Effect of a Novel Dihydroartemisinin Dimer Containing Nitrogen Atoms SM 1044 on Apoptosis of Human Leukemia Cell Line NB4-R1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of a water-soluble novel dihydroartemisinin dimer containing nitrogen atoms SM 1044 on the apoptosis of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanism.@*METHODS@#The effects of SM 1044 on cell apoptosis, mitochondrial transmembrane potential, and the level of reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of apoptosis-related proteins were determined by Western blot. The effects of SM 1044 on MAPK (ERK, JNK) signaling pathway, PML/RARα fusion protein, and expressions of apoptosis-related proteins were detected by Western blot.@*RESULTS@#SM 1044 could significantly induce apoptosis and the loss of mitochondrial transmembrane potential in NB4-R1 cells, and activate apoptosis-related proteins caspase-3, caspase-8, caspase-9 and poly (ADP-ribose) polymerase (PARP). SM 1044 could also induce NB4-R1 cells to produce ROS. Western blot showed that SM 1044 activated the phosphorylation of MAPK (ERK, JNK) signaling pathway and down-regulated the expression of PML/RARα fusion protein.@*CONCLUSION@#SM 1044 can induce apoptosis of ATRA resistant APL NB4-R1 cells, which may be related to ROS/ERK and ROS/JNK signaling pathway, and can also induce by down-regulating PML/RARα fusion protein.

Mechanism and experimental verification of Dachengqi Decoction in treatment of sepsis based on network pharmacology / 中国中药杂志

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P<0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1β(IL-1β), IL-6 and tumor necrosis factor α(TNF-α)(P<0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P<0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.

Quality control of Dandeng Tongnao Ruanjiaonang based on UPLC fingerprint combined with chemical pattern recognition / 中国中药杂志

To establish the ultra performance liquid chromatography (UPLC) fingerprint of Dandeng Tongnao Ruanjiaonang and conduct a systemic, comprehensive quality evaluation of the drug by combining with a chemical pattern recognition method. In this study, Waters UPLC ultra-high performance liquid chromatography instrument and ACQUITY UPLCHSS T3 chromatographic colum n were employed to perform the separation with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution; and the detection wavelength was set at 256 nm to establish the UPLC fingerprint of 10 batches of Dandeng Tongnao Ruanjiaonang. Then, the further quality assessment of the drug was carried out by similarity evaluation, Cluster Analysis(CA), Principal Component Analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, 77 peaks were recognised as common peaks in the fingerprint, and 15 peaks of them were identified using standard references. The similarity value of these 10 batches of drugs was all above 0.960, indicating a relatively stable quality. But minor differences were still discovered between the batches of the drug by CA and PCA. Finally, 6 common peaks were recognised as the quality makers using OPLS-DA method. The analysis method established in this study was scientific, accurate, reliable and simple; fingerprint combined with chemical pattern recognition technique can be used to systematically and comprehensively evaluate the drug quality of Dandeng Tongnao Ruanjiaonang; what's more, it could also provide a reference for the quality control of traditional Chinese medicine and its preparations at the same time.

Intermediate-conductance Ca2+-activated K+ channel: Research advances / 国际药学研究杂志

Intermediate-conductance Ca2+-activated K+ channel, also known as KCa3.1, IKCa and SK4, is widely distributed in fibroblasts, proliferating smooth muscle cells, endothelial cells, T lymphocytes, plasma cells, macrophages, and epithelial cells, and involved in the pathological and physiological processes such as vascular contraction, inflammation, calcification, tissue fibrosis, immune response, malignant tumor, internal and external secretory glands. In recent years, it has been found that blocking the KCa3.1 pathway or knockouting the gene can significantly prevent the pathophysiological process of its involvement. The recent use of the specific blocker TRAM-34 in animals and humans shows its safety and tolerability, providing a new direction for the treatment of related diseases. In this article, the research progress in KCa3.1 related diseases in recent years is reviewed.

Analysis on quality and differences of Mentha haplocalyx from different regions / 中国中药杂志

A gas chromatography-mass spectrometry(GC-MS)method was established for the analysis of volatile components in Mentha haplocalyx, and seven principal components were quantified by gas chromatography(GC). Based on these analyses, the differences of volatile components in M. haplocalyx from Jiangsu, Anhui and other regions were compared. The results showed that the volatile oil of M. haplocalyx was divided into four chemical types：menthol-menthone type, pulegone-menthone type, piperitone-menthol type, piperitone epoxide type, and menthol-menthone type was the principal type. Menthol was the highest and pulegone was the lowest. The differences of M. haplocalyx from Anhui and other regions were obvious. The major volatile components and the differences of M. haplocalyx from different regions were confirmed and a quantitative method was established for the determination of volatile components, which provided the basis for improving the quality standard of M. haplocalyx.

