Clinical significance of tumor suppressor genes methylation in circulating tumor DNA of patients with pancreatic cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential diagnostic and prognostic biomarker in various tumors. However, the role of tumor suppressor genes (TSGs) methylation in ctDNA of patients with pancreatic cancer (PC) remains largely unclear. METHODS: Patients with PC (n = 43), pancreatic benign diseases (n = 39), and healthy controls (n = 20) were enrolled in the study. Quantitative analysis of methylation pattern of five candidate TSGs including NPTX2, RASSF1A, EYA2, p16, and ppENK in ctDNA was performed by next generation sequencing (NGS). The diagnostic performances of these 5-TSGs methylation were assessed by the operating characteristic (ROC) curve and clinicopathological features correlation analysis. Meanwhile, the changes in methylation levels of these 5-TSGs on the 7th postoperative day were evaluated in 23 PC patients who underwent radical resection. RESULTS: The methylation levels of RASSF1A, EYA2, ppENK and p16 genes in patients with PC were significantly higher than those in healthy controls. EYA2, p16 and ppENK genes showed significantly hypermethylation in PC than those in pancreatic benign diseases. NPTX2, RASSF1A, EYA2, p16 and ppENK genes showed significantly hypermethylation in pancreatic benign diseases than those in healthy controls (P < 0.05). The methylation levels of these 5 candidate TSGs were not correlated with the tumor size, nerve invasion, lymph node metastasis and TNM stage of PC. The AUC of these biomarkers for diagnosis of PC ranged from 0.65 to 0.96. The AUC values of these methylated genes and CpG sites for differentiating malignant and benign pancreatic diseases were ranging from 0.68 to 0.92. Combined the hypermethylated genes improved the detective ability of PC than single gene. The methylation levels of NPTX2, EYA2 and ppENK genes were significantly decreased after radical resection of PC. CONCLUSION: Quantitative analysis of methylation pattern of NPTX2, RASSF1A, EYA2, p16 and ppENK in ctDNA by NGS could be a valuable non-invasive tool for detection and monitoring of PC.

Establishment of a novel signature to predict prognosis and immune characteristics of pancreatic cancer based on necroptosis-related long non-coding RNA.

BACKGROUND: Necroptosis plays an important role in tumorigenesis and tumour progression. Long noncoding RNAs (lncRNAs) have been proven to be regulatory factors of necroptosis in various tumours. However, the real role of necroptosis-related lncRNAs (NRLs) and their potential to predict the prognosis of pancreatic cancer (PC) remain largely unclear. The goal of this study was to identify NRLs and create a predictive risk signature in PC, explore its prognostic predictive performance, and further assess immunotherapy and chemotherapy responses. METHODS: RNA sequencing data, tumour mutation burden (TMB) data, and clinical profiles of 178 PC patients were downloaded from The Cancer Genome Atlas (TCGA) database. NRLs were identified using Pearson correlation analysis. Then, patients were divided into the training set and the validation set at a 1:1 ratio. Subsequently, Cox and LASSO regression analyses were conducted to establish a prognostic NRL signature in the training set and validation set. The predictive efficacy of the 5-NRL signature was assessed by survival analysis, nomogram, Cox regression, clinicopathological feature correlation analysis, and receiver operating characteristic (ROC) curve analysis. Furthermore, correlations between the risk score (RS) and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anticancer drug sensitivity were analysed. Finally, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to validate the 5-NRLs. RESULTS: A 5-NRL signature was established to predict the prognosis of PC, including LINC00857, AL672291.1, PTPRN2-AS1, AC141930.2, and MEG9. The 5-NRL signature demonstrated a high degree of predictive power according to ROC and Kaplan‒Meier curves and was revealed to be an independent prognostic risk factor via stratified survival analysis. Nomogram and calibration curves indicated the clinical adaptability of the signature. Immune-related pathways were linked to the 5-NRL signature according to enrichment analysis. Additionally, immune cell infiltration, immune checkpoint molecules, somatic gene mutations and the half-maximal inhibitory concentration (IC50) of chemotherapeutic agents were significantly different between the two risk subgroups. These results suggested that our model can be used to evaluate the effectiveness of immunotherapy and chemotherapy, providing a potential new strategy for treating PC. CONCLUSIONS: The novel 5-NRL signature is helpful for assessing the prognosis of PC patients and improving therapy options, so it can be further applied clinically.

