Integrated transcriptomic and proteomic analyses of two sugarcane (Saccharum officinarum Linn.) varieties differing in their lodging tolerance.

BACKGROUND: Lodging seriously affects sugarcane stem growth and sugar accumulation, reduces sugarcane yield and sucrose content, and impedes mechanization. However, the molecular mechanisms underlying sugarcane lodging tolerance remain unclear. In this study, comprehensive transcriptomic and proteomic analyses were performed to explore the differential genetic regulatory mechanisms between upright (GT42) and lodged (GF98-296) sugarcane varieties. RESULTS: The stain test showed that GT42 had more lignin and vascular bundles in the stem than GF98-296. The gene expression analysis revealed that the genes that were differentially expressed between the two varieties were mainly involved in the phenylpropanoid pathway at the growth stage. The protein expression analysis indicated that the proteins that were differentially expressed between the two varieties were related to the synthesis of secondary metabolites, the process of endocytosis, and the formation of aminoacyl-tRNA. Time-series analysis revealed variations in differential gene expression patterns between the two varieties, whereas significant protein expression trends in the two varieties were largely consistent, except for one profile. The expression of CYP84A, 4CL, and CAD from the key phenylpropanoid biosynthetic pathway was enhanced in GT42 at stage 2 but suppressed in GF98-296 at the growth stage. Furthermore, the expression of SDT1 in the nicotinate and nicotinamide metabolism was enhanced in GT42 cells but suppressed in GF98-296 cells at the growth stage. CONCLUSION: Our findings provide reference data for mining lodging tolerance-related genes that are expected to facilitate the selective breeding of sugarcane varieties with excellent lodging tolerance.

Oral mycobiota and pancreatic ductal adenocarcinoma.

Early detection of pancreatic ductal adenocarcinoma (PDAC) is essential for survival. Preliminary research demonstrated significant associations between structural alternation of mycobiota and PDAC. In this study, we investigated the associations between oral mycobiota and PDAC. We further explored mycobiota biomarkers for PDAC detection. We enrolled 34 PDAC patients and 35 matched healthy controls from West China hospital in Southwest China. Demographic data, clinical information, and salivary samples were collected. Mycobiota characteristics were defined using Internal Transcribed Spacer (ITS) ribosomal RNA sequencing. We found that the PDAC patients had significant increase in fungal abundance (P < 0.001) and significant decrease in fungal diversity (P < 0.001) in comparison to the healthy controls. A higher abundance of Basidiomycota and Unclassifed_p_Ascomycota was associated with an increased risk of PDAC. With each increase of abundance of g__unclassified_k__Fungi and g__unclassified_p__Ascomycota in PDAC patients, the risk of pancreatic cancer increased by 1.359 odds and 1.260 odds, respectively. Aspergillus (AUC = 0.983, 95% CI 0.951-1.000) and Cladosporium (AUC = 0.969, 95% CI 0.921-1.000) achieved high classification powers to distinguish PDAC patients from the healthy controls. The rapid, inexpensive tests of ITS1 sequencing of mycobiota and PCR detection of potential fungal biomarkers make it promising for the clinical practice to use oral microbes for PDAC early detection and prevention. Results of our study provide evidence that salivary mycobiota may provide insights into cancer risk, prevention, and detection.

Comparison of subtotal vertebral resection with reconstruction and percutaneous vertebroplasty for treatment of metastasis in the lumbar spine.

Purpose: Tumor metastasis in the spine can cause pain and fractures, leading to deformities, and deficits in movement, sensation, and bowel/bladder function. Percutaneous vertebroplasty (PVP) and subtotal vertebral resection with reconstruction (SVR) are suitable treatments, but their relative clinical efficacy is uncertain. The purpose of this retrospective cohort study was to compare the management and clinical effect of SVR for lumbar metastatic tumor with PVP.Methods: Sixty-seven patients (mean age: 58.6 years) with metastases in the lumbar spine received SVR or PVP at our institution between 2010 and 2013. Thirty-three patients received SVR via a posterior approach, in which vertebrae were resected, with the anterior and lateral walls retained using polymethylmethacrylate (PMMA), followed by reconstruction and pedicle screw fixation. Thirty-four patients received PVP via the vertebral pedicle. Patients were followed for 3-26 months.Results: None of the patients experienced serious complications after surgery, and all patients experienced significant amelioration of pain. Twelve patients (8 in the PVP group and 4 in the SVR group) died during the follow-up, and the survival time was significantly longer in the SVR group. Two patients in the SVR group and 7 patients in the PVP groups experienced recurrence during follow-up, but the groups had no significant difference in local recurrence. Both treatments significantly reduced scores for pain on a visual analog scale (pain-VAS) and disability (Oswestry Disability Index [ODI]), and increased performance status (Karnofsky Performance Status [KPS]). Compared with the PVP group, the SVR group had better ODI score at 1 month and 3 months after surgery and a higher KPS score at 1 month after surgery. The two groups had no significant difference in pain-VAS scores during follow-up.Conclusions: SVR is a reliable treatment for lumbar metastatic tumor and provides good survival rate and satisfying follow-up results.

