Prevalence and molecular characterization of Clostridioides difficile infection in China over the past 5 years: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to provide an overview of the prevalence and molecular characteristics of Clostridioides difficile infection (CDI) in China in the past 5 years. METHODS: A systematic literature review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Nine databases were searched for relevant studies published between January 2017 and February 2022. The Joanna Briggs Institute critical appraisal tool was used to assess the quality of included studies, and R software version 4.1.3 was used for data analysis. Funnel plots and Egger regression tests were also performed to assess publication bias. RESULTS: A total of 50 studies were included in the analysis. The pooled prevalence of CDI in China was 11.4% (2696/26,852). The main circulating C. difficile strains in southern China were ST54, ST3, and ST37, consistent with the overall situation in China. However, the most prevalent genotype in northern China was ST2, which was previously underappreciated. CONCLUSION: Based on our findings, increased awareness and management of CDI is necessary to reduce the prevalence of CDI in China.

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity / 药物分析学报

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis.

OBJECTIVE: Collectin 11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. We undertook this study to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). METHODS: A murine collagen-induced arthritis (CIA) model was used and combined two approaches, including gene deletion of Colec11 and treatment with recombinant CL-11 (rCL-11). Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines, and adaptive immune responses were assessed in mice with CIA. Splenic CD11c+ cells were used to examine the influence of CL-11 on antigen-presenting cell (APC) function. Serum CL-11 levels in RA patients were also examined. RESULTS: Colec11-/- mice developed more severe arthritis than wild-type mice, as determined by disease incidence, clinical arthritis scores, and histopathology (P < 0.05). Disease severity was associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c+ cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacologic treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum CL-11 levels were lower in RA patients (n = 51) compared to healthy controls (n = 53). Reduction in serum CL-11 was inversely associated with the Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and C-reactive protein level (P < 0.05). CONCLUSION: Our findings demonstrate a novel role of CL-11 in protection against RA, suggesting that the underlying mechanism involves suppression of APC activation and subsequent T cell responses.

Carriage of Clostridioides difficile in healthy infants in the community of Handan, China: A 1-year follow-up study.

OBJECTIVE: Clostridioides difficile may colonize healthy infants and young children asymptomatically and for the long-term. C. difficile genotypes and the rate and determinants of colonization differ substantially and vary among countries and regions. A 1-year follow-up study was performed to determine the incidence, kinetics and influencing factors of C. difficile intestinal colonization. METHODS: Twenty-nine healthy infants (14 girls and 15 boys) living at home with their parents in Handan City were followed by survey from birth to 1 year of age, specifically from October 2014 through December 2015. C. difficile isolates were typed by PCR ribotyping and analyzed for the presence of toxin genes. RESULTS: During the follow-up study period in the first year of life, 20 of the 29 total enrolled infants acquired C. difficile. A total of 437 fecal samples were obtained, and 111 (25.4%) samples contained C. difficile, including 79 (71.2%) toxigenic strains. The toxigenic isolates comprised six PCR ribotypes, and two PCR ribotypes were identified as nontoxigenic strains. CONCLUSION: Our study showed that C. difficile colonization increase with age during the 12-month period, and the dominant toxigenic types of C. difficile isolates in infants were those involved in long-term colonization. Feeding patterns may affect the dynamic progress of C. difficile colonization.

The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway.

