Sulfur fertilization integrated with soil redox conditions reduces Cd accumulation in rice through microbial induced Cd immobilization.

Sulfate and water management can be respectively applied to control Cd accumulation in rice, but the interaction mechanisms remain unclear. Three water management coupled with five sulfate application concentrations were employed to investigate rice Cd uptake. Results showed there was a significant interaction between sulfate application and soil redox state, and the highest sulfate treatments reduced rice grain Cd by 63.2, 53.5, and 59.4% under the flooding, flooding-moist alternate (FM), and moist irrigation (M) conditions, respectively. It could be explained by the reduction in rhizosphere soil available Cd and lower transport coefficient from root to aboveground. The Desulfovibrio was demonstrated to participate in CdS precipitation, and its abundance was promoted by sulfate especially under flooding. Additionaly, sulfate application facilitated Cd bounded to FeMn oxides, as rhizosphere soil pH raising under flooding. Under FM and M treatments, sulfate application reduced the abundance of Fe-reducing bacteria Geobacter, and correspondingly reduced Fe and Cd availability in rhizosphere soil. Summarily, Cd transfer from soil to rice can be reduced by applying sulfate fertilizer; which is favored by higher soil moisture because of the higher abundance of Desulfovibrio and lower abundance of Geobacter.

Downregulation of ERRα inhibits angiogenesis in human umbilical vein endothelial cells through regulating VEGF production and PI3K/Akt/STAT3 signaling pathway.

The human estrogen related receptor α (ERRα) is a pivotal regulator involved in energy homeostasis and mitochondrial biogenesis. It has been demonstrated that activation of ERRα in various breast cancer cells results in a significant increase of vascular endothelial growth factor (VEGF) mRNA and protein secretion. However, little is known about the relationship between ERRα and angiogenesis. Thus, the present study is aimed to investigate the effects and mechanism of ERRα suppression on the angiogenesis in human umbilical vein endothelial cells (HUVECs). Here we show that ERRα suppression powerfully inhibits proliferation, migration and capillary-like structures formation of HUVECs. Importantly, we demonstrate that these inhibitory effects are associated with the significantly reduced expression and production of VEGF. Results from further experiments using western blot and luciferase reporter assay exhibit that ERRα suppression inhibits hypoxia-inducible factor 1α (HIF-1α) expression, and phosphorylation of protein kinase B (Akt) and signal transducer and activator of transcription (STAT3) which up-regulated VEGF expression. In summary, we show that ERRα suppression inhibits angiogenesis in HUVECs and deserves further studies for application of rationale therapeutic target for patient with diseases related with aberrant angiogenesis.

Development of acquired factor V inhibitor after treatment with ceftazidime: a case report and review of the literature.

We report the case of a 59-year-old Chinese man who showed an asymptomatic coagulation factor V deficiency pattern after second intravenous treatment with ceftazidime. Normal pooled plasma failed to correct the abnormalities in a mixing test, and the presence of factor V inhibitor was confirmed by the Bethesda method. The coagulopathy was not corrected by transfusion of fresh frozen plasma and prothrombin complex concentrate, but rather by treatment with prednisone and withdrawal of dubious drugs. The findings reported here should prompt clinicians to watch for drug-induced coagulation factor deficiency.

Efficacy and safety of immunosuppressive therapy in the treatment of seronegative hepatitis associated aplastic anemia.

OBJECTIVE: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA) (SNHAA) and hepatitis B virus (HBV) infection complicating AA (HBVAA), and thereby compare the efficacy of immunosuppressive therapy (IST). METHODS: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes. RESULTS: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60%) of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00), a quicker response to IST (2.5 months versus 4.5 months, P=0.018), a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03), and lower white blood cell and absolute neutrophil count (0.8 × 10(9)/L versus 1.23 × 10(9)/L and 0.26 × 10(9)/L versus 0.58 × 10(9)/L, P=0.026 and P=0.0009, respectively). No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. CONCLUSION: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly. Neither hepatitis prior to AA nor AA complicating HBV infection have been shown to influence the early efficacy of IST and adverse events, and HBV may not be the causative agent of AA.

Photosensitizing effectiveness of a novel chlorin-based photosensitizer for photodynamic therapy in vitro and in vivo.

