Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

[Experimental study of cardioprotective effects of Cinnamomi Ramulus and Cinnamomi Cortex formula granules on myocardial ischemia/reperfusion injury in rats based on efficacy of "warming and coordinating heart Yang"].

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1ß(IL-1ß), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1ß, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1ß in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.

Dickkopf-1 drives tumor immune evasion by inducing PD-L1 expression in hepatocellular carcinoma.

Understanding the mechanisms regulating PD-L1 expression in hepatocellular carcinoma (HCC) is important to improve the response rate to PD-1/PD-L1 blockade therapy. Here, we show that DKK1 expression is positively associated with PD-L1 expression and inversely correlated with CD8+ T cell infiltration in human HCC tumor specimens. In a subcutaneous xenograft tumor model, overexpression of DKK1 significantly promotes tumor growth, tumoral PD-L1 expression, but reduces tumoral CD8+ T cell infiltration; whereas knockdown of DKK1 has opposite effects. Moreover, enforced expression of DKK1 dramatically promotes PD-L1 expression, Akt activation, ß-catenin phosphorylation and total protein expression in HCC cells. By contrast, knockdown of DKK1 inhibits all, relative to controls. In addition, CKAP4 depletion, Akt inhibition, or ß-catenin depletion remarkably abrogates DKK1 overexpression-induced transcriptional expression of PD-L1 in HCC cells. Reconstituted expression of the active Akt1 largely increased PD-L1 transcriptional expression in HCC cells. Similarly, expression of WT ß-catenin, but not the phosphorylation-defective ß-catenin S552A mutant, significantly promotes PD-L1 expression. Correlation analysis of human HCC tumor specimens further revealed that DKK1 and PD-L1 expression were positively correlated with p-ß-catenin expression. Together, our findings revealed that DKK1 promotes PD-L1 expression through the activation of Akt/ß-catenin signaling, providing a potential strategy to enhance the clinical efficacy of PD-1/PD-L1 blockade therapy in HCC patients.

Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial-mesenchymal transition in clear-cell renal cell carcinoma.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial-mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

HGF/c-MET pathway contributes to cisplatin-mediated PD-L1 expression in hepatocellular carcinoma.

Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8+ T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

Corrigendum: PKM2-Induced the Phosphorylation of Histone H3 Contributes to EGF-Mediated PD-L1 Transcription in HCC.

[This corrects the article DOI: 10.3389/fphar.2020.577108.].

Yap1-2 Isoform Is the Primary Mediator in TGF-ß1 Induced EMT in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive human malignancy and intrinsically resistant to conventional therapies. YAP1, as a key downstream effector of the Hippo pathway, plays an important role in tumorigenesis including PDAC. Alternative mRNA splicing of YAP1 results in at least 8 protein isoforms, which are divided into two subgroups (YAP1-1 and YAP1-2) based on the presence of either a single or double WW domains. We investigated the functions and regulatory mechanisms of YAP1-1 and YAP1-2 in PDAC cells induced by TGF-ß to undergo epithelial-to-mesenchymal transition (EMT). CRISPR-Cas9 and shRNA were used to silence YAP1 expression in pancreatic cancer cells. Re-constituted lentivirus mediated overexpression of each single YAP1 isoform was generated in the parental knockout L3.6 cells. EMT was induced by treatment with TGF-ß, EGF and bFGF in parental and the constructed stable cell lines. Western blot and qPCR were used to detect the expression of EMT markers. Scratch wound healing and transwell assays were used to detect cell migration. The stability and subcellular localization of YAP1 proteins were determined by Western blot analysis, immunofluorescence, as well as ubiquitination assays. We showed that TGF-ß, EGF and bFGF all significantly promoted EMT in PDAC cells, which was inhibited by knockdown of YAP1 expression. Interestingly, YAP1-1 stable cells exhibited a stronger migratory ability than YAP1-2 cells under normal culture condition. However, upon TGF-ß treatment, L3.6-YAP1-2 cells exhibited a stronger migratory ability than L3.6-YAP1-1 cells. Mechanistically, TGF-ß treatment preferentially stabilizes YAP1-2 and enhances its nuclear localization. Furthermore, TGF-ß-induced EMT and YAP1-2 activity were both blocked by inhibition of AKT signaling. Our results showed that both YAP1-1 and YAP1-2 isoforms are important mediators in the EMT process of pancreatic cancer. However, YAP1-2 is more important in mediating TGF-ß-induced EMT, which requires AKT signaling.

Full-Endoscopic Approach Forchronic Low Back Pain from Baastrup's Disease: Interspinous Plasty.

