Chronic kidney disease (CKD) is a global health epidemic that greatly increases mortality due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiac injury in CKD. High serum levels of fibroblast growth factor (FGF) 23 in patients with CKD may contribute mechanistically to the pathogenesis of LVH by activating FGF receptor (FGFR) 4 signaling in cardiac myocytes. Mitochondrial dysfunction and cardiac metabolic remodeling are early features of cardiac injury that predate development of hypertrophy, but these mechanisms have been insufficiently studied in models of CKD. We found in wild-type mice with CKD induced by adenine diet, that morphological changes occurred in mitochondrial structure and cardiac mitochondrial and that metabolic dysfunction preceded the development of LVH. In bioengineered cardio-bundles and neonatal rat ventricular myocytes grown in vitro, FGF23-mediated activation of FGFR4 caused mitochondrial pathology, characterized by increased bioenergetic stress and increased glycolysis that preceded the development of cellular hypertrophy. The cardiac metabolic changes and associated mitochondrial alterations in mice with CKD were prevented by global and cardiac-specific deletion of FGFR4. Our findings indicate that metabolic remodeling and mitochondrial dysfunction are early cardiac complications of CKD that precede structural remodeling of the heart. Mechanistically, FGF23-mediated activation of FGFR4 causes mitochondrial dysfunction, suggesting that early pharmacologic inhibition of FGFR4 might serve as novel therapeutic intervention to prevent development of LVH and heart failure in patients with CKD.

The specific protein targets involved in pancreatic cancer (PC) pathogenesis and its varying levels of differentiation remain incompletely understood. Advanced proteomic methodologies provide a powerful means of identifying key regulatory proteins and signaling pathways central to cancer progression. In this study, proteomic analyses were performed on PC tissue samples of different differentiation grades, along with adjacent non-cancerous (para-PC) tissues. Bioinformatics techniques were used to identify differentially expressed proteins (DEPs) and their associated pathways. Key target proteins were validated using the GEPIA database, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, immunohistochemistry (IHC), and immunofluorescence (IF). A total of 431 DEPs were identified between PC and para-PC tissues, while 470 DEPs distinguished poorly differentiated from moderately differentiated PCs. Functional enrichment analysis revealed that these DEPs participate in various biological processes and signaling pathways. Five DEPs were common to both comparisons, with UPP1, LACTB, and AHSA1 showing particularly notable differences. UPP1 and AHSA1 were significantly upregulated in PC tissues relative to adjacent tissues and exhibited even higher expression in poorly differentiated PCs compared to moderately differentiated ones. These findings were consistently supported by GEPIA, RT-qPCR, western blotting, IHC, and IF analyses. This study identifies UPP1 and AHSA1 as key proteins linked to PC differentiation and progression, highlighting their potential as diagnostic markers and therapeutic targets. These insights enhance our understanding of the molecular mechanisms underlying PC and open new avenues for precision treatment strategies.

Engineered human cardiac tissues hold great promise for disease modeling, drug development, and regenerative therapy. For regenerative applications, successful engineered tissue engraftment in vivo requires rapid vascularization and blood perfusion post-implantation. In the present study, we engineered highly functional, vascularized cardiac tissues ("cardiopatches") by co-culturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) and endothelial cells (hiPSC-ECs) in optimized serum-free media. The vascularized cardiopatches displayed stable capillary networks over 4 weeks of culture, the longest reported in the field, while maintaining high contractile stress (>15 mN/mm2) and fast conduction velocity (>20 cm/s). Robustness of the method was confirmed using two distinct hiPSC-EC sources. Upon implantation into dorsal-skinfold chambers in immunocompromised mice, in vitro vascularized cardiopatches exhibited improved angiogenesis compared to avascular implants. Significant lumenization of the engineered human vasculature and anastomosis with host mouse vessels yielded the formation of hybrid human-mouse capillaries and robust cardiopatch perfusion by blood. Moreover, compared to avascular tissues, the implanted vascularized cardiopatches exhibited significantly higher conduction velocity and Ca2+ transient amplitude, longitudinally monitored in live mice for the first time. Overall, we demonstrate successful 4-week vascularization of engineered human cardiac tissues without loss of function in vitro, which promotes tissue functionality upon implantation in vivo. STATEMENT OF SIGNIFICANCE: Complex interactions between cardiac muscle fibers and surrounding capillaries are critical for everyday function of the heart. Tissue engineering is a powerful method to recreate functional cardiac muscle and its vascular network, which are both lost during a heart attack. Our study demonstrates in vitro engineering of dense capillary networks within highly functional engineered heart tissues that successfully maintain the structure, electrical, and mechanical function long-term. In mice, human capillaries from these engineered tissues integrate with host mouse capillaries to allow blood perfusion and support improved implant function. In the future, the developed vascularized engineered heart tissues will be used for in vitro studies of cardiac development and disease and as a potential regenerative therapy for heart attack.

