Search

Background: Femoral nerve block (FNB) is a prevalent method used for postoperative pain management after knee surgery; however, it decreases the strength of the quadriceps muscle and is not conducive to early recovery after surgery. Pectineus muscle plane (PMP) block involves the injection of a local anaesthetic into the fascial plane below the pectineus muscle, where it blocks the obturator and saphenous nerves. However, there is little evidence on the effectiveness of PMP block for analgesia after knee surgery. The aim of this trial is to assess whether PMP block can improve postoperative analgesia, promote early recovery and reduce the length of hospital stay., Methods and Analysis: In this randomised controlled study, 46 patients will be randomly allocated into two groups: the PMP block group (n=23) and the FNB group (n=23). The primary outcome measures will include Visual Analog Scale scores for pain at rest and during movement at various time points following knee surgery. Secondary outcomes will include the degree of active flexion, straight leg raise test performance, get-out-of-bed test result, 20 m walk test result, total dose administered via patient-controlled analgesia infusion pumps, hospital stay duration, patient satisfaction and postoperative complications, such as pulmonary embolism and deep vein thrombosis.This study protocol adheres to rigorous standards for ethical conduct and patient safety. The findings from this trial are expected to contribute valuable insights to the optimisation of postoperative pain management strategies and the improvement of early recovery outcomes for patients who undergo knee surgery., Ethics and Dissemination: This trial has been approved by the ethics committee of Zhejiang Hospital (2022(128K)) on 17 November 2022, and inpatients who meet the inclusion criteria and diagnostic requirements are eligible for this study. Any subsequent protocol and informed consent document amendments must be approved by the responsible ethics committee. All communications with the regulatory authorities and the ethics committee must be recorded. All recruited patients will be informed of the trial purposes and their duties within the trial before randomisation. Recruited patients can withdraw from the study at any time without providing any specific reason. The patient data will be stored in a separate, safe place, but that it may be reviewed by the relevant investigator. The results will be published in international peer-reviewed medical journals., Trial Registration Number: http://www.chictr.org.cn, ID: ChiCTR2300076018. Registered on 21 September 2023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This study aimed to determine the relationship between the expression of epidermal growth factor receptor (EGFR) and pathological indicators in papillary thyroid carcinoma (PTC)., Evidence Acquisition: PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library databases were searched for relevant clinical trials. The odds ratio (OR) and 95% confidence interval (CI) showed the effect magnitude of the expression of EGFR, age, gender, tumor size, lymph node metastasis (LNM), extrathyroid extension, and tumor, lymph node, metastasis) stage. Stata 12.0 was used for statistical analysis of data., Evidence Synthesis: A total of 845 cases of PTC were included through the retrieval of 8 studies performed abroad. EGFR significantly correlated with extrathyroid extension (OR=3.25; 95% CI: 1.25-8.43; Z=2.42; P=0.015), LNM (OR=8.40; 95% CI: 5.44-12.97; Z=9.61; P=0.000), TNM stage (OR=2.30, 95% CI: 1.51-3.51; Z=3.87; P=0.000), and tumor size (OR=1.68; 95% CI: 1.06-2.68; Z=2.19; P=0.03). EGFR had no correlation with age (OR=1.13; 95% CI: 0.83-1.53; Z=0.77; P=0.44), gender (OR=0.93; 95% CI: 0.66-1.33; Z=0.38; P=0.70). Sensitivity analysis demonstrated that the studies by Cui Tang and Alfred King Yin Lam in LNM impacted the pooled OR. After removing these two studies, relatively stable results between the expression of EGFR and LNM were obtained., Conclusions: The results in the expression of EGFR is frequent and cancer-specific event in PTC. Besides, the expression of EGFR was involved in the progression and metastasis of PTC.

Objective: A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions., Methods: Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels., Results: Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group., Conclusion: Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy., (© 2024. Huazhong University of Science and Technology.)

Aim: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children., Methods: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing., Results: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj. P <0.05), and 328 of these were identified with a significance of Adj. P <0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like ( TCERG1L , cg07684215) gene was hypermethylated in the four T1DM children with DR ( P =0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P >0.05) between participants with and without DR., Conclusion: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM., Competing Interests: Conflicts of Interest: Qian Y, None; Xiao Y, None; Lin QR, None; Xiang ZY, None; Cui LP, None; Sun JQ, None; Li SC, None; Qin XR, None; Zou HD, None; Yang CH, None; Jin PY, None., (International Journal of Ophthalmology Press.)

Background: The order Rickettsiales contains a group of vector-borne gram-negative obligate intracellular bacteria, which often cause human emerging infectious diseases and economic losses for dairy and meat industries. The purpose of this study is to investigate the distribution of the pathogens including Rickettsia spp., Anaplasma spp., and Ehrlichia spp. in the order Rickettsiales in ticks from Yueyang, a prefecture-level city of Hunan Province in Sothern China, and assess the potentiality of transovarial transmission of these rickettsial organisms., Methods: Ticks were collected from cattle in a farm in Yueyang City and the tick DNA was used as template to amplify the htrA, rrs, gltA, ompA and ompB genes of Rickettsia as well as rrs and groEL genes of Anaplasma and Ehrlichia., Results: All ticks (465) collected were the cattle tick, Rhipicephalus microplus. PCR showed the minimum infection rate (MIR) was 1.5% (7/465) for Candidatus Rickettsia xinyangensis, 1.9% (9/465) for C. Anaplasma boleense, 1.3% (6/465) for Anaplasma platys, 0.6% (3/465) for A. marginale, and 1.17% (2/465) for each of A. bovis, Ehrlichia minasensis, and a non-classified Ehrlichia sp. A human pathogen, C. Rickettsia xinyangensis and A. platys were detected in 100% (3/3) and 33.3% (2/6) laboratory-hatched larval pools from infected females respectively., Conclusion: Our study revealed a diversity of pathogenic rickettsial species in R. microplus ticks from Hunan Province suggesting a threat to people and animals in China. This study also provided the first molecular evidence for the potential transovarial transmission of C. Rickettsia xinyangensis and A. platys in R. microplus, indicating that R. microplus may act as the host of these two pathogens., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In recent years, the contamination of antibiotics and their resistance genes (ARGs) has attracted the extensive attention of researchers at home and abroad. Soil is an important sink for the migration and transformation of antibiotics and ARGs, which pose a threat to soil organisms and human health. According to the relevant investigations in the past 15 years, the soil has been polluted by antibiotics to varying degrees in China. Bioremediation is a green and environment-friendly remediation technology, which has great potential in the remediation of antibiotic-contaminated soil. This review summarized the spatial and temporal characteristics of antibiotic pollution of soils in China in the past 15 years and the application of plants, animals, and microorganisms in the remediation of antibiotic-contaminated soil. In particular, the recent research advances of microbial electrochemical systems in removing antibiotics and ARGs in soil were reviewed, and the unaddressed issues of relevant research and the direction of future development were proposed, in order to provide a scientific basis for soil pollution remediation.