The objective was to introduce a new endoscopic technique-interspinous plasty for low back pain from Baastrup's disease; based on clinical manifestations, imaging findings and diagnostic test, to discuss a detailed diagnostic procedure for Baastrup's disease; and to explore the mechanism of interspinous plasty in pain relief. To our knowledge, there is no report about the results of endoscopic lumbar technique for Baastrup's disease. This study described the successful full-endoscopic surgical treatment for Baastrup's disease, providing a brand-new therapeutic method for patients. Clinical manifestations, imaging findings, including X-ray, computed tomography (CT) and magnetic resonance imaging, and a "positive" diagnostic test with local anesthetic were used to confirm Baastrup's disease in the three included patients. The interspinous plasty procedure, which aimed to recover a physiological gap between the adjacent spinous processes, was performed by full-endoscopic resection of marginal osteophytes. The removal of local inflamed tissue and reducing inflammation via intraoperative saline irrigation also lead to pain relief. Clinical outcomes included visual analog scale (VAS) for low back pain and the Oswestry Disability Index (ODI). The distance between the adjacent spinous processes was measured from the preoperative and postoperative CT scan. We calculated and recorded the difference between preoperative and postoperative measurements. Technical procedures and advantages of interspinous plasty are introduced. The three patients showed improvement in terms of the postoperative VAS of low back pain (from 8 to 2, from 7 to 1 and from 8 to 2) and ODI (from 68.9% to 33.3%, from 77.8% to 28.9% and from 71.1% to 28.9%, respectively) at the 12-month follow-up. Compared postoperative ODI index, the ODI index increased from 26.7% to 33.3% and from 24.4% to 28.9% in two of the cases at the 12-month follow-up. At 1 week, CT confirmed an obvious reduction in the marginal osteophytes between the adjacent spinous processes. Compared with those on preoperative CT images, the distance between adjacent spinous processes on postoperative CT was enlarged from 1 to 4 mm, and a repeated CT scan 3 months later reconfirmed little recrudescent osteoproliferation. In selected cases, full-endoscopic surgical treatment for chronic mechanical back pain as part of the phenomena of Baastrup's disease may be beneficial. The operations in this study were performed under local anesthesia, with satisfactory early clinical outcomes and a low incidence of complications or adverse events. This may be a feasible therapeutic method or an alternative option for patients who cannot tolerate general anesthesia surgery.

P300-dependent acetylation of histone H3 is required for epidermal growth factor receptor-mediated high-mobility group protein A2 transcription in hepatocellular carcinoma.

High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma (HCC) cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in HCC cells remains largely unclear. Here, we showed that the expression HMGA2 was upregulated in HCC, and that elevated HMGA2 could promote tumor metastasis. Incubation of HCC cells with epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through the PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, whereas a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified that p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.

PKM2-Induced the Phosphorylation of Histone H3 Contributes to EGF-Mediated PD-L1 Transcription in HCC.

High expression of programmed death-ligand-1 (PD-L1) in hepatocellular carcinoma (HCC) cells usually inhibits the proliferation and functions of T cells, leading to immune suppression in tumor microenvironment. However, very little has been described regarding the mechanism of PD-L1 overexpression in HCC cells. In the present study, we found epidermal growth factor (EGF) stimulation promoted the expression of PD-L1 mRNA and protein in HCC cells. Inhibition of epidermal growth factor receptor (EGFR) could reverse EGF-induced the expression of PD-L1 mRNA and protein. Subsequently, we also observed that the phosphorylation level of Pyruvate kinase isoform M2 (PKM2) at Ser37 site was also increased in response to EGF stimulation. Expression of a phosphorylation-mimic PKM2 S37D mutant stimulated PD-L1 expression as well as H3-Thr11 phosphorylation in HCC cells, while inhibition of PKM2 significantly blocked EGF-induced PD-L1 expression and H3-Thr11 phosphorylation. Furthermore, mutation of Thr11 of histone H3 into alanine abrogated EGF-induced mRNA and protein expression of PD-L1, Chromatin immunoprecipitation (ChIP) assay also suggested that EGF treatment resulted in enhanced H3-Thr11 phosphorylation at the PD-L1 promoter. In a diethylnitrosamine (DEN)-induced rat model of HCC, we found that the expression of phosphorylated EGFR, PKM2 nuclear expression, H3-Thr11 phosphorylation as well as PD-L1 mRNA and protein was higher in the livers than that in normal rat livers. Taken together, our study suggested that PKM2-dependent histone H3-Thr11 phosphorylation was crucial for EGF-induced PD-L1 expression at transcriptional level in HCC. These findings may provide an alternative target for the treatment of hepatocellular carcinoma.

EGF promotes DKK1 transcription in hepatocellular carcinoma by enhancing the phosphorylation and acetylation of histone H3.

