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Hair cells (HCs) in the mammalian cochleae cannot spontaneously regenerate once damaged, resulting in permanent hearing loss. It has been shown that Atoh1 overexpression induces hair cell-like cells (HCLCs) in the cochlea of newborn rodents, but this is hard to achieve in adult mammals. In this study, we used a three-dimensional cochlear culture system and an adenoviral-mediated delivery vector to overexpress Atoh1 in adult mouse cochleae. HCLCs were successfully induced from 3 days after virus infection (3 DVI) in vitro, and the number increased with time. HCLCs were myosin7a positive and distinguishable from remnant HCs in a culture environment. Meanwhile, patch-clamp results showed that noninactive outward potassium currents (sustained outward potassium currents) could be recorded in HCLCs and that their magnitude increased with time, similar to normal HCs. Furthermore, transient HCN currents were recorded in some HCLCs, indicating that the HCLCs experienced a developmental stage similar to normal HCs. We also compared the electrophysiological features of HCLCs from adult mice with native HCs and found the HCLCs gradually matured, similar to the normal HCs. Meanwhile, HCLCs from adult mice possessed the same bundles as developmental HCs. However, these HCLCs did not express prestin, which is a special marker for outer hair cells (OHCs), even at 13 DVI. These results demonstrate that Atoh1 overexpression induces HCLC formation in the adult mammalian cochlea and that these HCLCs were functional and experienced a developmental process similar to that of normal HCs.

After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury progression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase (MAPK) signaling pathway was the most significantly enriched pathway among 24- and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction confirmed the persistent overexpression of miR-22-3p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020 (Research) 01].

Deferoxamine, deferiprone, and deferasirox are used for the treatment of systemic iron overload, although they possess limitations due to lack of oral activity, lower efficacy, and side effects. These limitations led to a search for an orally active iron chelator with an improved therapeutic index. The lower efficacy of deferiprone is due to rapid glucuronidation, leading to the formation of a nonchelating metabolite. Here, we demonstrate that the influence of metabolism can be reduced by introducing a sacrificial site for glucuronidation. A log P-guided investigation of 20 hydroxpyridinones led to the identification of CN128. The Fe(III) affinity and metal selectivity of CN128 are similar to those of deferiprone, the log P value is more lipophilic, and its iron scavenging ability is superior. Overall, CN128 was demonstrated to be safe in a range of toxicity assessments and is now in clinical trials for the treatment of β-thalassemia after regular blood transfusion.

Objective: The objective of this study was to evaluate whether the Chinese herbal medicine formula Guilu Erxian Jiao can improve the T-score in osteoporosis patients and even decrease the fracture rate.Design: This is a retrospective study.Subjects and Setting: Osteoporosis participants were selected from the Chang Gung Memorial Hospital (CGMH) database from 2000 to 2019.Interventions: The patients were administered Guilu Erxian Jiao pills.Outcome measures: We analyzed the change of T-score and the associated cumulative incidence of fracture.Results: Eighty-five patients administered GEJ met the inclusion criteria. After propensity score matching (1:5), 425 patients who were not administered GEJ were included in the control group. There were no significant differences about the baseline characteristics between the study and control groups. In the study group, GEJ improved the osteoporosis of the lumbar vertebrate and osteopenia of the hip joint but did not improve osteoporosis of the femoral neck. The cumulative rate of fracture between these two groups was not significantly different. Patients who took at least 600 GEJ pills over the treatment period had a decreased risk for fracture at fracture-prone sites.Conclusion:The use of Guilu Erxian Jiao may improve osteoporosis of the lumbar vertebrate and osteopenia of the hip joint. In addition, it may help decrease fractures of the lumbar spine. Administering at least 600 GEJ pills over the treatment period might result in a decreased risk for fracture at fracture-prone sites.

Background: Persistent müllerian duct syndrome (PMDS) is an autosomal recessive congenital abnormality for which müllerian derivatives, uterus, cervix, upper 2/3 vagina and fallopian tubes, persist in an otherwise normally virilized males. Mutations in the AMH gene and AMHR2 gene have been identified as causative. However, there has been no functional experimental analysis of AMHR2 or AMH variants that caused PMDS. We ascertained a Chinese PMDS pedigree. To elucidate the pathogenic mechanisms of variant, we used complementation-based NanoLuciferase Binary Technology (NanoBiT) to examine AMH and AMHR2 variants interaction in vivo. Using an ID-1 luciferase assay, we probed the effect of the two variants on the transcriptional activity of the TGFβ/BMP pathway. Results: Molecular studies revealed two novel variants [c.118G>C/p. Gly40Arg, c.1222G>C/p. Ala408Pro] in the AMHR2 gene of our monozygotic boys. The AMHR2 p. Ala408Pro variants affect a functional domain, result in impaired substrate recognition and affinity. For p.Gly40Arg variant, the arginine residue will disfigure the local backbone and alter function. The AMHR2 p.Gly40Arg variant reduces its ability to bind to AMH, while the p.Ala408Pro variant alters the kinase domain structure. Conclusion: Both variants significantly reduce TGFβ/BMP signaling. This study provides new methods and concepts as to the study of the molecular pathogenic mechanism of PMDS.

