Tribofilm Formation of Zinc Dialkyldithiophosphate as Oil Additives Impregnated in Porous Polyimide under Different Contacts.

To improve the tribological properties of porous polyimide (PPI), ZDDP-mixed PAO4 was impregnated in PPI (denoted as ZPPI), and the tribological properties of ZPPI under single- and double-contacts were investigated. In the single-contact of ZPPI-steel, a rough and thick tribofilm was formed on the steel ball, which could protect the steel surface but resulted in large fluctuations in the friction coefficient. In the double-contact of ZPPI-steel-steel, ZDDP formed a uniform and thinner tribofilm on steel surfaces, leading to a lower friction. ZDDP could inhibit the formation of iron oxides significantly in the double-contact, while the antioxidant effect of ZDDP in the single-contact of ZPPI-steel was not obvious. ZnS and ZnO generated from ZDDP were adsorbed in the ZPPI pores, which aggravated the blackening of the ZPPI worn surface.

Correlation Analysis of the Pneumatization of the Supraorbital Ethmoid Cell and the Position of the Anterior Ethmoidal Artery.

OBJECTIVES: This study aimed to measure the supraorbital ethmoid cell (SOEC) and characterize the relationship between the degree of SOEC pneumatization and the position of the anterior ethmoidal artery (AEA) in relation to the skull base. METHODS: Computed tomography (CT) scans of 100 patients were analyzed. The correlation between the pneumatization of SOEC and the distance of the AEA from the skull base was explored by Spearman's correlation rho efficient test. RESULTS: The distance of the AEA from skull base was 3.10 (2.60,3.60) mm in patients with SOEC compared with 0.6(0.40,2.10)mm in those without(P < .001). In 50.5% of the patients, the AEA was located below the skull base; the incidence of this localization was significantly higher in those with SOEC than in those without (78.79%vs22.77%, P < .001). Compared to female patients, male patients owned greater SOEC height (9.65vs8.20mm, P = .007). The SOECs volume (r = 0.45, P < .001), height (r = .30, P = .003), and transverse diameter (r = 0.28, P = .005) were all significantly correlated with the distance of the AEA from the skull base. CONCLUSIONS: The pneumatization of SOEC critically impact the distance between the AEA and skull base. The higher the degree of pneumatization, the farther from the skull base the AEA will be, increasing the risk of complications during nasal endoscopic surgery. These results provide an important reference for protecting the AEA during nasal endoscopic surgery.

A sequentially responsive cascade nanoplatform for increasing chemo-chemodynamic therapy.

Poly(lactide-co-glycolide) (PLGA) is promising carrier material for drugs delivery in cancer therapy. However, the slow degradation and lack of targeting have greatly limited the clinical effectiveness of PLGA-based nanomedicines. Herein, we fabricated a hybrid nanosystem (3 P @ He/Pt-NPs) comprising of acid-sensitive polymer (mPOE-PLGA), active-targeting polymer (PBA-PLGA) and therapeutic agents (hemin+cisplatin) to combat these problems. In neutral environment, PEGylation can effectively improve the blood stability and circulation time of hybrid nanosystem. After reaching tumor regions, this nanosystem efficiently increased cellular uptake by dePEGylation and PBA-mediated active-targeting. Furthermore, encapsulated hemin could catalyze the oxygen bubbles generation, which remarkably increasing the drugs release rate. Subsequently, hybrid particles produced a higher cell-killing effect to lung cancer cells (A549) by the combination therapy (chemotherapy and chemodynamic therapy (CDT)). Importantly, cisplatin further amplified CDT effect by inducing H2O2 regeneration owing to the cascade enzymatic reactions, while hemin decreased intracellular glutathione (GSH) level, resulting in a low detoxification effect to cisplatin. Thus, hybrid particles could efficiently inhibit drug-resistant tumor growth and the inhibition rate reached 83.2%. Overall, this hybrid polymer nanosystem improve the drawbacks of PLGA-based nanocarriers, and can realize a cascading enhanced tumor treatment.

Short-term exposure of HFD depresses intestinal cholinergic anti-inflammatory activity through hypothalamic inflammation in mice.

