Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

Lonicera Japonica Caulis Ameliorates LPS and TNF-α-Induced HT-29 Cell Injury by Inhibiting the MAPK/ERK/JNK/p38 Pathway

Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the intestinal tract,and shows a high rate of recurrence.Clinicians have accumulated extensive experience in the treatment of IBD,with biologics and small molecule drugs having greatly expanded the therapeutic scope of IBD in recent years.Nonetheless,such treatments involve a high price and a single target of drug action.

Ocular surface changes in moderate-to-severe acne vulgaris

AIM:To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye.METHODS:This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls.The participants completed the Ocular Surface Disease Index(OSDI)questionnaire.The following ocular surface-related parameters were measured:tear meniscus height(TMH),noninvasive tear breakup time(NIBUT),Schirmer I test(SIT),lipid layer thickness(LLT)score of the tear film,meibum score,meibomian gland orifice obstruction score,the ratio of meibomian gland loss,conjunctival hyperemia score,and corneal fluorescein staining(CFS)score.RESULTS:The stability of the tear film decreased in acne vulgaris patients.In the acne group,the TMH and NIBUT were lower,whereas the OSDI,meibum score,meibomian gland orifice obstruction score,ratio of meibomian gland loss,and conjunctival hyperemia score were higher compared with controls(P<0.05).There were no significant differences in the CFS score,SIT,or LLT score between the groups(P>0.05).In two dry eye groups,the TMH,NIBUT,and LLT score were lower in the acne with dry eye(acne-DE)group,and the meibum score,meibomian gland orifice obstruction score,ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher(P<0.05).There were no significant differences between OSDI,SIT,and CFS score(P>0.05).CONCLUSION:Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris.Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Personalized assessment and training of neurosurgical skills in virtual reality:An interpretable machine learning approach

Background Virtual reality technology has been widely used in surgical simulators,providing new opportunities for assessing and training surgical skills.Machine learning algorithms are commonly used to analyze and evaluate the performance of participants.However,their interpretability limits the personalization of the training for individual participants.Methods Seventy-nine participants were recruited and divided into three groups based on their skill level in intracranial tumor resection.Data on the use of surgical tools were collected using a surgical simulator.Feature selection was performed using the Minimum Redundancy Maximum Relevance and SVM-RFE algorithms to obtain the final metrics for training the machine learning model.Five machine learning algorithms were trained to predict the skill level,and the support vector machine performed the best,with an accuracy of 92.41%and Area Under Curve value of 0.98253.The machine learning model was interpreted using Shapley values to identify the important factors contributing to the skill level of each participant.Results This study demonstrates the effectiveness of machine learning in differentiating the evaluation and training of virtual reality neurosurgical performances.The use of Shapley values enables targeted training by identifying deficiencies in individual skills.Conclusions This study provides insights into the use of machine learning for personalized training in virtual reality neurosurgery.The interpretability of the machine learning models enables the development of individualized training programs.In addition,this study highlighted the potential of explanatory models in training external skills.

Single-center retrospective study of the diagnostic value of doubleballoon enteroscopy in Meckel’s diverticulum with bleeding

BACKGROUND The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel’s diverticulum(MD)complicated by digestive tract hemorrhage.Moreover,we aimed to evaluate the value of double-balloon enteroscopy(DBE)in MD diagnosis and the prognosis after laparoscopic diverticula resection.AIM To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding.METHODS The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations,auxiliary examination,and follow-up after laparoscopic resection of diverticula.RESULTS(1)Among 84 MD patients complicated with hemorrhage,77 were male,and 7 were female with an average age of 31.31±10.75 years.The incidence was higher in men than in women of different ages;(2)Among the 84 MD patients,65(78.40%)had defecated dark red stools,and 50(58.80%)had no accompanying symptoms during bleeding,indicating that most MD bleeding appeared a dark red stool without accompanying symptoms;(3)The shock index of 71 patients(85.20%)was<1,suggesting that the blood loss of most MD patients was less than 20%–30%,and only a few patients had a blood loss of>30%;(4)The DBE-positive rate was 100%(54/54),99mTcpertechnetate-positive scanning rate was 78%(35/45)compared with capsule endoscopy(36%)and small intestine computed tomography(19%).These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding,especially DBE was a highly precise examination method in MD diagnosis;(5)A total of 54 MD patients with hemorrhage underwent DBE examination before surgery.DBE endoscopy revealed many mucosal manifestations including normal appearance,inflammatory changes,ulcerative changes,diverticulum inversion,and nodular hyperplasia,with ulcerative changes being the most common(53.70%).This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding;and(6)Laparoscopic dissection of diverticulae was performed in 76 patients,The patients who underwent postoperative follow-up did not experience any further bleeding.Additionally,follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding.These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis.CONCLUSION Bleeding associated with MD was predominantly observed in male adolescents,particularly at a young age.DBE was a highly precise examination method in MD diagnosis.Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.

