BACKGROUNDCandida albicans is the most frequently seen opportunistic human fungal pathogen. Terbinafine is an allylamine antifungal agent that has been proven to have high clinical efficacy in the therapy of fungal infections, the mechanism of action of terbinafine involves the specific inhibition of fungal squalene epoxidase, resulting in ergosterol deficiency and accumulation of intracellular squalene. We used cDNA microarray analysis technology to monitor global expression profile changes of Candida albicans genes in response to terbinafine treatment, and we anticipated a panoramic view of the responses of Candida albicans cells to the representatives of allylamine antifungal agents at the molecular level in an effort to identify drug class-specific and mechanism-independent changes in gene expression.

METHODSCandida albicans strain ATCC 90028 was exposed to either medium alone or terbinafine at a concentration equivalent to the 1/2 minimal inhibitory concentrations (MICs, 4 mg/L) for 90 minutes. RNA was isolated and gene expression profiles were compared to identify the changes in the gene expression profile using a cDNA microarray analysis. Differential expression of 10 select genes detected by cDNA microarray analysis was confirmed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSA total of 222 genes were found to be responsive to terbinafine, including 121 up-regulated genes and 101 down-regulated genes. These included genes encoding membrane transport proteins belonging to the members of the ATP-binding cassette (ABC) or major facilitator superfamily (MFS; CDR1, AGP2, GAP6, PHO84, HOL3, FCY23, VCX1), genes involved in stress response and detoxification (CDR1, AGP2, HOL3), and gene involved in the ergosterol biosynthesis pathway (ERG12). The results of semi-quantitative RT-PCR were consistent with that of the cDNA microarray analysis.

CONCLUSIONSThe up-regulation of the gene encoding the multidrug resistance efflux pump CDR1 may contribute to the terbinafine resistance in Candida albicans. However, the precise roles of other affected genes remain unclear, further studies of these genes and their respective products that play roles in the context of antifungal resistance are warranted.

Antifungal Agents ; pharmacology ; Candida albicans ; drug effects ; genetics ; Ergosterol ; biosynthesis ; Fungal Proteins ; genetics ; Gene Expression Profiling ; Genome, Fungal ; Membrane Transport Proteins ; genetics ; Naphthalenes ; pharmacology ; Oligonucleotide Array Sequence Analysis

OBJECTIVETo study on needling safe depth of Fengfu (GV 16) with CT, so as to provide reference for safe needling depth of Fengfu (GV 16) in clinical acupuncture treatment.

METHODSForty-one adult volunteers were divided into 3 groups, a thin person group, a moderate person group and a fat person group according to Luo's indexes, and computer-aided tomography (CT) was used to measure the needling depth of Fengfu (GV 16).

RESULTSThe safe depths of perpendicular needling of Fengfu (GV 16) were different for persons of different somatotypes. The safe needling depth was (27.73 +/- 3.45) mm for the thin person group, (30.78 +/- 2.90) mm for the moderate person group, and (33.39 +/- 4.27) mm for the fat person group.

CONCLUSIONThe safe needling depth < or = the dangerous depth x 75% can be used for reference for the safe needling depth of Fengfu (GV 16) for different somatotypes persons.

Acupuncture Points ; Acupuncture Therapy ; Female ; Humans ; Male ; Neck ; Somatotypes ; Tomography, X-Ray Computed

To investigate whether influenza virus (IFZ) could up-regulate the expression of mucin 1 (MUC1) which exists in epithelial cells of upper respiratory track to restrict the inflammation, as respiratory syncytial virus (RSV) does. Quantitative RT-PCR and Western Blot were performed to detect the expression level of MUC1 induced by two single-strand RNA viruses in A549 cell lines. HEp-2 and MDCK cells were used respectively to culture RSV and IFZ. At 24h post A549 cells infection with the same titer of RSV or IFZ, the total RNA was harvest, qRT-PCR was then performed to observe the expression level of MUC1 mRNA. Meanwhile, at 24 h and 48 h post A549 cells infection with the same titer of RSV or IFZ, the total protein and supernatant were collected respectively after cell lysis, Western Blot was then used to detect the expression level of MUC1. Results showed that RSV could up-regulate the expression of MUC1 in airway epithelial cells with a significant dose-effect correlation, whereas IFZ could not. This study firstly investigated the differences of the regulation on the expression of MUC1 induced by two single-strand RNA viruses, and demonstrated initially that the mechanism of IFZ self-limiting differed from RSV, which attributed to up-regulation of the expression level of MUC1.
Animals ; Cell Line ; Dogs ; Epithelial Cells ; metabolism ; virology ; Gene Expression Regulation ; Humans ; Influenza, Human ; genetics ; metabolism ; virology ; Madin Darby Canine Kidney Cells ; Mucin-1 ; genetics ; metabolism ; Orthomyxoviridae ; genetics ; physiology ; Respiratory Syncytial Virus Infections ; genetics ; metabolism ; virology ; Respiratory Syncytial Viruses ; genetics ; physiology ; Up-Regulation

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

BACKGROUNDPatient characteristics may be an internal factor influencing patient complaints, but in China patient characterization is restricted to patient satisfaction surveys, and few studies have considered the relationship between patient characteristics and patient complaints. The aim of this research was to determine the reasons for complaints.

