Introduction: In December 2019, COVID 19 spread worldwide, but did not officially start in MOROCCO until March 02, 2020. Since then, this pandemic has significantly impacted the health status of patients in general an...Introduction: In December 2019, COVID 19 spread worldwide, but did not officially start in MOROCCO until March 02, 2020. Since then, this pandemic has significantly impacted the health status of patients in general and cancer patients in particular. The main objective of our study is to evaluate the prognosis of patients treated for cancer and infected with COVID-19. Material and method: A descriptive study with prospective collection was carried out at the medical oncology department of CHU Hassan II in FEZ over a period of two years, from March 2020 to March 2022. Data was carried out on the software SPSS. Results: One hundred cancer patients tested positive for COVID-19 infection and were collected within our department. The average age was 56 years [22-91]. The sex ratio was 1.2. Patients with breast cancer were the most affected by this infection (34%). The clinical symptomatology was dominated by the respiratory syndrome (45%).The diagnosis was made through thoracic CT scan in 62% of cases. 76% of patients were in a metastatic stage. 96% of patients were undergoing oncological treatment. For symptomatique patients, the standard treatment approach involved using antibiotics in 76% of cases. Evolution was marked by recovery in 79% of patients, with a death rate of 12% in this cancer patient population. Conclusion: COVID-19 infection is particularly severe in cancer patients. Mortality among these patients remains high and is associated with overall patient characteristics. However, anticancer treatments have not shown deleterious effects on the course of COVID-19.展开更多
Clear cell sarcoma(CCS)of soft tissue is extremely rare,accounting for approximately 1%of all soft tissue tumours.It is very difficult to diagnose CCS based on clinical manifestations.Magnetic resonance imaging(MRI)pr...Clear cell sarcoma(CCS)of soft tissue is extremely rare,accounting for approximately 1%of all soft tissue tumours.It is very difficult to diagnose CCS based on clinical manifestations.Magnetic resonance imaging(MRI)provides highresolution images of soft tissues and pathological features such as mucus,necrosis,bleeding,and fat through high and low signals on T1 weighted image(T1WI)and T2 weighted image(T2WI).On the other hand,the paramagnetism of melanin in CCS shortens the relaxation time of T1 and T2,and high signal intensity on T1WI and low signal intensity on T2WI can be found.This is different from most other soft tissue sarcomas.At present,the treatment method for CCS is surgical resection.MRI can effectively display the tumour edge,extent of surrounding oedema,and extent of fat involvement,which is highly important for guiding surgical resection and predicting postoperative recurrence.As an invasive sarcoma,CCS has a high risk of metastasis.Regardless of the pathological condition of the resected tumour,MRI or computed tomography(CT)should be performed every 1-2 years to assess recurrence at the primary site and to screen for metastasis in the lungs,liver,and bones.If necessary,PET-CT can be performed to evaluate the overall condition of the patient.展开更多
Introduction: Medical imaging is a medical specialty that involves producing images of the human body and interpreting them for diagnostic, therapeutic purposes, and for monitoring the progress of pathologies. We aime...Introduction: Medical imaging is a medical specialty that involves producing images of the human body and interpreting them for diagnostic, therapeutic purposes, and for monitoring the progress of pathologies. We aimed to assess the theoretical knowledge of doctors and interns in medical imaging in the northern region of Burkina Faso. Methodology: This was a descriptive cross-sectional survey based on a self-administered questionnaire. Prescribers knowledge was estimated based on scores derived from questionnaire responses. Results: We collected 106 questionnaires out of 163, i.e. a participation rate of 65.03%. The average knowledge score was 81.71% for the contribution of medical imaging to patient management. It was 60.02% for the indications/counter-indications of radiological examinations and 72.56% for the risks associated with exposure to radiation during these examinations. The score was 59.83% for the methods used to select the appropriate radiological examination. As regards the completeness of the clinical and biological information on the forms requesting imaging examinations, the score was 96.65%. Specialist doctors had the highest overall level of knowledge (74.68%). Conclusion: Improved technical facilities, good initial and in-service training, and interdisciplinary collaboration will help to ensure that imaging tests are properly prescribed, leading to better patient care.展开更多