Deregulated expression of miR-107 inhibits metastasis of PDAC through inhibition PI3K/Akt signaling via caveolin-1 and PTEN.

Pancreatic ductal adenocarcinoma (PDAC) displays a highly aggressive malignancy and is considered to be an incurable and rapidly lethal disease. MicroRNAs (miRNAs) are small non-coding RNAs of approximately nucleotides that regulate several aspects of tumors pathogenesis, including migration, invasion, metastasis and epithelial-mesenchymal transition. We have found that miR-107 was significantly high expression in PDAC tissues and cells. High miR-107 expression is associated with poor clinicopathological parameters and prognosis in PDAC patients. Deregulated expression of miR-107 in PDAC cells (AsPC-1 and Panc-1) is sufficient to reduce cell migration and invasion, and to induce upregulation of epithelial markers (ß-catenin, ZO-1 and E-cadherin) and a decrease of mesenchymal marker expression (ZEB-1 and vimentin). We also found that the caveolin-1, PTEN and p-Akt expression are modulated by miR-107 in PDAC cells. Moreover, our study clearly demonstrated that deregulated expression of miR-107 inhibited cell migration and invasion and EMT by up-regulation of caveolin-1 and PTEN, and inhibition of PI3K/Akt signaling in PDAC cells. Our study suggested that miR­107 expression might both be a useful indicator of the metastatic potential and provided a new potential therapeutic target in PDAC.

[Expression of TWEAK/Fn14 in Pancreatic Cancer].

OBJECTIVES: To investigate the effect of tumor necrosis factor -related weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) on the proliferation and growth of pancreatic cancer. METHODS: Human pancreatic cancer (50 cases), chronic pancreatitis (40 cases) and normal pancreatic tissues (30 cases) were collected in West China Hospital from January 2012 to December 2013. TWEAK and Fn14 expressions in these tissues were checked with hematoxylin-eosin (HE) staining and immunohistochemistry method. Relationship between TWEAK expression and clinicopathological features of pancreatic cancer was analyzed. RESULTS: TWEAK expression rate was 36% (18/50) in pancreatic cancer, higher than that in chronic pancreatitis (17.5%, 7/40) and normal pancreatic tissues (13.3%, 4/30) ( P<0.05) .Expression intensity of TWEAK in three groups was also obviously ( P<0.05). The expression rate of Fn14 was 4.0% in pancreatic cancer , 7.0% in normal pancreatic tissues , and 0% in chronic pancreatitis. TWEAK positive expression rate and high expression rate in pancreatic cancer were higher in IIB group ( P<0.05). Pathological grade was not related to TWEAK expression. CONCLUSIONS: TWEAK/Fn14 involved in the progression of pancreatic cancer. In the tissue of pancreatic cancer, TWEAK was highly expressed, and Fn14 was lowly expressed.

Protection of carboxymethylated chitosan on chondrocytes from nitric oxide-induced apoptosis by regulating phosphatidylinositol 3-kinase/Akt signaling pathway.