High-fat diet (HFD) exposure has been proven to impair vagus nerve function. However, it is not yet known whether the HFD challenge impacts vagal efferent-based intestinal cholinergic anti-inflammation activity. This investigation aims to evaluate the effect of HFD on intestinal cholinergic anti-inflammatory activity in mice. Mice with or without intracerebroventricular treatment with an antibody against toll-like receptor 4 (TLR4) were fed with HFD or standard chow for 2 weeks. Vagus nerve-based anti-inflammatory activity was analyzed by heart rate variability. Acetylcholine (ACh) content, nicotinic acetylcholine receptor α7 subtype (α7nAChR), and pro-inflammatory cytokines were analyzed by biochemical kits or qRT-PCR. HFD feeding mice exhibit a significant increase in high frequency (HF) and a decrease in the ratio of low frequency/HF, which were accompanied by lower ACh levels and α7nAChR mRNA expression in the intestinal segments. However, anti-TLR4 antibody-treated HFD mice showed normal ACh levels and α7nAChR mRNA expression in the intestinal segments. Moreover, TNF-α production in small intestine was significantly reduced in HFD + antibody group compared with HFD + vehicle group. Collectively, our present results reveal that HFD challenge depresses intestinal cholinergic anti-inflammatory activity, which is mediated by hypothalamic inflammation. Impairment of intestinal cholinergic anti-inflammatory pathway is the cause of intestinal low-grade inflammation by HFD consumption.

Long-Term Effect of Pancreaticoduodenectomy Combined with Revascularization for Resectable Pancreatic Carcinoma in Elderly Patients.

BACKGROUND Pancreaticoduodenectomy combined with revascularization (PDR) is the main surgical procedure for resectable pancreatic ductal adenocarcinoma (PDAC) with venous system invasion, but this procedure is discouraged in elderly patients because of physical complexity. Our aim was to explore the differences of perioperative and survival in patients of different ages who underwent PDR. MATERIAL AND METHODS We reviewed data from PDAC patients undergoing PDR from 2007 to 2018. Patients were subdivided into 3 groups according to age: <60 years, 60-70 years, and ≥70 years. Postoperative complications and long-term survival were compared among the 3 groups. RESULTS From 626 patients, 185 had en bloc venous resection who underwent PDR (103, 55, and 27 patients from young to elderly). Increasing age was linked to a higher prevalence of ICU management (P=0.035) and more serious complications (grade ≥III, P=0.043); overall mortality was 8.1% and did not significantly differ among age-matched groups. Further, there was no difference in overall survival (OS) or progression-free survival (PFS) based on age (<60, 60-70, ≥70, median OS were 9.7, 8.4 vs 9.1 months, respectively, P=0.787; median PFS were 6.9, 6.1 vs 8.4 months, respectively, P=0.603). However, patients <60 years whose tumors invaded the superior mesenteric vascular had better survival outcomes when compared with the other 2 groups (11.5 vs 8.4, 9.1 months, P=0.049). CONCLUSIONS The results show that age should not be considered an absolute contraindication for PDR, as elderly patients can achieve the same surgical efficacy and long-term survival prognosis.

Clinical application of collagen membrane with umbilical cord-derived mesenchymal stem cells to repair nasal septal perforation.

Objective. We aimed to investigate the clinical efficacy of collagen membrane with umbilical cord-derived mesenchymal stem cells in the endoscopic repair of nasal septal perforation.Methods.We performed a prospective clinical trial between March 2017 and October 2019. Nasal septal perforations were repaired by the endoscopic sandwich technique with the collagen membrane and umbilical cord-derived mesenchymal stem cells. These patients were followed up postoperatively. Their outcomes were comprehensively evaluated by assessing the healing process of the perforations, the visual analog scale (VAS) for nasal discomfort, and the nasal mucociliary transit time (MTT) for the regenerated nasal mucosa.Results. Our study included a total of eight patients with nasal septal perforation (six males and two females, age 36.6 ± 12.8 years, diameter of perforation 1.0 ± 0.2 cm). Seven patients successfully underwent surgical repair. These patients had significantly improved VAS scores 1 month after the operations (1.1 ± 0.4) compared with the preoperative period (5.9 ± 0.7) (P< 0.05). Although the nasal MTT in the nasal septum and the inferior turbinate surface were within the normal limits before the operation and at 1 month after the operation, the postoperative transit time (11.1 ± 2.0 m) was significantly shorter than the preoperative transit time (12.1 ± 2.4 m) (P< 0.05). There were no recurrences of perforation, scab formations, or epistaxis after the operation.Conclusions. The application of the collagen membrane with umbilical cord-derived mesenchymal stem cells is a simple and feasible endoscopic procedure to repair perforated nasal septa and restore satisfactory functional mucosa.