Solid Pseudopapillary Neoplasm of the Pancreas: A Multi-Institution Study of 118 Cases.

OBJECTIVES: The aim of the study is to summary the clinicopathological characteristics and surgical outcomes of solid pseudopapillary neoplasm (SPN) of the pancreas. METHODS: In this retrospective study, the information of 118 patients with SPN from 3 hospitals were analyzed. RESULTS: A total of 118 patients. The mean age was 30.8 (standard deviation, 14.7) years and the majority were female (n = 95, 80.5%). Sixty-seven patients (56.8%) had clinical symptoms, of which the most common symptom was abdominal pain (49.6%). The mean tumor size was 5.9 (standard deviation, 2.9) cm. Pseudopapillary architecture was the commonest histologic feature, and ß-catenin, CD56, vimentin, neuron-specific enolase, CD10, a1-antitrypsin, cytokeratins showed different degrees of positive expression in immunohistochemical staining. Fourteen patients (11.9%) presented aggressive pathologic behavior, which was correlated to the incomplete tumor capsule. At a median follow-up of 59.2 months, the recurrence rate was 1.8% and the overall 5-year survival rate was 97.7%. CONCLUSIONS: Solid pseudopapillary neoplasm of the pancreas is a potentially low-grade malignant tumor that most frequently found in young females. Its clinical manifestations are nonspecific and the diagnosis mostly depends on pathological examination. Surgical resection is the first choice of treatment for SPN with a good prognosis.

Distribution characteristics and clinical significance of infiltrating T cells in the tumor microenvironment of pancreatic cancer.

Tumor-infiltrating lymphocytes (TILs) are important components of the tumor microenvironment (TME). However, the distribution characteristics of TILs and their significance in pancreatic cancer (PC) remain largely unexplored. The levels of TILs, including the total number of T cells, cluster of differentiation (CD)4+ T cells, CD8+ cytotoxic T lymphocytes (CTLs), regulatory T-cells (Tregs), programmed cell death protein 1+ T cells and programmed cell death ligand 1 (PD-L1)+ T cells, in the TME of patients with PC were detected using multiple fluorescence immunohistochemistry. The associations between the number of TILs and the clinicopathological characteristics were investigated using χ2 tests. In addition, Kaplan-Meier survival and Cox regression analyses were used to assess the prognostic value of these TIL types. Compared with paracancerous tissues, in PC tissues, the proportions of total T cells, CD4+ T cells and CD8+ CTLs were markedly decreased, while those of Tregs and PD-L1+ T cells were significantly increased. The levels of CD4+ T cell and CD8+ CTL infiltrates were inversely associated with tumor differentiation. Higher infiltrates of Tregs and PD-L1+ T cells were closely associated with advanced N and TNM stages. It is important to note that the infiltrates of total T cells, CD4+ T cells, Tregs and PD-L1+ T cells in the TME were independent risk factors for the prognosis of PC. PC was characterized by an immunosuppressive TME with a decrease in the number of CD4+ T cells and CD8+ CTLs, and an increase in the number of Tregs and PD-L1+ T cells. Overall, the number of total T cells, CD4+ T cells, Tregs and PD-L1+ T cells in the TME was a potential predictive marker for the prognosis of PC.

Biliary Tract Exploration After Laparoscopic Left-sided Hepatectomy: A Comparative Study of Left Hepatic Duct Orifice Versus Common Bile Duct Approach.

