Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Influenza surveillance among children in Songjiang District of Shanghai, 2014-2018 / 上海预防医学

Objective To investigate the epidemiological characteristics of influenza in Songjiang District, Shanghai during 2014-2018, and to provide scientific evidence for the prevention of influenza. Methods We collected the data including influenza-like illness(ILI)report, etiological examination and influenza outbreak in Songjiang, and further characterized the epidemic of influenza using descriptive statistics. Results Data from the sentinel hospital-based surveillance system showed two peaks of influenza incidence in winter and summer in Songjiang, in which the winter peak was more significant. The largest proportion of ILI was the age group 0-4 years(57.90%). The proportion of being positive for influenza nucleic acid was 18.44%. All principal types of influenza were prevalent in Songjiang with a certain pattern of alternative circulation, in which influenza B virus accounted for 41.18% among all the types, followed by seasonal H3(36.95%)and H1N1(21.98%). A total of 650 influenza strains were isolated. The total proportion of isolation was 67.08%, which fluctuated by year with a peak of 79.37% in 2016. Of all the 27 outbreaks of influenza, 88.89% of them were identified in primary and middle schools and 70.37% occurred in December. Conclusion Different subtypes of influenza viruses were prevalent alternatively in Songjiang during 2014-2018. The etiological results and influenza outbreaks are generally in consistent with ILI report. It warrants necessary prevention in primary and middle schools in epidemic seasons of influenza.

Retrospective analysis of diabetic hyperosmolar hyperglycemia complicated with rhabdomyolysis / 中国基层医药

Objective@#To investigate the clinical characteristics and treatment strategies of diabetic hyperosmolar hyperglycemia (HHS) with rhabdomyolysis (RM).@*Methods@#The clinical data of 40 patients with HHS treated in the General Hospital of Shenyang Military Command from November 2013 to November 2017 were retrospectively analyzed.According to the serum levels of creatine phosphokinase and myoglobin, they were divided into RM group (12 cases) and non-RM group (28 cases). The clinical characteristics and treatment results of the two groups were compared.@*Results@#There were 12 cases in the RM group, 6 cases were diagnosed RM at the time of consultation, and 6 cases developed RM during the course of treatment.Compared with the non-RM group, RM group had lower systolic pressure[(98.3±17.8)mmHg vs.(128.0±18.1)mmHg, t=4.823, P=0.000], higher blood glucose level[(44.4±14.0)mmol/L vs.(32.6±8.1)mmol/L, t=2.717, P=0.016], and more acidosis, mainly manifested by lower pH[(7.16±0.15)vs.(7.32±0.13), t=3.355, P=0.002], lower bicarbonate[(12.92±5.23)mmol/L vs.(19.07±6.80)mmol/L, t=2.792, P=0.008], higher blood D-3 hydroxybutyric acid [(5.84±2.98)mmol/L vs.(2.55±2.13)mmol/L, t=4.012, P=0.000], and renal function was worse[creatinine (257.1±149.8)μmol/L vs.(148.1±85.3)μmol/L, t=2.925, P=0.006]. Individualized rehydration and low dose insulin were given to control blood sugar, and increasing blood pressure, kidney protection, correction of electrolyte disturbance, anti-infection and inhibition of gland secretion were given to the complications.Hydration and alkalization were given to 7 cases of RM, and continuous renal replacement therapy (CRRT) was given to 5 cases.In 10 cases of HHS with RM, creatine kinase decreased, renal function recovered, and 2 patients died.@*Conclusion@#It is very important to improve the understanding of RM in HHS patients, routinely monitor the dynamic changes of muscle enzymes, make a good early diagnosis and prevention of RM.Urine hydration and alkalization should be given in time after RM occurs, and CRRT treatment as early as possible can improve the survival rate of diabetic patients.

NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tissue plasminogen activator-induced haemorrhagic transformation after cerebral ischaemia / 中国药理学与毒理学杂志

OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.

