OBJECTIVE:To probe into the utilization status of carbopenem antibacterials in our hospital.METHODS:The antimicrobial use density(AUD),the antimicrobial average daily cost(AADC),and the antimicrobial cost density(ACD) of carbopenem antibacterials used in our hospital during 2000～2006 were analyzed statistically using DDDs analytical method. RESULTS:DDDs and AUD of the carbopenem antibacterials used in our hospital showed an upward trend;the AADC of each kind was decreasing year by year but ACD presented an upward trend.CONCLUSION:Safe,effective,economical and rational use of carbopenem antibacterials is in the interest of protection of drug resources used for bacterial infection.

OBJECTIVE To investigate the resistance of Enterobacter cloacae and its gene of chlorhexidine-sulfadiazine-resistance(qacE△1-sul1) isolated from two hospitals. METHODS Microdilute tests were performed to detect the susceptibility of 20 kinds of antimicrobial agents in 74 strains of E.cloacae.The qacE△1-sul1gene was detected by PCR. RESULTS There was no strain resistant to imipenem and meropenem.The resistant rates to other antimicrobial agents were between 44.6% and 94.6%.The positive rate of qacE△1-sul1gene was 74.3%. CONCLUSIONS The 74 strains were multiple-drug-resistant.There was a high positive rate of qacE△1-sul1gene in E.cloacae isolated from two hospitals.

Objective To characterize CD4+CD8+double-positive T ( DPT) cells in PBMCs from patients with tuberculosis(TB).Methods PBMCs were isolated from peripheral blood samples collected from patients with TB and healthy subjects.The subsets and percentages of CD4+T, CD8+T and DPT cells in PBMCs were determined by flow cytometry.Cell surface markers ( CD45RO, CCR7 and CD25 ) and intracellular cytokines ( IFN-γand TNF-α) were detected directly and after ESAT-6/PPD stimulation.Re-sults Patients with TB showed a significantly increased DPT cells as compared with the cured individuals and healthy subjects (P<0.005).The levels of DPT cells were gradually decreased down to normal upon the treatment of pharmacotherapy.DPT cells expressed higher levet of CD25 than CD4+T and CD8+T cells ( P<0.005 ) . DPT cells could express more IFN-γand TNF-αupon the stimulation of ESAT-6/PPD (P<0.005).The analysis of memory phenotype indicated that DPT cells were memory T cells.Conclusion DPT cells in peripheral blood of the patients with tuberculosis played a critical role in protective immunity against tuberculosis.The alterations of DPT cells in PBMCs during the period of pharmacotherapy might be a potential indicator for the prognosis of pulmonary tuberculosis.

Objective To examine the prevalence of depressive symptoms and related factors among HIV-positive men who have sex with men (MSM) in Shanghai.Methods All of the HIV-positive MSM were enrolled to participate in a cross-sectional study with questionnaire-based interview during Nov.,2014 to Nov.,2015.Depression was measured with a 12-item version of the Center for Epidemiological Studies Depression Scale (CES-D),where a score of 9 had been recommended as the cutoff score to indicate possible depressive symptoms.Results A total of 505 participants were recruited with a median age of 30.Among them,the majority were aged 21-44 (77.2％),non-local resident (64.6％),unmarried (73.1 ％) and university graduate or above (62.1 ％).Depressive symptoms were detected from 235 MSM and the prevalence of depression was 46.5 ％.Multiple logistic regression analysis showed that MSM who were non-local residents (OR =1.66,95 ％ CI:1.01-2.49)and had more than one male sex partner in the past year (OR=2.21,95％ CI:1.43-3.41) were more likely to have depressive symptoms compared with local residents and had only one male sex partner or less.On the contrary,compared with the education level of junior middle school or below and having no long-term partners,those who were senior high school educated (OR=0.39,95％ CI:0.21-0.74) and had homosexual behavior with main long-term partners without condoms (OR =0.38,95 ％ CI:0.17-0.85) had lower risk to be depressive.Conelusions The prevalence of depressive symptoms among HIV-infected MSM is high.Residence,education level,homosexual behavior with main long-term partner and number of male sex partner are significantly associated with depressive symptoms,suggesting psychological interventions should be further explored and studied.

