The new landscape of differentially expression proteins in placenta tissues of gestational diabetes based on iTRAQ proteomics.

INTRODUCTION: Gestational diabetes mellitus (GDM) refers to abnormal glucose tolerance that occurs or is firstly diagnosed during pregnancy. GDM is related to various adverse pregnancy outcomes, but GDM pathogeny has not been fully elucidated. Nevertheless, previous studies have observed that many proteins in the placentas of patients with GDM are dysregulated. The present study aimed to establish a novel differentially expressed protein (DEP) landscape of GDM and normal maternal placentas and to explore the possible connection between DEPs and GDM pathogenesis. This study provides new insights into the mechanism of GDM and should make an important contribution to the development of biomarkers. METHODS: The morphological characteristics of the placenta were observed on 30 GDM and normal maternal placental tissues stained with haematoxylin and eosin. Isobaric tags for relative and absolute quantitation (iTRAQ) was used in the proteomics screening of the DEPs of the normal and GDM maternal placentas. Bioinformatics analysis was performed on the DEPs, and parallel reaction monitoring (PRM) was performed to verify the DEPs. Finally, the quantitative analysis of iTRAQ and PRM was verified by immunohistochemical assay. RESULTS: A total of 68 DEPs in the GDM placenta were identified with iTRAQ proteomics experiment, comprising 21 up-regulated and 47 down-regulated DEPs. Bioinformatics analysis showed that the regulation of transport, catabolic process of non-coding RNA, cytoskeleton and cell binding were the most abundant Gene Ontology terms, and RNA degradation was an important pathway for significant enrichment. Protein-protein interaction network analysis showed that heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1), heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB), heterogeneous nuclear ribonucleoprotein L (HNRNPL) and heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) were the cores of the up-regulated proteins. Band 3 anion transport protein (SLC4A1), spectrin beta chain erythrocytic (SPTB), ankyrin-1 (ANK1), spectrin beta chain non-erythrocytic 2 (SPTBN2), D-3-phosphoglycerate dehydrogenase (PHGDH) and exosome complex component RRP42 (EXOSC7) were the cores of the down-regulated proteins. These proteins are involved in the binding, splicing, processing, transport and degradation of RNA and in the formation and maintenance of the cytoskeleton. PRM verification results showed that seven proteins, namely, epiplakin (EPPK1), cold-inducible RNA-binding protein (CIRBP), HNRNPA2B1, HNRNPAB, HNRNPL, Ras-related protein Rab-21 (RAB21) and Ras-related protein Rab-3B (RAB3B), were up-regulated, whereas SPTB and SLC4A1 were down-regulated. The results of immunohistochemical assay also showed that the expression of five proteins, namely EPPK1, HNRNPA2B1, HNRNPAB, CIRBP and RAB21, were significantly higher in GDM placental tissues (P < 0.01). The GDM placentas showed changes in the morphological evaluation, including poor villous maturation, obvious increase in the number of syncytiotrophoblast nodules, thickening of the wall of dry villous arterioles with lumen stenosis, increased fibrinous exudation and excessive filling of villous interstitial vessels. DISCUSSION: Differentially expressed proteins related to a variety of biological processes in the GDM placenta were found. Fourteen proteins, namely, HNRNPA2B1, HNRNPAB, HNRNPL, HNRNPA3, EPPK1, CIRBP, RAB21, RAB3B, SLC4A1, SPTB, ANK1, SPTBN2, PHGDH and EXOSC7, which were differentially expressed in the placenta, may play an important role in regulating the occurrence and development of gestational diabetes through multi-channel and multi-link regulation.

Silver Nanoparticles Improve the Biocompatibility and Reduce the Immunogenicity of Xenogeneic Scaffolds Derived from Decellularized Pancreas.

