CAR directs T cell adaptation to bile acids in the small intestine.

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high concentrations of bile acids in the small intestine lamina propria (siLP). CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1 (encoded by Abcb1a) in the siLP to prevent bile acid toxicity and suppress Crohn's disease-like small bowel inflammation4. Here we identify the nuclear xenobiotic receptor CAR (encoded by Nr1i3) as a regulator of MDR1 expression in T cells that can safeguard against bile acid toxicity and inflammation in the mouse small intestine. Activation of CAR induced large-scale transcriptional reprogramming in Teff cells that infiltrated the siLP, but not the colon. CAR induced the expression of not only detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine IL-10. Accordingly, CAR deficiency in T cells exacerbated bile acid-driven ileitis in T cell-reconstituted Rag1-/- or Rag2-/- mice, whereas pharmacological activation of CAR suppressed it. These data suggest that CAR acts locally in T cells that infiltrate the small intestine to detoxify bile acids and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn's disease and defines lymphocyte sub-specialization in the small intestine.

Upregulation of HLA-II related to LAG-3+CD4+ T cell infiltration is associated with patient outcome in human glioblastoma.

Glioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)-1/PD ligand-1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte-activation gene 3 (LAG-3) binding to human leukocyte antigen-II (HLA-II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti-PD-1 treatment; however, the value of LAG-3-HLA-II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA-II in human GBM samples and the correlation with LAG-3+CD4+ T cell infiltration. Human leukocyte antigen-II was highly expressed in GBM and correlated with increased LAG-3+CD4+ T cell infiltration in the stroma. Additionally, HLA-IIHighLAG-3High was associated with worse patient survival. Increased interleukin-10 (IL-10) expression was observed in GBM, which was correlated with high levels of HLA-II and LAG-3+ T cell infiltration in stroma. HLA-IIHighIL-10High GBM associated with LAG-3+ T cells infiltration synergistically showed shorter overall survival in patients. Combined anti-LAG-3 and anti-IL-10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68+ macrophages upregulated HLA-II expression in GBM cells through tumor necrosis factor-α (TNF-α). Blocking TNF-α-dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell-tumor cell interactions, such as LAG-3-HLA-II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG-3-HLA-II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients.

Intensive Surveillance of Porcine-Rhesus Kidney Xenotransplant Using Different Ultrasound Techniques.

BACKGROUND: Significant progress has been made in kidney xenotransplantation in the past few years, and this field is accelerating towards clinical translation. Therefore, surveillance of the xenograft with appropriate tools is of great importance. Ultrasonography has been widely used in kidney allotransplantation and served as an economical and non-invasive method to monitor the allograft. However, questions remain whether the ultrasonographic criteria established for human kidney allograft could also be applied in xenotransplantation. METHODS: In the current study, we established a porcine-rhesus life sustaining kidney xenotransplantation model. The xenograft underwent intensive surveillance using gray-scale, colorful Doppler ultrasound as well as 2D shear wave elastography. The kidney growth, blood perfusion, and cortical stiffness were measured twice a day. These parameters were compared with the clinical data including urine output, chemistry, and pathological findings. RESULTS: The observation continued for 16 days after transplantation. Decline of urine output and elevated serum creatinine were observed on POD9 and biopsy proven antibody-mediated rejection was seen on the same day. The xenograft underwent substantial growth, with the long axis length increased by 32% and the volume increased by threefold at the end of observation. The resistive index of the xenograft arteries elevated in response to rejection, together with impaired cortical perfusion, while the peak systolic velocity (PSV) was not compromised. The cortical stiffness also increased along with rejection. CONCLUSION: In summary, the ultrasound findings of kidney xenograft shared similarities with those in allograft but possessed some unique features. A modified criteria needs to be established for further application of ultrasound in kidney xenotransplantation.

Plant species diversity and functional diversity relations in the degradation process of desert steppe in an arid area of northwest China.

