Coronary stent implantation links to the occurrence of eosinophilia and interstitial pneumonia: a case report and systematic review.

BACKGROUND: Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential harms of rapamycin-eluting stents. Herein, We report a case of eosinophilia and interstitial pneumonia caused by a cobalt-based alloy stent eluted with rapamycin. CASE PRESENTATION: The patient was admitted due to fever, cough, and expectoration symptoms. Previously, the patient had undergone a procedure of percutaneous coronary stent implantation in our hospital's cardiology department, which led to a gradual rise in blood eosinophil count. This time, the eosinophil count was higher than the previous admission. A chest CT scan revealed multiple flocculent density increases in both lungs and bronchiectasis. The rapamycin-eluting stents may have caused eosinophilia and interstitial pneumonia, which improved after administering corticosteroids. A systematic review of relevant literature was conducted to summarize the characteristics of interstitial pneumonia caused by drug-eluting stents. CONCLUSION: Paclitaxel, everolimus, zotarolimus, and rapamycin are the types of drugs that can lead to drug-eluting stents, and because of the rarity of their onset, clinical doctors must be precise and prompt in diagnosing suspected cases to avoid misdiagnosis and delayed treatment.

Vinpocetine represses the progression of nonalcoholic steatohepatitis in mice by mediating inflammasome components via NF-KB signaling / La vinpocetina reprime la progresión de la esteatohepatitis no alcohólica en ratones por mediación de los componentes del inflamasoma a través de la señalización NF-KB

Background: Inflammasome activation is known to be involved in nonalcoholic steatohepatitis (NASH). Vinpocetine is a derivative of vincamine and is reported to suppress the activation of inflammasome. Methods: This study explored the therapeutical potential of Vinpocetine on NASH. Mice were fed with a choline-deficient (MCD) or chow diet in the presence or absence of Vinpocetine for 8 weeks. H&E staining and biochemical assays were determined to evaluate the hepatic steatosis and fibrosis symptoms. In addition, primary hepatocytes and Kupffer cells were isolated and induced by MCD or lipopolysaccharides/cholesterol crystals with or without Vinpocetine. ELISAs, qPCR, and Western blotting were applied to determine the levels of NASH-related biomarkers in both in vivo mouse model and in vitro cell models. Results: Treatment of Vinpocetine did not cause observable side effects against and MCD-induced cells and mouse NASH model. However, treatment of Vinpocetine ameliorated hepatic steatosis and fibrosis and suppressed the levels of alanine transaminase and aspartate transferase in the mouse NASH model. In addition, treatment of Vinpocetine suppressed the mRNA and protein levels of inflammasome components both in vitro and in vivo. Conclusion: Vinpocetine suppressed NASH in mice by mediating inflammasome components via nuclear factor κB signaling. (AU)

Antecedentes: Se sabe que la activación del inflamasoma está implicada en la esteatohepatitis no alcohólica (EHNA). La vinpocetina es un derivado de la vincamina que, según los informes, suprime la activación del inflamasoma. Métodos: Este estudio exploró el potencial terapéutico de la vinpocetina en la EHNA. Durante 8 semanas se alimentó a ratones con una dieta deficiente en colina (MCD) o con una dieta chow en presencia o ausencia de vinpocetina. Se realizaron tinciones de H&E y ensayos bioquímicos para evaluar los síntomas de esteatosis hepática y fibrosis. Además, se aislaron hepatocitos primarios y células de Kupffer y se indujeron mediante MCD o cristales de lipopolisacáridos/colesterol con o sin vinpocetina. Se aplicaron ELISA, qPCR y Western blotting para determinar los niveles de biomarcadores relacionados con la EHNA tanto en el modelo de ratón in vivo como en los modelos celulares in vitro. Resultados: El tratamiento con vinpocetina no causó efectos secundarios observables contra las células y el modelo de ratón de EHNA inducidos por MCD. Sin embargo, el tratamiento con vinpocetina mejoró la esteatosis hepática y la fibrosis y suprimió los niveles de alanina transaminasa y de aspartato transferasa en el modelo de EHNA de ratón. Además, el tratamiento con vinpocetina suprimió los niveles de ARNm y proteínas de los componentes del inflamasoma tanto in vitro como in vivo. Conclusiones: La vinpocetina suprimió la EHNA en ratones por mediación de los componentes del inflamasoma a través de la señalización del factor nuclear κB. (AU)

Nuclear translocation of cleaved PCDH9 impairs gastric cancer metastasis by downregulating CDH2 expression.