Xenogeneic scaffolds derived from the decellularized pancreas are plausible biomedical materials for pancreatic tissue engineering applications. During the decellularized process, the ultrastructure of extracellular matrices, including collagen fibers, was destructed, which leads to the decrease of mechanical strength and the immune-inflammatory response after transplantation in vivo. The cross-linking method plays an important role in increasing mechanical strength and reducing the inflammatory potential of decellularized scaffolds. However, no ideal cross-linking agent has been identified for decellularized pancreatic scaffolds yet. In this study, a cyclic perfusion system was used to cross-link decellularized pancreatic scaffolds from Sprague Dawley rat with silver nanoparticles (AgNPs). The optimum concentration of AgNPs was selected according to the scanning electron microscope observation and mechanical evaluation, as well as cytotoxicity to human umbilical vein endothelial cells and MIN-6 cell lines in vitro. The inflammation after transplantation in vivo was evaluated by hematoxylin and eosin staining; M1/M2 polarization phenotype of macrophages was further evaluated. Our results showed that after cross-linking, the scaffold possessed better mechanical property and biocompatibility, with the polarization of M2 macrophages increased. Thus, AgNP-cross-linked pancreatic acellular scaffold can provide an ideal scaffold source for pancreatic tissue engineering.

ZNF488 Promotes the Invasion and Migration of Pancreatic Carcinoma Cells through the Akt/mTOR Pathway.

OBJECTIVE: Studies have demonstrated that zinc finger protein 488 (ZNF488) is highly expressed in pancreatic carcinoma (PC), but its effect on PC and its molecular mechanism remains unclear. METHODS: Real-time fluorescent quantitative PCR (RT-qPCR) was employed to detect the ZNF488 expression in PC patients' cancer tissues and cell lines. After interfering with or overexpressing ZNF488 in PANC-1 and AsPC-1 cells, respectively, the CCK-8, cell cloning, Transwell, and scratch assays were performed to detect cell proliferation, cell viability, invasion ability, and migration ability. In addition, Western blot was applied to assess the protein expression of Akt, p-Akt, mTOR, and p-mTOR in the Akt-mTOR pathway. RESULTS: The ZNF488 expression was evidently raised in PC tissues and cell lines, and the starBase V3.0 database indicated that the higher the ZNF488 expression, the lower the survival rate of PC patients. Furthermore, we discovered that overexpressing ZNF488 can markedly promote the proliferation, invasion, and migration of PC cells. At the same time, highly expressed ZNF488 distinctly increased the p-Akt and p-mTOR expressions and the p-Akt/Akt and p-mTOR/mTOR ratios. However, after knocking down the ZNF488 expression, it had the opposite results. In addition, the Akt agonist SC79 can alleviate the effect of ZNF488 knockdown on Akt/mTOR pathway-related proteins, while Akt inhibitor AZD5363 had the opposite effect. CONCLUSION: ZNF488 could promote the proliferation, invasion, and migration of PC cells, and its mechanism may be related to the activation of the Akt/mTOR pathway. This study demonstrated that ZNF488 could be used as a molecular target for diagnosing and treating PC.

Comparisons of short-term and long-term results between laparoscopic between open pancreaticoduodenectomy for pancreatic tumors: A systematic review and meta-analysis.

