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.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Leveraging machine learning for early recurrence prediction in hepatocellular carcinoma:A step towards precision medicine

The high rate of early recurrence in hepatocellular carcinoma(HCC)post curative surgical intervention poses a substantial clinical hurdle,impacting patient outcomes and complicating postoperative management.The advent of machine learning provides a unique opportunity to harness vast datasets,identifying subtle patterns and factors that elude conventional prognostic methods.Machine learning models,equipped with the ability to analyse intricate relationships within datasets,have shown promise in predicting outcomes in various medical disciplines.In the context of HCC,the application of machine learning to predict early recurrence holds potential for personalized postoperative care strategies.This editorial comments on the study carried out exploring the merits and efficacy of random survival forests(RSF)in identifying significant risk factors for recurrence,stratifying patients at low and high risk of HCC recurrence and comparing this to traditional COX proportional hazard models(CPH).In doing so,the study demonstrated that the RSF models are superior to traditional CPH models in predicting recurrence of HCC and represent a giant leap towards precision medicine.

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Early Triassic Volcanic Rocks in the Western Yarlung Zangbo Suture Zone:Implications for the Opening of the Neo-Tethys Ocean

In this study,zircon U-Pb dating of volcanic rocks from the Zhongba ophiolite of the Yarlung Zangbo Suture Zone(YZSZ)in southern Xizang(Tibet)yielded an age of 247±3 Ma.According to whole rock geochemical and Sr-NdPb isotopic data,the Early Triassic samples could be divided into two groups:Group 1 with P-MORB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70253–0.70602,ε_(Nd)(t)values of 4.2–5.3,(^(206)Pb/^(204)Pb)_(t)ratios of 16.353–18.222,(^(207)Pb/^(204)Pb)_(t)ratios of 15.454–15.564,and(^(208)Pb/^(204)Pb)_(t)ratios of 35.665–38.136;Group 2 with OIB affinity,showing initial^(87)Sr/^(86)Sr ratios of 0.70249–0.70513,ε_(Nd)(t)values of 4.4–4.9,(^(206)Pb/^(204)Pb)_(t)ratios of 17.140–18.328,(^(207)Pb/^(204)Pb)_(t)ratios of 15.491–15.575,and(^(208)Pb/^(204)Pb)_(t)ratios of 36.051–38.247.Group 2 rocks formed by partial melting of the mantle source enriched by a former plume,and assimilated continental crustal material during melt ascension.The formation of Group 1 rocks corresponds to the mixing of OIB melts,with the same components as Group 2 and N-MORBs.The Zhongba Early Triassic rocks belong to the continental margin type ophiolite and formed in the continental–oceanic transition zone during the initial opening of the Neo-Tethys in southern Xizang(Tibet).

Early warning method for thermal runaway of lithium-ion batteries under thermal abuse condition based on online electrochemical impedance monitoring

Early warning of thermal runaway(TR)of lithium-ion batteries(LIBs)is a significant challenge in current application scenarios.Timely and effective TR early warning technology is urgently required considering the current fire safety situation of LIBs.In this work,we report an early warning method of TR with online electrochemical impedance spectroscopy(EIS)monitoring,which overcomes the shortcomings of warning methods based on traditional signals such as temperature,gas,and pressure with obvious delay and high cost.With in-situ data acquisition through accelerating rate calorimeter(ARC)-EIS test,the crucial features of TR were extracted using the RReliefF algorithm.TR mechanisms corresponding to the features at specific frequencies were analyzed.Finally,a three-level warning strategy for single battery,series module,and parallel module was formulated,which can successfully send out an early warning signal ahead of the self-heating temperature of battery under thermal abuse condition.The technology can provide a reliable basis for the timely intervention of battery thermal management and fire protection systems and is expected to be applied to electric vehicles and energy storage devices to realize early warning and improve battery safety.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Early detection of multiple endocrine neoplasia type 1: A case report

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is low.MEN type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical diagnosis.CASE SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hos-pital.Blood tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid lesion.Gastroscopy findings suggested a duodenal bulge and ulceration.Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb.Further blood tests revealed elevated levels of serum gastrin.Surgery was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy.The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year.CONCLUSION For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

Early Treatment Outcome of Humeral Shaft Fracture Non-Union in Adults: Comparative Study of Plating versus Interlocking Nailing