In Vitro Identification and Characteristics of CD34Leukemia Stem Cell in t(8;21) Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To preliminarily identify the existence of CD34leukemia stem cell (LSC) in t(8;21) acute myeloid leukemia (AML) by in vitro test.</p><p><b>METHODS</b>Bone marrow samples collected from newly diagnosed t(8;21) AML patients were tested. LinCD34CD38(abbreviation, CD34CD38), LinCD34CD38(abbreviation, CD34CD38) and LinCD34CD38CD45SSC(abbreviation, CD34"LSC") cell fractions were gated by flow cytometry after staining with fluorescent antibodies. Cells in Gphase were identified through Hoechst 33342 and pyronin Y staining. Aldefluor reagent was used to test aldehyde dehydrogenase (ALDH) activity. The above-mentioned 3 cell fractions were sorted, and mRNA levels of AML1-ETO and WT1 were measured by real-time quantitative PCR.</p><p><b>RESULTS</b>The 3 tested samples displayed the same tendency in ratio of the cells in Gphase: CD34"LSC">CD34CD38>CD34CD38. The paired t-test of 53 patients showed that frequency of ALDHcells of both CD34CD38and CD34"LSC" cell fractions was significantly higher than that of CD34CD38(P<0.01), furthermore, the ALDHcell frequency was significantly higher in CD34"LSC" than that in CD34CD38(P<0.01). AML1-ETO mRNA levels of cells sorted from 3 patients were similar among the 3 cell fractions within each patient, whereas WT1 mRNA levels were significantly higher in CD34"LSC" than that in other 2 cell fractions.</p><p><b>CONCLUSION</b>CD34LSC may exist in t(8;21) AML, and may be more primitive than CD34LSC. These results promote the necessity to perform in vivo xenogeneic transplantation mice.</p>

Genetic Analysis of A Case of Congenital Dysfibrinogenemia Caused by Arg16His Mutation in Exon 2 of FGA / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the phenotype and genotype of a family with congenital dysfibrinogenemia.</p><p><b>METHODS</b>Assays of coagulation, including activated partial thromboplastin time(APTT), pro-thrombin time(PT)and thrombin time(TT) were carried out with Sysmex CA-7000 in the proband and his family members. The quality and quantity of fibrinogen in plasma were determined by Clauss and electrophoresis, respectively. Fibrinogen and inconstituent were analyzed by Native-PAGE. All exon and exon intron boundaries of fibringen genes were analyzed by direct sequencing.</p><p><b>RESULTS</b>The proband had normal APTT, but prolonged PT and TT. The activity of fibrinogen in plasma was decreased while its quantity was normal. These abnormalities were also found in his sisters and daughter, while his wife was normal. Genetic analysis revealed heterozygous G1233A in the exon 2 of FGA which resulted in Arg16His missense mutation.</p><p><b>CONCLUSION</b>Inherited dysfibrinogenemia is caused by Arg16His mutation in exon 2 of FGA.</p>

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats / 亚洲男科学杂志(英文版)

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

Molecular Mechanism for Regulation of INS-1 Rat Insulinoma Cell Proliferation by Orexin-A / 中国医科大学学报

Objective To investigate the interference effects of orexin A on cell proliferation of the insulin?secreting beta?cell line(INS?1 cells) through the orexin receptor 1(OX1R)and the AKT/PKB signaling pathway. Methods INS?1 cells were exposed to different concentrations of orexin A in vitro,and treated with OX1R antagonist(SB334867),PI3K antagonist(wortmannin),or AKT antagonist(PF?04691502). The INS?1 cell proliferation and apoptosis,insulin secretion,OX1R protein activity and AKT phosphorylation level were determined. Results Orexin A(10-10 to 10-6 mol/L)stimulated the proliferation and activation of INS?1 cells,prevented apoptpsis,and increased insulin secretion. Additionally,AKT phosphorylation was stimulated by orexin A(10-10 to 10-6 mol/L). The OX1R antagonist SB334867(10-6 mol/L),the PI3K antagonist wortmannin (10-8 mol/L)and the AKT antagonist PF?04691502(10-6 mol/L)weakened the effects of orexin A. Conclusion Orexin A activated the AKT sig?naling pathway through the mediation of orexin A?OX1R,and promoted cell proliferation in INS?1 cells.