Species and functional diversity play a major role in the stability and sustainability of grassland ecosystems. However, changes in species and functional diversity during grassland degradation in arid areas as well as the underlying mechanisms remain unclear. In this study, we surveyed the vegetation and soil properties of arid regions across a degradation gradient to explore the shifts in species and functional diversity in plant communities, their relationships and key determinants during desert steppe degradation. Our results found significant variability in species diversity and functional diversity across degradation stages. Species diversity (Shannon-Wiener index (H), and Pielou index) and functional diversity (functional evenness (FEve) index, and Rao's quadratic entropy (RaoQ) index) tended to increase initially and then decrease with increasing grassland degradation. The Patrick index, Simpson index, functional richness (FRic) index, functional divergence (FDiv) index, and functional dispersion (FDis) index declined as grassland degradation increased. The relationships between species diversity and functional diversity indices at different stages of degradation in the desert steppe were inconsistent. From no to heavy degradation grasslands, the correlation between species diversity and functional diversity gradually weakened. Specifically, there was a significant correlation between Patrick (R) and FRic indices (R2 > 0.7) on both non-degraded and light degraded grasslands, but there was no significant correlation between R and FRic indices in moderately and heavily degraded grasslands (R2 < 0.7), and R2 gradually decreased. Redundancy analysis and partial least squares path modeling showed that grassland degradation has a significant direct effect on the species diversity and functional diversity. In addition grassland degradation has direct and indirect effects on the species diversity through soil available nitrogen, organic matter and total nitrogen. Functional diversity is directly or indirectly affected by species diversity, soil available nitrogen, organic matter and total nitrogen, soil moisture content, soil bulk density, and pH value. In summary, the relationship between species and functional diversity indices gradually weakened from areas with no degradation to heavy degradation in arid desert grasslands. Our study reveals the patterns and relationships between species diversity and functional diversity throughout the process of grassland degradation, demonstrating a gradual decrease in ecosystem stability and sustainability as degradation advances. Our results have significant implications for the restoration of grassland degradation and the management of ecosystem services in arid steppe regions.

Ribosomal protein L22-like1 promotes prostate cancer progression by activating PI3K/Akt/mTOR signalling pathway.

Prostate cancer (PCa) is one of the most common malignancies in men. Ribosomal protein L22-like1 (RPL22L1), a component of the ribosomal 60 S subunit, is associated with cancer progression, but the role and potential mechanism of RPL22L1 in PCa remain unclear. The aim of this study was to investigate the role of RPL22L1 in PCa progression and the mechanisms involved. Bioinformatics and immunohistochemistry analysis showed that the expression of RPL22L1 was significantly higher in PCa tissues than in normal prostate tissues. The cell function analysis revealed that RPL22L1 significantly promoted the proliferation, migration and invasion of PCa cells. The data of xenograft tumour assay suggested that the low expression of RPL22L1 inhibited the growth and invasion of PCa cells in vivo. Mechanistically, the results of Western blot proved that RPL22L1 activated PI3K/Akt/mTOR pathway in PCa cells. Additionally, LY294002, an inhibitor of PI3K/Akt pathway, was used to block this pathway. The results showed that LY294002 remarkably abrogated the oncogenic effect of RPL22L1 on PCa cell proliferation and invasion. Taken together, our study demonstrated that RPL22L1 is a key gene in PCa progression and promotes PCa cell proliferation and invasion via PI3K/Akt/mTOR pathway, thus potentially providing a new target for PCa therapy.

A Dual-Responsive Artificial Skin for Tactile and Touchless Interfaces.

The progress from intelligent interactions and supplemented/augmented reality requires artificial skins to shift from the single-functional tactile paradigm. Dual-responsive sensors that can both detect pre-contact proximal events and tactile pressure levels enrich the perception dimensions and deliver additional cognitive information. Previous dual-responsive sensors show very limited utilizations only in proximity perception or approaching switches. Whereas, the approaching inputs from the environment should be able to convey more valuable messages. Herein, a flexible iontronic dual-responsive artificial skin is present. The artificial skin is sensitive to external object's applied pressure as well as its approaching, and can elicit information of target material categories encoded in the proximal inputs. Versatile applications are then demonstrated. Dual-mode human-machine interfaces are developed based on the devices, including a manipulation of virtual game characters, navigation and zooming in of electronic maps, and scrolling through electronic documents. More importantly, the proof-of-concept application of an entirely touchless material classification system is demonstrated. Three types of materials (metals, polymers, and human skins) are classified and predicted accurately. These features of the artificial skin make it highly promising for next-generation smart engineered electronics.

