[The prognostic significance of pretransplantation evaluation of IPSS-R and WPSS in patients with myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation].

Objective: This study aimed to explore the prognostic value of the revised international prognostic scoring system (IPSS-R) and the WHO prognostic scoring system (WPSS) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The clinical data of 184 patients with MDS who received allo-HSCT from July 2016 to June 2019 were retrospectively analyzed. IPSS-R and WPSS were performed at diagnosis and before transplantation. The prognostic values of IPSS-R and WPSS and potential risk factors were explored. Results: With a median follow-up of 21.9 (0.5-47.5) months, the two-year overall survival (OS) and progression-free survival (PFS) rates were (75.1±3.4)% and (71.6±3.6)% , respectively. The two-year cumulative relapse rate and nonrelapse mortality rate were (11.9±0.1)% and (16.5±0.1)% , respectively. There were no significant differences in OS and PFS between the IPSS-R ≤3.5 and >3.5 groups at diagnosis (P=0.409; P=0.724). No significant differences in OS and PFS between the WPSS ≤2 and >2 groups (P=0.426; P=0.726) were observed as well. When the patients were reevaluated before transplantation, the OS and PFS of the IPSS-R ≤3.5 group were significantly better than >3.5 group [OS: (88.6±4.1)% vs (65.8±5.3)% , P=0.003; PFS: (87.6±4.2)% vs (60.5±5.8)% , P=0.002]. However, there were no significant differences in OS and PFS among the WPSS ≤2 and >2 groups (P=0.584; P=0.565). In addition, the OS and PFS of the improved group based on IPSS-R were significantly better than those of the unimproved group before transplantation [OS: (83.8±4.6)% vs (69.3±5.8)% , P=0.027; PFS: (82.8±4.4)% vs. (64.0±7.2)% , P=0.006]. Multivariate analysis indicated that a pretransplant IPSS-R of >3.5 (P=0.021, HR=2.510, 95% CI 1.151-5.476) and TP53 mutation (P=0.047, HR=2.460, 95% CI 1.014-5.971) were independent risk factors for OS, whereas a pretransplant IPSS-R of >3.5 (P=0.017, HR=2.457, 95% CI 1.175-5.141) and pretransplant cytogenetic poor and very poor (P=0.008, HR=2.765, 95% CI 1.305-5.856) were independent risk factors for PFS. Conclusion: A pretransplantation evaluation of IPSS-R could help determine the prognosis of patients with MDS undergoing allo-HSCT. In addition, patients with improved IPSS-R scores before undergoing allo-HSCT had a better prognosis.

[Efficacy and safety of venetoclax combined with azacitidine versus CAG regimen combined with decitabine in elderly patients with relapsed acute myeloid leukemia].

Objective: To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) versus CAG regimen combined with decitabine (DAC) in elderly patients with relapsed acute myeloid leukemia (AML). Methods: From January 2018 to August 2020, the clinical data of forty-five elderly patients with relapse AML at the First Affiliated Hospital of Soochow University were retrospectively analyzed, including 31 males and 14 females. The median age was 66 (60-80) years old. Eighteen patients were administrated with VEN and AZA, while the other 27 were in CAG with DAC. The complete remission (CR) rate, partial remission (PR) rate, total remission rate (ORR), adverse events and overall survival (OS) were compared between the two groups. Results: At the end of the treatment, the ORR in VEN with AZA group was 77.8% (14/18); including 11 CR and 3 PR. In CAG with DAC group, the ORR was 37.0% (10/27); including 8 CR and 2 PR (P=0.007). Subgroup analysis suggested that VEN with AZA had a higher ORR in patients stratified as intermediate and poor-risk (P=0.013) or with DNA methylation mutations (P=0.007). Main adverse events in both groups were bone marrow suppression, infections, nausea and vomiting, anorexia and fatigue. Grade Ⅲ-Ⅳ cytopenia developed in lower incidence of VEN with AZA group, such as leukopenia (66.7% vs. 100%, P=0.002), anemia (50.0% vs. 92.6%, P=0.002), thrombocytopenia (72.2% vs. 96.3%, P=0.031) and neutropenia (61.1% vs. 92.6%, P=0.014). In addition, less grade Ⅲ-Ⅳ infections occurred in VEN with AZA group (66.7% vs. 33.3%, P=0.028), as well as grade Ⅲ-Ⅳ gastrointestinal events (40.7% vs. 11.1%, P=0.032), grade Ⅲ-Ⅳ fatigue (55.6% vs.11.1%, P=0.003) compared with CAG with DAC group. The 1-year OS in VEN with AZA group versus CAG with DAC group was 42.9% and 31.6% respectively (P=0.150). Conclusion: VEN combined with AZA proves favorable efficacy and tolerablity in elderly patients with relapsed AML.

