OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury. METHODS: A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group, CLP group and CLP + baicalein (Bai) group (n=16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate, bacterial load, and organ damage were assessed. Then each group was evaluated at 6, 12, and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats. RESULTS: Baicalein treatment significantly improved the survival of septic rats, decreased the bacterial burden, and moderated tissue damage (spleen, liver, and lung), as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3⁺CD4⁺ T cells and ratios of CD4⁺/CD8⁺ T cells in the peripheral blood and spleen (all P<0.05). Moreover, baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery (P<0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10, and the expression levels of galectin 9 were also raised in the spleen (P<0.01). CONCLUSION Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.
Animals ; CD8-Positive T-Lymphocytes ; Flavanones ; Inflammation/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Sepsis/drug therapy*

OBJECTIVE: To clarify the significance of inflammasome NLRP3 in children with immune thrombocytopenia (ITP) by detecting its changes before and after treatment. METHODS: Twenty children with ITP diagnosed and treated in Xuzhou Children's Hospital were enrolled as observation group, and 10 healthy children as control group. The mRNA levels of NLRP3, ASC, and Caspase-1 were measured by real-time quantitative PCR (RT-qPCR), the serum levels of IL-18, IL-1β, and high mobility group protein B1 (HMGB1) were detected by ELISA, and the protein level of NLRP3 was detected by Western blot. RESULTS: In newly diagnosed ITP children, the serum levels of IL-18, IL-1β and HMGB1 significantly decreased after treatment (P<0.05). After treatment, NLRP3, ASC, and Caspase-1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those before treatment (P<0.05). NLRP3 protein expression decreased significantly after treatment. CONCLUSION Expression of NLRP3 inflammasome and downstream inflammatory factors are decrease after treatment in children with ITP, which may be used as effective prognostic markers.
Child ; HMGB1 Protein ; Humans ; Inflammasomes ; Leukocytes, Mononuclear ; NLR Family, Pyrin Domain-Containing 3 Protein ; Purpura, Thrombocytopenic, Idiopathic

Pericytes, endothelial cells (EC), astrocytes and extracellular space together constitute the blood-brain barrier. Pericytes and EC participate in the various regulations of blood-brain barriers through many mechanisms to maintain the stability of neurovascular units (NVU). The injury and repair of NVU involve a lot of signal transduction at molecular levels, and angiogenesis is primarily about the generation and maturation of EC and the supporting adhesion process of pericytes. This article briefly reviewed EC-related angiogenesis signaling pathways in pericytes after NVU ischemic injury.

Objective: To establish enzalutamide-resistant human prostate cancer cell lines and screen out the lncRNA and mRNA expression profiles associated with enzalutamide resistance. METHODS: Human prostate cancer cell lines LNCAP and C4-2B were cultured with 10 μmol/L enzalutamide for 6 months in vitro for the establishment of enzalutamide-resistant subclones LNCAP-ENZA and C4-2B-ENZA. The IC50 value and enzalutamide resistance index of each cell line were examined by MTT assay, the expressions of enzalutamide-related genes FL-AR, AR-V7 and HnRNPA1 were determined by Western blot, and the lncRNA and mRNA differential expressions of C4-2B and C4-2B-ENZA were detected by high-throughout lncRNA microarray. RESULTS: Compared with LNCAP and C4-2B, the IC50 values of enzalutamide-resistant subclones LNCAP-ENZA (60.83 μmol/L) and C4-2B-ENZA (88.32 μmol/L) were increased significantly (P < 0.05) and the enzalutamide-resistance indexes of the LNCAP-ENZA and C4-2B-ENZA cells were 4.94 and 4.67, respectively. The expressions of AR-V7 and HnRNPA1 were markedly up-regulated in the LNCAP-ENZA and C4-2B-ENZA cells as compared with those in the LNCAP and C4-2B cells, but that of FL-AR showed no significant change. A total of 1 440 lncRNAs and 1 236 mRNAs were identified as differentially expressed in the C4-2B-ENZA cells. CONCLUSIONS Enzalutamide -resistant human prostate cancer cell subclones LNCAP-ENZA and C4-2B-ENZA were successfully established and enzalutamide resistance-associated lncRNA and mRNA were identified, which may provide some molecular evidence for the management of enzalutamide-resistant human prostate cancer.
Cell Line, Tumor ; drug effects ; Drug Resistance, Neoplasm ; Humans ; Male ; Phenylthiohydantoin ; analogs & derivatives ; pharmacology ; Prostatic Neoplasms ; drug therapy ; genetics ; pathology ; RNA, Long Noncoding ; metabolism ; RNA, Messenger ; metabolism ; RNA, Neoplasm ; metabolism ; Receptors, Androgen