Coating matching design is one of the important parts of ship coating process design. The selection of coating matching is influenced by various factors such as marine corrosive environment, anti-corrosion period and working conditions. There are also differences in the coating performance requirements for different ship types and different coating parts. At present, the design of coating matching in shipyards depends on the experience of technologist, which is not conducive to the scientific management of ship painting process and the macro control of ship construction cost. Therefore, this paper proposes a hybrid algorithm of fuzzy comprehensive evaluation and collaborative filtering based on user label improvement (IFCE-CF). Based on the analytic hierarchy process (AHP), the evaluation index system of coating matching is constructed, and the weight calculation process of fuzzy comprehensive evaluation is optimized by introducing the user label weight. The collaborative filtering algorithm based on matrix decomposition is used to realize the accurate recommendation of coating matching. Historical coating process data of a shipyard between 2010 and 2020 are selected to verify the recommendation ability of the method in the paper. The results show that using the coating matching intelligent recommendation algorithm proposed in this paper, the root mean square error is

Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitously reported in global water bodies and exhibits various environmental and human health risks. However, the effects of DEHP chronic exposure on the intestinal microbiota and associated host health concerns in aquatic species are still largely unexplored. In this study, chronic exposure to DEHP at environmental levels significantly increased the body weight, length, and body mass index (BMI), especially in male fish. The microbial community was disrupted with the relative abundance of phylum Firmicutes and genera diversity for Prevotella-7, Deefgea, PeM15, Halomonas, Akkermansia, Chitinibacter, and Roseomonas, which are significantly activated in zebrafish after exposure to DEHP. The height of the gut villus, the thickness of muscularis layer, and the number of goblet cells per villus were significantly decreased, as well as showed differences between female and male zebrafish. Further, the levels of energy-related metabolites in gut tissues were increased, compared to the control group. The expression levels of immune-related genes (interleukin 8, il-8, also referred to as cxcl8a), microbial defense-related genes (lysozyme, lyz, interleukin 10, and il-10), and obesity-related genes (aquaporin 8a, aqp8, mucin 2.1, muc2.1, fibroblast growth factor 2, fgf2, and proopiomelanocortin a, pomca) were significantly up-regulated in zebrafish, except the down-regulated expressions of toll-like receptor-5 (tlr-5) and interleukin 1β (il-1β) in the females and pomca in the males, respectively. Importantly, Spearman’s correlation analyses revealed that the levels of metabolites and gene expressions in the gut were closely related to the dominant microbial genera, such as Aeromonas, Deefgea, Akkermansia, PeM15, Mycobacterium, and Rhodobacter. Taken together, chronic exposure to DEHP at environmental levels disturbed bacterial composition accompanied by the altered expressions of intestinal metabolites and the critical immune and intestinal function-related genes, which provided novel insights into DEHP effects on perturbation of gut microbiota and metabolic homeostasis in zebrafish.

In recent years, subacute care units (SCUs) have emerged as alternatives to acute hospitalization for selected emergency department (ED) patients who might benefit from a short period of inpatient stay within a less acute setting. We developed a new protocol to directly admit selected older patients from our acute hospital's (AH) ED to the SCU of a partner community hospital, making use of our ED's short-stay ward as a transit area to overcome administrative, financial, and clinical barriers. The new protocol has removed the need for intervening stays of longer than 24 hours at our AH, reduced overall length of stay across both institutions, decreased hospital admissions, and reduced the number of patient hand-offs.

Melioidosis and leptospirosis, caused by two different bacteria, Burkholderia pseudomallei and Leptospira spp., are potentially fatal infections that share a very similar spectrum of clinical features and cause significant mortality and morbidity in humans and livestock. Early detection is important for better clinical consequences. To our knowledge, there is no diagnostic tool available to simultaneously detect and differentiate melioidosis and leptospirosis in humans and animals. In this study, we described a duplex TaqMan probe-based qPCR for the detection of B. pseudomallei and Leptospira spp. DNA. The performance of the assay was evaluated on 20 B. pseudomallei isolates, 23 Leptospira strains, and 39 other microorganisms, as well as two sets of serially diluted reference strains. The duplex qPCR assay was able to detect 0.02 pg (~ 4 copies) Leptospira spp. DNA and 0.2 pg (~ 25.6 copies) B. pseudomallei DNA. No undesired amplification was observed in other microorganisms. In conclusion, the duplex qPCR assay was sensitive and specific for the detection of B. pseudomallei & Leptospira spp. DNA and is suitable for further analytical and clinical evaluation.

This meta-analysis aimed to assess the diagnostic efficiency of blood-based septin 9 (SEPT9) methylation assay for the detection of colorectal cancer (CRC). Studies were searched in the Springer, Wiley, Cochrane Library, PubMed, Ovid, Embase, Web of Science, China BioMedicine, Wanfang and China National Knowledge Infrastructure databases until July 2017. Methodological quality assessment was performed based on the guidelines of the Quality Assessment of Diagnostic Accuracy Studies. According to 1/3 and 2/3 algorithms, the meta-analyses for the diagnostic effect of SEPT9 in CRC were compared with healthy subjects and subjects with polyps, adenoma, and non-CRC, respectively. The random effects model was applied and publication bias was evaluated. The included 29 studies comprised 10,486 subjects (3202 patients with CRC and 7284 controls). In comparison with healthy subjects, the pooled sensitivity with 95% confidence intervals (CIs) of SEPT9 methylation for the diagnosis of CRC was 0.74 (95% CI: 0.61-0.84) in the 1/3 algorithm group, whereas the specificity was 0.96 (95% CI: 0.95-0.97) in the 2/3 algorithm group. Additionally, positive likelihood ratio was less than 10 and negative likelihood ratio more than 0.1 in the 2/3 algorithm group for patients with CRC vs. polyps and adenoma. The P value of Deeks' funnel plot was 0.36, suggesting that there was no publication bias. SEPT9 methylation can be used to diagnose CRC in healthy individuals under the 2/3 algorithm. The determination of SEPT9 methylation does not distinguish well between CRC and polyps or adenoma.