NPAS2 promotes aerobic glycolysis and tumor growth in prostate cancer through HIF-1A signaling.

BACKGROUND: Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. METHODS: Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. RESULTS: Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. CONCLUSION: NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

PdP2 Nanoparticles on Reduced Graphene Oxide: A Catalyst for the Electrocatalytic Reduction of Nitrate to Ammonia.

Palladium phosphides are explored as efficient catalysts for the electrocatalytic reduction of nitrate to ammonia (NRA). The explored PdP2 nanoparticles on reduced graphene oxide exhibit the maximum NH3 Faradaic efficiency of 98.2% with a corresponding NH3 yield rate of 7.6 mg h-1 cm-2 at -0.6 V (RHE). Theoretical calculations reveal that a PdP2 (011) surface can not only effectively activate and hydrogenate NO3- via a NOH pathway but also retard H adsorption to inhibit the competitive hydrogen evolution reaction.

Design and Application of Materials for Sequestration and Immobilization of 99Tc.

99Technetium (99Tc) is a hazardous radionuclide that poses a serious environmental threat. The wide variation and complex chemistries of liquid nuclear waste streams containing 99Tc often create unique, site specific challenges when sequestering and immobilizing the waste in a matrix suitable for long-term storage and disposal. Therefore, an effective management plan for 99Tc containing liquid radioactive wastes (such as storage (tanks) and decommissioned wastes) will likely require a variety of suitable materials/matrixes capable of adapting to and addressing these challenges. In this review, we discuss and highlight the key developments for effective removal and immobilization of 99Tc liquid waste in inorganic waste forms. Specifically, we review the synthesis, characterization, and application of materials for the targeted removal of 99Tc from (simulated) waste solutions under various experimental conditions. These materials include (i) layered double hydroxides (LDHs), (ii) metal-organic frameworks (MOFs), (iii) ion-exchange resins (IERs) as well as cationic organic polymers (COPs), (iv) surface modified natural clay materials (SMCMs), and (v) graphene-based materials (GBMs). Second, we discuss some of the major and recent developments toward 99Tc immobilization in (i) glass, (ii) cement, and (iii) iron mineral waste forms. Finally, we present future challenges that need to be addressed for the design, synthesis, and selection of suitable matrixes for the efficient sequestration and immobilization of 99Tc from targeted wastes. The purpose of this review is to inspire research on the design and application of various suitable materials/matrixes for selective removal of 99Tc present globally in different radioactive wastes and its immobilization in stable/durable waste forms.

CircACTR2 in macrophages promotes renal fibrosis by activating macrophage inflammation and epithelial-mesenchymal transition of renal tubular epithelial cells.

The crosstalk between macrophages and tubular epithelial cells (TECs) actively regulates the progression of renal fibrosis. In the present study, we revealed the significance of circular RNA ACTR2 (circACTR2) in regulating macrophage inflammation, epithelial-mesenchymal transition (EMT) of TECs, and the development of renal fibrosis. Our results showed UUO-induced renal fibrosis was associated with increased inflammation and EMT, hypertrophy of contralateral kidney, up-regulations of circACTR2 and NLRP3, and the down-regulation of miR-561. CircACTR2 sufficiently and essentially promoted the activation of NLRP3 inflammasome, pyroptosis, and inflammation in macrophages, and through paracrine effect, stimulated EMT and fibrosis of TECs. Mechanistically, circACTR2 sponged miR-561 and up-regulated NLRP3 expression level to induce the secretion of IL-1ß. In TECs, IL-1ß induced renal fibrosis via up-regulating fascin-1. Knocking down circACTR2 or elevating miR-561 potently alleviated renal fibrosis in vivo. In summary, circACTR2, by sponging miR-561, activated NLRP3 inflammasome, promoted macrophage inflammation, and stimulated macrophage-induced EMT and fibrosis of TECs. Knocking down circACTR2 and overexpressing miR-561 may, thus, benefit the treatment of renal fibrosis.

