Medin synergized with vascular amyloid-beta deposits accelerates cognitive decline in Alzheimer's disease:a potential biomarker

Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.

Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Comprehensive effects of traditional Chinese medicine treatment on heart failure and changes in B-type natriuretic peptide levels: A meta-analysis

BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,systematic evalua-tions of its impact on clinical outcomes,TCM syndrome scores,and B-type natriuretic peptide(BNP)levels are lacking.This study fills this gap through a comprehensive analysis of randomized controlled trials(RCTs)focusing on TCM for HF treatment.It encompasses an assessment of methodological quality,a meta-analysis,and an evaluation of evidence quality based on established standards.The results offer crucial insights into the potential advantages and constraints of TCM in HF management.RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases,including China National Knowledge Infrastructure,Wanfang,VIP Information Chinese Science and Technology Journal,and PubMed.Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool,and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software.Finally,the quality of evidence was rated according to the GRADE criteria.RESULTS A total of 1098 RCTs were initially retrieved.After screening,16 RCTs were finally included in our study,which were published between 2020 and 2023.These RCTs involved 1660 HF patients,including 832 in the TCM group[TCM combined with conventional Western medicine(CMW)treatment]and 828 in the CWM group(CWM treatment).The course of treatments varied from 1 wk to 3 months.TCM syndrome differentiation was analyzed in 11 of the included RCTs.In all included RCTs,outcome indicators included comprehensive clinical outcomes,TCM syndrome scores,and BNP levels.The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes[risk ratio=-0.54;95%confidence interval(CI)=-0.61,-0.47;P<0.00001],TCM syndrome scores[weighted mean difference(WMD)=-142.07;95%CI=-147.56,-136.57;P<0.00001],and BNP levels(WMD=-142.07;95%CI=-147.56,-136.57;P<0.00001).According to the GRADE criteria,RCTs where"TCM improves clinical comprehensive outcomes"were rated as low-quality evidence,and RCTs where"TCM reduces TCM syndrome scores"or"TCM decreases BNP levels"were rated as medium-quality evidence.CONCLUSION TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients.Given the low and medium quality of the included RCTs,the application of these results should be cautious.

Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity:Insight from recent research

Obesity is a prevalent cause of diabetes mellitus(DM)and is a serious danger to human health.Type 2 DM(T2DM)mostly occurs along with obesity.Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy.Bariatric surgery can improve the symptoms of T2DM in some obese patients.But different types of bariatric surgery may have different effects.There are some models built by researchers to discuss the surgical procedures’effects on me-tabolism in diabetes animal models and diabetes patients.It is high time to conclude all this effects and recommend procedures that can better improve metabolism.

Effectiveness of intravitreal ranibizumab for diabetic macular edema in vitrectomized versus non-vitrectomized eyes:a Meta-analysis

AIM:To evaluate the effectiveness and safety of intravitreal ranibizumab(IVR)for diabetic macular edema(DME)in vitrectomized versus non-vitrectomized eyes.METHODS:The PubMed,EMBASE,Web of Science,Cochrane,EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME.Clinical outcomes of best-corrected visual acuity(BCVA),central macular thickness(CMT),the mean number of intravitreal injection and adverse events were extracted and analyzed.RESULTS:Six studies involving 641 eyes were included.Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits(P<0.05).Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo[mean difference(MD)=53.57,95%confidence interval(CI):28.03 to 78.72,P<0.0001]and 12mo(MD=49.65,95%CI:19.58 to 79.72,P=0.01),no significant difference was detected in improvement in BCVA at either 6mo(MD=0.05,95%CI:-0.02 to 0.13,P=0.14)or 12mo(MD=0.03,95%CI:-0.04 to 0.09,P=0.43).Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period(MD=0.60,95%CI:0.16 to 1.04,P=0.008),while there was no statistically significant difference between the two groups during 12mo of follow-up.CONCLUSION:Evidence from current study suggests that IVR was useful for both vitrectomized group and nonvitrectomized group with DME.Although less reduction in macular thickness is found in vitrectomized group,visual improvement between two groups is similar.

