Search

Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA–arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. Experimental Design: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). Results: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. Conclusions: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

Preeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated.Preeclampsia patients (We observed that preeclampsia patients exhibited significantly elevated plasma TC (Our findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.

Background/Aims: Cardiac surgery-associated severe acute kidney injury (SAKI) is associated with high mortality and poor quality of life. A prognostic score for SAKI may enable prevention of complications. Methods: This observational study of 2,552 patients undergoing cardiac surgery from January 2006 to December 2011 in our institution established associations between predictor variables and postoperative SAKI from a cohort of 1,692 patients and developed a clinical score that was assessed in a validation cohort of 860 patients. Results: Postoperative SAKI occurred in 262 ­patients (10.3%). We identified 7 independent and significant risk factors in the derivation model (adjusted OR 95% CI): age ≥81 years (vs. age < 40 years, 4.30, 1.52–12.21), age 61–80 years (vs. age 2O (3.53, 2.38–5.23), and low postoperative cardiac output (4.78, 2.97–7.69). The 7-variable risk prediction model had acceptable performance characteristics in the validation cohort (C statistic 0.80, 95% CI 0.74–0.85). The difference in the C statistic was 0.21 (95% CI 0.12–0.29, p < 0.001) compared with the Cleveland Clinic score. Conclusion: We developed and validated a practical risk prediction model for SAKI after cardiac surgery based on routinely available perioperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

A pneumonia outbreak caused by a novel coronavirus (COVID-19) has spread around the world. A total of 2,314,621 laboratory-confirmed cases, including 157,847 deaths (6.8%) were reported globally by 20 April 2020. Common symptoms of COVID-19 pneumonia include fever, fatigue, and dry cough. Faced with such a sudden outbreak of emerging infectious disease, traditional models for predicting the peak of the epidemic often show inconsistent results. With the aim to timely judge the epidemic peak and provide support for decisions for resuming production and returning to normal life based on publicly reported data, we used a seven-day moving average of log-transformed daily new cases (LMA) to establish a new index named the &ldquo, epidemic evaluation index&rdquo, (EEI). We used SARS epidemic data from Hong Kong to verify the practicability of the new index, and then applied it to the COVID-19 epidemic analysis. The results showed that the epidemic peaked, respectively, on 9 February and 5 February 2020, in Hubei Province and other provinces in China. The proposed index can be applied for judging the epidemic peak. While the global COVID-19 epidemic reached its peak in the middle of April, the epidemic peaks in some countries have not yet appeared. Global and united efforts are still needed to eventually eliminate the epidemic.

Objectives: Brain arteriovenous malformations (AVMs) are the most common cause of non-traumatic intracerebral hemorrhage in young adults. The genesis of brain AVM remains enigmatic. We investigated microRNA (miRNA) expression and its contribution to the pathogenesis of brain AVMs. Methods: We used a large-scale miRNA analysis on 16 samples including AVMs, hemangioblastoma, and controls to identify a distinct AVM miRNA signature. AVM smooth muscle cells (AVMSMCs) were isolated and identified by flow cytometry and immunohistochemistry and candidate miRNAs were then tested in these cells. Migration, tube formation, and CCK-8-induced proliferation assays were used to test the miRNAs effect on phenotypic properties of AVMSMCs. A quantitative proteomics approach was used to identify protein expression changes in AVMSMCs treated with miRNA mimics. Results: A distinct AVM miRNA signature comprising a large portion of lowly expressed miRNAs was identified. Among these miRNAs, miR-137 and miR-195* levels were significantly decreased in AVMs and constituent AVMSMCs. Experimentally elevating the level of these microRNAs inhibited AVMSMC migration, tube formation and survival in vitro and the formation of vascular rings in vivo. Proteomics showed the protein expression signature of AVMSMCs and identified downstream proteins regulated by miR-137 and miR-195* which were key signaling proteins involved in vessel development. Interpretation: Our results indicate that miR-137 and miR-195* act as vasculogenic suppressors in AVMs by altering phenotypic properties of AVMSMCs, and that the absence of miR-137 and miR-195* expression leads to abnormal vasculogenesis. This article is protected by copyright. All rights reserved.

