Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Blood circulation activating effect of Sanqi (Radix Notoginseng) on venous thromboembolism rat.

OBJECTIVE: To explore the blood circulation activating effect and mechanism of Sanqi (Radix Notoginseng) in vivo, using a venous thromboembolism (VTE) rat model. METHODS: We established the VTE rat model, and then intervened with low molecular weight heparin (LMWH), as well as low, medium and high doses of Sanqi (Radix Notoginseng), to observe the blood circulation activating effect of Sanqi (Radix Notoginseng) on VTE rats. RESULTS: After the treatment with high concentrations of Sanqi (Radix Notoginseng), the pulmonary thromboembolism was alleviated, and the lower limb thrombosis was markedly improved. Moreover, the expression quantities of plasma activated partial thromboplastin time, prothrombin time and D-dimer, as well as endothelin, von Willebrand factor, and plasminogen activator inhibitor-1 in thrombosis segment tissues were markedly down-regulated; while those of nitric oxide and tissue-type plasminogen activator were up-regulated. After low and medium concentration Sanqi (Radix Notoginseng) treatment, no obvious improvement was observed in each index. Moreover, the high concentration Sanqi (Radix Notoginseng) showed comparable efficacy to the positive drug LMWH. CONCLUSION: This data suggests that high concentration of Sanqi (Radix Notoginseng) is effective in preventing and treating VTE.

Sufentanil Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury by Suppressing Inflammation.

BACKGROUND Inflammation is one of the most significant mechanisms of hepatic ischemia-reperfusion injury (IRI). Sufentanil has a protective effect against liver injury by reducing inflammatory response. In this study, we used a cellular hepatic ischemic/reoxygenated (IR) model to determine whether sufentanil preconditioning protects against hepatic IRI. MATERIAL AND METHODS The human normal liver cells line L-O2 was studied. The levels of glutamic oxaloacetic transaminase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured using corresponding assay kits. The protein levels of total and phosphorylated ERK1/2, JNK, and p38, and the expression of p65 and COX2 genes, were measured by Western blotting. The levels of inflammatory factors were examined by ELISA. The Cell Counting Kit-8 (CCK-8) was used to determine if the viability of L-O2 cells was affected by sufentanil. The effects of sufentanil on IR-induced cell apoptosis were examined by flow cytometry. RESULTS IR-induced caused L-O2 cells to become rounded and to have a lower adhesive rate than normal cells. The levels of AST, LDH, and MDA were higher but the level of SOD was lower in the IR group than in the control group. The phosphorylated protein levels of ERK1/2, JNK, and p38, along with the expression of p65 and COX2, were upregulated in the IR group compared to the normal group. In addition, a variety of inflammatory factors were secreted in L-O2 cells after IR. The viability of L-O2 cells decreased and cell apoptosis increased significantly after IR treatment. All indexes of cell injury were reversed by sufentanil in a concentration-dependent manner. CONCLUSIONS Sufentanil stimulation triggers downregulation of inflammatory factors such as HIF-1alpha, TNF-alpha, IL-1ß, and IL-6, possibly through suppressing the p38/ERK/JNK/NF-kappaB-p65/COX2 pathways, and thereby reduces the damage to IR hepatic cells.

Salvage tigecycline in high risk febrile neutropenic patients with hematological malignancies: a prospective multicenter study.

The purpose of this prospective, multi-center study was to examine the efficacy and safety of tigecycline as empirical treatment in neutropenic patients with hematological malignancies who failed to respond to first-line antibiotics. A total of 125 patients with persistent fever (>72 h) despite first-line antibiotics received empirical treatment with tigecycline (loading dose of 100 mg, followed by 50 mg every 12 h). The use of other antimicrobial agents was not restricted. Treatment success rate was 68.0%. Subgroup analysis revealed a success rate of 73.1% in patients with pneumonia and 35.3% in patients with bacteremia. Toxicities were moderate with gastrointestinal symptoms being the main side effects. In conclusion, tigecycline-based antibacterial regimen was a justifiable empirical treatment in febrile neutropenic patients who failed to respond to first-line antibiotics except those with bacteremia. For patients with bacteremia, trials on higher-dose of tigecycline are needed.

Construction of a high-quality genomic BAC library for Chinese peanut cultivar Zhonghua 8 with high oil content.

