hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1-mediated THBS1 transcription.

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.

CA19­9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy.

BACKGROUND: Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 - 9 (CA19-9) and carbohydrate antigen 72 - 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy. METHODS: A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan-Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients. RESULTS: Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS. CONCLUSION: Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma.

BACKGROUND: Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification. METHODS: RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa_circ_0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa_circ_0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa_circ_0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa_circ_0007919, FOXA1, TET1 and the LIG1 promoter. RESULTS: We identified a highly expressed circRNA, hsa_circ_0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa_circ_0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa_circ_0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa_circ_0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa_circ_0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa_circ_0007919. CONCLUSIONS: Hsa_circ_0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa_circ_0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC.

Plasma exosome-derived circGAPVD1 as a potential diagnostic marker for colorectal cancer.

BACKGROUND: Although circular RNAs (circRNAs) have recently garnered interest as disease markers, they have been relatively poorly studied as a biomarker in colorectal cancer (CRC). In this study, we aimed to screen the exosome-derived circRNAs in CRC and explore their potential as diagnostic and prognostic biomarkers of CRC METHODS: Exosomes were extracted from the plasma using a kit and validated by immunoblotting, transmission electron microscopy, and particle size analysis. The microarray datasets were employed to identify differentially-expressed circRNAs from plasma exosomes. Real-time quantitative reverse transcription PCR (RT-qPCR) verified the results of the microarray analysis, and Receiver operating characteristic (ROC) curve revealed the diagnostic ability of a single circRNA. The Starbase combined with microT, miRmap, and RNA22 were used to establish a circRNA-miRNA-mRNA network. Gene ontology, Kyoto Encyclopedia of Genes, Genomes pathway enrichment analysis, and Gene Set Enrichment Analysis were applied to determine potential functions of the identified mRNAs RESULTS: Comparing the microarray of plasma exosome-derived circRNAs and the microarray downloaded from the GEO database, 15 candidate circRNAs with up-regulated expression were identified. RT-qPCR verified that hsa_circ_0003270 (circGAPVD1) was upregulated in CRC plasma exosomes. ROC analysis showed that circGAPVD1 in plasma exosomes has potential diagnostic value for CRC. The sensitivity and specificity of circGAPVD1 in the diagnosis of CRC were found to be 75.64 and 71.79%, respectively (area under ROC = 0.7662). Furthermore, the lymph node metastasis and TNM staging of patients were positively correlated with high expression of circGAPVD1. Combined with the ENCORI database and GEO datasets, we identified the circGAPVD1-related ceRNA network. The enrichment analysis revealed that key nodes in the ceRNA network participate in many important signaling pathways such as protein post-translational modifications CONCLUSION: Our results revealed the diagnostic efficiency of circGAPVD1 in plasma exosomes. The highly expressed circGAPVD1 is expected to be a novel diagnostic marker for CRC.

LINC01615 maintains cell survival in adaptation to nutrient starvation through the pentose phosphate pathway and modulates chemosensitivity in colorectal cancer.

Numerous mechanisms involved in promoting cancer cell survival under nutrient starvation have been described. Long noncoding RNAs (lncRNAs) have emerged as critical players in colorectal cancer (CRC) progression, but the role of lncRNAs in the progression of CRC under nutrient starvation has not been well clarified. Here, we identified a lncRNA, LINC01615, that was significantly upregulated in response to serum starvation. LINC01615 can contribute to the adaptation of CRC cells to serum-deprived conditions and enhance cell survival under similar conditions. LINC01615 activated the pentose phosphate pathway (PPP) under serum starvation, manifested as decreased ROS production and enhanced nucleotide and lipid synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a key rate-limiting enzyme of the PPP, and LINC01615 promoted G6PD expression by competitively binding with hnRNPA1 and facilitating G6PD pre-mRNA splicing. Moreover, we also found that serum starvation led to METTL3 degradation by inducing autophagy, which further increased the stability and level of LINC01615 in a m6A-dependent manner. LINC01615 knockdown combined with oxaliplatin achieved remarkable antitumor effects in PDO and PDX models. Collectively, our results demonstrated a novel adaptive survival mechanism permitting tumor cells to survive under limiting nutrient supplies and provided a potential therapeutic target for CRC.

