Study on mechanism of cryptotanshinone against non-small cell lung cancer based on network pharmacology / 中国药理学通报

Aim To explore the mechanism of cryptotanshinone (CTS) against non-small cell lung cancer (NSCLC) by using network pharmacology and bioinformatics methods. Methods Taking CTS as the research object, TCMSP database, SwissTargetPrediction and PharmMapper target prediction platform were used to collect CTS related targets; OMIM database, Gene-Cards data-base and TCGA database were employed to collect NSCLC related targets; String database and Cytoscape software were applied to construct PPI of intersection targets Network diagram, the hub targets were screened out, and AutoDock Vina was used for molecular docking verification; the R language clusterProfiler package was used to perform GO and KEGG enrichment analysis on the intersection targets; Cytoscape software was employed to construct the "CTS intersection targets-KEGG pathway" network. Results As a result, 75 intersecting targets were obtained, mainly involving various biological processes such as signal transduction, phosphorylation and dephosphorylation, apoptosis and vascular regulation, mainly through pancreatic cancer, colorectal cancer, cancer pathways and JAK-STAT signaling pathways. And cellular pathways such as apoptosis and natural killer cell-mediated cytotoxicity exerted their anti-NSCLC effects. Conclusions CTS exerts its anti-NSCLC effect through multiple targets and multiple pathways, which provides the theoretical support for further in-depth research.

Clinical manifestations and gene mutation analysis of children with noncompaction of the ventricular myocardium: an analysis of 6 cases / 中国当代儿科杂志

This article summarizes and analyzes the clinical features and gene mutation characteristics of children with noncompaction of the ventricular myocardium (NVM). For the 6 children with NVM (4 boys and 2 girls), the age of onset ranged from 3 months to 12 years. Of the 6 children, 5 had arrhythmia, 3 had cardiac insufficiency, 1 had poor mental state, and 1 had chest distress and sighing. NVM-related gene mutations were detected in 4 children, among whom 2 had

Study on metabolic dynamics,metabolic enzyme phenotype and species difference of hepatic and intestinal microsome of psoralidin / 中国中药杂志

This study aims to investigate metabolic activities of psoralidin in human liver microsomes( HLM) and intestinal microsomes( HIM),and to identify cytochrome P450 enzymes( CYPs) and UDP-glucuronosyl transferases( UGTs) involved in psoralidin metabolism as well as species differences in the in vitro metabolism of psoralen. First,after incubation serial of psoralidin solutions with nicotinamide adenine dinucleotide phosphate( NADPH) or uridine 5'-diphosphate-glucuronic acid( UDPGA)-supplemented HLM or HIM,two oxidic products( M1 and M2) and two conjugated glucuronides( G1 and G2) were produced in HLM-mediated incubation system,while only M1 and G1 were detected in HIM-supplemented system. The CLintfor M1 in HLM and HIM were 104. 3,and57. 6 μL·min~(-1)·mg~(-1),respectively,while those for G1 were 543. 3,and 75. 9 μL·min~(-1)·mg~(-1),respectively. Furthermore,reaction phenotyping was performed to identify the main contributors to psoralidin metabolism after incubation of psoralidin with NADPH-supplemented twelve CYP isozymes( or UDPGA-supplemented twelve UGT enzymes),respectively. The results showed that CYP1 A1( 39. 5 μL·min~(-1)·mg~(-1)),CYP2 C8( 88. 0 μL·min~(-1)·mg~(-1)),CYP2 C19( 166. 7 μL·min~(-1)·mg~(-1)),and CYP2 D6( 9. 1 μL·min~(-1)·mg~(-1)) were identified as the main CYP isoforms for M1,whereas CYP2 C19( 42. 0 μL·min~(-1)·mg~(-1)) participated more in producing M2. In addition,UGT1 A1( 1 184. 4 μL·min~(-1)·mg~(-1)),UGT1 A7( 922. 8 μL·min~(-1)·mg~(-1)),UGT1 A8( 133. 0 μL·min~(-1)·mg~(-1)),UGT1 A9( 348. 6 μL·min~(-1)·mg~(-1)) and UGT2 B7( 118. 7 μL·min~(-1)·mg~(-1)) played important roles in the generation of G1,while UGT1 A9( 111. 3 μL·min~(-1)·mg~(-1)) was regarded as the key UGT isozyme for G2. Moreover,different concentrations of psoralidin were incubated with monkey liver microsomes( MkLM),rat liver microsomes( RLM),mice liver microsomes( MLM),dog liver microsomes( DLM) and mini-pig liver microsomes( MpLM),respectively. The obtained CLintwere used to evaluate the species differences.Phase Ⅰ metabolism and glucuronidation of psoralidinby liver microsomes showed significant species differences. In general,psoralidin underwent efficient hepatic and intestinal metabolisms. CYP1 A1,CYP2 C8,CYP2 C19,CYP2 D6 and UGT1 A1,UGT1 A7,UGT1 A8,UGT1 A9,UGT2 B7 were identified as the main contributors responsible for phase Ⅰ metabolism and glucuronidation,respectively. Rat and mini-pig were considered as the appropriate model animals to investigate phase Ⅰ metabolism and glucuronidation,respectively.