ObjectiveAlthough many studies worldwide have focused on the relationship between vitamin D and insulin resistance, results remain controversial. Furthermore, concentrations of serum 25-hydroxyvitamin D (25(OH)D) in the Chinese population are unclear. We aimed to investigate vitamin D status and its correlation with insulin resistance among a Chinese adult population.DesignSerum 25(OH)D, fasting blood glucose, fasting insulin, glycated Hb (HbA1c) and other metabolic parameters were assessed. Neck circumference, waist circumference, hip circumference, weight and height were also measured. Lifestyle factors including smoking and drinking status were obtained. Diabetes mellitus was diagnosed by HbA1c according to the 2010 American Diabetes Association criteria.SettingEastern China.SubjectsOf 7200 residents included, 6597 individuals were ultimately analysed.ResultsWe enrolled 2813 males (mean age 52·7 (sd 13·5) years) and 3784 females (52·3 (sd 13·5) years); mean serum 25(OH)D concentration was 43·1 (sd 11·6) and 39·6 (sd 9·8) nmol/l, respectively. Additionally, 83·3 % of participants were 25(OH)D deficient. A significant difference in 25(OH)D was observed between males and females in winter and spring (P<0·001). Furthermore, 25(OH)D concentrations were inversely associated with the homeostasis model assessment of insulin resistance (HOMA-IR) in the overweight and pre-diabetic populations. After adjusting for several variables, 25(OH)D was significantly associated with HOMA-IR in winter. When 25(OH)D values were categorized into quartiles, HOMA-IR was significantly associated with decreasing 25(OH)D.ConclusionsThe majority of the Chinese population was vitamin D deficient and this deficiency was negatively associated with insulin resistance, particularly in the overweight and pre-diabetic populations. Moreover, these associations might be more evident in the winter.

Preeclampsia (PE) is a pregnancy-specific complication that seriously threatens the health and safety of mothers and infants. The etiology of PE has not been fully elucidated, and no effective treatments are currently available. A pregnant woman with PE often has to make a tough choice on either endangering her own health to give a birth or being forced to terminate her pregnancy. It is recommended by the International Federation of Gynecology and Obstetrics that the combination of maternal high-risk factors and biomarkers could form a good strategy for predicting the risk of PE. Such a combination may also enable more effective monitoring and early clinical intervention in high-risk populations to reduce the risk of PE. Therefore, biomarkers validated by extensive clinical research may be formally applied for clinical PE risk prediction. In this review, we summarized data from clinical research on potential biomarkers and classified them according to the current four major hypotheses, namely placental or trophoblast ischemia and hypoxia, vascular endothelial injury, oxidative stress, and immune dysregulation. Additionally, we also discussed the underlying mechanisms by which these potential biomarkers may be involved in the pathogenesis of PE. Finally, we propose that multiple biomarkers reflecting different aspects of the disease pathogenesis should be used in combination to detect the high-risk PE population in support of clinically targeted intervention and prevention of PE. It is expected that tests made of more sensitive and reliable PE biomarkers based on the aforementioned major hypotheses could potentially improve the accuracy of PE prediction in the future.

Epidemiologic studies have indicated that early life nutrition influences later risk of obesity, type 2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is also considered a metabolic disease.The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period.In total, 5306 subjects from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and nonexposed (1963-1974, reference) group.The degrees of steatosis of NAFLD were determined by ultrasonography.The prevalences of NAFLD in the nonexposed (1963-1974), fetal-exposed, and childhood-exposed participants were 55.9%, 55.8%, and 55.4% in men and 33.0%, 46.3%, and 51.7% in women, respectively. Compared with those nonexposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P.05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, body mass index, diabetes, dyslipidemia, and hypertension (both P.05). Famine exposure during the fetal period (odds ratio 1.77, 95% confidence interval 1.22, 2.57) and childhood (odds ratio 1.82, 95% confidence interval 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model.Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief.