OBJECTIVE:To investigate the relationship between HLA-B*5801 gene polymorphism and allopurinol-induced ADR in the Han population of Hainan Province. METHODS:The in-situ hybridization fluorescence staining analysis technique was used to detect HLA-B*5801 allele of 149 inpatients receiving allopurinol in Hainan Provincial People's Hospital during Sept. 2015-Sept. 2017.They were divided into tolerance group and ADR group according to ADR.Woolf's formula was used to calculate OR. The correlation of HLA-B*5801 allele with the occurrence of allopurinol-induced ADR was analyzed. RESULTS:Of 149 patients,there were 133 cases in tolerance group,among which 17.29%(23/133)carried HLA-B*5801 allele.There were 16 cases in ADR group,among which 93.75%(15/16)carried HLA-B*5801 allele. Among 16 ADR patients,13 patients suffered from lesion of skin and its appendents;1 patient suffered from systemic damage;1 patient suffered from gastrointestinal systemic damage;1 patient suffered from central and peripheral nervous system damage. The risk of ADR in patients with HLA-B*5801 allele was significantly higher than patients without HLA-B*5801 allele(OR:71.74,95%CI:9.02-570.55,P<0.000). The lesion of skin and its appendents was strongly associated with HLA-B*5801 allele(OR:57.39,95%CI:7.11-463.50,P<0.000). CONCLUSIONS:HLA-B*5801 allele is strongly associated with allopurinol-induced ADR. It is suggested that HLA-B*5801 allele of Han patients should be detected before taking allopurinol,which helps to reduce the incidence of allopurinol-induced ADR.

Objective: To evaluate the effect of zinc ions on human umbilical vein endothelial cells biological functions. Methods: The primary human umbilical vein endothelial cells were cultured with the ECM medium, and cells were divided into 8 groups: the control group(routine culture,n=3), 20 μmol/L zinc group(20 μmol/L zinc chloride solution was added into the cell medium, n=3), 40 μmol/L zinc group(40 μmol/L zinc chloride solution was added into the cell medium, n=3),80 μmol/L zinc group(80 μmol/L zinc chloride solution was added into the cell medium, n=3), 100 μmol/L zinc group(100 μmol/L zinc chloride solution was added into the cell medium, n=3), 200 μmol/L zinc group(200 μmol/L zinc chloride solution was added into the cell medium, n=3),300 μmol/L zinc group(300 μmol/L zinc chloride solution was added into the cell medium, n=3), 500 μmol/L zinc group(500 μmol/L zinc chloride solution was added into the cell medium, n=3). The cell proliferation curve was derived from real time cell analysis (RTCA). The viability value was obtained via CCK-8 reagent, and the migration distance was tested by scratch-wound assay while the adhesion function was detected by RTCA. Results: (1)After 18 hours, RTCA showed that the proliferation cell indexes were 4.5±0.6, 3.7±0.4, 3.6±0.3, 2.5±0.4, and 2.5±0.4 in the 20, 40, 80, 100, and 200 μmol/L zinc groups, as compared with 3.5±0.3 in the control group (all P<0.05). Proliferation cell indexes were 0 in both of the 300 μmol/L and 500 μmol/L zinc groups. (2)After 96 hours, the viability were 1.21±0.05, 1.10±0.03, 0.99±0.05, 0.62±0.02, 0.45±0.04, 0.11±0.01, and 0.12±0.06, respectively in the 20, 40, 80, 100, 200, 300, and 500 μmol/L zinc groups, as compared with 0.75±0.05 in the control group (all P<0.05). (3)After 12 hours, the migration distances were (0.56±0.11),(0.96±0.07),(0.49±0.02), and (0.29±0.01)mm in the 20, 40, 80, and 100 μmol/L zinc groups, as compared with (0.24±0.04)mm in the control group (all P<0.05). (4)After 18 hours, the adhesion cell index were 0.40±0.05, 0.31±0.01, 0.38±0.05, and 0.40±0.03 in the 20, 40, 80, and 100 μmol/L zinc groups, as compared with 0.24±0.04 in the control group (all P>0.05). Conclusions Zinc ions at lower concentration (≤80 μmol/L) can promote proliferation, viability and migration of human umbilical vein endothelial cells, but the adhesion function was not significantly affected by zinc ions. Zinc ions at higher concentration (≥200 μmol/L) can inhibit the cellular function of the human umbilical vein endothelial cells.