Heterotopic 4T1 breast cancer transplantation induces hippocampal inflammation and depressive-like behaviors in mice.

Cancer and its accompanying treatments can lead to numerous physical and emotional concerns, including subclinical or clinical depression and anxiety, which could significantly impact one's well-being, quality of life, and survival. A large number of studies have elucidated that neuroinflammation is associated with depression. Here, we report the hippocampal pathological changes and depressive behaviors of a heterotopic breast cancer transplantation mouse model; hence, a heterotopic 4T1 breast cancer transplantation mouse model was established. Assessment of cognitive and locomotive functions of the experimental animals was conducted using open- and closed-field tests, including a tail suspension test. Expression levels of monoaminergic system markers, brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines, and nuclear factor-kappa B (NFκB) in the hippocampus and serum were detected using immunochemistry and western and enzyme-linked immunosorbent assay analysis. A comparison of the differences between model and control animals was performed. As per our findings, 4T1 tumor-bearing mice displayed cancer-related anorexia/cachexia with significant reductions in the travel distance and the total number of squares crossed in the open- and closed-field tests. Additionally, the 4T1 tumor-bearing mice withstood a more extended period of immobility during the tail suspension test. Immunohistochemistry studies revealed reduced levels of serotonin, norepinephrine, and BDNF in the hippocampus and serum. Elevated levels of NFκB and pro-inflammatory cytokines in the hippocampus were also observed. These findings suggest that hippocampal inflammation may have played an important role in the neurological function and depressive behavior in heterotopic 4T1 breast cancer transplantation mice.

Effect of total laparoscopic versus open pancreaticoduodenectomy on short-term and oncological outcomes: a single-institution comparative study.

BACKGROUND: Recently, the efficacy and outcomes of total laparoscopic pancreaticoduodenectomy (TLPD) have been well established; however, specific data regarding the clinical outcomes of total laparoscopic versus open pancreaticoduodenectomy (OPD) are still limited. The present study aims to directly compare the clinical and oncological outcomes following TLPD versus OPD at a single institution. METHODS: The clinical data of 127 consecutive patients who underwent TLPD (n = 69) and OPD (n = 58) and were admitted to our department between January 2017 and June 2019 were analysed retrospectively. The short-term and oncological outcomes in the two groups were compared. RESULTS: Compared to the OPD group, the TLPD group experienced a longer operative time [(399.1 ± 77.9) min vs. (247.9 ± 61.8) min] and significantly earlier oral intake [5.0 (IQR, 4.0-6.0) days vs. 8.0 (IQR, 6.0-8.0) days], earlier postoperative exhaust [3.0 (IQR, 3.0-4.0) days vs. 4.0 (IQR, 4.0-4.5) days], earlier out-of-bed activity [2.0 (IQR, 1.0-2.3) days vs. 3.0 (IQR, 2.0-3.0) days], earlier nasogastric tube removal [5.5 (IQR, 4.0-7.8) days vs. 8.0 (IQR, 6.0-11.0) days] and shorter postoperative length of hospital stay [14.0 (IQR, 11.0-21.0) days vs. 16.0 (IQR, 12.0-25.0) days] (P < 0.05). The estimated blood loss [(334.4 ± 157.8) mL vs. (344.6 ± 259.1) mL], presence of clinically relevant postoperative pancreatic fistula (grade B/C, 5.8% vs. 5.2%) and the overall complication rate (23.2% vs. 25.9%) did not significantly differ between the two groups (P > 0.05). Regarding the oncological outcomes, there were no significant differences in pathological types, tumour size, lymph nodes harvested, tumour stages or resection margins, or in overall survival (OS) (56.9% vs. 53.2%, P = 0.704) or progression-free survival (PFS) (48.3% vs. 46.8%, P = 0.881) with a median 26-month follow-up. CONCLUSION: TLPD is a safe and feasible procedure in select patients after a certain learning curve. Compared with OPD, TLPD has equivalent short-term and oncological outcomes and offers the advantages of faster postoperative recovery and shorter length of hospital stay.

CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner.

BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated. METHODS: Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC-MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis. RESULTS: We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice. CONCLUSIONS: The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.

RNA modifications act as regulators of cell death.

Currently, more than one hundred types of RNA modifications have been found, and many of these modifications are reversible and dynamically regulated. RNA modifications can regulate RNA stability and translation and are thus involved in multiple biological activities. Recently, RNA modifications have been shown to have important roles in the regulation of cell death. Cell death is a critical process that maintains tissue homoeostasis and is regulated by multiple pathways in response to specific stimuli. In this review, we summarize the current understanding of the roles of RNA modifications in cell death mediation and discuss the prospects of such research.Abbreviations: m6A, N6-Methyladenosine; m6Am, N6,2'-O-Dimethyladenosine; m1A, N1-Methyladenosine; m5C, 5-Methylcytosine; hm5C, 5-Hydroxymethylcytosine; Ψ, pseudouridine; A-to-I, adenosine-to- inosine; hnRNPs, heterogeneous nuclear ribonucleoproteins; MOMP, mitochondrial outer membrane permeabilization; DD, death domain; DISC, death-inducing signalling complex; DED, death effector domain; FADD, FAS-associated protein with the death domain; TRADD, TNF receptor-associated protein with death domain; CMA, chaperone- mediated autophagy; PE, phosphatidylethanolamine; AD, alzheimer's disease; AML, acute myeloid leukaemia; miR, microRNA; 6-OHDA, 6-hydroxydopamine hydrochloride; R-2HG, R-2-hydroxyglutarate; IRES, internal ribosome entry site; BMSCs, bone-derived mesenchymal stem cells; NPCs, nucleus pulposus cells; HsCG, human chorionic gonadotropin; snoRNAs, small nucleolar RNAs; ER, endoplasmic reticulum; lncRNAs, long noncoding RNAs; TNM, tumour-node-metastasis.

Analysis of the Submicrostructural Deformation of Amphibole in a Ductile Shear Zone Based on the TEM Technique.

Deformed amphibole in the plagioclase amphibolite mylonite of the Guandi Complex, Xishan, Beijing, is the research object in this study. The amphibole nanodeformation under the middle crust was analyzed using microstructural analysis and high-resolution transmission electron microscopy (TEM). Microscope observations show that the amphibolite deformations in the plagioclase amphibolite mylonite are δ and σ type porphyroclasts, and the porphyroclast tail is composed of new long-columnar crystals. Using transmission electron microscopy (TEM, and this acronyms would be defined only once), the authors observed the nanodeformation characteristics of the amphibole porphyroclast core and mantle. Dislocation tangles are dominant in the porphyroclast core, and inside the new crystal, there is little or no dislocation. Swelled new crystals surrounded by dislocation can be observed in the transition zone between the porphyroclasts and new crystals. The deformed amphibole microstructure and submicrostructure represent typical brittle-ductile transitional deformation. The deformation process can be divided into two stages: the disordered dislocation increment stage and the dislocation reduction and ordering stage. Crystalline plastic deformation occurs in the amphibole in the plagioclase amphibolite mylonite of the Xishan area, Beijing. The crystalline plastic deformation temperature in amphiboles is higher than that in plagioclase.

Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons.

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.

SMYD2 suppresses APC2 expression to activate the Wnt/ß-catenin pathway and promotes epithelial-mesenchymal transition in colorectal cancer.