BACKGROUND: Arachis hypogaea L. (2n = 4× = 40, AABB) is one of the most important oil and economic crop plants in the word. This species has the largest genome size of about 2,813 Mb among the oil crop species. Zhonghua 8 is a peanut cultivar planted widely in central China and has several superior traits including high oil content, high yield and disease resistance. A high-quality BAC library of Zhonghua 8 was constructed for future researches on the genomics of Chinese peanut cultivars. RESULTS: A Hin d III-digested genomic BAC (bacterial artificial chromosome) library was constructed with the genomic DNA from leaves of Zhonghua 8. This BAC library consists of 160,512 clones and the average insert is estimated about 102 kb ranging from 30 to 150 kb. The library represents about 5.55× haploid genome equivalents, and provides a 99.71% probability of finding specific genes. The empty-vector rate is under 5 percent detected from 200 randomly selected clones. Probing of 384 clones with the psbA gene of barley chloroplast and the atp6 gene of rice mitochondrion indicated that the contamination with organellar DNA is insignificant. Successive subculture of three clones showed that the inserts are stable in one hundred generations. CONCLUSIONS: This study presented the construction of a high-quality BAC library for the genome of Chinese cultivated peanut. Many essential experiences were summarized in the present study. This BAC library can serve as a substantial platform for development of molecular marker, isolation of genes and further genome research.

[Effects of aspirin on CX3CL1 and CX3CR1 in acute pulmonary embolism rats].

OBJECTIVE: To explore the intervention of aspirin and the changes of CX3CL1 and its receptor CX3CR1 in a rat model of acute pulmonary embolism (APE). METHODS: The autologous blood clot method was employed to establish the animal model of APE. A total of 64 rats were randomly divided into 4 groups: normal group (control), sham operation group (sham), model group (model) and aspirin group (aspirin). The profiles of pathology and tissue immunohistochemistry of CX3CL1 and CX3CR1 were compared at 4 h versus 72 h post-embolization. RESULTS: At 4 h and 72 h post-embolism, hematoxylin and eosin staining of lung tissue showed a high degree of expansion of alveolar wall vessels and congestion. Furthermore, several rats had hemorrhagic infarction under light microscope. After the dosing of aspirin, hyperemia of lung tissue and the number of rats with infarction significantly decreased. Immunohistochemistry: CX3CL1 was predominantly expressed in cytoplasm and membrane while CX3CR1 in cytoplasm and nuclear membrane. Both showed strongly positive expression in the model group (++++) and slightly positive expression in the aspirin group (+). At 4 h and 72 h post-embolization, the CX3CL1 and CX3CR1-positive cell counts of the control, sham and aspirin groups were significantly less than those of the model group (P < 0.05). CONCLUSION: Aspirin may improve the pathology and inhibit the expression of CX3CL1 and CX3CR1 in APE lung.

Effects of sodium copper chlorophyllin on mesenchymal stem cell function in aplastic anemia mice.

OBJECTIVE: To investigate the effects of sodium copper chlorophyllin (SCC) on the proliferation, differentiation and immunomodulatory function of mesenchymal stem cells (MSCs) from mice with aplastic anemia. METHODS: A mouse model of aplastic anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy Co60 γ radiation, followed by transplantation of 2×10(6) lymph node cells from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice were randomly divided into six groups: the treated groups, which received 25, 50, or 100 mg/kg/day SCC, respectively; a positive control group treated with cyclosporine A (CsA); and an untreated model control group (model group); while, the non-irradiated mice as the normal control group. SCC or CsA were administered by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral blood cells were counted and colony-forming fibroblasts (CFU-F) in the bone marrow were assayed. The ability of MSCs to form calcium nodes after culture in osteoinductive medium was also observed. The immunosuppressive effect of MSCs on T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia. RESULTS: Peripheral blood white cell and platelet counts were increased by medium and high SCC doses, compared with the untreated control. CFU-Fs were also increased compared with the untreated control, and the numbers of calcium nodes in MSCs in osteoinductive medium were elevated in response to SCC treatment. The percentage of Forkhead box protein 3 (FOXP3(+)) T cells was increased in T cell-MSC cocultures, and the cytokine transforming growth factor ß1 was up-regulated in SCC-treated groups. CONCLUSION: The results of this study suggest that SCC not only promotes the proliferation and differentiation of MSCs, but also improves their immunoregulatory capacity in mice with aplastic anemia.

Identification and characterization of a gene encoding a putative lysophosphatidyl acyltransferase from Arachis hypogaea.