Objective: To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR)., Methods: Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting., Results: Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats., Conclusion: Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiang, Chen, Qin, Lin, Xu, Lu and Zou.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus SFTSV with case fatality up to 30%. The reactivation of Epstein-Barr virus (EBV) has been proven to occur in individuals with various immune suppression conditions., Methods: Here, we diagnosed 22 SFTSV infected patients with PCR in a hospital in Shandong Province, China in 2020. To understand the consequences of SFTSV infection leading to EBV reactivation, we examined EBV reactivation in SFTSV-infected patients with PCR and RT-PCR., Results: We found that EBV was reactivated in 18.2% (4/22) of SFTS patients, suggesting that EBV reactivation is common in SFTS patients. Compared with SFTS patients without EBV reactivation, SFTS patients with EBV-reactivation had a significantly lower median level of serum albumin (32.45 g/L vs. 26.95 g/L,  p  = 0.03) and a significantly higher median number of urine red blood cells (0 cells/μL vs. 9 cells/μL,  p  = 0.04)., Conclusion: SFTS infection can reactivate EBV in patients, which may make the clinical condition of patients worsen., (© 2023 Published by Elsevier Ltd on behalf of Tsinghua University Press.)

Purpose: The goal was to develop a fully automated grading system for the evaluation of punctate epithelial erosions (PEEs) using deep neural networks., Methods: A fully automated system was developed to detect corneal position and grade staining severity given a corneal fluorescein staining image. The fully automated pipeline consists of the following three steps: a corneal segmentation model extracts corneal area; five image patches are cropped from the staining image based on the five subregions of extracted cornea; a staining grading model predicts a score for each image patch from 0 to 3, and automated grading score for the whole cornea is obtained from 0 to 15. Finally, the clinical grading scores annotated by three ophthalmologists were compared with automated grading scores., Results: For corneal segmentation, the segmentation model achieved an intersection over union of 0.937. For punctate staining grading, the grading model achieved a classification accuracy of 76.5% and an area under the receiver operating characteristic curve of 0.940 (95% CI 0.932 to 0.949). For the fully automated pipeline, Pearson's correlation coefficient between the clinical and automated grading scores was 0.908 (p<0.01). Bland-Altman analysis revealed 95% limits of agreement between the clinical and automated grading scores of between -4.125 and 3.720 (concordance correlation coefficient=0.904). The average time required for processing a single stained image during pipeline was 0.58 s., Conclusion: A fully automated grading system was developed to evaluate PEEs. The grading results may serve as a reference for ophthalmologists in clinical trials and residency training procedures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bartonella are vector-borne gram-negative facultative intracellular bacteria causing emerging infectious diseases worldwide, and two thirds of known Bartonella species are carried by rodents. We captured rodents, shrews and rodent ectoparasitic mites in rural areas of Qingdao City, Shandong Province, China from 2012 to 2021 and used the animal spleen tissues for the PCR amplification of Bartonella gltA and rpoB genes. PCR showed 9.4% (40/425) rodents, and 5.1% (12/235) shrews were positive for Bartonella. Seven Bartonella species including three novel species were identified in five rodent species and one shrew species, indicating the abundance and genetic diversity of Bartonella in rodents and shrews. The infection rate of each Bartonella species in the animal species was as below: novel Candidatus Bartonella crocidura in shrews Crocidura lasiura (5.1%, 12/235); novel Candidatus Bartonella cricetuli in hamsters Tscherskia triton (20%, 9/45); novel Candidatus Bartonella muris in striped field mice Apodemus agrarius (4.2%, 7/168) and house mice Mus musculus (1.5%, 2/135); Bartonella fuyuanensis in striped field mice (8.9%, 15/168) and house mice (0.7%, 1/135); Bartonella rattimassiliensis and Bartonella tribocorum in brown rats Rattus norvegicus (6.7%, 3/45 and 4.2%, 2/45, respectively); Bartonella queenslandensis in Chinese white-bellied rat Niviventer confucianus (12.5%, 1/8). These results suggest that Bartonella infected a variety of rodent and shrew species with high infection rate, but each Bartonella specie is restricted to infect only one or a few genetically closely related rodent species. In addition, Candidatus Bartonella cricetuli, Candidatus Bartonella muris and Bartonella coopersplainsensis were found in chigger Walchia micropelta (33.3%, 3/9), and B. fuyuanensis were found in chigger Leptotrombidium intermedium (4.1%, 1/24), indicating chiggers may be reservoirs of Bartonella. In conclusion, abundant genetic diversified Bartonella species are found to infect rodents, shrews and chiggers, but each Bartonella species has a strict rodent animal host specificity; and chigger mites may play a role in Bartonella transmission., (© 2022 Wiley-VCH GmbH.)