The flexibility in radiotherapy can be improved if patients can be moved between any one of the department’s medical linear accelerators (LINACs) without the need to change anything in the patient’s treatment plan. ...The flexibility in radiotherapy can be improved if patients can be moved between any one of the department’s medical linear accelerators (LINACs) without the need to change anything in the patient’s treatment plan. For this to be possible, the dosimetric characteristics of the various accelerators must be the same, or nearly the same. The purpose of this work is to describe further and compare measurements and parameters after the initial vendor-recommended beam matching of the five LINACs. Deviations related to dose calculations and to beam matched accelerators may compromise treatment accuracy. The safest and most practical way to ensure that all accelerators are within clinical acceptable accuracy is to include TPS calculations in the LINACs matching evaluation. Treatment planning system (TPS) was used to create three photons plans with different field sizes 3 × 3 cm, 10 × 10 cm and 25 × 25 cm at a depth of 4.5 cm in Perspex. Calculated TPS plans were sent to Mosaiq to be delivered by five LINACs. TPS plans were compared with five LINACs measurements data using Gamma analyses of 2% and 2 mm. The results suggest that for four out of the five LINACs, there was generally good agreement, less than a 2% deviation between the planned dose distribution and the measured dose distribution. However, one specific LINAC named “Asterix” exhibited a deviation of 2.121% from the planned dose. The results show that all of the LINACs’ performance were within the acceptable deviation and delivering radiation dose consistently and accurately.展开更多
Background: The inadequacy in the completeness of the Laboratory Request Form (LRF) has been reported as one of the major sources of errors during the pre-analytical step of laboratory analysis. To prevent the occurre...Background: The inadequacy in the completeness of the Laboratory Request Form (LRF) has been reported as one of the major sources of errors during the pre-analytical step of laboratory analysis. To prevent the occurrence of such errors, this study aimed at assessing the level of completeness of LRFs. Methods: A retrospective analysis of laboratory request forms was conducted at the Clinical Biology Laboratory of the Kinshasa University Clinic, DR Congo, between November 2021 to May 2022. The LRFs were evaluated according to the completeness of all sections including administrative data of the patient, data of physician who ordered the test, relevant patient’s clinical data and data of the biological sample. Results: From a total of 2842 LRFs evaluated, none was fully completed with all required information. Particularly, patient’s clinical data including the medical history, provisional diagnosis and current treatment, were the most absent in 99% LRFs. However, two sections related to patient’s ID and prescribed test were informed in 100% LRFs. Conclusion: The results of this preanalytical audit can serve as an improvement opportunity focused on strengthening awareness about complete filling of LRF.展开更多
In order to cultivate excellent clinical medical talents with a solid foundation, strong literacy, refined skills, excellent communication abilities, innovative thinking, and a strong focus on practicality, functional...In order to cultivate excellent clinical medical talents with a solid foundation, strong literacy, refined skills, excellent communication abilities, innovative thinking, and a strong focus on practicality, functional experiments have undergone a series of reforms in areas such as constructing new curriculum systems, improving teaching content, updating teaching equipment, introducing new teaching models, and enhancing teaching evaluation systems.展开更多
Right-sided colon cancers (RCC) and left-sided colon cancers (LCC) have different epidemiological, physiological, pathological, genetic, and clinical characteristics, which result in differences in the course, prognos...Right-sided colon cancers (RCC) and left-sided colon cancers (LCC) have different epidemiological, physiological, pathological, genetic, and clinical characteristics, which result in differences in the course, prognosis, and outcome of disease. The objective of our study is to compare right-sided colon cancers and left-sided colon cancers regarding clinicopathological and survival characteristics. This is a retrospective study of 664 patients with colon cancer treated at the medical oncology department of Fez over a period from December 2009 to September 2020. Rectosigmoid, descending colon, and splenic flexure tumors were considered left-sided colon cancers, whereas ascending colon tumors were considered right-sided colon cancers. The Kaplan Meier method was used to estimate median survival. The study included 664 patients (female, 47%) having colon cancer with a median age of 60 years (23 - 83). Of the patients, 78.5% (n = 519) had LCC and 19.36 % (n = 128) had RCC. The rate of patients aged ≥ 65 years and the rate of patients with a family history of colon cancer was higher in the LCC patients. The proportion of poorly differentiated adenocarcinomas represented 3%, of which 63% had cancer of the right colon. There was a significantly higher proportion of higher T stage (T3-4: 62% vs 38%) in right sided tumors as compared to left sided tumors. The rate of metastatic patients was 64.1% in the RCC group and 43% in the LCC group. The median follow-up period was 14 months in the RCC group and 19 months in the LCC group with higher median overall survival in the LCC group (32 vs 21 months). We found histopathological differences between right and left sided colon cancer. Tumors on the right colon were found to be more aggressive, as expressed by poorer differentiation, higher T stage associated with a median overall survival better in left colon cancer.展开更多