Chondrocyte apoptosis is the most important element of development and progression of osteoarthritis (OA). Nitric oxide (NO) was used as the agent to induce chondrocyte apoptosis. Carboxymethylated chitosan (CMCS) has anti-apoptosis effect on many cell types in vitro. This study was designed to investigate the protective effect of CMCS on NO-induced chondrocyte apoptosis and the probable molecular mechanisms. The newborn Sprague-Dawley (SD) rats were used in this study for isolation of chondrocytes. The cell viability was determined by cell counting kit (CCK-8), cell apoptosis was detected by Annexin-V/PI double staining assay kit. The levels of phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), Bcl-2 and Bax were determined by Western blot analysis. The caspase-3 activity was determined by a quantitative colorimetric assay. Results showed that pretreatment with CMCS could inhibit the apoptosis induced by NO. CMCS could decrease the activity of NO and decrease the expression of Bcl-2, p-PI3K and p-Akt, increase the expression of Bax, cytochrome c and caspase-3. CMCS also could reverse the effect of NO that prompted matrix metalloproteinase-13 (MMP-13) and inhibited tissue inhibitor of metalloproteinase-1 (TIMP-1) activity. All the present results indicated that CMCS can protect NO induced chondrocytes apoptosis by activate PI3K/Akt signaling pathway.

Clinical outcomes of combined necrotizing pancreatitis versus extrapancreatic necrosis alone.

INTRODUCTION: Extrapancreatic necrosis (EPN) alone, i.e., in the absence of pancreatic parenchyma necrosis has gradually come to be regarded as a separate entity of acute necrotizing pancreatitis (ANP). However, data regarding the prognostic significance of EPN are quite limited, and the outcomes of interventions for patients with EPN alone are not well elucidated. The aim of this study was to explore the differences in the outcomes of patients with EPN alone and patients with both the pancreatic parenchyma and extrapancreatic necrosis (combined necrosis). METHODS: From January 2009 to December 2013, a total of 334 patients with ANP who had received interventions in the West China Hospital in China were included. Based on the extent of necrosis as assessed with contrast-enhanced CT, the patients were divided into Group 1 (n = 285) in which the necrosis involved both the pancreatic parenchyma and extrapancreatic tissues (combined necrosis) and Group 2 (n = 49) in which the necrosis involved only the extrapancreatic tissues. Additionally, Group 3 included 443 patients with interstitial pancreatitis who were also included in the analyses. The demographic characteristics, support treatment information, organ failure information, infection necrosis, persistent systemic inflammatory response syndrome (SIRS) in the first week of onset, CT severity index, and intervention types, as well as the postoperative stay lengths, ICU utility, and complications were collected and compared. RESULTS: Compared with the patients in Group 1, the patients in Group 2 suffered less persistent SIRS in the first week of onset (12/24.5% vs. 145/50.9%; P < 0.05), less persistent organ failure (6/12.2% vs. 95/33.3%; P < 0.05), less persistent multiple organ failure (3/6.1% vs. 67/23.5%; P < 0.05), and less bacteremia (5/10.2% vs. 107/37.5%; P < 0.001). The intervention types were significantly different between the two groups (P < 0.001); initial open necrosectomy was performed in 174/61.6% and 8/16.3% of the patients in Groups 1 and 2, respectively, and initial percutaneous catheter drainage (PCD) was performed in 73/25.6% and 29/59.2% of the patients in the two respective groups. Second open necrosectomies following PCD were required in 61/83.5% and 9/31.0% of the patients in Groups 1 and 2, respectively (P < 0.001). A greater number of patients in Group 1 were diagnosed with infected necrosis (204/71.6% vs. 10/20.4%; P < 0.001) and had to be sent to the ICU for further postoperative care (221/77.5% vs. 23/46.9%; P < 0.001). The postoperative stay was longer for Group 1 (median: 43.0 vs. 26.5 days; P < 0.001). Residual necrotic tissue or abscess was the most common postoperative complication in both groups. The mortality was higher in Group 1 (52/18.2% vs. 1/2.1%; P < 0.05). Compared with the patients in Group 2, the patients with interstitial pancreatitis exhibited milder courses and better outcomes. Subgroup comparisons with Group 1 indicated that early multiple organ failure was significantly associated with higher mortality. CONCLUSION: The patients with EPN alone exhibited significantly better prognoses than those with combined necrosis, and EPN alone should be regarded as a separate group of acute necrotizing pancreatitis. Open necrosectomy can be avoided in the majority of patients with EPN alone, who receive PCD as the initial first intervention.

Major hepatectomy in Bismuth types I and II hilar cholangiocarcinoma.

