Objective:To evaluate the anti-HIV-1 activity of two new nonnucleoside reverse transcriptase inhibitors (NNRTIs), JB25 and JB26, in combination with 3 approved drugs (AZT, EFV, SQV)in vitro.Methods:The serially diluted 10 concentrations of JB25 and JB26 were combined with 7 serially diluted AZT, EFV and SQV respectively.The combination was added to 384 cell culture plates and then cocultured with HIV-1 ⅢB infected MT-2 cells for 3 days. Finally, the HIV-1 production was determined by measuring the expression of reporter genes of TZM bl cells. The data were analyzed by MacSynergy Ⅱ software.Results:The average capacity of synergism/antagonism of JB25 with AZT, EFV and SQV was 244.45/-5.05(nmol/L)~2%, 119.58/-65.93 (nmol/L)~2% and 145.83/-0.32 (nmol/L)~2% respectively;the average capacity of synergism/antagonism of JB26 with AZT, EFV and SQV was 398.90/0(nmol/L)~2%, 103.62/-0.49(nmol/L)~2% and 138.473/-0.27 (nmol/L)~2% respectively. Conclusion:Two new NNRTIs JB25 and JB26 develop synergism when combined with 3 approved drugs, respectively. MacSynergy Ⅱ software could evaluate the anti-HIV-1 activity of drug combination.

OBJECTIVETo investigate the clinical value of glycosylated G-CSF combined with middle-high dose cyclophosphamide (Cy) or conventional chemotherapy with increased dose of Cy for mobilizing peripheral blood progenitor cells in patients with tumor.

METHODSThirty patients from four hospitals in Beijing region were enrolled in this clinical study. Diagnoses of the patients were non-Hodgkin' lymphoma (n = 21), Hodgkin disease (n = 1), breast cancer (n = 7) and ovary cancer (n = 1). Autologous peripheral blood progenitor cells (APBPC) were mobilized by middle-high dose Cy or conventional chemotherapy with increased dose of Cy combined with G-CSF. G-CSF was given subcutaneously from the nadir of the white blood cell (WBC) count to the end of PBPC collection. The dosage of G-CSF was 250 microg/d in 29 patients and 500 microg/d in 1 patient. When WBC count was > 5 x 10(9)/L, APBPC were harvested with CS 3000 plus/COBE Spectra.

RESULTSThe average dosage of Cy was 3.95 g (2.3 g/m(2)). The doses of G-CSF were 3.1 approximately 6.4 microg x kg(-1) x d(-1). Thirteen patients (43%) were collected twice, 14 patients (47%) three times and 3 patients (10%) four times. All of the patients could tolerate the treatment regimens. Seven patients had bone pain after G-CSF injection and one was severe, one patient had headache and one had nausea and vomiting.

CONCLUSION250 microg glycosylated G-CSF combined with middle-high Cy or conventional chemotherapy with increased dose of Cy combined G-CSF is an optimal method for APBPC mobilization in tumor patients.

Adolescent ; Adult ; Antigens, CD34 ; analysis ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colony-Forming Units Assay ; Cyclophosphamide ; administration & dosage ; Dose-Response Relationship, Drug ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukocyte Count ; Leukocytes, Mononuclear ; cytology ; drug effects ; immunology ; Male ; Middle Aged ; Neoplasms ; blood ; drug therapy ; pathology ; Platelet Count ; Treatment Outcome

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.
Aminolevulinic Acid ; pharmacology ; therapeutic use ; Animals ; Brain Neoplasms ; blood supply ; drug therapy ; pathology ; Cell Line, Tumor ; Glioma ; blood supply ; drug therapy ; pathology ; Microvessels ; drug effects ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the role of enhanced recovery after surgery in treating cervical spondylotic myelopathy.

METHODSThe clinical data of 55 patients with cervical spondylotic myelopathy underwent surgical treatment from January 2012 to December 2015 were retrospectively analyzed. There were 30 males and 25 females, age from 36 to 71 years old with an average of (45.2±3.2) years, course of disease was for 1 to 12 months with an average of (4.5±1.8) months. The concept of enhanced recovery after surgery and perioperative management were applied to surgical treatment in 35 patients (study group), and the same period, 20 patients without strategy of enhanced recovery after surgery (control group). Thirty-eight patients were treated by anterior cervical discectomy decompression and fixation(ACDF), 17 patients were treated by posterior single-open door laminoplasty decompression. The activity time out of bed, hospitalization days after surgery were compared between two groups. Japanese Orthopaedic Association (JOA) score and visual analogue score(VAS) before operation, after operation at 1, 7, 30 days and 6, 12 months was respectively used to evaluate the neurological function and pain.

RESULTSAll the patients were followed up for 12 to 18 months with an average of (14.3±1.5) months. There was no significant difference in age, gender, surgical methods, preoperative VAS, JOA score between two groups (>0.05). The activity time out of bed was 3 to 8 h with an average of (5.54±1.54) h, postoperative hospitalization time was 3 to12 d with an average of (5.62±1.59) d in study group, while in control group, the activity time out of bed was 24 to 48 h with an average of (18.80±4.78) h, and postoperative hospitalization time was 7 to 17 d with an average of (9.85±1.94) d; there was significant difference between two groups (<0.01). There was significant difference in VAS and JOA scores between two groups at 1, 7, 30 d after operation (<0.01), and there was no significant difference at 6, 12 months after operation(>0.05). There were no neurologic function deterioration, hematoma, wound infection, internal fixation loosening and other complications in study group during hospitalization and following-up;there were 2 cases of superficial wound infection in the control group, who healed by dressing change for 2 weeks;there was no significant difference between two groups(>0.05).

CONCLUSIONSThe strategy of enhanced recovery after surgery in treating cervical spondylotic myelopathy can promote the early recovery, shorten the length of stay and improve the patient's degree of satisfaction.

