Abstract Triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. As an amplifier of the inflammatory response, TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival. TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders. More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases. There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease. This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury, renal fibrosis, diabetic nephropathy, immune nephropathy, and renal cell carcinoma.

Gemcitabine (GEM) is the gold-standard therapeutic regimen for patients with pancreatic cancer (PC); however, patients may receive limited benefits due to the drug resistance of GEM. LncRNA SNHG6 is reported to play key roles in drug resistance, but its role and molecular mechanism in PC remain incompletely understood. We found that LncRNA SNHG6 is drastically downregulated in GEM-resistant PC and is positively correlated with the survival of PC patients. With the help of bioinformatic analysis and molecular approaches, we show that LncRNA SNHG6 can sponge miR-944, therefore causing the upregulation of the target gene KPNA5. In vitro experiments showed that LncRNA SNHG6 and KPNA5 suppress PC cell proliferation and colony formation. The Upregulation of LncRNA SNHG6 and KPNA5 increases the response of GEM-resistant PANC-1 cells to GEM. We also show that the expression of KPNA5 is higher in patients without GEM resistance than in those who developed GEM resistance. In summary, our findings indicate that the LncRNA SNHG6/miR944/KPNA5 axis plays a pivotal role in overcoming GEM resistance, and targeting this axis may contribute to an increasing of the benefits of PC patients from GEM treatment.

为了适应临床医学八年制医学生的培养目标,推进医学免疫学教学改革,中南大学基础医学院免疫学系探索构建线下一流课程教学模式,在充分理解医学免疫学教学内容特点基础上,对每堂课课前、课中和课后三阶段进行整体设计,采用多元化的教学方法,融合多种教学改革举措,通过基础-临床融通改善教学效果,结合课程思政,以提高医学免疫学教学质量.文章结合课程设计、实践以及教师的体会,总结该线下课程教学模式的方法和特点,以期为培育创新型人才为导向的医学教育以及打造其他学科的线下一流课程提供经验.

Intravaginal infection of mice with Chlamydia muridarum has been used for investigating the mechanisms of Chlamydia trachomatis-induced pathogenicity and immune responses. In the current study, the mouse model was used to evaluate the impact of interleukin-27 (IL-27) and its receptor signaling on the susceptibility of the female genital tract to chlamydial infection. Mice deficient in IL-27 developed significantly shortened courses of chlamydial infection in the female genital tract. The titers of live Chlamydia recovered from the genital tract of IL-27-deficient mice declined significantly by day 7 following intravaginal inoculation. These observations suggest that IL-27 may promote chlamydial infection in the female mouse genital tract. This conclusion was validated using IL-27 receptor (R)-deficient mice. Further, the reduction in chlamydial burden corelated with the increase in gamma interferon (IFN-γ) and IL-17 in the genital tract tissues of the IL-27R-deificent mice. However, depletion of IFN-γ but not IL-17 from the IL-27R-deificent mice significantly increased the chlamydial burden, indicating that IL-27 may mainly suppress IFN-γ-mediated immunity for promoting chlamydial infection. Finally, knockout of IL-27R from T cells alone was sufficient for significantly shortening the infectious shedding courses of Chlamydia in the mouse genital tract. The above-described results have demonstrated that Chlamydia can activate IL-27R signaling in Th1-like cells for promoting its infection in the female genital tract, suggesting that attenuating IL-27 signaling in T cells may be used for enhancing genital tract immunity against chlamydial infection.

The obligate intracellular bacterium Chlamydia is a genital tract pathogen that can also colonize the gastrointestinal tract for long periods. The long‐lasting colonization is dependent on chlamydial spreading from the small intestine to the large intestine. We previously reported that a mutant Chlamydia was able to activate an intestinal barrier for blocking its own spreading to the large intestine. In the current study, we used the mutant Chlamydia colonization model to confirm the intestinal barrier function and further to determine the immunological basis of the barrier with gene‐deficient mice. Recombination activating gene 1−/− mice failed to block the mutant Chlamydia spreading, while mice deficient in toll‐like receptors, myeloid differentiation primary response 88 or stimulator of interferon genes still blocked the spreading, suggesting that the intestinal barrier function is dependent on lymphocytes that express antigen receptors. Mice deficient in CD4, but not CD8 nor μ chain failed to prevent the chlamydial spreading, indicating a protective role of CD4+ cells in the intestinal barrier. Consistently, adoptive transfer of CD4+ T cells reconstituted the intestinal barrier in CD4‐/‐ mice. More importantly, CD4+ but not CD8+ T cells nor B cells restored the intestinal barrier function in recombination activating gene 1−/− mice. Thus, CD4+ T cells are necessary and sufficient for maintaining the intestinal barrier function, indicating that the spread of an intracellular bacterium from the small intestine to the large intestine is regulated by an immunological barrier. This study has also laid a foundation for further illuminating the mechanisms by which a CD4+ T cell‐dependent intestinal barrier regulates bacterial spreading in the gut.

