The anesthesia management of totally thoracoscopic cardiac surgery: A single-center retrospective study.

Anesthesia management of Totally thoracoscopic cardiac surgery (TTCS) has been the subject of much debate and discussion. In this single center retrospective study, we summarize the experience of clinical anesthesia management for TTCS by review the medical records of our medical center and look forward to its future development. In this retrospective study, 103 patients (49 male and 54 female) were enrolled, the mean age was 56.7 ± 14.4 years old. The participants underwent Mitral Valve Replacement (MVR) + Tricuspid Valve Annuloplasty (TVA) (42, 40.8%), Mitral Valve Annuloplasty (MVA) + TVA (38, 36.9%), MVA (21, 20.4%), and MVR (2, 1.9%)，respectively. Intraoperative hypoxemia, radiographic pulmonary infiltrates, and pneumonia were observed in 19 (18.4%), 84 (81.6%), and 13 (12.6%) patients, respectively. The LOS of ICU and POD were as follows: MVR + TVA (55.1 ± 25h, 9.9 ± 3.5 d), MVA + TVA (56.5 ± 28.4h, 9.4 ± 4.2d), MVA (37.9 ± 21.9h, 8.1 ± 2.3d) and MVR (48 ± 4.2h, 7.5 ± 2.1d). No reintubation, reoperations, postoperative cognitive dysfunction, 30-day mortality were observed in the present study. The present study demonstrated that applying this anesthesia management for TTCS associated with acceptable morbidity, intensive care unit and postoperative hospital lengths of stay. The finding from the present study might provide some new approach for Anesthesia management of TTCS.

Esketamine versus Sufentanil Applied Prior to Placement of Suspension Laryngoscope.

OBJECTIVE: In laryngeal microsurgery, the insertion of the suspension laryngoscope is a strong stimulus that may cause hemodynamic fluctuations and adverse cardiovascular events. The purpose of this study was to compare the effect of preemptive treatment with esketamine and sufentanil on maintaining hemodynamics and reducing the occurrence of adverse cardiovascular events during the insertion of suspension laryngoscope. METHODS: In this double-blind randomized controlled trial, patients undergoing general anesthesia for laryngeal microsurgery were randomly assigned (1:1) to esketamine 0.5 mg kg-1 (esketamine group) and sufentanyl 0.125 µg kg-1 (sufentanil group) before inserting the laryngoscope, respectively. RESULTS: During the insertion of suspension laryngoscope, the incidence of bradycardia (HR < 60 beats/min) was 39.3% (22/56) in esketamine group, lower than 60.0% (33/55) in sufentanil group (odds ratio [OR], 2.32 [95% CI, 1.11-5.08]; p = 0.029). The incidence of hypotension (MAP <65 mmHg) was 33.9% (19/56) in esketamine group, lower than 56.4% (31/55) in sufentanil group (odds ratio [OR], 2.52 [95% CI, 1.91-5.27]; p = 0.018). The frequency of hypotension in esketamine group was lower than that in sufentanil group (0.36 ± 0.52 vs. 0.56 ± 0.50, p = 0.035). The time-weighted average of HR dropping above 30% of baseline was smaller in esketamine group than in sufentanil group (0.52 ± 2.06 vs. 1.08 ± 2.77, p = 0.006). CONCLUSIONS: These findings showed that compared with preemptive treatment of sufentanil (0.125 µg kg-1 ), esketamine (0.5 mg kg-1 ) was effective in reducing the incidence of cardiovascular adverse events, including bradycardia and hypotension induced by the insertion of suspension laryngoscope during the laryngeal microsurgery. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3021-3027, 2023.

Synergistic effect of endogenous gluten and oleic acid on wheat starch digestion by forming ordered starch-fatty acid-protein complexes during thermal processing.

The aim of this study was to understand the potential of endogenous gluten inhibiting the digestibility in vitro of wheat starch (WS) in starch-fatty acid-protein system. Therefore, the influences of gluten and whey protein isolate (WPI) on the properties, multi-scale structure and in vitro digestibility of WS in WS-oleic acid (OA)-protein system were compared. The results of digestibility in vitro indicated that the ternary system of starch-fatty acid-protein showed higher resistant starch (RS) content as well as lower rapidly digestible starch (RDS) content than the binary system of WS-OA, demonstrating protein decreased WS digestion of WS-OA system. The results of pasting properties showed that gluten and WPI both increased the viscosities of WS-OA system during the cooling period due to the formation of WS-OA-protein ternary complex. The results of swelling power and solubility analysis showed that gluten and WPI both decreased the swelling power and solubility of WS-OA binary system. Laser Confocal Raman and X-ray diffraction (XRD) studies indicated that gluten and WPI both increased the ordered degree of WS-OA binary system by decreasing the full width at half maximum (FWHM) of the peak at 480 cm-1 and increasing crystallinity degree. Strikingly, compared with WPI, gluten had greater effects on the digestibility in vitro, pasting properties and ordered degree of WS in WS-OA-protein system. Therefore, gluten as an endogenous protein has the potential application in reduction the enzymatic digestibility of WS by regulating the reassembly of starch and fatty acid during thermal processing.