Cancer metastasis is a significant challenge in colorectal cancer (CRC) therapy. SET and MYND domain-containing protein 2 (SMYD2) is highly expressed in multiple cancers but is rarely studied in CRC. This study aims to identify whether abnormal expression of SMYD2 is associated with cancer metastasis in CRC. In this study, we demonstrated that SMYD2 not only promoted cell proliferation but also increased the metastatic ability of CRC. The expression of adenomatous polyposis coli 2 (APC2), an inhibitor of the Wnt/ß-catenin pathway, was suppressed by SMYD2 overexpression. Overexpression of SMYD2 activated the Wnt/ß-catenin pathway and then induced the epithelial-mesenchymal transition (EMT) program in CRC. Mechanistically, low APC2 expression in CRC cells was due to SMYD2-mediated DNA methylation modification. This modification might require synergism with DNMT1. In summary, our study provides new insights into SMYD2-related transcriptional regulation patterns and indicates that SMYD2 could be a potential therapeutic target for CRC patients.

CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition.

Cullin-1 (CUL1) is an important factor for tumor growth and a potential therapeutic target for breast cancer therapy, but the molecular mechanism in triple-negative breast cancer (TNBC) is unknown. In the present study, CUL1 shRNA was transfected into BT549 and MDA-MB-231 breast cancer cells. Cell morphology, adhesion, invasion, and migration assays were carried out in the CUL1 knockdown cells. Additionally, protein expression levels of epithelial-mesenchymal transition (EMT)-related factors, Akt phosphorylation at S473 (pAkt), glycogen synthase kinase-3ß phosphorylation at ser9 (pGSK3ß), cytoplasmic and nuclear ß-catenin, and epidermal growth factor receptor phosphorylation at Tyr1068 (pEGFR) were detected by Western blot analysis. CUL1 knockdown significantly suppressed the adhesion, invasion and migration capabilities of the cells, and decreased the expression of Snail1/2, ZEB1/2, Twist1/2, Vimentin, and increased the expression of Cytokeratin 18 (CK18). Moreover, CUL1 knockdown significantly downregulated the phosphorylated levels of Akt, GSK3ß, and EGFR, inhibiting the translocation of ß-catenin from the cytoplasm to the nucleus. The results indicate that CUL1 knockdown prohibited the metastasis behaviors of breast cancer cells through downregulation (dephosphorylation) of the EMT signaling pathways of EGFR and Akt/GSK3ß/ß-catenin in breast cancer. These results strongly suggested that reinforcement of the EMT might be a key for CUL1 to accelerate TNBC metastasis.

Changes of serum lipopolysaccharide, inflammatory factors, and cecal microbiota in obese rats with type 2 diabetes induced by Roux-en-Y gastric bypass.

OBJECTIVES: Previous studies have shown that Roux-en-Y gastric bypass (RYGB) leads to rapid regression of obesity and type 2 diabetes (T2D). However, the underlying mechanism remains unclear. This study aimed to investigate the effect of RYGB on serum lipopolysaccharide (LPS), interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), and cecal microbiota in obese rats with T2D. METHODS: Obese Sprague-Dawley rats with T2D were randomly divided into RYGB diabetes operation (DO; n = 8), diabetes sham operation (DS; n = 8), and diabetic control (DC; n = 8) groups. Healthy Sprague-Dawley rats were grouped as normal control (NC; n = 8). Fasting plasma glucose and body weight were measured. The levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. The rats were sacrificed 12 wk after operation. Subsequently, a superior mesenteric venous blood sample was taken to measure serum LPS levels by enzyme-linked immunosorbent assay. The cecal contents of the DO and DS groups were taken to extract metagenomic DNA per the genomic DNA standardization procedure. The V4 region of the 16 S rRNA was sequenced with the Illumina Hiseq sequencing platform to compare the structure and relative abundance of cecal microbiota between the DO and DS groups. RESULTS: Twelve weeks after operation in the DO group, fasting plasma glucose and body weight showed a significant decrease (P < 0.05). Moreover, the levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were obviously decreased (P < 0.05). A change in the LPS level of superior mesenteric venous blood also revealed a dramatic decrease (P < 0.05). Additionally, RYGB resulted in a shift of cecal microbiota in obese rats with T2D. CONCLUSIONS: Hypoglycemic effects after RYGB may be associated with improved levels of LPS, IL-1, IL-6, and TNF-α. Changes in the structure of cecal microbiota may also play an important role.

