Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum

BACKGROUND Colorectal polyps,which are characterized by a high recurrence rate,represent preneoplastic conditions of the intestine.Due to unclear mechanisms of pathogenesis,first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection.Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps,the exact compositions and roles of bacteria in the mucosa around the lesions,rather than feces,remain unsettled.AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps.METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps(Ade),seven consistently with non-Ade(Pol),ten with current Pol but previous Ade,and six healthy individuals,and bacterial patterns were evaluated by 16S rDNA sequencing.Linear discriminant analysis and Student’s t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes.Pearson’s correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators.RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals.These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps,but also existed in histologically normal tissue 10 cm distal from the lesions.Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions,Pol,and Ade.Increased abundance of Gram-negative bacteria,including Klebsiella,Plesiomonas,and Cronobacter,was observed in Pol group and Ade group,suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment.Meanwhile,age and gender were linked to bacteria changes,indicating the potential involvement of sex hormones.CONCLUSION These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps,especially adenoma.Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

Site Management Strategy in Highway Project Management

Highway project management involves overseeing the on-site construction of a highway project,taking into account the specific circumstances and conditions of the site.This type of management requires a high level of expertise and is characterized by its dynamic and systematic approach.Effective on-site management can ensure the quality,cost-saving,smooth progress,and safety of highway construction.However,there are still some problems in the implementation of site management in some highway projects,which seriously affect the improvement of site management.This paper analyzes the characteristics and existing problems of highway engineering management,and puts forward the effective strategies of site management,hoping that this study will help to improve highway engineering site management.

Integral imaging-based tabletop light field 3D display with large viewing angle

Light field 3D display technology is considered a revolutionary technology to address the critical visual fatigue issues in the existing 3D displays.Tabletop light field 3D display provides a brand-new display form that satisfies multi-user shared viewing and collaborative works,and it is poised to become a potential alternative to the traditional wall and portable display forms.However,a large radial viewing angle and correct radial perspective and parallax are still out of reach for most current tabletop light field 3D displays due to the limited amount of spatial information.To address the viewing angle and perspective issues,a novel integral imaging-based tabletop light field 3D display with a simple flat-panel structure is proposed and developed by applying a compound lens array,two spliced 8K liquid crystal display panels,and a light shaping diffuser screen.The compound lens array is designed to be composed of multiple three-piece compound lens units by employing a reverse design scheme,which greatly extends the radial viewing angle in the case of a limited amount of spatial information and balances other important 3D display parameters.The proposed display has a radial viewing angle of 68.7°in a large display size of 43.5 inches,which is larger than the conventional tabletop light field 3D displays.The radial perspective and parallax are correct,and high-resolution 3D images can be reproduced in large radial viewing positions.We envision that this proposed display opens up possibility for redefining the display forms of consumer electronics.

Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury

Background: Traumatic colon injury(TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However, there is a lack of basic research in this field.This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield.Methods: A total of 669 Sprague–Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay(ELISA) was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase, D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis, the relative abundances of specific bacterial genera were detected using quantitative real-time PCR(qRT-PCR).Results: As a type of lethal injury, TCI induced acute disruption of intestinal homeostasis, characterized by inflammatory responses, intestinal barrier hyperpermeability and microbiota dysbiosis(P<0.05). Significant alterations in bacterial metabolic patterns were detected with decreases in many metabolites. After a series of screenings,we found that oral administration of asparagine(Asn) and 3-indolepropionic acid(IPA) effectively prolonged posttraumatic survival time [Asn plus IPA vs. Vehicle: hazard ratio(HR)=0.105, 95%CI 0.031–0.356, P=0.0003] and restored intestinal homeostasis in TCI rats(P<0.05). Mechanistically, this combinational strategy protected the rats against TCI through synergistic activation of Akt signaling in the intestinal epithelium(P<0.05).Conclusions: Abrupt dysregulation of intestinal homeostasis plays a critical role in the progression toward TCI induced death. Oral administration of Asn plus IPA may serve as an effective regimen to restore intestinal functions and prolong the posttraumatic survival time.