Research progress on the impact of lactate clearance rate on the prognosis of critically ill patients / 中国医师杂志

Lactic acid is one of the main metabolites in the body, and its clearance rate reflects the dynamic changes of lactic acid in the body. Recent studies have shown that lactate clearance rate is related to the prognosis of critically ill patients with sepsis/septic shock, cardiogenic shock, out-of-hospital cardiac arrest, postoperative cardiovascular surgery, and liver and kidney dysfunction. This article reviews the relevant research progress of lactate metabolism and lactate clearance rate in different critically ill patients.

Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases / 中华儿科杂志

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.

A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature / 中华儿科杂志

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.

Medicated Serum of Bupleuri Radix Regulates HFL1 Apoptosis and Fibroblast-myofibroblast Transition via Smad3/Rheb Axis / 中国实验方剂学杂志

ObjectiveTransforming growth factor-β1 （TGF-β1） was used to stimulate human fetal lung fibroblast 1 （HFL1） for simulating the pathological process of idiopathic pulmonary fibrosis （IPF） and thereby the effects and mechanism of medicated serum of Bupleuri Radix against IPF were investigated. MethodTGF-β1 （10 μg·L-1） was employed to stimulate HFL1， and cells were treated with medicated serum of Bupleuri Radix （5%， 10%， 15%， 20%） for 24 h. Then cell proliferation rate was determined with cell counting kit-8 （CCK-8）. Subsequently， cells were classified into the control group （20% blank serum）， TGF-β1 group （20% blank serum and 10 μg·L-1 TGF-β1）， TGF-β1 + medicated serum of Bupleuri Radix group （5% blank serum， 15% medicated serum， and 10 μg·L-1 TGF-β1）， and TGF-β1 + SIS3 group （3 μmol·L-1 SIS3， 20% blank serum， 10 μg·L-1 TGF-β1）. Based on in situ end labeling （TUNEL） staining， the apoptosis rate was examined， and mRNA expression of apoptosis-related proteins B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax） and myofibroblast marker α-smooth muscle actin （α-SMA） was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of α-SMA， Ras homolog enriched in brain （Rheb）， and phosphorylated （p）-Smad3 was determined by immunofluorescence. Expression of Rheb， p-Smad3， and Smad3 was examined by Western blot. ResultThe cell proliferation rate of TGF-β1 group increased compared with that of the control group （P<0.05）. The cell proliferation rate of TGF+15% medicated serum of Bupleuri Radix group and TGF+20% medicated serum of Bupleuri Radix group decreased compared with that of the TGF-β1 group （P<0.01）. Compared with the control group， TGF-β1 group showed decrease in apoptosis rate， increase in mRNA expression of Bcl-2 and α-SMA， reduction in Bax mRNA expression， and rise of α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. Compared with TGF-β1 group， TGF-β1 + medicated serum of Bupleuri Radix group and TGF-β1 + SIS3 group demonstrated high apoptosis rate， low Bcl-2 and α-SMA mRNA expression， high Bax mRNA expression， and low α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. ConclusionMedicated serum of Bupleuri Radix can inhibit TGF-β1-induced HFL1 proliferation and fibroblast-myofibroblast transition and promote fibroblast apoptosis by regulating the Smad3/Rheb axis.

ncRNAs-mediated high expression of TICRR promotes tumor cell proliferation and migration and is correlated with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.

TICRR is a regulatory factor of DNA replication with ToPBP1 interaction. At present, the underlying function and mechanisms of TICRR remain unclear in LIHC. Our objective was to assess the function and prognosis of TICRR in LIHC. We conducted a differential expression analysis, GO/KEGG, and GSEA enrichment analysis of TICRR in LIHC. We also carried out the gene frequency and SCNA of TICRR. We found that TICRR could serve as an independent prognostic marker in LIHC by univariate and multivariate analysis. In addition, we observed that TICRR was related to immune infiltration, and TICRR had positive correlation with PD1/PD-L1 and CTLA-4 in LIHC. The hsa-miR-126-3p/IPO9-AS1 may be the candidate ncRNAs to regulate the expression of TICRR. The high rate of SCNV of TICRR might have critical effect on the function of CTL cells in LIHC. We further demonstrate through a series of experiments that TICRR facilitated the proliferation and metastasis of liver cancer cells in vitro. Altogether, TICRR might be a potential biomarker and therapeutic target in LIHC.