The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of ß-catenin, a Wnt signaling effector. We investigated how DKK1 expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate DKK1 transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser37, which promoted its nuclear translocation. Also in these cells, EGFR-activated Akt phosphorylated the acetyltransferase p300 at Ser1834 Subsequently, PKM2 and p300 mediated the phosphorylation and acetylation, respectively, of histone H3 at the DKK1 promoter, which synergistically enhanced DKK1 transcription. The mechanism was supported with mutational analyses in cells and in a chemically induced HCC model in rats. The findings suggest that dual inhibition of the MEK and PI3K pathways might suppress the expression of DKK1 and, consequently, tumor metastasis in patients with HCC.

Corrigendum: An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness.

[This corrects the article DOI: 10.3389/fcell.2020.00287.].

Wnt5b/Ryk-mediated membrane trafficking of P2X3 receptors contributes to bone cancer pain.

Wnt5b, a member of Wnt family, plays multiple roles in tumor progression and metastasis. However, whether Wnt5b contributes to the sensitization of dorsal root ganglia (DRG) neurons and pathogenesis of bone cancer pain still remains unclear. Here, we found that the protein expression of Wnt5b and its atypical tyrosine protein kinase receptor Ryk was upregulated in ipsilateral DRGs in tumor-bearing mice. Application of Wnt5b evoked an increased discharge frequency in isolated DRG neurons and pain hypersensitivity in naïve mice which were almost completely prevented by anti-Ryk antibody. Moreover, intrathecal injection of anti-Ryk antibody to tumor-bearing mice significantly inhibited bone cancer-induced mechanic allodynia and thermal hyperalgesia. Subsequently, we also demonstrated that application of Wnt5b to cultured DRG neurons could enhance membrane P2X3 receptors and α,ß-meATP-induced currents. Intrathecal injection of calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 or P2X3 receptors antagonist A317491 almost completely abolished Wnt5b-induced mechanical allodynia and thermal hyperalgesia in mice. Meanwhile, pretreatment with anti-Ryk antibody or CaMKII inhibitor KN93 can attenuate bone-cancer induced the upregulation of P2X3 membrane protein as well as pain hypersensitivity. These findings suggested that Wnt5b/Ryk promoted the trafficking of P2X3 receptors to the membrane via the activation of CaMKII in primary sensory neurons, resulting in peripheral sensitization and bone cancer-induced pain. Our results may offer a potential therapeutic strategy for bone cancer pain.

An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness.

Cancer stemness is associated with high malignancy and low differentiation, as well as therapeutic resistance of tumors including pancreatic ductal adenocarcinoma (PDAC). Fibroblast growth factors (FGFs) exert pleiotropic effects on a variety of cellular processes and functions including embryonic stem cell pluripotency and cancer cell stemness via the activation of four tyrosine kinase FGF receptors (FGFRs). FGF ligands have been a major component of the cocktail of growth factors contained in the cancer stemness-inducing (CSI) and organoid culture medium. Although FGF/FGFR signaling has been hypothesized to maintain cancer stemness, its function in this process is still unclear. We report that inhibition of FGF/FGFR signaling impairs sphere-forming ability of PDAC in vitro, and knocking down FGFR1 and FGFR2 decreased their tumorigenesis abilities in vivo. Mechanistically, we demonstrated that SOX2 is down-regulated upon loss of FGFR signaling. The overexpression of SOX2 in SOX2-negative cells, which normally do not display stemness capabilities, is sufficient to induce spheroid formation. Additionally, we found that AKT phosphorylation was reduced upon FGFR signaling inhibition. The inhibition of AKT using specific pharmacological inhibitors in the context of CSI medium leads to the loss of spheroid formation associated with loss of SOX2 nuclear expression and increased degradation. We demonstrate that an FGFR/AKT/SOX2 axis controls cancer stemness in PDAC and therefore may represent an important therapeutic target in the fight against this very aggressive form of cancer.

Automatic Identification of Breast Ultrasound Image Based on Supervised Block-Based Region Segmentation Algorithm and Features Combination Migration Deep Learning Model.

Breast cancer is a high-incidence type of cancer for women. Early diagnosis plays a crucial role in the successful treatment of the disease and the effective reduction of deaths. In this paper, deep learning technology combined with ultrasound imaging diagnosis was used to identify and determine whether the tumors were benign or malignant. First, the tumor regions were segmented from the breast ultrasound (BUS) images using the supervised block-based region segmentation algorithm. Then, a VGG-19 network pretrained on the ImageNet dataset was applied to the segmented BUS images to predict whether the breast tumor was benign or malignant. The benchmark data for bio-validation were obtained from 141 patients with 199 breast tumors, including 69 cases of malignancy and 130 cases of benign tumors. The experiment showed that the accuracy of the supervised block-based region segmentation algorithm was almost the same as that of manual segmentation; therefore, it can replace manual work. The diagnostic effect of the combination feature model established based on the depth feature of the B-mode ultrasonic imaging and strain elastography was better than that of the model established based on these two images alone. The correct recognition rate was 92.95%, and the AUC was 0.98 for the combination feature model.