BACKGROUND: Historically, hilar bile duct resection (HBDR) has been regarded as the choice of treatment for Bismuth types I and II hilar cholangiocarcinoma (HCCA). The present study aimed to evaluate the advantages of major liver resection (MLR) in the treatment of patients with Bismuth types I and II HCCA when compared with HBDR. MATERIALS AND METHODS: Between January 2005 and September 2012, in total, 52 patients with Bismuth types I and II HCCA who underwent HBDR alone or MLR were included for retrospective analysis. The intraoperative outcomes, postoperative complications, and oncological outcomes including recurrence and overall or disease-free survival rate were compared. RESULTS: The MLR group had significantly higher curative resection rates compared with the HBDR group (95% versus 62.5%, P = 0.021) and lower tumor recurrence (28% versus 63%, P = 0.049), albeit with longer operating time (395.5 ± 112.7 versus 270.9 ± 98.8, P < 0.001), and higher blood transfusion requirements (70% versus 16%, P < 0.001). MLR resulted in significantly higher overall postoperative morbidity (70% versus 34.4%, P = 0.012), compared with HBDR alone. When restricted to R0 resections for all the procedures, MLR significantly increased the overall postoperative survival rate compared with the HBDR group (P = 0.016); the overall survival rate at 1, 3 y was 68.4% and 60.8% for MLR group and 59.6% and 21.9% for HBDR group, respectively. Also, the disease-free survival rate was significantly higher in patients who underwent MLR, as compared with those who underwent HBDR (53.2% versus 0% at 3 y, P = 0.005). CONCLUSIONS: Our study has shown that MLR results in higher curative resections, fewer recurrences, and increased postoperative survival rate for Bismuth types I and II HCCA as compared with HBDR alone. However, there is a need for well-designed, multicenter studies to be undertaken to better inform a decision on the standard treatment for Bismuth types I and II HCCA.

MuTrans: Multiple Transformers for Fusing Feature Pyramid on 2D and 3D Object Detection.

One of the major components of the neural network, the feature pyramid plays a vital part in perception tasks, like object detection in autonomous driving. But it is a challenge to fuse multi-level and multi-sensor feature pyramids for object detection. This paper proposes a simple yet effective framework named MuTrans (Mu ltiple Trans formers) to fuse feature pyramid in single-stream 2D detector or two-stream 3D detector. The MuTrans based on encoder-decoder focuses on the significant features via multiple Transformers. MuTrans encoder uses three innovative self-attention mechanisms: S patial-wise B oxAlign attention (SB) for low-level spatial locations, C ontext-wise A ffinity attention (CA) for high-level context information, and high-level attention for multi-level features. Then MuTrans decoder processes these significant proposals including the RoI and context affinity. Besides, the L ow and H igh-level F usion (LHF) in the encoder reduces the number of computational parameters. And the Pre-LN is utilized to accelerate the training convergence. LHF and Pre-LN are proven to reduce self-attention's computational complexity and slow training convergence. Our result demonstrates the higher detection accuracy of MuTrans than that of the baseline method, particularly in small object detection. MuTrans demonstrates a 2.1 higher detection accuracy on APS index in small object detection on MS-COCO 2017 with ResNeXt-101 backbone, a 2.18 higher 3D detection accuracy (moderate difficulty) for small object-pedestrian on KITTI, and 6.85 higher RC index (Town05 Long) on CARLA urban driving simulator platform.

Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA.

BACKGROUND: Using epigenetic markers and fragmentomics of cell-free DNA for cancer detection has been proven applicable. METHODS: We further investigated the diagnostic potential of combining two features (epigenetic markers and fragmentomic information) of cell-free DNA for detecting various types of cancers. To do this, we extracted cfDNA fragmentomic features from 191 whole-genome sequencing data and studied them in 396 low-pass 5hmC sequencing data, which included four common cancer types and control samples. RESULTS: In our analysis of 5hmC sequencing data from cancer samples, we observed aberrant ultra-long fragments (220-500 bp) that differed from normal samples in terms of both size and coverage profile. These fragments played a significant role in predicting cancer. Leveraging the ability to detect cfDNA hydroxymethylation and fragmentomic markers simultaneously in low-pass 5hmC sequencing data, we developed an integrated model that incorporated 63 features representing both fragmentomic features and hydroxymethylation signatures. This model achieved high sensitivity and specificity for pan-cancer detection (88.52% and 82.35%, respectively). CONCLUSION: We showed that fragmentomic information in 5hmC sequencing data is an ideal marker for cancer detection and that it shows high performance in low-pass sequencing data.

SurgSmart: an artificial intelligent system for quality control in laparoscopic cholecystectomy: an observational study.

