Circulating tumor DNA in liquid biopsy: Current diagnostic limitation

With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine.cfDNA is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic cells.Tumor cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of cancer.In this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the future.Although the future faces major challenges,it also con-tains great potential.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Comprehensive analysis of clinical and biological value of ING family genes in liver cancer

BACKGROUND Liver cancer(LIHC)is a malignant tumor that occurs in the liver and has a high mortality in cancer.The ING family genes were identified as tumor suppressor genes.Dysregulated expression of these genes can lead to cell cycle arrest,senescence and/or apoptosis.ING family genes are promising targets for anticancer therapy.However,their role in LIHC is still not well understood.AIM To have a better understanding of the important roles of ING family members in LIHC.METHODS A series of bioinformatics approaches(including gene expression analysis,genetic alteration analysis,survival analysis,immune infiltration analysis,prediction of upstream microRNAs(miRNAs)and long noncoding RNAs(lncRNAs)of ING1,and ING1-related gene functional enrichment analysis)was applied to study the expression profile,clinical relationship,prognostic significance and immune infiltration of ING in LIHC.The relationship between ING family genes expression and tumor associated immune checkpoints was investigated in LIHC.The molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily discussed.RESULTS mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases,showing that ING family genes were highly expressed in LIHC.In 47 samples from 366 LIHC patients,the ING family genes were altered at a rate of 13%.By comprehensively analyzing the expression,clinical pathological parameters and prognostic value of ING family genes,ING1/5 was identified.ING1/5 was related to poor prognosis of LIHC,suggesting that they may play key roles in LIHC tumorigenesis and progression.One of the target miRNAs of ING1 was identified as hsa-miR-214-3p.Two upstream lncRNAs of hsa-miR-214-3p,U91328.1,and HCG17,were identified.At the same time,we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint genes.CONCLUSION This study lays a foundation for further research on the potential mechanism and clinical value of ING family genes in the treatment and prognosis of LIHC.

Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remains unclear.Retrovirnl vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 OT1.Cellular proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle changes.RNA sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways.RT-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene expressions.The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts.Our data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase.RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cyde.RT qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene expressions.HCT116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude mice.Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

Risk factors for postpartum posttraumatic stress disorder after emergency admission

BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive measures.This retrospective study aimed to explore the incidence and risk factors for postpartum PTSD in women who give birth after emergency admission.METHODS:Medical records of women who gave birth after emergency admission were collected between March 2021 and April 2023.The patients’general conditions and perinatal clinical indicators were recorded.The puerperae were divided into PTSD group and control group based on symptom occurrence at six weeks postpartum.Multivariate logistic regression analysis was performed to identify risk factors.RESULTS:A total of 276 puerperae were included,with a PTSD incidence of 20.3% at six weeks postpartum.Multivariate logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,P<0.001),and cervical dilation(OR=3.203;95%CI:1.670–6.141,P=0.039)as independent risk factors for postpartum PTSD.Analgesia pump use(OR=0.500;95%CI:0.259–0.966,P=0.015)was found to be a protective factor against postpartum PTSD.CONCLUSION:Emergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTSD,while analgesic pump use was a protective factor.These findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.

Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature

BACKGROUND The management of hepatoblastoma(HB)becomes challenging when the tumor remains in close proximity to the major liver vasculature(PMV)even after a full course of neoadjuvant chemotherapy(NAC).In such cases,extreme liver resection can be considered a potential option.AIM To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC.METHODS We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023.We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC.RESULTS Sixty-seven children diagnosed with HB underwent surgical resection.The age at diagnosis was 21.4±18.8 months,and 40 boys and 27 girls were included.Fifty-nine(88.1%)patients had a single tumor,39(58.2%)of which was located in the right lobe of the liver.A total of 47 patients(70.1%)had PRE-TEXT III or IV.Thirty-nine patients(58.2%)underwent delayed resection.After a full course of NAC,16 patients still had close PMV(within 1 cm in two patients,touching in 11 patients,compressing in four patients,and showing tumor thrombus in three patients).There were 6 patients of tumors in the middle lobe of the liver,and four of those patients exhibited liver anatomy variations.These 16 children underwent extreme liver resection after comprehensive preoperative evaluation.Intraoperative procedures were performed according to the preoperative plan,and the operations were successfully performed.Currently,the 3-year event-free survival of 67 children with HB is 88%.Among the 16 children who underwent extreme liver resection,three experienced recurrence,and one died due to multiple metastases.CONCLUSION Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible.This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis.Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB,particularly for assessing vascular involvement,remnant liver volume and anatomical variations.