Basic performance of domestic surgical robot and the safety and effectiveness of integrated energy equipment. / å›½äº§æ‰‹æœ¯æœºå™¨äººåŸºæœ¬æ€§èƒ½å’Œæ•´åˆèƒ½é‡è®¾å¤‡çš„å®‰å ¨æ€§åŠæœ‰æ•ˆæ€§.

OBJECTIVES: Surgical robot system has broken the limitation of traditional surgery and shown excellent performance in surgery, and has been widely used in minimally invasive treatment in most areas of surgery. This study aims to verify the basic performance of the domestic surgical robot system and the safety and effectiveness of the integrated bipolar electrocoagulation and ultrasonic knife. METHODS: The basic performance of the domestic surgical robot system was evaluated by completing the square knot and surgical knot, vertical and horizontal perforation and right ring perforation and suture, as well as picking up beans. Compared with laparoscopy, the safety and effectiveness of the domestic surgical robot after integrated interconnection bipolar electrocoagulation and ultrasonic scalpel were evaluated by detecting the vascular closure performance and the degree of histopathological damage in animals. RESULTS: Compared with freehand knotting, domestic robot knotting speed and circumference were slightly worse, but better than laparoscopic knotting. There was no statistical significance in the tension difference of the surgical knots among the 3 methods (P>0.05), but the tension of the square knots made by the freehand and the domestic surgical robot was greater than that of the laparoscopy (P<0.05). The space required for both the left and right forceps heads of knots was smaller than that of laparoscopy (P<0.001), which successfully completed the 4 quadrant suture tasks, and the time of picking up beans was significantly less than that of laparoscopy (P<0.05). There was no significant difference in the temperature of the liver tissue after the bipolar electrocoagulation between the interconnected domestic surgical robot and the laparoscopy (P>0.05), and the acute thermal injury was observed under the light microscope. The temperature of the liver tissue treated by the domestic robotic ultrasound knife was higher than that of the laparoscopic ultrasound knife (P<0.05). CONCLUSIONS: Domestic surgical robots are obviously superior to laparoscopy in suturing, knotting, and moving objects, and domestic surgical robots' interconnect bipolar electrocoagulation and ultrasonic knife have achieved success in animal experiments, and hemostasis is considered to be safe and effective.

Circular RNA ACTR2 activates M2 polarization of macrophages through activating Yes-associated protein signalling and contributes to renal fibrosis.

Macrophages, associated with their heterogenous and dynamic polarization status, actively shape the development of renal fibrosis (RF). In this study, we revealed the significance of a signalling axis, circular RNA ACTR2 (circACTR2)/miR-200c/Yes-associated protein (YAP), in regulating macrophage polarization and the development of RF. A unilateral urethral obstruction (UUO)-induced RF model was established in vivo. In vitro, interferon-γ (IFNγ) and interleukin (IL)-4 were applied to induce M1 and M2 polarization, respectively. The abundance of M1 and M2 macrophages were examined by immunofluorescence (IF) or flow cytrometry on markers specific for each subtype. Expressions of circACTR2, miR-200c and YAP were measured by quantitative real-time-polymerase chain reaction and/or Western blotting. Interactions between circACTR2, miR-200c and YAP were examined by combining luciferase assay, RNA immunoprecipitation and IF. Impact of targeting circACTR2 on RF and macrophage polarization was also examined in vivo. UUO-induced RF was associated with increased M1 and M2 macrophages, up-regulations of circACTR2 and YAP and the down-regulation of miR-200c in the obstructed kidney. circACTR2 was essential for IL-4-induced M2 polarization, but not IFNγ-induced M1 polarization. This activity of circACTR2 was mediated by sponging miR-200c and activating the downstream YAP signalling. In vivo, knocking down circACTR2 boosted miR-200c expression, reduced YAP level, lowered M2 macrophages in obstructed kidney and ameliorated UUO-induced RF. circACTR2, by targeting and sponging miR-200c, activates YAP signalling, stimulates M2 macrophage polarization and promotes the development of RF. Therefore, targeting circACTR2 may benefit the treatment of RF.

Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called "liquid biopsy" has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.