BACKGROUND: The rate of bile duct injury in laparoscopic cholecystectomy (LC) continues to be high due to low critical view of safety (CVS) achievement and the absence of an effective quality control system. The development of an intelligent system enables the automatic quality control of LC surgery and, eventually, the mitigation of bile duct injury. This study aims to develop an intelligent surgical quality control system for LC and using the system to evaluate LC videos and investigate factors associated with CVS achievement. MATERIALS AND METHODS: SurgSmart, an intelligent system capable of recognizing surgical phases, disease severity, critical division action, and CVS automatically, was developed using training datasets. SurgSmart was also applied in another multicenter dataset to validate its application and investigate factors associated with CVS achievement. RESULTS: SurgSmart performed well in all models, with the critical division action model achieving the highest overall accuracy (98.49%), followed by the disease severity model (95.45%) and surgical phases model (88.61%). CVSI, CVSII, and CVSIII had an accuracy of 80.64, 97.62, and 78.87%, respectively. CVS was achieved in 4.33% in the system application dataset. In addition, the analysis indicated that surgeons at a higher hospital level had a higher CVS achievement rate. However, there was still considerable variation in CVS achievement among surgeons in the same hospital. CONCLUSIONS: SurgSmart, the surgical quality control system, performed admirably in our study. In addition, the system's initial application demonstrated its broad potential for use in surgical quality control.

SPD: Semi-Supervised Learning and Progressive Distillation for 3-D Detection.

Current learning-based 3-D object detection accuracy is heavily impacted by the annotation quality. It is still a challenge to expect an overall high detection accuracy for all classes under different scenarios given the dataset sparsity. To mitigate this challenge, this article proposes a novel method called semi-supervised learning and progressive distillation (SPD), which uses semi-supervised learning (SSL) and knowledge distillation to improve label efficiency. The SPD uses two big backbones to hand the unlabeled/labeled input data augmented by the periodic IO augmentation (PA). Then the backbones are compressed using progressive distillation (PD). Precisely, PA periodically shifts the data augmentation operations between the input and output of the big backbone, aiming to improve the network's generalization of the unseen and unlabeled data. Using the big backbone can benefit from large-scale augmented data better than the small one. And two backbones are trained by the data scale and ratio-sensitive loss (data-loss). It solves the over-flat caused by the large-scale unlabeled data from PA and helps the big backbone prevent overfitting on the limited-scale labeled data. Hence, using the PA and data loss during SSL training dramatically improves the label efficiency. Next, the trained big backbone set as the teacher CNN is progressively distilled to obtain a small student model, referenced as PD. PD mitigates the problem that student CNN performance degrades when the gap between the student and the teacher is oversized. Extensive experiments are conducted on the indoor datasets SUN RGB-D and ScanNetV2 and outdoor dataset KITTI. Using only 50% labeled data and a 27% smaller model size, SPD performs 0.32 higher than the fully supervised VoteNetqi2019deep which is adopted as our backbone. Besides, using only 2% labeled data, compared to the other fully supervised backbone PV-RCNNshi2020pv, SPD accomplishes a similar accuracy (84.1 and 84.83) and 30% less inference time.

Critical view of safety in laparoscopic cholecystectomy: A prospective investigation from both cognitive and executive aspects.

Background: The achievement rate of the critical view of safety during laparoscopic cholecystectomy is much lower than expected. This original study aims to investigate and analyze factors associated with a low critical view of safety achievement. Materials and Methods: We prospectively collected laparoscopic cholecystectomy videos performed from September 2, 2021, to September 19, 2021, in Sichuan Province, China. The artificial intelligence system, SurgSmart, analyzed videos under the necessary corrections undergone by expert surgeons. Also, we distributed questionnaires to surgeons and analyzed them along with surgical videos simultaneously. Results: We collected 169 laparoscopic cholecystectomy surgical videos undergone by 124 surgeons, among which 105 participants gave valid answers to the questionnaire. Excluding those who conducted the bail-out process directly, the overall critical view of safety achievement rates for non-inflammatory and inflammatory groups were 18.18% (18/99) and 9.84% (6/61), respectively. Although 80.95% (85/105) of the surgeons understood the basic concept of the critical view of safety, only 4.76% (5/105) of the respondents commanded all three criteria in an error-free way. Multivariate logistic regression results showed that an unconventional surgical workflow (OR:12.372, P < 0.001), a misunderstanding of the 2nd (OR: 8.917, P < 0.05) and 3rd (OR:8.206, P < 0.05) criterion of the critical view of safety, and the don't mistake "fundus-first technique" as one criterion of the critical view of safety (OR:0.123, P < 0.01) were associated with lower and higher achievements of the critical view of safety, respectively. Conclusions: The execution and cognition of the critical view of safety are deficient, especially the latter one. Thus, increasing the critical view of safety surgical awareness may effectively improve its achievement rate.