OBJECTIVE To develop a model for predicting cardiac risk among pregnant women with structural heart disease in Eastern China. METHODS The model was built using data from pregnant women (development cohort, n=566; validation cohort, n=314) who delivered at Shanghai Obstetrical Cardiology Intensive Care Center, Renji Hospital, Shanghai, between 2002 and 2015. Independent predictors of adverse cardiac events were determined by logistic regression. Discrimination and calibration of the model, termed the Renji score, were compared with the CARPREG score, ZAHARA score, and modified WHO risk classification. RESULTS There were 87 (15.4%) adverse cardiac events in the development cohort. Independent predictors of adverse cardiac events included left ventricular systolic dysfunction (ejection fraction

The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an “oncometabolite.” To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph–time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 μg/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2-HG plays in leukemogenesis.

Objective The aim of this study was to analyze the clinicopathologic characteristics and prognostic factors of adenoid cystic carcinoma of the head and neck (ACCHN). Study Design This was a retrospective study of 218 patients with ACCHN. Results The cohort included 110 men and 108 women; the parotid and the palate were the most common site of involvement. Of 203 patients with follow-up information (range 2-132 months), 57 had died of the tumor. Distant metastasis (DM) and local recurrence (LR) were documented in 83 (40.9%) and 34 (16.7%) patients, respectively. Cox regression analysis indicated that a solid pattern was a marker for LR and that positive margins and older age were risk factors for DM. Histologic pattern, T stage, N stage, LR, DM, and patient age contributed to the prediction of disease-specific survival. Conclusions A solid pattern, metastasis, LR, and older age are the most important factors for predicting poor prognosis in Chinese patients with ACCHN.

Background Poor postoperative wound healing after endoscopic sinus surgery (ESS) remains a significant problem. This study evaluates the efficacy and safety of a new absorbable hyaluronan hydrogel. Methods A prospective, randomized, controlled trial was conducted. Fifty-five patients with bilateral ESS were recruited and randomized to receive absorbable hyaluronan hydrogel in one side as treated and the opposite side without absorbable hyaluronan hydrogel as control. Clinical outcome measures were assessed at postoperative 1, 2, 4, 8, and 12 weeks. Results Fifty-four patients completed the study. Overall, absorbable hyaluronan hydrogel significantly promotes the reepithelization process and reduces the presence of obstructing synechia, nonobstructing synechia, edema, crust, and mild mucopurulent drainage (all p ≤ 0.0002). At all postoperative follow-up visits, the promotion in reepithelization is statistically significant at 2, 4, and 8 weeks, and the reductions in the presence of nonobstructing synechia, edema, crust, and mild mucopurulent drainage are all statistically significant except for the presence of crust at 12 weeks and mild mucopurulent drainage at 1 and 12 weeks. Although the presence of obstructing synechia at each follow-up visit between groups does not reach statistical significance, the incidence ranges from 5.56 to 12.96% in the control group and from 0 to 3.70% in the treated group. No adverse event related to treatment was observed. Conclusion In this clinical study, data analyses suggest that this new absorbable hyaluronan hydrogel, as nasal dressing/packing after ESS is safe and promotes the postoperative reepithelization process and reduces the presence of synechia, edema, crust, and mild mucopurulent drainage.

The present study was performed in China to compare the efficacy and safety of an advanced wound dressing made of crystalline cellulose (Veloderm) to a conventional treatment of three Vaseline gauzes in the management of skin donor sites of burns or reconstructive plastic surgery. In this prospective, multicenter, open-labeled, randomized clinical trial performed in three Chinese burn centers in China, 96 patients who required autologous split skin graft were randomized into either the test (Veloderm) group or the control (Vaseline gauze) group. Average healing times in the test group and in the control group were 8.40±2.90 and 8.92±2.58 days, respectively, with median values of 7.00 and 8.00 days, respectively: the difference between two groups was statistically significant (P=.045). Scores for exudates, pain intensity, and peripheral erythema showed no difference between the groups; however, composite scores of three variables on day 10 postoperatively was significantly lower in the test group (0.00±0.00 vs. 0.13±0.49; P = .043). The need for a dressing change was also significantly lower in the test group (12.5 vs. 31.25%; P = .036). Veloderm is a safe and effective dressing that may offer some advantages over the traditional application of Vaseline gauze in the management of donor sites in burn or reconstructive plastic surgery patients.