Urgent one-stage endoscopic treatment for choledocholithiasis related moderate to severe acute cholangitis: A propensity scorematched analysis

BACKGROUND During emergency endoscopic retrograde cholangiopancreatography(ERCP),the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis(AC)due to choledocholithiasis are unclear.AIM To investigate the safety and feasibility of one-stage endoscopic treatment for moderate to severe AC.METHODS We enrolled all patients diagnosed with moderate to severe cholangitis due to common bile duct stones from January 2019 to July 2023.The outcomes were compared in this study between patients who underwent ERCP within 24 h and those who underwent ERCP 24 h later,employing a propensity score(PS)frame-work.Our primary outcomes were intensive care unit(ICU)admission rates,ICU length of stay,and duration of antibiotic use.RESULTS In total,we included 254 patients and categorized them into two groups based on the time elapsed between admission and intervention:The urgent group(≤24 h,n=102)and the elective group(>24 h,n=152).Ninety-three pairs of patients with similar characteristics were selected by PS matching.The urgent ERCP group had more ICU admissions(34.4%vs 21.5%,P=0.05),shorter ICU stays(3 d vs 9 d,P<0.001),fewer antibiotic use(6 d vs 9 d,P<0.001),and shorter hospital stays(9 d vs 18.5 d,P<0.001).There were no significant differences observed in adverse events,in-hospital mortality,recurrent cholangitis occurrence,30-d readmission rate or 30-d mortality.CONCLUSION Urgent one-stage ERCP provides the advantages of a shorter ICU stay,a shorter duration of antibiotic use,and a shorter hospital stay.

Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

Detection and analysis of serum bile acid profile in patients with colonic polyps

BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.

Prospects of polyglycolic acid sheets for the treatment of esophageal stricture after esophageal endoscopic submucosal dissection

Esophageal cancer is the seventh most common type of cancer and the sixth leading cause of cancer-related mortality worldwide.Endoscopic submucosal dissection(ESD)is widely used for the resection of early esophageal cancer.However,post-ESD esophageal stricture is a common long-term complication,which requires attention.Patients with post-ESD esophageal stricture often experience dysphagia and require multiple dilatations,which greatly affects their quality of life and increases healthcare costs.Therefore,to manage post-ESD esophageal stricture,researchers are actively exploring various strategies,such as pharmaceutical interventions,endoscopic balloon dilation,and esophageal stenting.Although steroids-based therapy has achieved some success,steroids can lead to complications such as osteoporosis and infection.Meanwhile,endoscopic balloon dilatation is effective in the short term,but is prone to recurrence and perforation.Additionally,esophageal stenting can alleviate the stricture,but is associated with discomfort during stenting and the complication of easy displacement also present challenges.Tissue engineering has evolved rapidly in recent years,and hydrogel materials have good biodegradability and biocompatibility.A novel type of polyglycolic acid(PGA)sheets has been found to be effective in preventing esophageal stricture after ESD,with the advantages of a simple operation and low complication rate.PGA membranes act as a biophysical barrier to cover the wound as well as facilitate the delivery of medications to promote wound repair and healing.However,there is still a lack of multicenter,large-sample randomized controlled clinical studies focused on the treatment of post-ESD esophageal strictures with PGA membrane,which will be a promising direction for future advancements in this field.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management

As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

Advances in the function of traditional medicine for vitiligo treatment

Vitiligo has a significant impact on a substantial number of individuals worldwide.Traditional Chinese medicine has a long history of serving as a therapeutic treatment for vitiligo.Nevertheless,given the increasing volume of research on the utilization of traditional Chinese medicine for vitiligo treatment,it is imperative to conduct a comprehensive review that elucidates the efficacy of Chinese traditional medicine and other active ingredients in the treatment of vitiligo.This paper presents a comprehensive overview of the clinical preparations used to treat vitiligo,while also highlighting the potential monomers and extracts derived from traditional Chinese medicine for vitiligo treatment.A thorough analysis of the pharmacological effects of traditional Chinese medicine on vitiligo treatment will provide valuable insights and reliable information for the development of new treatment strategies.

