Xiaobei Chen

Knowledge, attitude and practice of antibiotics: a questionnaire study among 2500 Chinese students

BackgroundRecently, many scientists including bacteriologists have begun to focus on social aspects of antibiotic management especially the knowledge, attitude and practice (KAP) among the general population regarding antibiotic use. However, relatively few works have published on the relationship between KAP and medical education. In this study, we analyze the present status of Chinese medical (MS)- and non-medical (NS) students’ KAP on the use of antibiotics, and examine the influence of Chinese medical curriculum on the appropriate usage of antibiotics among medical students.MethodsIn this study, 2500 students from 3 universities (including one medical university) in Northeastern China participate in the questionnaire survey on students’ knowledge, attitude and practice toward antibiotic usage. Wilcoxon rank sum test and Chi square test were used to analyze questionnaire-related discrete and categorical variables respectively, in order to assess the impact of the medical curriculum on students’ KAP towards antibiotics.Results2088 (83.5%) respondents (MS-1236 and NS-852) were considered valid for analysis. The level of knowledge of MS on the proper use of antibiotics was significantly higher than that of NS (p < 0.0001). However, based on their responses on actual practice, MS were found to rely on antibiotics more than NS (p < 0.0001). Moreover, the knowledge and attitude of MS towards antibiotic use improved with the increase in grade with discriminate use of antibiotics concurrently escalating during the same period.ConclusionsThis study indicates that Chinese medical curriculum significantly improves students’ knowledge on antibiotics and raises their attention on antibiotic resistance that may result from indiscriminate use of antibiotics. The study also shows an excessive use of antibiotics especially among the more senior medical students, signifying a deficiency of antibiotics usage instruction in their curriculum. This might explain why there are frequent abuses of antibiotics in both hospital and community settings from a certain angle.

Specific patterns of gyrA mutations determine the resistance difference to ciprofloxacin and levofloxacin in Klebsiella pneumoniae and Escherichia coli

BackgroundWide use of ciprofloxacin and levofloxacin has often led to increased resistance. The resistance rate to these two agents varies in different clinical isolates of Enterobacteriaceae. Mutations of GyrA within the quinolone resistance-determining regions have been found to be the main mechanism for quinolone resistance in Enterobacteriaceae. It has been shown that only some of the mutations in the gyrA gene identified from clinical sources were involved in fluoroquinolone resistance. Whether different patterns of gyrA mutation are related to antimicrobial resistance against ciprofloxacin and levofloxacin is unclear.MethodsThe minimum inhibitory concentration (MIC) of ciprofloxacin and levofloxacin were determined by the agar dilution method followed by PCR amplification and sequencing of the quinolone resistance determining region of gyrA to identify all the mutation types. The correlation between fluoroquinolone resistance and the individual mutation type was analyzed.ResultsResistance differences between ciprofloxacin and levofloxacin were found in 327 isolates of K. pneumoniae and E. coli in Harbin, China and in the isolates reported in PubMed publications. GyrA mutations were found in both susceptible and resistant isolates. For the isolates with QRDR mutations, the resistance rates to ciprofloxacin and levofloxacin were also statistically different. Among the 14 patterns of alterations, two single mutations (Ser83Tyr and Ser83Ile), and three double mutations (Ser83Leu+Asp87Asn, Ser83Leu+Asp87Tyr and Ser83Phe+Asp87Asn) were associated with both ciprofloxacin and levofloxacin resistance. Two single mutations (Ser83Phe and Ser83Leu) were related with ciprofloxacin resistance but not to levofloxacin. Resistance difference between ciprofloxacin and levofloxacin in isolates harboring mutation Ser83Leu+Asp87Asn were of statistical significance among all Enterobacteriaceae (P<0.001).ConclusionsResistance rate to ciprofloxacin and levofloxacin were statistically different among clinical isolates of Enterobacteriaceae harboring GyrA mutations. Ser83Leu+Asp87Asn may account for the antimicrobial resistance difference between ciprofloxacin and levofloxacin.

Modulation of miR-122 on persistently Borna disease virus infected human oligodendroglial cells

Using RNAhybrid software we found the predicted binding of complementary sequences between miR-122 and viral mRNAs, may be important for the antiviral effect of miR-122 on Borna disease virus (BDV). A moderate expression of miR-122 was identified in human oligodendroglial cells (OL), but with a much lower level of miR-122 in BDV persistent infection (OL/BDV) and cells transfected with BDV gene expression vectors. Over-expression of miR-122 and specific blocking experiments demonstrated that miR-122 was able to specifically inhibit BDV protein synthesis, viral gene replication and transcription, and induce the secretion/synthesis of interferon (IFN) in OL and OL/BDV cells. The abolishment of miR-122 by AMO-122 inhibited endogenous IFN induction by IFN-beta. These results indicate that miR-122 can exert direct antiviral function by inhibiting BDV translation and replication on one hand, while acting indirectly through IFN to increase the host innate immunity to modulate the virus-host interactions on the other hand.

