Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients

BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

Assessment of spermatogenesis in camels via seminiferous tubule staging and testosterone profiling

Objective:To investigate the successive morphological stages of spermatogenesis,hormonal regulation,and testosterone profile in dromedary camel reproduction.Methods:Testicular tissue samples were obtained from 12 dromedary bull camels aged 7 to 8 at a local abattoir.The histological assessment involved tissue processing,hematoxylin and eosin(H&E)staining,and examination under a microscope.Stereological analysis,germ cell identification,and assessment of seminiferous tubules and maturation were conducted.Testosterone assay was performed by radioimmunoassay using blood samples collected at regular intervals.Results:The study revealed 12 phases of the dromedary camel's seminiferous epithelium cycle,highlighting distinct morphological characteristics and cellular processes.Acrosomal migration,maturation,cap formation,and the Golgi-mediated synthesis of proacrosomal vesicles were also explained in dimension,as were the steps of acrosome biogenesis.Spermatids and mature sperm cells were present when spermatogenesis phases were examined.An analysis of the dimensions of seminiferous tubules revealed specific measures for diameter,area,and epithelial height about luminal characteristics.Moreover,there were noticeable variations in the serum testosterone concentrations during the study period,indicating temporal dynamics.Conclusions:This study outlines the spermatogenesis process in dromedary camels across 12 stages,emphasizing cellular dynamics and acrosomal biogenesis.It also provides seminiferous tubule measurements and observes seasonal testosterone fluctuations,offering insights into reproductive regulation and potential strategies for camel breeding conservation.

Ecological network analysis reveals complex responses of tree species life stage interactions to stand variables

Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.

Feedback linearization and equivalent-disturbance compensation control strategy for piezoelectric stage

Piezoelectric stages use piezoelectric actuators and flexure hinges as driving and amplifying mechanisms,respectively.These systems have high positioning accuracy and high-frequency responses,and they are widely used in various precision/ultra-precision positioning fields.However,the main challenge with these devices is the inherent hysteresis nonlinearity of piezoelectric actuators,which seriously affects the tracking accuracy of a piezoelectric stage.Inspired by this challenge,in this work,we developed a Hammerstein model to describe the hysteresis nonlinearity of a piezoelectric stage.In particular,in our proposed scheme,a feedback-linearization algorithm is used to eliminate the static hysteresis nonlinearity.In addition,a composite controller based on equivalent-disturbance compensation was designed to counteract model uncertainties and external disturbances.An analysis of the stability of a closed-loop system based on this feedback-linearization algorithm and composite controller was performed,and this was followed by extensive comparative experiments using a piezoelectric stage developed in the laboratory.The experimental results confirmed that the feedback-linearization algorithm and the composite controller offer improved linearization and trajectory-tracking performance.

An Elite-Class Teaching-Learning-Based Optimization for Reentrant Hybrid Flow Shop Scheduling with Bottleneck Stage

Bottleneck stage and reentrance often exist in real-life manufacturing processes;however,the previous research rarely addresses these two processing conditions in a scheduling problem.In this study,a reentrant hybrid flow shop scheduling problem(RHFSP)with a bottleneck stage is considered,and an elite-class teaching-learning-based optimization(ETLBO)algorithm is proposed to minimize maximum completion time.To produce high-quality solutions,teachers are divided into formal ones and substitute ones,and multiple classes are formed.The teacher phase is composed of teacher competition and teacher teaching.The learner phase is replaced with a reinforcement search of the elite class.Adaptive adjustment on teachers and classes is established based on class quality,which is determined by the number of elite solutions in class.Numerous experimental results demonstrate the effectiveness of new strategies,and ETLBO has a significant advantage in solving the considered RHFSP.

Dry eye rate and its relationship with disease stage in patients with primary hypertension:a cross-sectional study in Vietnam

AIM:To determine the dry eye(DE)rate and its relationship with disease stage in patients with primary hypertension.METHODS:A cross-sectional study included 432 patients with primary hypertension(with an equal number of patients in each group:144 in stage Ⅰ,Ⅱ,and Ⅲ hypertension)and 144 healthy subjects as a control group.The Ocular Surface Disease Index(OSDI)and Schirmer Ⅰ test without anesthetics were conducted on all 576 subjects.Subjects with OSDI scores<13 and Schirmer Ⅰ values equal to or under 10 mm were diagnosed with DE.RESULTS:The ratio of DE in hypertension patients was higher than in the control group(41.7%versus 18.8%;P<0.001).The proportion of patients with DE increased gradually according to the hypertension stage:27.1% in stage Ⅰ,40.3% in stage Ⅱ,and 57.6% in stage Ⅲ,P<0.001.Age,duration of hypertension,plasma urea,creatinine,and high-sensitivity C-reactive protein(CRP-hs)levels in hypertension patients with DE were higher than those without DE,P<0.001.Advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma creatinine,and CRP-hs levels were independent factors associated with DE in primary hypertension patients,P<0.001.CONCLUSION:DE is a common disorder associated with advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma CRP-hs,and creatinine levels in patients with primary hypertension.