Chlamydia trachomatis (C. trachomatis) is a major pathogen implicated in the formation of hydrosalpinx in the female reproductive tract. In mice, a related strain of Chlamydia, Chlamydia trachomatis (C. trachomatis) can induce almost 100% bilateral hydrosalpinx. This model was used as a hydrosalpinx induction model to test whether oviduct delivery of platelet-rich plasma (PRP) can attenuate chlamydia induction of hydrosalpinx in a mouse model. Mice were infected intravaginally with Chlamydia muridarum organisms, and 21 days after the infection, PRP was instilled into the lumen of one oviduct, and a sham instillation with phosphate buffer solution was performed on the contralateral oviduct. Mice were then sacrificed at designated time points after infection for oviduct pathologic evaluation including incidence, severity, and histopathologic grade of chronic inflammation. Oviduct instillation of PRP was associated with a 36% reduction in the incidence of hydrosalpinx and a 33% reduction in severity compared with sham. The median grade of chronic inflammation on histopathology was significantly lower with PRP instillation compared with sham and control. No differences were observed in vaginal or rectal shedding of C. muridarum between the test group and the control group. In short, the results suggest that oviduct instillation of PRP can significantly reduce the incidence and severity of C. muridarum-induced hydrosalpinx without affecting chlamydial infection courses in CBA/J mice.

The cryptic plasmid is important for chlamydial colonization in the gastrointestinal tract. We used a combination of intragastric, intrajejunal, and intracolon inoculations to reveal the impact of the plasmid on chlamydial colonization in distinct regions of gastrointestinal tract. Following an intragastric inoculation, the plasmid significantly improved chlamydial colonization. At the tissue level, plasmid-positive Chlamydia produced infectious progenies throughout gastrointestinal tract. However, to our surprise, plasmid-deficient Chlamydia failed to produce infectious progenies in small intestine, although infectious progenies were eventually detected in large intestine, indicating a critical role of the plasmid in chlamydial differentiation into infectious particles in small intestine. The noninfectious status may represent persistent infection, since Chlamydia genomes proliferated in the same tissues. Following an intrajejunal inoculation that bypasses the gastric barrier, plasmid-deficient Chlamydia produced infectious progenies in small intestine but was 530-fold less infectious than plasmid-positive Chlamydia, suggesting that (i) the noninfectious status developed after intragastric inoculation might be induced by a combination of gastric and intestinal effectors and (ii) chlamydial colonization in small intestine was highly dependent on plasmid. Finally, following an intracolon inoculation, the dependence of chlamydial colonization on plasmid increased over time. Thus, we have demonstrated that the plasmid may be able to improve chlamydial fitness in different gut regions via different mechanisms, which has laid a foundation to further reveal the specific mechanisms.

The cryptic plasmid pCM is critical for chlamydial colonization in the gastrointestinal tract. Nevertheless, orally inoculated plasmid-free Chlamydia sp. was still able to colonize the gut. Surprisingly, orally inoculated Chlamydia sp. deficient in only plasmid-encoded pGP3 was no longer able to colonize the gut. A comparison of live organism recoveries from individual gastrointestinal tissues revealed that pGP3-deficient Chlamydia sp. survived significantly better than plasmid-free Chlamydia sp.

Sexually transmitted Chlamydia, which can cause fibrotic pathology in women's genital tracts, is also frequently detected in the gastrointestinal tract. However, the medical significance of the gastrointestinal Chlamydia remains unclear. A murine Chlamydia readily spreads from the mouse genital tract to the gastrointestinal tract while inducing oviduct fibrotic blockage or hydrosalpinx. We previously proposed a two-hit model in which the mouse gastrointestinal Chlamydia might induce the second hit to promote genital tract pathology, and we are now providing experimental evidence for testing the hypothesis. First, chlamydial mutants that are attenuated in inducing hydrosalpinx in the genital tract also reduce their colonization in the gastrointestinal tract, leading to a better correlation of chlamydial induction of hydrosalpinx with chlamydial colonization in the gastrointestinal tract than in the genital tract. Second, intragastric coinoculation with a wild-type Chlamydia rescued an attenuated Chlamydia mutant to induce hydrosalpinx, while the chlamydial mutant infection in the genital tract alone was unable to induce any significant hydrosalpinx. Finally, the coinoculated gastrointestinal Chlamydia failed to directly spread to the genital tract lumen, suggesting that gastrointestinal Chlamydia may promote genital pathology via an indirect mechanism. Thus, we have demonstrated a significant role of gastrointestinal Chlamydia in promoting pathology in the genital tract possibly via an indirect mechanism. This study provides a novel direction/dimension for further investigating chlamydial pathogenic mechanisms.