Lysophosphatidyl acyltransferase (LPAT) is the important enzyme responsible for the acylation of lysophosphatidic acid (LPA), leading to the generation of phosphatidic acid (PA) in plant. Its encoding gene is an essential candidate for oil crops to improve oil composition and increase seed oil content through genetic engineering. In this study, a full length AhLPAT4 gene was isolated via cDNA library screening and rapid amplification of cDNA ends (RACE); our data demonstrated that AhLPAT4 had 1631 nucleotides, encoding a putative 43.8 kDa protein with 383 amino acid residues. The deduced protein included a conserved acyltransferase domain and four motifs (I­IV) with putative LPA and acyl-CoA catalytic and binding sites. Bioinformatic analysis indicated that AhLPAT4 contained four transmembrane domains (TMDs), localized to the endoplasmic reticulum (ER) membrane; detailed analysis indicated that motif I and motifs II­III in AhLPAT4 were separated by the third TMD, which located on cytosolic and ER luminal side respectively, and hydrophobic residues on the surface of AhLPAT4 protein fold to form a hydrophobic tunnel to accommodate the acyl chain. Subcellular localization analysis confirmed that AhLPAT4 was a cytoplasm protein.Phylogenetic analysis revealed that AhLPAT4 had a high homology (63.7­78.3%) with putative LPAT4 proteins from Glycine max, Arabidopsis thaliana and Ricinus communis. AhLPAT4 was ubiquitously expressed in diverse tissues except in flower, which is almost undetectable. The expression analysis in different developmental stages in peanut seeds indicated that AhLPAT4 did not coincide with oil accumulation.

[Effect of purple sweet potato flavonoids on metabolism of glucose and lipids in diabetic rats].

OBJECTIVE: To investigate the effects of purple sweet potato flavonoids (PSPF) on blood glucose and lipids levels in diabetic rats. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg.kg(-1)) in rats. The changes of fasting blood glucose and lipids levels in serum and body weight, food and fluid intake of diabetic rats treated with PSPF were examined. RESULTS: Diabetic symptoms were ameliorated after rats were fed with PSPF. The fasting blood glucose (FBG), GSP, TC, TG, LDL-C were decreased and serum HDL-C levels were increased (P<0.01) in high, medium dose PSPF groups; while FBG, serum GSP, TG, LDL-C were also improved in low dose group (P<0.05 or P<0.01). CONCLUSION: Purple sweet potato flavonoids can decrease the blood glucose and lipids levels in diabetic rats.

[Differential expression of genes related to bacterial wilt resistance in peanut (Arachis hypogaea L.)].

Peanut bacterial wilt (BW) caused by Ralstonia solanacearum is one of the most devastating diseases for peanut production in the world. It is believed that breeding and subsequent planting BW-resistant cultivars of peanut (Arachis hypogaea L.) should represent the most effective and economic means of controlling the disease. To illustrate the molecular mechanism of peanut resistant to BW, a BW-resistant cultivar, 'Yuanza 9102', and a BW-sensitive one, 'Zhonghua 12', were infected with Ralstonia solanacearum and differential expression of the genes related to BW-resistance was analyzed using complementary DNA amplified length polymorphism (cDNA-AFLP) technique. The infected 3-leaflet seedlings were followed for 48 h and root samples were taken at 0, 2, 10, 24 and 48 h after inoculation, respectively. A total of 12596 transcript-derived fragments (TDFs) were amplified with 256 primer combinations, including 709 differential expressed TDFs, which were generated from 119 primer combinations. Ninety-eight TDFs were randomly chosen for DNA sequence analysis. BLASTx analysis of the obtained sequences revealed that 40 TDFs encoded gene products associated with energy, transcription, signal transduction, defense, metabolism, cell growth, cell structure or/and protein synthesis. Analysis of the expression of four genes by qRT-PCR verified the results from cDNA-AFLP. Strikingly, one of the identified TDFs, 32-54-1, occurred for 47 times in a known BW-resistant SSH library. These results suggest that resistance to BW in peanut involves multifaceted biochemical and physiological reactions, including regulation of the genes involved in different pathways, such as defense, singal transduction, metabolism, transcription and abiotic stresses. The TDF 32-54-1 was predicted to be closely related to BW resistance in peanut.

[Effect of chemotherapy preoperatively upon early postoperative cognitive dysfunction in eldly tumor patients].