ThyroidNet:A Deep Learning Network for Localization and Classification of Thyroid Nodules

Aim:This study aims to establish an artificial intelligence model,ThyroidNet,to diagnose thyroid nodules using deep learning techniques accurately.Methods:A novel method,ThyroidNet,is introduced and evaluated based on deep learning for the localization and classification of thyroid nodules.First,we propose the multitask TransUnet,which combines the TransUnet encoder and decoder with multitask learning.Second,we propose the DualLoss function,tailored to the thyroid nodule localization and classification tasks.It balances the learning of the localization and classification tasks to help improve the model’s generalization ability.Third,we introduce strategies for augmenting the data.Finally,we submit a novel deep learning model,ThyroidNet,to accurately detect thyroid nodules.Results:ThyroidNet was evaluated on private datasets and was comparable to other existing methods,including U-Net and TransUnet.Experimental results show that ThyroidNet outperformed these methods in localizing and classifying thyroid nodules.It achieved improved accuracy of 3.9%and 1.5%,respectively.Conclusion:ThyroidNet significantly improves the clinical diagnosis of thyroid nodules and supports medical image analysis tasks.Future research directions include optimization of the model structure,expansion of the dataset size,reduction of computational complexity and memory requirements,and exploration of additional applications of ThyroidNet in medical image analysis.

Recent advances in the application of MXenes for neural tissue engineering and regeneration

Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have excellent biocompatibility,electrical conductivity,surface hydrophilicity,mechanical properties and easy surface modification.However,at present,the stability of most MXenes needs to be improved,and more synthesis methods need to be explored.MXenes are good substrates for nerve cell regeneration and nerve reconstruction,which have broad application prospects in the repair of nervous system injury.Regarding the application of MXenes in neuroscience,mainly at the cellular level,the long-term in vivo biosafety and effects also need to be further explored.This review focuses on the progress of using MXenes in nerve regeneration over the last few years;discussing preparation of MXenes and their biocompatibility with different cells as well as the regulation by MXenes of nerve cell regeneration in two-dimensional and three-dimensional environments in vitro.MXenes have great potential in regulating the proliferation,differentiation,and maturation of nerve cells and in promoting regeneration and recovery after nerve injury.In addition,this review also presents the main challenges during optimization processes,such as the preparation of stable MXenes and long-term in vivo biosafety,and further discusses future directions in neural tissue engineering.

Effects of hospital–community integrated transitional care on quality of life in patients with chronic obstructive pulmonary disease

Objective: To explore the effects of “hospital–community integrated transitional care” model on quality of life in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 117 inpatients with COPD from the Department of Respiratory Medicine in a tertiary general hospital in Nanjing were enrolled by convenience sampling from January to December in 2016 and then were divided into intervention group (n = 60) and control group (n = 57) by random number table. Patients in the intervention group accepted both routine care and hospital– community integrated transitional care for 3 months after discharge. Assessment of quality of life by telephone follow-up or interview within a week before discharge and 1, 3, and 6 months after discharge was evaluated using the Short Form-36 (SF-36) health survey questionnaire. Results: For a total score of quality of life, there was a significant difference between the two groups (P < 0.05): 1, 3, and 6 months after discharge. In addition, for each dimension score of quality of life, there were no significant differences (P > 0.05) except vitality dimension, 1 month after discharge, and there were significant differences in all dimensions, 3 and 6 months after discharge (P < 0.05) Conclusions: Hospital–community integrated transitional care model can improve the quality of life of patients with COPD.