Loss of Protocadherin 9 (PCDH9) is associated with the metastasis and the prognosis of gastric cancer patients, while the molecular mechanism of PCDH9-impaired gastric cancer metastasis remains unclear. Here we show that PCDH9 is cleaved in gastric cancer cells. Intracellular domain of PCDH9 translocates into nucleus, where it interacts with DNA methyltransferase 1 (DNMT1) and increases DNMT1 activity. Activated DNMT1 downregulates cadherin 2 (CDH2) expression by increasing DNA methylation at its promoter, thereby dampening the migration and in vivo metastasis of gastric cancer cells. In addition, the levels of nuclear PCDH9 correlate with CDH2 expression, lymph node metastasis, and the prognosis of gastric cancer patients. Our finding demonstrates a unique mechanism of nuclear PCDH9-impaired gastric cancer metastasis by promoting DNA methylation of CDH2 promoter.

Diagnostic accuracy of thoracic CT to differentiate transudative from exudative pleural effusion prior to thoracentesis.

BACKGROUND: Computed tomography (CT) scan is commonly performed for pleural effusion diagnostis in the clinic. However, there are limited data assessing the accuracy of thoracic CT for the separation of transudative from exudative effusions. The study aimed to determine the diagnostic value of thoracic CT in distinguishing transudates from exudates in patients with pleural effusion. METHODS: This is a two-center retrospective analysis of patients with pleural effusion, a total of 209 patients were included from The First Affiliated Hospital of Henan University of Science and Technology as the derivation cohort (Luoyang cohort), and 195 patients from the First Affiliated Hospital of Zhengzhou University as the validation cohort (Zhengzhou cohort). Patients who underwent thoracic CT scan followed by diagnostic thoracentesis were enrolled. The optimal cut-points of CT value in pleural fluid (PF) and PF to blood CT value ratio for predicting a transudative vs. exudative pleural effusions were determined in the derivation cohort and further verified in the validation cohort. RESULTS: In the Derivation (Luoyang) cohort, patients with exudates had significantly higher CT value [13.01 (10.01-16.11) vs. 4.89 (2.31-9.83) HU] and PF to blood CT value ratio [0.37 (0.27-0.53) vs. 0.16 (0.07-0.26)] than those with transudates. With a cut-off value of 10.81 HU, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT value were 0.85, 88.89%, 68.90%, 43.96%, and 95.76%, respectively. The optimum cut-value for PF to blood CT value ratio was 0.27 with AUC of 0.86, yielding a sensitivity of 61.11%, specificity of 86.36%, PPV of 78.57%, and NPV of 73.08%. These were further verified in the Validation (Zhengzhou) cohort. CONCLUSIONS: CT value and PF to blood CT value ratio showed good differential abilities in predicting transudates from exudates, which may help to avoid unnecessary thoracentesis.

Vinpocetine represses the progression of nonalcoholic steatohepatitis in mice by mediating inflammasome components via NF-κB signaling.

BACKGROUND: Inflammasome activation is known to be involved in nonalcoholic steatohepatitis (NASH). Vinpocetine is a derivative of vincamine and is reported to suppress the activation of inflammasome. METHODS: This study explored the therapeutical potential of Vinpocetine on NASH. Mice were fed with a choline-deficient (MCD) or chow diet in the presence or absence of Vinpocetine for 8 weeks. H&E staining and biochemical assays were determined to evaluate the hepatic steatosis and fibrosis symptoms. In addition, primary hepatocytes and Kupffer cells were isolated and induced by MCD or lipopolysaccharides/cholesterol crystals with or without Vinpocetine. ELISAs, qPCR, and Western blotting were applied to determine the levels of NASH-related biomarkers in both in vivo mouse model and in vitro cell models. RESULTS: Treatment of Vinpocetine did not cause observable side effects against and MCD-induced cells and mouse NASH model. However, treatment of Vinpocetine ameliorated hepatic steatosis and fibrosis and suppressed the levels of alanine transaminase and aspartate transferase in the mouse NASH model. In addition, treatment of Vinpocetine suppressed the mRNA and protein levels of inflammasome components both in vitro and in vivo. CONCLUSION: Vinpocetine suppressed NASH in mice by mediating inflammasome components via nuclear factor κB signaling.