Background: Fractures of humeral shaft in adults are common injuries. Humeral shafts non-union either from late presentation after initial treatment by traditional bone setters or failed non-operative orthodox care is a major problem in this part of the world. This non-union is a major treatment challenge with increased cost of care and morbidity in this part of the world. Humeral shaft non-union can be treated with locked intra-medullary nailing (LIMN) or dynamic compression plating (DCP). Study on comparison of these methods of fixation in this part of the world is scarce in literature search, hence the reason for this study. Objective: The objectives of this study are: (1) to compare early clinical outcome following fixation of humeral shaft fracture nonunion with DCP versus LIMN;(2) to compare the time of radiologic fracture union of DCP with LIMN;(3) to compare complications following fixation of humeral shaft fracture nonunion with DCP versus LIMN. Patients and Methods: This was a randomized control study done for 2 years in which fifty adult patients with humeral shaft non-union were recruited. The patients were grouped into 2 (P = DCP & N = LIMN). Forty five of the patients completed the follow up periods of the study and then analyzed. The P group had ORIF with DCP while the N group had ORIF with LIMN. Both groups had grafting with cancellous bones. Each patient was followed up for a period of 6 months at the time which radiographic union is expected. Any patient without clinical and/or radiographic evidence of union after six months of surgery was diagnosed as having recurrent non-union. The data generated was analyzed using SPSS Version 23. The results were presented in charts and tables. The paired t-test was used while considering p value Result: Forty five patients completed follow up. There was a male preponderance (4:1), right humerus predominated (3:2). Motor vehicular accidents were the commonest cause of the fractures (62%). Most non-union fractures occurred at the level of the middle 3rd of the humeral shaft (60%). Failed TBS treatment was the commonest indication for the osteosynthesis (71%). More patients had plating (53%) compared to 47% who had LIMN. Most patients (93.4%) had union between 3 to 6 months irrespective of fixation type with no significant statistical difference between the union rate of DCP and LIMN (p value 0.06) with similar functional outcome and complication rates irrespective of the type of fixation. Conclusion: This study showed that the success rates in term of fracture union, outcome functional grades and complication rates were not directly dependent on the types of the fixation: plating or locked intra-medullary nailing.

Improving early diagnosis of multiple endocrine neoplasia type 1 by assessing the gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin

Despite advancements in the field,early diagnosis of multiple endocrine neoplasia type 1(MEN1)remains unachievable.This letter to the editor highlighted the importance of carefully assessing gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin levels,as suggested by Yuan et al in their paper.They focused on a patient with recurrent abdominal pain and diarrhea whose diagnostic path led to establishing a MEN1 diagnosis within a year.This emphasized the need for clinicians to consider MEN1 in patients with similar presentations,particularly when gastrointestinal symptoms persist or recur after discontinuation of proton pump inhibitors,especially knowing that early recognition and intervention are crucial for improving patient outcomes.

Early diagnosis of esophageal cancer:How to put“early detection”into effect?

This editorial comments on the article by Qu et al in a recent edition of World Journal of Gastrointestinal Oncology,focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving“early detection”.The five-year age-standardized net survival for esophageal cancer patients falls short of expectations.Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer.While advancements in endoscopic technology have been significant,there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques.Therefore,it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer,investigate the most cost-effective screening methods suitable for different regions,and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.

Arlenea delicata gen.et sp.nov.,a new ephedroid plant from the Early Cretaceous Crato Formation,Araripe Basin,Northeast Brazil

Ephedroid macrofossils have been widely documented in Cretaceous deposits,including numerous from the Lower Cretaceous Yixian Formation of NE China.However,few ephedroid macrofossils have been reported from South America.Herein,we describe a new plant of the family Ephedraceae,Arlenea delicata gen.et sp.nov.,from the Lower Cretaceous Crato Formation of the Araripe Basin,Northeast Brazil,based on the vegetative and reproductive structures.It has the typical morphological characteristics of ephedroid plants,including fertile reproductive branches,opposite phyllotaxy,terminal female cones,a sympodial branching system,longitudinally striated internodes,and swollen nodes.Our new finding is unusual in having inner chlamydosperms subtended by two pairs of bracts,reproductive units connected to branches through swollen receptacles and a smooth seed surface.This new ephedroid taxon from the Crato Formation increases our understanding of plant diversity of this group during the Early Cretaceous.Furthermore,the general morphology(fleshy bracts and enlarged receptacles)of this new fossil discovery indicates that seeds of this plant may have been dispersed by animals such as pterosaurs(mainly the Tapejaridae)and birds(Enantiornithes and Ornituromorpha).If true,this would explain the cosmopolitan distribution of Ephedraceae in the Lower Cretaceous.