METHODSIn this study, we analyzed the characteristics of hospitalized patients and explored their relationship with medical complaints.

RESULTSThe significant factors were age (P = 0.045), hospital cost (P = 0.003), household nature (P < 0.001), and education (P < 0.001). The complaint rate decreased when the patients' age increased (regression coefficient, -0.606; OR, 0.545, and 95%CI, 0.301 - 0.987). The complaint rate increased with an increase in hospital cost (regression coefficient, 0.818; OR, 2.266; and 95%CI, 1.320 - 3.889). Patients from non-agricultural households had a higher complaint rate (regression coefficient, 1.051; OR, 2.861; and 95%CI, 1.611 - 5.082). Patients with higher education levels had lower complaint rates (regression coefficient, -0.944; OR, 0.389; and 95%CI, 0.234 - 0.647).

CONCLUSIONThe survey confirms that older patients and patients with higher education levels had lower complaint rates, while non-agricultural population and patients with higher hospital expenses had higher complaint rates.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; Data Collection ; Female ; Hospitals ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Patient Satisfaction ; statistics & numerical data ; Young Adult

OBJECTIVETo determine the effect of albumin administration on lung injury in traumatic/hemorrhagic shock (T/HS) rats.

METHODSForty-eight adult Sprague-Dawley rats were divided into three groups randomly (n=16 in each group): Group A, Group B, Group C. In Group A, rats underwent laparotomy without shock. In Group B, rats undergoing T/HS were resuscitated with their blood plus lactated Ringer's (twice the volume of shed blood). In Group C, rats undergoing T/HS were resuscitated with their shed blood plus additional 3 ml of 5% human albumin. The expression of polymorphonuclear neutrophils CD18/CD11b in jugular vein blood was evaluated. The main lung injury indexes (the activity of myeloperoxidase and lung injury score) were measured.

RESULTSSignificant differences of the expression of CD18/11b and the severity degree of lung injury were founded between the three groups. (P<0.05). The expression of CD18/CD11b and the main lung injury indexes in Group B and Group C increased significantly compared with those in Group A (P<0.05). At the same time, the expression of CD18/CD11b and the main lung injury indexes in Group C decreased dramatically, compared those in Group B (P<0.05).

CONCLUSIONSThe infusion of albumin during resuscitation period can protect lungs from injury and decrease the expression of CD18/CD11b in T/HS rats.

Albumins ; therapeutic use ; Animals ; CD11b Antigen ; metabolism ; CD18 Antigens ; metabolism ; Disease Models, Animal ; Neutrophils ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; drug therapy ; etiology ; metabolism ; Shock, Hemorrhagic ; complications ; metabolism ; Treatment Outcome ; Wounds and Injuries ; complications ; metabolism

OBJECTIVESTo analyze the factors related to prognosis of hepatitis failure and to determine the factors which significantly affect it, and to build a scoring system for assessment of the prognosis of hepatitis failure and also to examine its efficacy for clinical use.

METHODSClinical data from 301 patients were analyzed retrospectively. The correlated degree between those single factors and prognosis of hepatitis failure was explored by logistic regression analysis. Independent risk factors of prognosis and those correlated coefficients, which were from logistic regression analysis, were used to build a scoring system. This system was used in analyzing the clinical data of 275 patients to examine its efficacy of the prognostic assessment.

RESULTSThe factors that significantly affected the prognosis of hepatitis failure included age, clinical typing, hepatic coma, total bilirubin, and others (P < 0.01). Some factors, including PTA, blood urea, sodium and hepatic coma, were independent risk factors of prognosis. The scoring system built gave different scores between the effective treatment group and ineffective treatment group with statistical significance (P < 0.01). When the score was less than 40, the probability of a recovery was 76.9%; when the score was 40 to 80, the probability of a recovery was only 12.5%. When the score was more than 80, the probability of a recovery dropped to 0%.

CONCLUSIONSThe factors, including PTA, blood urea and sodium and hepatic coma, are important in building a scoring system to assess the prognosis of hepatitis failure. The scoring system we built is very effective in evaluating the prognosis of hepatitis failure.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; China ; epidemiology ; Evaluation Studies as Topic ; Factor Analysis, Statistical ; Female ; Hepatitis, Viral, Human ; complications ; epidemiology ; Humans ; Liver Cirrhosis ; epidemiology ; etiology ; Liver Failure ; epidemiology ; etiology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors

BACKGROUNDRecurrence of hepatitis B-related hepatocellular carcinoma (HCC) after curative resection is the leading factor influencing the prognosis of the disease. Therefore, further improvement of long-term survival may depend on the prevention and treatment of the recurrent tumor. The aim of this research was to investigate the role of antiviral therapy and postoperative transcatheter arterial chemoembolization (TACE) in the prevention and treatment of hepatitis B-related HCC recurrence.