BACKGROUND AND OBJECTIVE: Oxidative stress has been suggested as an important pathogenic factor contributing to chronic periodontitis with diabetes mellitus (CPDM). Previous studies have revealed the potential therapeutic properties of baicalein (BCI) in oxidative stress-related diseases; however, the antioxidant effects of BCI on therapy for individual with CPDM remain largely unexplored. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in cellular defence against oxidative stress. In this study, we aim to determine whether BCI prevents diabetes-related periodontal tissue destruction by regulating Nrf2 signaling pathway. MATERIAL AND METHODS: Human gingival epithelial cells (hGECs) were challenged with high glucose (HG, 25 mmol/L) and/or lipopolysaccharide (LPS, 20 µg/mL). Reactive oxygen species (ROS) were detected by fluorescence-activated cell sorting. The changes of antioxidant-related genes, including Nrf2, catalase (Cat), glutamate-cysteine ligase catalytic subunit (Gclc), superoxide dismutase 1 (Sod1), and superoxide dismutase 2 (Sod2), were quantified by real-time PCR. The localization of phospho-Nrf2 (pNrf2, S40) in the nucleus was detected by immunofluorescence staining and laser scanning confocal microscope (LSCM). PNrf2 and total form of Nrf2 were determined using western blot. The above indicators together with mitochondrial membrane potential (MMP) were further investigated in hGECs pre-treated with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL) before stimulated with HG plus LPS (GP). Finally, the role of BCI in activating Nrf2 signaling pathway and relieving the alveolar bone absorption was examined in the CPDM model of Sprague Dawley rats. CPDM rats were oral gavaged with BCI (50, 100, or 200 mg/kg daily). The pNrf2 was detected by immunohistochemistry, and the alveolar bone absorption was examined by microcomputed tomography. RESULTS: Our results showed that ROS were significantly increased in both groups of HG and LPS, with the strongest generation in the GP group. In terms of ROS-related gene expression, we found that the mRNA levels of Nrf2, Cat, Gclc, Sod1, and Sod2 were significantly decreased in HG and LPS groups. In consistent with the strongest induction of ROS in GP group, the gene expression in GP group was further decreased as compared to those of HG and LPS groups. Also, the expression of pNrf2 exhibited the same trend with the expression of those antioxidant genes. However, the generation of ROS and the loss of mitochondrial membrane potential induced by GP were abolished by pre-treatment with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL). Interestingly, we observed that BCI promoted the nucleus translocation of pNrf2, as well as the gene expression levels of pNrf2 and its target genes (Cat, Gclc, Sod1, and Sod2). Finally, in the CPDM animal model, we found that BCI (at concentrations: 50, 100, and 200 mg/kg) markedly increased the number of pNrf2-positive cells in periodontal tissue and mitigated the alveolar bone loss. CONCLUSIONS: Our data revealed a potential role for clinic application of BCI under CPDM conditions, suggesting a new therapeutic drug for CPDM patients.

Modified Xiaochaihu Decoction () Promotes Collagen Degradation and Inhibits Pancreatic Fibrosis in Chronic Pancreatitis Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Modified Xiaochaihu Decoction (MXD, ) on collagen degradation in rats with chronic pancreatitis (CP).@*METHODS@#Rats were injected dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right caudal vein to induce CP model. Thirty heallhy male Wistar rats were randomly divided into three groups by a random number table: the control, the model and the treatment groups. Rats of treatment group were administered MXD (10 g/kg of body weight) orally once daily starting from the day post-model establishment. Pancreatic tissues were harvested after 28-day feeding and fibrosis was evaluated by picro-sirius red staining. The contents of collagen type I and III were detected using enzymelinked immunosorbent assay (ELISA), the expression of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase 1 (TIMP1) was analyzed by Western blot and real-time polymerase chain reaction (PCR).@*RESULTS@#The fibrosis scoring of pancreatic tissues, the concentrations of collagen type I and III, the expression levels of MMP13 and TIMP1 proteins and mRNA in the model group were all increased compared with the control group (P0.05).@*CONCLUSIONS@#MXD could promote collagen degradation and reverse pancreatic fibrosis in CP rats via a mechanism involve up-regulation of MMP13 expression.