OBJECTIVE: To investigate whether preoperative chemotherapy history could influence the incidence of early postoperative cognitive dysfunction (POCD) in elderly tumor patients. METHODS: A total of 107 tumor patients (> or = 60 years old, tumor TNM stages T2 - T3, N0 - N3, ASA I -III class) undergoing elective radical surgery of gastric or colorectal cancer were selected and assigned into two groups according to preoperative chemotherapy history: with preoperative chemotherapy history group (C group, n = 52) and without preoperative chemotherapy history group (N group, n = 55). Patients in two groups received radical surgery under intravenous-inhalation general anesthesia combined with epidural anesthesia. Cognitive function was assessed using a battery of neuropsychological tests from five aspects including memory, verbal intelligence, visual-motor, executive function and motor function at 1 day preoperatively and 3 days postoperatively. RESULTS: There was no significant difference in general state of patient preoperatively health including sex ratio, body mass index, complications, cancer types and stages, ASA classification between two groups (P > 0.05). Neither significant difference was found in duration of anesthesia and surgery, intra-operative bleeding volume and transfusion volume between two groups (P > 0.05). There was no significant difference in ICU admission rate, ICU stay, incidence of complications, hospitalization duration and mortality rate between two groups (P > 0.05). Preoperative neuropsychological test score in group C was slightly lower than that in group N, but the difference was not significant (P > 0.05). Impaired incidence rate of digit-symbol substitution test, controlled oral word association test, grooved pegboard non-dominant hand test and semantic fluency test at 3 days postoperation in group C were significantly higher than those in N group (P < 0.05). Incidence of POCD at 3 days postoperation in group C was significantly higher than that in group N (42.3% vs 15.4% , P < 0.05). CONCLUSION: Chemotherapy preoperatively could increase the incidence of early postoperative cognitive dysfunction in elderly with tumor.

[Intensive insulin therapy in critically ill patients].

OBJECTIVE: To observe the effect of intensive insulin therapy on improving the condition of critically ill patients. METHODS: A prospective, randomized, controlled study involving adults receiving mechanical ventilation was performed. On admission, critically ill patients were randomly assigned to receive intensive insulin therapy (infusion of insulin only if the blood glucose level exceeded 6.1 mmol/L and maintenance of blood glucose at a level 4.4-6.1 mmol/L, IT group) and conventional treatment (infusion of insulin only if the blood glucose level exceeded 11.9 mmol/L and maintenance of blood glucose at a level 10.0-11.1 mmol/L, CT group). The blood glucose was detected every 4 hours. The days of stay in the intensive care unit (ICU), time of the ventilatory support needed, the time for retention of tracheal intubation, the morning blood glucose level (6 am), the intake of nonprotein calories per day, the dosage of required insulin per day,therapeutic intervention scoring system-28 (TISS-28) score,human leukocyte antigen (locus) DR (HLA-DR), CD4+/CD8+, the mortality rate,acute renal failure (serum creatine >221 micromol/L), bilirubinemia (total bilirubin >34.2 micromol/L),the number of patients who received red-cell transfusions,fever (temperature in mouth >38.5 centigrade) and the rate of hypoglycemia were determined and registered. RESULTS: In a total of 116 patients enrolled, intensive insulin therapy reduced mortality rate (44.83 % with conventional treatment, compared with 12.07 % with intensive insulin therapy,P< 0.01). Intensive insulin therapy reduced the days of stay in ICU, TISS-28 score per day, time of the ventilatory support needed, time for retention of tracheal intubation, mean morning blood glucose levels (6 am) compared with those in CT group (P<0.05 or P<0.01), and patients receiving intensive insulin therapy were less likely to require intensive care. Intensive insulin therapy also raised consumption of insulin per day, HLA-DR and CD4+/CD8+ obviously (P<0.05 or P<0.01). Compare with the morbidity between two groups, the incidence of fever due to infection, acute renal failure and red-cell transfusions were higher in CT group (all P<0.01). CONCLUSION: Intensive insulin therapy maintaining blood glucose at a level 4.4-6.1 mmol/L reduces mortality rate among critically ill patients.

[A SCAR marker for resistance to Aspergillus flavus in peanut (Arachis hypogaea L.)].

Aflatoxin contamination is an important constraint to peanut (Archis hypogaea L. ) industry worldwide. Genetic improvement for host resistance in peanut to fungal infection and aflatoxin (Aspergillus flavus) production is among the approaches for integrated management of the problem. However, the progress in peanut breeding for resistance to aflatoxin is slow due to various reasons, among which, lack of cost-effective method for resistance identification in breeding materials or segregating progenies has been encountered in most breeding programs. Hence there is a need to develop a rapid and reliable screening method for selecting A. flavus infection resistance in peanut. Here we report a SCAR (Sequence characterized Amplified Region) marker "AFs-412" converted from AFLP (amplified fragment length polymorphism) marker "E45/M53-440" which closely linked with resistance to A. flavus infection. Twenty peanut genotypes with resistance to infection of A. flavus were used to verify the reliability of the resistance markers, and high correlation between the molecular markers and the resistance result. The result shows that the potential of the markers which can be used in other resistant peanut genotypes to seed infection by Aspergillus flavus.