BACKGROUND:Clinical studies have found good analgesic effects of silver needle-thermal conduction therapy in patients with myofascial pain syndrome,but the exact mechanism remains unclear. OBJECTIVE:To observe the effect of silver needle-thermal conduction therapy on silent information regulator homolog 3(SIRT3)changes and mitochondrial ultrastructure in a rat model of myofascial pain syndrome. METHODS:Twenty rats were randomly selected from 26 Sprague-Dawley rats and were subjected to percussion combined with motor fatigue for replicating the rat model of myofascial pain syndrome.Sixteen rats that were successfully modeled were randomly divided into model group and silver needle-thermal conduction therapy group(treatment group),with eight rats in each group.The remaining rats were used as controls(normal group).The treatment group was treated with silver needle-thermal conduction therapy.Mechanical withdrawal threshold and thermal withdrawal latency of rats were measured at 1 day before modeling,1 day after modeling and 14 days after treatment.Electromyographic activities of the right medial femoral muscle were measured at 14 days after treatment.The right medial femoral muscle tissue was taken for hematoxylin-eosin staining to observe the local morphology and for transmission electron microscopy to observe the mitochondrial ultrastructure.Western blot assay was performed to detect SIRT3 expression. RESULTS AND CONCLUSION:Pain threshold:The mechanical withdrawal threshold and thermal withdrawal latency of the model and treatment groups were significantly decreased compared with those in the normal group and before modeling(P＜0.01).After treatment,the mechanical withdrawal threshold and thermal withdrawal latency of rats were significantly higher in the treatment group compared with the model group(P＜0.01).Electromyography:The rats in the model group showed spontaneous electrical activity in the right medial femur,while the rats in the treatment group showed reduced spontaneous electrical activity,longer time frame(P＜0.01)and lower wave amplitude(P＜0.05)compared with the model group.Hematoxylin-eosin staining:In the normal group,rat muscle fibers arranged closely and regularly.In the model group,the muscle fibers of rats were atrophied,degenerated,and disordered in arrangement.In the treatment group,rat muscle structure disorder improved.Mitochondrial microstructure:Under the transmission electron microscope,mitochondrial structure in the normal group was normal;mitochondrial swelling with broken or disappeared cristae appeared in the model group;mitochondrial swelling in the treatment group was obviously relieved or tended to be normal.SIRT3 expression:SIRT3 expression was significantly downregulated in the model group compared with the normal group,but was significantly upregulated in the treatment group compared with the model group(P＜0.05).To conclude,abnormalities in local muscle mitochondria and downregulation of SIRT3 expression suggest the presence of impaired energy metabolism in the rat model of myofascial pain syndrome.Mitochondrial changes recover and are close to normal after the silver needle-thermal conduction therapy,and the expression of SIRT3 is also upregulated close to the normal group,indicating the silver needle-thermal conduction therapy may play a therapeutic role by promoting mitochondrial repair and improving energy metabolism disorder.