Fat-poor renal angiomyolipoma with prominent cystic degeneration:A case report and review of the literature

BACKGROUND Angiomyolipoma(AML),the most common benign tumor of the kidney,is usually composed of dysmorphic blood vessels,smooth muscle,and mature adipose tissue.To our knowledge,AML with cystic degeneration has rarely been documented.Cystic degeneration,hemorrhage,and a lack of fat bring great challenges to the diagnosis.CASE SUMMARY A 60-year-old man with hypertension presented with a 5-year history of cystic mass in his left kidney.He fell 2 mo ago.A preoperative computed tomography(CT)scan showed a mixed-density cystic lesion without macroscopic fat density,the size of which had increased compared with before,probably due to hemorrhage caused by a trauma.Radical nephrectomy was performed.Histopathological studies revealed that the lesion mainly consisted of tortuous,ectatic,and thick-walled blood vessels,mature adipose tissue,and smooth muscle-like spindle cells arranged around the abnormal blood vessels.The tumor cells exhibited positivity for human melanoma black-45,Melan-A,smooth muscle actin,calponin,S-100,and neuron-specific enolase,rather than estrogen receptor,progesterone receptor,CD68,and cytokeratin.The Ki-67 labeling index was less than 5%.The final diagnosis was a fat-poor renal AML(RAML)with prominent cystic degeneration.CONCLUSION When confronting a large renal cystic mass,RAML should be included in the differential diagnosis.

The Syndrome of Sea Cucumber (Apostichopus japonicus) Infected by Virus and Bacteria

A outbreak of disease with symptoms of evisceration and skin ulteration led to mass mortality in sea cucumber Apostichopus japonicus cultivated in indoor ponds near the Dalian coast from December 2004 to April 2005. Spherical virus particles with a diameter of 75-200 nm were found in the cytoplasm of cells in the water-system, the alimentary canal and in the respiratory trees of the diseased and dying sea cucumber individuals by electron microscopic observation of ultrathin sections. Examination by negative stained samples revealed that all the diseased sea cucumbers were infected by the virus, while the healthly ones cultivated outside the contagious area were not. Two bacterial strains were also isolated from the diseased animals. When exposed to a medium containing the virus particles, regardless of whether the bacterial suspension was added, healthy sea cucumbers exhibited identical disease symptoms as the ones in the indoor ponds, and had a mortality of 90%-100%. However, when exposed to a medium in which there was only one of the two bacterial strains, 30%-80% of the sea cucumbers were infected and nearly 20% died. Negative staining showed that the viral particles were detected only in the bodies of the tested animals that were exposed to the viral medium. Histopathologically, the diseased sea cucumbers are characterized by karyopycnosis, and disintegration of the endoplasmic reticula and mitochondria in the epithelial cells in the water-system, the respiratory tree and the alimentary canal.

Synchronous multiple primary gastrointestinal cancers with CDH1 mutations:A case report

BACKGROUND Synchronous multiple primary cancers (SMPC) mean two or more malignant tumors occurring simultaneously and with different origins no matter what types they are or where they are located. The carcinogenesis of SMPC often involves variations of some specific genes. However, the correlation between CDH1 mutations and synchronous multiple primary gastrointestinal cancers is largely unknown. CASE SUMMARY A 62-year-old woman had sustained abdominal pain for one week and visited our hospital. Gastrointestinal endoscopy revealed multiple small polypoid lesions in both the stomach and colorectum. Computed tomography and laboratory results were within normal limits. Pathological evaluation confirmed signet ring cell carcinoma without obvious metastatic evidence. Malignant cells showed negativity for E-cadherin and positivity for β-catenin in the cytoplasm and nucleus. DNA sequencing performed on paraffin-embedded tissue revealed two exactly coincident alterations in CDH1, C.57T>G and C.1418A>T. CONCLUSION This case suggests that the combination of CDH1 mutations and WNT/β-catenin signaling activation contributes to the carcinogenesis of gastrointestinal SMPC.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A monoinstitutional propensity score-matched study in China