Introduction: Pain assessment is an essential step towards pain relief. In our context, however, it is insufficient in emergency departments. The aim was to assess the nature and effectiveness of the analgesia used in...Introduction: Pain assessment is an essential step towards pain relief. In our context, however, it is insufficient in emergency departments. The aim was to assess the nature and effectiveness of the analgesia used in the emergency department of the CHU-Donka. Method: This was a single-centre prospective observational study conducted over one month (November 2020) in the medical-surgical emergency department of CHU-Donka. All patients aged 18 or over admitted to the emergency department with moderate to severe acute pain were included. Results: We enrolled 880 patients, 615 of whom (69.88%) were in pain. Males predominated (65.2%), with a sex ratio of 1.87. The average age was 44.78 ± 16.41 years, with extremes ranging from 18 to 85 years. The most represented age group was 18 - 34 years, with 66.18%. Initial assessment of pain by nursing staff in 3 cases. Initial assessment of pain by the investigator was 100%, 74% moderate and 26% severe. No reassessment of pain by nursing staff. Reassessment by the interviewer was 100% and found 5% no pain, 61% mild pain, 24% moderate pain and 10% severe pain. With an average numerical scale of 3.77 ± 2.61 and extremes from 0 to 10. Average length of stay was 2.85 ± 1.48 hours, with extremes ranging from 45 minutes to 8 hours. Analgesia was administered with paracetamol alone (43.58%), combined with tramadol or nefopam. No patient received morphine. Conclusion: This study revealed a lack of pain assessment in our department.展开更多
Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic...Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.展开更多
Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well orga...Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well organized,has succeeded in reducing the incidence of colon and rectal cancer and improving the prognosis related to them.Despite considerable advancements in screening technologies and strategies,the effectiveness of CRC screening programs remains less than optimal.This paper examined the multifaceted reasons behind the persistent lack of effect-iveness in CRC screening initiatives.Through a critical analysis of current methodologies,technological limitations,patient-related factors,and systemic challenges,we elucidated the complex interplay that hampers the successful reduction of CRC morbidity and mortality rates.While acknowledging the ad-vancements that have improved aspects of screening,we emphasized the necessity of addressing the identified barriers comprehensively.This study aimed to raise awareness of how important CRC screening is in reducing costs for this disease.Screening and early diagnosis are not only important in improving the prognosis of patients with CRC but can lead to an important reduction in the cost of treating a disease that is often diagnosed at an advanced stage.Spending more sooner can mean saving money later.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most count...Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.展开更多
Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of...Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians.Moreover,some potentially useful quantitative information in medical images,especially that which is not visible to the naked eye,is often ignored during clinical practice.In contrast,radiomics performs high-throughput feature extraction from medical images,which enables quantitative analysis of medical images and prediction of various clinical endpoints.Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis,demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine.However,radiomics remains in a developmental phase as numerous technical challenges have yet to be solved,especially in feature engineering and statistical modeling.In this review,we introduce the current utility of radiomics by summarizing research on its application in the diagnosis,prognosis,and prediction of treatment responses in patients with cancer.We focus on machine learning approaches,for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling.Furthermore,we introduce the stability,reproducibility,and interpretability of features,and the generalizability and interpretability of models.Finally,we offer possible solutions to current challenges in radiomics research.展开更多
BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has graduall...BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.展开更多
Because of the features involved with their varied kernels,differential operators relying on convolution formulations have been acknowledged as effective mathematical resources for modeling real-world issues.In this p...Because of the features involved with their varied kernels,differential operators relying on convolution formulations have been acknowledged as effective mathematical resources for modeling real-world issues.In this paper,we constructed a stochastic fractional framework of measles spreading mechanisms with dual medication immunization considering the exponential decay and Mittag-Leffler kernels.In this approach,the overall population was separated into five cohorts.Furthermore,the descriptive behavior of the system was investigated,including prerequisites for the positivity of solutions,invariant domain of the solution,presence and stability of equilibrium points,and sensitivity analysis.We included a stochastic element in every cohort and employed linear growth and Lipschitz criteria to show the existence and uniqueness of solutions.Several numerical simulations for various fractional orders and randomization intensities are illustrated.展开更多
Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,Br...Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.展开更多
Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma...Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.展开更多
Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrate...Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.展开更多
Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and aff...Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.展开更多
BACKGROUND Magnetic resonance imaging(MRI)scanning with susceptibility weighted imaging(SWI)sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy(HIE...BACKGROUND Magnetic resonance imaging(MRI)scanning with susceptibility weighted imaging(SWI)sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy(HIE).AIM To observe the role of MRI multi-parameter quantitative indexes in the diagnosis of neonatal HIE.METHODS The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Ganyu District People's Hospital of Lianyungang City and 23 neonates without HIE admitted during the same period were analyzed retrospectively from August,2021 to December,2023.The results of clinical judgment were compared with the results of computed tomography(CT)and MRI examinations.RESULTS The degree of cerebral edema(more than moderate),the number of damaged brain regions(>2),the number of cerebral hemorrhages(>2),and the percentage of small venous dilatation detected were higher in MRI than in CT examination,and the differences were statistically significant(P<0.05).The total area of the largest region of cerebral damage and of cerebral hemorrhage observed by MRI examination were significantly larger than those of CT examination(P<0.01).Multiparametric quantitative MRI combined with diffusion weighted imaging and SWI had higher sensitivity and accuracy than CT diagnosis,and the difference was statistically significant(P<0.05).The difference in the specificity of the two modes of diagnosis was not significant(P>0.05).CONCLUSION The use of MRI multi-parameter quantitative indexes can accurately diagnose and evaluate neonatal HIE.展开更多
文摘Introduction: In December 2019, COVID 19 spread worldwide, but did not officially start in MOROCCO until March 02, 2020. Since then, this pandemic has significantly impacted the health status of patients in general and cancer patients in particular. The main objective of our study is to evaluate the prognosis of patients treated for cancer and infected with COVID-19. Material and method: A descriptive study with prospective collection was carried out at the medical oncology department of CHU Hassan II in FEZ over a period of two years, from March 2020 to March 2022. Data was carried out on the software SPSS. Results: One hundred cancer patients tested positive for COVID-19 infection and were collected within our department. The average age was 56 years [22-91]. The sex ratio was 1.2. Patients with breast cancer were the most affected by this infection (34%). The clinical symptomatology was dominated by the respiratory syndrome (45%).The diagnosis was made through thoracic CT scan in 62% of cases. 76% of patients were in a metastatic stage. 96% of patients were undergoing oncological treatment. For symptomatique patients, the standard treatment approach involved using antibiotics in 76% of cases. Evolution was marked by recovery in 79% of patients, with a death rate of 12% in this cancer patient population. Conclusion: COVID-19 infection is particularly severe in cancer patients. Mortality among these patients remains high and is associated with overall patient characteristics. However, anticancer treatments have not shown deleterious effects on the course of COVID-19.
基金Supported by Fundamental Research Funds for the Central Universities,No.2022CDJYGRH-004.
文摘Clear cell sarcoma(CCS)of soft tissue is extremely rare,accounting for approximately 1%of all soft tissue tumours.It is very difficult to diagnose CCS based on clinical manifestations.Magnetic resonance imaging(MRI)provides highresolution images of soft tissues and pathological features such as mucus,necrosis,bleeding,and fat through high and low signals on T1 weighted image(T1WI)and T2 weighted image(T2WI).On the other hand,the paramagnetism of melanin in CCS shortens the relaxation time of T1 and T2,and high signal intensity on T1WI and low signal intensity on T2WI can be found.This is different from most other soft tissue sarcomas.At present,the treatment method for CCS is surgical resection.MRI can effectively display the tumour edge,extent of surrounding oedema,and extent of fat involvement,which is highly important for guiding surgical resection and predicting postoperative recurrence.As an invasive sarcoma,CCS has a high risk of metastasis.Regardless of the pathological condition of the resected tumour,MRI or computed tomography(CT)should be performed every 1-2 years to assess recurrence at the primary site and to screen for metastasis in the lungs,liver,and bones.If necessary,PET-CT can be performed to evaluate the overall condition of the patient.