Pre-treatment with galectin-1 attenuates lipopolysaccharide-induced myocarditis by regulating the Nrf2 pathway.

Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins, plays a crucial role in controlling inflammation and neovascularization. However, the potential role of Gal-1 in preventing myocarditis remains uncertain. We aimed to explore the functions and mechanisms of Gal-1 in preventing myocarditis. In vivo, C57/BL6 mice were pre-treated with or without Gal-1 and then exposed to lipopolysaccharide (LPS) to induce myocarditis. Subsequently, cardiac function, histopathology, inflammation, oxidative stress, and apoptosis of myocardial tissues were detected. Following this, qRT-PCR and Western blotting were applied to measure iNOS, COX2, TXNIP, NLRP3 and Caspase-1 p10 expressions. In vitro, H9c2 cells pre-treated with different doses of Gal-1 were stimulated by LPS to induce myocarditis models. CCK8, flow cytometry and reactive oxygen species (ROS) assay were then employed to estimate cell viability, apoptosis and oxidative stress. Furthermore, Nrf2 and HO-1 protein expressions were evaluated by Western blotting in vivo and in vitro. The results showed that in vivo, Gal-1 pre-treatment not only moderately improved cardiac function and cardiomyocyte apoptosis, but also ameliorated myocardial inflammation and oxidative damage in mice with myocarditis. Furthermore, Gal-1 inhibited TXNIP-NLRP3 inflammasome activation. In vitro, Gal-1 pre-treatment prevented LPS-induced apoptosis, cell viability decrease and ROS generation. Notably, Gal-1 elevated HO-1, total Nrf2 and nuclear Nrf2 protein expressions both in vivo and in vitro. In conclusion, pre-treatment with Gal-1 exhibited cardioprotective effects in myocarditis via anti-inflammatory and antioxidant functions, and the mechanism may relate to the Nrf2 pathway, which offered new solid evidence for the use of Gal-1 in preventing myocarditis.

Zinc-Rutin Particles Ameliorate DSS-Induced Acute and Chronic Colitis via Anti-inflammatory and Antioxidant Protection of the Intestinal Epithelial Barrier.

In patients suffering from inflammatory bowel diseases (IBDs), the immune system is disrupted and the intestinal barrier function is compromised. Here, six zinc-flavonoid particles were produced by one-step reaction via changing flavonoids (myricetin, quercetin, and rutin) and solvent (water and ethanol), and then their cytocompatibility and ability to scavenge H2O2, free radicals, and LPS-induced ROS were compared. Zinc-rutin particles (W-ZnRT) composed of rutin (78.92 wt %), Na12[ZnPO4]12·12H2O (6.76 wt %), and crystal water were screened out because W-ZnRT exhibited 80.8 ± 15% cell viability against RAW264.7, could rapidly scavenge 78.1 ± 1% of H2O2 and 71.6 ± 2% of DPPH within 30 min, and reduced LPS-increased intracellular ROS to normal levels. In addition, the therapeutic effects of rutin and W-ZnRT were also compared in dextran sulfate sodium (DSS)-induced acute and chronic colitis in mice. W-ZnRT was superior to rutin alone in chronic colitis (n = 9), although they were equally effective in acute colitis (n = 7). Compared to rutin, 11 oral doses of W-ZnRT (40 mg kg-1) significantly improved intestinal permeability (p = 0.0299) and colon length (p = 0.0025), reduced intestinal proinflammatory factors (IL-6, IL-1ß, and TNF-α), and upregulated tight junction proteins to maintain intestinal barrier function. Taken together, these results identified W-ZnRT as an efficient and safe therapeutic strategy for IBD.

Pathogenic Nocardia amamiensis infection: A rare case report and literature review.

Background: To date, only six cases of Nocardia amamiensis infection have been reported, including two ocular cases, three pulmonary cases, and one disseminated case. However, no Nocardia amamiensis pulmonary infection cases have been reported in immunocompetent patients without structural pulmonary disease. This study describes a rare case and provides a detailed review of all previous cases. Methods: A pulmonary infection caused by Nocardia amamiensis in a 64-year-old man with low-grade fever, night sweats, and weight loss was reported. All previously reported cases of Nocardia amamiensis infection were searched and reviewed. Results: The pathogen was identified as Nocardia amamiensis using bronchoalveolar lavage fluid (BALF) mNGS, and the current case was successfully treated with trimethoprim-sulfamethoxazole (ST) monotherapy. mNGS and 16S rRNA PCR are standard tests to identify Nocardia.Conclusion: mNGS has high diagnostic performance for Nocardia amamiensis. Further studies are needed to clarify the clinical characteristics and explore more effective treatment protocols for this rare pathogen.