The potential survival benefit of neoadjuvant chemotherapy(NC)in patients with advanced gastric cancer has been widely recognized.With the development of minimally invasive surgery,which is represented by laparoscopy,the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored.AIM To compare the short-term outcomes of laparoscopic total gastrectomy(LTG)after NC(NC-LTG)with LTG alone.METHODS A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study.We used propensityscore matching(PSM)to balance baseline bias.After 1:1 PSM,73 patients were included in each group with no statistically significant difference in baseline characteristics.RESULTS The NC-LTG group exhibited a longer operation time(244.10±48.13 min vs 225.74±45.33 min,P=0.019)and increased intraoperative blood loss[150(100-300)mL vs 100(100-200)mL,P=0.011]compared to the LTG group.The 30-d postoperative morbidity of the NC-LTG group was 20.5%(15/73),and that of the LTG group was 13.7%(10/73).There were no significant differences in 30-d severe complication rates or anastomotic leakage rates.Subgroup analysis showed that the patients with pTNM(pathological tumor-node-metastasis classification)T0N0-II in the NC-LTG group underwent a longer operation than the LTG group,while no significant difference was found in any perioperative index for the pTNM III patients.A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor(odds ratio=3.021,95%confidence interval:1.160-7.868,P=0.024),while NC was not an independent risk factor for postoperative complications in LTG.CONCLUSION Despite a longer operation time and more blood loss after NC-LTG,which indicate surgical difficulty,NC-LTG exhibits acceptable short-term outcomes compared to LTG,suggesting the safety and feasibility of NC-LTG.

Interaction between circulating cancer cells and platelets:clinical implication

Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.

Comparison of short-term efficacy between totally laparoscopic gastrectomy and laparoscopic assisted gastrectomy for elderly patients with gastric cancer

BACKGROUND Totally laparoscopic gastrectomy(TLG)entails both gastrectomy and gastrointestinal reconstruction under laparoscopy.Compared with laparoscopic assisted gastrectomy(LAG),TLG has been demonstrated in many studies to require a smaller surgical incision,result in a faster postoperative recovery and less pain and have comparable long-term efficacy,which has been a research hotspot in recent years.Whether TLG is equally safe and feasible for elderly patients remains unclear.AIM To compare the short-term efficacy of and quality of life(QOL)associated with TLG and LAG in elderly gastric cancer(GC)patients.METHODS The clinicopathological data of 462 elderly patients aged≥70 years who underwent LAG or TLG(including distal gastrectomy and total gastrectomy)between January 2017 and January 2022 at the Department of General Surgery,First Medical Center,Chinese PLA General Hospital were retrospectively collected.A total of 232 patients were in the LAG group,and 230 patients were in the TLG group.Basic patient information,clinicopathological characteristics,operation information and QOL data were collected to compare efficacy.Compared with those in the LAG group,intraoperative blood loss in the TLG group was significantly lower(P<0.001),and the time to first flatus and postoperative hospitalization time were significantly shorter(both P<0.001).The overall incidence of postoperative complications in the TLG group was significantly lower than that in the LAG group(P=0.01).Binary logistic regression results indicated that LAG and an operation time>220 min were independent risk factors for postoperative complications in elderly patients with GC(P<0.05).In terms of QOL,no statistically significant differences in various preoperative indicators were found between the LAG group and the LTG group(P>0.05).Compared with the laparoscopic-assisted total gastrectomy group,patients who received totally laparoscopic total gastrectomy had lower nausea and vomiting scores and higher satisfaction with their body image(P<0.05).Patients who underwent laparoscopic-assisted distal gastrectomy were more satisfied with their body image than patients in the totally laparoscopic distal gastrectomy group(P<0.05).CONCLUSION TLG is safe and feasible for elderly patients with GC and has outstanding advantages such as reducing intracorporeal blood loss,promoting postoperative recovery and improving QOL.