Although Chlamydia trachomatis is a human genital tract pathogen, chlamydial organisms have frequently been detected in both vaginal and rectal swab samples of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential for Chlamydia muridarum to colonize the mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization ability of a pGP3-deficient C. muridarum mutant, suggesting that pGP3 is required for C. muridarum to reach but not to colonize the large intestine. The pGP3-deficient mutant was rapidly cleared in the stomach and was 100-fold more susceptible to gastric killing. In mice genetically deficient in gastrin, a key regulator for gastric acid production, or pharmacologically treated with a proton pump inhibitor, the ability of pGP3-deficient C. muridarum to colonize the gastrointestinal tract was rescued. The pGP3-dependent resistance was further recapitulated in vitro with treatments with HCl, pepsin, or sarkosyl. In the genital tract, deficiency in pGP3 significantly reduced C. muridarum survival in the mouse vagina and increased C. muridarum susceptibility to vaginal killing by similar to 8 times. The pGP3-deficient C. muridarum was more susceptible to lactic acid killing, and the pGP3 deficiency also significantly increased C. trachomatis susceptibility to lactic acid. The above-described observations together suggest that Chlamydia may have acquired the plasmid-encoded pGP3 to overcome the gastric barrier during its adaptation to the gastrointestinal tract and the pGP3-dependent resistance may enable chlamydial evasion of the female lower genital tract barrier during sexual transmission.

Purpose: This study was designed to compare the longterm outcomes of patients with gastric carcinoma after open or laparoscopic total gastrectomy.Methods: A case-matched controlled prospective analysis of 136 patients who underwent laparoscopic total gastrectomy for stage I-III gastric carcinoma from 2007 to 2014 was performed. Patients who at the same period underwent open total gastrectomy were matched to the laparoscopy group at the ratio of 1:1 for comparison. The perioperative clinical outcomes, postoperative pathology, and survival were compared between the 2 groupsResults: The patient characteristics between the two groups were comparable. Laparoscopic resection resulted in less blood loss, shorter postoperative hospital stay, and longer operating time. The two groups had similar complication rates. Pathological data were similar for both procedures. Cumulative incidence of recurrence, disease-free, or overall survival rates were statistically similar.Conclusion: This study showed that laparoscopic total gastrectomy for gastric carcinoma is acceptable in terms of short-term clinical outcomes and long-term survival results.

Objective to find a appropriate marker for the early diagnosis of pulmonary hypertension in serum .Methods 60 rats were randomly divided into normal control group (n=12) and experimental group (n=48) .The experimental group was injected with MCT to make the pulmonary artery hypertension model of rats while the control group was injected with to make the same a-mount of normal saline .NF-κB、TNF-α、COX-2、PGE2、MMP-1 and iNOS levels of serum were determined by ELISA in all groups . Results the results showed that the model was successful .The concentration of NF-κB、TNF-α、COX-2、PGE2、MMP-1、iNOS in 2 ,4 ,6 weeks had statistical significance compared to the control group (P<0 .05) .And the 2 ,4 ,6 weeks in the the experiment were in the the early stage of PAH development .We found that the specificity of NF-κB ,TNF-α,PGE2 ,iNOS was the most obvious in the the early .Conclusion NF-κB ,TNF-α,PGE2 ,iNOS ,in the rat PAH model can reflect the early pathological changes of PAH ,which has important value for the research of early PAH .

As worldwide life expectancy rises, the number of candidates for surgical treatment of gastric carcinoma over 70 years will increase. This study aims to examine outcomes after gastric carcinoma in elderly patients. This study is a retrospective review of 697 patients undergoing gastrectomy with radical intent for gastric carcinoma during January 2007 to January 2013. A total of 534 patients were less than 70 years old (group A), and 163 patients 70 years or greater (group B). We analyzed the effect of age on short and long-term variables including overall survival and disease-free survival. Major morbidity was observed to occur in 19 patients of group A, and 15 of group B. Mortality, both 30-day and 90-day was observed in 1 and 3 of group A, and 3 and 6 of group B. Five-year overall survival and disease-free survival was 61% and 60% for group A, 50% and 43% for group B respectively. Gastrectomy should be carefully considered in patients 70 years old and can be justified with low mortality and acceptable long-term outcomes.

Objective: To analyze the influence of Ct persistent infection on the TLR4 /IL-6 /STAT3 signaling pathway of target cells. Method: The acute infection and IFN-γ-induced persistent infection model of Ct in Hela was established.Then the level of TLR4 / IL-6 / STAT3 transcription and cytokine IL-6 secretion in different Ct infection models was compared using qRT-PCR and ELISA respectively. Results: Ct infection upregulated the expression of TLR4,IL-6 and STAT3 mRNA and the secretion of cytokine IL-6 significantly,especially in IFN-γ-induced persistent infected Hela,the expression of IL-6 / STAT3 is related to TLR4 mRNA with temporal correlation. Conclusion: Persistent Ct infection in the process of continuous activation of TLR4 can significantly increase the IL-6 / STAT3 signaling pathway,which may participate in the chronic inflammatory injury during persistent Ct infection.