Objective: The efficacy of pancreaticoduodenectomy and open pancreaticoduodenectomy for pancreatic tumors is controversial. The study aims to compare the efficacy of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in the treatment of pancreatic tumors through systematic evaluation and meta-analysis. Methods: PubMed, Embase, Cochrane Library and Web of science databases were searched for clinical studies on the treatment of pancreatic tumors with LPD and OPD. The end time for the searches was 20 July 2022. Rigorous inclusion and exclusion criteria were used to screen the articles, the Cochrane manual was used to evaluate the quality of the included articles, and the stata15.0 software was used for statistical analysis of the indicators. Results: In total, 16 articles were included, including two randomized controlled trials and 14 retrospective studies. Involving a total of 4416 patients, 1275 patients were included in the LPD group and 3141 patients in the OPD group. The results of the meta-analysis showed that: the operation time of LPD was longer than that of OPD [WMD = 56.14,95% CI (38.39,73.89), p = 0.001]; the amount of intraoperative blood loss of LPD was less than that of OPD [WMD = -120.82,95% CI (-169.33, -72.30), p = 0.001]. No significant difference was observed between LPD and OPD regarding hospitalization time [WMD = -0.5,95% CI (-1.35, 0.35), p = 0.250]. No significant difference was observed regarding postoperative complications [RR = 0.96,95% CI (0.86,1.07, p = 0.463]. And there was no significant difference regarding 1-year OS and 3-year OS: 1-year OS [RR = 1.02,95% CI (0.97,1.08), p = 0.417], 3-year OS [RR = 1.10 95% CI (0.75, 1.62), p = 0.614%]. Conclusion: In comparison with OPD, LPD leads to less blood loss but longer operation time, therefore the bleeding rate per unit time of LPD is less than that of OPD. LPD has obvious advantages. With the increase of clinical application of LPD, the usage of LPD in patients with pancreatic cancer has very good prospect. Due to the limitations of this paper, in future studies, more attention should be paid to high-quality, multi-center, randomized controlled studies.

Breast Cancer Classification Prediction Based on Ultrasonic Image Feature Recognition.

Exploring an effective method to manage the complex breast cancer clinical information and selecting a suitable classifier for predictive modeling still require continuous research and verification in the actual clinical environment. This paper combines the ultrasound image feature algorithm to construct a breast cancer classification model. Furthermore, it combines the motion process of the ultrasound probe to accurately connect the ultrasound probe to the breast tumor. Moreover, this paper constructs a hardware and software system structure through machine vision algorithms and intelligent motion algorithms. Furthermore, it combines coordinate transformation and image recognition algorithms to expand the recognition process to realize automatic and intelligent real-time breast cancer diagnosis. In addition, this paper combines machine learning algorithms to process data and obtain an intelligent system model. Finally, this paper designs experiments to verify the intelligent system of this paper. Through experimental research, it can be seen that the breast cancer classification prediction system based on ultrasonic image feature recognition has certain effects.

Analysis of the Effect of Robots in the Treatment of Pancreatic Cancer Based on Smart Medicine.

In order to study the effect of robots in the treatment of pancreatic cancer in the context of smart medical, this paper improves the robot recognition technology and data processing technology and improves the system kernel algorithm through the hash algorithm. Unlike the traditional sequencing method that directly uses the gray average value as a feature, the hash algorithm calculates the gray three-average value of each frame block and uses the difference of the three-average value of adjacent frame blocks to perform detection. Moreover, this paper proposes a detection and localization scheme based on hash local matching, which consists of two parts: coarse matching and fine matching. In addition, this paper designs a control experiment to analyze the effect of robots in the treatment of pancreatic cancer, counts multiple sets of data, and uses mathematical statistics to process and visually display the experimental data. The research shows that the robot has a good clinical effect in the treatment of pancreatic cancer.

LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2.

BACKGROUND: Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its biological function in NSCLC cells remains unclear. METHODS: GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot. RESULTS: GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p. CONCLUSIONS: GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging.

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target.

Pancreatic extracellular matrix and platelet-rich plasma constructing injectable hydrogel for pancreas tissue engineering.

The development of pancreatic extracellular matrices enriched with insulin-secreting ß-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting ß cells.

Enhanced vascularization and biocompatibility of rat pancreatic decellularized scaffolds loaded with platelet-rich plasma.