Investigation of Paidu Qingzhi Tablets Based on UPLC-Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

Objective::To identify the active constituents of Paidu Qingzhi tablets by UPLC-Q-TOF-MS technique, and to reveal its potential targets and molecular mechanisms by network pharmacology. Method::Chromatography separation was achieved on an ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) with mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile for gradient elution (0-17 min, 95%-5%A; 17-17.01 min, 5%-95%A; 17.01-20 min, 95%A), the flow rate was 0.3 mL·min-1, the column temperature was 40 ℃. Data acquisition was carried out in electrospray ionization (ESI) under the negative ion mode, the scanning range was 50-1 200.Ingredients in Paidu Qingzhi tablets were identified according to reference substance, relative molecular weight, mass spectrometric cleavage rule and literature information. Multiple databases were used to retrieve the targets of these identified ingredients and related diseases treated by the tablets, and metabolic pathways. A visual network of " herbs-compounds-targets-pathways-diseases" was constructed by Cytoscape 3.7.1. Result::A total of 33 active compounds in methanol extract of Paidu Qingzhi tablets were identified by UPLC-Q-TOF-MS, including 27 compounds from Rhei Radix et Rhizoma, 4 compounds from Panacis Quinquefolii Radix, 2 compounds from Ophiopogonis Radix. Totally 18 direct targets and 58 indirect targets corresponding to 31 ingredients were obtained, 7 metabolic pathways including steroid hormone biosynthesis pathway, arachidonic acid metabolic pathway, insulin signaling pathway were strongly correlated with the treatment of hyperlipidemia, acne and simple obesity by Paidu Qingzhi tablets. Conclusion::Ingredients of Paidu Qingzhi tablets are revealed by UPLC-Q-TOF-MS, based on these identified ingredients, targets and related metabolic pathways are visualized by network pharmacology. The current research can provide theoretical basis for quality control and clinical application of Paidu Qingzhi tablets.

Progress in etiology of hypertrophic cardiomyopathy in children / 中国实用儿科杂志

Hypertrophic cardiomyopathy(HCM)in children is a kind of common cardiovascular genetic abnormalities disease,mostly single gene autosomal dominant inherited cardiomyopathy,although it does not exclude other genetic patterns. The main features of HCM are symmetrical or asymmetrical ventricular hypertrophy,and histopathological characteristics are myocyte hypertrophy,being disorganized,and fibrosis. Generally,HCM in children is divided into primary and secondary types. Mutation of sarcomere protein gene is the main cause of primary cardiomyopathy,followed by mutation of non-sarcomere protein gene.Mutation of MYH7,MYBPC3,TNNT and other genes are the main causes of sarcomere HCM. Secondary causes include obesity,diabetic mothers and babies,athlete syndrome,abnormal hormone elevation or drug-induced and so on.