Background Lymphoscintigraphy is widely used to image the lymphatic system. The aim of this study was to compare lymphoscintigraphy and dynamic magnetic resonance lymphangiography (MRL) in the investigation of extremity lymphoedema. Methods Sixteen patients with primary extremity lymphoedema and two with Klippel–Trenaunay syndrome with lymphoedema were examined by lymphoscintigraphy using the tracer 99Tc-labelled dextran, and by MRL using gadobenate dimeglumine as contrast agent. Morphological abnormalities and functional state of the lymphatic systems of affected limbs were compared between the two imaging methods. Results Lymphatic vessels were imaged in 14 of 18 limbs with lymphoedema using MRL, compared with one of 18 using lymphoscintigraphy. MRL detected the inguinal nodes in 16 of 17 patients, whereas lymphoscintigraphy revealed inguinal nodes in only nine. MRL revealed more precise information about structural and functional abnormalities of lymph vessels and nodes than lymphoscintigraphy by real-time measurement of lymph flow in vessels and nodes. Conclusion Dynamic MRL was more sensitive and accurate than lymphoscintigraphy in the detection of anatomical and functional abnormalities in the lymphatic system in patients with extremity lymphoedema.

Objective To compare the medical outcomes of infants delivered by cesarean section with those of infants delivered vaginally. Methods A total of 301 healthy women with cesarean section and a matched control group of 301 women delivered vaginally were identified at three district-level hospitals in Shanghai from May 2001 to February 2003. Two groups were matched according to their medical indications for cesarean section. Their infants were assessed at delivery, 1 month, 6 month and 1 year after birth. Results The incidence of neonatal complications and infant morbidities at all measurement occasions did not differ significantly between groups. Rehospitalization was found to be more likely among infants delivered by cesarean section in the first month after birth. However, there was no difference between two groups in the incidence of rehospitalization in the first year after birth. Cesarean section was also associated with a higher risk of infant diarrhea (adjusted relative risk=1.25, 95% CI: 1.01, 1.56). Conclusion Infants did not have health benefits from cesarean section if the pregnancy was at low risk.

SummaryBackground & aimsEpidemiologic studies have revealed that early-life conditions influence later risk of chronic diseases. We aimed to explore whether exposure to Chinese famine between 1959 and 1962 during fetal and childhood period was related with metabolic syndrome (MS) in adulthood.Methods6445 subjects from SPECT-China study were divided into fetal-exposed (1959–1962), childhood-exposed (1949–1958), adolescence/young adult-exposed (1921–1948), non-exposed (1963–1974) and non-exposed (after 1975). MS was defined by the International Diabetes Federation criteria.ResultsThe prevalences of MS in the non-exposed (1963–1974), fetal and childhood-exposed were 16.4%, 20.1% and 19.1% in men and 13.5%, 23.7% and 33.5% in women, respectively. After adjustment for age, compared with non-exposed (1963–1974), fetal and childhood-exposed women had significantly higher prevalences of MS (P

The Chinese were afflicted by great famine between 1959 and 1962. These people then experienced rapid economic development during which the gross domestic product per capita increased from $28 in 1978 to $6807 in 2013. We hypothesize that these two events are associated with the booming rate of diabetes in China.We aimed to explore whether exposure to famine in early life and high economic status in adulthood was associated with diabetes in later life.Our data of 6897 adults were from a cross-sectional Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study in 2014. Among them, 3844 adults experienced famine during different life stages and then lived in areas with different economic statuses in adulthood.Diabetes was considered as fasting plasma glucose of 7.0 mmol/L or greater, hemoglobin A1c of 6.5% or greater, and/or a previous diagnosis by health care professionals.Compared with nonexposed subjects, famine exposure during the fetal period (odds ratio [OR]1.53, 95% confidence interval [CI]1.09-2.14) and childhood (OR 1.82, 95% CI 1.21-2.73) was associated with diabetes after adjusting for age and gender. Further adjustments for adiposity, height, the lipid profile, and blood pressure did not significantly attenuate this association. Subjects living in areas with high economic status had a greater diabetes risk in adulthood (OR 1.46, 95% CI 1.20-1.78). In gender-specific analyses, fetal-exposed men (OR 1.64, 95% CI, 1.04-2.59) and childhood-exposed women (OR 2.81, 95% CI, 1.59-4.97) had significantly greater risk of diabetes.The rapid increase in the prevalence of diabetes in middle-aged and elderly people in China is associated with the combination of exposure to famine during the fetal stage and childhood and high economic status in adulthood. Our findings may partly explain the booming diabetes phenomenon in China.