Objective To observe treadmill exercise test (TET) characteristics in patients with myocardial bridging(MB).Methods TET results from January 2003 to December 2010 were retrospectively analyzed in 156 patients with confirmed MB diagnosis.MB patients were divided into smoking group (68 cases) and non-smoking group(88 cases).Coronary angiography results were used to analyze the relations between MB length,myocardial ischemia and exercising duration.Results ( 1 ) MB was documented on two coronary arteries in 2 patients ( 1％ ),MB was detected in single artery in 154 patients (99％),of whom 146 cases were located at left anterior descending artery,8 cases were located at right coronary artery.The degree of narrowing of MB was graded 1 ( less than 50％ ) in 16 patients ( 10％ ),grade 2 (50％ to 75％ ) in 108 patients (69％) and grade 3 (greater than 75％ ) in 32 patients (21％).The length of MB ranged between 4 to 40 mm,MB length was less than 10 mm in 40 patients( 26％ ),between 11 to 20 mm in 48 patients(31％ ),between 21 to 30 mm in 44 patients(28％ ),greater than 31 mm in 24 patients( 15％ ).(2) TET positive rate was 41％ (64/156) and the TET positive rate was significantly higher in smoking group than in non-smoking group [ 57％ (39/68) vs.28％ (25/88,P ＜ 0.01 ) ].(3) The length of MB was positively related to the ST-segment depression (r =0.723,P ＜ 0.01 )and negatively related to exercising duration ( r =- 0.828,P ＜ 0.01 ).Heart rate was positively related to the ST-segment depression ( r =0.368,P ＜ 0.01 ).Conclusions TET may serve as a good test to assess myocardial ischemia in patients with MB.The length of MB is positively related with myocardial ischemia and negatively related with exercising duration.Smoking might increase myocardial ischemic incidence in MB patients,MB patients should be advised to stop smoking.

BACKGROUNDIt is generally accepted that spleen plays a complex role in the tumor immunity, which would change in the different periods of cancer. In this study, we investigated the changes in the function of splenic macrophage (Mphi) in different stages of liver cancer induced by diethylnitrosamine (DEN) in rats. The aim was to support the characteristics of "two-way" and "phase" of spleen in tumor immunity.

METHODSThe model of pulmonary metastasis of liver cancer was established in forty male SD rats by DEN. In the 8th, 13th and 16th week, 10 rats were randomly chosen and sacrificed, and divided into cirrhosis, liver cancer and pulmonary metastasis groups depending on the pathological result, respectively. The other 10 rats were taken as control group. The Mphi was isolated by anchoring cultivation. The changes in ultrastructure, phagocytosis, cytokine secretion, antigen processing and presenting, and viability of splenic Mphi were detected by transmission electron microscopy, Vybrant(TM) Phagocytosis Assay, DQ(TM) Ovalbumin, and rat TNF-alpha ELISpot kits.

RESULTSUnder the electron microscope, the Mphi in the control group had some pseudopodium-like prominences, and mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in the cytoplasm, and phagocytized RBC. In the liver cirrhosis and liver cancer group, Mphi had more prominences, meanwhile much more mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in the cytoplasm, especially in the liver cancer group. In the pulmonary metastasis group, the Mphi was swelling, with few organelle. As compared to the control group, the function of splenic Mphi increased in cirrhosis and cancer groups, but decreased in metastasis group (phagocytosis rate: (84.7 +/- 1.9)%, (89.5 +/- 3.1)%, and (36.0 +/- 2.6)% vs (75.6 +/- 1.7)%, P < 0.05, P < 0.01; viability: (1.53 +/- 0.15)%, (1. +/- 0.14)%, and (1.12 +/- 0.29)% vs (1.48 +/- 0.17)%, P < 0.05, P < 0.01; TNF-alpha secretion: (741.0 +/- 52.9)%, (1126.2 +/- 174.5)%, and (313.8 +/- 50.8)% vs (626.6 +/- 24.6)%, P < 0.05, P < 0.01; positive cell rate of antigen processing and presenting: (24.03 +/- 1.87)%, (27.95 +/- 2.63)%, and (10.46 +/- 2.16)% vs (16.45 +/- 1.86)%, P < 0.01).

CONCLUSIONSIn the stage of cirrhosis and early cancer, the immune functions of splenic Mphi were reinforced. It may promote the non-specificity tumor immunity. On opposite, in the stage of pulmonary metastasis, the immune functions of splenic Mphi were impaired. It may lead to the decrease of tumor immunity.

Animals ; Cells, Cultured ; Diethylnitrosamine ; toxicity ; Disease Models, Animal ; Liver Cirrhosis ; immunology ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; complications ; immunology ; ultrastructure ; Lung Neoplasms ; immunology ; secondary ; ultrastructure ; Macrophages ; pathology ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Rats ; Rats, Sprague-Dawley ; Spleen ; pathology ; ultrastructure

OBJECTIVETo investigate the changes in function of splenic macrophages of hypersplenism due to portal hypertension (PH), and to provide experimental evidence for exploring the immune function of spleen in PH.