Tumor invasion inhibition of thiophene substituted long chain chalcones / 中国药理学通报

Aim To elucidate the structure-activity re-lationship between a new class of long chain chalcone compounds and tumor invasion. Methods The basic idea of the research was to enhance the specificity by prolonging the molecular structure. Based on the lead compound TSAHC, the thiophene was used as the main derivative at the carbonyl groups to obtain six new chalcones. Then we evaluated the anti-tumor activities of the compounds and the expression of key protein MMP-2 of the tumor invasion. Finally, six new com-pounds were docked to the protein by the SYBYL soft-ware. Results The structures of the six compounds were confirmed by H-NMR and MS. Among them, compound 2,3 showed fine capability to inhibit tumor invasion. The docking results also showed that the sul-fonamide and thiophene groups of the compounds had positive contribution to the target binding of the com-pounds. Conclusion Cell experiments and molecular docking show that the long chain modification of chal-cone by using thiophene as a derivative group can sig-nificantly enhance the anti-tumor invasion.

Effect of FK506 nanospheres on regeneration of allogeneic nerve after transplant

OBJECTIVE@#To discuss effect of FK506 nanospheres used at different time on the regeneration of allogeneic nerve after transplant.@*METHODS@#Single emulsion-solvent evaporation method (O/W) was adopted to prepare the FK506 nanospheres and the tibial nerve of rats after allogeneic transplantation. FK506 nanospheres were used in group A after operation immediately, in group B in 24 h after operation, and in group C in 3 d after operation while FK506 nanospheres were not used in group D; in the 4th, 8th and 12th week after operation respectively, general observation of transplanted nerves, histological examination, image analysis of myelinated fibers, wet-weight determination of musculi triceps surae, retrogradely labeling of neurons by the fluorescein and electrophysiological comparison of bilateral tibial nerve were carried out.@*RESULTS@#FK506 nanospheres can be degraded and absorbed quickly. The neural regenerations in group A and B were similar, which were both much better than those in group C and D. The difference was statistically significant and so was the difference between group C and D.@*CONCLUSIONS@#Drug release rate of FK506 nanospheres is accordant with the regeneration law of damaged nerves and the local application can promote the regenerations of nerves. The effect would be better if the drug is used in earlier period (within 24 h).

Construction and biological characteristics of H5N1 avian influenza viruses with different patterns of the glycosylation sites in HA protein / 病毒学报

The distribution of glycosylation sites in HA proteins was various among H5 subtype avian influenza viruses (AIVs), however, the role of glycosylation sites to the virus is still unclear. In this study, avian influenza H5N1 viruses with deletion of the glycosylation sites in HA were constructed and rescued by site direct mutation and reverse genetic method, and their biological characteristics and virulence were determined. The result showed that the mutants were confirmed to be corrected by HA gene sequencing and Western blot analysis. The EID50 and TCID50 tested in SPF chick embryo and MDCK cells of a mutant rSdelta158 with deletion of glycosylation site at position 158 were slight lower than that of wild type rescued virus rS, and the plaque diameter of rSdelta158 was significant smaller than that of rS. The EID50 and TCID50 of mutants rSdelta169 and rSdelta290 with deletion of glycosylation sites at position 169 and 290, respectively, were slight higher than that of wild type rescued virus rS, the plaque diameters of rSdelta169 and rSdelta290 were similar as that of rS, but the plaque numbers of rSdelta169 and rSdelta290 were 10-fold higher than that to rS. On the other hand, the rSdelta158, rSdelta169 and rSdelta290 showed similar growth rate in chicken embryo fibroblast as rS. All viruses remained high pathogenicity to SPF chickens. Therefore, the growth of AIV can be affected by changes of glycosylation sites in HA protein, by which the effect is variable in different cells.