AEG1 induces COX-2 expression via activation of NF-κB and AP-1 in hepatoma HepG2 cells

Objective： The aim of this study was to investigate whether astrecyte elevated gene 1 （AEG1） regulates COX-2 expression in human hepatoma HepG2 cells and related pathways involved in this process. Methods： Human hepatoma HepG2 cells were transfected with pcDNA3.1（-）-AEG1 plasmid or psilencer2.0-AEGl-shRNA1 plasmid to up/down-regulate AEG1 expression, pcDNA3.1（-） and psilencer 2.0 empty vector plasmids were transfected respectively as control. Real-time RT-PCR was carried out to measure the expression levels of AEG1 and COX-2 mRNA. The expression levels of AEG1 and COX-2 protein were detected by Western blot. NF-KB signaling was blocked by PDTC, and AP-1 signaling was blocked by curcumin. Results： AEG1 mRNA and protein levels were increased after pcDNA3.1（-）-AEG1 transfection, and decreased after psilencer2.0-AEGl-shRNAs transfection. COX-2 mRNA and protein levels were increased in AEGl-overexpressing cells and decreased in AEGl-knockdown cells. Phosphorylations of p65 and c-jun were up-regulated in AEGl-overexpressing cells. Both PDTC and curoumin reduced COX-2 expression in HepG2 cells with AEG1 overexpression. Conclusion： AEG1- overexpressing and -knockdown HepG2 cells are established successfully. AEG1 could induce COX-2 expression though activating NF-KB and AP-1 in human hepatoma HepG2 cells.

Exosomes in Sepsis Diagnosis and Treatment

Sepsis has been redefined as a disorder of host response to infection, systemic circulation and cell/metabolic abnormalities. Exosomes are small (30 - 150 nm) vesicles produced by all cells under physiological and pathological conditions, with the potential to transfer proteins, lipids, small RNAs, messenger RNAs, or DNA between cells. Exosomes are natural cargoes for proteins, carbohydrates, nucleic acids and lipids. Exosomes play a central role in cellular communication and contribute to many pathophysiological processes, including immune responses and tumor progression. Exosomes have made great progress in many subject areas, and their potential role in sepsis is now being explored. In this review, several topics are mentioned. Firstly, we discuss the biological characteristics and functions of exosomes. Next, we focus on the diagnostic and therapeutic potential of exosomes in sepsis. Finally, we discuss some of the problems encountered by the current exosomes research institute. Therefore, the exosomes with combined diagnostic and therapeutic functions play a huge clinical application for the future research in sepsis.

Serum folate status among blood donors in south-central China

Folate deficiency has been confirmed to be related to various diseases.Unfortunately,there are few reports on the folate status of Chinese adults.This study aims to evaluate the serum folate status of blood donors in south-central China.In this study,248 blood donors were included.The information on subjects was collected by a brief questionnaire concerning alcohol consumption habits,smoking habits,fruit and vegetable consumption and physical activity.The serum folate concentration was measured by electrochemiluminescence immunoassay.The geometric mean serum folate concentration was 13.4 nmoll-1(95%CI,12.7-14.1).The prevalence of serum folate concentrations below 6.8 nmoll-1 was 5.2%(95%CI,2.5-8.0).There were significant differences in serum folate concentrations with respect to sex(p-values<0.05),age(p-values<0.05),fruit and vegetable consumption(p-values<0.05),and alcohol consumption habits(p-values<0.05).The concentration of serum folate increased with age(p-values<0.05)and fruit and vegetable consumption(p-values<0.05).Individuals with an age of 30 years or younger were nearly 3.5 times as likely as those aged over 30 years to have an insufficient level of serum folate(OR=3.48;95%CI:1.01-11.99).An age of 30 years or younger was a risk factor for folate deficiency.Most blood donors had sufficient serum folate concentrations in south-central China.National surveys of folate status should be implemented in China.