The pathophysiology of breast cancer-related lymphedema (BCRL) is poorly understood. The present study evaluated the lymphatic collectors in the arms of patients with BCRL.In total, 123 patients with ipsilateral BCRL who had undergone magnetic resonance lymphangiography using gadobenate dimeglumine as a contrast agent were enrolled in this study. Morphological changes and the numbers of collecting lymphatic vessels were recorded. Associations between the number of visualized lymphatic collectors and edema accumulation, subcutis thickness, and the BCRL duration and latency were analyzed. Tortuous and significantly dilated lymphatic collectors were visualized in the lymphedematous arms of 104 patients (85%). The median number of visualized lymphatic collectors was four. The duration of BCRL was weakly but significantly correlated with the number of lymphatic collectors (rs=0.2054, p=0.0226). The differences in the tissue water content and thickness of the subcutis between the bilateral arms demonstrated moderate correlations with the number of collecting lymphatics (rs=0.31 and 0.35, respectively; p0.01). More lymphatic collectors tended to be seen in more advanced cases. There was no statistical difference in the amount of lymphatic vessels among different breast cancer treatment methods.The number of functional remaining lymphatic collectors increases with the prolongation and severity of BCRL. This may imply persistent reactions of lymphatic collectors in response to lymphostasis.

International audience; Fas and PI3K/Akt signaling pathways pivotally impact on cancer cell death and survival respectively and are considered as promising targets for innovative anticancer therapies. To better characterize the combination effect of PI3K/Akt inhibitors and Fas agonists and understand the profile of the interaction between PI3K/Akt and Fas signaling, we qualitatively and quantitatively evaluated the combination effect of PI3K/Akt inhibitors LY294002, Akt inhibitor VIII and FasL. At the concentration that can block cell cycle progression and DNA synthesis but not elicit apoptosis, these inhibitors potentiate FasL to induce apoptosis. At higher concentrations, when the PI3K/Akt inhibitors induce apoptosis, they synergize FasL to induce apoptosis. In addition, PI3K/Akt inhibition significantly facilitates the Fas-mediated apoptotic signaling. Understanding the combination effects between PI3K/Akt inhibition and Fas activation not only leads to rational design of effective combination therapy of PI3K/Akt inhibitors but also improve our knowledge about the impact of PI3K-Akt pathway on Fas signaling and the potential modulation of innate immune system by PI3K-Akt-targeting drugs in anticancer treatment.

Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients, including those with normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study that identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of well-established markers. We further compared the gene expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and tricarboxylic [corrected] acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (Ara-C), whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML.

In addition to the clinicopathological parameters, molecular biomarkers are becoming increasingly important in the prognostic evaluation of cancer patients. This study aimed to determine the molecular alterations in the RAS association domain family protein1A gene (RASSF1A) in salivary adenoid cystic carcinoma (ACC) and to evaluate the potential of such alterations as prognostic markers. One hundred and sixty-seven ACC tumor tissues and 50 samples of matched normal salivary gland tissues from the same patients were analyzed for RASSF1A promoter methylation status by bisulfite sequencing PCR (BSP) and/or methylation-specific PCR (MSP). Fifty ACC tumor tissues and matched normal salivary gland tissues were analyzed for loss of heterozygosity (LOH) by examining two microsatellite markers (D3S1478, D3S1621) at 3p21. RASSF1A gene mutations were detected by direct sequencing of all six exons in 50 tumor and normal tissue specimens. Over-all, RASSF1A promoter hypermethylation was detected in 35.3% (59/167) of ACC tissues and was associated with histologically solid tumor pattern (P = 0.002) and advanced TNM stage (P = 0.014). RASSF1A LOH was observed in 18.0% (9/50) of cases, and no somatic mutation of RASSF1A was detected in any cases. RASSF1A promoter methylation was associated with the poor over-all survival (Log-rank test, P