Association between heat shock factor protein 4 methylation and colorectal cancer risk and potential molecular mechanisms:A bioinformatics study

BACKGROUND We previously demonstrated that heat shock factor protein 4(HSF4)facilitates colorectal cancer(CRC)progression.DNA methylation,a major modifier of gene expression and stability,is involved in CRC development and outcome.AIM To investigate the correlation between HSF4 methylation and CRC risk,and to uncover the underlying molecular mechanisms.METHODS Differences in β values of HSF4 methylation loci in multiple malignancies and their correlation with HSF4 mRNA expression were analyzed based on Shiny Methylation Analysis Resource Tool.HSF4 methylation-related genes were identified by LinkedOmics in CRC,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.Protein-protein interaction network of HSF4 methylation-related genes was constructed by String database and MCODE algorithm.RESULTS A total of 19 CpG methylation loci were identified in HSF4,and their β values were significantly increased in CRC tissues and exhibited a positive correlation with HSF4 mRNA expression.Unfortunately,the prognostic and diagnostic performance of these CpG loci in CRC patients was mediocre.In CRC,there were 1694 HSF4 methylation-related genes;1468 of which displayed positive and 226 negative associations,and they were involved in regulating phenotypes such as immune,inflammatory,and metabolic reprogramming.EGFR,RELA,STAT3,FCGR3A,POLR2K,and AXIN1 are hub genes among the HSF4 methylation-related genes.CONCLUSION HSF4 is highly methylated in CRC,but there is no significant correlation between it and the prognosis and diagnosis of CRC.HSF4 methylation may serve as one of the ways in which HSF4 mediates the CRC process.

Pharmacogenomics-based individualized treatment of hypertension in preterm infants: A case report and review of the literature

BACKGROUND Neonatal hypertension is a rare but potentially serious condition that requires careful monitoring and treatment.Pharmacogenomics can help guide individualized drug therapy and improve outcomes.CASE SUMMARY We report a case of a preterm infant with multiple complications,including bronchopulmonary dysplasia(BPD),sepsis,intracranial hemorrhage,and hypertension.The infant was treated with various drugs,including dexamethasone and amlodipine.The infant was diagnosed with neonatal hypertension based on blood pressure measurements exceeding the 95th percentile for his age and sex.The possible causes of hypertension included dexamethasone,hydrochlorothiazide,spironolactone,and BPD.The infant was treated with oral amlodipine to lower his blood pressure.A pharmacogenomic test was performed to evaluate the genetic polymorphisms of ABCB1 and CYP3A5,which are involved in the metabolism and transport of dexamethasone and amlodipine.The infant’s blood pressure was well controlled after the dose of amlodipine was reduced according to the pharmacogenomic results.The infant had a stable general condition and was discharged on the 100th d after birth.CONCLUSION This case illustrates the importance of regular blood pressure monitoring and etiological investigation in preterm infants with hypertension.Pharmacogenomics can provide useful information for individualized drug therapy and safety in this population.

Atorvastatin Alleviates Myocardial Ischemia-Reperfusion Injury via miR-26a-5p/FOXO1

Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart failure, and it is particularly important to seek new strategies to mitigate reperfusion injury. In this paper, we will investigate whether atorvastatin can alleviate myocardial ischemia-reperfusion injury and verify its molecular mechanism. Methods: We successfully constructed a hypoxia-reperfusion (H/R) H9c2 cell model and transfected miR-26a-5p mimic, miR-26a-5p inhibitor and its negative control NC-mimic or NC-inhibitor into H9c2 cells using a transfection kit. The expression of miR-26a-5p and FOXO1 were detected by RT-qPCR assay, the expression of related proteins by Western blot assay, the cell viability of H9c2 cells by CCK-8 assay, the apoptosis rate of H9c2 cells by flow cytometry, the CK and LDH activity in cells by CK and LDH assay kits. The targeting relationship between miR-26a-5p and FOXO1 was verified by dual luciferase reporter gene assay. Results: MiR-26a-5p expression was decreased in H/R-induced cells and FOXO1 expression was increased in H/R-induced cells. Atorvastatin alleviated H/R injury in cardiomyocytes and was most effective at a concentration of 1 μM. Atorvastatin alleviated H/R injury in cardiomyocytes by upregulating miR-26a-5p expression, miR-26a-5p and FOXO1 were negatively regulated by targeting. Conclusion: Atorvastatin can alleviate H/R injury in cardiomyocytes by regulating miR-26a-5p/FOXO1.