Purpose: To develop a fully automated segmentation and morphometric parameter estimation system for assessing corneal endothelial cells from in vivo confocal microscopy images., Design: Artificial intelligence (neural network) study., Methods: First, a fully automated deep learning system for assessing corneal endothelial cells was developed using the development set (from 99 subjects). Second, 184 images (from 97 subjects) were used to construct the testing set to evaluate the clinical validity and usefulness of the automated segmentation and morphometric system. Third, the automatically calculated endothelial cell density (ECD) values, Topcon's cell density, and manually calculated ECD were compared., Results: After slit lamp examination, 88 healthy subjects, 2 Fuchs endothelial dystrophy patients, and 7 corneal endotheliitis patients were identified among the 97 subjects in the testing set. The automatedly estimated morphometric parameters for the testing set were an average number of 234 cells, an ECD of 2592 cells/mm 2 , a coefficient of variation in the cell area of 32.14%, and a percentage of hexagonal cells of 54.16%. Pearson's correlation coefficient between the automated ECD and Topcon's cell density and between the manually calculated ECD and Topcon's cell density was 0.932 (P < .01) and 0.818 (P < .01), respectively. The Bland-Altman plot of Topcon's cell density and the automated ECD yielded 95% limits of agreement between 271.94 and -572.46 (concordance correlation coefficient = 0.9)., Conclusions: A fully automated method for segmenting corneal endothelial cells and estimating morphometric parameters using in vivo confocal microscopy images is more efficient and accurate for assessing the normal corneal endothelium., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The delta variant (B.1.617.2) of SARS-CoV-2 was the dominant viral strain causing COVID-19 in China, 2021. We reported a SARS-CoV-2 delta variant outbreak in Jingmen City, Hubei Province, China., Methods: The data of epidemiological, clinical, laboratorial, and vaccination of COVID-19 cases were collected through field investigation and analyzed., Results: During the outbreak from 4 to 20 August 2021, 58 cases of the SARS-CoV-2 delta variant (B.1.617.2) were identified with 15 (25.9%) asymptomatic and 43 (74.1%) symptomatic (mild and moderate) patients. The mean serial interval was 2.6 days (standard deviation: 2.0, 95% CI: 1.9-3.6). The median age of the patients was 39 years (ranging from 1 to 60 years) with the high proportion in children (19.0%). The secondary attack rate was 9.8% higher from parents to their children (<18 years) (46.2%, 95% CI: 14.8-77.5%) than that between spouses (36.4%, 95% CI: 14.5-58.2%), but no significant difference was observed ( p > 0.05). Approximately half (27; 46.6%) of cases were vaccine breakthrough infections. In vaccine breakthrough cases (fully vaccinated), viral loads decreased 1.9-3.4-folds ( p < 0.05), duration of viral shedding shortened 5 days ( p < 0.05), and the risk of becoming symptomatic from asymptomatic decreased 33% (95% CI: 5-53%) (aged ≥12 years) than those in unvaccinated infections., Conclusions: Children are highly susceptible to the SARS-CoV-2 delta variant in the COVID-19 outbreak in Jingmen City in 2021. Inactivated vaccine derived from wide-type strain can effectively reduce the viral load, duration of viral shedding, and clinical severity in vaccine breakthrough cases. Our study indicates that protective measures that include full vaccination against COVID-19, especially in children, should be strengthened., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Li, Li, Bao, Liu, Qin and Yu.)

The pandemic COVID-19 is certainly one of the most severe infectious diseases in human history. In the last 2 years, the COVID-19 pandemic has caused over 418.6 million confirmed cases and 5.8 million deaths worldwide. Young people make up the majority of all infected COVID-19 cases, but the mortality rate is relatively lower compared to older age groups. Currently, about 55.04% individuals have been fully vaccinated rapidly approaching to herd immunity globally. The challenge is that new SARS-CoV-2 variants with potential to evade immunity from natural infection or vaccine continue to emerge. Breakthrough infections have occurred in both SARS-CoV-2 naturally infected and vaccinated individuals, but breakthrough infections tended to exhibit mild or asymptomatic symptoms and lower mortality rates. Therefore, immunity from natural infection or vaccination can reduce SARS-CoV-2 pathogenicity, but neither can completely prevent SARS-CoV-2 infection/reinfection. Fortunately, the morbidity and mortality of COVID-19 continue to decline. The 7-day average cumulative case fatality of COVID-19 has decreased from 12.3% on the February 25, 2020, to 0.27% on January 09, 2022, which could be related to a decreased SARS-CoV-2 variant virulence, vaccine immunization, and/or better treatment of patients. In conclusion, elimination of SARS-CoV-2 in the world could be impossible or at least an arduous task with a long way to go. The best strategy to prevent COVID-19 pandemic is to expand inoculation rate of effective vaccines. As the population reaches herd immunity, the mortality rate of COVID-19 may continue to decrease, and COVID-19 could eventually become another common cold., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne bunyavirus that could cause a severe hemorrhagic fever termed SFTS with a high fatality rate of up to 30%. Importantly, SFTSV is frequently transmitted from person-to-person and patients' blood or excreta are considered as the risk factors for transmission of SFTSV. However, the mechanism of person-to-person transmission of SFTSV is still elusive., Methods: In this study, wild-type (WT) C57BL/6 J mice and a lethal SFTSV mouse model IFNAR -/- A129 mice were utilized to evaluate whether SFTSV could be transmitted via oral or ocular routes. C57BL/6 J mice were inoculated with cell-cultured SFTSV via oral and ocular inoculation. IFNAR -/- A129 mice were inoculated with cell-cultured SFTSV or SFTSV infected mouse acute sera via oral and ocular inoculation., Results: We found that SFTSV antibody positive rates in C57BL/6 J mice were 70% (7/10) and 30% (3/10) in the oral inoculation group and ocular inoculation group, respectively on day 21 post SFTSV inoculation. The mortality rates of IFNAR -/- mice with oral and ocular inoculation of cell-cultured SFTSV were 100% and 83.33% (5/6), respectively on day 6 post inoculation. The mortality rates of IFNAR -/- mice with oral and ocular inoculation of SFTSV infected mouse acute serum were 100% and 66.67% (4/6), respectively on day 9 post inoculation., Conclusions: Together, our results show that SFTSV can be transmitted effectively through oral and ocular membrane, suggesting exposure to SFTS positive excreta may be a high-risk factor of nosocomial transmission of SFTSV in hospitals and/or families. Family members and healthcare workers should be protected properly during taking care of SFTS patients to prevent SFTSV nosocomial infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.)

During December 2012-July 2016, we tested small indoor and outdoor mammals in Qingdao, China, for Orientia tsutsugamushi infection. We found that outdoor Apodemus agrarius mice, Cricetulus barabensis hamsters, and Niviventer confucianus rats, as well as indoor Mus musculus mice, tested positive for O. tsutsugamushi by PCR.

We identified Candidatus Borrelia fainii, a human pathogenic bacterium causing New World relapsing fever in a Myotis bat in eastern China. This finding expands knowledge about the geographic distribution of Borrelia spp. and the potential for infection with New World relapsing fever in China.