Methods for Creating Medium and Large Animal Models of Peripheral Atherosclerosis / 中国医学科学院学报

Atherosclerosis (AS) is the main pathological basis for the occurrence of many vascular diseases and has a strong association with metabolic syndrome. Peripheral arterial diseases caused by AS have high morbidities and mortalities but lack still effective treatment. AS animal models are highly valuable for research on peripheral arteriosclerotic diseases. While small and medium AS animal models based on high-fat feeding and balloon injuries have been successfully established,few literatures have described the creation of large animal models for AS treatment. This article elucidates the current methods for creating medium and large animal models of peripheral atherosclerotic disease,with an attempt to further promote the clinical translation of AS treatment research.

The C5a/C5aR1 axis promotes progression of renal tubulointerstitial fibrosis in a mouse model of renal ischemia/reperfusion injury.

C5a is a potent proinflammatory agonist that mediates renal ischemia reperfusion (IR) injury, but the potential for modulating chronic post-ischemic fibrosis and use of therapeutic antagonist are undefined. Here we determine whether C5a receptor 1 (C5aR1) signaling is essential to the development of post-ischemic fibrosis and if it is a valid target for therapeutic blockade with soluble receptor antagonist. C5aR1 is required for the development of renal tubulointerstitial fibrosis in a murine model of renal ischemia/reperfusion injury. Deficiency of C5aR1 protected mice from the development of the fibrosis. This protection was associated with attenuated deposition of extracellular matrix components (fibronectin, collagen I), reduced cellular infiltrates (CD45, F4/80), and gene expression of proinflammatory and profibrogenic mediators in the kidney. In an in vitro model of hypoxia/reoxygenation, C5a stimulation caused renal fibroblast proliferation and activation, and upregulated gene expression of interleukin-1α (IL-1α), IL-6 and transforming growth factor-α (TGF-α) in renal tubular epithelial cells and monocytes/macrophages. Administration of a C5aR1 antagonist (PMX53) significantly reduced renal injury and tubulointerstitial fibrosis. Thus, our results demonstrate a pathogenic role for C5aR1 in the progression of tubulointerstitial fibrosis following renal IR injury and support that C5aR1-mediated local inflammatory responses to hypoxic renal injury contribute to tubulointerstitial fibrosis through several cellular pathways, namely, promoting tubule injury, interstitial fibroblast proliferation and epithelial-to-mesenchymal transition of renal tubular epithelial cells. Our results also suggest the C5a-C5aR1 interaction is a therapeutic target for chronic post-ischemic fibrosis.

Epidemiological investigation of Clostridioides difficile colonization in Chinese community infants.

Clostridioides difficile is a colonizer of the human gut; asymptomatic colonization has been reported to be more common in infants and is highly variable across regions even with no symptoms of diarrhea or death. Antibiotic treatment strategies might increase the antibiotic resistance of C. difficile. We performed a one-point study involving 1098 healthy infants (0-36 months) to address the deficiency of reports on C. difficile colonization in Chinese community infants. The C. difficile colonization rate was 22.8% (250/1098), and more than half of the strains (55.2%) were toxigenic isolates. Among the 138 toxigenic isolates, 111 were of the A+B+CDT- genotype, 26 strains were A-B+CDT-, and one strain was A+B+CDT+. Fifteen different PCR ribotypes were found among the 250 isolates, and PCR-ribotype HB03 appeared to be dominant type, accounting for 19.6% (49/250). High levels of resistance to antimicrobial agents were observed. Our study showed that age and hospitalization before stool collection were positively correlated with the C. difficile colonization rate, whereas the delivery term was negatively related to the colonization rate. Particular attention should be paid to the increasing resistance of C. difficile to rifamycin.

First line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China / 中华医学杂志(英文版)

Background@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*Methods@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*Results@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*Conclusion@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

First line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China / 中华医学杂志(英文版)

BACKGROUND@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*METHODS@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*RESULTS@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*CONCLUSION@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

Modified Da-chai-hu Decoction regulates the expression of occludin and NF-κB to alleviate organ injury in severe acute pancreatitis rats / 中国天然药物

Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·Lvs (5626.4 ± 795.1)U·L], DAO [(1100.1 ± 334.3) U·Lvs (1666.4 ± 525.3) U·L] and CRP [(7.6 ± 1.2) μg·mLvs (17.8 ± 3.8) μg·mL]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mLvs (90.1 ± 14.9) pg·mL] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

Kindlin-2-mediated upregulation of ZEB2 facilitates migration and invasion of oral squamous cell carcinoma in a miR-200b-dependent manner.