LncRNA-NEAT1 inhibits the occurrence and development of pancreatic cancer through spongy miR-146b-5p/traf6.

To investigate the inhibitory effect of LNCNA-NEA1 on pancreatic cancer development and progression via spongiosa miR-146b-5p/TRAF6, 60 pancreatic cancer patients diagnosed from December 2017 to December 2019 were selected as a general source of information. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression level of NEAT1 in cancerous and adjacent non-cancerous tissues. Cell counting kit-8 (CCK-8) and transwell were used to determine the effect of LNCNA-NEA1 on the proliferation and migration of pancreatic cancer cells (Panc-1). The results of dual luciferase reporter gene assay showed that nea 1 could target and regulate the expression of spongy miR-146b-5p/TRAF6, and reducing the expression of spongy miR-146b-5p/TRAF6 could reverse the inhibitory effects of nea 1-siRNA on proliferation, migration and invasion of pancreatic cancer cells. Therefore, it was concluded that knockdown of nea 1 could inhibit the proliferation, migration and invasion of pancreatic cancer cells by upregulating the level of miR-146b-5p/TRAF6, and the expression of lnc RNA-nea 1 could be used as an indicator for preoperative diagnosis and postoperative prognosis of pancreatic cancer patients. .

Identification of crucial genes of pediatric inflammatory bowel disease in remission by protein-protein interaction network and module analyses.

BACKGROUND: Although the main treatments of inflammatory bowel disease (IBD) aim at the induction and maintenance of clinical remission, several studies have demonstrated inflammation still present in clinical remission. The goal of this study was to analyze the gene expression profiles between the pediatric IBD and control samples, aiming to further investigate the underlying therapeutic target in remission. METHODS: Gene expression profiles data of GSE33943 were downloaded from Gene Expression Omnibus, which included 45 pediatric IBD samples and 13 control samples. The differentially expressed genes (DEGs) between IBD and control samples were identified by LIMMA package in R and the function of DEGs were predicted by Gene Ontology and KEGG pathway enrichment analyses using GeneAnswer package. Furthermore, a protein-protein interaction (PPI) network was constructed through the STRING database and functional module was obtained using ClusterONE. RESULTS: A total of 224 DEGs were screened between IBD and control samples. These DEGs (e.g. up-regulated FAS and down-regulated CCL5) were mainly enriched in cytokine‒cytokine receptor interaction and chemokine signaling pathway. In addition, some hub genes (e.g. up-regulated PSMA2 and PSMA6) were obtained through PPI network and functional module. These two genes were involved in Proteasome alpha-subunit and conserved site by functional module analysis. CONCLUSIONS: The immune and Proteasome mechanisms are still active during remission and FAS, PMSF6 and PMSF2 may be underlying targets for therapy of this disease.

Case Report: Clinical characteristics and genetic analysis of two patients with hereditary hemorrhagic telangiectasia.

Objective: To analyze the clinical features and genetic characteristics of two patients with hereditary hemorrhagic telangiectasia (HHT) and to review the relevant literature. Methods: The clinical data of two HHT patients admitted to the author's hospital between April 2019 and February 2022 were retrospectively analyzed. Meanwhile, the genetic analysis was performed with their consent. Results: The first patient was a 62-year-old woman who had been complaining of shortness of breath and fever for 20 days. Her previous medical history included brain abscess drainage and video-assisted thoracoscopic surgery for a pulmonary hemangioma. A right heart catheterization revealed no pulmonary arterial hypertension, and an abdominal enhanced magnetic resonance imaging revealed multiple arteriovenous malformations in the liver. Her ACVRL1 heterozygous variants were discovered through whole-exon gene testing. The second case involved a 47-year-old woman who had been experiencing chest tightness for the past 2 years. Several years ago, she underwent brain abscess drainage and embolization of a pulmonary arteriovenous fistula. Ultrasound revealed generalized hepatic vascular dilation, and enhanced computed tomography revealed numerous pulmonary venous fistulas scattered in both lungs as well as multiple arteriovenous malformations in the liver. Her whole-exon gene testing revealed that she, like her son, had heterozygous ENG variants. Conclusion: HHT patients may experience infection, bleeding, dyspnea, and other symptoms. Imaging is important in disease diagnosis and management because early detection and treatment can prevent major complications and disability or even death.