The study of the expression and the prognostic value of Survivin and Ki67 in pancreatic endocrine tumors / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the expression of Survivin and Ki67 with prognosis of pancreatic endocrine tumors (PETs).</p><p><b>METHODS</b>Immunohistochemistry for Survivin and Ki67 was performed in 25 cases of normal pancreatic tissues and 81 cases of PETs by tissue microarrays and to observe the expression and evaluate the relationship with prognosis.</p><p><b>RESULTS</b>(1)The expression of Survivin and Ki67 in PETs was significantly higher than that in normal pancreatic tissues (P <0.01); (2)The expression of Survivin and Ki67 in PETs was correlated with tissue grading and the TNM-staging (P < 0.05), but not related with tumor size, location and functional status. In addition, the expression of nuclear Survivin was association with lymph node metastasis (P < 0.05). (3)The high expression of Ki67 was related with the expression of nuclear Survivin, but not related with the expression of cytoplasmic Survivin.</p><p><b>CONCLUSION</b>Survivin and Ki67 were both expressed in PETs, which were closely related to the clinical pathological characteristics. They could be used as new indicators in the evaluation of prognosis of PETs. The expression of Survivin in nucleus had more diagnostic significance than that in cytoplasm, and that could be highly correlated with lymph node metastasis, which would be used as a new marker of poor prognosis.</p>

The effects of Kangai injection on enzyme activities of macrophages in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of Kangai injection on the enzyme activities of macrophages and morphology of spleen and thymus from rats.</p><p><b>METHODS</b>Twenty four male SD rats were randomly divided into two groups (n = 12), normal control group and experimental group. The rats in experimental group were injected with Kangai injection at the dosage of 5 ml/kg x d for 30 days peritoneally and those in control group were injected with nomal saline at the same volume. The content of supermicro protein was assayed by BCA method, the activities of lactate dehydrogenase (LDH), glutathione peroxidase(GSH-Px), and inducible nitric oxide synthase (iNOS) from alveolar macrophages(AM) and peritoneal macrophages (PM) were detected biochemically. The activities of acid phosphatase (ACP), superoxide dismutase(SOD) and succinate dehydrogenase (SDH) from AM and PM were detected by ELISA. The morphology of spleen and thymus were observed by light microscopy.</p><p><b>RESULTS</b>The activities of LDH, GSH-Px and iNOS within AM and PM from experimental group were increased significantly compared with those of control group (P < 0.05). The activities of ACP, SOD and SDH in AM and PM from experimental group were also higher than those from control group (P < 0.05). Microscopically, there was thickening of peripheral arterial lymphatic sheath, enlargement of splenic lymphoid nodules with expended germinal center in the spleen of experimental group. There was no significant difference in the mophology of thymus between the two groups.</p><p><b>CONCLUSION</b>Kangai injection may improve immune function by activating macrophages.</p>

Synthesis and identification of artificial antigen of forsythin / 中国中药杂志

The establishment of high specificity and sensitivity method of small molecule monoclonal antibody-based immunoassay has a great importance in the study of small molecule compounds in Chinese medicine, wherein synthesis of small molecule artificial antigen is a critical step in the preparation of small molecule antibodies. Oxidation method using sodium iodide was used to synthesize immunogenic antigen (FRn-BSA) and coating antigen (FRn-OVA) of forsythin. UV spectroscopy and thin layer chromatography showed that forsythin was successfully conjugated with BSA and OVA. After immuned FRn-BSA, the mice could specifically produce anti-forsythin antibodies with titer up to 1:8 000, and the linear range was from 1 mg x L(-1) to 100 mg x L(-1). In this paper, the artificial antigen of forsythin was successfully synthesized, which can be applied for preparation of monoclonal antibodies and establishment of appropriate immune method.

Synthesis and experimental study of a novel polymer/gene compound drug controlled release system for the treatment of erectile dysfunction / 中华男科学杂志

<p><b>OBJECTIVE</b>To overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy.</p><p><b>METHODS</b>We synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures.</p><p><b>RESULTS</b>When the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05).</p><p><b>CONCLUSION</b>The polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.</p>