A combined approach using slightly acidic electrolyzed water and UV exposure to improve egg internal quality during storage.

This study investigated the combined efficacy of slightly acidic electrolyzed water (SAEW) and UV light (UV) in improving egg internal quality (weight loss, Haugh unit, yolk index, albumen pH) over a 6-wk storage time at 25°C. Eggs were preserved after immersion for 4 min in SAEW (30 mg/L), irradiation for 4 min under a UV lamp, or a combination of SAEW and UV treatment for 4 min. The combination of SAEW and UV inhibited the deterioration of yolk index over the storage period, as well as reducing the extent of decrease in Haugh unit and of weight loss during storage at 25°C, and it was more effective than SAEW or UV alone in maintaining egg internal quality (P < 0.05). The results highlight the promising use of a SAEW and UV combination treatment to improve egg internal quality during storage.

Functional and Structural Connectivity Patterns Associated with Clinical Outcomes in Deep Brain Stimulation of the Globus Pallidus Internus for Generalized Dystonia.

BACKGROUND AND PURPOSE: Deep brain stimulation is a well-established treatment for generalized dystonia, but outcomes remain variable. Establishment of an imaging marker to guide device targeting and programming could possibly impact the efficacy of deep brain stimulation in dystonia, particularly in the absence of acute clinical markers to indicate benefit. We hypothesize that the stimulation-based functional and structural connectivity using resting-state fMRI and DTI can predict therapeutic outcomes in patients with generalized dystonia and deep brain stimulation. MATERIALS AND METHODS: We performed a retrospective analysis of 39 patients with inherited or idiopathic-isolated generalized dystonia who underwent bilateral globus pallidus internus deep brain stimulation. After electrode localization, the volumes of tissue activated were modeled and used as seed regions for functional and structural connectivity measures using a normative data base. Resulting connectivity maps were correlated with postoperative improvement in the Unified Dystonia Rating Scale score. RESULTS: Structural connectivity between the volumes of tissue activated and the primary sensorimotor cortex was correlated with Unified Dystonia Rating Scale improvement, while more anterior prefrontal connectivity was inversely correlated with Unified Dystonia Rating Scale improvement. Functional connectivity between the volumes of tissue activated and primary sensorimotor regions, motor thalamus, and cerebellum was most correlated with Unified Dystonia Rating Scale improvement; however, an inverse correlation with Unified Dystonia Rating Scale improvement was seen in the supplemental motor area and premotor cortex. CONCLUSIONS: Functional and structural connectivity with multiple nodes of the motor network is associated with motor improvement in patients with generalized dystonia undergoing deep brain stimulation. Results from this study may serve as a basis for future development of clinical markers to guide deep brain stimulation targeting and programming in dystonia.

Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes.

BACKGROUND AND PURPOSE: Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. MATERIALS AND METHODS: Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. RESULTS: Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. CONCLUSIONS: This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline.

Investigation of the association between interleukin-10 polymorphisms and risk of acute pancreatitis in a Chinese population.

We conducted a case-control study to investigate the possible association between three common single nucleotide polymorphisms in interleukin-10 (IL-10) and the development of acute pancreatitis in a Chinese population. Between January 2013 and December 2014, 255 patients with acute pancreatitis and 255 control subjects were recruited for the study. Genotyping of IL-10 rs1800896, rs1800871, and rs1800872 was performed using polymerase chain reaction coupled with restriction fragment length polymorphism. Using logistic regression analysis, we found that the AA genotype of IL-10 rs1800896 was correlated with an increased risk of acute pancreatitis in a codominant model (OR = 2.44, 95%CI = 1.28-4.77). In a dominant model, we found that the GA+AA genotype of IL-10 rs1800896 was associated with an elevated risk of acute pancreatitis (OR = 1.51, 95%CI = 1.05-2.18). In a recessive model, the AA genotype of IL-10 rs1800896 was correlated with an increased risk of acute pancreatitis (OR = 1.98, 95%CI = 1.06-3.77). In conclusion, IL-10 rs1800896 was correlated with an increased risk of acute pancreatitis in codominant, dominant, and recessive models.

Surgical excision promotes tumor growth and metastasis by promoting expression of MMP-9 and VEGF in a breast cancer model.