The miR-200 family suppresses epithelial-mesenchymal transition by inhibiting ZEB1 and ZEB2 mRNA translation in several types of cancers. Kindlin-2 is a target gene of miR-200b and its expression level correlates positively to ZEB2 in oral squamous cell carcinoma (OSCC). Whether Kindlin-2 and ZEB2 share a competitive endogenous RNAs regulatory network in OSCC remains unclear. Here, we studied the expression levels of miR-200b, Kindlin-2, and ZEB2 and found direct interaction between miR-200b, ZEB2, and Kindlin-2 mRNA in OSCC. A series of experiments was performed to elucidate the role of miR-200b and Kindlin-2 in OSCC cells. To further investigate whether Kindlin-2 regulates ZEB2 as a "ceRNA", we utilized pools of siRNAs to deplete Kindlin-2 or ZEB2 in Tca-8113 cells. Significantly elevated expression levels of Kindlin-2 and ZEB2, down-regulated mRNA levels of miR-200b, and a positive correlation between Kindlin-2 and ZEB2 were found in OSCC cells. Additional results suggest that miR-200b directly targets ZEB2 and that Kindlin-2 3'UTR miR-200b repressed both the migration and invasive functionality of Tca-8113. Kindlin-2 and ZEB2 are involved in accelerated migration and invasion of Tca-113 cells in vitro and Kindlin-2 controlled ZEB2 expression. However, Kindlin-2-mediated ZEB2 regulation did not depend on miRNAs. These results indicate that Kindlin-2 does not act as ZEB2 ceRNA and modify the migration of Tca-8113 cells. Our results improve our understanding of the underlying molecular and cellular mechanisms of oral cancer metastasis.

The promotion function of Berberine for osteogenic differentiation of human periodontal ligament stem cells via ERK-FOS pathway mediated by EGFR.

Coptidis Rhizoma binds to the membrane receptors on hPDLSC/CMC, and the active ingredient Berberine (BER) that can be extracted from it may promote the proliferation and osteogenesis of periodontal ligament stem cells (hPDLSC). The membrane receptor that binds with BER on the cell surface of hPDLSC, the mechanism of direct interaction between BER and hPDLSC, and the related signal pathway are not yet clear. In this research, EGFR was screened as the affinity membrane receptor between BER and hPDLSC, through retention on CMC, competition with BER and by using a molecular docking simulation score. At the same time, the MAPK PCR Array was selected to screen the target genes that changed when hPDLSC was simulated by BER. In conclusion, BER may bind to EGFR on the cell membrane of hPDLSC so the intracellular ERK signalling pathways activate, and nuclear-related genes of FOS change, resulting in the effect of osteogenesis on PDLSC.

Circulating high mobility group AT-hook 2 and pleomorphic adenoma gene 1 in blood of patients with oral squamous cell carcinoma.

BACKGROUND: High mobility group AT-hook 2 (HMGA2) and pleomorphic adenoma gene 1(PLAG1) have been demonstrated to be elevated in many malignant tumors. However, the aim of this study was to evaluate HMGA2 and PLAG1 levels in blood as a non-invasive biomarker for oral squamous cell carcinoma (OSCC) diagnosis. METHODS: qRT-PCR was performed to measure circulating HMGA2 and PLAG1 levels in OSCC patients (n=43) and matched cancer-free blood control group (n=21). Clinical data of all patients were recorded. RESULTS: Circulating HMGA2 and PLAG1 in the 43 OSCC patients was significantly higher than in control group (P<.001, P=.038, respectively). Furthermore, HMGA2 expression in OSCC patients with poor-moderate differentiation was increased compared with well-differentiated group. However, no significant differences in PLAG1 expression were detected when differentiation was considered. In addition, the receiver operating characteristic (ROC) curve analysis for circulating HMGA2 revealed an area under the ROC curve of 0.876 (95% confidence interval, 0.793-0.959; P<.001) with 65.1% sensitivity and 100% specificity in discriminating OSCC from controls at a cutoff value of 14.380, demonstrating significant diagnostic value for OSCC. CONCLUSION: Circulating HMGA2 levels are increased in OSCC patients and may potentially serve as a significant index to evaluate OSCC diagnosis.