Mechanistic research:Selenium regulates virulence factors,reducing adhesion ability and inflammatory damage of Helicobacter pylori

BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.

Cellular Senescence and SENEX Gene on the Peripheral CD4+CD25+ Treg Cells Enhancement in Elderly

Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. However, this process is also associated with apoptosis, upregulated secretion of inflammatory cytokine, and promoted surrounding tissue damage. When cellular senescence accumulates to a certain extent, it triggers geriatric diseases, such as chronic inflammation, immune senescence-associated tumors and incontrollable infections. Cellular senescence gene SENEX, which was cloned in 2004, has been demonstrated to play a unique gatekeeper function in human endothelial cells when stress-induced pre-mature senescence and apoptosis occurr. The phenomenon that CD4+CD25+ Treg cells accumulated in the aged population has been well studied in recent years. Now Treg accumulation related to immune-pathology has attracted more interest. CD4+CD25+ Treg did not decline and age, but accumulated and suppressed immunoreaction. The enhanced Treg number and function may be associated with stress-induced premature senescence-mediated unique cellular senescence protection mechanisms, and SENEX may play a critical role in this process. In this article, we summarize the cellular senescence and SENEX gene in the accumulation and functional activity of CD4+CD25+ Treg in the elderly.

Prevalence and related factors of post-traumatic stress disorder among medical staff members exposed to H7N9 patients

Objective: This study aimed to evaluate the prevalence and related factors of post-traumatic stress disorder (PTSD) symptoms among doctors and nurses who were exposed to H7N9 patients during the H7N9 influenza epidemic.To provide scientific basis for promoting the physical and psychological health of these staff members.Method: The 102 medical staff workers who were exposed to H7N9 patients were recruited through convenient sampling between January 2015 and May 2016.We used a self-reported questionnaire,the PTSD Checklist-Civilian Version (PCL-C),to evaluate the PTSD symptoms among doctors and nurses from an intensive care unit (n =61),a respiratory department (n =20),and an emergency department (n =21).We then analyzed the related factors.Results: Around 20.59% of the tested doctors and nurses showed PTSD symptoms.The sample had a mean PCL-C score of 30.00 ± 9.95.The differences in the scores of doctors and nurses with different genders,ages,professional titles,contact frequencies,trainings,and experiences were statistically significant (P < 0.05,P < 0.01).Moreover,t-tests and one-way analysis of variance showed that nurses received higher scores than doctors,female participants received higher scores than male participants,and the participants with low professional title and high contact frequency,aged between 20 years and 30 years,with less than five years of work experience,having not received related training and with no related experience obtained higher PCL-C scores than the others (P < 0.05,P < 0.01).Conclusion: The PTSD level of doctors and nurses after their exposure to H7N9 patients was high,which warrant further research.Health and medical institutions should pay attention to the physical and psychological health of these staff members.

Risk factors of recurrent choledocholithiasis following therapeutic endoscopic retrograde cholangiopancreatography

Background:The risk factors for the recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography(ERCP)have not been well studied.The aim of this study was to explore the risk factors of recurrent choledocholithiasis.Methods:We carried out a retrospective analysis of data collected between January 1,2010 and January 1,2020.Univariate analysis and multivariate analysis were used to explore the independent risk factors of recurrent choledocholithiasis following therapeutic ERCP.Results:In total,598 patients were eventually selected for analysis,299 patients in the recurrent choledocholithiasis group and 299 patients in the control group.The overall rate of recurrent choledocholithiasis was 6.91%.Multivariate analysis showed that diabetes[odds ratio(OR)=3.677,95%confidence interval(CI):1.875-7.209;P<0.001],fatty liver(OR=4.741,95%CI:1.205-18.653;P=0.026),liver cirrhosis(OR=3.900,95%CI:1.358-11.201;P=0.011),history of smoking(OR=3.773,95%CI:2.060-6.908;P<0.001),intrahepatic bile duct stone(OR=4.208,95%CI:2.220-7.976;P<0.001),biliary stent(OR=2.996,95%CI:1.870-4.800;P<0.001),and endoscopic papillary balloon dilation(EPBD)(OR=3.009,95%CI:1.921-4.715;P<0.001)were independent risk factors of recurrent choledocholithiasis.However,history of drinking(OR=0.183,95%CI:0.099-0.337;P<0.001),eating light food frequently(OR=0.511,95%CI:0.343-0.760;P=0.001),and antibiotic use before ERCP(OR=0.315,95%CI:0.200-0.497;P<0.001)were independent protective factors of recurrent choledocholithiasis.Conclusions:Patients with the abovementioned risk factors are more likely to have recurrent CBD stones.Patients who eat light food frequently and have a history of drinking are less likely to present with recurrent CBD calculi.

Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer’s disease?

Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.

A Novel SE-CNN Attention Architecture for sEMG-Based Hand Gesture Recognition

In this article,to reduce the complexity and improve the generalization ability of current gesture recognition systems,we propose a novel SE-CNN attention architecture for sEMG-based hand gesture recognition.The proposed algorithm introduces a temporal squeeze-and-excite block into a simple CNN architecture and then utilizes it to recalibrate the weights of the feature outputs from the convolutional layer.By enhancing important features while suppressing useless ones,the model realizes gesture recognition efficiently.The last procedure of the proposed algorithm is utilizing a simple attention mechanism to enhance the learned representations of sEMG signals to performmulti-channel sEMG-based gesture recognition tasks.To evaluate the effectiveness and accuracy of the proposed algorithm,we conduct experiments involving multi-gesture datasets Ninapro DB4 and Ninapro DB5 for both inter-session validation and subject-wise cross-validation.After a series of comparisons with the previous models,the proposed algorithm effectively increases the robustness with improved gesture recognition performance and generalization ability.

Analysis of characteristic features in ultrasound diagnosis of fetal limb body wall complex during 11-13+6 weeks

BACKGROUND Limb body wall complex(LBWC)is a fatal malformation characterized by major defects in the fetal abdominal or thoracic wall,visceral herniation,significant scoliosis or spina bifida,limb deformities,craniofacial deformities,and umbilical cord abnormalities(short or absent umbilical cord).Early diagnosis of this condition is of great clinical significance for clinical intervention and pregnancy decision-making.With the rapid development of fetal ultrasound medicine,early pregnancy(11-13+6 wk)standardized prenatal ultrasound examinations have been widely promoted and applied.AIM To explore the value of prenatal ultrasound in the diagnosis of fetal LBWC syndrome during early pregnancy.METHODS The ultrasonographic data and follow-up results of 18 cases of fetal LBWC diagnosed by prenatal ultrasound during early pregnancy(11-13+6 wk)were retrospectively analyzed,and their ultrasonographic characteristics were analyzed.RESULTS Among the 18 fetuses with limb wall abnormalities,there were spinal dysplasia(18/18,100%),varying degrees of thoracoschisis and gastroschisis(18/18,100%),limb dysplasia in 6 cases(6/18,33%),craniocerebral malformations in 4 cases(4/18,22%),thickening of the transparent layer of the neck in 5 cases(5/18,28%),and umbilical cord abnormalities in 18 cases(18/18,100%),single umbilical artery in 5 cases.CONCLUSION Prenatal ultrasound in early pregnancy can detect LBWC as early as possible,and correct prenatal evaluation provides important guidance value for pregnancy decision-making and early intervention.

Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage

BACKGROUND Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and cortisol(Cor)and the prognosis of patients with hypertensive cerebral hemorrhage.METHODS A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group.Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group.Peripheral venous blood was collected,and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay.RESULTS A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment(P<0.05).Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group.Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses.Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage(P<0.05).CONCLUSION Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells

In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy.We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H2O2 to release GEM.Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM.For the lung cancer cell lines that are resistant to the epidermal growth factor receptor(EGFR)-targeting inhibitor osimertinib,GEM-ZZQ showed less growth inhibition than GEM;however,GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups.In summary,we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.

Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation

BACKGROUND Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori(H.pylori)infections.Therefore,there is an urgent need to develop new antimicrobial agents to replace antibiotics.Our previous study found that linolenic acid-metronidazole(Lla-Met)has a good antibacterial effect against H.pylori,both antibiotic-resistant and sensitive H.pylori.Also,H.pylori does not develop resistance to Lla-Met.Therefore,it could be used for preparing broad-spectrum antibacterial agents.However,since the antibacterial mechanism of Lla-Met is not well understood,we explored this phenomenon in the present study.AIM To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections.METHODS H.pylori cells were treated with the Lla-Met compound,and the effect of the compound on the cell morphology,cell membrane permeability,and oxidation of the bacteria cell was assessed.Meanwhile,the differently expressed genes in H.pylori in response to Lla-Met treatment were identified.RESULTS Lla-Met treatment induced several changes in H.pylori cells,including roughening and swelling.In vivo experiments revealed that Lla-Met induced oxidation,DNA fragmentation,and phosphatidylserine ectropionation in H.pylori cells.Inhibiting Lla-Met with L-cysteine abrogated the above phenomena.Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes,both anti-oxidation-related genes.CONCLUSION Lla-Met kills H.pylori mainly by inducing oxidative stress,DNA damage,phosphatidylserine ectropionation,and changes on cell morphology.