Comprehensive identification of protein orthologs in the family Ascoviridae facilitates an understanding of phylogenomics, protein conservation, and phosphorylation.

Analysis of orthology is important for understanding protein conservation, function, and phylogenomics. In this study, we performed a comprehensive analysis of gene orthology in the family Ascoviridae based on identification of 366 protein homologue groups and phylogenetic analysis of 34 non-single-copy proteins. Our findings revealed 90 newly annotated proteins, five newly identified core proteins for the family Ascoviridae, and 14 core proteins for the genus Ascovirus. A phylogenomic tree of 11 Ascoviridae members was constructed based on a concatenation of 35 of the 45 ortholog groups. In combination with phosphoproteomic results and conservation estimations, 30 conserved phosphorylation sites on 17 phosphoproteins were identified from a total of 176 phosphosites on 57 phosphoproteins from Heliothis virescens ascovirus 3h (HvAV-3h), providing potential research targets for investigating the role of these protein in the regulation of viral infection. This study will facilitate genome annotation and comparison of further Ascoviridae members as well as functional genomic investigations.

Micro-Hand Robot-Assisted Versus da Vinci Robot-Assisted Cholecystectomy: A Multi-centre, Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical effectiveness of micro-hand robot-assisted cholecystectomy (MRC) by comparing the clinical outcomes of patients with benign gallbladder disease treated with micro-hand or da Vinci robot-assisted cholecystectomy (DRC). METHODS: This is a prospective, multi-centre, single-blind, and randomized controlled trial. In this study, 166 patients of benign gallbladder disease were randomized enrolled into two groups and received MRC or DRC (83 in the MRC group; 83 in the DRC group). The primary endpoint was surgical success rate. Secondary endpoints were the docking time, console time, total operation time, intraoperative blood loss, gallbladder breakage rate, postoperative pain, time of first flatus, the comprehensive complication index (CCI), and the hospital stay of the subjects. The duration of follow-up was 30 days. RESULTS: No conversion occurred. Compared with MRC, the DRC group showed longer docking time (12.04 min vs. 16.39 min, P = 0.025) and higher gallbladder breach rate (4.8% vs. 15.7%, P = 0.021). The MRC group showed higher postoperative pain scores compared to DRC (4.0 vs 3.0, P = 0.038). The console time, intraoperative blood loss, and gallbladder breach rate were comparable in these two groups (P > 0.05). No differences were observed in postoperative outcomes and complications between the two groups (P > 0.05). CONCLUSIONS: In patients with benign gallbladder disease, the MRC showed no obvious clinical disadvantage compared with the da Vinci surgical robot. MRC is effective and safe and provides more options for surgical treatment. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT04122261). URL: https://clinicaltrials.gov/ct2/show/NCT04122261.

Comparison of the operative outcomes and learning curves between laparoscopic and "Micro Hand S" robot-assisted total mesorectal excision for rectal cancer: a retrospective study.

BACKGROUND: The Micro Hand S robot is a new surgical tool that has been applied to total mesorectal excision (TME) surgery for rectal cancer in our center. In this study, we compared the operative outcomes, functional outcomes and learning curves of the Micro Hand S robot-assisted TME (RTME) with laparoscopic TME (LTME). METHODS: A total of 40 patients who underwent RTME and 65 who underwent LTME performed by a single surgeon between July 2015 and November 2018 were included in this retrospective study. Clinicopathologic characteristics, operative and functional outcomes, and learning curves were compared between the two groups. The learning curve was analyzed using the cumulative sum method and two stages (Phase 1, Phase 2) were identified and analyzed. All patients were followed up for at least 12 months. RESULTS: The clinicopathologic characteristics of the two groups were similar. The learning curve was 17 cases for RTME and 34 cases for LTME. Compared with LTME, RTME was associated with less blood loss (148.2 vs. 195.0 ml, p = 0.022), and shorter length of hospital stay (9.5 vs. 12.2 days, p = 0.017), even during the learning period. With the accumulation of experience, the operative time decreased significantly from Phase 1 to Phase 2 (RTME, 360.6 vs. 323.5 min, p = 0.009; LTME, 338.1 vs. 301.9 min, p = 0.005), whereas other outcomes did not differ significantly. CONCLUSIONS: Micro Hand S robot-assisted TME is safe and feasible even during the learning period, with outcomes comparable to laparoscopic surgery but superior in terms of blood loss, length of hospital stay, and learning curve. Trial registration Clinicaltrial.gov, NCT04836741, retrospectively registered on 5 April 2021.