Plasma Angiopoietin-2 as a Promising Biomarker for the Prognosis of Acute Pulmonary Embolism.

BACKGROUND: Endothelial damage is one of the pathogenic conditions of acute pulmonary embolism (APE). The essential role of angiogenin, ribonuclease A family, member 2 (Ang-2) in APE remains unclear. This study aimed to investigate the predictive value of Ang-2 in the clinical outcomes of patients with APE. METHODS: Plasma Ang-2 levels were measured by an enzyme-linked immunosorbent assay kit using a DuoSet methodology in 118 APE patients and 53 healthy controls. Baseline data relevant to mortality over time were obtained from hospital databases or by patient's follow-up (median follow-up time: 25.0 ± 13.2 months). The main outcome was all-cause mortality. RESULTS: Plasma Ang-2 level was significantly higher in APE patients than in healthy controls (p < 0.001). Patients dying during the first 30 days presented higher baseline levels of Ang-2 than the survivors (p < 0.001). Patients dying during the follow-up also showed higher baseline levels of Ang-2 than the survivors (p < 0.001). The multi-variable logistic regression analysis showed that the N-terminal propeptide of B-type natriuretic peptide (NT-proBNP) [odds ratio (OR): 19.8; 95% CI: 1.5 - 255.8; p = 0.022] and Ang-2 (OR: 9.9; 95% CI: 1.4 - 70.5; p = 0.022) emerged as independent predictors of the 30-day mortality. Furthermore, the multivariable Cox's regression identified plasma Ang-2 [hazards ratio (HR): 1.35; 95% CI: 1.10 - 1.66; p = 0.004] as an independent predictor of long-term mortality in patients with APE. CONCLUSIONS: A high circulating level of Ang-2 can be considered as an independent predictor for the poor outcome of APE and may serve as a biomarker for the risk stratification in patients with APE.

Establishment and Clinical Application of a Highly Sensitive Time-Resolved Fluorescence Immunoassay for Tumor-Associated Trypsinogen-2.

To establish a rapid and highly sensitive assay for tumor-associated trypsinogen-2 (TAT-2) based on the time-resolved fluorescence immunoassay (TRFIA) and evaluate its potential clinical value in patients with lung cancer. The double-antibody sandwich method was used in detecting TAT-2 antigen concentrations, and two types of TAT-2 antibodies (coating antibodies and Eu3+ labeled antibodies) were used. A TAT-2-TRFIA method was then established, evaluated, and used in detecting the serum TAT-2 levels of healthy subjects and patients with lung cancer. The linear range of the TAT-2-TRFIA method was 1.53-300 ng/mL, the intra-assay coefficient of variation (CV) were between 1.67% and 8.42%, and the inter-assay CV were between 4.29% and 11.44%. The recovery rates of TAT-2-TRFIA were between 99.17% and 107.06%. The cross-reactivities of trypsin and T-cell immunoglobulin mucin 3 were 0.02% and 0.82%, respectively. The serum TAT-2 levels of patients with lung cancer were higher than those of healthy subjects (P < 0.001). Combined with TAT-2, the sensitivity and specificity of CEA and CA-125 for lung cancer improved significantly. Conclusion: We successfully established a highly sensitive TAT-2-TRFIA method, which was able to facilitate the timely diagnosis of lung cancer.

In vitro evidence of oncofetal antigen and TLR-9 agonist co-delivery by alginate nanovaccines for liver cancer immunotherapy.