Sphingosine 1-phosphate receptor 1 regulates bloodbrain barrier permeability in epileptic mice

Destruction of the blood-brain barrier is a critical component of epilepsy pathology.Several studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular integrity.However,its effect on blood-brain barrier permeability in epileptic mice remains unclear.In this study,we prepared pilocarpine-induced status epilepticus models and pentylenetetrazol-induced epilepsy models in C57BL/6 mice.S1P1 expression was increased in the hippocampus after status epilepticus,whereas tight junction protein expression was decreased in epileptic mice compared with controls.Intraperitoneal injection of SEW2871,a specific agonist of sphingosine-1-phosphate receptor 1,decreased the level of tight junction protein in the hippocampus of epileptic mice,increased blood-brain barrier leakage,and aggravated the severity of seizures compared with the control.W146,a specific antagonist of sphingosine-1-phosphate receptor 1,increased the level of tight junction protein,attenuated blood-brain barrier disruption,and reduced seizure severity compared with the control.Furthermore,sphingosine 1-phosphate receptor 1 promoted the generation of interleukin-1βand tumor necrosis factor-αand caused astrocytosis.Disruption of tight junction protein and blood-brain barrier integrity by sphingosine 1-phosphate receptor 1 was reversed by minocycline,a neuroinflammation inhibitor.Behavioral tests revealed that sphingosine 1-phosphate receptor 1 exacerbated epilepsy-associated depression-like behaviors.Additionally,specific knockdown of astrocytic S1P1 inhibited neuroinflammatory responses and attenuated blood-brain barrier leakage,seizure severity,and epilepsy-associated depression-like behaviors.Taken together,our results suggest that astrocytic sphingosine 1-phosphate receptor 1 exacerbates blood-brain barrier disruption in the epileptic brain by promoting neuroinflammation.

Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology

BACKGROUND Sepsis exacerbates intestinal microecological disorders leading to poor prognosis.Proper modalities of nutritional support can improve nutrition,immunity,and intestinal microecology.AIM To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology.METHODS Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University,China,between 2019 and 2021 with indications for nutritional support,were randomly assigned to one of three different modalities of nutritional support for a total of 5 d:Total enteral nutrition(TEN group),total parenteral nutrition(TPN group),and supplemental parenteral nutrition(SPN group).Blood and stool specimens were collected before and after nutritional support,and changes in gut microbiota,short-chain fatty acids(SCFAs),and immune and nutritional indicators were detected and compared among the three groups.RESULTS In comparison with before nutritional support,the three groups after nutritional support presented:(1)Differences in the gut bacteria(Enterococcus increased in the TEN group,Campylobacter decreased in the TPN group,and Dialister decreased in the SPN group;all P<0.05);(2)different trends in SCFAs(the TEN group showed improvement except for Caproic acid,the TPN group showed improvement only for acetic and propionic acid,and the SPN group showed a decreasing trend);(3)significant improvement of the nutritional and immunological indicators in the TEN and SPN groups,while only immunoglobulin G improved in the TPN group(all P<0.05);and(4)a significant correlation was found between the gut bacteria,SCFAs,and nutritional and immunological indicators(all P<0.05).CONCLUSION TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators,as well as changes in intestinal microecology.

Common susceptibility variants of KDR and IGF-1R are associated with poststroke depression in the Chinese population