文摘Introduction: Medical imaging is a medical specialty that involves producing images of the human body and interpreting them for diagnostic, therapeutic purposes, and for monitoring the progress of pathologies. We aimed to assess the theoretical knowledge of doctors and interns in medical imaging in the northern region of Burkina Faso. Methodology: This was a descriptive cross-sectional survey based on a self-administered questionnaire. Prescribers knowledge was estimated based on scores derived from questionnaire responses. Results: We collected 106 questionnaires out of 163, i.e. a participation rate of 65.03%. The average knowledge score was 81.71% for the contribution of medical imaging to patient management. It was 60.02% for the indications/counter-indications of radiological examinations and 72.56% for the risks associated with exposure to radiation during these examinations. The score was 59.83% for the methods used to select the appropriate radiological examination. As regards the completeness of the clinical and biological information on the forms requesting imaging examinations, the score was 96.65%. Specialist doctors had the highest overall level of knowledge (74.68%). Conclusion: Improved technical facilities, good initial and in-service training, and interdisciplinary collaboration will help to ensure that imaging tests are properly prescribed, leading to better patient care.
文摘The flexibility in radiotherapy can be improved if patients can be moved between any one of the department’s medical linear accelerators (LINACs) without the need to change anything in the patient’s treatment plan. For this to be possible, the dosimetric characteristics of the various accelerators must be the same, or nearly the same. The purpose of this work is to describe further and compare measurements and parameters after the initial vendor-recommended beam matching of the five LINACs. Deviations related to dose calculations and to beam matched accelerators may compromise treatment accuracy. The safest and most practical way to ensure that all accelerators are within clinical acceptable accuracy is to include TPS calculations in the LINACs matching evaluation. Treatment planning system (TPS) was used to create three photons plans with different field sizes 3 × 3 cm, 10 × 10 cm and 25 × 25 cm at a depth of 4.5 cm in Perspex. Calculated TPS plans were sent to Mosaiq to be delivered by five LINACs. TPS plans were compared with five LINACs measurements data using Gamma analyses of 2% and 2 mm. The results suggest that for four out of the five LINACs, there was generally good agreement, less than a 2% deviation between the planned dose distribution and the measured dose distribution. However, one specific LINAC named “Asterix” exhibited a deviation of 2.121% from the planned dose. The results show that all of the LINACs’ performance were within the acceptable deviation and delivering radiation dose consistently and accurately.
文摘Background: The inadequacy in the completeness of the Laboratory Request Form (LRF) has been reported as one of the major sources of errors during the pre-analytical step of laboratory analysis. To prevent the occurrence of such errors, this study aimed at assessing the level of completeness of LRFs. Methods: A retrospective analysis of laboratory request forms was conducted at the Clinical Biology Laboratory of the Kinshasa University Clinic, DR Congo, between November 2021 to May 2022. The LRFs were evaluated according to the completeness of all sections including administrative data of the patient, data of physician who ordered the test, relevant patient’s clinical data and data of the biological sample. Results: From a total of 2842 LRFs evaluated, none was fully completed with all required information. Particularly, patient’s clinical data including the medical history, provisional diagnosis and current treatment, were the most absent in 99% LRFs. However, two sections related to patient’s ID and prescribed test were informed in 100% LRFs. Conclusion: The results of this preanalytical audit can serve as an improvement opportunity focused on strengthening awareness about complete filling of LRF.
文摘In order to cultivate excellent clinical medical talents with a solid foundation, strong literacy, refined skills, excellent communication abilities, innovative thinking, and a strong focus on practicality, functional experiments have undergone a series of reforms in areas such as constructing new curriculum systems, improving teaching content, updating teaching equipment, introducing new teaching models, and enhancing teaching evaluation systems.