Background Pancreatic endocrine insufficiency is more likely to occur after acute pancreatitis (AP), but the risk factors affecting pancreatic endocrine function remain controversial. Therefore, exploring the incidence and risk factors of fasting hyperglycaemia following first-attack AP is important. Methods Data were collected from 311 individuals with first-attack AP without previous diabetes mellitus (DM) or impaired fasting glucose (IFG) history treated in the Renmin Hospital of Wuhan University. Relevant statistical tests were performed. A two-sided p-value < 0.05 was considered statistically significant. Results The incidence of fasting hyperglycaemia in individuals with first-attack AP was 45.3%. Univariate analysis showed that age (χ 2 = 6.27, P = 0.012), aetiology (χ 2 = 11.184, P = 0.004), serum total cholesterol (TC) (χ 2 = 14.622, P < 0.001), and serum triglyceride (TG) (χ 2 = 15.006, P < 0.001) were significantly different between the hyperglycaemia and non-hyperglycaemia groups ( P < 0.05). The serum calcium concentration (Z=-2.480, P = 0.013) was significantly different between the two groups ( P < 0.05). Multiple logistic regression analysis showed that age- ≥60 years ( P < 0.001, OR = 2.631, 95%Cl = 1.529–4.527) and TG ≥ 5.65 mmol/L ( P < 0.001, OR = 3.964, 95%Cl = 1.990–7.895) were independent risk factors for fasting hyperglycaemia in individuals with first-attack AP ( P < 0.05). Conclusions Old age, serum triglycerides, serum total cholesterol, hypocalcaemia, and aetiology are associated with fasting hyperglycaemia following first-attack AP. Age ≥ 60 years and TG ≥ 5.65 mmol/L are independent risk factors for fasting hyperglycaemia following first-attack AP.

Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome's impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as Streptococcus, Neisseria, and Gemella, and increased Prevotella, Veillonella, Granulicatella, Actinomyces, and Peptostreptococcus in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as Neisseria, Haemophilus, and Gemella in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that Prevotella, Peptostreptococcus, Actinomyces, and Porphyromonas were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.

T and B cell receptor signaling involves the activation of Akt, MAPKs, and PKC as well as an increase in intracellular Ca2+ and calmodulin activation. While these coordinate the rapid turnover of gap junctions, also implicated in this process is Src, which is not activated as part of T and B cell receptor signaling. An in vitro kinase screen identified that Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) phosphorylate Cx43. Mass spectroscopy revealed that BTK and ITK phosphorylate Cx43 residues Y247, Y265, and Y313, which are identical to the residues phosphorylated by Src. Overexpression of BTK or ITK in the HEK-293T cells led to increased Cx43 tyrosine phosphorylation as well as decreased gap junction intercellular communication (GJIC) and Cx43 membrane localization. In the lymphocytes, activation of the B cell receptor (Daudi cells) or T cell receptor (Jurkat cells) increased the BTK and ITK activity, respectively. While this led to increased tyrosine phosphorylation of Cx43 and decreased GJIC, the cellular localization of Cx43 changed little. We have previously identified that Pyk2 and Tyk2 also phosphorylate Cx43 at residues Y247, Y265, and Y313 with a similar cellular fate to that of Src. With phosphorylation critical to Cx43 assembly and turnover, and kinase expression varying between different cell types, there would be a need for different kinases to achieve the same regulation of Cx43. The work presented herein suggests that in the immune system, ITK and BTK have the capacity for the tyrosine phosphorylation of Cx43 to alter the gap junction function in a similar manner as Pyk2, Tyk2, and Src.