BACKGROUND: Laparoscopic left-sided hepatectomy (LLH) and additional biliary tract exploration are effective methods to treat left-sided hepatolithiasis (LSH) combined with extrahepatic bile duct stones. Although biliary tract exploration through common bile duct (CBD) incision has been widely accepted, the safety and effectiveness of the left hepatic duct (LHD) orifice approach after LLH is still in debate. METHODS: One hundred and forty-four patients with LSH who underwent LLH and biliary tract exploration in our institution from April 2014 to September 2021 were enrolled in the retrospectively study. They were divided into 3 groups: LHD group (n=67), CBD/T-tube group (n=58), and CBD/PC group (n=19). Patients' demographic characteristics, intraoperative, and postoperative outcomes were retrospectively analyzed. RESULTS: LHD group exhibited a shorter operative time (202.8±42.2 vs. 232.7±47.5 min, P =0.000), time to first bowel movement (2.3±0.5 vs. 2.9±0.7 d, P =0.000) and postoperative hospital stay (7.5±2.1 vs. 9.8±5.2 d, P =0.001) compared with the CBD/T-tube group. The lithotomy time in the LHD group was significantly longer than that in the CBD/T-tube group (33.6±7.3 vs. 29.0±6.3 min, P =0.000) and CBD/PC group (33.6±7.3 vs. 28.7±3.7, P =0.006). Intraoperative blood loss, blood transfusion rate, initial stone clearance rate, and stone recurrence rate all had no significant differences between the 3 groups (all P >0.05). LHD group showed less rate of electrolyte imbalance than that of the CBD/T-tube group (3.0% vs. 19.0%, P =0.004) but it was equivalent to the CBD/PC group ( P >0.05). The type of biliary tract exploration (odds ratio: 5.43, 95% confidence interval: 0.04-0.95, P =0.032) as independent predictors of electrolyte imbalance. No reoperation and mortality occurred in the 3 groups. The conversion rate was comparable among 3 groups (1.5% vs. 1.7% vs. 0, all P >0.05). No significant difference in stone recurrence rate was seen (1.5% vs. 3.4% vs. 0, all P >0.05). CONCLUSION: Biliary tract exploration through LHD orifice after LLH is a safe and effective treatment for selected patients with LSH, with an advantage over the T-tube drainage in the field of operative time, the incidence of electrolyte imbalance, recovery of gastrointestinal function, and postoperative hospital stay.

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods.

Background: As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated. Methods: Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson's correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature's predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied. Results: In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. Conclusion: The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.

Effects of Obstructive Sleep Apnea-Hypopnea Syndrome and Cognitive Function in Ischemic Stroke Based on Linear Regression Equation.

The objective of this research is to study the effect of obstructive sleep apnea-hypopnea syndrome on cognitive function of stroke. Based on linear regression equation and Montreal Cognitive Assessment Scale, the degree of cognitive impairment in OSAHS patients was evaluated and the influencing factors of OSAHS-induced cognitive impairment and the correlation between the degree of OSAHS and cognitive impairment were explored. The results are as follows: about 68% of OSAHS patients have cognitive dysfunction, and the incidence of cognitive dysfunction is positively correlated with OSAHS; cognitive impairment of OSAHS patients was associated with age, obesity, years of schooling, and intermittent nocturnal hypoxia or hypoventilation; the severity of cognitive dysfunction of OSAHS patients was positively correlated with age and obesity but negatively correlated with education level; Logistic regression analysis results showed that there were three factors that were finally entered into the regression equation, namely, LSaO2, BMI, and AHI, and the Logistic regression equation obtained was as follows: LogistP = -0.109X 1 + 0.785X 2 + 1.228X 3. This study helps clinical workers to detect and intervene the impaired cognitive ability of patients with OSAHS early, so as to reduce the incidence and mortality of related complications and improve the quality of life of patients.

Hsa_circ_0046523 Mediates an Immunosuppressive Tumor Microenvironment by Regulating MiR-148a-3p/PD-L1 Axis in Pancreatic Cancer.