Computer-assisted rescue of the inferior mesenteric artery in a child with a giant ganglioneuroblastoma: A case report

BACKGROUND Ganglioneuroblastoma(GNB)is a peripheral neuroblastoma(NB)with malignant degree between highly malignant NB and benign ganglioma(GN).Pathology is the gold standard of diagnosis.Although GNB is not uncommon in children,biopsy alone may lead to an inaccurate diagnosis,especially for giant tumors.However,surgical resection may be associated with significant complications.Here,we report a case of computer-assisted surgical resection of a giant GNB in a child and successful rescue of the inferior mesenteric artery.CASE SUMMARY A 4-year-old girl was admitted to our department for a giant retroperitoneal lesion,which was considered to be an NB by her local hospital.The symptoms of the girl disappeared spontaneously without treatment.On physical examination,a mass of about 10 cm×7 cm could be palpated in her abdomen.Ultrasonography and contrast-enhanced computed tomography performed in our hospital also showed an NB,and there was a very thick blood vessel inside the tumor.However,aspiration biopsy revealed GN.Surgical resection is the best treatment option for this giant benign tumor.For precise preoperative evaluation,threedimensional reconstruction was performed.It was clear that the tumor was close to the abdominal aorta.The superior mesenteric vein was pushed forward,and the inferior mesenteric artery passed through the tumor.Because GN generally does not invade blood vessels,we split the tumor with a CUSA knife during the operation and found that there was indeed a straight and intact vascular sheath.Arterial pulsation was observed in the completely exposed inferior mesenteric artery.The pathologists interpreting the tissue finally diagnosed it as a mixed GNB(GNBi),which is more malignant than GN.However,both GN and GNBi usually have a good prognosis.CONCLUSION This was a case of successful surgical resection of a giant GNB,and aspiration biopsy underestimated the pathological staging of the tumor.Preoperative three-dimensional reconstruction assisted with the radical resection of the tumor and rescue of the inferior mesenteric artery.

Changing trends in gastric and colorectal cancer among surgical patients over 85 years old:A multicenter retrospective study,2001–2021

BACKGROUND Whether patients over 85 years old with gastrointestinal cancer should undergo surgery remains controversial.We aimed to describe the changing trends of characteristics to provide more information to decision makers,and strive to find appropriate surgical plan.AIM To describe the changing trends of characteristics to provide more information to decision makers,and strive to find appropriate surgical plan.METHODS A total of 218 gastric cancer(GC)patients and 563 colorectal cancer(CRC)patients who underwent surgery between 2001 and 2021 were enrolled in this retrospective analysis.Changes in clinicopathological features,surgical treatments,and survival status were analyzed longitudinally at 5-year intervals.RESULTS Only 14 GC patients underwent laparoscopic surgery where 219 CRC patients had this procedure.Cardia and esophagogastric junction cancer increased in GC patients,and the proportion of sigmoid colon cancer decreased in CRC patients.Pulmonary infection gradually became the most common postoperative complication,its incidence in period 4 reached 48.79%.However,the incidence of anastomotic leakage decreased from 26.79%to 9.38%(P<0.01).Additionally,30-d mortality significantly decreased from 32.14%to 9.01%.Increases were observed in 5-year overall survival(OS)in GC patients from period 1 to period 4(18.18%vs 33.32%,respectively)and CRC patients(0 vs 36.32%,respectively).Disease-free survival(DFS)also increased in GC and CRC patients(7.14%vs 27.74%and 0 to 36.03%,respectively).The average survival time of GC patients following radial lymphadenectomy was higher than in patients that underwent limited lymphadenectomy(26 vs 22 mo,respectively),the same was seen in CRC patients(44 vs 33 mo,respectively).This advantage was particularly evident in patients with TNM I,but not in patients with TNM II/III period cancer.CONCLUSION The safety as well as effectiveness of surgery in ultra-elderly patients is increasing.Radical lymphadenectomy has advantages in patients with TNM I gastrointestinal cancer,but not TNM II/III.