Borna disease virus encoded phosphoprotein inhibits host innate immunity by regulating miR-155

It has been reported that the Borna disease virus (BDV) encoded phosphoprotein (P protein) can inhibit the activity of Traf family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK-1), thus preventing the induction of type I interferon (IFN). However, the effects of microRNA on the regulation of BDV infection and the hosts immune response have not been characterized. miR-155 was predicted to be complementary to the BDV P mRNA by RNAhybrid software. Here, we showed that miR-155 was down-regulated in BDV persistently infected human oligodendroglial (OL/BDV) cells and that the BDV P protein, but not the X protein, directly inhibited miR-155 expression in cells. When miR-155 was over-expressed, the inhibition of type I IFNs by BDV in cells was reversed, and the expression of type I IFNs was increased. When miR-155 expression was specifically blocked, cellular IFN expression and the induction of IFN by poly I:C treatment were suppressed. Furthermore, miR-155 promoted type I IFN production by targeting suppressor of cytokine signaling 1 (SOCS1) and SOCS3. Mutations in the nt1138-nt1158 region of SOCS3 abandoned the impact of miR-155 on the expression of SOCS3-enhanced green fluorescent protein (EGFP). The levels of BDV P mRNA and protein were significantly decreased in OL/BDV cells when miR-155 was over-expressed; however, miR-155-mutation did not affect the expression of BDV P-EGFP. Thus, BDV persistent infection inhibited the expression of type I IFNs through the suppression of miR-155, and miR-155 played an important immune regulatory role in BDV persistent infection.

Alteration of GyrA Amino Acid Required for Ciprofloxacin Resistance in Klebsiella pneumoniae Isolates in China

ABSTRACT Resistance to ciprofloxacin was detected in 111 (48.1%) isolates of Klebsiella pneumoniae from China. GyrA alterations were identified in the ciprofloxacin-resistant and ciprofloxacin-susceptible isolates. The results, including previously published data, indicate that the single substitution Ser83→Ile and three types of double mutations at Ser83 and Asp87 were required for ciprofloxacin resistance (P < 0.05).

Role of nitric oxide in ischemia-reperfusion injury and acute rejection in rat intestinal transplantation.

OBJECTIVE This study was designed to evaluate the role of nitric oxide (NO) in ischemia-reperfusion injury (IRI) and acute rejection (AR) in rat intestinal transplantation, using administration of the NO inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). MATERIALS AND METHODS Rats that underwent orthotopic allogeneic intestinal transplantation were assigned to 2 groups. In the normal allograft group (Wistar to Sprague-Dawley rats), L-NAME 0 mg/kg/d (group 1-1), 4 mg/kg/d (group 1-2), 8 mg/kg/d (group 1-3), or 12 mg/kg/d (group 1-4) was injected intraperitoneally. In the high responder allograft group (Dark Agouti to Lewis rats), L-NAME 0 mg/kg/d (group 2-1) or 8 mg/kg/d (group 2-2) was injected intraperitoneally. Survival times were observed and maltose absorption tests performed as well as light microscopic examination of the grafts. RESULTS The mean survival time of group 1-3 was significantly prolonged compared with group 1-1 (P < .01). In group 2, the survival time of group 2-2 was significantly prolonged compared with group 2-1 (P < .01). Histological changes showed IRI was attenuated in group 1-2 compared with group 1-1, whereas it was aggravated in groups 1-3 and 1-4. Treatment with L-NAME (8 mg/kg/d) attenuated the graft damage of AR in groups 1 and 2. Maltose absorption tests showed that inhibition of NO impaired maltose absorption. CONCLUSION This study suggested that NO plays a dual role as both a cytotoxic and a cytoprotective factor in IRI, and may serve as a kind of cytotoxic medium in AR in rat intestinal allotransplantation.