Background: Circular RNAs (circRNAs) are a novel type of non-coding RNA, play an important role in the progression of tumors. However, the function and mechanism of circRNAs in regulating immune microenvironment of pancreatic cancer (PC) remain largely unclear. Methods: The effects of hsa_circ_0046523 expression on proliferation, migration and invasion of PC cells were analyzed by CCK8 and Transwell assays. Flow cytometry was used to detect the proportion of CD4+ T cells, CD8+ T cells and Tregs in peripheral blood mononuclear cells (PBMCs) after co-culture, and the apoptosis, depletion and function of CD8+ T cells. The expression levels of immunoregulatory cytokines were detected by enzyme linked immunosorbent assay (ELISA). The dual-luciferase reporter was performed to determine the interaction between hsa_circ_0046523, miR-148a-3p, and PD-L1. Rescue experiments and PD-L1 blocking experiments were employed to investigate whether hsa_circ_0046523 exerts its biological function by miR-148a-3p/PD-L1 in PC. Furthermore, an immunocompetent murine PC model was established to confirm these findings. Results: Hsa_circ_0046523 expression was remarkably upregulated in PC tissues and cell lines. Moreover, high expression of hsa_circ_0046523 was correlated with advanced pathological stage and poorer prognosis. Hsa_circ_0046523 overexpression promoted the proliferation, migration and invasion of PC cells in vitro. Co-culture experiments confirmed that forced expression of hsa_circ_0046523 could decrease the proportion of CD4+ and CD8+ T cells, as well as increase the proportion of Tregs among peripheral blood mononuclear cells (PBMCs). Meanwhile, hsa_circ_0046523 overexpression promoted the apoptosis and exhaustion of CD8+ T cells, inhibited CD8+ T cell function, increased the secretion of immunosuppressive cytokines IL-10 and TGF-ß, and decreased the secretion of immune effector cytokines IFN-γ and IL-2 among PBMCs. Mechanistically, hsa_circ_0046523 exerted its biological function by binding to miR-148a-3p to upregulate PD-L1 expression in PC. Moreover, these immune modulating functions of miR-148a-3p/PD-L1 axis were also confirmed in an immunocompetent murine PC model. Conclusions: Our study suggests that hsa_circ_0046523/miR-148a-3p/PD-L1 regulatory axis mediates PC immunosuppressive microenvironment and these molecules are expected to be new targets for remodeling tumor immune microenvironment of PC.

Adaptation insights from comparative transcriptome analysis of two Opisthopappus species in the Taihang mountains.

Opisthopappus is a major wild source of Asteraceae with resistance to cold and drought. Two species of this genus (Opisthopappus taihangensis and O. longilobus) have been employed as model systems to address the evolutionary history of perennial herb biomes in the Taihang Mountains of China. However, further studies on the adaptive divergence processes of these two species are currently impeded by the lack of genomic resources. To elucidate the molecular mechanisms involved, a comparative analysis of these two species was conducted. Among the identified transcription factors, the bHLH members were most prevalent, which exhibited significantly different expression levels in the terpenoid metabolic pathway. O. longilobus showed higher level of expression than did O. taihangensis in terms of terpenes biosynthesis and metabolism, particularly monoterpenoids and diterpenoids. Analyses of the positive selection genes (PSGs) identified from O. taihangensis and O. longilobus revealed that 1203 genes were related to adaptative divergence, which were under rapid evolution and/or have signs of positive selection. Differential expressions of PSG occurred primarily in the mitochondrial electron transport, starch degradation, secondary metabolism, as well as nucleotide synthesis and S-metabolism pathway processes. Several PSGs were obviously differentially expressed in terpenes biosynthesis that might result in the fragrances divergence between O. longilobus and O. taihangensis, which would provide insights into adaptation of the two species to different environments that characterized by sub-humid warm temperate and temperate continental monsoon climates. The comparative analysis for these two species in Opisthopappus not only revealed how the divergence occurred from molecular perspective, but also provided novel insights into how differential adaptations occurred in Taihang Mountains.

Primary hepatic epithelioid angiomyolipoma: a small case series.

