OBJECTIVETo perform a transcriptomics study in differential genes after Xianglian External Lotion (XEL) induced the recovery of drug-resistant Candida albicans strains sensitive to Fluconazole.

METHODSBroth microdilution antifungal susceptibility test was used to detect minimal inhibitory concentration (MIC) of drug-resistant Candida albicans strains induced by XEL. Transcriptome sequencing (RNA-Seq) was used to determine and compare the transcription of primary drug-resistant Candida aIbicans strains and sensitive strains induced by XEL. High expressed genes and signaling pathways strains were analyzed by gene ontology (GO) method.

RESULTSXEL could induce drug-resistant strains of the 6th generations to recover sensitivity. Transcriptome sequencing showed that, as compared with primary drug-resistant strains, there were 165 genes with up-regulated RPKM index and 144 genes with down-regulated RPKM index after XEL induction. GO analyses found that all genes were mainly classified as GO:0015903 (fluconazole transport).

CONCLUSIONSXEL could induce the recovery of drug-resistant Candida albicans strains sensitive to Fluconazole. By analyzing transcriptomes, authors speculated that XEL could recover strain sensitivity to fluconazole by opening fluconazole transport pathway.

Antifungal Agents ; pharmacology ; therapeutic use ; Candida ; Candida albicans ; drug effects ; genetics ; Candidiasis ; drug therapy ; Drug Resistance, Fungal ; drug effects ; genetics ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fluconazole ; pharmacology ; Microbial Sensitivity Tests

Objective To enhance the awareness of diagnose and treatment of venous thrombus in premature infants. MethodsThe clinical features, treatment and prognosis of lower limb vein thrombus in three case of premature infants were retrospectively analyzed.ResultsThree premature infants of gestational age 29-36 weeks were found thrombosis in 1-57 days after birth. One case received peripherally inserted central cathete (PICC). All of three cases had infection signs and trauma. One case received thrombolytic and anticoagulant therapy, one case received high dose thrombolytic therapy, and both of them were treated successfully without bleeding complication. However, another case was deteriorated after giving up treatment.ConclusionsCritically ill premature infants are at high risk of thrombosis. Infection, indwelling tube, thrombophilia constitution, and maternal risk factors were the high risk factors of thrombosis. Early detection, early diagnosis, and effective individualized treatment can improve the prognosis.

The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.

Objective To investigate the effects of output power,action time and radiofrequency(RF) needle on the cool-tip radiofrequency ablation(RFA) by experimental tools and to determine the value of ultrasonography in size evaluation of RFA zone.Methods The cool-tip RFA to fresh calf liver were monitored by ultrasound.The experiments by single electrode needle were performed with different combination of output power (80 W,120 W) and time (5 min,8 min,10 min).The cluster needle was used for assessment at 5 min with different output power(80 W,120 W).After the end of trial,the longitudinal specimens were cut open.The view and size of the ablation zone were recorded with naked eyes.The pathological changes displayed by optical microscope were recorded as well.Results The measurement of ablation zone with naked eyes showed with the ablation zone expanded with time in 80 W-power cases,but the pace of expansion slowed down,but in 120 W-power cases,expansion of the ablation zone was not obvious; the ablation zone in 120 W-power was bigger than that in 80 W-power at 5 min,their difference decreased with time,and the ablation zones were similar at 10 min.The cluster needle can produce ablation zone with lesser aspect ratio than that of single electrode needle,consequently similar to circle.Ultrasonic measurement of the ablation zone had real discrepancy.Most of longitudinal diameters were greater than the real ones,while in large ablation lesions,vertical diameters were often less than the real ones.Under optical microscope,no change could be found in shape and structure of the cells in ablation zone.Conclusion The output power and performing time have impact on ablation.The high-power output increased heat production as well as reduction of heat conduction.Compared with single electrode needle,the cluster needle produced ablation zone closer to real hepatic tumor,thus has more reliable effect to small hepatocellular carcinoma with diameter around 2 cm.The ultrasond has a great significance in RFA guidance,but it could not accurately define the border of ablation zone.