Prognostic value of platelet distribution width and mean platelet volume in patients with laryngeal cancer.

Aims: To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. Patients & methods: The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. Results: In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Conclusions: Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.

Robot-assisted sleeve gastrectomy in patients with obesity with a novel Chinese domestic MicroHand SII surgical system.

BACKGROUND: A new device has been added to the Chinese MicroHand surgical robot family, developed based on the successful application of control algorithms. As a benefit of using these specialized control algorithms, the motion mapping relation can be accommodated into the system without the help of a built-in image system, resulting in a novel Chinese domestic surgical robot with two arms called MicroHand SII, which is different from the former MicroHand S and da Vinci systems. In this study, we investigate the performance of a novel MicroHand SII robotic platform in patients with obesity. METHODS: From March 2018 to April 2019, a total of 7 patients whose BMI ranged from 29.9 to 49.8 kg/m2 were operated on with the robot-assisted technique using the MicroHand SII surgical system. Data regarding demography, surgical procedure and the 3-month outcome postoperation were collected. RESULTS: There were 2 female and 5 male patients with a median age (range) of 35 (20-51) years. The median operative time was 160 (149-195) minutes. None were converted to open surgery. All anthropometry indices improved significantly (p < 0.05) at 3 months postoperatively. There were no cases of surgical site infection, gastrointestinal/abdominal bleeding, or conversion to an open operation. CONCLUSIONS: The initial experience showed that the Chinese domestic robot surgical system MicroHand SII could be feasibly and safely applied in sleeve gastrectomy in patients with obesity. Because of the unique design of this system such as a two-hand robot, an array of master-slave motion strategies, and a roll joint at the end of the instruments that allows 7 degrees of freedom, this robotic platform has presented its own obvious advantages.

Prognostic Significance of Lactate Dehydrogenase in Patients Undergoing Surgical Resection for Laryngeal Squamous Cell Carcinoma.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

PM2.5 induces liver fibrosis via triggering ROS-mediated mitophagy.

BACKGROUND: The increasing epidemic of fine particulate matter (PM2.5) is a serious threat to human health. It induces the occurrence of liver fibrosis, but its molecular mechanism is not yet clear. The molecular mechanisms of PM2.5 inducing liver fibrosis were investigated in this study. METHODS: The cell viability of LX-2 cells and primary hepatic stellate cells (HSCs) was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro enzyme-linked immune sorbent assay (ELISA) kits were used to detect the concentrations of antioxidant enzymes and reactive oxygen species (ROS). The mitochondrial transmembrane potential (MTP) was determined by JC-1 dye. Knockdown of Parkin was carried out by Parkin-specific siRNA transfection. Relative mRNA and protein expressions were evaluated by qRT-PCR, Western blotting, and immunofluorescence analysis. RESULTS: PM2.5 activated LX-2 cells and primary HSCs, inducing the liver fibrosis along with down-regulation of the gelatinases MMP-2, and up-regulation of myofibroblast markers collagen type I and α-SMA. The levels of ROS and reactive nitrogen species (RNS), as well as the lipid peroxidation marker malondialdehyde (MDA) were significantly up-regulated in LX-2 cells and primary HSCs treated with PM2.5. Also, the enzymatic antioxidants levels were disturbed by PM2.5. Furthermore, PM2.5 decreased the MTP, releasing cytochrome c from the mitochondria to the cytosol. The dynamics of mitochondria were regulated by PM2.5 via facilitating mitochondrial fission. The excess ROS induced by PM2.5 triggered the mitophagy by activating PINK1/Parkin pathway, and inhibition of mitophagy induced by PM2.5 diminished the liver fibrosis. CONCLUSION: PM2.5 may induce mitophagy via activating PINK1/Parking signal pathway by increasing ROS, thereby activating HSCs and causing liver fibrosis.