Expression of CSN Complex in ATRA-induced APL Cell Differentiation and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of CSN complex (COP9 signal some subunits) in the patients with acute promyelocytic leukemia (APL) and its significance in the ATRA-induced APL differentiation.</p><p><b>METHODS</b>Using the NB4 cells as a model, morphologic observation and myeloid differentiation marker CD11b detection were used to monitor ATRA-induced APL differentiation, the expression of CSN complex in cell differentiation was detected by Western blot and reverse transcription real time fluorescent quantitative PCR (RT-qPCR) method. RT-qPCR was also used to detect the relative expression level of COP9 signalosome subunits in the APL patients and remission after treatment.</p><p><b>RESULTS</b>ATRA could obviously enhance CD11b expression; the cell morphology showed obvious differentiation characteristics. During the differentiation, the expression of COP9 signalosome subunits was down-regulated by ATRA. Meanwhile, the CSN expression level in newly diagnosed APL patients was much higher than that in controls (non-leukemia) (P < 0.05). The level of CSN expression was obviously down-regulated when APL patients achieved complete remission.</p><p><b>CONCLUSION</b>The high CSN expression level in APL patients can be down-regulated by ATRA. CSN complex may have a significant effect on the pathogenesis and therapy of APL.</p>

CD34(+)CD19(+) cells with CD123 overexpression are a novel prognostic marker in Ph chromosome-positive acute lymphoblastic leukemia / 中国实验血液学杂志

This study was aimed to investigate the characteristics of CD123 expression on CD34(+)CD19(+) cells and its prognostic significance as a novel MRD biomarker in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) patients. Consecutive newly diagnosed Ph(+)ALL patients (n = 49) in Peking University Institute of Hematology from January 2010 to April 2012 were prospectively enrolled in this study. At diagnosis and different time points during treatment, CD123 expression on CD34(+)CD19(+) cells was examined by multiparameter flow cytometry(MFC). More than 10 CD34(+)CD19(+) cells with CD123 overexpression in bone marrow samples after complete remission were defined as FCM positive (FCM(+)). The BCR-ABL1[STBZ] transcript was detected by real-time quantitative polymerase chain reaction (RQ-PCR) concurrently. The results showed that mean fluorescence intensity of CD123 on CD34(+)CD19(+) cells in newly diagnosed Ph(+)ALL and relapsed Ph(+)ALL patients was significantly higher than that of normal B-cell progenitors [8.52(3.71-32.35) vs 8.93(4.79-29.74) vs 1.31(0.21-1.75), P < 0.05]. In addition, ratio of the CD34(+)CD19(+) cells with CD123 overexpression in newly diagnosed Ph(+)ALL and relapsed Ph(+)ALL patients were significantly higher than that of normal B-cell progenitors [84.63% (55.07%-99.96%) vs 84.50% (57.68%-99.80%) vs 0.99% (0.45%- 1.83%), P < 0.05]. CD34(+)CD19(+) cells with CD123 overexpression were detected in all newly diagnosed and relapsed Ph(+)ALL patients. A good correlation was found between the MRD results of CD34(+)CD19(+) cells with CD123 overexpression detected by MFC and that detected by RQ-PCR (n = 360 pairs, Spearman r = 0.90, P < 0.0001). Among 13 cases relapsed during follow up, 11 cases of them were detected by FCM(+) at a median time of 60 (30-73) days before the recurrence. It is concluded that as a complementary to RQ-PCR, detection of the CD34(+)CD19(+) cells with CD123 overexpression by MFC promises to be an efficient tool for MRD assessment and risk stratification in human Ph(+)ALL.

