OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Objective To examine the effect of the integrated schistosomiasis control measures in Hunan Province from 2004 to 2019, so as to provide insights into the development of the schistosomiasis elimination strategy. Methods The integrated schistosomiasis control measures implemented by the health, agriculture, water resources, forestry, land and resources sectors were retrospectively collected in Hunan Province from 2004 to 2019, and the completion of each measure, cost of control measures, Schistosoma japonicum infections in humans and bovines, and snail status were analyzed each year. An index system for assessing the integrated schistosomiasis control effect was constructed using the Delphi method to calculate the integrated schistosomiasis control effect index. In addition, a cost-effect analysis was performed in terms of the decline in the prevalence of S. japonicum infections in humans and bovines, areas with snails in inner embankments, and areas with infected snails. Results A total of 7 110 926 500 Yuan were invested into the integrated schistosomiasis control program of Hunan Province from 2004 to 2019. During the 16-year period, a total of 277 437.12 hm² snail habitats received molluscicidal treatments, 6 927 230 person-times given expanded chemotherapy, 2 116 247 bovine-times given expanded chemotherapy, 954 850 harmless toilets built, 290 359 bovines fenced, 136 666 bovines eliminated, 141 905 machines used to replace bovines, 39 048.63 hm² water lands improved as dry lands, 724.12 km irrigation regions improved, 3 994 300 populations covered with safe water, 191 102.89 hm² forests planted and 38 535.27 hm² lands leveled. The prevalence of S. japonicum infections was 4.29% in humans and 4.48% in bovines in Hunan Province in 2004, with 2 449.37 hm² snail habitats in inner embankments and 3 423.74 hm² infected snail areas. In 2019, the prevalence of S. japonicum infections reduced to 0 in both humans and bovines, and areas of snail habitats reduced to 540.92 hm² (77.92% reductions), while the areas with infected snails reduced to 0. The overall integrated schistosomiasis control effect index appeared a tendency towards a rise over years since 2004, and the integrated schistosomiasis control effect index was 97.35 in 2019; the annual mean costs for a 1% reduction in the prevalence of S. japonicum infections in 100 populations and 100 bovines were 70.11 Yuan and 4 204.78 Yuan, and the annual mean costs for a 1% reduction in the snail areas in inner embankments and infected snail areas were 2 010.20 Yuan and 1 298.09 Yuan, respectively. Conclusions The integrated control measures achieve remarkable effectiveness for schistosomiasis control in Hunan Province, with a remarkable decline in the prevalence of S. japonicum infections in humans and bovines and great shrinking of snail areas in inner embankments and infected snail areas. Adequate fund investment is required to improve the integrated schistosomiasis control measures and consolidate the control achievements.

Objective To analyze the endemic situation of schistosomiasis in Hunan Province in 2019, so as to provide insights into the achievement of transmission interruption of schistosomiasis in the province in 2020. Methods The data pertaining to Schistosoma japonicum infections in humans and livestock and snail status were captured from Hunan Province in 2019 and analyzed. Results Schistosomiasis was endemic in 281 townships (towns) from 41 counties (districts) of 6 cities in Hunan Province by the end of 2019. A total of 991 900 persons received blood testing in Hunan Province in 2019, and 22 773 were positive for the blood testing, with sero-prevalence of 2.30%. All stool examinations were negative in 22 933 individuals detected. The high sero-prevalence was seen in Nanxian County, Anxiang County and Ziyang District. Currently, there were 5 034 cases with advanced schistosomiasis detected in Hunan Province, and they were predominantly identified in Yuanjiang City, Heshan District and Yueyang County. There were 44 963 bovines fenced in schistosomiasis-endemic villages in Hunan Province in 2019, which were predominantly distributed in Yuanjiang City, Hanshou County and Ziyang District, and no positives were detected in 1 996 bovines receiving blood testing or 20 684 bovines receiving stool examinations. In 2019, there were snail habitats of 1.73 billion m² found in Hunan Province, which were mainly found in Yuanjiang City, Hanshou County and Yueyang County. Conclusion The endemic situation of schistosomiasis further decreases in Hunan Province in 2019; however, there is still a risk of schistosomiasis transmission in local areas of the province.

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning

Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.
Adolescent ; Adult ; Child ; Child, Preschool ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3/genetics*

To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (<0.05), and the ratio of Bcl-2/Bax was decreased (<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.

Objective To investigate the protective effect of modified Qianjin Weijing Decoction(MQJWJD)on TNF-α and NF-κB in rats with lung injury induced by particulate matter; To discuss relevant mechanism of action. Methods A tracheal drip 15 mg/kg fine particles of saline solution was used to establish modeling, every other day, three times. Thirty-two Wistar rats were randomly divided into normal group, model group and MQJWJD high-dose and low-dose groups, with eight rats in each group. Medication groups were given relevant medicine for gavage. The level of TNF-α in bronchoalveolar lavage fluid (BALF) was measured by ELISA. The expression of NF-κB protein in lung tissues was measured by immunohistochemistry. The histopathology of the lung injury was observed by light microscope. Results Compared with normal group, the level of TNF-α and the expression of NF-κB protein in the model group were higher than those in the normal group (P<0.01). Compared with model group, the level of TNF-α and the expression of NF-κB protein in MQJWJD low-dose and high-dose groups were lower than those in the model group (P<0.05, P<0.01). Pathological observation showed that, compared with normal group, model group showed intratracheal, alveolar and interstitial bacteria within a large number of fine particles calm, alveolar and pulmonary interstitial visible large amounts of phagocytic fine particles of macrophages and accompanied by more neutrophils and lymphocyte infiltration; Lung tissue pathological changes were significantly lighter in MQJWJD high-dose and low-dose groups than the model group. MQJWJD high-dose group showed mild inflammation, alveolar and pulmonary interstitial visible phagocytic fine particles of macrophages, a small amount of neutrophils and lymphocyte infiltration. Conclusion MQJWJD can reduce the pulmonary injury in rats induced by particulate matter and has protective effects on the rat model through decreasing the levels of TNF-α and the expressions of NF-κB protein in injured lung tissues.