BACKGROUND: Hepatic epithelioid angiomyolipomas (HEAMLs) are rare and usually arise in case reports, and thus, we aimed to study the clinicopathological features, treatment and prognosis of these lesions. METHODS: We identified patients from institutional database with HEAMLs and retrospectively collected clinical data. RESULTS: Of 12 patients, 10 were females, and the median age was 49 years. A liver mass was found on chance upon routine health screening in nine patients. Imaging features included clear border (9/12), internal heterogeneity (8/12), arterial enhancement (12/12), fat (5/12), intra-tumour vessel (3/12), draining hepatic vein (2/12) and pseudocapsule (1/12). The preoperative diagnoses contained HEAML (n = 5), hepatocellular carcinoma (n = 6), and hepatic cystadenocarcinoma (n = 1). All cases had received surgery and obtained a negative margin. All specimens showed positive findings for HMB-45 and Melan A. No tumour recurrence or mortality was described with a mean follow-up time of 23.5 months. CONCLUSIONS: HEAML is a low potential malignancy tumour that frequently appears in middle-aged females. It has nonspecific symptoms and may present special imaging features including intra-tumour vessel, early draining hepatic vein and lack of a pseudo capsule. The lesion is confirmed by pathological and immunohistochemical findings. Surgery and subsequent long-term follow-up are the most appropriate management approaches.

Organ-Sparing Pancreatectomy for Benign or Low-Grade Malignant Pancreatic Tumors: A Single-Center Experience with 101 Consecutive Patients.

BACKGROUND Pancreaticoduodenectomy (PD) and distal pancreatectomy with splenectomy (DPS) are considered the standard procedures for pancreatic lesions. However, long-term metabolic consequences of PD and DPS applied for benign or low-grade malignant tumors need to be addressed. This study aimed to investigate the short- and long-term outcomes of organ-sparing pancreatectomy for benign or low-grade malignant pancreatic tumors in our institution. MATERIAL AND METHODS The clinical data of 101 patients with benign or low-grade malignant pancreatic tumors who underwent organ-sparing pancreatectomy from January 2009 to September 2021 were retrospectively analyzed, including 40 tumor enucleations (EN), 22 central pancreatectomies (CP), 25 spleen-preserving distal pancreatectomies (SPDP), 7 pylorus-preserving pancreaticoduodenectomies (PPPD) and 7 duodenum-preserving pancreatic head resections (DPPHR). RESULTS The mean operative time, intraoperative blood loss, and length of hospital stay were 182.9±74.6 min, 191.9±127.8 mL, and 11.6±8.1 days, respectively. EN had the shortest operative time, while DPPHR had the longest operative time. The mean intraoperative blood loss of DPPHR and PPPD was significantly greater than the others (all P<0.05). The length of hospital stay of PPPD was longest. The overall morbidity was 33.6%. The reoperation rate was 1.0% and there was no mortality. The incidence of pancreatic endocrine insufficiency and exocrine insufficiency were 5.9% and 6.9%, respectively. None patients had tumor recurrence during the follow-up period. CONCLUSIONS Organ-sparing pancreatectomy is associated with acceptable perioperative risk and postoperative complications and better long-term outcomes in the aspects of preservation of function and curability in benign or low-grade malignant pancreatic tumors.

Variation in Plastome Sizes Accompanied by Evolutionary History in Monogenomic Triticeae (Poaceae: Triticeae).

To investigate the pattern of chloroplast genome variation in Triticeae, we comprehensively analyzed the indels in protein-coding genes and intergenic sequence, gene loss/pseudonization, intron variation, expansion/contraction in inverted repeat regions, and the relationship between sequence characteristics and chloroplast genome size in 34 monogenomic Triticeae plants. Ancestral genome reconstruction suggests that major length variations occurred in four-stem branches of monogenomic Triticeae followed by independent changes in each genus. It was shown that the chloroplast genome sizes of monogenomic Triticeae were highly variable. The chloroplast genome of Pseudoroegneria, Dasypyrum, Lophopyrum, Thinopyrum, Eremopyrum, Agropyron, Australopyrum, and Henradia in Triticeae had evolved toward size reduction largely because of pseudogenes elimination events and length deletion fragments in intergenic. The Aegilops/Triticum complex, Taeniatherum, Secale, Crithopsis, Herteranthelium, and Hordeum in Triticeae had a larger chloroplast genome size. The large size variation in major lineages and their subclades are most likely consequences of adaptive processes since these variations were significantly correlated with divergence time and historical climatic changes. We also found that several intergenic regions, such as petN-trnC and psbE-petL containing unique genetic information, which can be used as important tools to identify the maternal relationship among Triticeae species. Our results contribute to the novel knowledge of plastid genome evolution in Triticeae.