Drug-induced liver injury (DILI) is complicated and difficult to predict. It has been observed that drugs with extensive hepatic metabolism have a higher likelihood of causing DILI. Cytochrome P450 (P450) enzymes are primarily involved in hepatic metabolism. Identifying the associations of DILI with drugs that are P450 substrates, inhibitors, or inducers will be extremely helpful to clinicians during the decision-making process of caring for a patient suspected of having DILI. We collected metabolism data on P450 enzymes for 254 orally administered drugs in the Liver Toxicity Knowledge Base Benchmark Dataset with a known daily dose, and applied logistic regression to identify these associations. We revealed that drugs that are substrates of P450 enzymes have a higher likelihood of causing DILI [odds ratio (OR), 3.99; 95% confidence interval (95% CI), 2.07-7.67; P0.0001], which is dose-independent, and drugs that are P450 inhibitors have a higher likelihood of generating DILI only when they are administered at high daily doses (OR, 6.03; 95% CI, 1.32-27.5; P = 0.0098). However, drugs that are P450 inducers are not observed to be associated with DILI (OR, 1.55; 95% CI, 0.65-3.68; P = 0.3246). Our findings will be useful in identifying the suspected medication as a cause of liver injury in clinical settings.

To compare the efficacy of pars plana vitrectomy (PPV) with that of scleral buckling (SB) in the treatment of uncomplicated, primary rhegmatogenous retinal detachment (RRD).Meta-analysis of randomized controlled trials (RCTs) were performed. Phakic and pseudophakic/aphakic eyes were analyzed separately. Searches of PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials were conducted. Outcome measures included primary and final anatomic success, final visual success, and development of post-operative proliferative vitreoretinopathy (PVR) and/or post-operative cataract.Three RCTs of phakic eyes (n = 523) and four RCTs of pseudophakic/aphakic eyes (n = 690) were included in the meta-analysis. For the phakic group, searches of PPV and SB yielded similar results in terms of primary/final retinal re-attachment and post-operative PVR. In the SB arm, visual acuity (VA) was better (heterogeneity p = 0.14; OR = 0.50, 95%CI, 0.31-0.82; p = 0.005) and the rate of post-operative cataract lower (heterogeneity p = 0.42; OR = 4.18; 95%CI, 2.75-6.35, p 0.00001) than in the PPV group. In the pseudophakic/aphakic group, re-attachment rates after a single operation did not differ between the two procedures (random effect model: OR = 1.77; 95% CI, 0.80-3.91; p = 0.16). Final anatomic success outcomes were in favor of PPV (OR = 1.97; 95% CI, 1.04-3.73; p = 0.04). Final visual success and post-operative PVR rates did not differ statistically between the two arms (OR = 1.49; 95%CI, 0.82-2.68; p = 0.19; and OR = 0.85; 95% CI, 0.58-1.26; p = 0.42, respectively).SB is superior in terms of final VA and occurrence of post-operative cataract in uncomplicated phakic RRDs. PPV is more likely to achieve a favorable final re-attachment in pseudophakic/aphakic RRDs.