Early monitoring drug-resistance of patients with BCR/ABL(+) ALL by DCDF-FISH / 中国实验血液学杂志

This study was aimed to investigate the application value of the dual color dual fusion fluorescence in situ hybridization (DCDF-FISH) in BCR/ABL (+) acute lymphoblastic leukemia patients with complex chromosomal translocation. The clinical presentations of a patient with ALL were monitored regularly by bone marrow cell morphology test, chromosome analysis, flow cytometry and DCDF-FISH technique, and the reaction of patients to treatment and disease progression were dynamically observed by DCDF-FISH. The results indicated that the patient showed the typical presentation of B lineage acute lymphoblastic leukemia (B-ALL) with expression of CD10, CD19 and CD34; the chromosome analysis showed 46,XY, i(8), ider(9)t (9; 22) [23]/47, idem, +der(22) t (9;22) [7] karyotype in the bone marrow cells, FISH showed that 83% cells contained BCR/ABL fusion gene in the patient's bone marrow, among which 5% cells showed 1R1G2F signalling model, 14% cells showed 1R1G3F, and 64% cells showed 1R1G4F. The patient got complete remission when the imatinib chemotherapy combined with VTLP was carried out, and the tumor cells decreased to 19%, but the cells with 1R1G2F signal model increased to 18%. The 1R1G2F cell signal model increased up to 38% when patient relapsed. The patient died of the drug-resistance. It is concluded that the BCR/ABL (+) leukemia patient with complex translocation has multiple tumor cell subsets, and the responses of different cell subsets to the treatment are different, therefore the response to therapy and drug resistance of patient can be monitored early by the signal model of DCDF-FISH and the observation of dynamical changes of different cell subset.

Establishment of mouse model with humanized Philadelphia chromosome-positive acute lymphoblastic leukemia / 中国实验血液学杂志

The purpose of this study was to establish a novel xenotransplant mouse model with human Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). The bone marrow mononuclear cells (BMMNC) were separated from newly diagnosed Ph(+)ALL patients, and injected into 2.1 Gy of (60)Co irradiated and anti-CD122-conditioned NOD/SCID mice through intra femoral injection. Human hematopoietic chimerism in bone marrow and spleen of the recipients was detected by flow cytometry. Morphological analysis of murine marrow cells were performed using May-Giemsa staining. BCR/ABL1 level was detected by RQ-PCR and FISH assays. Furthermore, leukemia infiltration in the organs was evaluated by hematoxylin-eosin staining, immunohistochemical staining with anti-human CD19 and anti-human CD34 antibodies. The results indicated that the unsorted BMMNC from Ph(+)ALL patients were able to repopulate human Ph(+)ALL in vivo. The percentages of human CD45(+)CD19(+) cells in bone marrow, and spleen of the recipient mice were 87.2% ± 10.1% and 79.9% ± 9.2%, respectively. Furthermore, the engrafted cells possessed same morphology, phenotypic and cytogenetic characteristics as cells from the original Ph(+)ALL patients. Compatible with the clinical features, transplanted Ph(+)ALL cells infiltrated into the brain, liver, and kidney of the recipients. It is concluded that the human-mouse xenotransplant established model using intra femoral injection of an anti-CD122-conditioned NOD/SCID repopulation may provide a promising system to study the biology of human Ph(+)ALL in vivo.

Analysis of risk factors for secondary cytopenia after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence and risk factors for secondary cytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of a total of 260 patients received allo-HSCT between Jan 1, 2006 to Jan 1, 2008 were retrospectively analyzed for the incidence and risk factors of secondary cytopenia. According to the hematopoietic reconstitution after transplantation, the patients were divided into (1) secondary neutropenia group; (2) secondary thrombocytopenia group and (3)secondary poor graft function group.</p><p><b>RESULTS</b>During the 100 days after allo-HSCT, the secondary neutropenia (38.8% vs 18.0%, P=0.0005) or secondary thrombocytopenia (25% vs 12%, P=0.01) occurred in haploidentical HSCT (haplo-HSCT) patients were more often than that in HLA-matched group. Poor graft function showed no significant difference between the above two groups (5.6% vs 2.0%, P=0.21). Multivariate analyses revealed that cytomegalovirus (CMV) infection significantly increased the risk of secondary neutropenia. GVHD and CMV infection were independent risk factors for secondary thrombocytopenia. Meanwhile, CMV infection was an independent risk factor for secondary poor graft function.</p><p><b>CONCLUSION</b>Secondary cytopenia remains a serious complication following allo-HSCT, especially in haplo-HSCT. Higher occurrence of GVHD and CMV infection may lead to higher incidence of secondary cytopenia in haplo-HSCT.</p>