METHODSTwelve patients with hypersplenism due to PH and four patients with traumatic rupture of spleen, from September 2005 to March 2006, were enrolled into PH group and control group, respectively. Splenic M phi were isolated and purified by anchoring cultivation from all the patients, and were resuspended by RPMI-1640. Phagocytosis, cytokine secretion and antigen processing and presenting of splenic M phi were detected by Vybrant Phagocytosis Assay, the human TNF-alpha Elispot kits and DQ ovalbumin.

RESULTSCompare to the normal splenic M phi, the phagocytosis rate, antigen presentation positive cells and secretion positive cells, were all significantly increased in PH splenic M phi (86.4 +/- 7.1 vs. 61.8 +/- 4.1, 26.3 +/- 1.6 vs. 15.6 +/- 1.8, 387.0 +/- 24.3 vs. 240.3 +/- 13.0, P<0.01).

CONCLUSIONSThe phagocytosis, cytokine secretion and antigen processing and presenting of splenic M phi in PH spleen were all significantly increased, and the M phi retained at activated state. It means that the PH spleen still possessed the immune function, but these functions might be in disorder. It still needs more research to get the precious evaluation for immune function in the PH spleen.

Adult ; Antigen Presentation ; immunology ; Female ; Humans ; Hypersplenism ; etiology ; immunology ; Hypertension, Portal ; complications ; immunology ; Macrophages ; immunology ; Male ; Middle Aged ; Phagocytosis ; immunology ; Spleen ; immunology ; Tumor Necrosis Factor-alpha ; immunology

BACKGROUNDThe pathogenesis of hypersplenism and the immune function of the spleen in patients with portal hypertension (PH) remain obscure. This study aimed to evaluate the morphological changes of blood spleen barrier in spleen with hypersplenism due to PH and provide evidence for an in-depth investigation of the immune function of the spleen with hypersplenism and the mechanism of hypersplenism.

METHODSSpleen samples from 12 portal hypertensive patients and 4 patients with traumatic ruptures of spleen were examined. The samples of spleen were made into pathological sections, stained with Masson trichrome stain, Gomori stain, and CD68, CD34 immunohistochemistry, and were examined microscopically for the changes in the distribution of collagen fibers, reticular fibers, macrophages, and vascular endothelial cells. The changes in ultrastructure of macrophages and endothelial cells in marginal zone were also evaluated by transmission electron microscopy.

RESULTSAs compared to the normal spleen, the density of macrophage in the PH spleen was decreased, but the macrophages were mainly located in the marginal zone and distributed around the splenic corpuscle, with many villi and pseudopodium-like protrusion on the cell surface. The accrementition of collagen fibers was obvious around the splenic corpuscle and central artery. The increased reticulate fibers encircled the splenic corpuscle with more connection between the fibers. The vascular endothelial cells were in diffused distribution, without any regionality in PH spleen, but the vessel with enlarged lumina increased in red pulp.

CONCLUSIONSThe morphological changes of the blood spleen barrier can be one of the pathological fundaments for the abnormality of the immune function and the increased destruction of blood cells located in the spleens of patients with PH. However, this still entails clarification.

Adult ; Collagen ; analysis ; Endothelial Cells ; pathology ; ultrastructure ; Female ; Humans ; Hypertension, Portal ; immunology ; pathology ; Macrophages ; pathology ; ultrastructure ; Male ; Microscopy, Electron ; Middle Aged ; Spleen ; blood supply ; immunology ; pathology ; ultrastructure

OBJECTIVETo investigate the efficacy of the combination of gemcitabine with capecitabine in the chemotherapy for patients with relapsed or metastatic biliary tract carcinoma.

METHODSForty-one patients with unresectable relapsed or metastatic carcinoma of the biliary tract were treated from March 2000 to December 2004. The regimen consisted of intravenous administration of gemcitabine plus oral intake of capecitabine every 3 weeks for more than 2 cycles. The parameters including tumor response, clinical benefit rate,survival and safety were observed.

RESULTSThirty-six patients were valuable and 5 patients were excluded from this series due to various reasons. Eleven patients (30.1%) had a partial response and another 11 patients (30.1%) experieced stable disease with a clinical benefit rates of 61.1%. The median overall survival time and time to progression were 10 months and 6 months, respectively. The one-year survival rate was 40.0%. The adverse events including nausea, diarrhea and hand-foot syndrome, fatigue, neutropenia, thrombocytopenia were frequently observed, which were usually in grade I or II, rarely in grade III and none in grade IV (NCI-CTC).

CONCLUSIONOur results show that the regimen of gemcitabine combined with capecitabine is effective and well tolerated in patients with unresectable relapsed or metastatic carcinoma of the biliary tract.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bile Duct Neoplasms ; drug therapy ; pathology ; Bile Ducts, Intrahepatic ; Capecitabine ; Cholangiocarcinoma ; drug therapy ; pathology ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Diarrhea ; chemically induced ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neutropenia ; chemically induced ; Remission Induction ; Survival Rate