PURPOSE: Photodynamic therapy (PDT) is a promising noninvasive treatment, which has been approved by the US Food and Drug Administration for the treatment of localized tumors. With the aim to select an appropriate photosensitizer for tumor treatment in PDT, the antitumor effect of a novel chlorin-based photosensitizer, meso-tetra (3-morphlinomethyl-4-methoxyphenyl) chlorin (TMMC) (Fig. 1a) on two types of human malignant tumor cells in vitro and a esophageal cancer model in nude mice, was evaluated in the present paper. Fig. 1 Chemical structure and spectrum properties of TMMC in DMF. a Chemical structure of TMMC in DMF. b UV-Vis absorption spectrum of TMMC in DMF. Its maximum absorbance is at 423 nm, and at 527, 555, 600, 655 nm and 712 nm, also it has absorption. c Emission spectrum of TMMC, which was excited at 514 nm, and its peaks were at 656 and 720 nm. d The matrix of excitation and emission spectra (Ex: 300-550 nm, Em: 600-780 nm) METHODS: The efficiency of TMMC-PDT in vitro was analyzed by MTT assay and clonogenic assay. The intracellular distribution of photosensitizers was detected with laser scanning confocal microscopy. The accumulation of TMMC in human malignant tumor cells was measured by Fluorescence Spectrometer, and the pathway of cell death was analyzed by flow cytometry. Eca-109 tumor model was used to evaluate the antitumor effects of TMMC-mediated PDT. And the singlet oxygen quantum yield of TMMC was also measured using DPBF as substrate. RESULTS: TMMC shows a singlet oxygen quantum yield of 0.59 and displays a characteristic long wavelength absorption peak at 655 nm. The accumulation of TMMC increased in time-dependent manner, and it was found in cytoplasm and nuclear membranes. TMMC-PDT induced cell death by the major death pathway of necrosis and significantly reduced the growth of Eca-109 tumors in nude mice (180 mW/cm(2), 120 J/cm(2)). CONCLUSION: The studies suggest that TMMC is an effective photosensitizer for PDT to tumors. Therefore, TMMC has great potentials for tumor treatment in PDT and deserves further investigation.

Valproic acid-associated low fibrinogen and delayed intracranial hemorrhage: case report and mini literature review.

A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.

Clinical study of thalidomide combined with dexamethasone for the treatment of elderly patients with newly diagnosed multiple myeloma.

OBJECTIVE: To investigate the relationship between the efficacy and safety of different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiple myeloma (MM). METHODS: Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groups according to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overall response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) were compared between the two groups. RESULTS: A total of 28 patients were followed up with a median of 18 months. The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS values were not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patients with a grading above 3 in group B was significantly higher than in group A (P=0.033). CONCLUSIONS: The TD regimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM. TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas with financial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.

Extramedullary plasmacytoma in the presence of multiple myeloma: clinical correlates and prognostic relevance.

OBJECTIVE: We studied the clinical and laboratory features and outcomes of multiple myeloma (MM) with extramedullary plasmocytoma (EP) disease both at diagnosis and during the course of MM. PATIENTS AND METHODS: Forty-two patients of 467 patients with MM were retrospectively analyzed from both the 100th Hospital of the People's Liberation Army and Shanghai Changzheng Hospitals. The clinical characteristics, laboratory parameters, responses, risk factors, and outcomes were analyzed. RESULTS: The median age was 53 years with a male/female sex ratio of 34:8. Twenty-six patients had EP disease at the time of diagnosis, and 16 patients developed EP during the course of the disease. We found that the Durie-Salmon stage, serum lactate dehydrogenase level, beta-2-microglobulin, complete blood counts, albumin, and the type of immunoglobulin (Ig) were not associated with the development of EP disease. Patients who developed EP during the course of MM had a higher ratio of plasmocytes and premature plasmocytes in the bone marrow with lower C-reactive protein level and earlier stage of International Staging System for Lung Cancer at the diagnosis of MM compared with patients who presented with EP at diagnosis. Once the patients developed EP disease, they frequently showed resistance to chemotherapy. With a median follow-up of 30 months, 19 patients were alive. Log-rank univariate analysis showed that patients with EP who had normal C-reactive protein, higher hemoglobin, lower serum lactate dehydrogenase, and stage I of International Staging System for Lung Cancer had longer survival. However, cyclooxygenase multivariate analysis failed to show statistical significance for any factor. CONCLUSIONS: EP disease is the MM end-phase and is not a rare manifestation of MM with a cumulative incidence of 9% of MM. The prognosis is very poor once the diagnosis of EP disease is concurrent with MM.