Coxiella burnetii is the causative agent of query fever (Q fever), and distributes broadly in environment. Livestock are identified as main reservoirs, which may infect people through their contaminative urine, feces, milk, and birth products. Wild animals can also be the potential carriers and transmitters of C. burnetii . To understand the geographic distribution and host species of C. burnetii in China, we investigated the prevalence of C. burnetii in hedgehogs ( Erinaceus amurensis ) in Hubei Province. Hedgehogs were tested for C. burnetii with PCR targeting three genes ( com1 , rrs , and icd ) followed by multispacer sequence typing (MST). We found that 12.2% (5/41) hedgehogs were PCR positive for C. burnetii . MST revealed presence of two novel genotypes and phylogenetic analysis revealed that the strains were similar to a group of isolates from chronic Q fever patients and mammals. This study showed that C. burnetii are highly prevalent in hedgehogs in Hubei Province in central China, suggesting that hedgehogs may play an important role in the ecology and transmission of C. burnetii to humans because it is captured and used as traditional medicine in China.

Background: Leptospira is the causative agent of leptospirosis, a zoonotic disease of global importance. To have a better understanding on the host species of Leptospira , we investigated the prevalence of Leptospira species in hedgehogs in Central China. Materials and Methods: Hedgehogs were captured in Hubei Province, China in May and October, 2018. Total DNA was extracted from the kidney tissues of hedgehogs for determining the Leptospira species by PCR amplification of the rrs2 , secY , and flaB genes with genus-specific primers. Results: PCR amplification indicated that the positive rate of hedgehogs to the rrs2 , secY , and flaB genes were 19.5% (8/41), 12.2% (5/41), and 9.8% (4/41), respectively. The homology of the partial sequence of rrs2 , secY , and flaB genes were 99.0-100% among the Leptospira strains from hedgehogs. Phylogenetic analysis revealed that Leptospira species detected in this study clustered together with Leptospira interrogans. Conclusions: We detected L. interrogans from hedgehogs in Central China, suggesting hedgehogs are the hosts of L. interrogans.

Currently, Zika virus (ZIKV) is spreading across the world and no ZIKV infection cases have ever been reported in China. Here, we aimed to determine whether ZIKV infection exists in China. Blood samples of 273 healthy individuals were collected from Nanning City, Guangxi Province, China in March 2019. We found that 9.5% (26/273) and 1.8% (5/273) of healthy persons were positive to ZIKV total antibody (IgG and/or IgM) IgM antibody, respectively. All ZIKV positive plasma samples were negative to Dengue virus and West Nile virus. Among the ZIKV antibody positive plasma samples, 65.4% (17/26) exhibited neutralizing activity to ZIKV. Followed up studies showed that none had clinical symptoms of ZIKV infection and oversea experience. Together, our study indicates that endemic ZIKV infections emerge in China, which not only suggested that ZIKV posed a potential threat to public health in China, but also expand the ZIKV epidemic areas in East and Southeast Asia., Competing Interests: The authors have declared that no competing interests exist.

The pathogenicity of the shrew-borne Imjin virus (MJNV) is unknown. The objective of our study was to find serological evidence of MJNV infection in humans. Partial MJNV nucleocapsid protein (NP) was cloned and expressed as an antigen for double-antigen sandwich ELISA, IgM capture ELISA, and dot blot to detect MJNV specific antibodies in hemorrhagic fever with renal syndrome (HFRS) patients' and healthy persons' sera from endemic areas in China. The purified recombinant NP reacted with neither the 90 healthy individuals' sera from non-endemic areas of MJNV nor the 100 antisera to HFRS-causing virus, indicating that the MJNV NP had no cross-reaction with normal human sera and HFRS-causing viral antibodies. As determined by screening ELISA and dot blot analysis, IgG antibodies against MJNV NP were detected in sera from two of 385 healthy individuals from MJNV-endemic areas, suggesting infection with MJNV or MJNV-like thottimvirus. Based on the suggestive evidence, healthcare workers should be alert to febrile diseases occurring among individuals with exposure to shrew-infested habitats.

Bats have been identified as the hosts of hepatitis B virus (HBV) in recent years and bats HBV can infect human hepatocyte. We investigated the prevalence and genetic diversity of HBV in bats in China. In this study, a total of 197 insectivorous bats belonging to 10 bat species were captured from karst caves in Mengyin County, Shandong Province and Xianning City, Hubei Province, China. PCR amplification indicated that in total 6.6% (13/197) bats were positive to HBVs. The HBV positive rate in bats was 7.1% (9/127) and 5.7% (4/70) in Shandong Province and Hubei Province, respectively. Phylogenetic analysis indicated that HBV from the two places were in the same cluster with 90.5%-99.5% homology, but distinct from bat HBVs from other places in China and other countries. We concluded that HBV was prevalent and genetic diversified in bats, supporting the hypothesis that bats may be the origin of primate hepadnaviruses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bartonella are vector borne gram-negative facultative intracellular bacteria. Bartonella species are associated with rodents and their flea parasites worldwide. The genetic variation and distribution of Bartonella species in rodents are not clear in China. We investigated the presence and genetic diversity of Bartonella species in rodents from eastern China. We captured rodents from 2015 to 2016 in Jiaonan County, Shandong Province, and detected Bartonella species in the spleen of rodents by PCR amplification of the citrate synthase ( gltA ) gene and RNA polymerase beta subunit ( rpoB ) gene. We found that 8.38% (16/191) of the rodents were Bartonella positive by PCR for both gltA and rpoB genes; that Bartonella sequences from the rodents were phylogenetically divided into five clades, which were closely related to B. tribocorum , B. rattimassiliensis , B. grahamii , B. fuyuanensis , and B. queenslandensis , respectively; and that each Bartonella species is rodent species-specific with B. rattimassiliensis and B. tribocorum for Rattus norvegicus , B. grahamii for Tscherskia triton , B. fuyuanensis for Apodemus agrarius , and B. queenslandensis for Niviventer confucianus . This study indicated that Bartonella organisms have a broad distribution and a variety of genotypes in rodents in eastern China and the threats to public health by these Bartonella species should be monitored in China.

Snakes are popular as food and traditional medicine in China. However, information about parasitic and bacterial infections in snakes from China is scarce. We investigated the prevalence of selected zoonotic agents including Cryptosporidium , Hepatozoon and Spirometra , in snakes in central China from June to October in 2018 by PCR amplification using parasite-specific primers. PCR amplification and DNA sequencing showed that 10.1% (15/149) of snakes were positive for Cryptosporidium spp., while 2.7% (4/149) were positive for Hepatozoon . Additionally, we found 36.9% (55/149) of snakes were infected with Spirometra erinaceieuropaei . The spargana burden per infected snake ranged from 1 to 26. BLAST and phylogenetic analysis of small subunit ribosomal RNA (SSU rRNA) gene and 60-kDa glycoprotein ( gp60 ) gene showed that the parasites belonged to Cryptosporidium parvum genotype IIdA15G1, C. baileyi , C. serpentis and a Hepatozoon species. We conclude that intensively farmed snakes excrete C. parvum and C. baileyi oocysts due to ingestion of infected feeder animals, and that wild snakes in central China were commonly infected with S. erinaceieuropaei , suggesting that eating improperly cooked snakes could be risky to human health., Competing Interests: The authors declare that they have no competing interests., (© 2019 The Authors.)