Cornelia de Lange syndrome: report of a case and the review of literature on 17 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics of Cornelia de Lange Syndrome (CdLS) and to review the latest clinical research reports.</p><p><b>METHOD</b>Clinical and laboratory data of one case of neonatal CdLS are reported, and literature on 17 cases of CdLS in China and the international reports of the clinical and molecular biological research on this disease were reviewed.</p><p><b>RESULT</b>(1) The patient was an infant with intrauterine growth retardation and born as a term small for gestational age infant with specific facial features, bone abnormality of extremities, and patent ductus arteriosus (PDA). She also had severe feeding difficulty and slow weight gain. She was followed up till 4 months of age and showed severe developmental retardation. (2) The total number of past reported case of CdLS in China was 17 with a male to female ratio of 6:12. The average age of diagnosis was 17 months. The following specific facial features could be observed: synophrys, long and curved eyelashes, hirsutism, microcephalus, low hairline, broad depressed nasal bridge, long prominent philtrum, and high palate. Most of the patients were complicated with mental retardation, recurrent vomiting or feeding difficulty, abnormal muscle tone, cutis marmorata, hypophalangism, and genitalia anomaly. Clinical manifestations of Chinese patients were similar to those of the overseas reports. The karyotype of 15 cases was investigated and was normal. The etiology of CdLS is unknown. There is no specific treatment. The commonest causes of death are lung diseases caused by gastroesophageal reflex/aspirate related pneumonia.</p><p><b>CONCLUSION</b>Typical clinical manifestations of CdLS are specific facial features (mainly synophrys, long and curved eyelashes, long prominent philtrum), complications of multi-system malformations (mainly growth and developmental retardation, esophagogastric reflex, hypophalangism), related gene mutations occurred in NIPBL, SMC1A, and SMC3 gene.</p>

Effects of low-dose chlorpyrifos exposure on dopaminergic neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the effects of low-dose chlorpyrifos (CPF) exposure on dopaminergic (DA) neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats.</p><p><b>METHODS</b>Postnatal 11 day old Sprague-Dawley rats were randomly assigned into CPF, menstruum dimethysulfoxide (DMSO) and normal saline (NS) groups. The rats in the CPF group were injected with low-dose CPF (5 mg/kg?d) on postnatal days 11-14. The two control groups were injected with DMSO or NS respectively. The rats were sacrificed on postnatal days 15, 20, 30, and 60. Body weight gain, outward appearance of brain tissue, the coefficient of brain and the water content of brain tissue were measured. Tyrosine hydroxylase (TH) expression in DA neurons in the midbrain substantial nigra was examined by immunohistochemical straining. Immune electron microscopy was used to examine the subcellular structure of DA neurons. Open field test, grip strength test, slope test and Morris water maze test were used to examine the neurobehavioral changes.</p><p><b>RESULTS</b>The outward appearance of brain tissue was normal in the three groups. There were no significant differences in the absolute value of body weight gain, the coefficient of brain and the water content of brain tissue among the three groups. CPF exposure decreased the level of TH immunoreactivity (P<0.05) in the substantia nigra of CPF group since postnatal day 30 compared with the DMSO and NS groups. The subcellular structures of some DA neurons in the CPF group were impaired. Decreased motor activity and learning and memory impairments were observed in the CPF group compared with those in the DMSO and NS groups (P<0.05) since postnatal day 30.</p><p><b>CONCLUSIONS</b>CPF exposure during the neonatal period can cause long-term motor activity and learning and memory impairments in accompany with DA neurons damage in the midbrain substantia nigra.</p>

Impact of Cryptotanshinone on the reproductivity and metabolism of male mice with Akt2 deletion / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the impact of protein kinase B (Akt2) allele deletion on testicular reproductive function, and to discuss the regulatory effect of Cryptotanshinone on the reproductivity of male mice with Akt2 allele deletion and its molecular mechanism.</p><p><b>METHODS</b>Fifteen Akt2 +/+ male mice were randomly divided into Groups A (baseline control, n = 7) and B (stimulation, n = 8), and another 29 Akt2 -/- male mice into C (baseline control, n = 7), D (stimulation, n = 8), E (solvent, n = 7) and F (Cryptotanshinone, n = 7). Groups B and D underwent human chorionic gonadotropin (HCG) stimulation tests at 5 IU / 20 g, while A and C received physiological saline, all for 4 hours; Group F were given gastric lavage of Cryptotanshinone, while E solvent only, at 600 mg/kg twice a day for 8 weeks, both subjected to oral glucose tolerance tests (OGTT) at 2 g/kg before and after the treatment. The body and bilateral testis weights were obtained, the serum testosterone (T) level measured, and the expressions of testicular steroid hormone synthesis and glycometabolism-related genes determined by RT-PCR.</p><p><b>RESULTS</b>OGTT showed that the level of blood glucose was significantly higher in Groups C and D than in A and B ([10.38 +/- 1.42] and [10.96 +/- 1.81] mmol/L vs [7.92 +/- 0.63] and [8.32 +/- 0.44] mmol/L, P < 0.05), but had no significant differences at different time points in E and F (P > 0.05). The testis weight was remarkably higher in Groups C and D than in A and B ([0.17 +/- 0.01] and [0.17 +/- 0.01] g vs [0.15 +/- 0.01] and [0.15 +/- 0.02] g, P < 0.05), but exhibited no obvious difference in E and F, nor were there any significant differences in body weight among different groups (P > 0.05). The serum T level was markedly higher in Group C than in A ([9.08 +/- 1.59] nmol/L vs [6.42 +/- 0.95] nmol/L, P < 0.05), but evidently lower in F than in E ([5.94 +/- 0.49] nmol/L vs [8.18 +/- 1.44] nmol/L, P < 0.05). The baseline expression levels of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA were significantly higher in Group C than in A (P < 0.05). After HCG stimulation, the expressions of Cyp11, Cyp17, 3B-HSD, and Star mRNA were remarkably increased in B and D, but with no obvious difference between the two groups (P > 0.05), while the expressions of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA markedly decreased in F as compared with E (P < 0.05).</p><p><b>CONCLUSION</b>Akt2 gene deletion may affect glycometabolism and testicular function, and cause abnormal glycometabolism and androgen secretion in male mice, whose molecular mechanism is associated with the elevated expressions of the key glycometabolic molecules and of the key enzymes for androgen synthesis. Cryptotanshinone can reduce the levels of androgens by down-regulating the expressions of the key enzymes for androgen synthesis.</p>