CmMYB3-like negatively regulates anthocyanin biosynthesis and flower color formation during the post-flowering stage in Chrysanthemum morifolium

Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.

Single-cell profiling of the pig cecum at various developmental stages

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

Novel method for identifying the stages of discharge underwater based on impedance change characteristic

It is difficult to determine the discharge stages in a fixed time of repetitive discharge underwater due to the arc formation process being susceptible to external environmental influences. This paper proposes a novel underwater discharge stage identification method based on the Strong Tracking Filter(STF) and impedance change characteristics. The time-varying equivalent circuit model of the discharge underwater is established based on the plasma theory analysis of the impedance change characteristics and mechanism of the discharge process. The STF is used to reduce the randomness of the impedance of repeated discharges underwater, and then the universal identification resistance data is obtained. Based on the resistance variation characteristics of the discriminating resistance of the pre-breakdown, main, and oscillatory discharge stages, the threshold values for determining the discharge stage are obtained. These include the threshold values for the resistance variation rate(K) and the moment(t).Experimental and error analysis results demonstrate the efficacy of this innovative method in discharge stage determination, with a maximum mean square deviation of Scrless than 1.761.

Development of a novel staging classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy

BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification for Siewert Ⅱ AEG with NAC.METHODS A nomogram was established based on Cox regression model that analyzed variables associated with overall survival(OS)and disease-specific survival(DSS).The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test,Akaike information criterion,Harrell concordance index,time-receiver operating characteristic curve,and decision curve analysis.RESULTS Data from 725 patients with Siewert type Ⅱ AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate analyses revealed that sex,marital status,race,ypT stage,and ypN stage were independent prognostic factors of OS,whereas sex,race,ypT stage,and ypN stage were independent prognostic factors for DSS.These factors were incorporated into the OS and DSS nomograms.Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer.Finally,a user-friendly web application was developed for clinical use.CONCLUSION The nomogram established specifically for patients with Siewert type Ⅱ AEG receiving NAC demonstrated good prognostic performance.Validation using external data is warranted before its widespread clinical application.

Prediction of Lung Cancer Stage Using Tumor Gene Expression Data

Lung cancer remains a significant global health challenge and identifying lung cancer at an early stage is essential for enhancing patient outcomes. The study focuses on developing and optimizing gene expression-based models for classifying cancer types using machine learning techniques. By applying Log2 normalization to gene expression data and conducting Wilcoxon rank sum tests, the researchers employed various classifiers and Incremental Feature Selection (IFS) strategies. The study culminated in two optimized models using the XGBoost classifier, comprising 10 and 74 genes respectively. The 10-gene model, due to its simplicity, is proposed for easier clinical implementation, whereas the 74-gene model exhibited superior performance in terms of Specificity, AUC (Area Under the Curve), and Precision. These models were evaluated based on their sensitivity, AUC, and specificity, aiming to achieve high sensitivity and AUC while maintaining reasonable specificity.

Nutritional Composition and Distribution of Heracleum dissectum Ledeb.at Different Growth Stages

Heracleum dissectum Ledeb.(HD)with high edible and medicinal values is distributed in Northeast Asia.To provide a reference for selecting appropriate parts and periods to harvest HD,the nutrient contents in different parts of HD at three growth stages were determined.The nutrients being determined are essential nutrients closely related to human needs,and the crude protein content of HD was 3.58‒28.43 g•100 g^(-1)DW(dry weight),sugar content was 2.33‒30.92 g•100 g^(-1)DW,and soluble dietary fiber content was 9.71‒26.09 g•100 g^(-1)DW.Crude protein was mainly distributed in leaf blades and inflorescences,sugar was primarily found in roots,and dietary fiber was predominantly located in leaves.From the leaf development stage to the flowering stage and then to the late seed harvest stage,the content of moisture,crude protein and soluble sugar first decreased and then increased.In contrast,the content of dietary fiber and crude fat first increased and then decreased.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease:A meta-analysis

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.

Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging,invasion,and metastasis

BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.