OBJECTIVETo investigate the effect of Dachengqi Decoction (DCQD) on the key signaling molecules in lung and large intestine of mice with endotoxemia for exploring the exterior-interior relation between Fei and Dachang.

METHODSA total of 32 BALB/c mice were randomly and equally allocated into four groups: mice in Group C and D were made into endotoxemia model by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); while those in Group A and B were not modeled but given intraperitoneal injection of saline instead. Thirty min after then, saline to Group A and C, and DCQD to Group B and D were given by gastric infusion, and mice were sacrificed 6 h later. Their tissues of lung and large intestine were taken for observing pathological changes by inverted microscopy with HE staining; detecting expressions of tumor necrosis factor-alpha (TNF-alpha) by LiquiChip system; determining gene transcription and protein expression of toll-like receptor 4 (TLR4) using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and the correlation of TNF-alpha and TLR4 levels in the lung and the large intestine tissue was analyzed. RESULTED: Compared with Group C, hemorrhage, pathologic toxemic features, including pulmonary edema and inflammatory cell infiltration as well as intestinal wall congestion and neutrophil infiltration, were significantly alleviated in Group D. Levels of TNF-alpha expression, TLR4 protein expression and gene transcription raised significantly in the modeled mice (P < 0.01), but comparison between the two modeled groups showed that the three parameters were lower in Group D than in Group C (P < 0. 01 or P < 0.05) respectively. Correlation analysis showed that the levels of TNF-alpha expression, TLR4 protein expression and gene transcription in pulmonary tissues were positively correlated with those in large intestinal tissues respectively (r = 0.973, P < 0.01, r = 0.906, P < 0.01, and r = 0.880, P < 0.01).

CONCLUSIONSThe effects of DCQD in alleviating pulmonary and large intestinal inflammation induced by endotoxemia might be correlated to its reduction on levels of TNF-alpha expression, TLR4 protein expression and gene transcription. Levels of the three parameters in the lung are correlated with the corresponding levels in the large intestine, which suggested the existence of exterior-interior relation between Fei and Dachang.

Animals ; Endotoxemia ; metabolism ; pathology ; Intestine, Large ; drug effects ; metabolism ; Lung ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; pharmacology ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer.

METHODSC57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments.

RESULTSMI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P<0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05).

CONCLUSIONMI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.

Animals ; Biological Products ; therapeutic use ; Carcinoma, Lewis Lung ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Dose Fractionation ; Dose-Response Relationship, Radiation ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Radiation-Sensitizing Agents ; therapeutic use ; Streptococcus

Fatigue is a common complication of type 2 diabetes mellitus (T2DM). We examined the relationship between T2DM fatigue and the skeletal muscle 5-hydroxytryptamine (5-HT) system. In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT_2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP) (separately and in combination). In cell culture experiments, C2C12 cells were stimulated with D-glucose, palmitic acid or 5-HT. 5-HT_2AR, 5-HT synthesis and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT_2AR, 5-HT synthase and MAO-A were expressed in mouse skeletal muscle and C2C12 cells. The expression of these proteins was significantly up-regulated in T2DM mice or when C2C12 cells were exposed to palmitic acid and D-glucose; palmitic acid was a stronger stimulant of their expression than D-glucose. Rotating rod experiments and biochemical index tests have shown that T2DM fatigue is associated with an increase in skeletal muscle 5-HT_2AR, 5-HT synthesis and 5-HT degradation. 5-HT_2AR mediates the expression of MAO-A and the synthesis of 5-HT, which indirectly regulates the degradation of 5-HT. MAO-A regulates cell inflammation, mitochondrial ROS production and membrane potential depolarization by mediating 5-HT degradation. MAO-A also inhibits the expression of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1), carnitine palmitoyltransferase-1 (CPT1) and ATP synthase-6 (ATP6), thus inhibiting mitochondrial functions such as fatty acid β oxidation and ATP synthesis. SH and CDP can effectively treat T2DM fatigue, and can also reduce blood glucose and blood lipid, and the combination of SH and CDP has a clear synergistic effect.

OBJECTIVETo investigate the effect of curcumin (Cur) on radiosensitivity of nasopharyngeal carcinoma cell CNE-2 and its mechanism.