Umbilical venous catheterization related infection in the neonatal intensive care unit / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the incidence and pathogens of umbilical venous catheterization (UVC) related infection in the neonatal intensive care unit (NICU).</p><p><b>METHODS</b>A total of 112 neonates (birth weight 1,500 g) who received UVC within 24 hrs after birth were included. Blood culture was performed right after UVC. At 24 hrs and 1 week after UVC, umbilical skin scrub cultures were performed. Skin redness and swelling for more than 24 h, or severe abdominal distension, or poor general condition for unknown reason after UVC, or positive blood culture results, were the criteria for catheterization related infection.</p><p><b>RESULTS</b>The incidence rate for UVC related infection was 8.9%. Total culture positive rate was 9.4%. At 24 hrs and 1 week after UVC, the umbilical skin scrub culture positive rate was 7.1% and 16.2%, respectively. Rate of Gram positive and Gram negative pathogens was 55.2% and 44.8%, respectively. Group B Streptococcus was main Gram positive pathogen. Klebsiella and E.coli were the main Gram negative pathogens.</p><p><b>CONCLUSIONS</b>UVC is, to some extent, related to nosocomial infection in the NICU. Among UVC related infection, Gram positive and Gram negative pathogens take almost the chance.</p>

Research progress on gene mutation of jak2 / 中国实验血液学杂志

Chronic myeloproliferative disease (CMPD) is a group of malignant blood disorders including polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic myeloid leukemia, and so on. CMPD is characterized by proliferation of one or several lineages in hematopoietic system. The pathogenesis of CMPD is not clear except chronic myeloid leukemia associated with the bcr/abl fusion gene. In recent years, more studies demonstrated that CMPD have a higher mutation rate of gene jak2. In this review, the association of jak2 gene mutation with clinical diagnosis, clinical feature and molecular target therapy in CMPD and other hematological disease were summarized.

Preoperation risk factor analysis in orthotopic liver transplantation with pre-transplant artificial liver support therapy / 中华肝脏病杂志

<p><b>OBJECTIVES</b>Orthotopic liver transplantation (OLT) is an accepted therapy for selected patients with advanced liver diseases. However, the early mortality rate after OLT remains relatively high due to the poor selection of candidates with various serious conditions. The aim of this study is to assess the value of pretransplantation artificial liver support treatment in reducing the pre-operation risk factors relating to early mortality after OLT.</p><p><b>METHODS</b>50 adult patients in various stages of different etiologies who underwent OLT procedures had been treated with molecular adsorbent recycling system (MARS) preoperatively. The study was designed in two parts: the first one was to evaluate the effectiveness of a single MARS therapy by using some clinical and laboratory parameters which were supposed to be therapeutical pretransplantation risk factors. The second part was to study the patients undergoing OLT by using the regression analysis on preoperation risk factors relating to early (within 30 d after OLT) mortality rate.</p><p><b>RESULTS</b>Among the 50 patients, a statistically significant improvement of the biochemical parameters was observed (pretreatment vs posttreatment). 8 patients cancelled their scheduled LTXs due to significant improvements in their clinical conditions or recovery of their failing liver functions. 8 patients died and 34 patients successfully underwent LTX. The immediate outcome (within 30 postoperative days) of these 34 patients was that 28 were kept alive and 6 died.</p><p><b>CONCLUSIONS</b>Preoperation sequential organ failure assessment (SOFA), level of creatinine, INR, TNFalpha, and IL-10 are the main preoperative risk factors relating to early death after an operation. MARS treatment before a transplant operation can relieve these factors significantly, hence improve survival rate of liver transplantation or even make the transplantation unnecessary.</p>