The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.
Antifungal Agents ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Drug Synergism ; Fungi ; drug effects

Animals ; Female ; Hypoxia ; prevention & control ; Ketamine ; pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Selenium ; pharmacology ; Tea

Ribavirin is a widely used nucleoside antiviral drug. During the epidemic of coronavirus disease 2019 (COVID-19), ribavirin was recommended for empirical treatment in the Clinical Management of Human Infection with COVID-19 (trial guidance v6). However, due to the large inter-individual variations in dose-response relationship, and extremely long terminal half time, it is necessary to perform therapeutic drug monitoring and individualized dose adjustment for ribavirin in special populations. In this article, the pharmacokinetics and therapeutic drug monitoring of ribavirin in different populations are reviewed in order to provide reference for clinical rational use and individualized medication of ribavirin for treatment of COVID-19.

Objective:To study the effects of Astragalus Root Injection(a traditional Chinese herb medicine) on oxaliplatin-induced apoptosis of hippocampal neurons. Motheds: The primary culture of hippocampus neurons from SD rats (aged within 24h) were treated with different concentrations of oxaliplatin( L-OHP) (0, 3, 5 and 10 ?g/mL) and Astragalus Root Injection (0.05, 0.2 and 0.5 g/mL). The apoptosis of the neurons and the nerve growth factor(NGF)level were analyzed. Results: Astragalus Root Injection dose-dependently decreased neuronal cell apoptosis induced by oxaliplatin (P

Objective - （ ） To investigate the effects of nuclear factor erythroid 2 related factor 2 NRF2 on the oxidative stress （ ） Methods ） ，， induced by trichloromethane TCM in human normal hepatocyte L02 cells. i L02 cells were stimulated with 1 2 ， ， ， （ ）， 4 8 12 16 and 20 mmol/L TCM solution dissolved in dimethyl sulfoxide and the control group and blank group were set ， - ， up. After culturing for 24 hours the cell viability was detected by CCK 8 colorimetric method and the concentration of TCM ） -， - stimulation was screened. ii L02 cells in logarithmic growth phase were randomly divided into control group and low medium - ， ， ， and high dose groups. After 24 hours of exposure to 0 4 8 and 12 mmol/L TCM the cells were collected. The activity of （ ）， （ ）， （ - ） （ ） superoxide dismutase SOD catalase CAT glutathione peroxidase GSH Px and the level of malondialdehyde MDA NRF2， - （HO-1）， were detected by colorimetric analysis. The mRNA expression levels of heme oxygenase 1 glutamate cysteine （GCLC） （） （NQO1） - ligase catalytic subunit and NAD P H quinone dehydrogenase 1 were detected by real time fluorescence ， - ， polymerase chain reaction. The protein levels of NRF2 HO 1 GCLC and NQO1 were detected by Western blotting.Results ） ， ， ， ， i When the concentration of TCM was 4 8 12 16 and 20 mmol/L the survival rate of L02 cells decreased （ P ） ， ， significantly compared with the control group all <0.05 . The concentration of 0 4 8 and 12 mmol/L were selected as the ） ， - stimulation doses for subsequent experiments. ii Compared with the control group the activities of SOD and GSH Px in L02 （ P ） （ P ）， - cells in the three doses groups decreased all <0.05 and the levels of MAD increased all <0.05 with a dose effect - （P ）， relationship. The CAT activity of L02 cells in the medium dose group was lower than that in the control group <0.05 and the - （ P ） CAT activity of L02 cells in the high dose group was lower than that in the others three groups all <0.05 . Compared with the ， NRF2 - （P ），NRF2 control group the relative expression levels of mRNA in L02 cells in the low dose group decreased <0.05 - （P ）， NRF2 mRNA in L02 cells in the medium dose group increased <0.05 mRNA and NRF2 protein expression in L02 cells in （ P ） HO-1，GCLC， NQO1 ， the highdose group increased both <0.05 . The relative expression level of mRNA and GCLC NQO1 （ P ） protein expression in L02 cells in the three doses groups increased compared with the control group all <0.05 . The relative NRF2 - - - expression level of mRNA in L02 cells in the high dose group was higher than that in the low and medium dose groups （ P ）， - （P ）， both <0.05 and the relative expression of NRF2 protein was higher than that in the low dose group <0.05 but the HO-1 GCLC - - （ relative expression levels of and mRNA and HO 1 protein level were lower than those in the medium dose group all P ）Conclusion - <0.05 . TCM exposure can inhibit the proliferation of L02 cells by inducing oxidative stress with a dose effect ， relationship. In this process the antioxidant mechanism mediated by NRF2 was activated. The expression of antioxidant defense ， - ， and detoxification related target genes downstream of NRF2 signaling pathway was activated and the expression of HO 1 - GCLC and NQO1 was up regulated to alleviate the oxidative damage caused by TCM.