A size-shrinkable matrix metallopeptidase-2-sensitive delivery nanosystem improves the penetration of human programmed death-ligand 1 siRNA into lung-tumor spheroids.

Given the maturation of small-interfering RNA (siRNA) techniques with nanotechnology, and because overexpression of human programmed death-ligand 1 (PD-L1) is crucial for T cell inactivation and immunosuppression of the tumor microenvironment, application of siRNA-PD-L1 has demonstrated positive progress in preclinical studies; however, the limited penetration of this compound into solid tumors remains a challenge. To decrease PD-L1 expression and increase the penetration efficacy of solid tumors, we synthesized a novel tumor-microenvironment-sensitive delivery polymer by conjugating hyaluronic acid (HA) to polyethyleneimine (PEI), with a matrix metalloproteinase-2 (MMP-2)-sensitive peptide acting as the linker (HA-P-PEI), for use in delivery of PD-L1-siRNA. Concurrent synthesis of a linker-less HA-PEI compound allowed confirmation that negatively charged siRNA can be complexed onto the positively charged HA-PEI and HA-P-PEI compounds to form nanoparticles with the same particle size and uniform distribution with serum stability. We found that the size of the HA-P-PEI/siRNA nanoparticles decreased to <10 nm upon addition of MMP-2, and that H1975 cells overexpressing CD44, PD-L1, and MMP-2 aided confirmation of the delivery efficacy of the HA-P-PEI/siRNA nanocomplexes. Additionally, the use of HA-P-PEI caused less cytotoxicity than PEI alone, demonstrating its high cellular uptake. Moreover, pretreatment with MMP-2 increased nanocomplex tumor permeability, and western blot showed that HA-P-PEI/PD-L1-siRNA efficiently downregulated the PD-L1 expression in H1975 cells. These results demonstrated a novel approach for siRNA delivery and tumor penetration for future clinical applications in cancer treatment.

Primary hepatic myelolipoma: A case report and review of the literature.

BACKGROUND: Primary hepatic myelolipoma is a rare hepatic mesenchymal tumor mixed by adipose tissue and bone marrow, and there is a lack of general guidelines related to its epidemiology and clinical management. CASE SUMMARY: A 26-year-old woman was admitted to our department complaining of a newly found tumor on her left lobe of the liver. The tumor was painless and not associated with any systemic or localized compressive symptoms. Serological tests disclosed a slight increase of gamma-glutamyl transpeptidase (70.0 U/L) and total bilirubin (19.2 µmol/L). Ultrasonography showed a mass about 5.0 cm × 5.0 cm in size that was located in the left lobe of the liver and displayed hyperechoic and well-encapsulated characteristics. Surgical resection was applied, and the following histopathological examination observed a variable proportion of myeloid tissues scattering throughout mature fibrotic adipose tissues, in which myeloid, erythroid, and megakaryocytic cells can be found in magnified view. The follow-up did not show any changes 6 mo after surgery. CONCLUSION: This case highlights an extremely rare hepatic mesenchymal tumor, the primary hepatic myelolipoma, and discloses the common characteristics behind this disease and gives clinical recommendations.

Blumgart anastomosis reduces the incidence of pancreatic fistula after pancreaticoduodenectomy: a systematic review and meta-analysis.