Thiamethoxam (TMX) is one of the major compounds of neonicotinoids, the most widely used class of insecticides worldwide. Previously, TMX was considered a non-toxic neonicotinoid insecticide to mammals. However, the genotoxicity, cytotoxicity, and hepatotoxicity of TMX in mammals were recently reported. Thus far, the effects of TMX on the mouse liver and its detailed mechanism remain unclear. NNMT, strongly expressed in the liver, plays a critical role in body energy expenditure. To confirm the potential pathogenesis of liver dysfunction induced by TMX, ICR mice were exposed to TMX at a dose of 4 mg/kg and 20 mg/kg by gavage administration for 12 weeks. The data showed that chronic TMX exposure caused dyslipidemia and nonalcoholic fatty liver disease (NAFLD) in mice. Moreover, aggravated oxidative stress, dysfunction, and disorganized structure were also observed in TMX-treated mouse livers. In addition, increases of PPARγ, fatty acid synthase, and NNMT expression, as well as decreases of PPARα and GNMT expression, S-adenosylmethionine deficiency, and methionine metabolism disorder were also observed in TMX-treated mouse livers. These results suggest that chronic TMX exposure induces dyslipidemia and NAFLD in mice. Moreover, inhibition of NNMT in hepatocytes significantly reversed the effects of TMX. The molecular mechanism of TMX-induced NAFLD is mostly through NNMT-mediated methionine metabolism and methyl donor balance, which ultimately regulates PPARα signaling pathway. Inhibition of NNMT could be a potentially novel strategy for blocking the progression of NAFLD induced by TMX.

Background: Predicting the risk of recurrence during hospitalization in patients with minor ischemic stroke (MIS) is of great significance for clinical and treatment. Compared with early models and prognostic scores, nomogram is a better visualization tool for predicting clinical outcomes. It combines different factors to develop a graphical continuous scoring system, and accurately calculates the risk probability of adverse outcomes based on individual characteristics. Our goal is to develop and validate a nomogram for individualized prediction of hospitalization recurrence in patients with mild ischemic stroke in the Chinese population.Methods: Based on retrospective collection, a single center study was conducted in the first affiliated Hospital of Anhui Medical University from January 2014 to December 2019. The subjects were stroke patients with NIHSS≤5.In order to generate the nomogram, age, systolic blood pressure,previous heart disease, serum total bilirubin, ferritin and smoking were integrated into the model. The predictive accuracy of the nomogram model to predict the probability of unfavorable outcome was assessed by calculation of the area under the receiver operating characteristic curve (AUC–ROC). Calibration of the risk prediction model was assessed by the plot comparing the observed probability of unfavorable outcome against the predicted, and by using the Hosmer–Lemeshow test.Results: Age at admission (OR,0.946; 95% CI,-0.002 to 0.048), SBP (OR,0.012,95%CI,0.000 to 0.024), previous heart disease (OR,0.867,95%CI, 0.084 to 1.651), UA (OR,-0.003,95%CI,-0.006 to 0.001), serum total bilirubin (OR,-0.022,95%CI,-0.036 to -0.008), ferritin (OR,0.004,95%CI, 0.002 to 0.005), smoking (OR,0.494,95%CI,-0.115 to 1.103) are significant predictors of in-hospital recurrence in Chinese patients with minor ischemic stroke.The model shows good discrimination, the AUC-ROC value is 0.737 (95%CI:0.676-0.798), and has perfect calibration performance. Calibration was good (p=0.1457 for the Hosmer-Lemesshow test), which could predict the risk of recurrence of MIS patients during hospitalization.Conclusion: The nomogram developed and validated in this study can provide individualized, intuitive and accurate prediction of recurrence in Chinese patients with minor ischemic stroke during hospitalization.

Transmembrane and ubiquitin-like domain-containing 1 (Tmub1) encodes a protein (TMUB1) containing an ubiquitin-like domain and plays a negative regulatory role during hepatocyte proliferation, but its mechanism in this process is still unknown. Here, TMUB1 interfered with the binding of calcium-modulating cyclophilin ligand (CAML) to cyclophilin B, which may represent a key role in the negative regulatory process of TMUB1 in hepatocyte proliferation. Co-immunoprecipitation assays in rat BRL-3A cells confirmed the interaction between TMUB1 and CAML; significant regulation of the influx of Ca2+ ([Ca2+]i) and hepatocyte proliferation occurred following TMUB1 overexpression or knockout. Deletion of the TM1 hydrophobic domain of TMUB1 completely abolished this interaction and led to loss of TMUB1’s regulatory effects on cytological behavior. Furthermore, overexpression of TMUB1 completely abolished the interaction between CAML and its downstream protein cyclophilin B, which can act upstream of calcineurin by increasing [Ca2+]i during cell proliferation. Taken together, our results indicate that TMUB1 regulates BRL-3A hepatocyte proliferation by interacting with CAML and further interferes with the binding of CAML to cyclophilin B to decrease cellular [Ca2+]i.

To observe the clinical efficacy of Yi Jin Jing (Sinew-transforming Qigong Exercises) for primary osteoporosis in the elderly. Eighty old patients with primary osteoporosis were randomized into a Yi Jin Jing group and a medication group, 40 cases in each group. The Yi Jin Jing group was intervened by Yi Jin Jing (Sinew-transforming Qigong Exercises) training, while the medication group was intervened by oral administration of alendronate sodium tablet. Prior to and after 6-month intervention, the bone mineral density (BMD) of the proximal femur, visual analog scale (VAS) and activities of daily living (ADL) were estimated. There were no significant differences in the BMD of the proximal femur, and VAS and ADL scores between the two groups before the intervention (P>0.05). After 6-month intervention, the above items all improved significantly in both groups (both P 0.05). Practice of Yi Jin Jing (Sinew-transforming Qigong Exercises) can effectively ameliorate the BMD in the elderly with primary osteoporosis, and it can reduce the pain and improve ADL, with a better general effect compared to oral administration of alendronate sodium tablet.