Treatment of vitamin K-dependent coagulation factor deficiency and subarachnoid hemorrhage.

BACKGROUND: In adults, vitamin K-dependent coagulation factor deficiency (VKCFD) increases in the recent years. We treated a VKCFD patient with subarachnoid hemorrhage, with favorable outcomes. METHODS: A 19-year-old male student with VKCFD was treated at our hospital. The initial treatment was injection of a large dose of vitamin K and fresh plasma, and then with oral high dose of vitamin K4. RESULTS: At 4 weeks after admission, the focus of hemorrhage subsided, neurological examination was normal, and the patient was discharged. CONCLUSIONS: VKCFD is rare and its diagnosis should be based on the history of the patient and the results of laboratory examinations. A large dose of vitamin K is the first choice of treatment.

[Pathology, diagnosis and treatment of a patient with hemotidrosis.].

OBJECTIVE: To investigate the pathology, diagnosis and treatment of a patient with hemotidrosis. METHODS: Coagulation tests, coagulation factor activities, von Willebrand factor concentration, bleeding time and platelet aggregation were measured. The bloody exudates from the skin was examined under light microscopy. The involved skin area biopsy was examined histologically. RESULTS: The bloody exudates contained all kinds of normal blood cells mixed with sweat-like fluid, rather than true-sweat. Histopathologic examination showed normal sweat gland structure without blood cells. The patient was successfully treated with propranolol. CONCLUSION: Sympathetic nerve activation in the vasculature might play a role in hemotidrasis, and beta-blockers might be an effective drug for treatment.

[Detection of serum free light chain and its clinical significance in nonsecretory multiple myeloma].

OBJECTIVE: To explore the clinical significance of serum free light chain (sFLC) levels in nonsecretory multiple myeloma (NSMM). METHODS: Nine NSMM patients were hospitalized in our department from Feb 2002 to Sep 2006 and no M-components was found in their serum and urine by immunofixation electrophoresis (IFE). sFLC was assayed by immuno-nephelometry. The clonality of sFLC was estimated by serum kappa:lambda sFLC ratio. Meanwhile, serum immunoglobulin, total kappa and lambda light chain level were also determined in these patients. RESULTS: Increased serum concentrations of either kappa or lambda sFLC (and abnormal kappa/lambda ratios) were detected in 6 of 9 patients with NSMM although their serum immunoglobulin levels were not elevated and total kappa:lambda light chain ratios (1.32 - 2.20) were in the reference range. All the 9 patients had clonal IgH gene rearrangements. CONCLUSION: Quantification of sFLC by immuno-nephelometry is more sensitive than that of serum total light chain measurement and is helpful in estimating the clonality of the light chain in patients with NSMM.

Increased leukotriene c4 synthesis accompanied enhanced leukotriene c4 synthase expression and activities of ischemia-reperfusion-injured liver in rats.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is an important clinical issue and relates to cysteinyl leukotrienes (LTs), the first committed synthesis step of which is that LTC4 synthesis enzymes including leukotriene C4 synthase (LTC4S), microsomal glutathione-S-transferase (mGST)2, and mGST3-catalyzed LTA4 and reduced glutathione (GSH), to generate LTC4. However, the mechanisms of LTC4 generation during hepatic I/R are far from being elucidated. MATERIALS AND METHODS: Adult male Sprague Dawley rats were divided into two groups: sham group (control) and I/R group. Liver was subjected to 60 min of partial hepatic ischemia followed by 5 h of reperfusion; saline was administered intravenously. LTC4 content, the activities, and expressions of LTC4 synthesis enzymes were examined with reversed phase high-performance liquid chromatography, reverse transcriptase-polymerase chain reaction, immunoblot, and immunohistochemistry, respectively. Liver damage was assessed by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) measurements and histological observation. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in liver tissue were used to evaluate lipid peroxidation, and oxidative stress was estimated by the reduced GSH level in liver tissue in the pathological process. RESULTS: Compared with control, LTC4 content, the LTC4 synthesis enzymes' activities, and the mRNA and protein expressions of LTC4S were significantly increased, while the mRNA expressions of mGST2 and mGST3 were declined obviously in rat liver during I/R (P < 0.05); most hepatocytes and sinusoidal endothelial cells expressed intensively LTC4S in an I/R-sensitive manner. This was accompanied by the increase in serum ALT and AST levels together with liver tissue MDA content (P < 0.05), the decrease in liver tissue GSH level, and SOD activity (P < 0.05), as well as histological damage. There were no differences in the protein expression of mGST3 between control and I/R groups. CONCLUSIONS: These results demonstrated that hepatic I/R injury up-regulated the mRNA and protein expressions of LTC4S in hepatocytes and sinusoidal endothelial cells and enhanced the activities of the LTC4 synthesis enzymes. It suggests that LTC4 accumulation after hepatic I/R can be caused partially by LTC4S expression up-regulation and the LTC4 synthesis enzymes' activities augment to which LTC4S rather than mGST2 or mGST3 may mainly contribute.

