in vivo.

BACKGROUND: Immunotherapy is an effective method for preventing metastasis and recurrence of carcinoma. Hepatocellular carcinoma (HCC) is a common malignancy with a high rate of recurrence, and has not successfully been introduced to immunotherapy. METHODS: Peripheral blood mononuclear cells were isolated from whole blood of HCC patients and stimulated to transform into dendritic cells (DCs). These DCs were then transfected with RNA extracted from HepG-2 hepatoma cells to induce expression of specific antigens. RESULTS: The transfected DCs stimulated T lymphocytes to produce cytotoxic T lymphocytes, which specifically attacked HepG-2 cells. Injection of T lymphocytes from HCC patients and transfected DCs into severe combined immunodeficiency mice limited the growth of HepG-2 tumors. CONCLUSION: A specific immune response against hepatoma can be generated in vivo by administering DCs transfected with RNA from a specific tumor. This method may have therapeutic application in humans to reduce recurrence of HCC.

Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib.

BACKGROUND: Sorafenib represents the standard of care targeted therapy for patients with advanced hepatocellular carcinoma (HCC). However, biomolecules that predict a patient's response to sorafenib treatment for HCC remain largely unknown. Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients. METHODOLOGY: From December 2008 to October 2011, pathological specimens from 54 advanced HCC patients received sorafenib treatment were obtained. Clinicopathological variables, treatment response, survival and time to progression (TTP) were recorded. Immunophenotypical analysis was carried out using antibodies against pERK, phosphorylated S6K (pS6K), VEGFR2 and PTEN. RESULTS: The median overall survival (OS) and TTP were 14.2 and 3.4 months, respectively, and the disease control rate (DCR) was 59.3%. Better Eastern Cooperative Oncology Group Performance Status (ECOG PS) (95% CI: 3.27-4.93 m vs. 1.15-2.85 m, p = 0.01), Child-Pugh class A score (95% CI: 3.47-4.53 vs. 1.14-2.06 m, p < 0.01), and higher pERK (3.34-6.66 m vs. 1.33-2.67 m, p = 0.03) and VEGFR2 (3.49-6.52 m vs. 2.15-2.73 m, p = 0.04) immunohistochemical staining score were associated with increased TTP by univariate analysis. The ECOG PS (p = 0.022), Child-Pugh class (p = 0.045) and pERK staining score (p = 0.012) were found to be associated with TTP using multivariate analysis. CONCLUSION: Sorafenib treatment outcome is favorable in advanced HCC patients who received tumor resection and who have a good ECOG PS and Child-Pugh class A liver function. The pERK immunohistological staining score, ECOG PS and Child-Pugh class may be helpful in determining patients most likely to benefit from sorafenib therapy.

Phylogenetic, molecular and drug-sensitivity analysis of HA and NA genes of human H3N2 influenza A viruses in Guangdong, China, 2007-2011.

Annual H3N2 subtype influenza outbreaks in Guangdong, China are a severe public health issue and require ongoing monitoring of emerging viral variants. The variation and evolution of haemagglutinin (HA) and neuraminidase (NA) genes of influenza isolates from Guangdong during 2007-2011 and others from GenBank were analysed using Lasergene 7.1 and MEGA 5.05, and serological analysis of antigens was determined by haemagglutination inhibition (HI). Susceptibility to antiviral drugs was correlated with genetic mutations. Phylogenetic analysis and alignment of HA and NA genes were performed on 18 Guangdong isolates and 26 global reference strains. The non-synonymous (dN) evolutionary rate of HA1 was 3.13 times that of HA2. Compared with the A/Perth/16/2009 vaccine HA gene, homologies of Guangdong isolates were between 98.8-99.7% and 98.0-98·4% in 2009 and 2010, respectively. Amino-acid substitutions were found in five epitopes of HA1 from Guangdong isolates between 2007 and 2011, especially in epitopes B (N160K) and D (K174R/N). The K189E/N/Q and T228A mutations in the receptor-binding site (RBS) occurred in the 2010 strains, which affected the antigenicity of HA1. The antigenicity of the epidemic H3N2 isolates in 2010 was somewhat different from that of A/Perth/16/2009. The Guangdong H3N2 isolates were determined to be oseltamivir-resistant with IC50 of 0.396 ± 0.085 nmol/l (n=17) and zanamivir-resistant with IC50 of 0.477 ± 0.149 nmol/l (n=18). Variations were present in epitopes B and D, two sites in the RBS and two glycosylation sites in the Guangdong H3N2 HA1 gene. The majority of the Guangdong H3N2 isolates were sensitive to oseltamivir and zanamivir. Compared to the World Health Organization 2012 vaccine strains, Guangdong H3N2 strains varied genetically and antigenically to some degree.