Pulmonary artery aneurysm protruding into the bronchus as an endobronchial mass:A case report

BACKGROUND Pulmonary artery(PA)aneurysms are usually diagnosed radiographically and present as small or large lesions resembling inflammation or a neoplasm on chest radiography.It has rarely been reported as an endobronchial mass.CASE SUMMARY We report the case of a 64-year-old man who presented with recurrent hemoptysis.Bronchoscopy revealed a tumorous protrusion blocking the right middle lobe bronchus,which was confirmed to be a PA aneurysm using endobronchial ultrasound bronchoscopy and computed tomography angiography.CONCLUSION Although endobronchial PA aneurysms are rare,bronchoscopists need to add this lesion to the list of endobronchial masses for which a biopsy is to be assiduously avoided.

Clinical usefulness of linked color imaging in identifying Helicobacter pylori infection:A systematic review and meta-analysis

BACKGROUND Accurate diagnosis of Helicobacter pylori(H.pylori)infection status is a crucial premise for eradication therapy,as well as evaluation of risk for gastric cancer.Recent progress on imaging enhancement endoscopy(IEE)made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H.pylori infection in real time.As a novel IEE modality,linked color imaging(LCI)has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone.AIM To compare the efficacy of LCI for H.pylori active infection vs conventional white light imaging(WLI).METHODS PubMed,Embase,Embase and Cochrane Library were searched up to the end of April 11,2022.The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI.The calculation of sensitivity,specificity,and likelihood ratios were performed;symmetric receiver operator characteristic(SROC)curves and the areas under the SROC curves were computed.Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool.RESULTS Seven original studies were included in this study.The pooled sensitivity,specificity,positive likelihood rate,and negative likelihood rate of LCI for the diagnosis of H.pylori infection of gastric mucosa were 0.85[95%confidence interval(CI):0.76-0.92],0.82(95%CI:0.78-0.85),4.71(95%CI:3.7-5.9),and 0.18(95%CI:0.10-0.31)respectively,with diagnostic odds ratio=26(95%CI:13-52),SROC=0.87(95%CI:0.84-0.90),which showed superiority of diagnostic efficacy compared to WLI.CONCLUSION Our results showed LCI can improve efficacy of diagnosis on H.pylori infection,which represents a useful endoscopic evaluation modality for clinical practice.

Hepatitis B virus genotypes and genome characteristics in China

AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database(information including:genotype,territory and clinical status).HBV genotypes were classified by a direct reference from the Genbank sequence annotation,phylogenetic tree and online software analysis(http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi).The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software.HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods.Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms.Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages.The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software.Recombination analysis was performed by using Simplot software.RESULTS:In China,HBV genotype C was the predominant in Northeastern,genotype B was predominant in Central Southern areas,genotype B and C were both dominant in Southwestern areas,and the recombinant genotype C/D was predominant in Northwestern areas.C2 and B2 were identified as the two major sub-genotypes,FJ386674 might be a putative sub-genotype as B10.The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms.In addition to ATG,many other HBV initiation codons also exist.HBV has codon usage bias;the termination codon of X,C and P open reading frames(ORF) were TAA,TAG,and TGA,respectively.The major stop codons of S-ORF were TAA(96.45%) and TGA(83.60%) in B2 and C2 subtype,respectively.CONCLUSION:This study recapitulated the epidemiology of HBV in China,and the information might be meaningful critical for the future prevention and therapy of HBV infections.

Positron-emission tomography for hepatocellular carcinoma:Current status and future prospects

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer mortality worldwide.Various imaging modalities provide important information about HCC for its clinical management.Since positron-emission tomography(PET)or PET-computed tomography was introduced to the oncologic setting,it has played crucial roles in detecting,distinguishing,accurately staging,and evaluating local,residual,and recurrent HCC.PET imaging visualizes tissue metabolic information that is closely associated with treatment.Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis.The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance.The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.

Hepatitis B virus genetic mutations and evolution in liver diseases

Hepatitis B virus(HBV)belongs to the genus Orthohepadnavirus of the Hepadnaviridae family and is approximately 3.2 kb in length.Owing to a lack of proofreading capacity during reverse transcription and a high replication rate,HBV exhibits as quasispecies.To detect the genetic mutations of HBV,many methods with different sensitivities and throughputs were developed.According to documentary records,HBV mutation and evolution were important vial parameters in predicting disease progression and therapeutic outcome.In this review,we separately discussed the correlation between HBV genomic mutations in four open reading frames and liver disease progression.Since some of the results were controversial from different laboratories,it remains to be seen whether functional analyses will confirm their role in modifying the course of infection.