MicroRNA-148a-3p suppresses epithelial-to-mesenchymal transition and stemness properties via Wnt1-mediated Wnt/ß-catenin pathway in pancreatic cancer.

Although miR-148a-3p has been reported to function as a tumour suppressor in various cancers, the molecular mechanism of miR-148a-3p in regulating epithelial-to-mesenchymal transition (EMT) and stemness properties of pancreatic cancer (PC) cells remains to be elucidated. In the present study, we demonstrated that miR-148a-3p expression was remarkably down-regulated in PC tissues and cell lines. Moreover, low expression of miR-148a-3p was associated with poorer overall survival (OS) in patients with PC. In vitro, gain-of-function and loss-of-function experiments showed that miR-148a-3p suppressed EMT and stemness properties as well as the proliferation, migration and invasion of PC cells. A dual-luciferase reporter assay demonstrated that Wnt1 was a direct target of miR-148a-3p, and its expression was inversely associated with miR-148a-3p in PC tissues. Furthermore, miR-148a-3p suppressed the Wnt/ß-catenin pathway via down-regulation of Wnt1. The effects of ectopic miR-148a-3p were rescued by Wnt1 overexpression. These biological functions of miR-148a-3p in PC were also confirmed in a nude mouse xenograft model. Taken together, these findings suggest that miR-148a-3p suppresses PC cell proliferation, invasion, EMT and stemness properties via inhibiting Wnt1-mediated Wnt/ß-catenin pathway and could be a potential prognostic biomarker as well as a therapeutic target in PC.

Evolutionary patterns of plastome uncover diploid-polyploid maternal relationships in Triticeae.

To investigate the diploid-polyploid relationships and the role of maternal progenitors in establishment of polyploid richness in Triticeae, 35 polyploids representing almost all genomic constitutions together with 48 diploid taxa representing 20 basic genomes in the tribe were analyzed. Phylogenomic reconstruction, genetic distance matrix, and nucleotide diversity patterns of plastome sequences indicated that (1) The maternal donor of the annual polyploid species with the U- and D-genome are related to extant Ae. umbellulata and Ae. tauschii, respectively. The maternal donor to the annual polyploid species with the S-, G-, and B-genome originated from the species of Sitopsis section of the genus Aegilops. The annual species with the Xe-containing polyploids were donated by Eremopyrum as the female parent; (2) Pseudoroegneria and Psathyrostachys were the maternal donor of perennial species with the St- and Ns-containing polyploids, respectively; (3) The Lophopyrum, Thinopyrum and Dasypyrum genomes contributed cytoplasm genome to Pseudoroegneria species as a result of incomplete lineage sorting and/or chloroplast captures, and these lineages were genetically transmitted to the St-containing polyploid species via polyploidization; (4) There is a reticulate relationship among the St-containing polyploid species. It can be suggested that genetic heterogeneity might associate with the richness of the polyploids in Triticeae.

Intracoronary pressure gradient measurement in acute myocardial infarction patients with the no-reflow phenomenon during primary percutaneous coronary intervention.