METHODThe effect of curcumin on radiosensitivity was determined by the clone formation assay. The cell survival curve was fitted by Graph prism 6. 0. The changes in cell cycle were analyzed by flow cytometry (FCM). The differential expression of long non-coding RNA was detected by gene chip technology. Part of differentially expressed genes was verified by Real-time PCR.

RESULTAfter 10 micro mol L-1 Cur had worked for 24 h, its sensitization enhancement ratio was 1. 03, indicating that low concentration of curcumin could increase the radiosensitivity of nasopharyngeal carcinoma cells; FCM displayed a significant increase of G2 phase cells and significant decrease of S phase cells in the Cur combined radiation group. In the Cur group, the GUCY2GP, H2BFXP, LINC00623 IncRNA were significantly up-regulated and ZRANB2-AS2 LOC100506835, FLJ36000 IncRNA were significantly down-regulated.

CONCLUSIONCur has radiosensitizing effect on human nasopharyngeal carcinoma CNE-2 cells. Its mechanism may be related to the changes in the cell cycle distribution and the expression of long non-coding IncRNA.

Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Curcumin ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; radiation effects ; Humans ; RNA, Long Noncoding ; genetics ; Radiation Tolerance ; drug effects

Aim To clarify the differential proteins of mammary tissues in Xihuang pills(XHP)against hy-perplasia of mammary glands(HMG)based on quanti-tative proteomics technology and validate them,and to explore the mechanism of action.Methods SD rats were randomly divided into blank group,model group and XHP group,with 10 rats in each group.Except for the blank group,estrogen and progesterone were injec-ted intramuscularly to establish a rat model of mamma-ry hyperplasia for 30 d.After XHP was administered for 14 d,the rats in each group were observed to have morphological changes in the apparent morphology of the mammary tissues,and pathological changes in the mammary tissues were stained with hematoxylin-eosin staining(HE),and the differentially expressed pro-teins(DEPs)in the groups were screened by quantita-tive proteomics technology and subjected to bioinforma-tics analysis,and Western blot to verify the key DEPs.Results Compared with the model group,the appar-ent pathological morphology of the XHP group was sig-nificantly improved,the diameter of the nipple height of the rats was significantly reduced(P＜0.01),and the degree of histopathology was significantly allevia-ted.Quantitative proteomics identified 4,299 DEPs in mammary tissue,and bioinformatics analysis of 14 DEPs with consistent changes between the XHP group and the blank group relative to the model group re-vealed that they were related to the regulation of mus-cular systemic processes,regulation of muscle contrac-tion,DNA replication,and pre-initiation of DNA repli-cation.Western blot results showed that,compared with the model group,rat mammary tissue of the XHP group showed significantly lower levels of ACLY and ALDOC protein expression levels were significantly re-duced and BIN1 protein expression levels were signifi-cantly increased(P＜0.01).Conclusions XHP may exert its anti-mammary hyperplasia effect through the regulation of BIN1,ACLY and ALDOC protein lev-els,the regulation of DNA replication,the regulation of pre-initiation of DNA replication and muscular sys-temic processes,and the regulation of muscle contrac-tion.

OBJECTIVETo investigate effects of biejiajian pill (BP) on the proliferation, adhesion, and invasion of hepatoma carcinoma cells (HepG2), and to primarily explore the mechanisms for fighting against metastasis and invasion.

METHODSUsing sero-pharmacological methods, HepG2 cells were respectively cultured by high and middle dose BP containing serums and the vehicle serum. Using MTT colorimetry, cell adhesion test, and Transwell invasion test, effects of BP on the proliferation, adhesion, and invasion of HepG2 cells were detected, thus further exploring the mechanisms for fighting against the metastasis and invasion of HepG2 cells.

RESULTSHigh and middle dose BP containing serums could significantly prohibit the growth and proliferation, the adhesion and invasion of HepG2 cells on the basilar membrane. Besides, these effects were correlated with the concentrations of BP.

CONCLUSIONBP could effectively inhibit the growth and proliferation, adhesion and invasion of HepG2 cells.

Animals ; Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hep G2 Cells ; Humans ; Liver Neoplasms ; pathology ; Male ; Rats