Gemcitabine resistance is a frequently occurring and intractable obstacle in pancreatic cancer treatment. However, the underlying mechanisms require further investigation. Adaptive regulation of oxidative stress and aberrant activation of the NF-κB signaling pathway are associated with resistance to chemotherapy. Here, we found that gemcitabine upregulated the expression of CASC9 in a dose-dependent manner, partially via induction of reactive oxygen species, whereas inhibition of CASC9 expression enhanced gemcitabine-induced oxidative stress and apoptosis in pancreatic cancer cells. Furthermore, suppression of CASC9 level inhibited the expression of NRF2 and the downstream genes NQO1 and HO-1, and vice versa, indicating that CASC9 forms a positive feedback loop with NRF2 signaling and modulates the level of oxidative stress. Silencing CASC9 attenuated NF-κB pathway activation in pancreatic cancer cells and synergistically enhanced the cytotoxic effect of gemcitabine chemotherapy in vivo. In conclusion, our findings suggest that CASC9 plays a key role in driving resistance to gemcitabine through a reciprocal loop with the NRF2-antioxidant signaling pathway and by activating NF-κB signaling. Our study reveals potential targets that can effectively reverse resistance to gemcitabine chemotherapy.

Increasing evidence indicates the dysregulations and pivotal roles of lncRNAs in the development and progression of various cancers, including pancreatic cancer. Enhanced glycolytic flux and epithelial-to-mesenchymal transition (EMT) have been considered as important factors in driving the malignance of pancreatic cancer. Here, we sought to evaluate the biological role and involved mechanism of lncRNA CASC9 (CASC9) in pancreatic cancer. Our present study showed that CASC9 was upregulated in various pancreatic cancer cell lines. Loss- and gain-of function of CASC9 demonstrated its critical roles in promoting the glycolysis and EMT phenotypes of pancreatic cancer. Moreover, knockdown of CASC9 inhibited the tumorigenicity and metastasis in vivo. Additionally, our findings showed that hypoxia induced the expression of CASC9 and enhanced the binding of HIF-1α to its promoter. We also demonstrated that the positive feedback loop of CASC9 and the AKT/HIF-1α signaling cascade partially mediated this biological process. Altogether, our results suggest that CASC9 promotes the glycolysis and EMT of pancreatic cancer by a positive feedback loop with AKT/HIF-1α signaling, which is synergistically enhanced by the tumor hypoxic niche. Our study will provide potential therapeutic targets for treating pancreatic cancer.

华中科技大学同济医学院附属同济医院陈孝平院士在深入的理论和临床研究基础上,创建了一种贯穿纵向"U"型胰肠吻合术.该术式通过全层贯穿胰腺实质和肠壁的间断交锁"U"型缝合或者连续缝合,将胰腺断端的主胰管、副胰管、小叶导管引流的胰液全部引流入肠腔内无遗漏.经过多家大通量胰腺外科中心的大样本临床病例验证,该术式操作简便,能显著降低术后胰瘘和出血的发生率,在临床上得到了广泛应用,是一种能有效降低胰腺消化道重建术后胰瘘、出血等严重并发症发生率的吻合技术,适用于各种类型的胰腺残端.

BACKGROUND:Pancreatic cancer (PC), characterized with high growth rate and metastatic rate. It's urgently necessary to explore new mechanism of PC. Circular RNA/miRNA/mRNA network was widely reported to participate in the cancer progression.METHODS:In this research, circular RNA CDR1as (circCDR1as) was identified by microarray analysis and detected in pancreatic cancer (PC) tissues and cells. Transwell, colony-forming assay, nude mouse tumorigenicity assay were used to determine the function of circCDR1as in PC. Western blot, dual luciferase reporting test were applied to investigate the mechanism.RESULTS:We found that circCDR1as was highly expressed in PC tissues. The levels of circCDR1as in PC tissues and cells were higher than those in controls. CircCDR1as promoted the migration, invasion and proliferation of PC cells in vitro and tumor growth in vivo via mediating E2F3 expression by sponging miR-432-5p.CONCLUSIONS:In conclusion, circCDR1as could promote the development of PC and might be a novel diagnostic target for PC.

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.