Hypoxia preconditioning protects Ca2+-ATPase activation of intestinal mucosal cells against R/I injury in a rat liver transplantation model

Quercetin, a natural antiglycative agent, was incorporated into steamed bread to produce a functional food that has high potential to lower the risk of diabetes. With the incorporation of quercetin at 1.20, 2.40, and 3.60%, the volume of steamed bread significantly decreased and the hardness of the crumb correspondingly increased with incremental quercetin content, while incorporation levels below 1.20% had no impact. Within this range of enrichment (1.2-3.6%), quercetin negatively affected the yeast activity with significantly less CO2 produced in dough during proofing. The wheat protein structure was altered by quercetin in terms of a higher level of β-sheets and a lower level of β-turns. The antioxidant capacity of the steamed bread with quercetin (0.05-0.2%) was significantly enhanced dose-dependently. A high inhibitory activity of quercetin-enriched steamed bread (0.05-0.2%) against fluorescent advanced glycation endproducts (AGEs) via several different mechanisms was observed. The inhibition of total AGEs from 0.2% quercetin-enriched steamed bread was around 40% during in vitro protein glycation. Overall, the results support quercetin-enriched steamed bread to be a promising functional food with high antioxidant and antiglycation properties.

Objective Insulin resistance (IR) is a key defect in type 2 diabetes mellitus (T2DM); therefore, effective means of ameliorating IR are sought. Methods We performed a retrospective cohort study of 154 patients with T2DM and 39 with pre-diabetes (pre-DM). The effects of IR and a high concentration of FFA on gene expression were determined using microarray analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) in patients with T2DM or pre-DM. Results Serum FFA concentration and homeostasis model assessment of IR (HOMA-IR) were significantly higher in patients with T2DM but no obesity and in those with pre-DM than in controls. HOMA-IR was significantly associated with T2DM. RT-qPCR showed that the expression of FBJ murine osteosarcoma viral oncogene homolog ( FOS) and AE binding protein 1 ( AEBP1) was much lower in the circulation of participants with obesity and diabetes. RT-qPCR showed that the expression of docking protein 1 ( DOK1) was significantly lower in the blood of participants with diabetes but no obesity and in those with pre-DM than in controls. Conclusions FFA and DOK1 are associated with IR in patients with T2DM but no obesity or pre-DM. The downregulation of DOK1 might inhibit lipid synthesis and induce lipolysis, inducing or worsening IR.

Tumour necrosis factor receptor associated factor 3 (TRAF3) is a crucial transducing protein for linking upstream receptor signals and downstream antiviral signalling pathways. Previous studies mostly clarified the functions of TRAF3 in mammals, birds and fish, but little is known about the characterization and function of TRAF3 in amphibians. In this study, the molecular and functional identification of two TRAF3 genes, AdTRAF3A and AdTRAF3B, were investigated in the Chinese giant salamander Andrias davidianus. The complete open reading frames (ORFs) of AdTRAF3A and AdTRAF3B were 1698 bp and 1743 bp in length, encoding 565 and 580 amino acids, respectively. Both AdTRAF3A and AdTRAF3B deduced proteins contained a RING finger, two TRAF-type zinc fingers, a coiled-coil and a MATH domain. Phylogenetic analysis showed that the AdTRAF3 protein clustered together with other known TRAF3 proteins. Gene expression analysis showed that AdTRAF3s were broadly distributed in all examined tissues with similar distribution patterns. AdTRAF3s in the blood or spleen positively responded to Giant salamander iridovirus (GSIV) and poly (I:C) induction but exhibited distinct response patterns. Silencing AdTRAF3A/B remarkably suppressed the expression of IFN signalling pathway-related genes when leukocytes were treated with DNA virus and the viral RNA analogue. Moreover, overexpression of AdTRAF3A may induce the activation of the IFN-β promoter, and the zinc finger, coiled coil and MATH domains of AdTRAF3A were essential for IFN-β promoter activation. However, the overexpression of AdTRAF3B significantly suppressed IFN-β promoter activity, and its inhibitory effect was enhanced when the RING finger or MATH domain was deleted. Furthermore, AdTRAF3A rather than AdTRAF3B significantly induced NF-κB activation, implying that AdTRAF3A may function as an enhancer in both the IFN and NF-κB signalling pathways. Taken together, our results suggest that the two TRAF3 genes play different crucial regulatory roles in innate antiviral immunity in Chinese giant salamanders.

To evaluate the roles of climate and hydrology in continental-scale silicate weathering, we applied Li isotopes to the Yellow River and systematically investigated seasonal Li flux, Li isotopic compositions and potential sources. We collected samples from the middle reaches of the Yellow River weekly over the full hydrological year of 2013. We find that the dissolved Li is mainly derived from silicates and evaporites in the arid to semi-arid Yellow River basin. Silicate weathering of loess during the monsoonal season dominates the Li flux in the middle reaches of the Yellow River, with a positive relationship between dissolved Li flux and physical erosion rate. Evaporite contribution for riverine Li was relatively constant in the middle reaches of the Yellow River but slightly increased after the storm event, with an average proportion of ∼25%, which might represent the proportion of evaporite contribution to global oceans. Seasonal variations in the riverine Li isotopic compositions are dominantly controlled by temperature with a fractionation gradient as −0.182‰ per °C over the full year with deviations likely driven by re-dissolution of suspended particulate matter, extreme hydrological events, and groundwater contribution. Temperature dependent δ7Li value variation of river water inputted into oceans indicates that Cenozoic climate cooling itself may be able to explain ∼2‰ of the 9‰ rise of Cenozoic seawater δ7Li value (Misra and Froelich, 2012). The seasonal variation in riverine Li isotopes highlights that erosion and weathering of loess may provide valuable clues on secular chemical weathering and seawater δ7Li variation spanning a range of time scales.

