AIM To investigate the preventive effects of herbal pair,Scutellariae Radix and Coptidis Rhizoma (SC),on Alzheimer's disease (AD),and its mechanism of action.METHODS Dementia mice induced by 8-week s.i.d subcutaneous injection of D-galactose (100 mg/kg),were simultaneously given respective,intragastric administration of SC crude drug at doses of 5,10,20 g/kg,or piracetam support at 0.75 g/kg,and isometrical distilled water was applied to the mice of normal control group.The mice had their learning and memory abilities checked by Morris water maze at intervals of four weeks and eight weeks since the start of the trial,and their blood and brain tissue biochemical indices measured at the end of the test.RESULTS Significantly shortened latent period in place navigation test and the time of enter into the original platform in the space exploration test were observed in the mice treated with 4-week D-galactose and SC (P ＜0.05 或 P ＜0.01).The 8-week intervention demonstrated SC capacity in the significant promotion of T-SOD activity,decreased blood MDA levels (P ＜ 0.01)and the brain AchE levels,and increased brain GSH-Px activity (P ＜ 0.01).CONCLUSION SC increases the concentration of acetylcholine in brain tissue and protects the central nervous tissue under oxidative stress,highlighting its therapeutic effect on AD.

OBJECTIVETo study the characteristics of cell cycle and proliferation of CD34+ hematopoietic stem cells in patients with myelodysplastic syndromes (MDS).

METHODSPropidium iodide staining was used to examine cell cycle parameters (G(0)/G(1), S and G(2)/M) of bone marrow mononuclear cells (BMMNCs) while immunofluorescent double staining and FACS techniques were used to measure Ki67 expression in BM CD34+ cells from normal control, patients with MDS, acute myeloid leukemia preceded by MDS (MDS-AML) and primary AML.

RESULTSThere was a statistical up-tendency in G(0)/G(1) phase proportion of BMMNCs whereas a statistical down-tendency in S and G(2)/M phase proportions among normal control, MDS and primary AML. Compared to primary AML, MDS-AML had significantly higher ratios of S (P < 0.05), G(2)/M (P < 0.05) and S + G(2)/M (P < 0.05) phase cells while lower ratio of G(0)/G(1) phase cells (P < 0.05). The proportion of CD34+Ki67+ cells in MDS patients was significantly higher than that in normal control (P = 0.004). So were the percentages of CD34+Ki67+ cells in low-risk [(0.54 +/- 0.49)%, P < 0.05] and high-risk MDS patients [(1.69 +/- 1.66)%, P = 0.022]. Furthermore, there was statistical difference between low-risk and high-risk MDS (P < 0.05). Compared to normal control and primary AML, MDS-patients had the highest proportion of CD34+Ki67+ cells [(16.75 +/- 13.58)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS patients [(48.50 +/- 20.49)%] was significantly higher than that in normal control [(27.71 +/- 16.04)%, P < 0.01]. So were the low-risk [(51.85 +/- 21.80)%, P = 0.002] and high-risk MDS [(43.93 +/- 18.57)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS-AML patients [(60.92 +/- 30.12)%] was the highest, and was statistically higher than that in both normal control (P < 0.01) and primary AML patients [(17.01 +/- 15.93)%, P < 0.001]. The proportion of CD34+Ki67+ cells in Ki67+ cells in MDS patients [(4.91 +/- 4.68)%, P < 0.01] was significantly higher than that [(2.43 +/- 2.37)%] in normal controls. In the low-risk MDS group it was (4.11 +/- 3.94)%, (P > 0.05) and in high-risk MDS group it was (5.76 +/- 5.38)%, (P < 0.05).

CONCLUSIONHigh proportion of G(0)/G(1) cells and G(1) phase arrest occurred in MDS. High proliferation capacity of MDS clone, especially that derived from CD34+ cells, might play an important role in the clonal expansion, diseases deterioration and worse prognosis of MDS.

Acute Disease ; Adolescent ; Adult ; Aged ; Antigens, CD34 ; blood ; Bone Marrow Cells ; metabolism ; pathology ; Cell Cycle ; Cell Proliferation ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Ki-67 Antigen ; blood ; Leukemia, Myeloid ; blood ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; Young Adult

BACKGROUNDMyelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).

METHODSLeukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.

RESULTSDuring the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1 - 23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83 +/- 24.50)%], CD13 [(36.38 +/- 33.84)%], monocytic antigen CD14 [(38.50 +/- 24.60)%], and stem cell marker CD34 [(34.67 +/- 30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1 - 28) months, were found in patients with MDS-AML treated by induction chemotherapy.

CONCLUSIONSMDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.

Adolescent ; Adult ; Aged ; Chromosome Aberrations ; Female ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; etiology ; genetics ; immunology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; complications ; genetics ; immunology ; Prognosis

OBJECTIVETo investigate micro-metastasis in mediastinal lymph nodes (mLN) of patients with clinical stage I approximately II lung cancer and its clinical significance.

METHODSA total of 181 mLN from 32 lung cancer patients in clinical stage I approximately II were collected during operation and their frozen sections at two different levels were examined immunohistochemically (IHC) with an anti-epithelial cell monoclonal antibody Ber-Ep4. Routine HE staining was done for comparison. The results were processed by Chi-square tests in SPSS 10.0 soft ware.

RESULTSFifteen of the 32 patients (46.9%) were found to have micro-metastasis in 21 of 181 mLN (11.6%) examined by immunohistochemical staining though routine histopathological examinations were negative. Of those 15 cases, micro-metastasis was detected in 9 only by IHC and in 6 both by IHC and HE stainings. The positive rate of micro-metastasis in N0, N1, and N2 stratified by routine pathology was 36.8% (7/19), 33.3% (2/6) and 85.7% (6/7), respectively (N0 vs N2, P < 0.05). When stratified according to clinical staging (cTNM), pathological staging (pTNM) and pathological staging on the basis of IHC (iTNM), the frequencies of N2 cases were 0, 18.8% and 46.9%, respectively (differences among the three groups: P < 0.01). Nine cases reported as N0(7) and N1(2) by routine histopathological examination were found to have micro-metastasis in mLN by IHC staining, therefore they were actually N2 cases.

CONCLUSIONIHC staining with a monoclonal antibody specific for epithelial cells (Ber-Ep4) is more sensitive in the detection of mediastinal micro-metastais than routine HE staining. Underestimation of the extent of mLN metastasis by cTNM and/or pTNM stagings frequently exists in patients with clinically early lung cancer.

Adenocarcinoma ; pathology ; secondary ; Adult ; Aged ; Antibodies, Monoclonal ; Carcinoma, Squamous Cell ; pathology ; secondary ; Female ; Humans ; Lung Neoplasms ; pathology ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mediastinum ; Middle Aged ; Neoplasm Staging

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*