Nitrogen isotope stratigraphy of the Early Cambrian successions in the Tarim Basin:Spatial variability of nitrogen cycling and its implication for paleo-oceanic redox conditions

The Early Cambrian represents a critical time period characterized by extraordinary biological innovations and dynamic redox conditions in seawaters.Nitrogen isotopic signatures of ancient sediments have the potential to elucidate the evolutionary path of marine redox states and the biogeochemical nitrogen cycle within the water column of the Early Cambrian ocean.While existing research on this topic has predominantly focused on South China,the exploration of other continental margins has been limited,leaving contradictory hypotheses untested.In this study,pairedδ^(15)N andδ^(13)C org analyses were performed on the Lower Cambrian successions from the Shiairike section(inner ramp)and Well Tadong 2(deep shelf/basin)in the northwestern and eastern Tarim Basin,respectively.Our data from the Shiairike section reveal a discernible shift in the operation of different nitrogen cycles for the black chert-shale unit,also referred to as the black rock series in Chinese literature,of the Yurtus Formation(Fortunian stage to lower Stage 3).Oscillatingδ^(15)N values for its lower part are suggestive of alternating anaerobic assimilation of NH 4+and denitrification/anammox.This is likely attributed to a shallow,unstable chemocline consistent with the upwelling and incursion of deep,anoxic waters during a major transgression.In contrast,aerobic nitrogen cycling,indicated by positiveδ^(15)N values of>2‰,dominated the upper part alongside a reduction in upwelling intensity.On the other hand,theδ^(15)N signatures of Xishanbulake and Xidashan Formations of Well Tadong 2,which encompass a time interval from the Cambrian Fortunian Age to Age 4,are indicative of N_(2)fixation by diazotrophs as the major nitrogen source.The two studied intervals,although not time-equivalent,exhibit separated states of nitrogen cycling at least during the deposition of the Yurtus black rock series.The spatially different nitrogen cycling of the studied sections is compatible with a redox-stratified ocean during the deposition of the Yurtus black rock series.The build-up of a NO_(3)−reservoir and aerobic nitrogen cycling in seawater was largely restricted to near-shore settings whereas anaerobic nitrogen cycling dominated by N_(2)fixation served as the main nitrogen uptake pathway in off-shore settings.

Teffichthys wui sp. nov., a new perleidid fish from the Early Triassic of Jiangsu and Anhui, China

Perleididae is a group of stem neopterygian fishes known only from the Triassic.Here,we report the discovery of a new perleidid,Teffichthys wui sp.nov.,based on six well-preserved specimens from the late Smithian(Olenekian,Early Triassic)marine deposits of Jurong,Jiangsu and Chaohu,Anhui,China.This new discovery documents the third and youngest species of Teffichthys,which is slightly younger than the Dienerian(Induan)T.elegans from Guizhou and the early Smithian T.madagascariensis from Madagascar.The new species shows diagnostic features of Teffichthys(presence of a spiracular,38-41 lateral line scales,and no more than three epaxial rays in the caudal fin)but differs from T.madagascariensis and T.elegans in some autapomorphies(e.g.,a horizontal opercle/subopercle contact and smooth scales with a nearly straight posterior margin).The diagnostic features for the genus Teffichthys and the family Perleididae are emended based on detailed comparisons of the new taxon with other perleidids.The phylogenetic relationships of perleidids with other stem neopterygians are discussed using a cladistic approach,and the results provide new insights into the phylogeny and classification of main stem neopterygian clades.

Early identification of stroke through deep learning with multi-modal human speech and movement data

Early identification and treatment of stroke can greatly improve patient outcomes and quality of life.Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized training.In this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute settings.We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the FAST.We compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and MViT.We found that the findings of our deep learning model had a higher clinical value compared with the other approaches.Moreover,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech audio.These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.