Postoperative pancreatic fistula (POPF) is the most serious complication after pancreaticoduodenectomy (PD). Recently, Blumgart anastomosis (BA) has been found to have some advantages in terms of decreasing POPF compared with other pancreaticojejunostomy (PJ) using either the duct-to-mucosa or invagination approach. Therefore, the aim of this study was to examine the safety and effectiveness of BA versus non-Blumgart anastomosis after PD. The PubMed, EMBASE, Web of Science and the Cochrane Central Library were systematically searched for studies published from January 2000 to March 2020. One RCT and ten retrospective comparative studies were included with 2412 patients, of whom 1155 (47.9%) underwent BA and 1257 (52.1%) underwent non-Blumgart anastomosis. BA was associated with significantly lower rates of grade B/C POPF (OR 0.38, 0.22 to 0.65; P = 0.004) than non-Blumgart anastomosis. Additionally, in the subgroup analysis, the grade B/C POPF was also reduced in BA group than the Kakita anastomosis group. There was no significant difference regarding grade B/C POPF in terms of soft pancreatic texture between the BA and non-Blumgart anastomosis groups. In conclusion, BA after PD was associated with a decreased risk of grade B/C POPF. Therefore, BA seems to be a valuable PJ to reduce POPF comparing with non-Blumgart anastomosis.

In Vivo-Like Morphology of Intercalated Discs Achieved in a Neonatal Cardiomyocyte Culture Model.

In vitro cultures to be used in various analytical investigations of cardiomyocyte (CM) growth and function for enhancing insight into physiological and pathological mechanisms should closely express in vivo morphology. The aim of the studies is to explore how to use microfabrication and physical-cue-addition techniques to establish a neonatal rat CM culture model that expresses an end-to-end connected rod shape with in vivo-like intercalated discs (ICDs). Freshly isolated neonatal rat CMs were cultured on microgrooved polydimethylsiloxane substrate. Cell alignment and ICD orientation were evaluated using confocal fluorescence and transmission electron microscopy under various combinations of different culture conditions. Cyclic stretch and blebbistatin tests were conducted to explore mechanical and electrical effects. Laboratory-made MATLAB software was developed to quantify cell alignment and ICD orientation. Our results demonstrate that the mechanical effect associated with the electrical stimulation may contribute to step-like ICD formation viewed from the top. In addition, our study reveals that a suspended elastic substrate that was slack with scattered folds, not taut, enabled CM contraction of equal strength on both apical and basal cell surfaces, allowing the cultured CMs to express a three-dimensional rod shape with disc-like ICDs viewed cross-sectionally. Impact statement In this article, we describe how the tugging forces generated by cardiomyocytes (CMs) facilitate the formation of the morphology of the intercalated discs (ICDs) to achieve mechanoelectrical coupling between CMs. Correspondingly, we report experimental techniques we developed to enable the in vivo-like behavior of the tugging forces to support the development of in vivo-like morphology in ICDs. These techniques will enhance insight into physiological and pathological mechanisms related to the development of tissue-engineered cardiac constructs in various analytical investigations of CM growth and function.

Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer.

BACKGROUND: The high lethal rate of pancreatic cancer is partly due to a lack of efficient biomarkers for screening and early diagnosis. We attempted to develop effective and noninvasive methods using 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) markers from circulating cell-free DNA (cfDNA) for the detection of pancreatic ductal adenocarcinoma (PDAC). RESULTS: A 24-feature 5mC model that can accurately discriminate PDAC from healthy controls (area under the curve (AUC) = 0.977, sensitivity = 0.824, specificity = 1) and a 5hmC prediction model with 27 features demonstrated excellent detection power in two distinct validation sets (AUC = 0.992 and 0.960, sensitivity = 0.786 and 0.857, specificity = 1 and 0.993). The 51-feature model combining 5mC and 5hmC markers outperformed both of the individual models, with an AUC of 0.997 (sensitivity = 0.938, specificity = 0.955) and particularly an improvement in the prediction sensitivity of PDAC. In addition, the weighted diagnosis score (wd-score) calculated with the 5hmC model can distinguish stage I patients from stage II-IV patients. CONCLUSIONS: Both 5mC and 5hmC biomarkers in cfDNA are effective in PDAC detection, and the 5mC-5hmC integrated model significantly improve the detection sensitivity.

Oral microbiome and pancreatic cancer.