Butyrate Ameliorates Intestinal Epithelial Barrier Injury Via Enhancing Foxp3+ Regulatory T-Cell Function in Severe Acute Pancreatitis Model.

BACKGROUND: This study aimed to examine the effect of sodium butyrate on severe acute pancreatitis-related gut barrier injury in a rat model and explore its mechanism. METHODS: Male rats randomly fell into 3 groups, that is, the control, the severe acute pancreatitis group, and the severe acute pancreatitis+butyrate group. Rats in the control group received sham operation, while rats in the severe acute pancreatitis group and severe acute pancreatitis+butyrate group received severe acute pancreatitis induction by intraductal infusion of 4% sodium taurocholate. After that, rats in the severe acute pancreatitis+butyrate group were fed with sodium butyrate solution with free access. Intestinal barrier injury was measured based on the expression of tight junction proteins by reverse transcription polymerase chain reaction, Western blotting assay as well as immunohistochemical staining. The variation of Treg cells was measured by reverse transcription polymerase chain reaction, Western blotting assay, immunohistochemical staining, and flow cytometry analysis. RESULTS: Compared to rats in the control, rats in the severe acute pancreatitis group showed significantly higher pathohistological scores (P < .001) in the intestine, as well as decreased expression of occludin and ZO-1. While, rats in the severe acute pancreatitis+butyrate group showed mitigated histologic lesions (P < .05) and increased expressions of occludin and ZO-1. In addition, rats in the severe acute pancreatitis group showed the obvious reduction in the expressions of Foxp3 and GPR109a and the decreased percentage of Treg cells in the intestine (P < .001) compared to rats in the control. However, rats in the severe acute pancreatitis+butyrate group showed markedly increased expressions of Foxp3 and GPR109a and the upregulated percentage of Treg cells (P < .01). CONCLUSION: Butyrate could significantly mitigate the intestinal injury induced by severe acute pancreatitis, probably by inducing the differentiation of Treg cells.

Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota.

Background and aims: Inflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear. Methods: Acute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg-1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation. Results: GML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1ß and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-ß). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus. Conclusions: We showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8+ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3+ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

Systematic analysis of the mechanism of Xiaochaihu decoction in hepatitis B treatment via network pharmacology and molecular docking.

Hepatitis B (HB) is a globally prevalent infectious disease caused by the HB virus. Xiaochaihu decoction (XCHD) is a classic herbal formula with a long history of clinical application in treating HB. Although the anti-HB activity of XCHD has been reported, systematic research on the exact mechanism of action is lacking. Here, a network pharmacology-based approach was used to predict the active components, important targets, and potential mechanism of XCHD in HB treatment. Investigation included drug-likeness evaluation; absorption, distribution, metabolism, and elimination (ADME) screening; protein-protein interaction (PPI) network construction and cluster analysis; Gene Ontology (GO) analysis; and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation. Molecular docking was adopted to investigate the interaction between important target proteins and active components. Eighty-seven active components of XCHD and 155 anti-HB targets were selected for further analysis. The GO enrichment and similarity analysis results indicated that XCHD might perform similar or the same GO functions. Glycyrrhizae Radix (GR), one of the seven XCHD herbs, likely exerts some unique GO functions such as the regulation of interleukin-12 production, positive regulation of interleukin-1 beta secretion, and regulation of the I-kappaB/NF-kappaB complex. The PPI network and KEGG pathway analysis results showed that XCHD affects HB mainly through modulating pathways related to viral infection, immunity, cancer, signal transduction, and metabolism. Additionally, molecular docking verified that the active compounds (quercetin, chrysin, and capsaicin) could bind with the key targets. This work systematically explored the anti-HB mechanism of XCHD and provides a novel perspective for future pharmacological research.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1ß through the MEK-Erk1/2 and Jak/Stat3 Pathways.

OBJECTIVE: We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1ß. Methodology. Osteoblasts were treated with 20 ng/ml IL-1ß and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1-3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. RESULTS: Relative to the control group, IL-1ß induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. CONCLUSION: Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.

Dissipativity Analysis for Neural Networks With Time-Varying Delays via a Delay-Product-Type Lyapunov Functional Approach.

This article is concerned with the problem of dissipativity and stability analysis for a class of neural networks (NNs) with time-varying delays. First, a new augmented Lyapunov-Krasovskii functional (LKF), including some delay-product-type terms, is proposed, in which the information on time-varying delay and system states is taken into full consideration. Second, by employing a generalized free-matrix-based inequality and its simplified version to estimate the derivative of the proposed LKF, some improved delay-dependent conditions are derived to ensure that the considered NNs are strictly ( Q , S , R )- γ -dissipative. Furthermore, the obtained results are applied to passivity and stability analysis of delayed NNs. Finally, two numerical examples and a real-world problem in the quadruple tank process are carried out to illustrate the effectiveness of the proposed method.

