Objective:To analyze the genotypes distribution of common and rare thalassemia in people of reproductive age in Huadu district of Guangzhou,enhance the database of thalassemia.Methods:Peripheral blood samples were collected for genotype analysis in Maternity and Child Health Hospital of Huadu District from January 2016 to October 2022.Gap-PCR and Reverse dot blot hybridization were used to detect common thalassemia genotypes.DNA sequencing was performed in samples suspected of rare genotypes.Results:A total of 16 171 subjects were identified as thalassemia carriers,and the positive rate was 44.41％(16 171/36 412).The genotypes of 114 cases(0.31％)were rare.A total of 10 845 cases were identified as α-thalassemia carriers(29.78％),and--SEA/αα was the most common genotype in those people,followed by-α3.7/αα and-α4.2/αα.A total of 4 531 subjects were identified as common β-thalassemia carriers(12.44％).The most common β-thalassemia mutation in the population was β41-42/βN,followed by β654/βN and β-28/β N.A total of 681 subjects were identified as αβ thalassemia carriers(1.87％),among them--SEA/αα compounded withβ CD41-42/β N was the most common genotype.A total of 48 cases were identified as rare α-thalassemia carriers,14 types of mutations,in which Fusion gene/αα was the most common.A total of 52 cases were identified as rare β-thalassemia carriers,11 types of mutation,in which βSEA-HPFH/βN was the most common.Conclusion:The thalassemia genotypes in Huadu district are complex and diverse.We should attach great importance to the detection of rare thalassemia genotypes.

To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP) prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g·kg⁻¹; i.e. 3×, 6× and 12× equivalent doses) were given orally to dogs for 39 consecutive weeks. At the same time, the same volume of deionized water was used as the solvent control group, one time a day. The general condition of the animals was observed every day during the period of administration, and the blood was collected before and 13, 26, 39, 43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after 13, 39, and 43 weeks of administration to observe the pathological changes of the animal organs, weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group, 11 liver hepatotoxicity traditional biomarkers such as ALT, AST were found no ZYP-related changes at month 3, 6, 9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore, no obvious hepatotoxicity was shown by ZYP administered up to 6.0 g·kg⁻¹ for 9 months in normal dogs at doses of 1.5, 3.0, and 6.0 g·kg⁻¹.

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers ; Cohort Studies* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Lymph Nodes ; Nasopharynx ; Plasma ; Prognosis ; Radiotherapy* ; Tumor Burden*

OBJECTIVETo investigate the expression of N-cadherin in bone marrow leukemic cells derived from acute leukemia patients and its clinical significances.

METHODSA total of 113 patients with acute leukemia were enrolled in this study. Flow cytometry was employed to detect the expression of N-Cadherin in bone marrow leukemic cells from acute leukemia patients and the relationships between the N-cadherin expression and the clinical characteristics of patients with acute leukemia were analyzed.

RESULTSThe expression of N-Cadherin in bone marrow leukemic cells deriveted from patients with acute leukemia was variable with 0%-99.7%. For adult AML patients, the positive rate of CD34 in N-cadheringroup was significantly higher than that in N-cadheringroup(67.39% vs 33.33%)(P=0.013), while the differences of total CR rate and rate of CR after 1 cycle of induction treatment were not significant between these 2 groups(P>0.05). As to ALL patients, N-cadheringroup had significant lower WBC count (21.31±7.07 vs 51.10±23.69)(P=0.008) and lower percentage of peripheral blood blast (43.22±5.75% vs 66.45±5.65%)(P=0.015). The CR rate after 1 cycle of induction treatment and rate of overall CR were lower and the relapse rate was higher in N-cadherinALL group than those in N-cadherinALL group, but the differences were not significant (P>0.05). For childhood ALL, the positive rate of CD33 in N-cadheringroup was significantly higher than that in N-cadheringroup(47.62% vs 0%)(P=0.012). The relapse rate was higher in N-cadheringroup than that in N-cadheringroup (30.00% vs 0%)(P=0.115). The median survival time, 3-year overall OS rate and 3-year relapse-free survival rate in N-cadheringroups of adult AML, non-M3 AML, ALL and chidhood ALL paients were superior to N-cadheringroups, but the differences were not significant.

CONCLUSIONThe expression of N-cadherin in bone marrow leukemic cells relates to some clinical features of patients with acute leukemia and to some extent has inferior effect on survival of patients with acute leukemia.

OBJECTIVETo investigate the CD25 expression in patients with acute myeloid leukemia (AML) and its significance.