OBJECTIVE： To evaluate the application of individualization dosage auxiliary system JPKD and SmartDose in individualization administration of vancomycin. METHODS： A retrospective study was conducted among adult inpatients in Hainan Provincial People’s Hospital from Apr. 2018 to Mar. 2019 with intravenous use of vancomycin. SmartDose was used to predict the steady blood trough concentration of vancomycin in the initial dosage regimen， and the absolute weight deviation and relative prediction error between the measured concentration and the predicted concentration were calculated. The effects of body mass index （BMI） and acute kidney injury （AKI） on absolute weight deviation were analyzed by χ2 test or continuously corrected χ2 test. Vancomycin drug delivery scheme was adjusted for patients with ungualified steady blood drug trough concentration. JPKD and SmartDose system were used to predict the blood concentration of vancomycin after adjusting the dosage regimen. The absolute weight deviation and relative prediction error between the measured concentration and the predicted concentration were calculated. The prediction ability of the two systems was evaluated and 3 examples was analyzed. RESULTS： Predicted steady blood trough blood concentration of 85 included patients in SmartDose predicted initial dosage regimen were （11.36±5.96） μg/mL （2.34-29.33   μg/mL）； the measured concentration was （11.44±6.57） μg/mL （3.10-29.50 μg/mL）； absolute weight deviation was 22.95％， and the relative prediction error was 2.72％. Whether BMI was normal or not had significant effects on the absolute weight deviation   （χ2＝4.75， P＝0.029）， and whether AKI occurred or not had no significant effects on the absolute weight deviation （χ2＝0.236， P＝0.627）. JPKD and SmartDose predicted that predicted steady blood trough concentrations of vancomycin in 22 included patients were （11.06±3.58） and （12.15±4.35） μg/mL， and the measured concentration was （12.57±4.50） μg/mL； absolute weight deviations were 18.30％ and 18.68％； relative prediction errors were －8.65％ and －0.44％， respectively. The absolute weight deviations of the predicted values of the two systems were less than 30％. The absolute weight deviations of prediction results were also less than 30％ in 3 patients. CONCLUSIONS： JPKD and SmartDose system have good predictive ability for blood concentration of vancomycin in clinical application， and can be used to optimize the individualized administration of vancomycin.

ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation， mitigate anxiety-like behavior， and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB （p38 MAPK/NF-κB） signaling pathway in the rat model of generalized anxiety disorder （GAD）. MethodTwelve out of 74 Wistar rats were randomly selected as the blank group， and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test （OFT） and elevated Porteus maze test （PMT） were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model， low-， medium-， and high-dose （6， 12， and 24 g·kg^-1， respectively） Chaihu Longgu Mulitang， and diazepam （1 mg·kg^-1） groups （n=12） and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was conducted to determine the mRNA levels of p38 MAPK， NF-κB p65， nuclear factor κB inhibitor α （IκBα）， and ionized calcium binding adaptor molecule 1 （Iba-1）. The protein levels of p38 MAPK， phosphorylated （p）-p38 MAPK， NF-κB p65， p-NF-κB p65， and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group， the model group had decreased body weight， scattered dark yellow fur， increased irritability， and preference to hibernation in the corner. In addition， the modeled rats showed increased edge movement distance and time in OFT （P<0.01） and decreased movement distance and time and the number of entries in the open arm in PMT （P<0.01）. The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus （P<0.01）， elevated the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamus （P<0.01）， up-regulated the protein and mRNA levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and down-regulated the protein and mRNA levels of IκBα （P<0.01） in the hypothalamus. Compared with the model group， medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight， improved the fur and behaviors， decreased the edge movement distance and time in OFT （P<0.05， P<0.01）， and increased the movement distance and time in the open arm in PMT （P<0.05， P<0.01）. Furthermore， they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia （P<0.05， P<0.01）， lowered the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamic tissue （P<0.05， P<0.01）， down-regulated the mRNA and protein levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of IκBα （P<0.05， P<0.01） in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.