Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex

Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

Intricate roles of estrogen and estrogen receptors in digestive system cancers:a systematic review

Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

Effi cacy of partial and complete resuscitative endovascular balloon occlusion of the aorta in the hemorrhagic shock model of liver injury

BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.

Advances in Cuproptosis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) has already become a severe health risk and brings a lot of healthcare burden to the world. Apart from traditional HCC treatment strategies (surgery, liver transplantation, etc.), the emergence of immunotherapy targeting the immune microenvironment of HCC has brought new promise to patients with advanced HCC. However, adverse effects like drug resistance still exist. The liver is the main organ for storing copper ions, in copper overload can lead to liver function impairment and even the development of HCC. In recent years, a new mode of cell death has been identified, namely cuproptosis, a mode of programmed cell death that is dependent on copper ions and the tricarboxylic acid (TCA) cycle with mitochondria. Interestingly, a potential relationship between cuproptosis and the development of HCC has been found. Conclusively, this review provides an in-depth discussion of copper homeostasis in humans, the mechanism of cuproptosis, the potential impact of cuproptosis with HCC, and the therapeutic modalities of HCC that target cuproptosis, which provide new insights to promote the development of research targeting cuproptosis in HCC.

Prevalence and incidence of heart failure among community in China during a three-year follow-up

BACKGROUND Epidemiological surveys on heart failure(HF)in Chinese community are relatively lacking.This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.METHODS Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged≥35years in Guangzhou,China.The same survey process was carried out for individuals aged≥65 years after a three-year follow-up.RESULTS The overall prevalence of HF in community residents aged≥35 years was 1.06%.Male had significantly higher risk of HF prevalence[odds ratio(OR)=1.50,P=0.027].The gender-adjusted risk of HF was 1.48 times higher per 10 years aging.HF prevalence was statistically associated with atrial fibrillation,valvular heart disease,hypertension and chronic obstructive pulmonary disease after adjusting for age and gender(OR=8.30,5.17,1.11,2.28,respectively;all P<0.05).HF incidence in individuals aged≥65 years were 847 per 100,000 person-years.Baseline atrial fibrillation,valvular heart disease,and diabetes mellitus were risk factors for HF incidence for individuals aged≥65 years adjusting for age and gender(OR=5.05,3.99,2.11,respectively;all P<0.05).Besides,residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF(OR=14.41,8.54,respectively;all P<0.05).CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China.Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Predictive value of co-expression patterns of immune checkpoint molecules for clinical outcomes of hematological malignancies

Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical outcome.It is worth establishing and optimizing an ideal prediction model based on the co-expression patterns of IC molecules to evaluate the immune status of HM patients and predict their clinical outcome.In this perspective,we summarize the co-expression patterns of IC molecules and their importance as biomarkers that predict the prognosis of patients with different HMs,providing new insights for designing dual IC blockades(ICBs).

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy

BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unresectable HCC who received conversion therapy.METHODS One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort(n=120)and a validation cohort(n=30).Using the independent risk factors in the training cohort,a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection.The nomogram was internally validated with the bootstrapping method.The predictive performance of nomogram was assessed by Harrell’s concordance index(C-index),calibration plot and timedependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.RESULTS Multivariate Cox analysis identified that albumin,blood urea nitrogen,gamma-glutamyl transpeptidase to platelet ratio,platelet to lymphocyte ratio,macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model.The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS,which were higher than those of the six conventional HCC staging systems(0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort).The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS.Decision curve analyses indicated satisfactory clinical utility.With a total nomogram score of 196,patients were accurately classified into low-risk and high-risk groups.Furthermore,we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.CONCLUSION The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy,which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Noninvasive Characterization of Metabolic Changes in Ischemic Stroke Using Z-spectrum-fitted Multiparametric Chemical Exchange Saturation Transfer-weighted Magnetic Resonance Imaging