Long non-coding RNA (lncRNA) ADAM metallopeptidase with thrombospondin type 1 motif 9 antisense RNA 2 (ADAMTS9-AS2) is involved in various types of cancer, such as ovarian cancer, lung cancer and clear cell renal cell carcinoma. However, the roles of ADAMTS9-AS2 in liver cancer are not completely understood. The present study aimed to determine the functional role of ADAMTS9-AS2 in human liver cancer and investigate the potential underlying molecular mechanisms. The expression levels of ADAMTS9-AS2 and ADAMTS9 were determined following ADAMTS9-AS2 overexpression and knockdown. The results indicated that ADAMTS9-AS2 overexpression and knockdown increased and decreased ADAMTS9 mRNA and protein expression levels, respectively, indicating that alterations in ADAMTS9 expression corresponded with ADAMTS9-AS2 expression. Subsequently, the effects of ADAMTS9-AS2 on liver cancer cell proliferation, migration and invasion were analyzed by performing Cell Counting Kit-8, wound healing and Transwell assays, respectively. The results demonstrated that ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion. Finally, the effect of ADAMTS9 on PI3K/AKT/mTOR signaling pathway-associated proteins [AKT, phosphorylated-AKT, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit β (PIK3CB), mTOR and phosphorylated-mTOR], several key autophagy-related proteins [light chain 3-I/II (LC3-I/II), beclin 1 (BECN1) and sequestosome 1 (SQSTM1)] and apoptosis-related proteins (Bax and Bcl-2) was detected via western blotting. The results suggested that ADAMTS9-AS2 downregulated the phosphorylation of AKT and mTOR, the protein expression level of PIK3CB, as well as the expression levels of autophagy protein SQSTM1 and antiapoptotic protein Bcl-2. By contrast, ADAMTS9-AS2 upregulated the expression levels of autophagy proteins LC3-II and BECN1, and the proapoptotic protein Bax. Collectively, ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion via inhibiting the PI3K/AKT/mTOR signaling pathway. The present study provided a novel insight into the role of ADAMTS9-AS2 in liver cancer.

Background: Profound chemoresistance is a prominent and intractable problem in pancreatic cancer. Gemcitabine, a first-line chemotherapeutic drug for pancreatic cancer, has provided only minimal benefits for patients; however, the underlying mechanisms remain to be investigated. Enhanced aerobic glycolysis has been suggested to be correlated with the phenotype of drug resistance, while MALAT1 has been indicated to be associated with poor gemcitabine response. However, the implicated regulatory mechanisms still need to be further explored.Methods: The mRNA level of MALAT1, HIF-1α, and glycolytic enzymes were analyzed by qRT-PCR. The protein level of HIF-1α and glycolytic enzymes were detected by western blot analysis. The glucose uptake and lactate level were measured by glucose uptake and lactate production assay, respectively. The cell apoptosis was evaluated by apoptosis analysis using Annexin V/propidium iodide (PI) staining. The sensitivity to gemcitabine was measured by MTT assay. The binding of HIF-1α to the promoter of MALAT1 was tested by ChIP assay. The xenograft model of pancreatic cancer was established to examine the combined effect of MALAT1 knockdown and gemcitabine chemotherapy in vivo. Results: In this study, we showed that low concentrations of gemcitabine promoted the expression of key glycolytic enzymes, such as GLUT1, HK2, and LDHA, as well as glucose uptake and lactate production in pancreatic cancer cells, while inhibition of glycolysis suppressed gemcitabine chemoresistance. In addition, we found that MALAT1 expression was induced by gemcitabine and mediated enhanced glycolysis and chemoresistance. Silencing MALAT1 inhibited the level of gemcitabine-induced HIF-1α expression and reinforced gemcitabine-induced apoptosis in vitro and in vivo. Furthermore, HIF-1α could bind the promoter of MALAT1 transcriptionally and mediate the glycolysis induced by gemcitabine. Conclusions: Our data suggest a critical role of glycolytic metabolism in acquired gemcitabine resistance through the positive feedback loop of MALAT1 and the HIF-1α signaling pathway. Our results will provide a basis for developing potential therapeutic targets to reverse gemcitabine resistance.