Analysis on Role of mTORC1/4E-BP1 Axis in Idiopathic Pulmonary Fibrosis and Research Progress of Bupleuri Radix on Its Intervention / 中国实验方剂学杂志

Idiopathic pulmonary fibrosis （IPF） is a common， lethal interstitial lung disease characterized by airway remodeling， inflammation， alveolar destruction， and fibrosis. The mammalian target of rapamycin complex 1/4E binding protein 1 （mTORC1/4E-BP1） axis is closely related to the expression of collagen by fibroblasts， and its role in pulmonary fibrosis remains to be further elucidated. Traditional Chinese medicine （TCM） has shown promising efficacy in improving the lung function， exercise capacity， and quality of life in patients with IPF. The theory of "same treatment for different diseases" provides a TCM theoretical basis for the treatment of pulmonary fibrosis with Bupleuri Radix， while the research in western medicine has preliminarily shown that both the formulation and single herb as well as the active ingredients of Bupleuri Radix have good therapeutic effects on pulmonary fibrosis. Therefore， this review will elaborate on the role of the mTORC1/4E-BP1 axis in the pathomechanism of IPF， as well as the research results of the active components of Bupleuri Radix on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin protein（PI3K/AKT/mTOR） pathway， so as to provide a reference for the treatment and drug development of IPF.

Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats / 中西医结合学报

OBJECTIVE@#Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats.@*METHODS@#HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations.@*RESULTS@#In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α).@*CONCLUSION@#This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.

Continuous-Time Laser Frames Associating and Mapping via Multilayer Optimization.

To achieve the ability of associating continuous-time laser frames is of vital importance but challenging for hand-held or backpack simultaneous localization and mapping (SLAM). In this study, the complex associating and mapping problem is investigated and modeled as a multilayer optimization problem to realize low drift localization and point cloud map reconstruction without the assistance of the GNSS/INS navigation systems. 3D point clouds are aligned among consecutive frames, submaps, and closed-loop frames using the normal distributions transform (NDT) algorithm and the iterative closest point (ICP) algorithm. The ground points are extracted automatically, while the non-ground points are automatically segmented to different point clusters with some noise point clusters omitted before 3D point clouds are aligned. Through the three levels of interframe association, submap matching and closed-loop optimization, the continuous-time laser frames can be accurately associated to guarantee the consistency of 3D point cloud map. Finally, the proposed method was evaluated in different scenarios, the experimental results showed that the proposed method could not only achieve accurate mapping even in the complex scenes, but also successfully handle sparse laser frames well, which is critical for the scanners such as the new Velodyne VLP-16 scanner's performance.

Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice.

Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through Egr-1-mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock-down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis-associated colorectal cancer (CAC) mouse model treated with lentiviral-based overexpression and knocked-down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR-Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c-Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS-induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin-deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.

Estradiol-17ß regulates proliferation and apoptosis of sheep endometrial epithelial cells by regulating the relative abundance of YAP1.

Yes-associated protein 1 (YAP1) transcription regulator of the Hippo protein kinase pathway, serves as a key regulator of tissue growth and organ size by regulating cell proliferation and apoptosis. Effects of YAP1 on proliferation and apoptosis of sheep endometrial epithelial cells (EEC) as a result of estradiol-17ß (E2) treatment, however, remain unclear. In the present study, the abundance of YAP1 protein in the uterine horn was greater than that in the uterine body or cervix. The YAP1 protein was primarily localized in the endometrial luminal and glandular epithelial cells of the uterine horn of ewes on day 2 of the estrous cycle. Compared with control samples, there was a lesser abundance of YAP1 mRNA transcript that was associated with a lesser proliferation and greater apoptosis of EEC. There were also lesser concentrations of epidermal growth factor and insulin-like growth factor 1 in the spent culture medium when there was a lesser abundance of YAP1 mRNA in EEC compared with those in the control group. When there was a greater abundance of YAP1 mRNA transcript, there were greater concentrations of epidermal growth factor and insulin-like growth factor 1 in the spent media. Furthermore, with estradiol-17ß treatment the abundance of YAP1 mRNA transcript was similar to that of the control samples. Taken together, estradiol-17ß may function as an essential regulator of EEC proliferation and apoptosis by modulation of concentrations of YAP1 protein in the sheep uterus. These results indicate there are molecular mechanisms of estradiol-17ß and YAP1 in EEC proliferation and apoptosis of ewes.