The ultimate goal of pancreatic tissue engineering is to create a long-lived substitute organ to treat diabetes. However, the lack of neovascularization and the occurrence of immune response limit the efficacy of tissue-engineered pancreas after in vivo transplantation. Platelet-rich plasma (PRP) is an autologous platelet concentrate containing a large number of growth factors and immunoregulatory factors. The aim of this study was to evaluate rat pancreatic decellularized scaffold (PDS) loaded with PRP for vascularization, host inflammatory response and macrophage polarization in an animal model. The study results indicated that compared to PDS, PRP-loading PDS exhibited the enhanced mechanical properties and released growth factors in a slow and sustained manner to supplement the loss of growth factors during decellularization. In vitro, human umbilical vein endothelial cells (HUVECs) were seeded in PDS and PRP-loading PDS, and cultured in the circular perfusion system. When compared with PDS, PRP-loading PDS significantly promoted the colonization, proliferation and pro-angiogenic genes expression of cells on scaffolds. In vivo, PDS loaded with PRP then re-endothelialized with HUVECs were implanted subcutaneously in rats, which enhanced the angiogenesis of scaffolds, inhibited the host inflammatory response, and induced the polarization dominated by pro-regenerative M2 macrophages that also facilitated tissue vascular regeneration. Thus, the re-endothelialized PRP-loading PDS may represent a promising bioengineered pancreas with sustained vascularization and excellent biocompatibility.

Long noncoding RNA TP73-AS1 in human cancers.

Long noncoding RNAs (lncRNAs) play an important role in tumor development. With the development of sequencing technology, many new lncRNAs have been discovered. lncRNA TP73-AS1 is abnormally expressed in many cancers. A summary of the current literature related to TP73-AS1 reveals that TP73-AS1 mainly regulates the occurrence and development of tumors through the mechanism of competitive endogenous RNA (ceRNA). In addition, the abnormal expression of TP73-AS1 can regulate the malignant function of tumor cells through a variety of possible mechanisms. All evidence suggests that TP73-AS1 may be a potential diagnostic biomarker or a new cancer therapeutic target.

pH-Sensitive Hydrogel for Micro-Fluidic Valve.

The deformation behavior of a pH-sensitive hydrogel micro-fluidic valve system is investigated using inhomogeneous gel deformation theory, in which the fluid-structure interaction (FSI) of the gel solid and fluid flow in the pipe is considered. We use a finite element method with a well adopted hydrogel constitutive equation, which is coded in commercial software, ABAQUS, to simulate the hydrogel valve swelling deformation, while FLUENT is adopted to model the fluid flow in the pipe of the hydrogel valve system. The study demonstrates that FSI significantly affects the gel swelling deformed shapes, fluid flow pressure and velocity patterns. FSI has to be considered in the study on fluid flow regulated by hydrogel microfluidic valve. The study provides a more accurate and adoptable model for future design of new pH-sensitive hydrogel valves, and also gives a useful guideline for further studies on hydrogel fluidic applications.

Socioeconomic and racial differences in treatment for breast cancer at a low-volume hospital.

PURPOSE: Population-based studies have revealed higher mortality among breast cancer patients treated in low-volume hospitals. Other studies have demonstrated disparities in race and socioeconomic status (SES) in breast cancer survival. The purpose of our study was to determine whether nonwhite or low-SES patients are disproportionately treated in low-volume hospitals. METHODS: A population-based cohort of 2,777 Medicare breast cancer patients who underwent breast cancer surgery in 2003 participated in a survey study examining breast cancer outcomes. Information was obtained from survey responses, Medicare claims, and state tumor registry data. RESULTS: On univariate analysis, patients treated at low-volume hospitals were less likely to be white, less likely to live in an urban location, and more likely to have a low SES with less social support and live a greater distance from a high-volume hospital. Education, marital status, total household income, having additional insurance besides Medicare, population density of primary residence, and tangible support were associated with distance to the nearest high-volume hospital. On multivariate analysis, the independent predictors of treatment at a low-volume hospital were being nonwhite (P = 0.003), having a lower household income (P < 0.0001), residence in a rural location (P = 0.01), and living a greater distance from a high-volume hospital (P < 0.0001). CONCLUSIONS: In this large population-based cohort, women who were poorer, nonwhite, and who lived in a rural location or at a greater distance from a high-volume hospital were more likely to be treated at low-volume hospitals. These differences may partially explain racial and SES disparities in breast cancer outcomes.

Electrodiagnostic consultation and identification of neuromuscular conditions in persons with diabetes.