Background Depression,one of the most frequent complications after stroke,increases the disease’s burden and physical disability.Poststroke depression(PSD)is a multifactorial disease with genetic,environmental and biological factors involved in its occurrence.Genetic studies on PSD to date have mainly focused on the monoamine system and brain-derived neurotrophic factors.However,understanding is still limited about the influence of the single nucleotide polymorphism(SNP)of other neurotrophic factors on PSD.Aims The present study aimed to investigate the relationship between seven vascular endothelial growth factor(VEGF)family gene variants that occur with PSD.Methods A multicentre candidate gene study from five hospitals in Jiangsu Province from June 2013 to December 2014 involved 121 patients with PSD and 131 patients with non-PSD.Demographic characteristics and neuropsychological assessments were collected.Theχ^(2)test was used to evaluate categorical variables,while the independent t-test was applied to continuous variables.SNPs in seven genes(VEGFA,VEGFB,KDR,FLT-1,IGF-1,IGF-1R and PlGF)were genotyped.Single-marker association for PSD was analysed byχ^(2)tests and logistic regression using SPSS and PLINK software.Results Patients with PSD included more women and those with lower education levels,lower body mass indexes,lower Mini-Mental State Examination scores,and higher scores on the 17-item Hamilton Depression Rating Scale than non-PSD patients.Ninety-two SNPs with seven genes were genotyped and passed quality control.The rs7692791 CC genotypes,the C allele of KDR and the rs9282715 T allele of IGF-1R increased the risk for PSD(χ^(2)=7.881,p=0.019;χ^(2)=4.259,p=0.039;χ^(2)=4.222,p=0.040,respectively).In addition,the SNP rs7692791 of KDR was significantly associated with PSD by the logistic regression of an additive model(p=0.015,OR=9.584,95%CI:1.549 to 59.31).Conclusions Patients with rs7692791 C allele carriers or the CC genotype of KDR and the rs9282715 T allele of IGF-1R may have PSD susceptibility.Findings such as these may help clinicians to identify the high-risk population for PSD earlier and,thus,enable them to provide more timely interventions.

mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months,and conventional chemotherapeutics are the main treatment strategy.Poly(ADP-ribose)polymerase(PARP)inhibitors have been recently approved for BRCA1/2-mutant pancreatic cancer,opening a new era for targeted therapy for this disease.However,most pancreatic cancer patients carry wild-type BRCA1/2 with resistance to PARP inhibitors.Here,we reported that mammalian target of rapamycin complex 2(mTORC2)kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion.Moreover,we found that knockdown of the mTORC2 obligate subunit Rictor sensitized pancreatic cancer cells to the PARP inhibitor olaparib.Mechanistically,we showed that mTORC2 positively regulates homologous recombination(HR)repair by modulating BRCA1 recruitment to DNA double-strand breaks(DSBs).In addition,we confirmed that combination treatment with the mTORC2 inhibitor PP242 and the PARP inhibitor olaparib synergistically inhibited pancreatic cancer growth in vivo.Thus,this study provides a novel target and strategy for optimizing PARP inhibitor efficiency in pancreatic cancers.

Effectiveness of Post-Traumatic Growth Intervention to Promote Positive Post-Traumatic Traits in Chinese Breast Cancer Patients:A Randomized Controlled Trial

Objective:The purpose of this study was to evaluate the effectiveness of post-traumatic growth(PTG)model-based intervention to improve positive psychological traits in Chinese breast cancer patients.Design:A randomized control trial of a psychological group intervention based on PTG model.Methods:The Clinical Trial was registered on 17 August 2019 at Chinese Clinical Trials.gov with Registration number ChiCTR1900025264.A total of 92 patients with breast cancer were recruited.The participants were randomly assigned to the experimental group(n=46)and the control group(n=46).A six-session psychological group intervention based on PTG model was implemented in the experimental group,and a six-session health education was implemented in the control group.The outcomes weremeasured at baseline(pre-intervention),3 weeks,6 weeks after the intervention.The primary outcome was posttraumatic growth assessed by the Chinese version of the Post-Traumatic Growth Inventory(PTGI);Secondary outcomes included psychological resilience,family resilience,rumination,and self-disclosure.Results:A total of 87 patients with breast cancer completed this study,including 44 patients in the experimental group and 43 patients in the control group.There was no significant difference in baseline data of breast cancer patients between the two groups except for the treatment regimen(p>0.05).The two groups were compared after the intervention;the interaction effects between the total scores of posttraumatic growth,family resilience,and self-disclosure and the time term were statistically significant(p<0.05),indicating that the trend of change in total scores of post-traumatic growth,family resilience,and self-disclosure differed between the experimental and control groups over time,and the scores improved in the experimental group were significantly higher than those in the control group.The comparison of psychological resilience and total score of rumination at each time point was statistically significant(p<0.05),indicating that group intervention based on the PTG model could improve the psychological recovery ability and rumination level of the experimental group.Conclusion:The psychological group intervention based on the PTG model significantly improved post-traumatic growth,family resilience,and self-disclosure in patients with breast cancer.However,the impact on psychological resilience and rumination was relatively small.Long-term intervention is needed to further test the effect of the PTG model on psychological resilience and rumination.