Short and long-term outcomes between laparoscopic and open total gastrectomy for advanced gastric cancer after neoadjuvant chemotherapy

BACKGROUND Neoadjuvant chemotherapy(NACT)combined with surgery is regarded as an effective treatment for advanced gastric cancer(AGC).Laparoscopic surgery represents the mainstream of minimally invasive surgery.Currently,surgeons focus more on surgical safety and oncological outcomes of laparoscopic gastrectomy after NACT.Thus,we sought to evaluate short-and long-term outcomes between laparoscopic total gastrectomy(LTG)and open total gastrectomy(OTG)after NACT.AIM To compare the short and long-term outcomes between LTG and OTG for AGC after NACT.METHODS We retrospectively collected the clinicopathological data of 136 patients who accepted gastrectomy after NACT from June 2012 to June 2019,including 61 patients who underwent LTG and 75 who underwent OTG.Clinicopathological characteristics between the LTG and OTG groups showed no significant difference.SPSS 26.0,R software,and GraphPad PRISM 8.0 were used to perform statistical analyses.RESULTS Of the 136 patients included,eight acquired pathological complete response,and the objective response rate was 47.8%(65/136).The LTG group had longer operation time(P=0.015),less blood loss(P=0.003),shorter days to first flatus(P<0.001),and shorter postoperative hospitalization days(P<0.001).LTG spent more surgical cost than OTG(P<0.001),while total hospitalized cost of LTG was less than OTG(P<0.001).21(28.0%)patients in the OTG group and 14(23.0%)in the LTG group had 30-d postoperative complications,but there was no significant difference between the two groups(P=0.503).The 3-year overall survival(OS)rate was 60.6%and 64.6%in the LTG and OTG groups,respectively[hazard ratio(HR)=0.859,95%confidence interval(CI):0.522-1.412,P=0.546],while the 3-year disease-free survival(DFS)rate was 54.5%and 51.8%in the LTG and OTG group,respectively(HR=0.947,95%CI:0.582-1.539,P=0.823).Multivariate cox analysis showed that body mass index and pTNM stage were independent risk factors for OS while vascular invasion and pTNM stage were independent risk factors for DFS(P<0.05).CONCLUSION After NACT,LTG shows comparable 30-d postoperative morbidity as well as 3-year OS and DFS rate to OTG.We recommend that experienced surgeons select LTG other than OTG for proper AGC patients after NACT.

Lignocellulosic fraction-induced niche differentiation within dissimilatory iron reducing bacterial groups in a paddy soil

Responses of soil DIRB to lignocellulosic fractions during a 6-week microcosm incubation were investigated.Anaeromyxobacter,Bacillus,and Clostridium maintained their domi-nance throughout the incubation.Distinct DIRB groups proliferated under specific lignocellulosic fraction amendments.Limits of insufficient ferric iron on the proliferation varied by DIRB group.Dissimilatory iron reducing bacteria(DIRB)are phylogenetically and physi-ologically diverse in paddy soils,where iron reduction closely couples with the oxidation of rice straw-derived carbon in the straw returning scenarios.However,few studies have addressed the niche differentiation within DIRB groups during the degradation of lignocellulosic fractions of rice straw.This study conducted a 6-week microcosm incubation experiment to reveal the distinct responses of DIRB groups under specific lignocellulosic fraction amendments with and without ferrihydrite(Fh)addition in a flooded paddy Ultisol.Results showed that the total absolute abundance of the 19 detected DIRB groups did not vary significantly during the incubation.Anaeromyxobacter,Bacillus,and Clostridium were the dominant DIRB groups for all lignocellulosic treatments whereas Thermincola was dominant but only under xylan amendment with Fh addition.DIRB-nodes in the co-occurrence networks of bacterial community mainly belonged to Anaeromyxobacter and Bacillus.Clostridium and Thermincola,Alkaliphilus and Anaeromyxobacter,and Alicyclobacillus,Desulfobulbus,and Desulfosporosinus were specifically proliferated under xylan,cellulose,and lignin amendments,respectively.Whether the proliferation was limited by insufficient ferric iron varied by bacterial group.These findings suggested the lignocellulosic fraction-induced niche differentiation within DIRB groups,which advanced our understanding of the ecology of DIRB in paddy soils under straw returning.