BACKGROUND: Various experimental and clinical studies have reported on coronary microcirculatory dysfunction ("no-reflow" phenomenon). Nevertheless, pathogenesis and effective treatment are yet to be fully elucidated. This study aimed to measure the intracoronary pressure gradient in the no-reflow artery during emergent percutaneous coronary intervention and explore the potential mechanism of no-reflow. METHODS: From September 1st, 2018 to June 30th, 2019, intracoronary pressure in acute myocardial infarction patient was continuously measured by aspiration catheter from distal to proximal segment in the Department of Coronary Care Unit, Tianjin Chest Hospital, respectively in no-reflow arteries (no-reflow group) and arteries with thrombolysis in myocardial infarction-3 flow (control group). At least 12 cardiac cycles were consecutively recorded when the catheter was pulled back. The forward systolic pressure gradient was calculated as proximal systolic pressure minus distal systolic pressure. Comparison between groups was made using the Student t test, Mann-Whitney U-test or Chi-square test, as appropriate. RESULTS: Intracoronary pressure in 33 no-reflow group and 26 in control group were measured. The intracoronary forward systolic pressure gradient was -1.3 (-4.8, 0.7) and 3.8 (0.8, 8.8) mmHg in no-reflow group and control group (Z = -3.989, P < 0.001), respectively, while the forward diastolic pressure gradient was -1.0 (-3.2, 0) and 4.6 (0, 16.5) mmHg in respective groups (Z = -3.851, P < 0.001). Moreover, the intracoronary forward pressure gradient showed significant difference between that before and after nicorandil medication (Z = -3.668, P < 0.001 in systolic pressure gradient and Z = -3.530, P < 0.001 in diastolic pressure gradient). CONCLUSIONS: No reflow during emergent coronary revascularization is significantly associated with local hemodynamic abnormalities in the coronary arteries. Intracoronary nicorandil administration at the distal segment of a coronary artery with an aspiration catheter could improve the microcirculatory dysfunction and resume normal coronary pressure gradient. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov (No. NCT03600259).

The design of hollow PdO-Co3O4 nano-dodecahedrons with moderate catalytic activity for Li-O2 batteries.

Hollow PdO-Co3O4 nano-dodecahedrons with moderate catalytic activity were designed as electrocatalysts for Li-O2 batteries, and not only reduce the overpotentials effectively but also improve the reversibility of the ORR and OER, and cycle for more than 90 cycles stably with extremely low overpotentials.

The interaction between miR­148a and DNMT1 suppresses cell migration and invasion by reactivating tumor suppressor genes in pancreatic cancer.

DNA methylation is an epigenetic mechanism that cells use to control gene expression, which serves an important role in tumorigenesis. DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of the pattern of DNA methylation. Overexpression of DNMT1 is observed in numerous malignant tumors, including pancreatic cancer, and results in silencing of several key tumor suppressor genes (TSGs). Recent studies have suggested that microRNAs (miRNAs/miRs) contribute to the regulation of DNMT1 expression, and promoter hypermethylation caused by DNMT1 overexpression is associated with the dysfunction of some miRNAs. The present study aimed to reveal the interaction between miR­148a and DNMT1, and its effects on cell proliferation, migration and invasion of pancreatic cancer cells. Initially, the expression levels of DNMT1 and miR­148a were detected in pancreatic cancer tissues and AsPC­1 cells by reverse transcription­quantitative polymerase chain reaction (PCR). Secondly, the regulatory effects of DNMT1 on miR­148a were evaluated using methylation­specific PCR. Furthermore, bioinformatics analysis and dual luciferase reporter assay were used to verify the target relationship between miR­148a and DNMT1. Finally, in vitro rescue experiments were conducted to evaluate the effects of miR­148a on the expression of TSGs and the malignant phenotype in AsPC­1 cells. The results demonstrated that DNMT1 was aberrantly upregulated in pancreatic cancer, and was responsible for hypermethylation of the miR­148a promoter. Furthermore, DNMT1 was revealed as a direct target of miR­148a by dual luciferase reporter assay, and restoration of miR­148a could reactivate TSGs, such as p16, preproenkephalin and Ras association domain family member 1 by targeting DNMT1 in the AsPC­1 pancreatic cancer cell line. These results indicated that an interaction exists between miR­148a and DNMT1 in pancreatic cancer. Notably, miR­148a overexpression significantly inhibited cell proliferation, migration and invasion in AsPC­1 cells. Therefore, miR­148a may serve as a novel therapeutic target for the treatment of pancreatic cancer.

Isolated Langerhans cell histiocytosis of the spleen: A case report.