Inactivation of resistant Mycobacteria mucogenicum in water: chlorine resistance and mechanism analysis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To better understand the mechanism of chlorine resistance of mycobacteria and evaluate the efficiency of various disinfection processes.</p><p><b>METHODS</b>Inactivation experiments of one strain Mycobacteria mucogenicum, isolated from a drinking water distribution system in South China were conducted with various chlorine disinfectants. Inactivation efficiency and disinfectant residual, as well as the formation of organic chloramines, were measured during the experiments.</p><p><b>RESULTS</b>This strain of M. mucogenicum showed high resistance to chlorine. The CT values of 99.9% inactivation by free chlorine, monochloramine and chlorine dioxide were detected as 29.6 +/- 1.46, 170 +/- 6.16, and 10.9 +/-1.55 min. (mg/L) respectively, indicating that chlorine dioxide exhibited significantly higher efficiency than free chlorine and monochloramine. It was also found that M. mucogenicum reacted with chlorine disinfectants more slowly than 5. aureus, but consumed more chlorine disinfectants during longer time of contact. Lipid analysis of the cell construction revealed that 95.7% of cell membrane lipid of M. mucogenicum was composed of saturated long chain fatty acids. Saturated fatty acids were regarded as more stable and more hydrophilic which enabled the cell membrane to prevent the diffusion of chlorine.</p><p><b>CONCLUSION</b>It was concluded that different compositions of cell membrane might endow M. mucogenicum with a higher chlorine resistance.</p>

Successful pregnancy following the transfer of vitrified blastocyst which developed from poor quality embryos on day 3

The selection of pre-embryos for transferred is based on morphological appearance. But some poor quality cleaved embryos also can be cultured to the blastocyst stage and implanted. To assess the clinical pregnancy outcomes of blastocyst transfer which developed from poor quality embryos. A total of 109 cleaved embryos with poor quality were cultured to day 5/day 6 and 27 [24.8%] blastocysts were collected from the 15 cycles/patients undergoing conventional IVF. All the blastocysts were cooling with fast-freezing. Then the blastocysts were warmed for transfer. All of 25 vitrified blastocysts [92.6%] survived after warming and were transferred to 15 patients. Five of the women became pregnant. Our results suggest that vitrified human day 5/day 6 blastocyst transfer which develop from poor quality embryo at day 3 can contribute to increasing cumulative pregnancy rates in assisted reproduction

Simultaneous control of microorganisms and disinfection by-products by sequential chlorination / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To introduce a new sequential chlorination disinfection process in which short-term free chlorine and chloramine are sequentially added.</p><p><b>METHODS</b>Pilot tests of this sequential chlorination were carried out in a drinking water plant.</p><p><b>RESULTS</b>The sequential chlorination disinfection process had the same or better efficiency on microbe (including virus) inactivation compared with the free chlorine disinfection process. There seemed to be some synergetic disinfection effect between free chlorine and monochloramine because they attacked different targets. The sequential chlorination disinfection process resulted in 35.7%-77.0% TTHM formation and 36.6%-54.8% THAA5 formation less than the free chlorination process. The poorer the water quality was, the more advantage the sequential chlorination disinfection had over the free chlorination.</p><p><b>CONCLUSION</b>This process takes advantages of free chlorine's quick inactivation of microorganisms and chloramine's low disinfection by-product (DBP) yield and long-term residual effect, allowing simultaneous control of microbes and DBPs in an effective and economic way.</p>