Objective This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging(CEST-MRI).Methods Three sets of Z-spectrum data with saturation power(B_(1))values of 1.5,2.5,and 3.5µT,respectively,were acquired from 17 patients with ischemic stroke.Multiple contrasts contributing to the Z-spectrum,including fitted amide proton transfer(APT_(fitted)),+2 ppm peak(CEST@2ppm),concomitantly fitted APT_(fitted) and CEST@2ppm(APT&CEST@2ppm),semisolid magnetization transfer contrast(MT),aliphatic nuclear Overhauser effect(NOE),and direct saturation of water(DSW),were fitted with 4 and 5 Lorentzian functions,respectively.The CEST metrics were compared between ischemic lesions and contralateral normal white matter(CNWM),and the correlation between the CEST metrics and the apparent diffusion coefficient(ADC)was assessed.The differences in the Z-spectrum metrics under varied B1 values were also investigated.Results Ischemic lesions showed increased APTfitted,CEST@2ppm,APT&CEST@2ppm,NOE,and DSW as well as decreased MT.APT&CEST@2ppm,MT,and DSW showed a significant correlation with ADC[APT&CEST@2ppm at the 3 B_(1) values:R=0.584/0.467/0.551;MT at the 3 B_(1) values:R=−0.717/−0.695/−0.762(4-parameter fitting),R=−0.734/−0.711/−0.785(5-parameter fitting);DSW of 4-/5-parameter fitting:R=0.794/0.811(2.5µT),R=0.800/0.790(3.5µT)].However,the asymmetric analysis of amide proton transfer(APT_(asym))could not differentiate the lesions from CNWM and showed no correlation with ADC.Furthermore,the Z-spectrum contrasts varied with B_(1).Conclusion The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues.

A novel model of drug cue-induced behaviours in rhesus macaque subjected to chronic ketamine exposure

To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive behavioural training paradigm,relatively expensive apparatus and invasive surgical procedures.

miR-103-3p regulates the differentiation of bone marrow mesenchymal stem cells in myelodysplastic syndrome

The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.

Tra2βEnhances Cell Proliferation by Inducing the Expression of Transcription Factor SP1 in Cervical Cancer

Objective In this study,the role and potential mechanism of transformer 2β(Tra2β)in cervical cancer were explored.Methods The transcriptional data of Tra2βin patients with cervical cancer from Gene Expression Profiling Interactive Analysis(GEPIA)and cBioPortal databases were investigated.The functions of Tra2βwere evaluated by using Western blot,MTT,colony formation,Transwell assays,and nude mouse tumor formation experiments.Target genes regulated by Tra2βwere studied by RNA-seq.Subsequently,representative genes were selected for RT-qPCR,confocal immunofluorescence,Western blot,and rescue experiments to verify their regulatory relationship.Results The dysregulation of Tra2βin cervical cancer samples was observed.Tra2βoverexpression in Siha and Hela cells enhanced cell viability and proliferation,whereas Tra2βknockdown showed the opposite effect.Alteration of Tra2βexpression did not affect cell migration and invasion.Furthermore,tumor xenograft models verified that Tra2βpromoted cervical cancer growth.Mechanically,Tra2βpositively regulated the mRNA and protein level of SP1,which was critical for the proliferative capability of Tra2β.Conclusion This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo,which provides a comprehensive understanding of the pathogenesis of cervical cancer.

A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum

The current animal models of stroke primarily model a single intracerebral hemorrhage(ICH)attack,and there is a lack of a reliable model of recurrent ICH.In this study,we established 16-month-old C57 B L/6 male mouse models of ICH by injecting collagenaseⅦ-S into the left striatum.Twenty-one days later,we injected collagenaseⅦ-S into the right striatum to simulate recurrent ICH.Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage,delayed recovery in locomotor function,motor coordination,and movement speed,and more obvious emotional and cognitive dysfunction than mice subjected to unilate ral striatal hemorrhage.These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH.These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

Association between the extent of public health measures and other respiratory infectious diseases cases amidst the COVID-19 pandemic in Thailand

Public health strategies have resulted in declines in some respiratory infectious viruses during the COVID-19 pandemic[1],while the way to assess the extent of public health measures and their impacts on respiratory infectious diseases varies[2-4].During the pandemic,Thailand has implemented a strong and rapid governmental response according to its incidence rate[3],and we attempted to investigate the association between the extent of public health measures and other respiratory infectious diseases cases amidst the COVID-19 pandemic in Thailand.In this way,the level of public health measures and their impacts on other kinds of non-SARS-CoV-2 respiratory infections will help the government formulate more efficient policies.

Cardiopulmonary prognosis of prophylactic endotracheal intubation in patients with upper gastrointestinal bleeding undergoing endoscopy

BACKGROUND:It is controversial whether prophylactic endotracheal intubation(PEI)protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding(UGIB).The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy.METHODS:Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database(eICU-CRD).The composite cardiopulmonary outcomes included aspiration,pneumonia,pulmonary edema,shock or hypotension,cardiac arrest,myocardial infarction,and arrhythmia.The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups.Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes.Moreover,restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes(yes/no)in the PEI group.RESULTS:A total of 946 patients were divided into the PEI group(108/946,11.4%)and the non-PEI group(838/946,88.6%).After propensity score matching,the PEI group(n=50)had a higher incidence of cardiopulmonary outcomes(58.0%vs.30.3%,P=0.001).PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders(odds ratio[OR]3.176,95%confidence interval[95%CI]1.567-6.438,P=0.001).The subgroup analysis indicated the similar results.A shock index>0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI(P=0.015).The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index(OR 1.465,95%CI 1.079-1.989,P=0.014)and shock index>0.77(compared with shock index≤0.77[OR 2.981,95%CI 1.186-7.492,P=0.020,AUC=0.764]).CONCLUSION:PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy.Furthermore,a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Clinical Outcomes and Prehabilitation Strategies of Patients Treated with Cement-Screw Technique for Tibial Defects in Total Knee Arthroplasty