To evaluate the efficacy and safety of motherwort (herba leonuri/leonurus heterophyllus sweet) injection for preventing postpartum hemorrhage after caesarian section.The prospective study was designed as a randomized and single blind multi-center research matched with positive agent as controls from Apr 2007 to Aug 2007. 440 women underwent caesarian section (CS) indicated by obstetric factors were enrolled from 15 teaching hospitals in China and assigned into three groups: group of motherwort: 147 cases were administered by motherwort 40 mg uterine injection during CS and 20 mg intramuscular injection per 12 hours 3 times after CS; group of motherwort+oxytocin: 144 cases were administered by motherwort 40 mg and oxytocin 10 U uterine injection during CS and motherwort 20 mg intramuscular injection per 12 hours 3 times after CS and group of oxytocin: 149 cases were administered by oxytocin 10 U uterine injection and oxytocin 10 U+5% glucose 500 ml intravenously injection during operation and oxytocin 10 U intramuscular injection per 12 hours 3 times after CS. The following clinical parameter were collected and analyzed: (1) The amount of blood loss during operation, at 2, 6, 12, 24, 48 hours after operation. (2) The total amount of blood loss in 24 hours after CS and the incidence of postpartum hemorrhage. (3) The change of level of hemoglobin (Hb) and counting of red blood cell (RBC) from prepartum to postpartum. (4) Adverse reaction.(1) The mean amount of blood loss during operation were (368+/-258) ml in group of motherwort, (255+/-114) ml in group of motherwort+oxytocin and (269+/-141) ml in group of oxytocin, which exhibited significant difference among three groups (P0.01). Meanwhile, no statistical different amount of blood loss among three groups were observed at 2, 6, 12, 24, 48 hours after CS. (2) The amount of blood loss of postpartum at 24 hours were (480+/-276) ml in group of motherwort, (361+/-179) ml in group of motherwort+oxytocin, (381+/-179) ml in group of oxytocin, which showed significant difference among 3 groups (P0.01). (3) The incidence of postpartum hemorrhage were 32.0% (47/147) in group of motherwort, 11.1% (16/144) in group of motherwort+oxytocin, and 18.8% in (28/149) in group of oxytocin. When comparing the lowest rate of postpartum blood loss in group of motherwort+oxytocin and the highest rate in group of motherwort, it displayed statistical difference (P0.01). (4) The decreased level of RBC and Hb were shown that RBC (0.3+/-0.5)x10(12)/L and Hb (9+/-13) g/L in group of motherwort, RBC (0.2+/-0.4)x10(12)/L and Hb (6+/-10) g/L in group of motherwort+oxytocin and RBC (0.2+/-0.4)x10(12)/L and Hb (7+/-30) g/L in group of oxytocin respectively. However, the comparison of different value of RBC and Hb in group of oxytocin and motherwort+oxytocin showed significant difference (P0.05). (5) Two cases with allery reaction was observed.It is safe and efficacious that combined use of motherwort injection and oxytocin was to prevent postpartum hemorrhage during or after caesarian section.

A Williams design is a special and useful type of cross-over design. Balance is achieved by using only one particular Latin square if there are even numbers of treatments, and by using only two appropriate squares if there are odd numbers of treatments. PROC PLAN of SAS/STAT is a practical tool, not only for random construction of the Williams square, but also for randomly assigning treatment sequences to the subjects, which makes integration of the two procedures possible. The present paper provides a general SAS program for the random construction of a Williams design and the relevant procedure for randomization. Examples of a three-treatment, three-period (3 x 3) and a four-treatment, four-period (4 x 4) cross-over designs are given to illustrate the function of the SAS program. The results can be regenerated and replicated with the same random number seed. The general SAS program meets the practical needs of researchers in the application of Williams designs.