Metachronous primary esophageal squamous cell carcinoma and duodenal adenocarcinoma:A case report and review of literature

BACKGROUND The prevalence of multiple primary malignant neoplasms(MPMNs)is increasing in parallel with the incidence of malignancies,the continual improvement of diagnostic models,and the extended life of patients with tumors,especially those of the digestive system.However,the co-existence of MPMNs and duodenal adenocarcinoma(DA)is rarely reported.In addition,there is a lack of compre-hensive analysis of MPMNs regarding multi-omics and the tumor microenvir-onment(TME).CASE SUMMARY In this article,we report the case of a 56-year-old man who presented with a complaint of chest discomfort and abdominal distension.The patient was diagnosed with metachronous esophageal squamous cell carcinoma and DA in the Department of Oncology.He underwent radical resection and chemotherapy for the esophageal tumor,as well as chemotherapy combined with a programmed death-1 inhibitor for the duodenal tumor.The overall survival was 16.6 mo.Extensive evaluation of the multi-omics and microenvironment features of primary and metastatic tumors was conducted to:(1)Identify the reasons responsible for the poor prognosis and treatment resistance in this case;and(2)Offer novel diagnostic and therapeutic approaches for MPMNs.This case demonstrated that the development of a second malignancy may be independent of the location of the first tumor.Thus,tumor recurrence(including metastases)should be distinguished from the second primary for an accurate diagnosis of MPMNs.CONCLUSION Multi-omics characteristics and the TME may facilitate treatment selection,improve efficacy,and assist in the prediction of prognosis.Core Tip:Multiple primary malignant neoplasms(MPMNs)are increasingly prevalent in clinical practice,most frequently in the digestive system.We report a rare case of MPMN with a combination of esophageal squamous cell carcinoma and duodenal adenocarcinoma.According to PubMed-indexed literature,there are no standard guidelines or expert consensus on the etiology and comprehensive treatment.We also conducted a detailed study of the features of primary and metastatic tumors.The aim of this report was to identify the reasons responsible for the poor prognosis and treatment resistance in this case through histological data and provide new diagnostic and treatment directions for MPMNs.INTRODUCTION Multiple primary malignant neoplasms(MPMNs),also termed multiple primary cancers,refer to two or more primary tumors that occur simultaneously or sequentially in a single or multiple organs[1].According to the time interval from the diagnosis of the first tumor,MPMNs are divided into synchronous cancer(SC)(<6 mo)and metachronous cancer(MC)(≥6 mo)[2].The detection rate of the second or multiple primary tumors is also on the rise due to newer diagnostic methods and treatments,as well as the longer survival times of patients with cancer.MPMNs are most commonly reported in the digestive system;however,their occurrence in combination with duodenal adenocarcinoma(DA)is extremely rare.In this article,we describe the case of a patient who had metachronous esophageal squamous cell carcinoma(ESCC)and DA with multiple metastases.In this analysis,we thoroughly examined the multi-omics features and tumor-related immune microenvironment.OUTCOME AND FOLLOW-UP The patient was eventually followed up until clinical death on June 18,2022(Figure 2),with an overall survival 16.6 mo.