Objective: To investigate the clinical efficacy of the cement-screw technique in repairing tibial plateau bone defects in total knee arthroplasty (TKA) recipients and summarize the preoperative prehabilitation strategies for such surgeries. Methods: A total of 33 TKA recipients (45 knees) in our department underwent repair of unilateral or bilateral tibial defects using the cement-screw technique. The subjects were divided into two groups based on the differences in preoperative interventions. The control group received routine preoperative health education according to the consensus, while the observation group received instructive and standardized prehabilitation exercises for four weeks in addition to the routine education. Scale scores, intraoperative parameters, and postoperative recovery indicators were recorded at different time pointsand subjected to statistical analysis for intra-group and inter-group differences. All subjects underwent long-term follow-up for at least 24 months. Results: Within each group at different time points, there were statistically significant differences in VAS, ROM, and HSS scores (p Conclusions: Cement-screw technique for repairing tibial plateau bone defects in TKA recipients can significantly relieve pain, and improve joint function. Prehabilitation can improve preoperative rehabilitation reserves in these patients, accelerate postoperative recovery, and contribute to better short-term clinical outcomes.

Association of baseline hemoglobin A1c levels with bleeding in patients with non-ST-segment elevation acute coronary syndrome underwent percutaneous coronary intervention:insights of a multicenter cohort study from China

OBJECTIVE To investigate the association between baseline hemoglobin A1c(HbA1c)levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome(NSTE-ACS)who underwent percutaneous coronary intervention(PCI).METHODS This observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1,2010 to December 31,2014.Based on baseline HbA1c levels,the patients were divided into the group with HbA1c<7%(n=4740)and the group with HbA1c≥7%(n=1543).The primary outcomes are major bleeding(BARC grades 3-5)and all-cause death during follow-up.RESULTS Of patients enrolled,4705(74.9%)were male,and 2143(34.1%)had a history of diabetes mellitus,with a mean(SD)age of 64.13(10.32)years.The median follow-up duration was 3.21 years.Compared with the patients with HbA1c<7%,the risk of major bleeding events during follow-up was higher in patients with HbA1c≥7%(adjusted hazard ratio[HR]=1.57;95%con-fidence interval[CI]:1.01-2.44;P=0.044),while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels(adjusted HR=0.88;95%CI:0.66-1.18;P=0.398).CONCLUSIONS Compared with the lower baseline HbA1c levels,the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI,though higher baseline HbA1c levels were not associ-ated with the higher risk in all-cause death.

Radiomics approach for preoperative identification of stages Ⅰ-Ⅱand Ⅲ-Ⅳ of esophageal cancer

Objective： To predict preoperative staging using a radiomics approach based on computed tomography （CT）images of patients with esophageal squamous cell carcinoma （ESCC）.Methods： This retrospective study included 154 patients （primary cohort： n： t 14; validation cohort： n：40） withpathologically confirmed ESCC. All patients underwent a preoperative CT scan from the neck to abdomen. Highthroughput and quantitative radiomics features were extracted from the CT images for each patient. A radiomicssignature was constructed using the least absolute shrinkage and selection operator （Lasso）. Associations betweenradiomics signature, tumor volume and ESCC staging were explored. Diagnostic performance of radiomicsapproach and tumor volume for discriminating between stages Ⅰ-Ⅱand Ⅲ-Ⅳ was evaluated and compared usingthe receiver operating characteristics （ROC） curves and net reclassification improvement （NRI）.Results= A total of 9,790 radiomics features were extracted. Ten features were selected to build a radiomicssignature after feature dimension reduction. The radiomics signature was significantly associated with ESCCstaging （P〈0.001）, and yielded a better performance for discrimination of early and advanced stage ESCC comparedto tumor volume in both the primary [area under the receiver operating characteristic curve （AUC）： 0.795 vs. 0.694,P=0.003; NRI=0.424）] and validation cohorts （AUC： 0.762 vs. 0.624, P=0.035; NRI=0.834）.Conclusions： The quantitative approach has the potential to identify stage Ⅰ-Ⅱand Ⅲ-Ⅳ ESCC beforetreatment.