UNLABELLED: Surgery is still the main curative therapeutic modality for breast cancer. Although surgery often results in the successful removal of the primary tumor, its process could increase the risk of metastases of residual cancer cells. Understanding of the connection between breast cancer metastasis and surgical wound will lead to the establishment of a proper treatment strategy for postoperative cancer patient. AIM: To study the influence of surgical procedure on the metastasis of primary breast cancer. METHODS: We established MDA-MB-435 human breast cancer xenograft model. Levels of Pro-matrix metalloproteinase 9 (Pro-MMP-9) and vascular endothelial growth factor (VEGF) in host serum and tumors were tested at different time points with ELISA and zymography and correlated to tumor growth and postoperative metastasis. RESULTS: Our study demonstrated surgical wound had promoting effect on tumor growth and pulmonary metastasis of human breast cells, if tumor cells remain in bodies. This effect might be related to the postoperative interaction of cancer and host cells, which resulted in expression of Pro-MMP-9. Surgical process could also increase the VEGF expression in tumor tissues. CONCLUSIONS: Surgical wound-produced host Pro-MMP-9 and tumor cell VEGF might be important mediators leading to metastasis of residual breast cancer after surgery.

Estrogenic Effects of Cimicifuga racemosa (Black Cohosh) in Mice and on Estrogen Receptors in MCF-7 Cells.

The estrogenic effects of Cimicifuga racemosa or Actacea racemosa (black cohosh, CR) extracts were tested in mice, and their effects on estrogen receptor (ER) levels in human breast cancer MCF-7 cells were also investigated. Four groups of weanling female Kunming mice were given 0 (control), 75, 150, or 300 mg/kg body weight CR extracts orally for 14 days. The estrus cycle and the weights of the uterus and ovary of mice, as well as serum estradiol (E(2)) were measured. The proliferation patterns of MCF-7 cells exposed to CR extracts or 17beta-estradiol were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, growth of MCF-7 cells in 0 (control) or 4.75 &mgr;g/L of CR extracts or 0.3 nmol/L of 17beta-estradiol groups were observed for 5 days. ER levels in MCF-7 cells were analyzed by indirect immunofluorescence assay using flow cytometry. The uterine weights of mice increased with the increase in dosage of CR extracts, and the estrus duration was significantly prolonged in the group receiving 300 mg/kg body weight (P <.05). However, CR extracts did not increase the serum E(2) concentration significantly. In the in vitro study, a dose-response relationship was demonstrated when cells were treated with low doses of CR extracts, and the optimal enhancement concentration of CR extracts was 4.75 &mgr;g/L on MCF-7 cells. The doubling times (T(D)) of cell growth in the CR extracts group and the 17beta-estradiol group were 32.1 and 31.7 hours, respectively, both shorter than that of the negative control group (T(D) = 35.3 hours). Additionally, 4.75 &mgr;g/L of CR extracts resulted in significantly increased ER levels compared with the control group (P <.01). In conclusion, CR extracts produced an estrogenic action. The effect of increasing ER levels by CR extracts may be one of the potential mechanisms of its phytotherapeutic effects for postmenopausal symptoms.

Changes in ganglioside contents, plasma sialic acid and cAMP levels in experimental hepatoma in mice.

The present study was designed to assess whether changes in glycolipids and cyclic AMP contents might serve as markers for the diagnosis of malignancy in the liver. The experimental model was a transplantable murine hepatoma. Experimental mice were divided into three groups: (1) a therapeutic group, which had been transplanted with hepatoma and treated with the antimetabolism drug 5-fluorouracil (0.2 mg/day i.p.), (2) a control group, which had been transplanted with hepatoma and treated with 0.2 ml 0.9% NaCl/day and (3) a normal group of mice. The ganglioside and cAMP contents in the hepatoma tissue, plasma cAMP, total- and lipid-bound sialic acid levels and red blood cell membrane sialic acid levels were determined. Results showed that the ganglioside content, total and lipid-bound sialic acid levels in the control group were significantly higher than those in the livers of normal mice (p < 0.01) while these respective values in the therapeutic group were significantly lower than those in the control group (p < 0.01). The cAMP levels of tumor tissues and plasma in the control group were lower than those in normal mice. No significant difference in red blood cell membrane sialic acid content was observed between the therapeutic and control groups though levels for both were higher than those in normal mice. These results indicate that ganglioside content and sialic acid levels in hepatoma tissues were significantly elevated, and cAMP levels in hepatoma tissues were significantly decreased during proliferation and abnormal differentiation.