Synergetic inactivation of microorganisms in drinking water by short-term free chlorination and subsequent monochloramination / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To introduce synergetic inactivation of microorganisms in drinking water by short-term free chlorination for less than 15 minutes followed by monochloramination.</p><p><b>METHODS</b>Indicator microorganisms such as Escherichia coli, Staphylococcus aureus, Candida albicans, and spores of Bacillus subtilis were used to assess the efficiency of sequential chlorination and free chlorination.</p><p><b>RESULTS</b>The sequential chlorination was more efficient in inactivating these microorganisms than free chlorination, indicating that synergy was provided by free chlorine and monochloramine. Ammonia addition time, temperature and pH had influences on this synergy.</p><p><b>CONCLUSIONS</b>The possible mechanism of this synergy might involve three aspects: free chlorine causing sublethal injury to microorganisms and monochloramine further inactivating them; different ability of free chlorine and monochloramine to penetrate and inactivate microorganism congeries; and higher concentration of residual chlorine in sequential chlorination than in free chlorination.</p>

Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the response and tolerance in hepatocellular carcinoma (HCC) patients treated by three-dimensional conformal radiotherapy (3DCRT) combined with. transcatheter arterial chemoembolization (TACE).</p><p><b>METHODS</b>Fourty-six HCC patients confirmed by cytology or histology were studied. All patients underwent TACE 1 to 3 courses. Then they received 3DCRT after an interval of about one month. 3DCRT was given with the field covering the tumor with a generous margin. 6 MV X-ray was used. The total dose was 30 - 54 Gy, in daily 2 Gy fractions. Immediate response was recorded according to the WHO criteria carried out by serial CT scan one month after 3DCRT. Irradiation toxicities were scored by the RTOG criteria. Acute liver toxicity was graded according to the common toxicity criteria (CTC) of National Cancer Institute. Late toxicity was focused on radiation-induced liver disease (RILD).</p><p><b>RESULTS</b>Partial response was observed in 8 (17.4%) patients. Stable disease and progressive disease was observed in 35 (76.1%) patients and 3 (6.5%) patients, respectively. No complete response was observed at the time of the response evaluation. The overall survival rate at 1-, 2- and 3-year was 60.9%, 39.1% and 28.3%, respectively, with a median survival period of 16 months. The 1-, 2- and 3-year local progression-free rate was 73.9%, 56.5% and 39.1%, respectively. The 1-, 2- and 3-year distant metastasis rate was 15.2%, 21.7% and 34.8%. Univariate analysis showed that favorable prognostic predictors for survival were: T3 stage, CACA 2001 stage I, absence of portal thrombosis, Child-Pugh grade A and irradiation dose of >45 Gy. Irradiation dose and liver cirrhosis were identified by Cox-regression analysis as independent predictors for survival. Two patients experienced CTC grade 1 acute hepatic toxicity and three patients experienced grade 3 acute hepatic toxicity. Two patients developed RILD. Three patients experienced RTOG grade 1 acute gastrointestinal complication and one patient experienced acute gastrointestinal bleeding. Five patients experienced RTOG grade 1 leucopenia, and five patients experienced grade 2 leucopenia.</p><p><b>CONCLUSION</b>3DCRT combined with TACE is safe and effective for HCC. It is worthy of a further dose escalation study.</p>

Waste water disinfection during SARS epidemic for microbiological and toxicological control / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the disinfection of wastewater in China.</p><p><b>METHODS</b>During the SARS epidemic occurred in Beijing, a study of different disinfection methods used in the main local wastewater plants including means of chlorine, chlorine dioxide, ozone, and ultraviolet was carried out in our laboratory. The residual coliform, bacteria and trihalomethanes, haloacetic acids were determined after disinfection.</p><p><b>RESULTS</b>Chlorine had fairly better efficiency on microorganism inactivation than chlorine dioxide with the same dosage. Formation of THMs and HAAs does not exceed the drinking water standard. UV irradiation had good efficiency on microorganism inactivation and good future of application in China. Organic material and ammonia nitrogen was found to be significant on inactivation and DBPs formation.</p><p><b>CONCLUSION</b>Chlorine disinfection seems to be the best available technology for coliform and bacteria inactivation. And it is of fairly low toxicological hazard due to the transformation of monochloramine.</p>