The Outlook of the Development of Innovative Products from Biocompatible Natural Spider Silk in the Beauty Thread-Lifting Industry

Embedding thread lift rhytidectomy,also known as“thread lifting”in China,with the natures of simple operation,less trauma and quick recovery,is progressively used in clinical practice as a new technology of face lifting.Herewith,a brief introduction of the previous advances of thread lifting techniques and materials in the facial beauty industry,combined with the discussion on various types of sutures,common complications,and the site of actions were provided.The main limitations of present thread lifting material include:(1)the use of non-absorbable sutures is liable to cause allergies and a series of complications;(2)the absorbable sutures are easily degradation,and people need to reshape in a relatively short period.Therefore,the high biocompatible spider silk was proposed as a novel material of thread lifting suture and related devices,the advantages and preliminary achievements on spider silk were also addressed.

Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma masquerading as Behcet’s disease: A case report and review of literature

BACKGROUND Anaplastic large cell lymphoma(ALCL)is a CD30-positive T cell lymphoma,a rare type of non-Hodgkin lymphoma.The current World Health Organization classification system divides ALCLs into anaplastic lymphoma kinase(ALK)-positive and ALK-negative groups.ALCL rarely presents in the gastrointestinal tract.CASE SUMMARY A 54-year-old male was admitted to the department of gastroenterology for abdominal pain.He presented with lower abdominal pain,diarrhea and recurrent oral and penile ulcers.He was misdiagnosed with Behcet's disease and treated with prednisone.But after one month,he was hospitalized in another hospital for reexamination.This time,the lesion on the penis was biopsied for histological examination.The final pathological diagnosis was ALCL,ALKnegative.The patient was treated with cyclophosphamide,doxorubicin,vincristine,prednisolone chemotherapy.However,he died within one month.CONCLUSION Gastrointestinal ALCL needs to be considered in the differential diagnosis to avoid delaying treatment.Repeated biopsy is the most important for early diagnosis and treatment.

Correlations between the optic nerve head morphology and ocular biometrics in highly myopic eyes

AIM： To analyze peripapillary atrophy β/γ zone （PPA-β/γ） and the optic disc ovality index, and to assess their associations with the axial length （AL）, refractive error, best corrected visual acuity （BCVA）, choroidal thickness （CT）, and age in highly myopic eyes. METHODS： This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes [spherical equivalent ≤-6.0 diopters （D） and AL≥26 mm] with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography （SD-OCT） of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-β/γ area were measured from optic disc photographs. RESULTS： A significant association was seen between PPA-β/γ area and the ovality index （P=0.000, r=-0.232）. The PPA-β/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid （P〈0.01）. The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-β/γ area, and thinner choroid （P〈0.01）. CONCLUSION： The PPA-β/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia(2021 Edition)

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Forkhead Box q1 promotes invasion and metastasis in colorectal cancer by activating the epidermal growth factor receptor pathway

BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.

Pregnancy complications effect on the nickel content in maternal blood,placenta blood and umbilical cord blood during pregnancy

BACKGROUND Nickel(Ni)may accumulate in the human body and has biological toxicity and carcinogenicity.Ni has an extensive impact on the health of pregnant women and fetuses during gestation.AIM To evaluate Ni exposure in pregnant women in Kunming,Yunnan Province,China;to describe the distribution of Ni in the maternal-fetal system and placental barrier function;and to investigate the effect of Ni exposure on fetal health in mothers with pregnancy complications.METHODS Seventy-two pregnant women were selected using a case-control design.The women were divided into two groups:The control group(no disease;n=29)and the disease group[gestational diabetes(GDM),hypertensive disorder complicating pregnancy(HDCP),or both;n=43].The pregnant women in the disease group were further divided as follows:14 cases with GDM(GDM group),13 cases with HDCP(HDCP group)and 16 cases with both GDM and HDCP(disease combination group).Basic information on the pregnant women was collected by questionnaire survey.Maternal blood,placenta blood and cord blood were collected immediately after delivery.The Ni content in paired samples was determined using inductively coupled plasma mass spectrometry.RESULTS Compared to the control group,age was higher and body mass index was greater in pregnant women in the disease groups(28.14±2.54 vs 28.42±13.89,P<0.05;25.90±3.86 vs 31.49±5.30,P<0.05).The birth weights of newborns in the HDCP group and the control group were significantly different(2.52±0.74 vs 3.18±0.41,P<0.05).The content of Ni in umbilical cord blood in the entire disease group was higher than that in the control group(0.10±0.16 vs 0.05±0.07,P<0.05).CONCLUSION In the maternal-fetal system of women with pregnancy complications,the barrier effect of the placenta against Ni is weakened,thus affecting healthy growth of the fetus in the uterus.