Effect of curcumin combined with ATRA on differentiation of ATRA-resistant acute promyelocytic leukemia cells / 中国实验血液学杂志

In order to investigate the effect of curcumin combined with all-trans retinoid acid (ATRA) on differentiation of ATRA-resistant acute promyelocytic leukemia (APL) cells and its molecular mechanism, the NB4-R1, an ATRA-resistant APL cells, was used as a model, counting of NB4-R1 and cell morphologic observation were performed, the effect of curcumin alone or combined with ATRA on proliferation, differentiation of NB4-R1 cells was detected by flow cytometry (FCM), the change of AKT phosphorylation in cell differentiation was detected by Western blot. The results showed that ATRA had no influence on NB4-R1 cell proliferation, but enhanced the inhibitory effect of curcumin on NB4-R1 cell growth; the curcumin or ATRA alone did not affect NB4-R1 differentiation; curcumin combined with ATRA could obviously induce CD11b expression; the cell morphology showed obvious differentiation characteristics. ATRA could promote phosphorylation of AKT in NB4 cells at short time, but not had effect on phosphorylation of AKT in NB4-R1 cells; the curcumin could enhance the phosphorylation of AKT in NB4-1R cells, the curcumin combined with ATRA could further enhance the phosphorylation of AKT. It is concluded that PI3K/AKT pathway inactivation may be one of the factors of drug resistance in APL and curcumin promotes differentiation of NB4-R1 through activating PI3K/AKT pathway.

A new method for rating dyspnea during exercise in patients with chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The Borg scale is most commonly used to measure dyspnea in China. However, many patients that find it is difficult to distinguish the labeled numbers corresponding to different dyspnea scores. We developed a new method to rate dyspnea, which we call the count scale (CS). It includes the count scale number (CSN) and count scale time (CST). The aims of the present study were to determine the reproducibility and sensitivity of the CS during exercise in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Fourteen male patients with COPD (aged 58.00 ± 7.72 years) participated in this study. A progressive incremental exercise and a 6-minute constant work exercise test were performed every 2 to 3 days for a total of 3 times. The CS results were evaluated at rest and at 30% and 70% of maximal workload (Wmax) and Wmax. The Borg scales were obtained during exercise.</p><p><b>RESULTS</b>No significant differences occurred across the three trials during exercise for the CS and Borg scores. The CSN and CST were more varied at Wmax (coefficient of variation (CV) = (22.28 ± 16.96)% for CSN, CV = (23.08 ± 19.11)% for CST) compared to 30% of Wmax (CV = (11.92 ± 8.78)% for CSN, CV = (11.16 ± 9.96)% for CST) and 70% of Wmax (CV = (9.08 ± 7.09)% for CSN, CV = (12.19 ± 12.32)% for CST). Dyspnea ratings with either CSN or CST tended to decrease at the higher workload compared to the lower workload. CSN and CST scores were highly correlated (r = 0.861, P < 0.001). CSN was negatively correlated with Borg scores (r = -0.363, P = 0.001). Similar results were obtained for the relationship between CST and Borg scores (r = -0.345, P = 0.003).</p><p><b>CONCLUSION</b>We concluded that the CS is simple and reproducible when measuring dyspnea during exercise in patients with COPD.</p>