1. Although increased oxidative stress has been shown repeatedly to be implicated in diabetes, the cardiovascular anti-oxidant state and heart response to ischaemia in long-term Type 1 diabetes remain largely unknown. The present study was designed to observe heart tolerance to ischaemia-reperfusion and endogenous anti-oxidants in the cardiovascular system in long-term hyperglycaemic rats. 2. Hearts from Sprague-Dawley rats surviving up to 6 months with streptozocin-induced severe hyperglycaemia (blood glucose > 20 mmol/L) were isolated and subjected to global ischaemia and reperfusion. Cardiac function, electrocardiogram and anti-oxidants in the myocardium and aorta were examined. In addition, the morphology of the myocardial mitochondria and the in vitro function of aortic vessels were assessed. 3. Hearts from diabetic rats demonstrated lower baseline heart function but had higher postischaemic coronary flow and left ventricular developed pressure compared with their respective controls (P < 0.05). In addition, hearts from diabetic animals had fewer arrhythmias (P < 0.01) and lower left ventricular end-diastolic pressure during reperfusion (P < 0.05). Higher catalase and heme oxygenase-1 content was found in the aorta and myocardium from diabetic rats (P < 0.01). In aortas from diabetic animals, acetylcholine-induced vasodilatation was enhanced and was approximately 15% after inhibition of nitric oxide synthase, compared with 0% in controls. The 15% relaxation was abrogated by heme oxygenase blockade. Mitochondria from the myocardium of diabetic rats showed significant increases in both size and number (P < 0.05). 4. Hearts of long-term Type 1 diabetic rats demonstrated improved recovery of postischaemic cardiac function and reduced reperfusion arrhythmia. Hyperglycaemia may enhance cardiovascular anti-oxidant capacity and mitochondrial neogenesis, which renders the heart resistant to ischaemia and oxidative injury.

To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar- Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis , and Salvia miltiorrhiza , with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro . ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G 1 /G 0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RARα degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.

To study the effects of caesarean section on breastfeeding.Six hundred and two [301 cases was caesarean section (caesarean section group) and 301 cases was vaginal delivery (vaginal delivery group)] nulliparas were interviewed face-to-face at antepartum and postpartum in an indication-matched prospective study.There was a significantly lower postpartum prolactin (PRL) level in the caesarean section group (8.48 nmol/L, 95% CI: 7.80 - 9.21 nmol/L) compared with vaginal delivery group (9.61 nmol/L, 95% CI: 8.99 - 10.26 nmol/L) during 6 - 24 hours in the daytime after delivery. The median time of breastfeeding initiation was 12 hours and 2 hours after birth for caesarean section and vaginal delivery groups respectively. Caesarean section was an important hazard for a shorter duration of breastfeeding (RR = 1.21; 95% CI: 1.10 - 1.33) within one year after childbirth.Caesarean section is associated with significantly lower postpartum PRL, which is in line with the longer breastfeeding initiation and lower rate of successful breastfeeding. Necessary measures including promoting the secretion of postpartum PRL such as early contact, early sucking and analgesic method should be taken to improve the successful breastfeeding rate.

Background Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. Methodology and Findings 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p

Background Rates of caesarean section are progressively increasing in many parts of the world. As a result of psychosocial factors there has been an increasing tendency for pregnant women without justifiable medical indications for caesarean section to ask for this procedure in China. A critical examination of this issue in relation to maternal outcomes is important. At present there are no clinical trials to help assess the risks and benefits of caesarean section in low risk women. To fill the gap left by trials, this indication-matched cohort study was carried out to examine prospectively the outcomes of caesarean section on women with no absolute obstetric indication compared with similar women who had vaginal delivery. Methods An indication-matched cohort study was undertaken to compare maternal outcomes following caesarean section with those undergoing vaginal delivery, in which the two groups were matched for non-absolute indications. 301 nulliparous women with caesarean section were matched successfully with 301 women who delivered vaginally in the Maternal and Children's Hospitals (MCHs) in Shanghai, China. Logistic regression model or binomial regression model was used to estimate the relative risk (RR) directly. Adjusted RRs were calculated adjusting for propensity score and medical indications. Results The incidence of total complications was 2.2 times higher in the caesarean section group during hospitalization post-partum, compared with the vaginal delivery group (RR = 2.2; 95% CI: 1.1-4.4). The risk of haemorrhage from the start of labour until 2 hours post-partum was significantly higher in the caesarean group (RR = 5.6; 95% CI: 1.2-26.9). The risk of chronic abdominal pain was significantly higher for the caesarean section group (RR = 3.6; 95% CI: 1.2-10.9) than for the vaginal delivery group within 12 months post-partum. The two groups had similar incidences of anaemia and complicating infections such as wound complications or urinary tract infection. Conclusions In nulliparous women who were at low risk, caesarean section was associated with a higher rate of post-partum morbidity. Those requesting the surgical procedure with no conventional medical indication, should be advised of the potential risks.