Heart Defects, Congenital/diagnosis* ; Humans ; Hypertension ; MicroRNAs/genetics* ; Pulmonary Arterial Hypertension ; Pulmonary Artery/diagnostic imaging*

Objective:To observe clinical effect on chronic atrophic gastritis （CAG） with deficiency of stomach Yin when modified Shaoyao Gancaotang combined with Yiguanjian used on patients， and to study influence to prognostic risk. Method:One hundred and ten cases patients were randomly divided into control group 54 cases and observation group 56 cases. Two groups got treatment of eradication of Helicobacter pylori （Hp）. Patients in control group got Yangweishu capsules， 3 grains/time， 2 times/day. Patients in observation groups when Shaoyao Gancaotang combined with Yiguanjian modified， 1 dose/day. The treatment continued for 16 weeks. Before and after treatment， gastroscope was discussed and operative link for gastritis assessment （OLGA） and operative link on intestinal-metaplasia assessment （OLGIM） were recorded， scores of atrophic degree， intestinal metaplasia degree， Hp infection， chronic inflammatory reaction， activity， endoscopic mucosal signs， dyspepsia symptoms， reported outcome patients reported outcomes （PRO） of patients with gastrointestinal diseases were graded. And to test levels of pepsinogenⅠ （PG Ⅰ），PGⅡ， gastrin-17 （G-17）， cytotoxin associated gene A （CagA） and vacuolar cytotoxin （VacA）. Result:The effect of patients treated in observation group was better than the effect of patients received measures in control group （Z=2.068， P<0.05）. Scores of atrophic degree， intestinal metaplasia degree， chronic inflammatory reaction and activity were lower than the scores of patients received measures in control group （P<0.01）. Levels of OLGA （Z=2.037， P<0.05） and OLGIM （Z=2.014， P<0.05） of patients treated in observation group were better than the levels of patients received measures in control group. And levels of PGⅠ， G-17 and PG Ⅰ/PGⅡ of patients treated in observation group were higher than the dates of patients received measures in control group （P<0.01）. Positive rates of CagA and VacA were all lower than the dates in control group （P<0.05）. And gastroscopic mucosal signs and dyspepsia symptoms and scores of PRO were all lower than dates of patients received measures in control group （P<0.01）. Conclusion:On the basis of eradicating Hp， treatment of Shaoyao Gancaotang with Yiguanjian modified can relieve the clinical symptoms， improve the quality of life of patients， promote mucosal repair， improve the pathological changes， reduce the degree and scope of gastric mucosal atrophy， which is conducive to delay the progression of lesions and reduce the risk of canceration when it used on CAG. It has good clinical efficacy and was worthy of further study

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

Traditional Chinese medicine （TCM）， which owns abundant chemical components and complex action pathways， has been widely recognized in the prevention and treatment of diseases. Some analysis methods have been emerged in order to ensure the quality of TCM and to develop new TCM drugs. Matrix-assisted laser desorption ionization mass spectrometry （MALDI-MS） is a soft ionization mass spectrometric technique with the advantages of high throughput， high sensitivity， low cost and so on. It provides technical support for the molecular level study on TCM. At present， this technique has been used in the field of composition analysis and metabonomics research of TCM， and plays an important role in the identification of Chinese herbal medicines， real-time molecular screening and the construction of metabolic network pathway of active ingredients. Among them， the selection of appropriate matrix and sample preparation technology is the key to ensure the detection effect of MALDI-MS. With the development and optimization of new matrix， the continuous improvement of sample preparation technology and the combination of MALDI-MS with various analytical methods will greatly improve the detection effect. Based on this， this paper discusses the application of MALDI-MS in TCM， including high-throughput detection of active ingredients in TCM， monitoring of the original medicines and their metabolites in vivo， and in situ visualization and characterization of tissue distribution information of active ingredients in TCM. It also discusses the application prospect and existing problems of MALDI-MS in TCM， so as to provide technical support for the identification of active ingredients in TCM， drug utilization and metabolism.

OBJECTIVE: To investigate the risk factors for brain injury in preterm infants by a multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China. METHODS: Preterm infants who were hospitalized in the department of neonatology in 9 hospitals of Anhui Neonatal Collaboration Network between January 2016 and January 2017 were enrolled as subjects. The data of maternal pregnancy and clinical data of preterm infants were collected, and the logistic regression model was used to analyze the risk factors for brain injury in preterm infants. RESULTS: A total of 3 378 preterm infants were enrolled. Of the 3 378 preterm infants, 798 (23.56%) had periventricular-intraventricular hemorrhage (PVH-IVH), and 88 (2.60%) had periventricular leukomalacia (PVL). Intrauterine distress, anemia, hypoglycemia and necrotizing enterocolitis (NEC) were risk factors for PVH-IVH (OR=1.310, 1.591, 1.835, and 3.310 respectively; P<0.05), while a higher gestational age was a protective factor against PVH-IVH (OR=0.671, P<0.05). PVH-IVH, NEC and mechanical ventilation were risk factors for PVL (OR=4.017, 3.018, and 2.166 respectively; P<0.05), and female sex and use of pulmonary surfactant were protective factors against PVL (OR=0.514 and 0.418 respectively; P<0.05). CONCLUSIONS Asphyxia/anoxia, infection/inflammation, mechanical ventilation, anemia and hypoglycemia may increase the risk of brain injury in preterm infants.
Brain Injuries ; Cerebral Hemorrhage ; China ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Leukomalacia, Periventricular

Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal non-ribosomal peptide synthetases (NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs. Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed. Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out. Results: The putative tri-modular NRPS AncA was heterologous-expressed in A. nidulans to give anacine (1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line. Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.