RATIONALE: Langerhans cell histiocytosis (LCH) is a relatively rare disorder characterized by the proliferation of abnormal Langerhans cells. Splenic involvement usually presents in children with multisystem LCH, and isolated LCH of the spleen is a very rare disease. Herein, we report a case of isolated splenic LCH in an adult man. PATIENT CONCERNS: We report a case of isolated splenic LCH that first manifested with recurrent left upper abdominal pain. DIAGNOSIS: Unenhanced CT revealed multiple nodular lesions located at the spleen. Magnetic resonance imaging speculated that these lesions were lymphomas. On the basis of histopathological and immunohistochemical findings, the diagnosis of isolated splenic LCH was confirmed. INTERVENTION AND OUTCOMES: The patient underwent splenectomy. Histopathologic examination revealed the proliferation of Langerhans cell. Immunohistochemical staining revealed that cells of the tumor were positive for S-100, CD1a, CD45RO, and Vimentin. The patient is alive without recurrence 9 years after operation. LESSONS: Isolated LCH of the spleen may have a favorable prognosis and splenectomy is an effective therapeutic method.

Laparoscopic common bile duct exploration in patients with previous upper abdominal surgery.

BACKGROUND: Although patients with previous upper abdominal surgery are no longer considered as a contraindication in laparoscopic surgery, laparoscopic common bile duct exploration (LCBDE) for these patients is still controversial. The aim of this study was to evaluate the safety and effectiveness of LCBDE for patients with previous upper abdominal surgery. METHODS: Two hundred and seventeen patients with common bile duct stones who underwent LCBDE in our institution from January 2010 to September 2017 were enrolled in the retrospective study. They were divided into two groups: group A, with previous upper abdominal surgery (n = 50) and group B, without previous upper abdominal surgery (n = 167). Patients' demographic, intraoperative, and postoperative outcomes were retrospectively analyzed. RESULTS: Group A exhibited a longer operative time compared to group B (179.7 ± 61.5 vs. 156.0 ± 46.8 min, p = 0.014). There was no significant difference in intraoperative blood loss (123.9 ± 99.5 vs. 99.5 ± 84.7 mL, p = 0.087), postoperative hospital stay (7.4 ± 2.6 vs. 6.8 ± 2.3 d, p = 0.193), and overall complication rate (8.0 vs. 5.4%, p = 0.732) between the two groups. There was no mortality in both groups. The initial stone clearance rate showed no significant difference between the two groups (98.0 vs. 98.2%, p = 1.000), and the final stone clearance rate was 100% in both groups (p = 1.000). The stone recurrence rate had no significant difference between the two groups (2.0 vs. 2.4%, p = 1.000). The conversion rate was comparable between group A and group B (6.0 vs. 4.8%, p = 0.718). CONCLUSIONS: LCBDE is a safe and feasible procedure for patients with previous upper abdominal surgery. The keys of this procedure are carefully separating the adhesions and clearly exposing the common bile duct, and using a variety of methods to remove the stones.

The role of central pancreatectomy in pancreatic surgery: a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to compare the clinical outcomes of central pancreatectomy (CP) with distal pancreatectomy (DP) and pancreaticoduodenectomy (PD). METHODS: A systematic literature research in PubMed/Medline, Embase and Cochrane Library was performed to identify articles reporting CP from January 1983 to November 2017. RESULTS: Fifty studies with 1305 patients undergoing CP were identified. The overall morbidity, mortality, pancreatic fistula (PF) rate and reoperation rate was 51%, 0.5%, 35% and 4% respectively. Endocrine and exocrine insufficiency were occurred in 4% and 5% of patients after CP. Meta-analysis of CP versus DP favored CP with regard to less blood loss (WMD = -143.4, P = 0.001), lower rates of endocrine (OR = 0.13, P < 0.001) and exocrine insufficiency (OR = 0.38, P < 0.001). CP was associated with higher morbidity and PF rate. In comparison with PD, CP had a lower risk of endocrine (OR = 0.14, P < 0.001) and exocrine insufficiency (OR = 0.14, P < 0.001), but a higher PF rate (OR = 1.6, P = 0.015). CONCLUSIONS: CP maintains pancreatic endocrine and exocrine function better than DP and PD, but is associated with a higher PF rate.