Subcategorization of Ultrasonographic BI-RADS Category 4: Assessment of Diagnostic Accuracy in Diagnosing Breast Lesions and Influence of Clinical Factors on Positive Predictive Value.

To evaluate the diagnostic accuracy of subcategories 4a-4c of the second edition of the Breast Imaging Reporting and Data System (BI-RADS) ultrasonography (US) lexicon, and to investigate whether clinical factors influence the positive predictive values (PPVs). Overall, 1240 breast lesions in 1227 women diagnosed on ultrasound as category 4 and with pathology were included. The PPV with 95% confidence interval (CI) was 13.6% (95% CI: 11%, 16%) in BI-RADS 4a, 50.0% (95% CI: 44%, 56%) in BI-RADS 4b and 86.0% (95% CI: 82%, 90%) in BI-RADS 4c. Patients' age significantly affected PPVs for subcategories 4a-4c, whereas radiologists' experience and application time had little influence on PPVs for subcategories 4a-4c. In conclusion, the diagnostic accuracies of subcategories 4b and 4c were superior to subcategory 4a. Patients' age significantly affected PPVs for subcategories 4a-4c. Utilizing the subcategories of category 4 was a feasible method regardless of radiologists' experience and application time.

The prognostic value of C-reactive protein/albumin ratio in nasopharyngeal carcinoma: a meta-analysis.

The C-reactive protein/albumin ratio (CRP/Alb ratio) has been reported to have promising prognostic value in several cancers. The current meta-analysis was conducted to better define the prognostic value of CRP/Alb ratio in patients with nasopharyngeal carcinoma (NPC). The Web of Science, Embase, Cochrane Library databases, and PubMed were searched up to 25 February 2018 for the information on CRP/Alb ratio and outcomes of NPC. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to evaluate the association between CRP/Alb ratio and survival outcomes in NPC. A total of five studies with 5533 patients with NPC were included. Pooled results showed that high CRP/Alb ratio was associated with poor overall survival (OS) (HR = 1.51, 95% CI: 1.30-1.75, P<0.001) and poor distant metastasis-free survival (DMFS) (HR = 1.23, 95% CI: 1.07-1.43, P=0.005). Subgroup analyses showed that patients with higher CRP/Alb ratio have worse OS in NPC. In conclusion, elevated CRP/Alb ratio was associated with worse prognosis in patients with NPC.

[Pollution Levels and Risk Assessment of Heavy Metals from Atmospheric Deposition in Nanjing].

In order to evaluate the pollution levels of and risk from heavy metals in the atmospheric deposition of different functional urban districts, dust samples were collected from 20 sampling sites in typical industrial, traffic, residential, and educational districts of Nanjing. The concentrations of As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Ti, V, and Zn were analyzed. The potential ecological risk and health risk were evaluated using the potential ecological risk index and U.S. EPA's health risk assessment models. Enrichment factors, correlation analysis, and principal component analysis were used to analyze the sources of heavy metals. Results showed that the concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn were the highest in the industrial district and the concentrations of Ba, Ni, Ti, and V were the highest in the traffic district. The value of the potential ecological risk index was the highest in the industrial district and lowest in the educational district. Meanwhile, the ecological risk of Cr was the highest, achieving a moderate ecological hazard level. None of the studied heavy metals had noncarcinogenic risk or carcinogenic risk, according to the results of health risk assessment. Source analysis indicated that heavy metals in the atmospheric deposition from the study areas were mainly from traffic and industrial activities, coal combustion, natural process and life sources.

High-fat-diet-induced obesity upregulates the expression of lymphoid chemokines and promotes the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter suis colonizes the stomachs of a variety of animals, including humans, and is more likely than other Helicobacter species to induce gastric mucosa-associated lymphoid tissue lymphoma. Obesity is a low-grade chronic inflammatory state in which the induction of a chemokine network contributes to a variety of diseases. However, the effect of obesity on the development of gastric MALT in the presence of H. suis infection remains unclear. Here, we reveal that high-fat-diet-induced obesity upregulates the expression of lymphoid chemokines in the stomach and accelerates the H. suis infection-induced formation of gastric lymphoid follicles, potentially via a mechanism that involves the activation of the nuclear factor kappa B (NF-κB) signaling pathway. These findings provide novel insight into the pathogenesis of obesity-related diseases, especially those induced by Helicobacter infection.

Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse ß-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans.