Role of triggering receptor expressed on myeloid cells-1 in kidney diseases: A biomarker and potential therapeutic target.

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.

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs.

Monitoring the prevalence of antimicrobial resistance genes (ARGs) is vital for addressing the global crisis of antibiotic-resistant bacterial infections. Despite its importance, the characterization of ARGs and microbiome structures, as well as the identification of indicators for routine ARG monitoring in pig farms, are still lacking, particularly concerning variations in antimicrobial exposure in different countries or regions. Here, metagenomics and random forest machine learning were used to elucidate the ARG profiles, microbiome structures, and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe. Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs ( P<0.05). ANT(6)-Ib, APH(3')-IIIa, and tet(40) were identified as shared core ARGs between the two pig populations. Furthermore, the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions. Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs, respectively. Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100% and 98.7%, respectively. Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy ( r=0.72-0.88). Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs. The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944.

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.

Interleukin-27 (IL-27) Promotes Chlamydial Infection in the Female Genital Tract.

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.

Sulfite as the substrate of C-sulfonate metabolism of α, ß-unsaturated carbonyl containing andrographolide: analysis of sulfite in rats' intestinal tract and the reaction kinetics of andrographolide with sulfite.

One-sixth of the currently known natural products contain α, ß-unsaturated carbonyl groups. Our previous studies reported a rare C-sulfonate metabolic pathway. Sulfonate groups were linked to the ß-carbon of α, ß-unsaturated carbonyl-based natural compounds through this pathway. However, the mechanism of this type of metabolism is still not fully understood, especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition. In this work, the enzyme-mediated and non-enzymatic pathways were studied. First, the sulfite content in rat intestine was determined by LC-MS/MS. The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383 µg·g-1, whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation (20 µg·g-1). Second, the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions (pH 6-8) was studied. The half-lives of andrographolide ranged from minutes to hours. This was suggested that the C-sulfonate reaction of andrographolide was very fast. Third, the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-conjugate andrographolide were incubated with the rat small intestine contents or sulfite, indicating that the sulfite amount in rat intestine contents was high enough to react with andrographolide, which assisted a significant portion of andrographolide metabolism. Finally, the comparison of andrographolide metabolite profiles among liver homogenate (with NADPH), liver S9 (with NADPH), small intestine contents homogenate (with no NADPH), and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic pathway. In summary, sulfite can serve as a substrate for C-sulfonate metabolism, and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of compounds containing α, ß-unsaturated carbonyl moiety.

[Effect of electroacupuncture at Baliao points on intrauterine residue and uterine volume restoration after uterine curettage of incomplete abortion].

OBJECTIVE: To observe the clinical therapeutic effect of the combination of electroacupuncture (EA) at Baliao points (bilateral Shangliao [BL 31], Ciliao [BL 32], Zhongliao [BL 33] and Xialiao [BL 34]) and oral administration of mifepristone tablets and its influence on uterine volume restoration after uterine curettage of incomplete abortion as compared with simple oral administration of mifeprstone tablets. METHODS: A total of 58 patients after uterine curettage of incomplete abortion were randomized into an EA group and a western medication group, 29 cases in each one. In the western medication group, mifepristone tablets were administered orally, 2 tablets each time, once daily. In the EA group, on the base of the treatment as the western medication group, EA was applied to Baliao points, with disperse-dense wave, once daily, 50 min each time. The treatment for 3 days was as one course and 2 courses of treatment were required, at the interval of 1 day in the two courses. Before and after treatment, the area of intrauterine residue and blood flow signal positive rate of color Doppler flow imaging (CDFI) were recorded in patients of the two groups respectively. The days of vaginal bleeding and the rate of second operation were recorded after treatment in patients of the two groups. Using the three-dimensional ultrasound B reconstruction, the uterine endometrial volume after menstruation resumption was measured in patients of the two groups, and the clinical therapeutic effect was evaluated. RESULTS: After treatment, the intrauterine residue area and CDFI blood flow signal positive rate were all reduced as compared with the values before treatment in patients of the two groups (P<0.05). After treatment, the intrauterine residue area and CDFI blood flow signal positive rate in the EA group were less than those in the western medication group (P<0.05). After treatment, the days of vaginal bleeding in patients of the EA group were less than that in the western medication group and the rate of second operation was lower than the western medication group (P<0.05). The uterine endomentrial volume after menstruation resumption in the EA group was larger than that in the western medication group after treatment (P<0.05). The total effective rate was 55.2% (16/29) in the EA group, higher than 37.9% (11/29) in the western medication group (P<0.05). CONCLUSION: The combined treatment of electroacupuncture at Baliao points and oral administration of mifepristone tablets effectively promotes uterine contraction, softens and discharges intrauterine residue and contributes to uterine volume restoration in the patients after uterine curettage of incomplete abortion. The therapeutic effect of this combined therapy is better than simple oral administration of mifepristone tablets.

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro.

BACKGROUND: Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM: To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms. METHODS: Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. RESULTS: TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells. CONCLUSION: Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

Regulation of Chlamydia spreading from the small intestine to the large intestine via an immunological barrier.

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.

Effectiveness of Platelet-Rich Plasma in the Prevention of Chlamydia-Induced Hydrosalpinx in a Murine Model.

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.

[Spatiotemporal variation of reference evapotranspiration in Shanxi Province, China]. / 山西省参考作物蒸散量的时空变化特征.

Based on data of daily precipitation, temperature, sunshine hours, relative humidity, wind speed and vapor pressure of 70 meteorological stations from 1960 to 2019 in Shanxi Province, the Penman-Monteith model was applied to calculate the reference evapotranspiration (ET0). The spatiotemporal variations of ET0 as well as the ET0 in different climatic zones and at different altitudes were quantitatively analyzed. The results showed that the mean annual ET0 decreased from west to east in 1960-2019. A jumping point was detected in 1982, with the mean annual ET0 increased both in 1960-1982 and 1983-2019. The monthly and ten-day changes of ET0 showed single peak curves. The variation of ET0 in different climatic zones was as follows: ET0 in temperate and semi-arid areas was higher than that in warm temperate and semi-humid areas and warm temperate and semi-arid areas in spring, summer, autumn and the whole year, while in winter, the highest ET0 was in warm temperate and semi-humid areas. ET0 varied with altitudes, with ET0 in <660 m altitude areas being higher than that in other altitudes in summer, autumn, winter and the whole year.

Combination of endoscopic submucosal dissection and laparoscopic sentinel lymph node dissection in early mucinous gastric cancer: Role of lymph node metastasis.

BACKGROUND: Recent evidence showed that combining endoscopic submucosal dissection (ESD) and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer (EMGC) patients with risks of positive lymph node metastasis (pLNM). AIM: To explore the predictive factors for pLNM in EMGC, and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC. METHODS: Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016. Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors, providing odds ratio (OR) with 95% confidence interval. And the association between the number of predictors and the pLNM rate was also investigated. RESULTS: Depth of invasion (OR = 7.342, 1.127-33.256, P = 0.039), tumor diameter (OR = 9.158, 1.348-29.133, P = 0.044), and lymphatic vessel involvement (OR = 27.749, 1.821-33.143, P = 0.019) turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis. For patients with 1, 2, and 3 risk factors, the pLNM rates were 9.1%, 33.3%, and 75.0%, respectively. pLNM was not detected in seven patients without any of these risk factors. CONCLUSION: ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size ≤ 2 cm, and when lymphatic vessel involvement is absent by postoperative histological examination. Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.

Chlamydia Deficient in Plasmid-Encoded pGP3 Is Prevented from Spreading to Large Intestine.