Liver cancer is the most common malignant tumor and liver cancer immunotherapy has been one of the research hotspots. To induce antigen-specific antitumor immune responses against liver cancer, we developed antigen and adjuvant co-delivery nanovaccines (APPCs). Polyanionic alginate (ALG) and polycationic polyethyleneimine (PEI) were utilized to co-deliver a glypican-3 peptide antigen and an unmethylated cytosine-phosphate-guanine (CpG) adjuvant by electrostatic interactions. A cellular uptake study confirmed that APPC could promote antigen and adjuvant uptake by dendritic cells (DCs). Importantly, APPC facilitated the endosomal escape of the peptide for antigen delivery into the cytoplasm. In addition, APPC showed significant stimulation of DC maturation in vitro. APPC could also efficiently prime DCs and induce cytotoxic T lymphocyte responses in vivo. The in vitro cell viability assay and the in vivo histocompatibility showed that APPC was non-toxic within the tested concentration. This study demonstrates that the peptide antigen and the CpG adjuvant co-delivery nanovaccine have potential applications in liver cancer immunotherapy.

LINC00630 as a miR-409-3p sponge promotes apoptosis and glycolysis of colon carcinoma cells via regulating HK2.

Long-chain non-coding RNAs (lncRNAs) belong to the family of non-coding RNAs and contain more than 200 nucleotides. They are involved in the growth, apoptosis, and glycolysis of carcinoma cells. A newly discovered lncRNA, LINC00630, has been reported in colon carcinoma. In this study, we found that the expression of LINC00630 was remarkably upregulated in colon carcinoma tissues and cell lines compared with that in adjacent tissues and the NCM-460 cell lines. Knocking out LINC00630 resulted in inhibition of proliferation and glycolysis but increase in apoptosis. In addition, we confirmed the direct interaction between LINC00630 and miR-409-3p in colon carcinoma cells using bioinformatics methods and dual luciferase reporter gene assay. Finally, we demonstrated that LINC00630 could promote cell growth and glycolysis and inhibit apoptosis by functioning as a miR-409-3p sponge, and further regulate hexokinase 2 (HK2) in colon carcinoma cells. Our results confirmed that LINC00630 regulates proliferation, glycolysis, and apoptosis mainly through targeting the miR-409-3p/HK2 axis, which may explain the progression of colon carcinoma and provide a potential target for the treatment of colon carcinoma.

Integrative effects of transcutaneous electrical acustimulation on abdominal pain, gastrointestinal motility, and inflammation in patients with early-stage acute pancreatitis.

BACKGROUND/AIMS: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients. METHODS: Forty-two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham-TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF-α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry. KEY RESULTS: Compared with Sham-TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham-TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF-α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05). CONCLUSIONS & INFERENCES: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF-α, probably mediated via the autonomic and ghrelin mechanisms.

The value of miR-510 in the prognosis and development of colon cancer.

PURPOSE: Colon cancer is one of the malignant tumors that threatens human health. miR-510 was demonstrated to play roles in the progression of various cancers; its dysregulation was speculated to be associated with the development of colon cancer. METHODS: One hundred and thirteen colon cancer patients participated in this research. With the help of RT-qPCR, the expression of miR-510 in collected tissues and cultured cells was analyzed. The association between miR-510 expression level and clinical features and prognosis of patients was evaluated. Moreover, the effects of miR-510 on cell proliferation, migration, and invasion of colon cancer were assessed by CCK8 and Transwell assay. RESULTS: miR-510 significantly upregulated in colon cancer tissues and cell lines relative to the adjacent normal tissues and colonic cells. The expression of miR-510 was significantly associated with the TNM stage and poor prognosis of patients, indicating miR-510 was involved in the disease progression and clinical prognosis of colon cancer. Additionally, the upregulation of miR-510 significantly promoted cell proliferation, migration, and invasion of colon cancer, while its knockdown significantly inhibited these cellular processes. SRCIN 1 was the direct target of miR-510 during its promoted effect on the development of colon cancer. CONCLUSION: The upregulation of miR-510 acts as an independent prognostic indicator and a tumor promoter by targeting SRCIN 1 in colon cancer, which provides novel therapeutic strategies for colon cancer.