To understand the potential role of bats in the epidemiology of Leptospira , we investigated the frequency of Leptospira in bats from Central China in 2018. Sixty bats belonging to four species of two families were captured from rural areas of Xianning City, Hubei Province, China. We extracted DNA from the kidneys of bats, and Leptospira spp. were determined by PCR amplification of the rrs2 , flaB , lipL32 , and secY genes. We found that 57% (34/60) of bats were positive for Leptospira with at least one of the four genes, and the positive rate of Leptospira in bats was 45% (27/60) with rrs2 , 50% (30/60) with flaB , 15% (9/60) with lipL32 , and 27% (16/60) with secY . Phylogenetic analysis indicated that bats were infected with two species of Leptospira , including Leptospira interrogans and Leptospira borgpetersenii . A high prevalence of Leptospira spp. in bats suggested that bats were important carriers of Leptospira in China.

Although bats were considered as a major host of trypanosomatid flagellates, information of trypanosomes in bats is unknown in China. We collected bats in 2015 from Shandong Province of China and used PCR to amplify the Trypanosoma glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) gene and 18S rRNA gene from the bat blood samples and heart tissues. The results showed that 10.3% (13/126) of bats (Eptesicus serotinus and Myotis pequinius) were positive for trypanosomatid DNA and DNA sequencing showed that all PCR amplified Trypanosoma DNA belonged to T. dionisii. We concluded that T. dionisii had a infection rate in bats from China. For the first time, Trypanosoma infections were detected in bats from China, providing valuable information on the prevalence of these parasites in Asia. This is also the first report of Trypanosoma dionisii in Myotis pequinius, suggesting that Trypanosoma dionisii has a broad host species., (Copyright © 2019 Elsevier B.V. All rights reserved.)

PCR amplification indicated the minimum infection rate of Rickettsia spp. was 0.66% in Haemaphysalis longicornis ticks collected from Shandong Province, China. Phylogenetic analysis based on the rrs, gltA, ompA, and ompB genes indicated that the ticks carried R. japonica, Candidatus Rickettsia longicornii, and a novel Rickettsia species related to R. canadensis.

Background: Genetic polymorphisms of Toll-like receptors play important roles in gastric carcinogenesis. The aim of this study was to determine the role of TLR2-196 to -174 ins/del polymorphism in gastric cancer susceptibility and prognosis., Methods: This study included 520 people from southern China. Samples were genotyped by the allele-specific polymerase chain reaction, among which 10% were randomly selected for sequencing. The serological method was used to determine Helicobacter pylori., Results: The TLR2 genotype was not associated with the risk of H. pylori infection. The del/del genotype exhibited significantly higher gastric cancer risk (adjusted OR 2.59, 95% CI 1.33‒5.07) than that of the ins/ins genotype. Further stratification analyses demonstrated that the del/del genotype was associated with a risk of intestinal gastric cancer (adjusted OR 2.62, 95% CI 1.34-5.14). In addition, the presence of the del/del genotype and the H. pylori infection conferred a synergistic effect (OR 3.04, 95% CI 1.33‒6.98) for the development of gastric cancer. The del/del genotype was not associated with a poor prognosis in gastric cancer patients., Conclusion: The del/del genotype is associated with an increased gastric cancer risk in the southern Chinese population. However, TLR2 polymorphism is neither associated with H. pylori infection, nor with a poor prognosis.

Background/aim: Helicobacter pylori (H. pylori) infection is a well-known risk factor for gastric cancer. Toll-like receptor 9 (TLR9) plays an important role in many cancers and is important for immunity to H. pylori infection. Thus, the present study aimed to evaluate the influence of H. pylori on TLR9 and explore its roles in gastric cancer., Materials and Methods: TLR9 expression in MKN45 cells, which were cocultured with or without H. pylori or H. pylori DNA, was detected using quantitative reverse transcription-polymerase chain reaction and Western blot assays. Then, TLR9 was knocked down through RNA interference technology in MKN45 cells. Cell Counting Kit-8 assay was performed to investigate cell proliferation, and the Transwell system was established to test the migrative and invasive abilities of MKN45 cells., Results: H. pylori infection or H. pylori DNA level was positively correlated with TLR9 upregulation in MKN45 cells. In vitro, H. pylori DNA significantly accelerated cell proliferation and promoted the migration and invasion in MKN45 cells. In contrast, the knockdown of TLR9 significantly suppressed cell proliferation and inhibited the migration and invasion in MKN45 cells., Conclusions: The present results suggest that the H. pylori DNA/TLR9-signaling pathway plays an important role in gastric cancer, which might be a potential therapeutic target., Competing Interests: None

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high fatality rate and high frequency of person-to-person transmission and is caused by SFTSV, a tick-borne Phlebovirus. Because SFTS has similar clinical manifestations and epidemic characters (such as spatial and temporal distributions) with hemorrhagic fever with renal syndrome (HFRS) in China, we reason that SFTS patients might be misdiagnosed as HFRS., Methodology/principal Findings: Acute-phase sera of 128 clinically diagnosed HFRS patients were retrospectively analyzed for Hantavirus IgM antibodies with ELISA. Hantavirus-negative patients' sera were further analyzed for SFTSV IgM antibodies with ELISA. ELISA showed that 73 of 128 (57.0%) of clinically diagnosed HFRS patients were IgM antibody positive to Hantaviruses. Among the 55 Hantavirus-IgM negative patients, four (7.3%) were IgM antibody positive to SFTSV. The results indicated that the four SFTS patients were misdiagnosed as HFRS. The misdiagnosed SFTS patients had clinical manifestations common to HFRS and were unable to be differentiated from HFRS clinically., Conclusions: Our study showed that SFTS patients could be clinically misdiagnosed as HFRS. The misdiagnosis of SFTS as HFRS causes particular concern because it may increase the risk of death of SFTS patients and person-to-person transmission of SFTSV without proper care for and isolation of SFTS patients., Competing Interests: The authors have declared that no competing interests exist.

Secreted Frizzled-Related Protein 4 (SFRP4), a member of secreted frizzled-related protein family, has been found as a vital modulator in cell proliferation, cell self-renew and apoptosis through Wnt signaling transduction pathway. In the present study, we re-analyzed the expression pattern of SFRPs in Gene Expression Omnibus (GEO) datasets and evaluated the expression of SFRP4 at protein level in both Kras G12D/+ ; Trp53 R172H/+ ; Pdx1-Cre; (KPC) mice and human pancreatic ductal adenocarcinoma (PDAC) tissue. We found that the expression of SFRP4 increased gradually in PanINs and PDAC lesions in KPC mice and high expression of SFRP4 was much more common in tumor lesions compared to the adjacent non-tumor tissues. Then we performed Kaplan-Meier survival and Cox regression analysis and found that high expression of SFRP4 in the serum and tumor lesions predicted poor prognosis for pancreatic cancer patients. Furthermore, we demonstrated that SFRP4 positively correlated with FOXP3+ Treg cells infiltration while the down-regulation of SFRP4 in tumor cells impaired the production of cytokines and the recruitments of T cells. This study suggested that SFRP4 can be a novel prognostic biomarker and potential therapeutic target for pancreatic cancer., Competing Interests: None.

Background: Studies about asymptomatic norovirus infections have been frequently reported. We aim to assess the global prevalence of asymptomatic infections., Method: We identified publications that included the proportion of asymptomatic norovirus infections by searching in PubMed, Ovid, Scopus, and Web of Science and by screening references from the articles reviewed. The principal summary data were the prevalence of asymptomatic norovirus infection. Random-effect models for meta-analysis were fitted to generate estimates of overall and subgroup prevalence., Findings: Of 81 studies included, asymptomatic norovirus prevalence was estimated at 7% (95% CI: 6%-9%). Africa, Meso America and South America had higher prevalence (15%, 14%, 11%, respectively) while the prevalence in Europe and North America was lower (4%). Prevalence was similar between community and hospital (9%). Prevalence was higher in children (8%) than adults (4%). For food handlers, prevalence was estimated at 3%. In context of outbreaks, prevalence estimated from 15 studies was as high as 18% (95% CI: 10%-30%)., Interpretation: This knowledge could have an impact on the development of transmission prevention strategies in the future. The high prevalence indicated asymptomatic individuals must not be overlooked., Outstanding Questions: The high prevalence indicated asymptomatic individuals must not be overlooked. Asymptomatic individuals may play an important role in norovirus transmission. This knowledge could have an impact on the development of transmission prevention strategies.

PCR amplification of the rrs2 gene indicated that 50% (62/124) of insectivorous bats from eastern China were infected with Leptospira borgpetersenii, L. kirschneri, and several potentially new Leptospira species. Multilocus sequence typing defined 3 novel sequence types in L. kirschneri, suggesting that bats are major carriers of Leptospira.

Background: To increase understanding of human bacterial and parasitic pathogens in bats, we investigated the prevalence of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii in bats from China., Methods: Bats were captured from Mengyin County, Shandong Province of China using nets. DNA was extracted from the blood and spleen of bats for molecular detection of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii with specific primers for each species., Results: A total of 146 spleen samples and 107 blood samples of insectivorous bats, which belonged to 6 species within two families, were collected from Mengyin County, Shandong Province of China. We found that two Eptesicus serotinus (2/15, 13.3%) were positive for Babesia vesperuginis. We were unable to detect genomic sequences for Rickettsia spp., Anaplasma spp. and Coxiella burnetii., Conclusions: To our knowledge, our study showed for the first time the presence of Babesia vesperuginis in Eptesicus serotinus collected from China, suggesting that Babesia vesperuginis has a broad host species and geographical distribution.

Anaplasma are tick-borne obligatory intracellular bacteria, which infect humans and other animals. The Anaplasma species carried by ticks in China are not well studied. We collected 3145 questing Haemaphysalis longicornis ticks including 120 larvae, 2460 nymphs and 565 adults from vegetation in Jiaonan County, Shandong Province, China from 2013 to 2015. All ticks were examined for the presence of Anaplasma species by nested PCR amplification of the 16S rRNA gene. For further differentiation of A. capra from A. centrale, gltA and msp2 genes were sequenced for A. capra. Three Anaplasma species were detected in the nymph and/or adult ticks with the minimum infection rate of ticks as follows: 1.55% for A. bovis, 0.10% for A. phagocytophilum, and 0.03% for A. capra. These results indicated that the H. longicornis tick in Jiaonan County carried multiple Anaplasma species, which may be a challenge for public health in the studying area., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Bats are considered as the reservoirs of several emerging infectious disease, and novel viruses are continually found in bats all around the world. Studies conducted in southern China found that bats carried a variety of viruses. However, few studies have been conducted on bats in northern China, which harbours a diversity of endemic insectivorous bats. It is important to understand the prevalence and diversity of viruses circulating in bats in northern China. In this study, a total of 145 insectivorous bats representing six species were collected from northern China and screened with degenerate primers for viruses belonging to six families, including coronaviruses, astroviruses, hantaviruses, paramyxoviruses, adenoviruses and circoviruses. Our study found that four of the viruses screened for were positive and the overall detection rates for astroviruses, coronaviruses, adenoviruses and circoviruses in bats were 21.4%, 15.9%, 20% and 37.2%, respectively. In addition, we found that bats in northern China harboured a diversity of novel viruses. Common Serotine (Eptesicus serotinu), Fringed long-footed Myotis (Myotis fimriatus) and Peking Myotis (Myotis pequinius) were investigated in China for the first time. Our study provided new information on the ecology and phylogeny of bat-borne viruses., (© 2017 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.)