Machine-learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection.

BACKGROUND AND AIMS: Up to 40%-65% of patients with perihilar cholangiocarcinoma (PHC) rapidly progress to early recurrence (ER) even after curative resection. Quantification of ER risk is difficult and a reliable prognostic prediction tool is absent. We developed and validated a multilevel model, integrating clinicopathology, molecular pathology and radiology, especially radiomics coupled with machine-learning algorithms, to predict the ER of patients after curative resection in PHC. METHODS: In total, 274 patients who underwent contrast-enhanced CT (CECT) and curative resection at 2 institutions were retrospectively identified and randomly divided into training (n = 167), internal validation (n = 70) and external validation (n = 37) sets. A machine-learning analysis of 18,120 radiomic features based on multiphase CECT and 48 clinico-radiologic characteristics was performed for the multilevel model. RESULTS: Comprehensively, 7 independent factors (tumour differentiation, lymph node metastasis, pre-operative CA19-9 level, enhancement pattern, A-Shrink score, V-Shrink score and P-Shrink score) were built to the multilevel model and quantified the risk of ER. We benchmarked the gain in discrimination with the area under the curve (AUC) of 0.883, superior to the rival clinical and radiomic models (AUCs 0.792-0.805). The accuracy (ACC) of the multilevel model was 0.826, which was significantly higher than those of the conventional staging systems (AJCC 8th (0.641), MSKCC (0.617) and Gazzaniga (0.581)). CONCLUSION: The radiomics-based multilevel model demonstrated superior performance to rival models and conventional staging systems, and could serve as a visual prognostic tool to plan surveillance of ER and guide post-operative individualized management in PHC.

The predictive value of the renal resistive index for contrast-induced nephropathy in patients with acute coronary syndrome.

BACKGROUND: Percutaneous coronary intervention (PCI) has been associated with contrast-induced nephropathy (CIN) at a rate that varies depending on the patient's risk factors. This study was conducted to evaluate the predictive value of the renal resistive index (RRI) for CIN in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: This prospective study enrolled 146 consecutive patients with ACS. Renal Doppler ultrasound examinations to measure RRI were performed pre-PCI and at 1 h and 24 h after PCI. The primary endpoint was CIN, defined as a relative (≥25%) or absolute (≥0.5 mg/dL; 44 µmol/L) increase in serum creatinine from baseline within 48 h after contrast exposure. RESULTS: CIN was identified in 31 patients (21.2%); however, none of the patients required haemodialysis. Compared to patients without CIN, higher RRIs were observed at 1 h (0.71 ± 0.05 vs. 0.65 ± 0.06, p < 0.05) and 24 h (0.70 ± 0.05 vs. 0.66 ± 0.06, p < 0.05) post-procedure in patients with CIN. The RRI rose transiently from baseline (0.68 ± 0.05) to 1 h (0.71 ± 0.05) and then tended to decline at 24 h (0.70 ± 0.05). A receiver operating characteristic curve analysis showed that the pre-procedure RRI was a powerful predictive indicator of CIN (area under the curve = 0.661, p = 0.006). The best cutoff value was 0.69 with 67.7% sensitivity and 67% specificity. Besides hyperuricemia and chronic kidney disease, the multivariate logistic regression analysis revealed that a high baseline RRI (≥0.69) was a significant predictor of CIN (odds ratio = 4.445; 95% confidence interval: 1.806-10.937; p = 0.001). CONCLUSIONS: A high pre-procedural RRI appears to be independently predictive of CIN in patients with ACS undergoing PCI.

eRF3b-37 inhibits the TGF-ß1-induced activation of hepatic stellate cells by regulating cell proliferation, G0/G1 arrest, apoptosis and migration.