Low-dose propranolol for infantile hemangioma of the head and neck: Analysis of 23 consecutive patients.

BACKGROUND: More and more infantile hemangiomas (IH) are being treated with propranolol, but the effectiveness, dosage, and treatment course are still in dispute. The aim of this observational study was to describe the therapeutic response, tolerance, and safety of low-dose propranolol in 23 children with IH of the head and neck. METHODS: Data were collected from the medical charts of patients treated with low-dose propranolol from December 2009 through November 2011. Oral dose was 1-1.5 mg/kg once per day. Blood pressure and heart rate were monitored during the first 24 h of treatment. In the absence of side-effects, treatment was continued at home and the child was re-evaluated every month. RESULTS: All patients had a good response, even if treated with corticosteroid previously. Color and growth changes within 1 week were noted. Treatment continued for a mean total duration of 6 months until the IH had totally disappeared or stabilized. There were no severe adverse reactions. Side-effects were limited and mild, including blood pressure decrease, somnolence, and nausea. No relapse was noted. CONCLUSIONS: Low-dose propranolol appears to be effective and safe for IH, especially for those patients previously treated with corticosteroid and who had no response or severe side-effects.

Safety and immunogenicity evaluation of 60μg recombinant hepatitis B vaccine (Saccharomyces Cerecisiae) in population aged 16 and above / 预防医学

Objective To evaluate the safety of 60μg recombinant hepatitis B vaccine(Saccharomyces Cerecisiae)in healthy population over 16 years old and immunogenicity in non-responders.Methods A total of 4345 eligible subjects over 16 years old were selected and vaccinated with 60 μg recombinant hepatitis B vaccine, including 3415 participants who have never been vaccined before and 930 non-responders. All participants were monitored for any adverse events occurring within 30 min after each injection and instructed to record selected injection-site reactions and systemic reactions on the day of vaccination and the subsequent 28 days. Blood samples were collected from non-responders at pre-vaccination and one month after vaccination,in order to determine anti-HBs levels,positive rates of anti-HBs and the mean geometric titre(GMT)of anti-HBs.Results Among 4345 vaccinated participants,16.39 % of them reported at least one injection-site or systemic adverse reaction. The most common injection-site and systemic adverse reactions were Grade 1 adverse reactions with the incidence of 15.12 %(657/4345)and 4.05%(176/4345)respectively. No serious adverse events were observed. Among 930 non-responders,the positive rate of anti-HBs was 87.03 % with active responder of 76.74 %(551 / 718)and the GMT of anti-HBs was 479.28 mIU / ml. The positive rate of anti-HBs was not associated with gender or age (P>0.05). The GMT of anti-HBs demonstrated significant differences between female and male(560.66 mIU / mL VS. 404.91 mIU / mL,P<0.05),but there was no significant differences in different age groups (P>0.05).Conclusion 60μg recombinant hepatitis B vaccine was safe for healthy adults above 16 years and had good immunity efficacy among non-responders who had no or low response to standard immunization regimen of hepatitis B vaccine.

Subinhibitory concentrations of phloretin repress the virulence of Salmonella typhimurium and protect against Salmonella typhimurium infection.