Caspase-11-Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic Steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an inflammatory disease with severe outcomes. Hepatocyte death, including apoptosis, necrosis, and pyroptosis, has been implicated in pathophysiology of NASH. Pyroptosis is mediated by inflammasome activation pathways including caspase-1-mediated canonical signaling pathway and caspase-11-mediated noncanonical signaling pathway. Until now, the precise role of caspase-11 in NASH remains unknown. In the present study, the potential roles of caspase-11 in NASH were explored. METHODS: We established methionine- and choline-deficient diet (MCD)-induced NASH mice model using wild-type caspase-11-deficient mice. The expression of caspase-11, liver injury, fibrosis, inflammation, and activation of gasdermin D and interleukin-1ß were evaluated. RESULTS: Upregulated caspase-11 was detected in liver of mice with NASH. MCD-treated caspase-11-deficient mice had significantly decreased liver injury, fibrosis, and inflammation. The activation of gasdermin D and interleukin-1ß was inhibited in caspase-11-deficient mice after MCD treatment. Overexpression of caspase-11 promoted steatohepatitis. CONCLUSIONS: Caspase-11-mediated hepatocytic pyroptosis promotes the progression of NASH.

Pyogenic Liver Abscess and Endogenous Endophthalmitis Due to K64-ST1764 Hypervirulent Klebsiella pneumoniae: A Case Report.

RATIONALE: Klebsiella pneumoniae (K. pneumoniae, KP) are divided into two types: classic K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). hvKP causes liver abscess and metastatic infection. Here, we report one case with pyogenic liver abscess (PLA) and endogenous endophthalmitis (EE) due to a relatively rarely reported serotype of K. pneumoniae in China. PATIENT CONCERNS: An 80-year old man presented with nausea, vomiting, and epigastric discomfort for 2 weeks. DIAGNOSES: PLA was identified by CT scan and abdominal ultrasound. Urgent ophthalmologic consultation was performed. B-scan ocular ultrasound was done and he was diagnosed as EE. INTERVENTIONS: Antibiotic treatment, intravitreal injection of eyes and eye drops were given. Percutaneous needle aspiration, evisceration, and drainage of the right eye were performed. OUTCOMES: Cultures of the blood, the aspirated pus from the liver abscess, and the contents of the eyeball all yielded K. pneumoniae with a positive string test. The capsular serotype was K64. According to the existence of multiple virulence genes and the severe invasive clinical manifestation, this strain is regarded as a hvKp strain. Multilocus sequence typing (MLST) revealed the sequence type (ST) of this strain was K64-ST1764. Antimicrobial resistance genes, bla NDM-1 and bla KPC-2, were not detected in the genome. The patient lost his eyesight but his symptoms subsided. During 15 months follow-up, the result was satisfactory. LESSONS: Here, we report one case with PLA due to a relatively rarely reported serotype of K. pneumoniae in China. This K64 K. pneumoniae strain is confirmed as hvKp by multiple methods. It is noteworthy that the sequence type is K64-ST1764 instead of the commonest ST11. Moreover, this strain is not considered a K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) or a carbapenem-resistant K. pneumoniae (CRKP) as it is usually. Further follow-up and research are required to investigate this strain.

Clinical Characteristics and Genetic Analysis of a Family With Birt-Hogg-Dubé Syndrome and Congenital Contractural Arachnodactyly.

Background: Birt-Hogg-Dubé (BHD) syndrome and congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome are clinically rare autosomal dominant genetic diseases. In this study, we describe an extremely rare family with BHD syndrome and CCA. Objective: To investigate the clinical and genetic characteristics of a family with BHD syndrome and CCA. Methods: We describe the clinical characteristics, family history, and clinical manifestations of the patient's family members. The patient underwent a blood test, computed tomography (CT) of the chest, color Doppler ultrasound of the abdomen and heart, and digital radiography of the hands. Whole exome sequencing was performed on his family members. Results: Two years ago, the male proband developed chest tightness and shortness of breath that was accompanied by an irritating cough as well as repeated (four times) spontaneous pneumothorax. The chest CT indicated spontaneous pneumothorax on the right side and cyst and bullae in both lungs. He had no kidney tumors or skin lesions. His son had a history of pulmonary bullae and experienced spontaneous pneumothorax twice. The proband, his mother, and his son were all born with a hand deformity. The sequencing results demonstrated that both the proband and his son had heterozygous variations of the folliculin (FLCN) gene c.1015C > T (p. Gln339Ter) and fibrillin-2 (FBN2) gene c.3485G > A (p. Cys1162Tyr), which are associated with BHD syndrome and CCA, respectively. Conclusion: For patients with chest tightness, shortness of breath, recurrent spontaneous pneumothorax, and congenital hand deformity without inducement, genetic testing should be carried out as soon as possible to make a clear diagnosis, which can then guide treatment and genetic counseling.