METHODSClinical data of 168 newly diagnosed AML patients (except APL) were collected. The expression of CD25 in AML patients and its clinical characteristics were retrospectively analyzed.

RESULTSThe leukemia cells of 29 out of 168 cases (17.26%) expressed CD25 antigen. Most of CD25 positive AML patients were occurred in patients with unfavourable or normal karyotype, higher WBC and Plt count at diagnosis and higher percentage of blasts in peripheral blood and bone marrow. Compared with CD25(-) AML patients, CD25(+) AML patients had lower CR rate (the CR rate of 1 course of treatment were 49.02% and 16.00%, respectively, P < 0.05, the CR rate of 2 courses of treatment were 74.60% and 46.67%, respectively, P < 0.05), and the OS time of CD25(+) AML patients were obviously shorter (P < 0.05). The OS in CD25(+) AML patients with unfavorable karyotype were not significantly different from that in patients with intermediate karyotype (P < 0.05).

CONCLUSIONThe CD25(+) AML patients have some typical clinical features, and the expression of CD25 in AML is an risk factor independent of the chromosome karyotype in terms of low complete remission rate and short survival time.

Bone Marrow ; Humans ; Interleukin-2 Receptor alpha Subunit ; genetics ; metabolism ; Karyotype ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Prognosis ; Remission Induction ; Retrospective Studies

Myeloid-derived suppressor cells (MDSC) play critical roles in immune escape of tumor. We hypothesized that elimination of tumor-induced MDSCs might help to block tumor growth. Therefore, we constructed a cholera toxin B based peptide vaccine that targets a MDSC surface marker S100A8. Immunized BALB/c mice with CTB-S100A8 plus aluminum hydroxide induced high titers of anti-S100A8 antibodies and reduced tumor burden significantly in 4T1 mice model. We also found the vaccination led to significant reduction of tumor-induced monocytic MDSC (M-MDSC), with no effect on innate MDSCs, dendritic cell (DC) and macrophage (Mφ), demonstrating that targeting tumor-induced MDSC may be a promising approach in cancer immunotherapy.

Objective To compared the influence on inflammatory factors of using ticagrelor and clopidogrel in patients with coronary heart disease after percutaneous coronary intervention ( PCI ) operation . Methods A total of 110 patients with coronary heart disease after PCI were divided into treatment group and control group ,55 cases in each group.Treatment group was given ticagrelor 90 mg, qd, and control group given clopidogrel 300 mg, qd.The course of two groups were both one month .The throm-bolysis in myocardial infarction ( TIMI ) blood flow and no reflow incidence of two groups were compared after treat-ment.Inflammatory factor C-reactive protein (CRP), interleukin 6 (IL-6), myelo peroxidase(MPO), and soluble CD40 receptor (sCD40L) levels were compared of the two groups before surgery and 1 week, 1, 3 and 6 months after treatment.The incidence of major cardiovascular adverse events was compared of two groups .Results There was no reflow case found in treatment group , and two cases of no reflow were founded in control group (3.64%, P>0.05 ). The number of patients in TIMI level 3 of treatment group and control group were 53 ( 96.36%) and 44 ( 88.00%, P<0.05).The levels of CRP, IL -6, MPO, sCD40L in one week of treatment group were ( 12.05 ±1.06 ) ng? mL-1 ,(3.38 ±0.83 ) pg? mL-1 , ( 233.16 ±25.24 )μg? mL-1 , ( 632.38 ±24.99 ) pg? mL-1 , and were (10.37 ±1.88 ) ng? mL-1 ,(7.96 ±0.99 ) pg? mL-1 ,(237.06 ±20.33 )μg? mL-1 ,(624.46 ±22.33 ) pg? mL-1 in control group(P<0.05).The levels of CRP, IL-6, MPO, sCD40L in one month of treatment group were (4.68 ± 1.38)ng? mL-1,(3.13 ±1.11)pg? mL-1,(204.49 ±21.38)μg? mL-1,(588.67 ±19.55)pg? mL-1, and were (3.04 ±1.17)ng? mL-1,(2.15 ±1.29)pg? mL-1,(179.06 ±20.29)μg? mL-1,(565.27 ±21.15)pg? mL-1in control group(P<0.05).The levels of CRP, IL-6, MPO, sCD40L in three months of treatment group were (4.26 ± 0.53)ng? mL-1,(3.07 ±1.09)pg? mL-1,(198.11 ±21.25)μg? mL-1,(574.17 ±26.31)pg? mL-1, and were (2.92 ±0.97)ng? mL-1,(2.12 ±1.34)pg? mL-1,(165.19 ±25.63)μg? mL-1,(522.17 ±23.42)pg? mL-1in control group(P<0.05).The levels of CRP, IL-6, MPO, sCD40L in six months were (4.14 ±0.49)ng? mL-1, (3.05 ±1.13)pg? mL-1,(200.16 ±22.17)μg? mL-1,(363.26 ±19.48)pg? mL-1 in treatment group, and were (2.79 ±1.11)ng? mL-1,(2.08 ±1.32)pg? mL -1,(174.06 ±22.01)μg? mL-1,(323.55 ±24.63)pg? mL-1 in control group ( P <0.05 ) .The adverse reactions mainly manifested as cardiac death , atrial fibrillation , recurrent myocardial infarction , the incidence of major cardiovascular adverse events in treatment group ( 9.09%) was signifi-cantly higher than that in control group ( 7.27%, P>0.05 ) .Conclusion Ticagrelor effectively reduce the level of inflammatory reaction in patients with coronary heart disease after PCI , improve the prognosis and reduce the incidence of adverse reactions.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.
Animals ; Breast Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplastic Stem Cells ; metabolism ; Receptor, Notch1 ; biosynthesis ; genetics ; Signal Transduction

OBJECTIVETo investigate the effects of prepubertal exposure to diethylstilbestrol (DES) on the testicular development and function of Sprague-Dawley (SD) rats.

METHODSNinety 21-day-old male SD rats were randomly and equally divided into 4 experimental groups (Da, Db, Dc and Dd), which were injected with DES dissolved in corn oil at the dose of 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) from postnatal day (PND) 22 to 35, and a control group (C), which received vehicle only. The testicular development of all the rats was observed, and their testes were harvested in the stages of late puberty (PND 50), sexual maturity (PND 64) and adulthood (PND 130) respectively to determine the weight and histological features of the testis and examine the quality of the sperm in the epididymal cauda of the PND 130 rats.

RESULTSThe testis descent in the C, Da, Db, Dc and Dd groups occurred on PND 26.17 +/- 1.94, 26.83 +/- 1.47, 28.68 +/- 1.03, 33.50 +/- 1.87 and 41.50 +/- 2.74 respectively, significantly delayed in the Db, Dc and Dd groups compared with the C group (P < 0.05 or P < 0.01). On PND 50, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.38 +/- 0.01) g, (1.38 +/- 0.12) g, (1.30 +/- 0.14) g, (0.86 +/- 0.18) g and (0.73 +/- 0.27) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.01). Compared with the C group, there was a slight decrease in the number of the cells in the epithelia of a few seminiferous tubules in the Db group on PND 50, maldevelopment of seminiferous tubules, reduced cell number in seminiferous epithelia, blocked spermatogenesis and aplasia of Leydig cells in the Dc and Dd groups in a dose-dependent manner. On PND 64, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.60 +/- 0. 06) g, (1.62 +/- 0.11) g, (1.58 +/- 0.08) g, (1.47 +/- 0.10) g and (0.99 +/- 0.37) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.05 or P < 0.01), and the histological alteration of the testis in the Dc and Dd groups was similar to or less than that on PND 50. On PND 130, no statistic difference was observed either in unilateral testis weight or in the histological features of the testis between any experimental group and the control (P > 0.05). The sperm concentration in the epididymal cauda in the C, Da, Db, Dc and Dd groups were (73.00 +/- 16.90) x 10(6)/ml, (68.00 +/- 19.67) x 10(6)/ml, (68.67 +/- 12.15) x 10(6)/ml, (35.17 +/- 15.64) x 10(6)/ml and (19.13 +/- 5.17) x 10(6)/ml, significantly lower in the Dc and Dd groups than in the C group (P < 0.01). There was a significant decrease in sperm motility in the Dd group (P < 0.01), the percentage of grade a sperm in the Db, Dc and Dd groups (P < 0.05) and the percentage of grade b sperm in the Dd group (P < 0.01).

CONCLUSIONPrepubertal exposure to low dose of DES (0.01 microg/[kg x d] x 14 d) does not significantly affect the testicular development and function of SD rats, while high dose (1.0-10.0 microg/[kg x d] x 14 d) has significant short- (PND 50 and 64) or long-term (PND 130) toxic effect, which increases with dose and decreases with age. The mechanism of the toxic effect involves the insults to the development and function of Leydig and Sertoli cells.

Animals ; Carcinogens ; toxicity ; Diethylstilbestrol ; toxicity ; Dose-Response Relationship, Drug ; Male ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sexual Maturation ; drug effects ; Testis ; drug effects ; growth & development ; physiology ; Time Factors