Effects of the mobilization with AMD3100, granulocyte-colony-stimulating factor (G-CSF) alone and in combination on the immunological function of the lymphocytes in mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the impact of the mobilization with the antagonist of the stromal cell-derived factor receptor CXCR4 (AMD3100) (plerixafor), granulocyte-colony-stimulating factor (G-CSF) alone and in combination on the proliferation and cytotoxic functions of the murine splenic lymphocytes.</p><p><b>METHODS</b>C57BL/6(H-2(b)) mice, as donors, were mobilized by, AMD3100, G-CSF alone or in combination (n = 10 mice in each group), and phosphate buffered saline (PBS). Then, the proliferation capacity of murine lymphocytes either in response to the phytohemagglutinin (PHA) stimulation or the mixed lymphocytes reaction (MLR) with allo-lymphocytes from the BALB/C(H-2(d)) mice were detected by CCK-8 method. The cytotoxic capacity of murine lymphocytes on Yac-1 tumor cells was examined by LDH assay.</p><p><b>RESULTS</b>The proliferation capacity and the responsiveness to alloantigen of the lymphocytes derived from the mice spleen mobilized by AMD3100, G-CSF alone or in combination were significantly lower than those by PBS control (P < 0.05), and those combination of AMD 3100 and G-CSF group were significantly lower than in other groups(P < 0.05). At the effector-target ration of 40:1, the cytotoxic capacity of murine lymphocytes in above mobilization groups was lower than in control group, but no statistically significant difference (P > 0.05).</p><p><b>CONCLUSION</b>Both the proliferation capacity and the responsiveness to alloantigen of the murine lymphocytes decreases significantly after the mobilization with AMD3100, G-CSF alone or in combination, whereas no significant alternations are demonstrated on the cytotoxic capacity of murine lymphocytes. Further studies are needed to clarify the underlying mechanisms.</p>

Establishment of human acute B-lymphoblastic leukemia NOD/SCID/IL2 receptor γ chain(null) neonatal mouse xenotransplant model / 中国实验血液学杂志

In order to study human acute B-lymphoblastic leukemia (B-ALL) in vivo, a novel xenotransplant model was established by using neonatal NOD/SCID/IL2 receptor γ chain(null) mouse. The CD34(+)CD19(+) bone marrow (BM) cells were sorted from the CD3(-)CD4(-)CD8(-) fraction of B-ALL patients by fluorescence-activated cell sorting (FACS), and injected into 100 cGy irradiated neonatal NOD/SCID/IL2rγ(null) mice through facial vein. The engraftment and proliferation of human B-ALL cells were monitored by the presence of human CD45(+)CD19(+) cells in peripheral blood (PB). Human hematopoietic chimerism in PB, BM and spleen of the recipients was examined by multiparameter flow cytometry. Morphological analyses of FACS-sorted murine marrow cells were performed by using May-Grunwald-Giemsa staining. Furthermore, leukemia cell infiltration in the organs was evaluated by hematoxylin-eosin staining. The results indicated that the sorted CD34(+)CD19(+) cells were able to initiate human B-ALL in vivo. The percentages of human CD45(+)CD19(+) cells in PB, BM and spleen of the recipient mice were (83.36 ± 10.05)%, (93.88 ± 5.05)% and (88.31 ± 5.01)%, respectively. Furthermore, the phenotype and morphology of the engrafted human cells were resemble to the original B-ALL cells from the patients. Similar to the clinical features, transplanted leukemic cells infiltrated into the organs, such as liver, lung, kidney and brain in the recipients. It is concluded that neonatal NOD/SCID/IL2rγ(null) mice can support efficient engraftment of the sorted CD34(+)CD19(+) cells from human B-ALL for a long-term period. Human-mouse xenotransplant model using neonatal NOD/SCID/IL2rγ(null) mouse may provide an important system to study the biology of human B-ALL in vivo.

Effect of Chinese herbs for nourishing shen-yin and removing xiang-fire on estrogen receptor expression in reproductive organ of rats contaminated with environmental endocrine disruptor / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chinese herbs for nourishing Shen-yin and removing Xiang-fire (NYRF) on estrogen receptor (ER) expression in uterus and ovary of rats contaminated with nonylphenol (NP) or its bisphenol A (BPA) mixture, for exploring the action mechanism of NYRF in antagonizing the estrogen-mimetic activity of environmental endocrine disruptors (EEDs).</p><p><b>METHODS</b>EEDs contaminated female SD rats, 3-week old, were divided into two groups, the treated group fed with NYRF and the control group with corn oil during the same period of contaminating for 15 days. The wet weight (WW) and organ coefficient (OC) of uterus in rats, as well as the ER protein and mRNA expressions in rat's uterus and ovary were detected and compared.</p><p><b>RESULTS</b>As compared with normal range, WW and OC increased significantly in the contaminated rats of the control group, with significantly down-regulated ER protein expression in uterus, and expressions of ER alpha and ER beta gene and protein in ovary (P<0.05). While in the treated group, the above-mentioned abnormalities of various indicators were markedly reversed to a certain extent (P<0.05).</p><p><b>CONCLUSION</b>EEDs show estrogenic-mimetic action on productive organs, which could be antagonized by NYRF, resulting in the down-regulated mRNA and protein expressions of ER in reproductive organs, so as to reduce the sensibility of reproductive organs to EEDs, which is probably one of the acting mechanisms of NYRF.</p>