Clinical application of oral contrast-enhanced ultrasound in evaluating the preoperative T staging of gastric cancer

BACKGROUND Oral contrast-enhanced ultrasound(OCEUS)is widely used in the noninvasive diagnosis and screening of gastric cancer(GC)in China.AIM To investigate the clinical application of OCEUS in evaluating the preoperative T staging of gastric cancer.METHODS OCEUS was performed before the operation,and standard ultrasound images were retained.The depth of infiltration of GC(T-stage)was evaluated according to the American Joint Committee on Cancer 8th edition of the tumor-nodemetastasis staging criteria.Finally,with postoperative pathological staging as the gold standard reference,the sensitivity,specificity,negative predictive value,positive predictive value,and diagnostic value of OCEUS T staging were evaluated.RESULTS OCEUS achieved diagnostic accuracy rates of 76.6%(T1a),69.6%(T1b),62.7%(T2),60.8%(T3),88.0%(T4a),and 88.7%(T4b),with an average of 75.5%.Ultrasonic T staging sensitivity exceeded 62%,aside from T1b at 40.3%,while specificity was over 91%,except for T3 with 83.5%.The Youden index was above 60%,with T1b and T2 being exceptions.OCEUS T staging corresponded closely with pathology in T4b(kappa>0.75)and moderately in T1a,T1b,T2,T3,and T4a(kappa 0.40-0.75),registering a concordance rate exceeding 84%.CONCLUSION OCEUS was effective,reliable,and accurate in diagnosing the preoperative T staging of GC.As a noninvasive diagnostic technique,OCEUS merits clinical popularization.

Functional assessment and influencing factors after staged functional training in patients with ankle fractures

BACKGROUND The recovery of limb function after ankle fracture surgery is a gradual process.The main purpose of implementing early functional exercise,joint mobility,muscle contraction function,passive ankle flexion and extension exercises,or physical factor therapy techniques is to achieve the rapid recovery of normal physiological limb function.However,currently the most effective rehabilitation training method is staged limb functional exercise,which promotes rapid recovery of limb function while preventing adverse consequences caused by overwork or insufficient training.Staged limb functional exercise divides the rehabilitation process into multiple stages,each of which has specific training objectives and contents.This method helps patients gradually restore limb function.Nevertheless,some patients still exhibit poor limb function after standardized exercise.Therefore,a functional evaluation should be performed to analyze the impact of staged functional training after ankle fracture surgery.AIM To perform a functional evaluation and determine the influencing factors of staged functional training in patients with ankle fracture.METHODS A retrospective study enrolled 150 patients who underwent surgical treatment for ankle fracture from May 2020 to May 2022 at our hospital.Univariate and multivariate linear regression analyses were performed on general data,functional exercise compliance scale for orthopedic patients,Social Support Rating Scale(SSRS),American Orthopedic Foot and Ankle Score(AOFAS)Ankle-Hindfoot Score,and pain factors[serum bradykinin(BK),prostaglandin E2(PGE2),5-hydroxytryptamine(5-HT)].RESULTS Based on the AOFAS Ankle-Hindfoot Scale,the cases were divided into the excellent function(n=111)and ordinary function(n=39)groups.Univariate analysis revealed that monthly family income,education level,diabetes mellitus,functional exercise compliance scale of orthopedic patients score,SSRS,BK,PGE2,and 5-HT significantly influenced limb function after ankle fracture(P<0.05);Multiple linear regression analysis showed that the functional exercise compliance scale score,SSRS,BK,PGE2,and 5-HT were independent risk factors affecting functional performance after staged functional exercise(P<0.05).CONCLUSION Exercise compliance,SSRS,and pain level are the independent risk factors affecting functional performance after staged functional training following ankle surgery.Clinical nursing care after ankle surgery should include analgesic and health education measures to ensure optimal recovery of limb function.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy

Diabetic retinopathy(DR),as one of the most common and significant microvascular complications of diabetes mellitus(DM),continues to elude effective targeted treatment for vision loss despite ongoing enrichment of the understanding of its pathogenic mechanisms from perspectives such as inflammation and oxidative stress.Recent studies have indicated that characteristic neuroglial degeneration induced by DM occurs before the onset of apparent microvascular lesions.In order to comprehensively grasp the early-stage pathological changes of DR,the retinal neurovascular unit(NVU)will become a crucial focal point for future research into the occurrence and progression of DR.Based on existing evidence,ferroptosis,a form of cell death regulated by processes like ferritinophagy and chaperone-mediated autophagy,mediates apoptosis in retinal NVU components,including pericytes and ganglion cells.Autophagy-dependent ferroptosis-related factors,including BECN1 and FABP4,may serve as both biomarkers for DR occurrence and development and potentially crucial targets for future effective DR treatments.The aforementioned findings present novel perspectives for comprehending the mechanisms underlying the early-stage pathological alterations in DR and open up innovative avenues for investigating supplementary therapeutic strategies.

Is there sufficient evidence to support the use of antibiotic holiday just before the second stage of an infected total hip or knee arthroplasty revision surgery?

The practice of implementing an antibiotic holiday before the second stage of hip or knee arthroplasty is currently controversial due to limited evidence for this approach,as per the International Consensus Meeting 2018 on Musculoskeletal Infection.A greater understanding of this issue could augment the quality of Alrayes and Sukeik’s mini-review(2023)on diagnosing,managing,and treating periprosthetic knee infections.However,a significant lack of literature exists concerning the optimal duration for the antibiotic holiday,calling for more research before establishing any clinical guidelines.