[Status of diagnosis and management of acute appendicitis in 2017: a national multi-center retrospective study].

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS: The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.

[Surgical site infection following abdominal surgery in China: a multicenter cross-sectional study].

OBJECTIVE: To determine the incidence of surgical site infection (SSI) after abdominal surgery and to further evaluate the related risk factors of SSI in China. METHODS: The multicenter cross-sectional study collected clinical data of all adult patients who underwent abdominal surgery from May 1, 2018 to May 31, 2018 in 30 domestic hospitals, including basic information, perioperative parameters, and incisional microbial culture results. The primary outcome was the incidence of SSI within postoperative 30 days. SSI was classified into superficial incision infection, deep incision infection, and organ/gap infection according to the US Centers for Disease Control and Prevention (CDC) criteria. The secondary outcome variables were ICU stay, postoperative hospital stay, total hospital stay, 30-day mortality and treatment costs. Multivariate logistic regression was used to analyze the risk factors of SSI. RESULTS: A total of 1666 patients were enrolled in the study, including 263 cases of East War Zone Hospital of PLA, 140 cases of Affiliated Hospital of Qingdao University, 108 cases of The First Affiliated Hospital of Nanchang University, 87 cases of Central War Zone Hospital of PLA, 77 cases of West China Hospital, 74 cases of Guangdong General Hospital, 71 cases of Chenzhou First People's Hospital, 71 cases of Zigong First People's Hospital, 64 cases of Zhangjiagang First People's Hospital, 56 cases of Nanyang City Central Hospital, 56 cases of Lanzhou General Hospital of Lanzhou Military Command, 56 cases of Shandong Provincial Hospital, 52 cases of Shangqiu First People's Hospital, 52 cases of People's Hospital of Xinjiang Uygur Autonomous Region, 48 cases of The Second Xiangya Hospital of Central South University, 48 cases of Chinese PLA General Hospital, 44 cases of Affiliated Hospital of Xuzhou Medical University, 38 cases of Hunan Province People's Hospital, 36 cases of Dongguan Kanghua Hospital, 30 cases of Shaoxing Central Hospital, 30 cases of Northern Jiangsu People's Hospital, 29 vases of The First Affiliated Hospital of Zhengzhou University, 27 cases of General Hospital of Tianjin Medical University, 22 cases of Zigong Fourth People's Hospital, 21 cases of The Second Hospital of University of South China, 18 cases of Tongji Hospital, 15 cases of Nanchong Central Hospital, 12 cases of The 901th Hospital of PLA, 11 cases of Hunan Cancer Hospital, 10 cases of Lanzhou University Second Hospital. There were 1019 males and 647 females with mean age of (56.5±15.3) years old. SSI occurred in 80 patients (4.8%) after operation, including 39 cases of superficial incision infection, 16 cases of deep incision infection, and 25 cases of organ/interstitial infection. Escherichia coli was the main pathogen of SSI, and the positive rate was 32.5% (26/80). Compared with patients without SSI, those with SSI had significantly higher ICU occupancy rate [38.8%(31/80) vs. 13.9%(220/1586), P<0.001], postoperative hospital stay (median 17 days vs. 7 days, P<0.001) and total hospital stay (median 22 days vs. 13 days, P<0.001), and significantly higher cost of treatment (median 75 000 yuan vs. 44 000 yuan, P<0.001). Multivariate analysis showed that male rise(OR=2.110, 95%CI:1.175-3.791, P=0.012), preoperative blood glucose level rise(OR=1.100, 95%CI: 1.012-1.197, P=0.026), operative time (OR=1.006, 95%CI:1.003-1.009, P<0.001) and surgical incision grade (clean-contaminated incision:OR=10.207, 95%CI:1.369-76.120, P=0.023; contaminated incision: OR=10.617, 95%CI:1.298-86.865, P=0.028; infection incision: OR=20.173, 95%CI:1.768-230.121, P=0.016) were risk factors for SSI; and laparoscopic surgery (OR=0.348, 95%CI:0.192-0.631, P=0.001) and mechanical bowel preparation(OR=0.441,95%CI:0.221-0.879, P=0.020) were protective factors for SSI. CONCLUSIONS: The incidence of postoperative SSI in patients with abdominal surgery in China is 4.8%. SSI can significantly increase the medical burden of patients. Preoperative control of blood glucose and mechanical bowel preparation are important measures to prevent SSI.

microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.

The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3' untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR, resulting in a downregulated epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator-epidermal growth factor (EGF)-can rescue the proliferation and migration suppression induced by miR-874 overexpression, and the rescue effects of the EGF were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a negative regulator of the DOR that can suppress tumor proliferation and metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential target for HCC treatment.

Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer.

Ubiquitin specific peptidase 9, X-linked (USP9X), a significant regulatory protease in protein ubiquitination, has been proven to act as a proto-oncogene in several types of cancers, such as cervix, colon, breast, brain and lung cancers. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to its high invasive and metastatic abilities. Nevertheless, whether USP9X acts as a proto-oncogene or a tumor-suppressor gene in PDAC is controversial and the mechanism of metastasis remains unknown. The present study focused on the effect of USP9X on the migration, invasion and apoptosis of PADC cells. We analyzed the expression of USP9X in pancreatic cancer tissues of different pathologic grades by immunohistochemical analysis. USP9X expression in the pancreatic cancer tissues was markedly increased in contrast to that noted in the adjacent non-tumor tissues. USP9X expression in PANC-1 cells was downregulated after transfection of shRNA-USP9X. Knockdown of endogenous USP9X expression evidently inhibited the migration and invasion of PANC-1 cells, and promoted cell apoptosis. Meanwhile, expression levels of Snail, Twist, N-cadherin and vimentin were downregulated. E-cadherin expression was negatively correlated with USP9X expression and the expression of survivin was also downregulated in the PANC-1 cells. In brief, USP9X promoted the migration and invasion of PANC-1 cells probably by provoking epithelial-mesenchymal transition, and also inhibited apoptosis. We believe that USP9X is a major oncogene that may play a significant role in the treatment and prognosis of PDAC.

Geochemical Characteristics and Origins of the Crude Oil of Triassic Yanchang Formation in Southwestern Yishan Slope, Ordos Basin.

Biomarker compounds that derived from early living organisms play an important role in oil and gas geochemistry and exploration since they can record the diagenetic evolution of the parent materials of crude oil and reflect the organic geochemical characteristics of crude oil and source rocks. To offer scientific basis for oil exploration and exploitation for study area, gas chromatography-mass spectrometry method is applied to study the biomarker compounds of crude oil in Southwestern Yishan Slope of Ordos Basin, through qualitatively and quantitatively analyzing separated materials. The crude oil of Yanchang Formation and the source rocks of Yan'an and Yanchang Formation were collected in order to systematically analyze the characteristics of the biomarker compounds in saturated hydrocarbon fractions and clarify the organic geochemical characteristics of crude oil. The distribution and composition of various types of hydrocarbon biomarker compounds in crude oil suggest that the parent materials of crude oil are composed of hydrobiont and terrigenous plants, and the crude oil is mature oil which is formed in the weak reducing fresh water environment. Oil source correlation results show that the crude oil of Yanchang Formation in Yishan Slope is sourced from the source rocks of Chang 7 subformation.