文摘Right-sided colon cancers (RCC) and left-sided colon cancers (LCC) have different epidemiological, physiological, pathological, genetic, and clinical characteristics, which result in differences in the course, prognosis, and outcome of disease. The objective of our study is to compare right-sided colon cancers and left-sided colon cancers regarding clinicopathological and survival characteristics. This is a retrospective study of 664 patients with colon cancer treated at the medical oncology department of Fez over a period from December 2009 to September 2020. Rectosigmoid, descending colon, and splenic flexure tumors were considered left-sided colon cancers, whereas ascending colon tumors were considered right-sided colon cancers. The Kaplan Meier method was used to estimate median survival. The study included 664 patients (female, 47%) having colon cancer with a median age of 60 years (23 - 83). Of the patients, 78.5% (n = 519) had LCC and 19.36 % (n = 128) had RCC. The rate of patients aged ≥ 65 years and the rate of patients with a family history of colon cancer was higher in the LCC patients. The proportion of poorly differentiated adenocarcinomas represented 3%, of which 63% had cancer of the right colon. There was a significantly higher proportion of higher T stage (T3-4: 62% vs 38%) in right sided tumors as compared to left sided tumors. The rate of metastatic patients was 64.1% in the RCC group and 43% in the LCC group. The median follow-up period was 14 months in the RCC group and 19 months in the LCC group with higher median overall survival in the LCC group (32 vs 21 months). We found histopathological differences between right and left sided colon cancer. Tumors on the right colon were found to be more aggressive, as expressed by poorer differentiation, higher T stage associated with a median overall survival better in left colon cancer.
文摘Introduction: Pain assessment is an essential step towards pain relief. In our context, however, it is insufficient in emergency departments. The aim was to assess the nature and effectiveness of the analgesia used in the emergency department of the CHU-Donka. Method: This was a single-centre prospective observational study conducted over one month (November 2020) in the medical-surgical emergency department of CHU-Donka. All patients aged 18 or over admitted to the emergency department with moderate to severe acute pain were included. Results: We enrolled 880 patients, 615 of whom (69.88%) were in pain. Males predominated (65.2%), with a sex ratio of 1.87. The average age was 44.78 ± 16.41 years, with extremes ranging from 18 to 85 years. The most represented age group was 18 - 34 years, with 66.18%. Initial assessment of pain by nursing staff in 3 cases. Initial assessment of pain by the investigator was 100%, 74% moderate and 26% severe. No reassessment of pain by nursing staff. Reassessment by the interviewer was 100% and found 5% no pain, 61% mild pain, 24% moderate pain and 10% severe pain. With an average numerical scale of 3.77 ± 2.61 and extremes from 0 to 10. Average length of stay was 2.85 ± 1.48 hours, with extremes ranging from 45 minutes to 8 hours. Analgesia was administered with paracetamol alone (43.58%), combined with tramadol or nefopam. No patient received morphine. Conclusion: This study revealed a lack of pain assessment in our department.
文摘Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.
文摘Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well organized,has succeeded in reducing the incidence of colon and rectal cancer and improving the prognosis related to them.Despite considerable advancements in screening technologies and strategies,the effectiveness of CRC screening programs remains less than optimal.This paper examined the multifaceted reasons behind the persistent lack of effect-iveness in CRC screening initiatives.Through a critical analysis of current methodologies,technological limitations,patient-related factors,and systemic challenges,we elucidated the complex interplay that hampers the successful reduction of CRC morbidity and mortality rates.While acknowledging the ad-vancements that have improved aspects of screening,we emphasized the necessity of addressing the identified barriers comprehensively.This study aimed to raise awareness of how important CRC screening is in reducing costs for this disease.Screening and early diagnosis are not only important in improving the prognosis of patients with CRC but can lead to an important reduction in the cost of treating a disease that is often diagnosed at an advanced stage.Spending more sooner can mean saving money later.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
基金supported in part by the National Natural Science Foundation of China(82072019)the Shenzhen Basic Research Program(JCYJ20210324130209023)+5 种基金the Shenzhen-Hong Kong-Macao S&T Program(Category C)(SGDX20201103095002019)the Mainland-Hong Kong Joint Funding Scheme(MHKJFS)(MHP/005/20),the Project of Strategic Importance Fund(P0035421)the Projects of RISA(P0043001)from the Hong Kong Polytechnic University,the Natural Science Foundation of Jiangsu Province(BK20201441)the Provincial and Ministry Co-constructed Project of Henan Province Medical Science and Technology Research(SBGJ202103038,SBGJ202102056)the Henan Province Key R&D and Promotion Project(Science and Technology Research)(222102310015)the Natural Science Foundation of Henan Province(222300420575),and the Henan Province Science and Technology Research(222102310322).