Multilocus sequence types and virulence determinants of hypermucoviscosity-positive Klebsiella pneumoniae isolated from community-acquired infection cases in Harbin, North China

We investigated the molecular epidemiologic characteristics and virulence of hypermucoviscosity-positive Klebsiella pneumoniae in mainland China. We detected 16 hypermucoviscosity-positive strains in 65 total clinical isolates (24.62%). We found that 68.75% (11/16) of the positive strains had K2 genotype and carried the rmpA and iucA genes. Multilocus sequence typing revealed 5 sequence types (STs): ST65 [7], ST23 [4], ST86 [3], ST412 [1], ST375 [1], whereas the remaining 4 isolates were defined as other STs. The order of the median lethal dose values for the ST types was ST23 (2.19 × 10(3) CFU/mouse) < ST86 (1.70 × 10(4) CFU/mouse) < ST65 (5.05 × 10(7) CFU/mouse) < the other STs (1.90 × 10(8) CFU/mouse). In conclusion, the K2 with ST65 carrying rmpA and iucA was the most predominant among the hypermucoviscosity-positive K. pneumoniae strains obtained from community-acquired infection cases in Harbin, North China. Sequence types are a valuable tool to predict the risk of K. pneumoniae infection.

Differential diagnosis of systemic lupus erythematosus and rheumatoid arthritis with complements C3 and C4 and C-reactive protein.

The aim of this study was to analyze the changes in complements C3 and C4 and C-reactive protein (CRP) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and to evaluate the role of these indices in the differential diagnosis of SLE and RA. The first 347 patients with SLE, 382 patients with RA and 66 patients with erythema nodosum were selected for the measurement of complement and CRP levels in the serum, the erythema nodosum patients were the control group. The roles of the complements and CRP in the differential diagnosis and disease activity evaluation of SLE and RA were analyzed with SPSS 13.0. Complement C3 and C4 levels were significantly reduced in patients with SLE compared with those in the control group. However, in RA patients, the CRP level was increased. In addition, the levels of complements C3 and C4 in patients with SLE were much lower than those in patients with RA and the level of CRP in RA patients was much higher than that in patients with SLE. The reduction of complement C3 levels in SLE patients, and increase of CRP and complement C4 in patients with RA were associated with a higher risk of joint pain, butterfly rash and oral ulcer. These results show that the disease activity of SLE was negatively correlated with complement C3 and C4, and the disease activity of RA was positively correlated with CRP. With the increase in disease activity, the levels of complements C3 and C4 in patients with SLE were gradually reduced and the level of CRP in patients with RA was increased. There were distinctive differences in the levels of complements C3 and C4 and CRP between SLE and RA patients. The differences are useful in disease activity evaluation and the differential diagnosis of the two diseases that have similar symptoms.

Novel Sulfated Glucomannan-Barium-Alginate Microcapsules in Islet Transplantation: Significantly Decreased the Secretion of Monocyte Chemotactic Protein 1 and Improved the Activity of Islet in Rats

The sulfated glucomannan can be used to filter the heparin-binding properties of cytokines. In this study, novel sulfated glucomannan-barium-alginate (SGA) microcapsules were prepared to encapsulate islets with barium-alginate (ABa) and calcium alginate-poly-l-lysine (APA) microcapsules as controls. SD rat islets were purified as donor cells to Lewis rats that had been treated with streptozotocin. Intraperitoneal transplantation was performed with about 3000 islet equivalent (IEQ) rat. At week three after transplantation, the concentrations of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-1 beta, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in intraperitoneal fluid were determined using ELISA. At week 8, the islet cell mass in the abdominal microcapsules was excised to test insulin release. The EB-FDA fluorescence staining method was used to observe the functional activity of the islet cells. Compared with ABa and APA microcapsules, SGA microcapsules showed significantly decreased MCP-1 secretion by beta-cells. Also, the concentrations of cytokines IL-1beta, IFN-gamma, and TNF-alpha were decreased significantly. The activity of the transplanted islets was significantly improved in SGA microcapsules, which shielded against cytokines better than ABa or APA microcapsules and may serve as novel method.

Pathogenic risk of endogenous retrovirus infection in immunodeficient hosts

To investigate the pathogenic risk of endogenous retroviruses (ERVs) infection in immunodeficient hosts, the ERV of N-type ecotropic murine leukemia virus (MuLV) isolated from SL mice, a kind of mice containing considerable infectious ERV particles determined with SC-XC test and developing leukemia spontaneously with average of high frequency of 30% and incubation period of 315days, was inoculated intraperitoneally into newborn CBA nude mice. The distinct marker of splenomegaly for leukemia was observed in 33% of homozygous (nu/nu) and 17% of heterozygous (nu/+) of CBA nude mice with average incubation period of 310days and 432days post-inoculation, respectively. Furthermore, the ERV induced leukemia in both the SL mice and CBA nude mice was identified to be B lymphatic, transplantable and with rearrangement of the Evi-1 locus. The higher induction of leukemia and rearrangement of the Evi-1 locus in CBA nude mice are considered to be dependent on the lower immune status of the hosts. These findings indicate that the ERV could present the host immune dependent leukemogenesis in immunodeficient hosts through the Evi-1 gene rearrangement and suggest that screening of ERVs may be necessary in clinical transplantation or transfusion.