术前复查尿培养在预测微通道经皮肾镜取石术相关感染并发症中的作用

目的探讨术前尿培养阳性肾结石患者经过敏感抗生素治疗后,复查尿培养对于预测微通道经皮肾镜碎石取石术(PCNL)相关感染并发症的作用。方法前瞻性、连续性收集在广州医科大学附属第一医院泌尿外科三区术前尿培养阳性并接受微通道PCNL治疗患者的临床资料,根据术前尿培养的药物敏感试验结果,对患者行敏感抗生素治疗,分别在第3、7天复查尿培养。患者经过敏感抗生素治疗7 d后接受微通道PCNL治疗,分析第3、7 d的尿培养结果与微通道PCNL术后相关感染并发症的相关性。结果2021年3月至2023年4月共收集100例患者临床资料,单因素分析的结果显示年龄、性别、糖尿病史、术前静脉血白细胞、手术时间≥90 min等与微通道PCNL术后相关感染并发症无明显相关性(P>0.05)。第3天复查尿培养,阴性95例,术后出现发热20例,其中脓毒症3例;尿培养阳性5例,术后发热1例,其中脓毒症1例。第7天复查尿培养,阴性95例,术后出现发热19例,其中脓毒血症4例;尿培养阳性5例,术后出现发热2例,无脓毒血症。单因素分析结果显示第3、7天尿培养结果与微通道PCNL相关感染并发症无明显相关性(P>0.05)。结论术前尿培养阳性肾结石患者经过敏感抗生素治疗,复查尿培养对微通道PCNL术后相关感染性并发症的预测价值有限。对于术前尿培养阳性患者,建议使用敏感抗生素治疗7 d后再行微通道PCNL。

Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.

Clinical analysis of 5-year survival and recurrence in giant retroperitoneal liposarcoma after surgery

To the Editor:Retroperitoneal liposarcoma(RLS)pertains to one of the rare malignant tumors originated from the retroperitoneum.It is evaluated as the most common type of retroperitoneal sarcoma.RLS can be divided into four subtypes according to the pathological classification,which includes well-differentiated liposarcoma(WDL),dedifferentiated liposarcoma(DDL),myxoid cell liposarcoma(MLS),and pleomorphic liposarcoma(PLS).

PI3K/AKT/mTOR pathway,hypoxia,and glucose metabolism:Potential targets to overcome radioresistance in small cell lung cancer

Small cell lung cancer(SCLC)is a highly aggressive tumor type for which limited therapeutic progress has been made.Platinum-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment,but most patients with SCLC acquire therapeutic resistance.Given the need for more effective therapies,better elucidation of the molecular pathogenesis of SCLC is imperative.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid tumors.This pathway is an important regulator of cancer cell glucose metabolism,and its activation probably effects radioresistance by influencing bioenergetic processes in SCLC.Glucose metabolism has three main branches-aerobic glycolysis,oxidative phosphorylation,and the pentose phosphate pathway-involved in radioresistance.The interaction between the PI3K/AKT/mTOR pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1(HIF-1)signaling.The PI3K/AKT/mTOR pathway also influences glucose metabolism through other mechanisms to participate in radioresistance,including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate pathway.This review summarizes our understanding of links among the PI3K/AKT/mTOR pathway,hypoxia,and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating disease.

Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity

Blocking the programmed death-ligand 1(PD-L1)on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy.However,only a minority of patients presented immune responses in clinical trials.To develop an alternative treatment method based on immune checkpoint blockade,we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells via specifically knocking out Cyclin-dependent kinase 5(Cdk5)gene in vivo.The expression of PD-L1 on tumor cells was significantly attenuated by knocking out Cdk5,leading to effective tumor growth inhibition in murine melanoma and lung metastasis suppression in triple-negative breast cancer.Importantly,we demonstrated that aPBAE/Cas9-Cdk5 treatment elicited strong T cell-mediated immune responses in tumor microenvironment that the population of CD8^+T cells was significantly increased while regulatory T cells(Tregs)was decreased.It may be the first case to exhibit direct in vivo PD-L1 downregulation via CRISPR-Cas9 genome editing technology for cancer therapy.It will provide promising strategy for preclinical antitumor treatment through the combination of nanotechnology and genome engineering.