Given the fact that tumor-associated macrophage-derived extracellular vesicles (EVs) are attributable to tumor aggressiveness, this research intends to decode the mechanism of M2 macrophage-derived EVs in the differentiation and activities of pancreatic cancer (PaCa) stem cells via delivering microRNA (miR)-21-5p. Polarized M2 macrophages were induced, from which EVs were collected and identified. miR-21-5p expression in M2 macrophage-derived EVs was tested. After cell sorting, CD24+CD44+EpCAM+ stem cells were co-cultured with M2 macrophages, in which miR-21-5p was upregulated or downregulated. The effects of M2 macrophage-derived EVs and miR-21-5p on Nanog/octamer-binding transcription factor 4 (Oct4) expression, sphere formation, colony formation, invasion and migration capacities, apoptosis, and in vivo tumorigenic ability were examined. Krüppel-like factor 3 (KLF3) expression and its interaction with miR-21-5p were determined. M2 macrophage-derived EVs promoted PaCa stem cell differentiation and activities. miR-21a-5p was upregulated in M2 macrophage-derived EVs. miR-21a-5p downregulation in M2 macrophage-derived EVs inhibited Nanog/Oct4 expression and impaired sphere-forming, colony-forming, invasion, migration, and anti-apoptosis abilities of PaCa stem cells in vitro and tumorigenic ability in vivo. miR-21-5p targeted KLF3 to mediate the differentiation and activities of PaCa stem cells, and KLF3 was downregulated in PaCa stem cells. This work explains that M2 macrophage-derived exosomal miR-21a-5p stimulates differentiation and activity of PaCa stem cells via targeting KLF3, paving a novel way for attenuating PaCa stemness.

Background: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) has been reported to be associated with hepatocellular carcinoma (HCC), which is considered as one of the most common cancers worldwide. However, the mechanism of action of KCNQ1OT1 in human HCC has not been fully explained. In this study, we aimed to explore the functional role and the potential mechanism of KCNQ1OT1 in human HCC.Methods: First, we analyzed the expression levels of KCNQ1OT1 in HCC tissues in starBase database and detected the expression of KCNQ1OT1 in HCC cell lines by quantitative real-time polymerase chain reaction assays. Next, we analyzed the role of KCNQ1OT1 in migration, invasion and proliferation of HCC by scratch wound healing, transwell and cell counting kit-8 assays. Finally, we analyzed the potential interrelationship between KCNQ1OT1 and PI3K/AKT signaling pathway through western blot assays.Results: Based on bioinformatics analyses, we found that KCNQ1OT1 was highly expressed in HCC tissues and its high expression was associated with a poor prognosis in HCC patients. We also confirmed an abnormal increase in the expression of KCNQ1OT1 in HCC cell lines. KCNQ1OT1 knockdown was found to have a negative impact on proliferation, migration and invasion of HCC cells. In addition, interference with the expression of KCNQ1OT1 reduced the phosphorylation level of AKT and the protein level of PI3K, indicating the association of KCNQ1OT1 with the PI3K/AKT signaling pathway.Conclusions: Collectively, this study confirmed the important role of KCNQ1OT1 in promoting HCC growth and revealed the inhibitory effect of KCNQ1OT1 on the PI3K/AKT signaling pathway. This work may contribute to a better understanding of HCC progression and provide a potential biomarker for HCC.

12 months.Hence, the risk profile including increasing age, male sex, lower socioeconomic strata, cumulative comorbidities, presence of components of metabolic syndrome, or clinically severe AP, can be utilized to closely monitor subjects for counseling, timely outpatient follow up, and early detection of AP-NOD. Su1477

Identification of proteins that interact with Cx43 has been instrumental in the understanding of gap junction (GJ) regulation. An in vitro phosphorylation screen identified that Protein tyrosine kinase 2 beta (Pyk2) phosphorylated purified Cx43CT and this led us to characterize the impact of this phosphorylation on Cx43 function. Mass spectrometry identified Pyk2 phosphorylates Cx43 residues Y247, Y265, Y267, and Y313. Western blot and immunofluorescence staining using HeLa cx43 cells, HEK 293 T cells, and neonatal rat ventricular myocytes (NRVMs) revealed Pyk2 can be activated by Src and active Pyk2 interacts with Cx43 at the plasma membrane. Overexpression of Pyk2 increases Cx43 phosphorylation and knock-down of Pyk2 decreases Cx43 phosphorylation, without affecting the level of active Src. In HeLaCx43 cells treated with PMA to activate Pyk2, a decrease in Cx43 GJ intercellular communication (GJIC) was observed when assayed by dye transfer. Moreover, PMA activation of Pyk2 could be inhibited by the small molecule PF4618433. This partially restored GJIC, and when paired with a Src inhibitor, returned GJIC to the no PMA control-level. The ability of Pyk2 and Src inhibitors to restore Cx43 function in the presence of PMA was also observed in NRVMs. Additionally, an animal model of myocardial infarction induced heart failure showed a higher level of active Pyk2 activity and increased interaction with Cx43 in ventricular myocytes. Src inhibitors have been used to reverse Cx43 remodeling and improve heart function after myocardial infarction; however, they alone could not fully restore proper Cx43 function. Our data suggest that Pyk2 may need to be inhibited, in addition to Src, to further (if not completely) reverse Cx43 remodeling and improve intercellular communication.