Factors affecting bacterial growth in drinking water distribution system / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To define the influence of some parameters, including assimilable organic carbon (AOC), chloramine residual, etc. on the bacterial growth in drinking water distribution systems.</p><p><b>METHODS</b>Three typical water treatment plants in a northern city (City T) of China and their corresponding distribution systems were investigated. Some parameters of the water samples, such as heterotrophic plate content (HPC), AOC, COD(Mn), TOC, and phosphate were measured.</p><p><b>RESULTS</b>The AOC in most water samples were more than 100 microg/L, or even more than 200 microg/L in some cases. The HPC in distribution systems increased significantly with the decrease of residual chlorine. When the residual chlorine was less than 0.1 mg/L, the magnitude order of HPC was 10(4) CFU/mL; when it was 0.5-0.7 mg/L, the HPC was about 500 CFU/mL.</p><p><b>CONCLUSION</b>For controlling the biostability of drinking water, the controlling of AOC and residual chlorine should be considered simultaneously. The influence of phosphors on the AOC tests of water is not significant. Phosphors may not be the limiting nutrient in the water distribution systems.</p>

Occurrence of haloacetic acids in drinking water in certain cities of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Since haloacetic acids (HAAs), which are nonvolatile and of high carcinogenic risk, are common species of chlorinated disinfection by-products(DBPs) in drinking water, and little has been known in China, it is necessary to make a survey about the kinds and levels of HAAs in drinking water of the nation.</p><p><b>METHOD</b>HAAs were analyzed using gas chromatography with electron capture detector(GC/ECD) and relatively complex pretreatment process of sample was applied. Five main cities in different areas of China were chosen in the survey.</p><p><b>RESULTS</b>Studies showed that the main species of HAAs in drinking water in China were DCAA and TCAA, ranging from 0.4 microg/L to 12.85 microg/L and from 0.56 microg/L to 10.98 microg/L, respectively. MBAA and DBAA were also detected in one city, ranging from 2.20 microg/L to 4.95 microg/L and 1.10 microg/L to 2.81 microg/L, respectively. Therefore, the contents of HAAs varied, usually no more than 25 microg/L. Based on the acquired data to date, it is known that the concentrations of HAAs in drinking water in China were surely under the limits of Sanitary Standard for Drinking Water Quality (China, 2001).</p><p><b>CONCLUSION</b>A wider survey of HAAs in drinking water should be conducted throughout the nation to get adequate data and information, the ultimate aim of which is to control HAAs pollution and keep the balance between microbiological safety insurance and chemical risk control, minimize the formation of DBPs and ensure the safety of water supply at the same time.</p>

Improving removal efficiency of organic matters by adding phosphorus in drinking water biofiltration treatment / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate phosphorus limitation and its effect on the removal efficiency of organic matters in drinking water biological treatment.</p><p><b>METHODS</b>Bacterial growth potential (BGP) method and a pair of parallel pilot-scale biofilters were used for the two objectives, respectively.</p><p><b>RESULTS</b>The addition of phosphorus could substantially increase the BGPs of the water samples and the effect was stronger than that of the addition of carbon. When nothing was added into the influents, both CODMn removals of the parallel biofilters (BF1 and BF2) were about 15%. When phosphate was added into its influent, BF1 performed a CODMn removal, 6.02 percentage points higher than the control filter (BF2) and its effluent had a higher biological stability. When the addition dose was < 20 micrograms.L-1, no phosphorus pollution would occur and there was a good linear relationship between the microbial utilization of phosphorus and the removal efficiency of organic matters.</p><p><b>CONCLUSIONS</b>Phosphorus was a limiting nutrient and its limitation was stronger than that of carbon. The addition of phosphate was a practical way to improve the removal efficiency of organic matters in drinking water biological treatment.</p>

Research development of endocrine disrupting chemicals (EDCs) in water in China / 生物医学与环境科学（英文）

More and more importance has been attached to the problem of endocrine disrupting chemicals (EDCs) since 1960s. This article elaborates the recent research progress of EDCs in water and the trends in the near future in China.