In this study,we investigated the clearance of C.muridarum,the production of antibodies,and the inflam- matory pathologies after the primary and secondary infection in the mice urogenital tract with C.muridarum.The female C57B6mice were infected with C.muridarumby intravaginal inoculation.Then the mice shedding of C.muridarumlive or- ganism was monitored by virginal swab culture.At the same time,the mice serum was collected to detect the production of an- tibodies.After killing the mice,the virginal tissues were taken to evaluate the histopathological changes.During the primary infection,the mice have more live C.muridarumorganisms to shed and the process was longer.In the secondary infection,the mice have less live C.muridarumorganisms to shed and the process was shorter.The anti-chlamydia antibody in serum could be detected at 2 weeks after infection and raised to a high level rapidly.The serum antibody kept in a high level without change after secondary infection.The pathological changes displayed severe inflammation,uterine horn and oviducts dilation,hydrops and stenosis,etc.It is concluded that although there is no increase in the serum antibody level after secondary infection,the host's ability to defense against Chlamydiais greatly enhanced,and there is no distinct difference in the inflammation between the secondary and primary infections.

Objective To identify the levels of serum soluble major histocompatibility complex class I chain-related gene A(sMICA) protein in patients with malignant tumor/infectious diseases and explore its clinical significance.Methods The serum sMICA levels were determined by enzyme-linked immunosorbent assay(ELISA),including patients(n=1041) suffering from several types of malignant tumors and infectious diseases and healthy controls(n=141).The correlation and diagnostic value were analyzed.Results Compared with the controls,serum sMICA elevation was significantly increased in patients of hepatic cancer(P<0.05).The sMICA levels of patients with bacterial(Enterobacteriaceae,Mycobacterium tuberculosis,non-fermenting Gram-negative bacteria and Gram-positive cocci),viral(hepatitis B and C) and the Microspironema pallidum infections were also significantly higher than that of the controls(P<0.05).Conclusion Serum sMICA levels may be informative for the diagnosis of hepatic cancer and some infectious diseases.Serum sMICA elevation may be caused by Enterobacteriaceae,Mycobacterium tuberculosis,non-fermenting Gram-negative bacteria,Gram-positive cocci,HBV,HCV and the Microspironema pallidum.

Background Elevation of soluble major histocompatibility complex class I chain-related gene A (sMICA) products in serum has been linked to tissue/organ transplantation, autoimmune diseases and some malignant disorders. Cells infected by microbiological pathogens may release sMICA, whereas less is known whether and to what extent serum sMICA levels may change in infectious diseases. Methods The present study determined serum sMICA levels by enzyme-linked immunosorbent assay (ELISA) in a southern China population, including patients (n = 1041) suffering from several types of malignant and infectious diseases and healthy controls (n = 141). Results Relative to controls, serum sMICA elevation was significant in patients of hepatic cancer, and was approaching statistical significance in patients with lung, gastric and nasopharyngeal cancers. sMICA elevation was also associated with some bacterial (Enterobacteriaceae, Mycobacterium tuberculosis, non-fermenting Gram-negative bacteria and Gram-positive cocci), viral (hepatitis B and C) and the Microspironema pallidum infections. Conclusion Serum sMICA levels may be informative for the diagnosis of some malignant and infectious diseases. The results also indicate that microbiological infections should be considered as a potential confounding clinical condition causing serum sMICA elevation while using this test to evaluate the status of other disorders, such as cancers, host-graft response and autoimmune diseases.

Objective: To explore the clinical application value of scattering turbidimetric method in detecting glycosylated hemoglobin;Method: Scattering turbidimetric method was used to detect glycosylated hemoglobin,analyzes its detection precision,linear relations,the anti-interference ability and correlation.Results: Scattering turbidimetric intra-batch CV were 3.1% and 4.3% respectively,inter-batch CV were 3.8% and 5.0% respectively;Linear relationship Y = 1.025 X + 0.024,R2 = 0.996;in anti-interference experiment,the measure value of Bilirubin,triacylglycerol and urea were in the confidence interval.The correlation equation for scattering turbidimetric method and chromatography is Y = 0.968 X + 0.364,R = 0.976,(P 0.05).Conclusion: Scattering turbidimetric method for glycosylated hemoglobin detection had a higher degree of precision,good linear relationship,strong anti-jamming ability,and good correlation,so it can be used in basic and clinical experiments.