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. in small intestinal tissues. However, the small intestinal pGP3-deficient Chlamydia sp. failed to reach the large intestine, explaining the lack of live pGP3-deficient Chlamydia sp. in rectal swabs following an oral inoculation. Interestingly, pGP3-deficient Chlamydia sp. was able to colonize the colon following an intracolon inoculation, suggesting that pGP3-deficient Chlamydia sp. might be prevented from spreading from the small intestine to the large intestine. This hypothesis is supported by the finding that following an intrajejunal inoculation that bypasses the gastric barrier, pGP3-deficient Chlamydia sp. still failed to reach the large intestine, although similarly inoculated plasmid-free Chlamydia sp. was able to do so. Interestingly, when both types of organisms were intrajejunally coinoculated into the same mouse small intestine, plasmid-free Chlamydia sp. was no longer able to spread to the large intestine, suggesting that pGP3-deficient Chlamydia sp. might be able to activate an intestinal resistance for regulating Chlamydia sp. spreading. Thus, the current study has not only provided evidence for reconciling a previously identified conflicting phenotype but also revealed a potential intestinal resistance to chlamydial spreading. Efforts are under way to further define the mechanism of the putative intestinal resistance.

Gastrointestinal Coinfection Promotes Chlamydial Pathogenicity in the Genital Tract.

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.

[Dynamic identification of double-early rice heat and its spatiotemporal characteristics in Jiangxi Province, China]. / 江西早稻高温热害等级动态判识及时空变化特征.

Constructing evaluation indicator for rice heat damage based on hot weather process (occurring time of hot weather and its duration) can realize the dynamic identification of rice high-temperature heat damage level, which is of great importance to the precisely monitoring, warning and assessment of rice heat. Meteorological, historical disaster and phenological data on double-early rice in Jiangxi Province were integrated to retrieve the historical heat of double-early rice. The dynamic index of high temperature heat injury on early rice based on high temperature weather process was constructed based on K-S distribution fitting test and confidence interval method. The results were verified with reserved independent samples. A rice heat index (M) was calculated, with which rice heat risk was analyzed. The results showed that the starting time and duration of hot weather were key factors affecting the occurrence of rice heat damage, with the effect of starting time greater than the duration. Light, moderate, and severe rice heat for 3-5 d was identified at 10-12, 5-9 and 2-4 d after heading respectively. Similarly, light, moderate and severe rice heat lasting for 6-8 d and >8 d started at 11-18, 8-10, 1-7 d after heading and 12-18, 8-11, 0-7 d after heading respectively. The coincident rate of rice heat damage indicator was 73.7%, and that verified to be identical or one grade different was 89.5%. The linear tendency rate of M from 1981 to 2015 was 0.04·a-1, with abrupt change from low to high around 1999. A high M (>0.18) was mainly found in the middle and the northeast part of the study area. Increasing trends of a high M occurred in the middle, northeast and south of Jiangxi, with tendency rates > 0.04·a-1. In general, the indicators constructed in this study realized the dynamic identification of process-based rice heat. The middle and northeast parts of Jiangxi Province were identified as high risk areas for double-early rice heat.

The Cryptic Plasmid Improves Chlamydia Fitness in Different Regions of the Gastrointestinal Tract.

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 Plasmid-Encoded pGP3 Promotes Chlamydia Evasion of Acidic Barriers in Both Stomach and Vagina.

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 ∼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.

Comparison of endoscopic submucosal dissection with surgical gastrectomy for early gastric cancer: An updated meta-analysis.