Apoptosis of retinoic acid resistant NB4-R1 cells induced with curcumin and its mechanism / 中国实验血液学杂志

This study was purposed to explore the inhibitory effect of Curcumin on growth of retinoic acid-resistant acute promyelocytic leukemia (APL) cells and its mechanism. The NB4-R1, an APL cell line resistant to retinoic acid, was used as a model. The growth level of NB4-R1 was detected by MTT assay, the morphologic features of cells were observed by light microscopy, the mitochondrial transmembrane potential was determined by flow cytometry, the expressions of apoptosis-related proteins procaspase 3, caspase 3, PARP and BCL-XL were measured by Western blot. The results indicated that the sensitivity of NB4-R1 to Curcumin was consistent with NB4 though NB4-R1 was resistant to retinoic acid, Curcumin displayed inhibitory effect on growth of NB4-R1 in time-and concentration-dependent manners. The morphologic observation showed existence of apoptotic bodies in NB4-R1 cells treated with 20 micromol/L of Curcumin. The flow cytometry indicated that the mitochondrial transmembrane potential in NB4-R1 cells treated with 20 micromol/L of Curcumin obviously decreased. The Western blot detection revealed that expressions of pro-caspase 3 and BCL-XL were down-regulated, expressions of caspase 3 and sheared PAPP were up-regulated in NB4-R1 cells treated with 20 micromol/L of Curcumin. It is concluded that the Curcumin can inhibit the growth and induce the apoptosis of NB4-R1.

Transfusion of mesenchymal stem cells combined with haploidentical HSCT improves hematopoietic microenvironment / 中国实验血液学杂志

The aim of this study was to investigate the role of mesenchymal stem cells in the hematopoietic reconstitution of patients who had received haploidentical allogeneic hematopoietic stem cell transplantation (hi-allo-HSCT). 15 patients who underwent treatment with both MSCs and HSCs, were selected as study group, while 20 patients receiving only HSCT were taken as control. Bone marrow samples were obtained from iliac crest aspirates at several times after HSCT for the isolation, purification and expansion of MSCs. The confluent ratio and time were measured and compared with those of the control. The peripheral blood samples were obtained from patients, then absolute neutrophil and platelet counts were assayed. From day 4 before transplantation to day 28 after transplantation, serum was obtained every four days from patients of the two groups, and then 3 cytokines as SDF-1alpha, TPO and IL-11 were detected by ELISA. The results indicated that as compared with the control group, the ratio of primary confluent layer formation of MSCs in study group was obviously higher (27.3%) (p < 0.01), and the confluence time in culture was significantly less (p < 0.05). In the study group, the concentration of SDF-1alpha amounted to peak value (2975.19 +/- 681.56 pg/ml) on the 8th day after HSCT, which was obviously higher than that before HSCT (2403.70 +/- 522.39 pg/ml, p < 0.05), whereas in the control, the concentration of highest point of SDF-1alpha reached to peak valve (2280.60 +/- 701.25 pg/ml) on the 16th day after HSCT, which was less than that before HSCT (2701.46 +/- 483.21 pg/ml, p < 0.05). The concentration of TPO and IL-11 was higher in study group compared with the control from day 16 to 28 after HSCT (p < 0.05). It is concluded that the transfusion of MSCs combined with hi-all-HSCT may improve the injured state of the hematopoietic microenvironment in bone marrow of patients during allo-HSCT.