文摘Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians.Moreover,some potentially useful quantitative information in medical images,especially that which is not visible to the naked eye,is often ignored during clinical practice.In contrast,radiomics performs high-throughput feature extraction from medical images,which enables quantitative analysis of medical images and prediction of various clinical endpoints.Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis,demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine.However,radiomics remains in a developmental phase as numerous technical challenges have yet to be solved,especially in feature engineering and statistical modeling.In this review,we introduce the current utility of radiomics by summarizing research on its application in the diagnosis,prognosis,and prediction of treatment responses in patients with cancer.We focus on machine learning approaches,for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling.Furthermore,we introduce the stability,reproducibility,and interpretability of features,and the generalizability and interpretability of models.Finally,we offer possible solutions to current challenges in radiomics research.
基金Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0308.
文摘BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.
文摘Because of the features involved with their varied kernels,differential operators relying on convolution formulations have been acknowledged as effective mathematical resources for modeling real-world issues.In this paper,we constructed a stochastic fractional framework of measles spreading mechanisms with dual medication immunization considering the exponential decay and Mittag-Leffler kernels.In this approach,the overall population was separated into five cohorts.Furthermore,the descriptive behavior of the system was investigated,including prerequisites for the positivity of solutions,invariant domain of the solution,presence and stability of equilibrium points,and sensitivity analysis.We included a stochastic element in every cohort and employed linear growth and Lipschitz criteria to show the existence and uniqueness of solutions.Several numerical simulations for various fractional orders and randomization intensities are illustrated.
基金supported by the National Natural Science Foundation of China(82203185,82230058,82172875 and 82073094)the National Key Research and Development Program of China(2021YFF1201300 and 2022YFE0103600)+3 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-014,2021-I2M-1-022,and 2022-I2M-2-001)the Open Issue of State Key Laboratory of Molecular Oncology(SKL-KF-2021-16)the Independent Issue of State Key Laboratory of Molecular Oncology(SKL-2021-16)the Beijing Hope Marathon Special Fund of Chinese Cancer Foundation(LC2020B14).
文摘Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.
文摘Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.
基金supported by the National Natural Science Foundation of China(Grant No.:32070740)Zhejiang Provincial Natural Science Foundation(Grant No.:LZ23H160005)+1 种基金Natural Science Foundation of Jiangsu Province(Grant No.:BK20201197)Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program,Zhejiang Provincial Qianjiang Talents Program to Jianbin Zhang.
文摘Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.
文摘Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.
文摘BACKGROUND Magnetic resonance imaging(MRI)scanning with susceptibility weighted imaging(SWI)sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy(HIE).AIM To observe the role of MRI multi-parameter quantitative indexes in the diagnosis of neonatal HIE.METHODS The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Ganyu District People's Hospital of Lianyungang City and 23 neonates without HIE admitted during the same period were analyzed retrospectively from August,2021 to December,2023.The results of clinical judgment were compared with the results of computed tomography(CT)and MRI examinations.RESULTS The degree of cerebral edema(more than moderate),the number of damaged brain regions(>2),the number of cerebral hemorrhages(>2),and the percentage of small venous dilatation detected were higher in MRI than in CT examination,and the differences were statistically significant(P<0.05).The total area of the largest region of cerebral damage and of cerebral hemorrhage observed by MRI examination were significantly larger than those of CT examination(P<0.01).Multiparametric quantitative MRI combined with diffusion weighted imaging and SWI had higher sensitivity and accuracy than CT diagnosis,and the difference was statistically significant(P<0.05).The difference in the specificity of the two modes of diagnosis was not significant(P>0.05).CONCLUSION The use of MRI multi-parameter quantitative indexes can accurately diagnose and evaluate neonatal HIE.