INTRODUCTION: Although the American Association of Neuromuscular and Electrodiagnostic Medicine recommends that electrodiagnostic procedures should be performed by physicians with specialty training, these procedures are increasingly being performed by non-specialists. METHODS: We used a nationally representative sample of Medicare beneficiaries with diabetes who used electrodiagnostic services in 2006 to examine whether specialists and non-specialists were different in the rates of identifying common neuromuscular conditions. RESULTS: Specialists (neurologists and physiatrists) performed 62% of electrodiagnostic consultations; non-specialist physicians and non-physicians performed 31% and 5%, respectively. After adjusting for age, race/ethnicity, diabetes severity, and comorbidities, specialists were 1.26-9 times more likely than non-physicians to diagnose polyneuropathy, lumbosacral radiculopathy, cervical radiculopathy, carpal tunnel syndrome, and ulnar neuropathy. Almost 80% of electrodiagnostic studies performed by specialists included electromyography testing; fewer than 13% by non-specialists did. CONCLUSIONS: Inadequate use of electromyography and fewer specific diagnoses suggest that many non-specialists perform insufficiently comprehensive electrodiagnostic studies.

Musculoskeletal disorders in referrals for suspected lumbosacral radiculopathy.

OBJECTIVE: An electrodiagnostic evaluation is often requested for patients with suspected lumbosacral radiculopathy. Although musculoskeletal disorders can produce lower-limb symptoms, their prevalence in this referral population is unknown. The purpose of this study was to determine the prevalence of common lower-limb musculoskeletal disorders in patients referred for lower-limb electrodiagnosis and determine whether these findings predict study outcome. DESIGN: Subjects undergoing an electrodiagnostic study for lower-limb symptoms and suspected lumbosacral radiculopathy constituted the sample. A standardized clinical and electrodiagnostic evaluation was performed for all patients. RESULTS: There were 170 subjects included. The mean age was 52 (SD = 17), and 45% were males. The total prevalence of musculoskeletal disorders in the sample was 32%. The prevalence in those with a normal study was 55% as compared with 21% in those with lumbosacral radiculopathy (P < 0.0001). CONCLUSIONS: Musculoskeletal disorders are common in patients suspected of having lumbosacral radiculopathy. The high prevalence among both patients with normal studies and those with radiculopathy and other disorders limits the usefulness of this information in predicting study outcome. In particular, it is common for patients to have two or more problems and the presence of a musculoskeletal disorder should not preclude such testing.

Musculoskeletal disorders in referrals for suspected cervical radiculopathy.

OBJECTIVES: To determine (1) the prevalence of selected common musculoskeletal disorders in patients referred for electrodiagnosis when cervical radiculopathy is suspected and (2) whether these findings predict electrodiagnostic study outcome. DESIGN: Prospective study. SETTING: Electrodiagnostic laboratories in departments of physical medicine and rehabilitation at 5 participating institutions. PARTICIPANTS: A total of 191 subjects undergoing electrodiagnostic evaluations for upper-limb symptoms when cervical radiculopathy was suspected. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of certain musculoskeletal disorders (myofascial pain, shoulder impingement, lateral epicondylitis, de Quervain's tenosynovitis) and outcomes of electrodiagnostic testing (normal study, cervical radiculopathy, or another electrodiagnostically confirmed diagnosis). RESULTS: The total prevalence of musculoskeletal disorders was 42%. The prevalence in those with a normal study was 69%, compared with 29% in those with cervical radiculopathy (P<.001) and 45% in those with another diagnosis (P=.02). CONCLUSIONS: Musculoskeletal disorders are common in patients with suspected cervical radiculopathy. Although the presence of certain musculoskeletal disorders makes having a normal electrodiagnostic evaluation significantly more likely, the high prevalence among both patients with normal studies and those with radiculopathy and other disorders limits the usefulness of this information in precisely predicting study outcome. The presence of musculoskeletal disorders should not preclude electrodiagnostic testing when otherwise indicated.