Objective: To evaluate the effects of retrograde colonic electrical stimulation (RCES) with trains of short pulses and RCES with long pulses on colonic transit in irritable bowel syndrome (IBS) rats and to investigate whether stress-induced visceral hypersensitivity could be alleviated by RCES so as to find a valuable new approach for IBS treatment., Methods: A total of 48 male rats were randomly divided into model group and control group. Visceral hypersensitivity model was induced by a 6-day HIS protocol composed of two stressors, restraint stress for 40 min and forced swimming stress for 20 min. The extent of visceral hypersensitivity was quantified by electromyography and abdominal withdrawal reflex scores (AWRs) of colorectal distension (use a balloon) at different pressures. After the modeling, all rats were equipped with electrodes in descending colon for retrograde electrical stimulation and a PE tube for perfusing phenol red saline solution in the ileocecus. After recovering from surgery, RCES with long pulses, RCES with trains of short pulses, and sham RCES were performed in colonic serosa of rats for 40 min in six groups of 8 each, including three groups of visceral hypersensitivity rats and three groups of health rats. Colonic transit was assessed by calculating the output of phenol red from the anus every 10 min for 90 min. Finally, the extent of visceral hypersensitivity will be quantified again in model group., Results: After the 6-day HIS protocol, the HIS rats displayed an increased sensitivity to colorectal distention, compared to control group at different distention pressures (P < 0.01). CRES with trains of short pulses and long pulses significantly attenuated the hypersensitive responses to colorectal distention in the HIS rats compared with sham RCES group (P < 0.01). The effects of RCES on rats colon transmission: In the IBS rats, the colonic emptying were (77.4 ± 3.4)%, (74.8 ± 2.4)% and (64.2 ± 1.6)% in the sham RCES group, long pulses group and trains of short pulses group at 90 min; In healthy rats, The colonic emptying was (65.2 ± 3.5)%, (63.5 ± 4.0)% and (54.0 ± 2.5)% in the sham RCES group, long pulses group and trains of short pulses group at 90 min., Conclusion: RCES with long pulses and RCES with trains of short pulses can significantly alleviate stress-induced visceral hypersensitivity. RCES with trains of short pulses has an inhibitory effect of colonic transit, both in visceral hypersensitivity rats and healthy rats., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Objective The ideal agents for conscious sedation during ambulatory inguinal hernia repair are still unclear. We aimed to compare the analgesic, sedative, haemodynamic, and side effects of dexmedetomidine with those of propofol in combination with fentanyl for conscious sedation in patients undergoing inguinal hernia repair. Methods Eighty patients undergoing unilateral inguinal hernia repair were prospectively randomized to receive either dexmedetomidine (n = 40) or propofol (n = 40). Dexmedetomidine and propofol dosages were adjusted to maintain the targeted level of sedation. Results After administration of sedative drugs, patients who received dexmedetomidine had a significantly lower heart rate. The intraoperative requirement of fentanyl was significantly lower in patients who received dexmedetomidine compared with patients who received propofol. Administration of dexmedetomidine was associated with a reduced postoperative pain score, longer time for onset of sedation, and a slightly longer recovery time. No serious adverse events occurred in either group. The patients' overall satisfaction score was comparable between the two groups. Conclusion Dexmedetomidine is an effective adjuvant when co-administered with fentanyl for conscious sedation in patients who undergo inguinal hernia repair. Administration of dexmedetomidine decreases the requirement of fentanyl and the pain score, but slightly prolongs the time to sedation and recovery.

Bartonella species are emerging human pathogens. Bats are known to carry diverse Bartonella species, some of which are capable of infecting humans. However, as the second largest mammalian group by a number of species, the role of bats as the reservoirs of Bartonella species is not fully explored, in term of their species diversity and worldwide distribution. China, especially Northern China, harbors a number of endemic insectivorous bat species; however, to our knowledge, there are not yet studies about Bartonella in bats in China. The aim of the study was to investigate the prevalence and genetic diversity of Bartonella species in bats in Northern China. Bartonella species were detected by PCR amplification of gltA gene in 25.2% (27/107) bats in Mengyin County, Shandong Province of China, including 1/3 Rhinolophus ferrumequinum, 2/10 Rhinolophus pusillus, 9/16 Myotis fimbriatus, 1/5 Myotis ricketti, 14/58 Myotis pequinius. Phylogenetic analysis showed that Bartonella species detected in bats in this study clustered into ten groups, and some might be novel Bartonella species. An association between Bartonella species and bat species was demonstrated and co-infection with different Bartonella species in a single bat was also observed. Our findings expanded our knowledge on the genetic diversity of Bartonella in bats, and shed light on the ecology of bat-borne Bartonella species., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous studies of an association between physical activity and inflammatory bowel disease have yielded conflicting results., Aim: This meta-analysis was conducted to clarify whether there is an association between physical activity and inflammatory bowel disease., Methods: The PubMed and Web of Science databases were searched for relevant studies published up to October 2015. Data were extracted and the summary relative risks (RRs) were calculated using a random effects or a fixed-effects model, according to heterogeneity., Results: Seven studies were included in the analysis. Relative to individuals with low physical activity, those who participated in high physical activity had an RR of 0.63 (95% CI, 0.50-0.79) for developing Crohn's disease. In stratified analyses, a significantly lower risk for Crohn's disease was associated with high physical activity in Europeans only (RR, 0.62; 95% CI, 0.43-0.91); population-based control studies (RR, 0.56; 95% CI, 0.41-0.76); and case-control studies (RR, 0.56; 95% CI, 0.41-0.75). The data of 6 studies were pooled to analyze the effect of physical activity on the risk of ulcerative colitis, and no significant association was found (RR, 0.82; 95% CI, 0.68-1.00)., Conclusions: The pooled results of observational studies support that physical activity has a protective effect against Crohn's disease., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the genotypic diversity and some virulence traits of Streptococcus sobrinus (S. sobrinus) isolated from caries-free children and children suffering severe early childhood caries (SECC)., Methods: S. sobrinus isolated from stimulated whole saliva samples of 91 caries-free children and 87 SECC children were subcultured, identified by polymerase chain reaction and genotyped by arbitrarily primed polymerase chain reaction. Polysaccharide synthesis ability, acidogenicity, aciduricity and the adherence ability of these S. sobrinus isolates were measured., Results: The frequency of S. sobrinus detection was 18.39% (16/87) in SECC children, which was significantly higher than that (3.30%, 3/91) in caries-free children. One to three different genotypes of S. sobrinus were detected in each SECC child. Only one genotype was colonised in each caries-free child. In SECC children, the production of water-insoluble glucan (WIG) was positively correlated with the ability of S. sobrinus adhering to a glass surface., Conclusion: The presence of S. sobrinus could be a risk factor for high caries activity in severe early childhood caries. The multi-genotypes could be related to different caries suceptibility. Water-insoluble glucan plays an important role in the adherence and accumulation of S. sobrinus on tooth surfaces.