Phloretin, a natural component of many fruits, exhibits anti-virulence effects and provides a new alternative to counter bacterial infection. The aim of this study was to determine the effect of subinhibitory concentrations of phloretin on the virulence of Salmonella typhimurium. At concentrations where growth of Salmonella was not inhibited, phloretin significantly inhibited bacteria biofilm formation and motility. Subinhibitory concentrations of phloretin repressed eight genes involved in the Salmonella pathogenicity island 1 and 3 genes involved in flagella production. Furthermore, subinhibitory concentrations of phloretin inhibited the adhesion and invasion of Salmonella in IEC-6 cells and reduced the LDH levels of S. typhimurium-infected IEC-6 cells. Additionally, phloretin significantly decreased the cecum bacterial loads of the mice infected with live S. typhimurium containing subinhibitory concentrations of phloretin by gavage. These results suggested that subinhibitory concentrations of phloretin attenuate the virulence of S. typhimurium and protect against S. typhimurium infection.

Molecular Characterization of Clostridium difficile Isolates from Human Subjects and the Environment.

Clostridium difficile is a spore-forming, gram-positive, anaerobic bacillus that can cause C. difficile infection (CDI). However, only a few studies on the prevalence and antibiotic resistance of C. difficile in healthy individuals in China have been reported. We employed a spore enrichment culture to screen for C. difficile in the stool samples of 3699 healthy Chinese individuals who were divided into 4 groups: infants younger than 2 years of age and living at home with their parents; children aged 1 to 8 years of age and attending three different kindergarten schools; community-dwelling healthy adult aged 23-60 years old; and healthcare workers aged 28-80 years old. The C. difficile isolates were analyzed for the presence of toxin genes and typed by PCR ribotyping and multilocus sequence typing (MLST). The minimum inhibitory concentration of 8 antimicrobial agents was determined for all of the isolates using the agar dilution method. The intestinal carriage rate in the healthy children was 13.6% and ranged from 0% to 21% depending on age. The carriage rates in the 1654 community-dwelling healthy adults and 348 healthcare workers were 5.5% and 6.3%, respectively. Among the isolates, 226 were toxigenic (225 tcdA+/tcdB+ and 1 tcdA+/tcdB+ ctdA+/ctdB+). Twenty-four ribotypes were found, with the dominant type accounting for 29.7% of the isolates. The toxigenic isolates were typed into 27 MLST genotypes. All of the strains were susceptible to vancomycin, metronidazole, fidaxomicin, and rifaximin. High resistance to levofloxacin and ciprofloxacin at rates of 39.8% and 98.3%, respectively, were observed. ST37 isolates were more resistant to levofloxacin than the other STs. The PCR ribotypes and sequence types from the healthy populations were similar to those from the adult patients.

Hepatitis B Immunoprophylactic Failure and Characteristics of the Hepatitis B Virus Gene in Mother-Infant Pairs in Parts of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus (HBV) infected mothers and to characterize HBV genes.</p><p><b>METHODS</b>HBV-serological testing was conducted for pregnant women and infants. The complete genomes of 30 HBV isolates were sequenced, and genetic characteristics were analyzed using MEGA 5 software.</p><p><b>RESULTS</b>The immunoprophylactic failure rate for infants who had completed the scheduled hepatitis B vaccination program was 5.76% (32/556). High sequence homology (99.8%-100%) was observed in 8 of the 10 mother-infant pairs. We identified 19 subgenotype C2 strains, 9 subgenotype B2 strains, and 2 subgenotype C1 strains. Three serotypes were detected: adr (19/30), adw (9/30), and ayw (2/30). The frequency of amino acid mutation of the 'a' determinant region was 16.67% (5/30), including that of Q129H, F134Y, S136Y, and G145E. We detected 67 amino acid mutations in the basal core promoter, precore, and core regions of the genome.</p><p><b>CONCLUSION</b>The immunoprophylactic failure rate in infants born to HBV-infected mothers is low in the regions of China examined during this study. Moreover, HBV mutation in the 'a' determinant region could not account for immunoprophylactic failure for all infants.</p>