Effect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal women.

AIM: The aim of this study was to determine and compare the effect of treatment with transdermal oestrogen and phytoestrogen on insulin sensitivity and sex hormone-binding globulin (SHBG) levels in healthy postmenopausal women. METHODS: Forty-three healthy postmenopausal women aged 68 ± 7 (mean ± SD) years who were not receiving hormonal replacement therapy completed a 3 month randomized drug therapy study. The participants were randomized to one of four groups: 0.05 mg or 0.1 mg transdermal oestrogen/day, or 40 or 80 mg oral phytoestrogen (Promensil)/day insulin sensitivity was indirectly measured using the quantitative insulin sensitivity check index (QUICKI). SHBG, total testosterone, oestradiol, and fasting glucose and insulin levels for calculation of insulin sensitivity were obtained at baseline and at monthly intervals during the 3 months of therapy. RESULTS: In healthy nondiabetic postmenopausal women, the rate of change in QUICKI was significantly different between the red clover based phytoestrogen and transdermal oestrogen groups, so that after three months of therapy, QUICKI with red clover based phytoestrogen therapy was lower than that in the transdermal oestrogen group, p = 0.01. Red clover based phytoestrogen therapy was not associated with any changes in SHBG levels whereas transdermal estrogen therapy significantly increased SHBG levels, p = 0.05. CONCLUSIONS: In contrast to transdermal oestrogen therapy, oral phytoestrogen therapy does not decrease androgenicity and is associated with a decrease in insulin sensitivity. These effects are similar to those of raloxifene and consistent with phytoestrogen's selective oestrogen receptor modulator properties.

Bipotential properties and proliferation of fetal liver epithelial progenitor cells in mice.

The potential of embryonal day 14 (ED) fetal liver epithelial progenitor (FLEP) cells to repopulate the normal and damaged liver was studied throughout a 3-month period in syngeneic mice. In normal liver, FLEP cells proliferated and differentiated into hepatocytes after transplantation, and liver repopulation was moderate (5%-10%) after 3 months. In diethylnitrosamine-treated livers FLEP cells continued to proliferate at 3 months after transplantation; both the number and size of clusters derived from FLEP cells gradually increased throughout time. Transplanted cells proliferated and differentiated into both hepatocytes and bile ducts to produce extensive liver repopulation (30%-50%). This report showed that isolated fetal liver epithelial cells exhibit bipotential properties of stem cells, which can engraft, proliferate, and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the injured liver.

WITHDRAWN: Adjuvant portal vein chemotherapy improves the efficacy of hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.

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Hepatocellular carcinoma: US-guided percutaneous microwave coagulation therapy.

PURPOSE: To evaluate the use of percutaneous microwave coagulation therapy for hepatocellular carcinoma, particularly with tumor nodules larger than 2 cm in diameter. MATERIALS AND METHODS: Fifty patients with 107 hepatocellular carcinoma nodules (mean diameter, 2.7 cm +/- 1.5 [SD]; range, 0.8-6.4 cm) were treated with percutaneous microwave coagulation therapy. Single electrode insertion was used in 46 nodules (43.0%) 2 cm or smaller, whereas multiple electrode insertion was applied in 61 (57.0%) nodules larger than 2 cm. RESULTS: At 1 month after therapy, technical success for tumors 2 cm or smaller and those larger than 2 cm was achieved in 45 (98%) and 56 (92%) nodules, respectively. After follow-up of 9 months or longer, local recurrence was found in one nodule (2%) sized 1.8 cm and in five nodules (8%) larger than 2 cm. At the end of the study, 26 (52%) of 50 patients were free of disease, and disease-free survival rates at 1 and 2 years were 55% and 41%, respectively. Overall survival rates at 1, 2, and 3 years were 96%, 83%, and 73%, respectively. CONCLUSION: Percutaneous microwave coagulation therapy is an effective and safe therapeutic modality for hepatocellular carcinoma. A multiple electrode insertion technique can enhance the effectiveness of this therapy in tumors 6 cm or smaller.