Aim: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer., Methods: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples., Results: IL-8 and CXCR1 proteins were both over-expressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels., Conclusion: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.

Unlabelled: Hepatocyte nuclear factor-1alpha (HNF1α) is one of the key transcription factors of the HNF family, which plays a critical role in hepatocyte differentiation. Substantial evidence has suggested that down-regulation of HNF1α may contribute to the development of hepatocellular carcinoma (HCC). Herein, human cancer cells and tumor-associated fibroblasts (TAFs) were isolated from human HCC tissues, respectively. A recombinant adenovirus carrying the HNF1α gene (AdHNF1α) was constructed to determine its effect on HCC in vitro and in vivo. Our results demonstrated that HCC cells and HCC tissues revealed reduced expression of HNF1α. Forced reexpression of HNF1α significantly suppressed the proliferation of HCC cells and TAFs and inhibited the clonogenic growth of hepatoma cells in vitro. In parallel, HNF1α overexpression reestablished the expression of certain liver-specific genes and microRNA 192 and 194 levels, with a resultant increase in p21 levels and induction of G(2)/M arrest. Additionally, AdHNF1α inhibited the expression of cluster of differentiation 133 and epithelial cell adhesion molecule and the signal pathways of the mammalian target of rapamycin and transforming growth factor beta/Smads. Furthermore, HNF1α abolished the tumorigenicity of hepatoma cells in vivo. Most interestingly, intratumoral injection of AdHNF1α significantly inhibited the growth of subcutaneous HCC xenografts in nude mice. Systemic delivery of AdHNF1α could eradicate the orthotopic liver HCC nodules in nonobese diabetic/severe combined immunodeficiency mice., Conclusion: These results suggest that the potent inhibitive effect of HNF1α on HCC is attained by inducing the differentiation of hepatoma cells into mature hepatocytes and G(2)/M arrest. HNF1α might represent a novel, promising therapeutic agent for human HCC treatment. Our findings also encourage the evaluation of differentiation therapy for tumors of organs other than liver using their corresponding differentiation-determining transcription factor., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Aim: To investigate the role of DKK-1/Wnt/beta-catenin signaling in high proliferation of LM-MCF-7 breast cancer cells, a sub-clone of MCF-7 cell line., Methods: Two cell lines (MCF-7 and LM-MCF-7) with different proliferation abilities were used. LM-MCF-7 cells were transiently transfected with the pcDNA3-DKK-1 plasmid encoding the DKK-1 gene (or MCF-7 cells were transfected siRNA targeting DKK-1 mRNA). Flow cytometry analysis and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay were applied to detect the cell proliferation. The expression levels of beta-catenin, phosphorylated beta-catenin, c-Myc, cyclin D1 and Survivin were examined by Western blot analysis. The regulation of Survivin was investigated by Luciferase reporter gene assay., Results: Western blot and RT-PCR analysis showed that the expression level of DKK-1 was downregulated in LM-MCF-7 relative to MCF-7 cells. Flow cytometry and BrdU incorporation assay showed DKK-1 could suppress growth of breast cancer cells. Overexpression of DKK-1 was able to accelerate phosphorylation-dependent degradation of beta-catenin and downregulate the expression of beta-catenin, c-Myc, cyclin D1 and Survivin. Luciferase reporter gene assay demonstrated that Survivin could be regulated by beta-catenin/TCF4 pathway., Conclusion: We conclude that the downregulation of DKK-1 is responsible for the high proliferation ability of LM-MCF-7 breast cancer cells via losing control of Wnt/beta-catenin signaling pathway, in which c-Myc, cyclinD1 and Survivin serve as essential downstream effectors. Our finding provides a new insight into the mechanism of breast cancer cell proliferation.

TRIM5alpha is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The TRIM5alpha(rh) protein from rhesus monkeys recognizes the human immunodeficiency virus type 1 (HIV-1) capsid as it enters the host cell and blocks virus infection prior to reverse transcription. HIV-1-restricting ability can be eliminated by disruption of the B-box 2 domain. Changes in the TRIM5alpha(rh) B-box 2 domain have been associated with alterations in TRIM5alpha(rh) turnover, the formation of cytoplasmic bodies and higher-order oligomerization. We present here the nuclear magnetic resonance structure of the TRIM5 B-box 2 domain and identify an unusual hydrophobic patch (cluster 1) on the domain surface. Alteration of cluster 1 or the flanking arginine 121 resulted in various degrees of inactivation of HIV-1 restriction, in some cases depending on compensatory changes in other nearby charged residues. For this panel of TRIM5alpha(rh) B-box 2 mutants, inhibition of HIV-1 infection was strongly correlated with higher-order self-association and binding affinity for capsid complexes but not with TRIM5alpha(rh) half-life or the formation of cytoplasmic bodies. Thus, promoting cooperative TRIM5alpha(rh) interactions with the HIV-1 capsid represents a major mechanism whereby the B-box 2 domain potentiates HIV-1 restriction.

Objective: To evaluate the genotypic diversity of Streptococcus sobrinus (Ss) between children suffering with severe early childhood caries (S-ECC) and caries-free children by arbitrarily primed-polymerase chain reaction (AP-PCR)., Methods: A total of 178 children aged from 42 to 54 months were recruited from 14 urban kindergartens. The S-ECC group contained 87 children with more than 5 decayed teeth, and the control group was composed of 91 caries-free children. Stimulated whole saliva was collected by chewing paraffin. All mutans streptococcus isolates were subcultured, biochemically characterised and identified by PCR as Streptococcus mutans (Sm) and Ss. Then the Ss isolates were genotyped by AP-PCR., Results: The frequency of Ss detection was 18% in S-ECC children, which was significantly higher than 3% in caries-free children (P < 0.01). Twenty-two distinct genotypes of Ss were identified from 53 clinical isolates. In S-ECC group, one to three genotypes of Ss were detected in each saliva sample. Only one genotype of Ss was detected in all the caries-free children. One genotype of Ss were shared by three S-ECC children. The genotypes of isolates in S-ECC group were relate to decayed-missing-filled teeth (r = 0.50, P < 0. 05)., Conclusions: The rate of Ss detection was significantly higher in S-ECC children than in caries-free children. Isolates of Ss displayed genetic polymorphism. The multi-genotypes of Ss was related to differences in caries susceptibility. Strains of Ss with same genotype were present in unrelated subjects.