Acne is a common inflammatory skin disease with the dysregulation of innate and adaptive immunity. However, the underlying mechanism of acne has not been completely elucidated. In this study, we identified gene signatures and the immune-related regulatory network in acne using integrated bioinformatics methods. Here, 303 Differentially expressed genes (DEGs) and 28 Hub genes were identified in acne (GSE53795 and GSE108110), which were associated with the inflammation-related signaling pathway. Subsequently, the CIBERSORT algorithm revealed the increased proinflammatory cells in acne. Moreover, we identified 3 kinases (FGR, HCK and LYN) and 2 transcription factors (TFs) (IRF8 and ZBTB16) from DEGs as the key genes, which regulated immune cell infiltration via targeting immune-related genes in acne. The upregulated 3 kinases (FGR, HCK and LYN) and IRF8, and the downregulated ZBTB16 were also confirmed in GSE6475 and in Acne mice. Based on the expression levels of these key genes, the tissues could be divided into 2 clusters using consensus cluster analysis. GSEA analysis showed that inflammation-related signaling pathways significantly enriched in cluster 2, indicating the important role of kinase and TFs on immune regulation in acne. Finally, we found that isotretinoin and trifarotene (CD5789) treatment repressed the expression of immune genes but not the expression of the kinases and TFs, indicating that kinases and TFs may be novel therapeutic target for acne. In conclusion, 3 kinases and 2 TFs were identified and validated as key regulators in the immune-related regulatory networks in acne, providing a more comprehensive understanding and novel therapeutic targets of acne.

OBJECTIVENosocomial outbreaks caused by Salmonella are rare. We describe the investigation and control of a cluster of novel extended-spectrum β-lactamase (ESBL) Salmonella enterica serotype Isangi in a hospital in southeastern Michigan.METHODSAn epidemiologic investigation, including case-control study, assessment of infection control practices and environmental cultures, was performed to identify modes of transmission. Healthcare workers (HCWs) exposed to case patients were screened. Strain relatedness was determined using pulsed-field gel electrophoresis (PFGE); ESBL confirmation was conducted using real-time PCR. Control measures were implemented to prevent further transmission.RESULTSBetween September 2 and October 22, 2015, 19 surgical patients, including 10 organ transplant recipients and 1 HCW, had positive S. Isangi cultures. Of these case patients and HCW, 13 had gastroenteritis, 2 had bacteremia, 1 had surgical-site infection, and 4 were asymptomatic. Pulsed-field gel electrophoresis (PFGE) showed 89.5% similarity among the isolates in these cases. Isolates with resistant-phenotypes possessed plasmid-mediated CTX-M15 ESBL. A total of 19 case patients were compared with 57 control participants. Case patients had significantly higher odds of exposure to an intraoperative transesophageal (TEE) probe (adjusted odds ratio 9.0; 95% confidence interval, 1.12–72.60; P=.02). Possible cross-transmission occurred in the HCW and 2 patients. Cultures of TEE probes and the environment were negative. The outbreak ended after removal of TEE probes, modification of reprocessing procedures, implementation of strict infection control practices, and enhanced environmental cleaning.CONCLUSIONSWe report the first nosocomial ESBL S. Isangi outbreak in the United States. Multiple control measures were necessary to interrupt transmission of this gastrointestinal pathogen. Exposure to possibly contaminated TEE probes was associated with transmission. Periodic monitoring of reprocessing procedures of TEE probes may be required to ensure optimal disinfection.Infect Control Hosp Epidemiol 2016;37:954–961

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor β was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1.

Acute myocardial infarction complicated by bleeding colon tumor is problematic with regard to management, and appropriate balance of antiplatelet or anticoagulation therapy and hemostasis or surgery is crucial for effective treatment. Here, we present a case of concomitant acute myocardial infarction and bleeding tumor in the transverse colon, and share our experience of successfully balancing anticoagulation therapy and hemostasis.

We investigated the effects of perioperative blood transfusion in the prognosis of hereditary and sporadic colon cancer. There are 1075 colon cancer patients, including 936 sporadic colon cancer and 139 with hereditary colon cancer undergoing surgery at our hospital. All patients underwent 10 years of follow-up. In the sporadic group, mortality, local recurrence rate and distant metastases rate of transfused patients were significantly higher than non-transfused patients. The 10-year survival rates were significantly lower in patients receiving blood transfusions compared to non-transfused patients. In the hereditary group, mortality was higher in transfused patients compared to non-transfused patients.

Human leukocyte antigen-G is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. Human leukocyte antigen-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulin-like transcripts. Here we observed significantly less human leukocyte antigen-G in plasma from immune thrombocytopenia patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls. Besides, human leukocyte antigen-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membrane-bound human leukocyte antigen-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant human leukocyte antigen-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. Human leukocyte antigen-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-α, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. Human leukocyte antigen-G-modulated dendritic cells from immune thrombocytopenia patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, human leukocyte antigen-G modulated cells from patients induced less platelet apoptosis. Human leukocyte antigen-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of human leukocyte antigen-G and immunoglobulin-like transcripts is involved in the pathogenesis of immune thrombocytopenia; Recombinant human leukocyte antigen-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that human leukocyte antigen-G can be a diagnostic marker and a therapeutic option for immune thrombocytopenia.

The treatment of dermatophytosis has improved considerably over the past several decades following the introduction of the oral antifungals such as azoles and amphotericin B. However, these drugs have had limited success because the treated fungi often develop drug resistance, resulting in recurrence when applied in various topical formulations. Thus, there are constant needs for new topical agents that are effective against dermatophytosis. Dipyrithione is an attractive candidate to become an antifungal agent due to its broad spectrum of antimicrobial activities. In this study, we determined that dipyrithione could potently inhibit the growth of Trichophyton rubrum, which is the most common cause of dermatophytosis. The MIC50 value of dipyrithione against T. rubrum was measured as 6.03 μM, as compared with miconazole (MIC50: 1.38 μM). Additionally, the compound caused morphological changes in the fungi, which was examined using the morphological interference assay. The in vivo experiment further revealed that dipyrithione had a healing effect on the skin of guinea pigs infected with T. rubrum. Our studies have demonstrated that dipyrithione had a potent antifungal activity in vitro and in vivo, suggesting that it could be formulated as a potential antifungal lead compound in search for novel therapeutic agents against dermatophytosis.