Although many long non-coding RNAs (lncRNAs) are modulators of biological events in hepatocellular carcinoma (HCC), the potential significance of most lncRNAs in HCC remains to be fully understood. The role of lncRNA ADAMTS9-AS1 in HCC was therefore determined. ADAMTS9-AS1 expression was higher in HCC cell lines compared to normal cells as determined by qPCR analyses. Furthermore, CCK-8, scratch wound healing, transwell migration, and invasion assays suggested that ADAMTS9-AS1 overexpression promoted the proliferation, migration, and invasion in MHCC97-H and HepG2 cells; ADAMTS9-AS1 knockdown showed the opposite results. Based on the results from GEO, the correlation between ADAMTS9-AS1 and PI3K/AKT/mTOR was identified. Thus, an association between ADAMTS9-AS1 and the PI3K/AKT/mTOR signaling pathway was further observed. To confirm the pathway protein levels, p-AKT, PIK3CB, and p-mTOR were selected. Western blot assays suggested that ADAMTS9-AS1 enhanced the expression levels of the three proteins. Because of their close relationship with PI3K/AKT/mTOR, apop tosisor autophagy-related proteins were further investigated. ADAMTS9-AS1 expression was negatively related with LC3-II, BECN1, and pro-apoptotic Bax, whereas it was positively correlated SQSTM1 and anti-apoptotic Bcl-2 expression. Western blot results suggested that ADAMTS9-AS1 decreased ADAMTS9 expression. Our data revealed that ADAMTS9-AS1 contributed to proliferation, migration, and invasion in HCC cells, likely due to the activation of the PI3K/AKT/mTOR signaling pathway, to influence autophagy and apoptosis. These findings suggest that ADAMTS9AS1 could serve as a molecular target in HCC treatment.

目的:回顾性分析急性胰腺炎(AP)患者空腹高血糖发生率及其危险因素.方法:收集2018-01—2018-12武汉大学人民医院胰腺外科133例AP且无糖尿病(DM)病史的住院患者病历资料,按照不同性别、年龄、AP临床分型、病因、CT指数评分(CISI)等分组,χ2检验分析各组临床因素与空腹高血糖(FPG≥6.1mmol/L)发生率的关系,多因素二元logistic回归分析空腹高血糖独立危险因素.结果:AP临床分型(χ2=5.494,P=0.019)和CTSI(χ2=6.236,P=0.013)与AP患者空腹高血糖相关(P<0.05).CTSI≥6分(P=0.015,OR=2.920,95％Cl=1.234—6.905)为AP患者空腹高血糖的独立危险因素(P<0.05).结论:临床分型中重症+重症及CTSI≥6分的AP患者易发生空腹高血糖,尤其CTSI≥6分是AP后空腹高血糖的独立危险因素,临床应高度关注.

OBJECTIVE: Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics, outcomes and analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes.RESEARCH DESIGN AND METHODS: This two-center, retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N=153) who were discharged or died from January 1, 2020, to March 8, 2020, were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients.RESULTS: Of 1561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (IQR, 56.0-72.0) years. A higher proportion of ICU admission (17.6% vs 7.8%, P=0.01) and more fatal cases (20.3% vs 10.5%, P=0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazards ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23) and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs 63.0 years), most were male (71.0% vs 29.0%), and were more likely to have underlying hypertension (83.9% vs 50.0%) and cardiovascular disease (45.2% vs 14.8%) (all P-values<0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes.CONCLUSIONS: COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.