The therapeutic management of liver fibrosis remains an unresolved clinical problem. The activation of hepatic stellate cells (HSCs) serves a pivotal role in the formation of liver fibrosis. In our previous study, matrix­assisted laser desorption/ionization time­of­flight mass spectrometry (MALDI­TOF MS) was employed to identify potential serum markers for liver cirrhosis, such as eukaryotic peptide chain releasing factor 3b polypeptide (eRF3b­37), which was initially confirmed by our group to serve a protective role in liver tissues in a C­C motif chemokine ligand 4­induced liver cirrhosis mouse model. Therefore, eRF3b­37 was hypothesized to affect the activation state of HSCs, which was determined by the expression of pro­fibrogenic associated factors in HSCs. In the present study, peptide synthesis technology was employed to elucidate the role of eRF3b­37 in the expression of pro­fibrogenic factors induced by transforming growth factor­ß1 (TGF­ß1) in LX­2 cells that were treated with either control, TGF­ß1 and TGF­ß1+eRF3b­37. 3­(4,5­Dimethyl­2­thiazolyl)­2,5­diphenyltetrazolium bromide and flow cytometric assays, and fluorescent microscope examinations were performed to evaluate the effects of eRF3b­37 on proliferation viability, G0/G1 arrest, apoptosis and cell migration. The results of the present study indicated that eRF3b­37 inhibited the activation of HSCs. The increased mRNA and protein expression of the pro­fibrogenic factors collagen I, connective tissue growth factor and α­smooth muscle actin (SMA) stimulated by TGF­ß1 were reduced by eRF3b­37 via the following mechanisms: i) Inhibiting LX­2 cell proliferation, leading to G0/G1 cell cycle arrest and inhibition of DNA synthesis by downregulating the mRNA expressions of Cyclin D1 and cyclin dependent kinase­4, and upregulating the levels of P21; ii) increasing cell apoptosis by upregulating the mRNA level of B­cell lymphoma-2 (Bcl­2)­associated X protein (Bax) and Fas, and downregulating the expression of Bcl­2; and iii) reducing cell migration by downregulating the mRNA and protein expression of α­SMA. In addition, eRF3b­37 is thought to serve a role in HSCs by inhibiting TGF­ß signaling. Therefore, eRF3b­37 may be a novel therapeutic agent for targeting HSCs for hepatic fibrosis.

Effect of histone modifications on hMLH1 alternative splicing in gastric cancer.

hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing. Our results showed that hMLH1 delEx10, delEx11, delEx10-11, delEx16 and delEx17 transcripts were ubiquitous in sporadic Chinese gastric cancer patients and gastric cancer cell lines. Lower level of H4K16ac and H3ac was detected in hMLH1 exon 10-11 region in gastric cancer cell lines when compared with human gastric mucosal epithelial cell line GES-1. A significant decrease of hMLH1 delEx11 and delEx10-11 was observed in gastric cancer cell lines after trichostatin A treatment. H3K36me3 and H3K4me2 levels were lower in hMLH1 exon 10-11 and exon 16-17 regions in gastric cancer lines when compared with GES-1. Aberrant transcripts such as hMLH1 delEx11 and delEx10-11 were significantly higher in gastric cancer cell lines after small interfering RNA-mediated knockdown of SETD2 (the specific methyltransferase of H3K36). The hMLH1 delEx10 and delEx10-11 transcripts were increased after interference of SRSF2. Taken together, our study demonstrates that lower level of histone acetylation and specific histone methylation such as H3K36me3 correlate with aberrant transcripts in hMLH1 exon 10-11 region. SRSF2 may be involved in these specific exons skipping as well.

[Clinical research progress of mesenteric internal hernia after Roux-en-Y reconstruction].

Postoperative internal hernia is a rare clinical complication which often occurs after digestive tract reconstruction. Roux-en-Y anastomosis is a common type of digestive tract reconstruction. Internal hernia after Roux-en-Y reconstruction, which occurs mainly in the mesenteric defect caused by incomplete closure of mesenteric gaps in the process of digestive tract reconstruction, is systematically called, in our research, as mesenteric internal hernia after Roux-en-Y reconstruction. Such internal hernia can be divided, according to the different structures of mesentric defect, into 3 types: the type of mesenteric defect at the jejunojejunostomy (J type), the type of Petersen's defect (P type), and the type of mesenteric defect in the transverse mesocolon (M type). Because of huge differences in the number of cases and follow-up time among existing research reports, the morbidity of internal hernia after LRYGB fluctuates wildly between 0.2% and 9.0%. Delayed diagnosis and treatment of mesenteric internal hernia after Roux- en-Y reconstruction may result in disastrous consequences such as intestinal necrosis. Clinical manifestations of internal hernia vary from person to person: some, in mild cases, may have no symptoms at all while others in severe cases may experience acute intestinal obstruction. Despite the difference, one common manifestation of internal hernia is abdominal pain. Surgical treatment should be recommended for those diagnosed as internal hernia. A safer and more feasible way to conduct the manual reduction of the incarcerated hernia is to start from the distal normal empty bowel and trace back to the hernia ring mouth, enabling a faster identification of hernia ring and its track. The prevention of mesenteric internal hernia after Roux-en-Y reconstruction is related to the initial surgical approach and the technique of mesenteric closure. Significant controversy remains on whether or not the mesenteric defect should be closed in laparoscopic Roux-en-Y anastomosis. This article is to review the reports and researches on internal hernia resulting from the mesenteric defect after Roux-en-Y digestive tract reconstruction in recent years, so as to promote understanding and attention on this disease. And more active preventive measures are strongly suggested to be taken in operations where digestive tract reconstruction is involved.