METHODSOne hundred and twenty patients who underwent curative resection of hepatitis B-related HCC between January 2005 and June 2008 at our hospital were enrolled. Patients were divided into four groups according to the post-operative adjuvant therapy they received, i.e., control, antiviral therapy group, TACE group, and combined group. The disease-free survival (DFS) and the 12-, 24-, 36-month cumulative recurrence rates were studied.

RESULTSThere was no significant difference between isolated postoperative antiviral therapy group and control in terms of disease-free survival (P = 0.283), while it was significantly higher in the TACE group compared to control (P = 0.019). In all patients, however, viral prophylactic therapy combined with/without TACE brought a favorable result compared to those only with/without TACE (P < 0.001). Similarly, no matter combined with or without antiviral treatment, postoperative TACE prolonged DFS (P = 0.015). Naturally, a combination of viral prophylactic therapy on the baseline TACE significantly benefited patients' postoperative DFS (P = 0.047) and vice verse (P = 0.002). The 24-month cumulative recurrence rates of combined group were significantly lower than that of isolated control group and antiviral therapy (P < 0.001 and P = 0.011 respectively). However, 36-month recurrence rate was significantly different in the control group compared to the TACE group and combined group (P = 0.040 and 0.002 respectively); same as the antiviral group compared to the combined group (P = 0.034).

CONCLUSIONSPost-operative TACE prevents early recurrence while antiviral therapy prevents late recurrence of HCC. Combination of antiviral therapy and TACE are suggested for prevention in HCC patients with high risk of recurrence.

Adult ; Aged ; Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; etiology ; therapy ; Chemoembolization, Therapeutic ; methods ; Female ; Hepatitis B ; complications ; drug therapy ; therapy ; Humans ; Liver Neoplasms ; drug therapy ; etiology ; therapy ; Male ; Middle Aged

Objective To assess the changes in iodine status and dietary iodine intake among Shanghai residents since common salt was iodized 20 years ago.Methods As-CE Catalysis spectrophotometry was used to determinate the urine iodine level in school-age children,pregnant women,wet nurse and adults of Shanghai between 1995 and 2015.B ultrasonic was used to determinate the thyroid volume of school-age children.And then the goiter rate was calculated.Direct titration or arbitration methods were applied to detect the household salt iodine level quantitatively.The survey was conducted by using 3 days 24-hour dietary questionnaire and condiment weighing methods to analyze the level of iodine intake and sources for the cases of all iodized salt consumption and all consumption of non-iodized salt.Results The median urine iodine concentration (UIC) of school age children was 72.3 μg/L in 1995,rose to 214-231 μg/L from 1997-1999,and then became stable between 100 μg/L and 200 μg/L since 2002.The goiter rate was below 5% among children aged 8-10 from 1995-2015 in Shanghai.The median urine iodine of pregnant women was between 126.5 μg/L and 139.8 μg/L.The median UIC of other populations were all between 100 μg/L and 200 μg/L: with adults,lactating women,infants and young children and women of childbearing age,the median urinary iodine was 138.4,123.1-131.1,150.1 and 125.6 μg/L.The qualified iodized salt at household consumption rate was 90% from 2001 to 2009,the percentage declined year by year from 2010.In the cases of all taking iodine salt,the median iodine intake volume for male aged 7-10,11-13,14-18 and over 18 was 200.3,235.5,252.7 and 215.4 μg/L;women aged 7-10,11-13,14-18 and over 18 was 193.0,213.8,208.3 and 186.1 μg/L.The contribution rate of iodine salt in the diet were 51.6%-54.1% and 49.1%-53% in men and women.Kelp,seaweed and fish and shrimp on the contribution of iodine are 7.6%-16.6% and 4.5%-7.4%.Conclusion In the past about 20 years,iodine nutritional status of residents in Shanghai has stabilized totally in a appropriate and safe level.However,the iodine nutrition of pregnant women was insufficient.As iodized salt is the major source of dietary iodine in coastal areas,it is still necessary to continue the policy of universal salt iodized in Shanghai to ensure residents'' needs for iodine and control the risk of iodine deficiency.

Objective To ascertain iodine nutritional status of pregnant women and children in Shanghai since the implementation of "Salt Iodine Content Standard" in 2011.Methods By population proportion probability sampling,30 sub-districts(towns) were chosen,with one primary school was randomly sampled in eachsub-districts(towns).And 50 students aged 8-10 in every school were randomly selected to test their urinary iodine and thyroid volume,and their household iodized salt concentration determined.And 20 pregnant women were selected to test their urinary iodine in each sub-districts(towns).Results The goiter rate of 8-10 aged children was 0.9%.The medians of urinary iodine concentration of 8-10 aged children and pregnant women were 171.40 μg/L and 126.53 μg/L,respectively.The consumption rates of qualified iodized salt were 72.52%.The median of iodine content concentration in salt was 24.8 mg/kg.Conclusion In Shanghai,the goiter rate of children was lower than that of the national standard.Iodine nutritional status of children was proper,but the pregnant women were deficient in iodine nutrition.Therefore,iodized salt concentration should be improved to the optimal level.Health education for pregnant women should be strengthened.