The removal of antibiotics and widespread of antibiotic resistance genes (ARGs) have received continuous attention due to the possible threats to environment. However, little information is available on the evolution of antibiotic resistance and the relationship between ARGs and microbial communities under long-term exposure to sub-inhibitory concentrations of antibiotics. In our study, two laboratory-scale anoxic-aerobic wastewater treatment systems were established and operated for 420 days to investigate the evolution of antibiotic resistance under exposure of 5 mg·L−1 tetracycline (TC) or 5 mg·L−1 TC and 1 mg·L−1 sulfamethoxazole (SMX). The average removal rates of TC and SMX were about 59% and 72%, respectively. The abundance of the main ARGs responsible for resistance to TC and SMX increased obviously after antibiotics addition, especially when TC and SMX in combination (increased 3.20-fold). The tetC and sul1 genes were the predominant genes in the development of TC and SMX resistance, in which gene sul1 had the highest abundance among all the detected ARGs. Network analysis revealed that under antibiotic pressure, the core bacterial groups carrying multiple ARGs formed and concentrated in about 20 genera such as Dechloromonas, Candidatus Accumulibacter, Aeromonas, Rubrivivax, in which intI1 played important roles in transferring various ARGs except sul3.

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Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, have been identified as critical regulators of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of circRNAs in HCC are largely unknown. In this study, we identified a novel circRNA, circ-IGF1R, in HCC tumour tissues and cell lines. Circ-IGF1R levels were found to be significantly upregulated in HCC tissues compared with levels in paired peritumoural tissues. The high expression levels of circ-IGF1R in HCC were associated with tumour size. Moreover, knocking down circ-IGF1R with siRNA significantly attenuated cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. Further investigation revealed that PI3K/AKT signalling pathway activation was involved in the oncogenic functions of circ-IGF1R in HCC. Our study suggests that circ-IGF1R may be a potential target for the prevention and treatment of HCC.

Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here, we report that the proapoptotic stress response factor TP53INP1 is often selectively downregulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 downregulation in early-stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings show how TP53INP1 plays a critical role in limiting the progression of early-stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC. Cancer Res; 77(17); 4602–12. ©2017 AACR.

There has been little research conducted regarding autophagy in oral squamous cell carcinoma (OSCC). Given the prevalence of oral cancers which are OSCC and the severe side effects of current treatments, there is a pressing need to develop effective alternative therapies. In this study, we have endeavored to explore the biological characteristics of oral squamous cell carcinoma cell line KB cells, in particular with regard to the role played by autophagy in their survival. Autophagy was activated by nutrient depletion via culturing cells in Earle's balanced salts (EBSS) and was measured via indices relating to Beclin 1, microtubule-associated protein light chain 3 (MAPLC3, LC3), p62, and Green fluorescent protein-light chain 3 plasmid transfection (GFP-LC3). Cell death and apoptosis induced by nutrient depletion was measured using both MTT assay and flow cytometry (FCM). Compared to initial levels at 0 h, Beclin 1 density in EBSS-treated cells was found to have increased at 6, 12, and 18 h in a time-dependent manner and was found to have subsequently declined at 24 and 48 h. p62 levels, LC3-II/LC3-I ratio, and GFP-LC3 levels increased at 6, 12, 18, 24, and 48 h in a time-dependent manner. 3-methyladenine (3-MA) was found to inhibit autophagy and the expression of Beclin 1 and significantly enhanced nutrient depletion-induced apoptosis and death. We concluded that nutrient depletion enhances OSCC cell autophagy in time-course patterns and that the inhibition of autophagy augments apoptosis in OSCC cells. We also deduced that Beclin 1 takes part in the development and progression of autophagy, potentially playing an important role in the crosstalk between apoptosis and autophagy in OSCC cells. These findings suggest that nutrient depletion may be an effective way to explore autophagy and that autophagy inhibitors should be investigated as a potential novel agent for the adjuvant treatment of human OSCC.

Background De Qi is a special sensational response upon acupuncture needling. According to traditional acupuncture theory, the treatment is “effective only after Qi arrival”; that is, De Qi is an important indicator of therapeutic efficacy and good prognosis. However, it is still disputable whether De Qi improves the efficacy of acupuncture therapy. This prospective, randomized controlled trial aims to explore the influence of De Qi induced by acupuncture on immediate and accumulated analgesic effects in patients with knee osteoarthritis (KOA). Methods/design Eighty-eight patients with KOA will be recruited and randomly assigned to the De Qi group (enhanced stimulation to evoke De Qi) and the control group (weak stimulation to avoid De Qi) in the Department of Acupuncture and Physical Therapy, Beijing Luhe Hospital Affiliated to Capital Medical University. Each patient will receive three 30-minute sessions per week for 4 consecutive weeks and undergo a 1 month follow-up. The severity of knee pain, as measured on a 100-mm visual analog scale (where 0 indicates no pain and 100 indicates intolerable pain) will be used as the primary outcome, and the Knee injury and Osteoarthritis Outcome Score will be used as the secondary outcome. Both indexes will be measured before and after the 1st (for evaluating the immediate analgesic effects), 3rd, 6th, 9th, and 12th (for evaluating the accumulated analgesic effects) treatments and at the end of the follow-up. The intensity of the De Qi sensation will be assessed by the Chinese-Modified Massachusetts General Hospital Acupuncture Sensation Scale at the end of each treatment. Side effects during the treatments will be recorded and analyzed as well. The comparisons between the De Qi group and the control group will be done by using both an intention-to-treat analysis and a per-protocol analysis. Discussion This prospective randomized controlled study will be helpful in enhancing our understanding of the analgesic effect of De Qi on patients with KOA and may provide a clinical basis for further investigation of the relationship between De Qi and the therapeutic efficacy of acupuncture, thereby offering some evidence for the role of De Qi in an efficacious acupuncture therapy. Trial registration Chinese Clinical Trial Registry, ChiCTR-IIR-16008972. Registered on 4 August 2016 Additional file 2. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1975-7) contains supplementary material, which is available to authorized users.

Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients. SummaryBackground Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and have diverse immunologic functions. Objectives To investigate the M1/M2 imbalance in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans-retinoic acid (ATRA) could restore this imbalance. Methods The numbers of M1 and M2 macrophages in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence. Monocyte-derived macrophages were cultured and induced with cytokines and drugs. The expression of M1 and M2 markers and functions of M1 and M2 macrophages before and after modulation by HD-DXM or ATRA were evaluated with flow cytometry and ELISA. Results There was preferred M1 polarization in ITP spleens as compared with healthy controls. Monocyte-derived macrophages from ITP patients had increased expression of M1 markers and impaired immunosuppressive functions. Either HD-DXM or ATRA corrected this imbalance by decreasing the expression of M1 markers and increasing the expression of M2 markers. Moreover, HD-DXM-modulated or ATRA-modulated macrophages suppressed both CD4+ and CD8+ T-cell proliferation and expanded CD4+CD49+LAG3+ type 1 T-regulatory cells. HD-DXM or ATRA modulated macrophages to shift the T-cell cytokine profile towards Th2. Treating patients with HD-DXM or ATRA revealed that macrophages induced from responders showed a predominant M2-like phenotype and immunosuppressive function. Conclusions Aberrant macrophage polarization is involved in the pathogenesis of ITP. Either HD-DXM or ATRA is able to correct this imbalance.

The SCARB1 gene encodes human scavenger receptor class B type I (SR-BI), the primary receptor for high-density lipoprotein (HDL)- cholesteryl ester uptake, and polymorphisms in this gene may influence SR-BI protein expression and serum lipid levels, modulating susceptibility to coronary heart disease (CHD) and cerebral infarction (CI). Therefore, we investigated the association between singlenucleotide polymorphisms (SNPs) in the SCARB1 gene and serum lipid levels as well as risk of CHD and CI in the Chinese Han population. Genotypes in 295 CHD patients, 302 CI patients and 312 healthy controls matched for age and gender were determined by high-resolution melting (HRM). Among the 5 SNPs investigated in this study, rs10846744 and rs2278986 were significantly associated with CHD risk. The frequency of the C allele for rs10846744 and that of the T allele for rs2278986 appeared to be significantly increased in the CHD group (OR: 1.416, 95%CI: 1.128-1.778, P=0.0058 and OR: 1.681, 95%CI: 1.327-2.130, P

For measurement and communication interrupt between earth station and reentry vehicle in blackout area, we analyze electromagnetic environment characteristic of plasma sheath. Methods of changing electrical characteristic of plasma medium or changing measurement and communication equipments are researched based on the analysis. Also technology of trajectory reconstruction is presented by using limited measurement data of target. The paper introduces technology status of measurement and communication for blackout area reentry vehicle. Also we analyze properties of common methods and propose key questions to research. It provides reference for related researchers.

Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML.

INTRODUCTION Recently, a genome-wide association study (GWAS) indicated that rs7216389 polymorphism on chromosome 17q21 was associated with paediatric asthma risk. However, the results remained controversial. Therefore, a meta-analysis was performed. EVIDENCE ACQUISITION A comprehensive literature retrieve was performed on PubMed, Embase and Science Direct databases up to Feb 20, 2016. The strength of association between 17q21 locus rs7216389 polymorphism and pediatric asthma risk was assessed by computing odds ratio (OR) with its corresponding 95% confidence interval (CI). EVIDENCE SYNTHESIS A total of 10 studies with 7797 cases and 38757 controls were included. A statistically significant association of rs7216389 polymorphism and pediatric asthma risk was found (OR=1.41, 95%CI=1.34-1.49, P

// Yuan-xin Sun 1 , Hui Li 2 , Qi Feng 1 , Xin Li 1 , Ying-yi Yu 1 , Li-wei Zhou 1 , Yan Gao 1 , Guo-sheng Li 3 , Juan Ren 4 , Chun-hong Ma 5 , Cheng-jiang Gao 5 , Jun Peng 1, 6 1 Department of Hematology, Qilu Hospital, Shandong University, Jinan, China 2 Department of Rheumatology, People’s Hospital of Bao’an, Shenzhen, China 3 Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China 4 Department of Hematology, First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China 5 Department of Immunology, Shandong University School of Medicine, Jinan, China 6 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, China Correspondence to: Jun Peng, email: junpeng88@sina.com.cn Keywords: aplastic anemia, miR34a, diacylglycerol kinase ζ, T cells Received: November 18, 2016 Accepted: December 13, 2016 Published: December 20, 2016 ABSTRACT Acquired aplastic anemia is an idiopathic paradigm of human bone marrow failure syndrome, which involves active destruction of hematopoietic stem cells and progenitors by cytotoxic T cells in the bone marrow. Aberrant expression of microRNAs in T cells has been shown to lead to development of certain autoimmune diseases. In the present study, we performed a microarray analysis of miRNA expression in bone marrow CD3 + T cells from patients with aplastic anemia and healthy controls. Overexpression of miR34a and underexpression of its target gene diacylglycerol kinase (DGK) ζ in bone marrow mononuclear cells were validated in 41 patients and associated with the severity of aplastic anemia. Further, the level of miR34a was higher in naive T cells from patients than from controls. The role of miR34a and DGKζ in aplastic anemia was investigated in a murine model of immune-mediated bone marrow failure using miR34a -/- mice. After T-cell receptor stimulation in vitro , lymph node T cells from miR34a -/- mice demonstrated reduced activation and proliferation accompanied with a less profound down-regulation of DGKζ expression and decreased ERK phosphorylation compared to those from wild-type C57BL6 control mice. Infusion of 5 × 10 6 miR34a -/- lymph node T cells into sublethally irradiated CB6F1 recipients led to increased Lin - Sca1 + CD117 + cells and less vigorous expansion of CD8 + T cells than injection of same number of wild-type lymph node cells. Our study demonstrates that the miR34a/DGKζ dysregulation enhances T-cell activation in aplastic anemia and targeting miR34a may represent a novel molecular therapeutic approach for patients with aplastic anemia.

A number of tumor markers had been reported to be useful in detecting free cancer cells in the peritoneal cavity and predict peritoneal recurrence in gastric cancer patients. The objective of this study was to compare the clinical impact of different tumor markers in peritoneal lavage fluid using the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) technique and to screen the most effective ones from them. The peritoneal lavage fluid of 116 patients with gastric cancer was sampled at laparotomy. After RNA extraction and reverse transcription, real-time quantitative polymerase chain reaction (PCR) was performed using the primers and probes for carcinoembryonic antigen (CEA), cytokeratin-20, matrix metalloproteinase-7 (MMP-7), carbohydrate antigen 125, and transforming growth factor-beta-1. Among the 116 patients, 45 (38.8%) were confirmed to have peritoneal recurrence. Any of the PCR-positive results of the five tumor markers could predict peritoneal recurrence in the univariate analysis (P < 0.001). In the multivariate analysis, the PCR results of CEA (P = 0.003) and MMP-7 (P = 0.028) were found to be independent prognostic factors. A real-time quantitative RT-PCR analysis of the CEA and MMP-7 transcripts in peritoneal lavage fluid could effectively predict peritoneal recurrence in advanced gastric cancer patients who underwent a potentially curative resection.

Background Immune regulation is important for the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). Th22 cells are recently-identified CD4 + T cells that implicated in the pathogenesis of many hematological diseases, such as AML. However, the role of Th22 cells in the pathophysiology of T-ALL remains unclear. We examined the Th22, Th17 and Th1 cell frequencies in peripheral blood of T-ALL patients. Methods We studied 24 newly-diagnosed (ND), 17 morphologic complete remission (CR) T-ALL patients and 30 healthy controls. Th subsets were examined by flow cytometry. Plasma IL-22 and IL-17 concentrations were measured by ELISA. Transcription factor RORC , T - bet and AHR mRNA expressions were examined by RT-PCR. Results Th22, Th17 frequencies, plasma IL-22 concentration and AHR expression were significantly increased in ND or CR T-ALL patients compared with controls. Moreover, Th22 showed positive correlation with Th17 or Th1 cells in T-ALL patients. However, a significant decrease of IL-17 concentration, Th1 frequency and T - bet expression was found in ND or CR ALL patients compared with controls. Furthermore, Th17 cells showed positive correlation but Th1 cells showed negative correlation with white blood cell counts. Conclusion The profile of Th subsets was distinct for T-ALL patients and showed some correlations with clinical index, which suggest that these Th subsets may be implicated in the pathogenesis of T-ALL and be reasonable targets for therapeutic intervention.

Ai-Min Gong,1,2,* Xin-Yuan Li,2,* Yi-Qiang Xie,1 Zhan-Dong Jia,3 Yuan-Xin Li,4 Yong-Yan Zou,5 Chang-Qing Xu,2,* Zhen-Yu Wang2,* 1Department of Internal Medicine of Traditional Chinese Medicine, Hainan Medical University, Hainan, 2Department of Pathophysiology, Harbin Medical University, Harbin, 3Department of Nephrology, Ningbo Tradition Chinese Medicine Hospital affiliated to Zhejiang Chinese Medical University, Ningbo, 4The Fifth Department of Acupuncture, 5Department of Nephrology, Jining Tradition Chinese Medicine Hospital, Jining, People’s Republic of China *These authors contributed equally tothis work Purpose: The association between CD14 -159C/T polymorphism and the susceptibility to gastric cancer (GC) has been reported. However, the results were inconclusive. In the present study, a case–control study and a meta-analysis were performed to assess the possible association between -159C/T in the CD14 gene and GC risk. Patients and methods: Relevant studies were searched in several databases including PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Wanfang database (last search was performed on December 30, 2015). In addition, a case–control study involving 164 GC cases and 169 controls was also performed in the analysis. Statistical analysis was performed by the software Revman5.3.Results: A total of ten published studies and the present case–control study involving 2,844 GC and 3,983 controls were included for the meta-analysis. The analysis result indicated that the T allele of CD14 -159C/T polymorphism did not confer risk for GC (in our study: [P=0.93]; in the meta-analysis: T vs 2N odds ratio =1.28 and 95% confidence interval (CI)=0.95–1.24, [P=0.24]). However, we found a significant association in the recessive model (in our study: TT vs TC+CC [P=0.04]; in the meta-analysis: TT vs TC+CC odds ratio =1.12 and 95% CI=1.01–1.26, [P=0.04]). Furthermore, a subgroup analysis by ethnicity showed that TT genotype was significantly associated with GC in Asian (odds ratio =1.17 and 95% CI =1.02–1.34, [P=0.02]) but not in Caucasian. Conclusion: Our results highlight the TT genotype of CD14 -159C/T as a genetic susceptibility factor for gastric cancer, particularly, in Asians and population-based controls. Keywords: gastric cancer, CD14, meta-analysis, polymorphism