BACKGROUND: There are several surgical options for treating early gastric cancers (EGCs), such as endoscopic resection, laparoscopic or open gastrectomy with D1 or D2 lymphadenectomy. Endoscopic resection for EGC with low risk of lymph node metastasis has been widely accepted as a therapeutic alternative. The role of endoscopic submucosal dissection (ESD) in treating EGC is not well established, especially when compared with resection surgery cases in a long-term follow-up scope. AIM: To compare the safety and efficacy of the short- and long-term outcomes between ESD and resection surgery. METHODS: We searched the databases of PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1990 to June 2018, enrolling studies reporting short- or long-term outcomes of ESD in comparison with resection surgery for EGC. The quality of the studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. Stata software (version 12.0) was used for the analysis. Pooling analysis was conducted using either fixed- or random-effects models depending on heterogeneity across studies. RESULTS: Fourteen studies comprising 5112 patients were eligible for analysis (2402 for EGC and 2710 for radical surgery). Our meta-analysis demonstrated that the ESD approach showed advantages through decreased operation time [weighted mean difference (WMD): -140.02 min, 95%CI: -254.23 to -34.82 min, P = 0.009], shorter hospital stay (WMD: -5.41 d, 95% CI: -5.93 to -4.89 d, P < 0.001), and lower postoperative complication rate [Odds ratio (OR) = 0.39, 95%CI: 0.28-0.55, P < 0.001). Meanwhile, EGC patients who underwent ESD had higher recurrence rate (OR = 9.24, 95%CI: 5.94-14.36, P < 0.001) than resection surgery patients. However, the long-term survival including overall survival [Hazard ratio (HR) = 0.51, 95%CI: 0.26-1.00, P = 0.05] and event-free survival (HR = 1.59, 95%CI: 0.66-9.81, P = 0.300) showed no significant differences between these two groups. CONCLUSION: In the treatment of EGC, ESD was safe and feasible in comparison with resection surgery, with advantages in several surgical and post-operative recovery parameters. Although the recurrence rate was higher in ESD group, the long-term survival was still comparable in these two groups, suggesting ESD could be recommended as standard treatment for EGC with indications.

Predictive factors for lymph node metastasis and defining a subgroup treatable for laparoscopic lymph node dissection after endoscopic submucosal dissection in poorly differentiated early gastric cancer.

AIM: To investigate the predictive factors of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC); to guide the individual application of a combination of endoscopic submucosal dissection (ESD) and laparoscopic lymph node dissection (LLND) in a suitable subgroup of patients with poorly differentiated EGC. METHODS: We retrospectively analyzed 138 patients with poorly differentiated EGC who underwent gastrectomy with lymphadenectomy between January 1990 and December 2015. The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95% confidence interval (95%CI) were calculated. We further examined the relationship between the positive number of the significant predictive factors and the LNM rate. RESULTS: The tumor diameter (OR = 13.438, 95%CI: 1.773-25.673, P = 0.029), lymphatic vessel involvement (LVI) (OR = 38.521, 95%CI: 1.975-68.212, P = 0.015) and depth of invasion (OR = 14.981, 95%CI: 1.617-52.844, P = 0.024) were found to be independent risk factors for LNM by multivariate analysis. For the 138 patients diagnosed with poorly differentiated EGC, 21 (15.2%) had LNM. For patients with one, two and three of the risk factors, the LNM rates were 7.7%, 47.6% and 64.3%, respectively. LNM was not found in 77 patients that did not have one or more of the three risk factors. CONCLUSION: ESD might be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2 cm in size and when LVI is absent upon postoperative histological examination. ESD with LLND may lead to the elimination of unnecessary gastrectomy in poorly differentiated EGC.

Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns.

Rapid repair of vascular injury is an important prognostic factor for electrical burns. This repair is achieved mainly via stromal cell-derived factor (SDF)-1α promoting the mobilization, chemotaxis, homing, and targeted differentiation of bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. Forming a concentration gradient from the site of local damage in the circulation is essential to the role of SDF-1α. In a previous study, we developed reactive oxygen species (ROS)-sensitive PPADT nanoparticles containing SDF-1α that could degrade in response to high concentration of ROS in tissue lesions, achieving the goal of targeted SDF-1α release. In the current study, a rat vascular injury model of electrical burns was used to evaluate the effects of targeted release of SDF-1α using PPADT nanoparticles on the chemotaxis of BMSCs and the repair of vascular injury. Continuous exposure to 220 V for 6 s could damage rat vascular endothelial cells, strip off the inner layer, significantly elevate the local level of ROS, and decrease the level of SDF-1α. After injection of Cy5-labeled SDF-1α-PPADT nanoparticles, the distribution of Cy5 fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly. Seven days after injury with nanoparticles injection, aggregation of exogenous green fluorescent protein-labeled BMSCs at the injury site was observed. Ten days after injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels. These results showed that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directing BMSC chemotaxis and homing, thereby promoting vascular repair in response to electrical burns.