BACKGROUND: Microbiota profiles differ between patients with pancreatic cancer and healthy people, and understanding these differences may help in early detection of pancreatic cancer. Saliva sampling is an easy and cost-effective way to determine microbiota profiles compared to fecal and tissue sample collection. AIM: To investigate the saliva microbiome distribution in patients with pancreatic adenocarcinoma (PDAC) and the role of oral microbiota profiles in detection and risk prediction of pancreatic cancer. METHODS: We conducted a prospective study of patients with pancreatic cancer (n = 41) and healthy individuals (n = 69). Bacterial taxa were identified by 16S ribosomal ribonucleic acid gene sequencing, and a linear discriminant analysis effect size algorithm was used to identify differences in taxa. Operational taxonomic unit values of all selected taxa were converted into a normalized Z-score, and logistic regressions were used to calculate risk prediction of pancreatic cancer. RESULTS: Compared with the healthy control group, carriage of Streptococcus and Leptotrichina (z-score) was associated with a higher risk of PDAC [odds ratio (OR) = 5.344, 95% confidence interval (CI): 1.282-22.282, P = 0.021 and OR = 6.886, 95%CI: 1.423-33.337, P = 0.016, respectively]. Veillonella and Neisseria (z-score) were considered a protective microbe that decreased the risk of PDAC (OR = 0.187, 95%CI: 0.055-0.631, P = 0.007 and OR = 0.309, 95%CI: 0.100-0.952, P = 0.041, respectively). Among the patients with PDAC, patients reporting bloating have a higher abundance of Porphyromonas (P = 0.039), Fusobacterium (P = 0.024), and Alloprevotella (P = 0.041); while patients reporting jaundice had a higher amount of Prevotella (P = 0.008); patients reporting dark brown urine had a higher amount of Veillonella (P = 0.035). Patients reporting diarrhea had a lower amount of Neisseria and Campylobacter (P = 0.024 and P = 0.034), and patients reporting vomiting had decreased Alloprevotella (P = 0.036). CONCLUSION: Saliva microbiome was able to distinguish patients with pancreatic cancer and healthy individuals. Leptotrichia may be specific for patients living in Sichuan Province, southwest China. Symptomatic patients had different bacteria profiles than asymptomatic patients. Combined symptom and microbiome evaluation may help in the early detection of pancreatic cancer.

Repairing peripheral nerve defects with tissue engineered artificial nerves in rats.

OBJECTIVE: To observe the effect of tissue engineered nerves in repairing peripheral nerve defects (about 1.5 cm in length) in rats to provide data for clinical application. METHODS: Glycerinated sciatic nerves (2 cm in length) from 10 Sprague Dawley (SD) rats (aged 4 months) were used to prepare homologous dermal acellular matrix. Other 10 neonate SD rats (aged 5-7 days) were killed by neck dislocation. After removing the epineurium, the separated sciatic nerve tracts were cut into small pieces, then digested by 2.5 g/L trypsin and 625 U/ml collagenase and cultured in Dulbecco's modified Eagle's medium (DMEM) for 3 weeks. After proliferation, the Schwann cells (SCs) were identified and prepared for use. And other 40 female adult SD rats (weighing 200 g and aged 3 months) with sciatic nerve defects of 1.5 cm in length were randomly divided into four groups: the defects of 10 rats bridged with proliferated SCs and homologous dermal acellular matrix (the tissue engineered nerve group, Group A), 10 rats with no SCs but homologous dermal acellular matrix with internal scaffolds (Group B), 10 with autologous nerves (Group C), and the other 10 with nothing (the blank control group, Group D). The general status of the rats was observed, the wet weight of triceps muscle of calf was monitored, and the histological observation of the regenerated nerves were made at 12 weeks after operation. RESULTS: The wounds of all 40 rats healed after operation and no death was found. No foot ulceration was found in Groups A, B and C, but 7 rats suffered from foot ulceration in Group D. The triceps muscles of calf were depauperated in the experimental sides in all the groups compared with the uninjured sides, which was much more obvious in Group D. The wet weight of triceps muscle of calf and nerve electrophysiologic monitoring showed no statistical difference between Group A and Group C, but statistical difference was found between Groups A and B and Groups B and D. And significant statistical difference was found between Group B and Group D. Obvious compound muscle (or motor) action potential (CMAP) could be evoked in Group A and Group C, but the evoked amplitude was very low in Group B and Group D. The axons of regenerated nerves penetrated through the whole graft in Group A and Group C, and partly penetrated through the graft in Group B, but did not penetrate in Group D. The two tips of the separated sciatic nerves of Groups A , B , and C were connected together, without formation of neuroma. But those of Group D were not connected together and neuroma formed in 6 rats. CONCLUSIONS: Tissue engineered nerves can be used for repairing long defects of the peripheral nerves of rats and ideal repairing effects can be obtained.