Effects of small interfering RNA-mediated downregulation of the Krüppel-like factor 4 gene on collagen metabolism in human hepatic stellate cells.

The nuclear transcription factor Krüppel-like factor 4 (KLF4) has an important role in cellular biological processes. However, the influence of KLF4 on collagen metabolism remains to be elucidated. In the present study, the effects and underlying mechanism of action of KLF4 on collagen metabolism was investigated in human hepatic stellate cells (HSC), by downregulating KLF4 expression using small interfering RNA (siRNA). The effects of KLF4 silencing by three predesigned siRNAs (siRNA1­3) were evaluated using both reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blotting in the human LX2 HSC line. The mRNA expression levels of KLF4 were decreased by ~34, 40, and 69% in the siRNA1, siRNA2, and siRNA3 groups, respectively, as compared with the control group. These results were concordant with the protein expression levels of KLF4, as determined by western blot analysis. In the siRNA3 group, the quantity of type Ⅰ and type III collagen, and the expression levels of collagen metabolism proteins including matrix metalloproteinase­1 (MMP­1) and tissue inhibitors of metalloproteinases­1 (TIMP­1), were determined using both RT­qPCR and western blotting. Both the mRNA and protein expression levels of type I and type III collagen were significantly decreased in the siRNA3 group, as compared with the control group. The mRNA and protein expression levels of TIMP­1 were also significantly reduced in the siRNA3­treated cells, whereas the mRNA and protein expression levels of MMP­1 were significantly upregulated. Furthermore, KLF4 gene silencing significantly decreased the expression levels of numerous cytokines, including transforming grow factor­ß1, tumor necrosis factor­α, and interleukin­1ß. The results of the present study provide evidence of siRNA­mediated silencing of KLF4 expression, which may promote extracellular matrix (ECM) degradation, and inhibition of ECM synthesis. Therefore, KLF4 may be a promising target for the development of novel antifibrotic therapies.

[Effects of taurine on tumor necrosis factor expression of lung in rats treated by silica].

OBJECTIVE: To evaluate the effects of taurine on the expression of tumor necrosis factor-alpha (TNF-alpha) protein of lung in rats treated by silica. METHODS: 144 Wistar rats were randomly divided into three experimental groups: saline-instilled with a control diet (saline-treated group), silica-instilled with a control diet (silica-treated group), and silica-instilled with a diet containing 2.5% taurine (taurine-treated group). There were 48 rats in every experimental group. Rats were treated by direct tracheal instillation of silica into rat lungs exposed surgically. 8 rats in every experimental group were killed at each at 6 time points (1, 3, 7, 14, 21 and 28 day) respectively. The taurine concentration of serum were analyzed by means of HPLC. The expression of TNF-alpha protein in paraffin-embedded lung sections with Streptavidin/ peroxidase(SP) immunohistochemistry on tissue microarray were measured by image-pro Plus. RESULTS: The concentration of taurine in serum of taurine-treated group were significantly elevated when compared with saline-treated and silica-treated groups (P < 0.05, P < 0.01). After instillation of silica, TNF-alpha positive area percent of the lung was elevated in silica-treated rats when compared with the corresponding saline-treated group, peaking at 7 days, and elevated by 6.57% and 2.37% at 7 days and 14 days respectively (P < 0.01 or P < 0.05). Taurine treatment significantly decreased silica-elevated TNF-alpha positive area percent by 3.52 at 7 day (P < 0.05). CONCLUSION: Treatment with taurine can effectively attenuate the pathological expression of TNF-alpha protein of lung in rats induced by silica.