[Clinical features of multiple myeloma patients with extramedullary disease: a report of 40 cases from a single center].

OBJECTIVE: To analyze the clinical and laboratory features and risk factors of multiple myeloma (MM) with extramedullary disease (EM) and its extraosseous localizations at diagnosis and during the course of MM. METHODS: The clinical features, survival rate and prognostic factors were retrospectively analyzed in 40 patients having EM from a total of 418 MM patients hospitalized in Changzheng Hospital from 1993 to 2006. RESULTS: Among the 40 patients, the first three localizations of EM involved soft tissue, pleura or peritoneum and central nervous system (CNS). Median duration of follow-up was 30 months. The median overall survival (OS) was 28 months. Twenty-five patients (6%) were found to have EM at diagnosis (group A), and their median OS was 16 months and 15 patients (3.6%) developed EM during the course of the disease (group B), and their expected median OS was 72 months. There was a significant difference between group A and B (P = 0.0045) for OS. Compared with those in group A, patients in group B had a higher percentage of plasmacytes (P = 0.022) and plasmablasts (P = 0.029) in bone marrow, and less advanced stage for international staging system (ISS) (P = 0.027). Log-rank univariate analysis showed that higher CRP level, higher serum LDH, Stage II and III for ISS, Hb < 110 g/L at diagnosis were poor prognostic factors. However, multivariate analysis with COX model showed none of them were statistically significant. CONCLUSION: EM tumors are not a rare manifestation of MM. Soft tissue in the commonest area involved. Higher serum CRP and LDH level, more advanced stage for ISS, anemia and having EM are poor prognostic factors of MM.

Further evidence that rat liver microsomal glutathione transferase 1 is not a cellular protein target for S-nitrosylation.

By adopting biotin switch method, we recently reported that liver microsomal glutathione transferase 1 (MGST1) might not be a protein target for S-nitrosylation in rat microsomes or in vivo. However, alternative analytic methods are needed to confirm this observation, as a single biotin switch method in judging specific protein S-nitrosylation in biological samples is increasingly recognized as insufficient, or even unreliable. Besides, only MGST1 localized on endoplasmic reticulum (ER), but not mitochondria which favors protein S-nitrosylation was examined in the previous report. Present study was therefore carried out to address these issues. Primary cultured hepatocytes were used. A physiological existing nitric oxide (NO) donor S-nitrosoglutathione (GSNO) was adopted to trigger protein S-nitrosylation. MGST1 was immunoprecipitated and its S-nitrosothiol content was measured by the NO probe 2,3-diaminonaphthalene. In parallel, S-nitrosylated proteins were immunoprecipitated by a monoclonal anti-S-nitrosocysteine antibody and probed with an anti-MGST1 antibody. In hepatocytes, neither ER nor mitochondria were found to contain S-nitrosylated MGST1 after GSNO treatment, showing that differently distributed MGST1 was consistently un-nitrosylable in the cellular environment. But under broken cell conditions, when samples were incubated directly with GSNO, MGST1 S-nitrosylation was indeed detectable in both the microsomal and mitochondrial proteins, indicating that previous failure in detecting MGST1 S-nitrosylation in microsomes is due to the limitations of biotin switch method. These results clearly, if not definitely, demonstrate that MGST1 is not a ready candidate for S-nitrosylation in the cellular content, despite its susceptibility to S-nitrosylation under broken cell conditions.