Nutritional efficacy of a fortified weaning rusk in a rural area near Beijing.

A micronutrient-fortified rusk for weanling children was tested in a rural area near Beijing. Two hundred twenty-six children aged 6-13 mo were randomly assigned by village to either a micronutrient-fortified or an unfortified rusk, daily for 3 mo. The fortified rusk contained extra zinc; iron; calcium; vitamins A, D, and B-12; thiamin, riboflavin, niacin, and folic acid. Infants receiving the fortified rusk exhibited no decline in hemoglobin concentrations during the study whereas those receiving the unfortified rusk exhibited a significant decline. Improvements were also seen in erythrocyte porphyrin, plasma vitamin A, and riboflavin status, but these improvements were seen in both of the groups. Micronutrient fortification was probably beneficial for iron status and the fortified rusk promises to be an effective vehicle for supplementation.

PIP: In February-June 1990, in China, researchers assigned, by village, 226 6-13 month old, full-term, healthy infants from 33 villages of the Mi-yun rural area near Beijing to receive daily either a micronutrient-fortified or an unfortified rusk for 3 months. 15% of all infants were initially anemic, but not severely so. Extra zinc; iron; calcium; vitamins A, D, and B-12; thiamin; riboflavin; niacin; and folic acid fortified the rusk. The study aimed to determine the efficacy of the micronutrient fortification. Mean hemoglobin levels decreased considerably in the infants in the unfortified rusk group (12.85 g/L vs. 12.95 g/L; p .01), but remained the same for the fortified rusk group. The change in the unfortified rusk group's hemoglobin levels was much greater than that of the fortified rusk group (p .01). The significance of the supplement-group effect fell when the researchers included initial ferritin and free erythrocyte porphyrin concentrations (p = .04-.08). There was a considerable reduction in free erythrocyte porphyrin in both groups of infants (p .001) and the response was basically the same for both groups. Even though the fortified rusk group experienced a significant increase in plasma vitamin A (.093 mcmol/L; p .01), the difference in response between the 2 groups was not significant. Infants in the fortified rusk group experienced a considerable fall in vitamin E levels (p .001) which was a significantly greater decline than that observed in the unfortified rusk group (2.6 mcmol/L vs. .79 mcmol/L; p = .012). The erythrocyte glutathione reductase index of riboflavin status improved significantly in the fortified rusk group (.07; p = .05), but it was not significantly different from that of the unfortified group. These results suggested that fortifying a commercial weaning risk with micronutrients benefited the iron status of these children.

The existence of a soluble plasmalogenase in guinea pig tissues.

The distribution of plasmalogenase for the hydrolysis of 1-alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmenylethanolamine) in the subcellular fractions of guinea pig tissues was examined. Plasmalogenase activity was found in high abundance in the cytosolic fractions of the brain and the heart. Assessment of microsomal marker enzyme activities in the cytosolic fraction revealed that plasmalogenase activity in the cytosol was not due to microsomal contaminations. The characteristics of the cytosolic plasmalogenase were very similar to the microsomal enzyme with respect to the pH profile of the reaction, the presence of divalent cations and Km values for plasmenylethanolamine. However, the cytosolic enzyme was slightly less stable at 55 degrees C than the microsomal enzyme. Cytosolic enzyme activity was eluted as a broad peak in Sepharose 6B chromatography with an average molecular weight of 250,000. Our results demonstrate that most of brain plasmalogenase activity is soluble which makes the brain cytosol an excellent source to initiate the purification of this enzyme.

Dietary patterns in 10 groups and the relationship with blood pressure. Collaborative Study Group for Cardiovascular Diseases and Their Risk Factors.

An epidemiological comparative study on dietary patterns and population means of blood pressure was undertaken in 10 groups (3 of workers, 6 of farmers, 1 of fishermen) of adult males and females of northeast, north, south, middle and east China. Standardized methods and record forms were used for blood pressure measurements and 24-hr dietary recall interviews. Simple correlation and linear regression, multiple regression (adjusted for age, sex and body mass index) and ridge regression were used to analyze the relationship of dietary electrolytes and animal protein to blood pressure. The results show a significant negative association of mean daily intake of Ca and animal protein with population mean blood pressure. Excluding the fishermen's group, mean daily intake of Na showed significant positive association with both systolic and diastolic blood pressure. The Chinese diet should probably be improved, increasing Ca and animal protein and cutting salt to a much lower level.