Objective To evaluate and compare the clinical efficacy and safety of intense pulsed light (IPL) versus 595-nm pulsed dye laser (PDL) for the treatment of post-acne erythema.Methods A randomized split-face clinical trial was conducted.A total of 20 patients with post-acne erythema were enrolled,and randomized to receive treatment with IPL on one half of the face and 595-nm PDL on the other facial side once every 4 weeks for 3 sessions.Digital photographs were taken using the VISIA,and erythema index was recorded before each treatment and one month after the last treatment.The severity of bilateral facial erythema was evaluated based on a 4-point grading scale before the first treatment and after the last treatment.Pain scores and adverse reactions were recorded using a visual analogue scale (VAS) after each treatment,and a patient satisfaction survey was conducted by questionnaire at the last follow-up.Results The mean erythema index on the IPL side before and after treatment was 472.25 ± 86.02 and 357.15 ±82.71 respectively,and that on the PDL side before and after treatment was 476.40 ± 74.25 and 360.05 ± 64.83 respectively.Repeated measures analysis of variance (ANOVA) showed that the erythema indices on both treated sides significantly decreased over time (F =197.666,P ＜ 0.001),and the efficacy of IPL was better than that of PDL (F =1 173.909,P ＜ 0.001).Erythema severity grades on the IPL side as well as on the PDL side significantly differed between before and after treatment (Z =28.735,31.450,respectively,both P ＜ 0.001).As VAS showed,the pain score on the PDL side was significantly lower than that on the IPL side (t =2.468,P ＜ 0.05).Among the 20 patients,17 and 15 assessed their improvement as good or excellent after PDL and IPL treatment respectively,but there was no significant difference between the two groups (Z =2.696,P ＞ 0.05).The adverse reactions included erythema,burning sensation,tense sensation,blistering and hyperpigmentation on IPL-treated side,and erythema and purpuric reactions on the PDL-treated side,which all disappeared in a few hours to several days.Conclusions Both IPL and 595-nm PDL are effective and safe for the treatment of post-acne erythema,and are worthy of clinical promotion and application.IPL shows superiority in the efficacy,but elicits higher pain sensation compared with PDL.

Objective To investigate short-stage results of audiological change of nasopharyngeal carcinoma patients after radiotherapy and chemotherapy treatment.Methods According to treatment modus of nasopharyngeal carcinoma,64 cases(128 ears)patients were divided to simple radiotherapy group(45 cases,90 ears)and radiotherapy with chemotherapy group(combination treatment group,19 cases,38 ears)Meanwhile,25 cases(50 ears)people took as control group,who had no obviously ear and nose disease.About two or three months after radiotherapy and chemotherapy treatment completion,three groups were detected by otoscopy,pure tone test,tympanogram and eustachian tube function,respectively.Then,hearing variation of all patients after radiotherapy and chemotherapy treatment were investigated and compared each other.At the same time,the character and level of audiological change were also analyzed.Results Eardrum character of nasopharyngeal carcinoma patients appeared change after radiotherapy.Simple radiotherapy and combination treatment groups were found having hearing impairment and eustachian tube functional disturbance.Moreover,most patients of simple radiotherapy group showed conductive deaf (24%,22/90),and combination treatment group exhibited mingle(24%,9/38)or sensorineural deafness (29%,11/38).Conclusions Recent hearing of nasopharyngeal carcinoma patients were damaged by radiotherapy and chemotherapy treatment,radiotherapy treatment induced middle ear or eustachian tube function disturbance,chemotherapy treatment had cochleotoxicity,compared with other treatment,combination treatment Was more aggravated heating impairment.

OBJECTIVETo establish a qualitative and quantitative reversed-phase high-performance liquid chromatography (RP-HPLC) with fingerprinting technique for quality control of compound dandelion enema.

METHODSHPLC was utilized for quality assessment of 10 batches of samples. RP-HPLC analysis was performed on a Hypersil BDS C18 column (4.6 mm x 250 mm, 5 microm) with the mixture of acetonitrile (A) and potassium phosphate solution (B) (pH3.2) as the mobile phase in gradient mode. The concentrations of solvent A were 10%, 80% and 80% at 0, 38 and 40 min, respectively. The column temperature was set at 35 degrees C, the flow rate at 0.7 ml/min and the detection wavelength at 254 nm.

RESULTSHPLC fingerprinting was established from the 10 batches, and the data showed 23 characteristic peaks in the compound dandelion enema for use as index peaks for qualitative identification. Comparison of the retention time and the on-line UV spectra of the samples with the chemical standards identified peaks 3, 4 and 8 as protocatechualdehyde, caffeic acid and ferulic acid, respectively. The contents of caffeic acid in the compound dandelion enema ranged between 63.7 and 136.8 microg/ml.

CONCLUSIONHigh specific chromatographic fingerprinting and quantitative measurement of caffeic acid allows rigorous quality control of compound dandelion enema.

Caffeic Acids ; analysis ; standards ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; Reference Standards ; Reproducibility of Results ; Taraxacum ; chemistry

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide ; toxicity ; Carcinogens ; toxicity ; Cell Line, Tumor ; DNA Damage ; drug effects ; Dose-Response Relationship, Drug ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests