Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary sa...Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.展开更多
In this editorial,we comment on the study of the Yu et al on psychological distress in patients with hepatobiliary and pancreatic malignancies.Hepatobiliary and pancreatic malignancies include hepatocellular carcinoma...In this editorial,we comment on the study of the Yu et al on psychological distress in patients with hepatobiliary and pancreatic malignancies.Hepatobiliary and pancreatic malignancies include hepatocellular carcinoma,cholangiocarcinoma,gallbladder cancer and pancreatic cancer.These cancers are among the most aggressive and difficult to treat.Although improvements in surgery,drug treatments and palliative care have led to better survival rates and quality of life,the significant psychological impact on patients remains underrecognized.Anxiety and depression are prevalent at every stage of the disease,from the initial diagnosis to treatment,recurrence and end-of-life care.However,these issues often take a backseat to the urgent need to manage physical symptoms.Mental health challenges can greatly affect how well patients follow treatment plans,recover and their overall outlook.Yu et al explore the causes of psychological distress in hepatobiliary and pancreatic cancers,including disease severity,symptom burden,financial stress and fears about life and death.We highlight the importance of regular mental health screenings,psychological support and teamwork in oncology care.By focusing on emotional health alongside physical treatment,doctors can build resilience,improve outcomes and address a frequently ignored aspect of cancer care.展开更多
Unwarranted death of neurons is a major cause of neurodegenerative diseases.Since mature neurons are postmitotic and do not replicate,their death usually constitutes an irreversible step in pathology.A logical strateg...Unwarranted death of neurons is a major cause of neurodegenerative diseases.Since mature neurons are postmitotic and do not replicate,their death usually constitutes an irreversible step in pathology.A logical strategy to prevent neurodegeneration would then be to save all neurons that are still alive,i.e.protecting the ones that are still healthy as well as trying to rescue the ones that are damaged and in the process of dying.Regarding the latter,recent experiments have indicated that the possibility of reversing the cell death process and rescuing dying cells is more significant than previously anticipated.In many situations,the elimination of the cell death trigger alone enables dying cells to spontaneously repair their damage,recover,and survive.In this review,we explore the factors,which determine the fate of neurons engaged in the cell death process.A deeper insight into cell death mechanisms and the intrinsic capacity of cells to recover could pave the way for novel therapeutic approaches to neurodegenerative diseases.展开更多
It was in the 1980s that research on somatostatin(SST)in Alzheimer’s disease(AD)truly gained traction,demonstrating consistent colocalization with amyloid-β(Aβ),along with massive SST/SST cell losses(Almeida,2024)....It was in the 1980s that research on somatostatin(SST)in Alzheimer’s disease(AD)truly gained traction,demonstrating consistent colocalization with amyloid-β(Aβ),along with massive SST/SST cell losses(Almeida,2024).Although the field already had some grasp over the neuroendocrine and hypothalamic functions of the peptide,very little was known about the GABAergic interneurons(SST-INs)that synthesize it in cortical/hippocampal regions.Quite excitingly,over 40 years later,research has grown effervescent.展开更多
Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewa...Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.展开更多
Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threa...Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.展开更多
Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyp...Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyperi Rhizoma varies significantly across different regions,potentially influencing its therapeutic efficacy.This study investigates the influence of geographic origin on the chemical composition and overall quality of Cyperi Rhizoma.Methods:A comprehensive approach,including traditional quality assessment,GC-MS(g as c hromatography-m ass s pectrometry),RP-HPLC(r everse p hase h igh-p erformance l iquid c hromatography),and FT-IR(f ourier t ransform i nfrared s pectroscopy)techniques,was employed to analyze Cyperi Rhizoma samples from Shandong Province.These methods examined the physical appearance,chemical profile,and content variations,particularly focusing onα-cyperone.Results:Traditional quality assessments revealed noticeable differences in the external characteristics of the samples.GC-MS analysis identified a variety of unique chemical constituents,while RP-HPLC and FT-IR showed significant variations inα-cyperone content,with higher levels found in Shandong samples.Conclusion:These results demonstrate that geographic origin is a critical determinant of Cyperi Rhizoma quality,with Shandong specimens exhibiting superiorα-cyperone levels and characteristic phytochemical profiles.This validates the geo-authenticity concept in TCM and provides actionable data for developing evidence-based quality standards,suggesting that provenance should be prioritized in medicinal material selection and pharmacopeial specifications.展开更多
Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytoki...Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.展开更多
Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic dat...Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.展开更多
Background: Exclusive breastfeeding is globally promoted as a preventive health measure. However, an increasing incidence of jaundice among exclusively breastfed neonates has been observed. In Jos, Nigeria, anecdotal ...Background: Exclusive breastfeeding is globally promoted as a preventive health measure. However, an increasing incidence of jaundice among exclusively breastfed neonates has been observed. In Jos, Nigeria, anecdotal evidence suggests a rise in jaundice cases among breastfed infants during their first week of life. This study investigates the relationship between neonatal jaundice and the biochemical composition of maternal breast milk in Jos, Nigeria. Objective: To evaluate the role of maternal milk protein status and other milk constituents in the development of neonatal jaundice among exclusively breastfed full-term infants. Methods: This cross-sectional study involved 152 participants, comprising of 76 neonates (38 jaundiced and 38 healthy controls) and their corresponding 76 mothers at Jos University Teaching Hospital. Biochemical analyses were conducted on maternal breast milk (albumin, proteins, casein, fat, lactose, enzymes) and infant serum (bilirubin, albumin, proteins, enzymes). Statistical analysis was performed using Mann-Whitney tests with significance set at p ≤ 0.05. Results: Maternal breast milk from mothers of jaundiced infants showed significantly lower protein (0.73 ± 0.07 g/100ml), albumin (0.62 ± 0.04 g/100ml), and casein (1.6 ± 0.12 g/100ml) levels compared to controls (p Conclusion: The study highlights a potential link between lower maternal milk protein levels and the occurrence of neonatal jaundice. Interventions aimed at enhancing maternal nutrition and promoting more frequent breastfeeding may mitigate the risk. Further research should explore additional maternal and neonatal factors contributing to this condition.展开更多
Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the...Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data,these models showcase remarkable efficacy across various tasks,including new drug design and drug target identification.The adaptability of pre-trained trans-former-based models renders them indispensable assets for driving data-centric advancements in drug discovery,chemistry,and biology,furnishing a robust framework that expedites innovation and dis-covery within these domains.Beyond their technical prowess,the success of transformer-based models in drug discovery,chemistry,and biology extends to their interdisciplinary potential,seamlessly combining biological,physical,chemical,and pharmacological insights to bridge gaps across diverse disciplines.This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields.In our review,we elucidate the myriad applications of transformers in drug discovery,as well as chemistry and biology,spanning from protein design and protein engineering,to molecular dynamics(MD),drug target iden-tification,transformer-enabled drug virtual screening(VS),drug lead optimization,drug addiction,small data set challenges,chemical and biological image analysis,chemical language understanding,and single cell data.Finally,we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.展开更多
Objective:To investigate the protective effects of naringin on doxorubicin(DOX)-induced liver injury.Methods:A total of 50 male rats were allocated into five groups:the control group,the DOX group,the DOX groups treat...Objective:To investigate the protective effects of naringin on doxorubicin(DOX)-induced liver injury.Methods:A total of 50 male rats were allocated into five groups:the control group,the DOX group,the DOX groups treated with 50 mg/kg and 100 mg/kg of naringin by gastric lavage for 10 days,as well as the group treated with 100 mg/kg of naringin alone.Liver and serum samples were collected for biochemical,histopathological,and molecular analyses,including liver enzyme activity,oxidative stress markers,inflammation,apoptosis-related proteins,and DNA damage indicators.Results:Naringin attenuated DOX-induced elevation in liver enzyme activity and inflammation markers while enhancing antioxidant activities.Naringin also activated the Nrf2-HO-1 signaling pathway,with the most pronounced effect in the high-dose naringin group.In addition,naringin modulated apoptotic signaling by downregulating the expression of PI3K-AKT and BAX,and upregulating Bcl-2,as well as reduced the level of 8-OHdG.Histopathological evaluation showed that DOX-induced structural liver alterations,such as cellular degeneration and necrosis,were notably attenuated by naringin treatment.Conclusions:Naringin treatment exerts protective effects against DOX-induced liver injury through its antioxidative,anti-inflammatory,and anti-apoptotic effects.展开更多
BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on ...BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on the knowledge,attitudes,and preventive practices regarding breast cancer and the associated factors among females in Wollo,Ethiopia,remain limited.AIM To assess the impact of family history(FH)of breast disease on knowledge,attitudes,and breast cancer preventive practices among reproductive-age females.METHODS A community-based cross-sectional study was conducted in May and June 2022 in Northeast Ethiopia and involved 143 reproductive-age females with FH of breast diseases and 209 without such a history.We selected participants using the systematic random sampling technique.We analyzed the data using Statistical Package for Social Science version 25 software,and logistic regression analysis was employed to determine odds ratios for variable associations,with statistical significance set at P<0.05.RESULTS Among participants with FH of breast diseases,the levels of knowledge,attitudes,and preventive practices were found to be 83.9%[95%confidence interval(CI):77.9-89.9],49.0%(95%CI:40.8-57.1),and 74.1%(95%CI:66.9-81.3),respectively.In contrast,among those without FH of breast diseases,these levels were significantly decreased to 10.5%(95%CI:6.4-14.7),32.1%(95%CI:25.7-38.4),and 16.7%(95%CI:11.7-21.8),respectively.This study also indicated that knowledge,attitudes,and preventive practices related to breast cancer are significantly higher among participants with FH of breast diseases compared to those without HF breast diseases.CONCLUSION Educational status,monthly income,and community health insurance were identified as significant factors associated with the levels of knowledge,attitudes,and preventive practices regarding breast cancer among reproductive-age females.展开更多
BACKGROUND Various stone factors can affect the net results of shock wave lithotripsy(SWL).Recently a new factor called variation coefficient of stone density(VCSD)is being considered to have an impact on stone free r...BACKGROUND Various stone factors can affect the net results of shock wave lithotripsy(SWL).Recently a new factor called variation coefficient of stone density(VCSD)is being considered to have an impact on stone free rates.AIM To assess the role of VCSD in determining success of SWL in urinary calculi.METHODS Charts review was utilized for collection of data variables.The patients were subjected to SWL,using an electromagnetic lithotripter.Mean stone density(MSD),stone heterogeneity index(SHI),and VCSD were calculated by generating regions of interest on computed tomography(CT)images.Role of these factors were determined by applying the relevant statistical tests for continuous and categorical variables and a P value of<0.05 was gauged to be statistically significant.RESULTS There were a total of 407 patients included in the analysis.The mean age of the subjects in this study was 38.89±14.61 years.In total,165 out of the 407 patients could not achieve stone free status.The successful group had a significantly lower stone volume as compared to the unsuccessful group(P<0.0001).Skin to stone distance was not dissimilar among the two groups(P=0.47).MSD was significantly lower in the successful group(P<0.0001).SHI and VCSD were both significantly higher in the successful group(P<0.0001).CONCLUSION VCSD,a useful CT based parameter,can be utilized to gauge stone fragility and hence the prediction of SWL outcomes.展开更多
Introduction: The Six Sigma methodology is an opportunity for a better understanding of the performance of analytical methods and for a better adaptation of the quality control management policy of the medical biology...Introduction: The Six Sigma methodology is an opportunity for a better understanding of the performance of analytical methods and for a better adaptation of the quality control management policy of the medical biology laboratory. Using the sigma metric, this study assessed the performance of the Biochemistry analytical system of a medical biology laboratory in Côte d'Ivoire. Methods: Six Sigma methodology was applied to 3 analytes (alanine aminotransferase, glucose and creatinine). Performance indicators such as measurement imprecision and bias were determined based on the results of internal and external quality controls. The sigma number was calculated using the total allowable error values proposed by Ricos et al. Results: For both control levels, ALT had a sigma number greater than 6 (7.6 for normal control and 7.9 for pathological control). However, low sigma numbers, less than or equal to 2 for creatinine (1.4 for normal control and 2 for pathological control) and less than 1 for glucose were found. Conclusion: This study revealed good analytical performance of ALT from the point of view of 6 sigma analysis. However, modifications to the overall quality control procedure for glucose and creatinine are needed to improve their analytical performance. The study should be extended to the entire laboratory’s analytes in order to modify the strategies of quality control procedures based on metric analysis for an overall improvement in analytical performance.展开更多
Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through iso...Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.展开更多
N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis a...N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.展开更多
This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinom...This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.展开更多
This manuscript features the promising findings of a study conducted by Ju et al,who used graphene nanocomposites for air disinfection in dental clinics.Their study demonstrated that,compared with conventional filters...This manuscript features the promising findings of a study conducted by Ju et al,who used graphene nanocomposites for air disinfection in dental clinics.Their study demonstrated that,compared with conventional filters,graphene nanocom-posites substantially improved air quality and reduced microbial contamination.This manuscript highlights the innovative application of graphene materials,emphasizing their potential to enhance dental clinic environments by minimizing secondary pollution.On the basis of the unique antimicrobial properties of gra-phene and the original study’s rigorous methodology,we recommend using gra-phene nanocomposites in clinical settings to control airborne infections.展开更多
Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and ...Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.展开更多
文摘Gastric cancer(GC)is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality.Major risk factors for GC include Helicobacter pylori infection,increasing age,high dietary salt intake,and diets deficient in vegetables and fruits.Due to the often subtle and nonspecific early symptoms,coupled with the lack of routine screening programs,a significant proportion of GC cases are diagnosed at advanced stages.The etiology of GC is multifactorial,and diagnosis is confirmed histologically through endoscopic biopsy,followed by staging via computed tomography,positron emission tomography,staging laparoscopy,and endoscopic ultrasound.Treatment strategies typically involve a multidisciplinary approach including chemotherapy,surgical resection,radiotherapy,and emerging immunotherapeutic options.Despite advances in diagnostic and therapeutic modalities,the prognosis of advanced GC remains poor,with high rates of recurrence and metastasis.In recent years,increasing attention has been given to the role of tight junction(TJ)proteins in the pathogenesis and progression of GC.TJ proteins,critical components of epithelial barrier function,have been implicated in various stages of gastric carcinogenesis,from intestinal metaplasia to invasion and metastasis.Infection and inflammation,particularly due to Helicobacter pylori,disrupt TJ integrity,compromising the gastric mucosal barrier and facilitating neoplastic transformation.This review synthesizes current evidence from PubMed,EMBASE,Google Scholar,ScienceDirect,SpringerLink,and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC.By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis,this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.
文摘In this editorial,we comment on the study of the Yu et al on psychological distress in patients with hepatobiliary and pancreatic malignancies.Hepatobiliary and pancreatic malignancies include hepatocellular carcinoma,cholangiocarcinoma,gallbladder cancer and pancreatic cancer.These cancers are among the most aggressive and difficult to treat.Although improvements in surgery,drug treatments and palliative care have led to better survival rates and quality of life,the significant psychological impact on patients remains underrecognized.Anxiety and depression are prevalent at every stage of the disease,from the initial diagnosis to treatment,recurrence and end-of-life care.However,these issues often take a backseat to the urgent need to manage physical symptoms.Mental health challenges can greatly affect how well patients follow treatment plans,recover and their overall outlook.Yu et al explore the causes of psychological distress in hepatobiliary and pancreatic cancers,including disease severity,symptom burden,financial stress and fears about life and death.We highlight the importance of regular mental health screenings,psychological support and teamwork in oncology care.By focusing on emotional health alongside physical treatment,doctors can build resilience,improve outcomes and address a frequently ignored aspect of cancer care.
基金supported by the following foundations:“Stichting Oogfonds Nederland(No.2023-26)”the“Landelijke Stichting voor Blinden en Slechtzienden(No.2023-24)”that contributed through UitZicht,ZonMw grant(No.435005020)a grant of the Chinese Scholarship Council(No.201809110169)(to TGMFG,CPMR,and WY).
文摘Unwarranted death of neurons is a major cause of neurodegenerative diseases.Since mature neurons are postmitotic and do not replicate,their death usually constitutes an irreversible step in pathology.A logical strategy to prevent neurodegeneration would then be to save all neurons that are still alive,i.e.protecting the ones that are still healthy as well as trying to rescue the ones that are damaged and in the process of dying.Regarding the latter,recent experiments have indicated that the possibility of reversing the cell death process and rescuing dying cells is more significant than previously anticipated.In many situations,the elimination of the cell death trigger alone enables dying cells to spontaneously repair their damage,recover,and survive.In this review,we explore the factors,which determine the fate of neurons engaged in the cell death process.A deeper insight into cell death mechanisms and the intrinsic capacity of cells to recover could pave the way for novel therapeutic approaches to neurodegenerative diseases.
文摘It was in the 1980s that research on somatostatin(SST)in Alzheimer’s disease(AD)truly gained traction,demonstrating consistent colocalization with amyloid-β(Aβ),along with massive SST/SST cell losses(Almeida,2024).Although the field already had some grasp over the neuroendocrine and hypothalamic functions of the peptide,very little was known about the GABAergic interneurons(SST-INs)that synthesize it in cortical/hippocampal regions.Quite excitingly,over 40 years later,research has grown effervescent.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.
基金supported by the National Natural Science Foundation of China(No.82204610)Qihang Talent Program(L2022046)+1 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2021A04013)Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyperi Rhizoma varies significantly across different regions,potentially influencing its therapeutic efficacy.This study investigates the influence of geographic origin on the chemical composition and overall quality of Cyperi Rhizoma.Methods:A comprehensive approach,including traditional quality assessment,GC-MS(g as c hromatography-m ass s pectrometry),RP-HPLC(r everse p hase h igh-p erformance l iquid c hromatography),and FT-IR(f ourier t ransform i nfrared s pectroscopy)techniques,was employed to analyze Cyperi Rhizoma samples from Shandong Province.These methods examined the physical appearance,chemical profile,and content variations,particularly focusing onα-cyperone.Results:Traditional quality assessments revealed noticeable differences in the external characteristics of the samples.GC-MS analysis identified a variety of unique chemical constituents,while RP-HPLC and FT-IR showed significant variations inα-cyperone content,with higher levels found in Shandong samples.Conclusion:These results demonstrate that geographic origin is a critical determinant of Cyperi Rhizoma quality,with Shandong specimens exhibiting superiorα-cyperone levels and characteristic phytochemical profiles.This validates the geo-authenticity concept in TCM and provides actionable data for developing evidence-based quality standards,suggesting that provenance should be prioritized in medicinal material selection and pharmacopeial specifications.
基金supported by the National Natural Science Foundation of China,Nos.32070735(to QL),82371321(to QL),82171270(to ZL)Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People's Republic of China,No.2020-0103-3-1(to ZL)+2 种基金the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)。
文摘Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82272008)The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2021KJ194)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.
文摘Background: Exclusive breastfeeding is globally promoted as a preventive health measure. However, an increasing incidence of jaundice among exclusively breastfed neonates has been observed. In Jos, Nigeria, anecdotal evidence suggests a rise in jaundice cases among breastfed infants during their first week of life. This study investigates the relationship between neonatal jaundice and the biochemical composition of maternal breast milk in Jos, Nigeria. Objective: To evaluate the role of maternal milk protein status and other milk constituents in the development of neonatal jaundice among exclusively breastfed full-term infants. Methods: This cross-sectional study involved 152 participants, comprising of 76 neonates (38 jaundiced and 38 healthy controls) and their corresponding 76 mothers at Jos University Teaching Hospital. Biochemical analyses were conducted on maternal breast milk (albumin, proteins, casein, fat, lactose, enzymes) and infant serum (bilirubin, albumin, proteins, enzymes). Statistical analysis was performed using Mann-Whitney tests with significance set at p ≤ 0.05. Results: Maternal breast milk from mothers of jaundiced infants showed significantly lower protein (0.73 ± 0.07 g/100ml), albumin (0.62 ± 0.04 g/100ml), and casein (1.6 ± 0.12 g/100ml) levels compared to controls (p Conclusion: The study highlights a potential link between lower maternal milk protein levels and the occurrence of neonatal jaundice. Interventions aimed at enhancing maternal nutrition and promoting more frequent breastfeeding may mitigate the risk. Further research should explore additional maternal and neonatal factors contributing to this condition.
基金supported in part by National Institute of Health(NIH),USA(Grant Nos.:R01GM126189,R01AI164266,and R35GM148196)the National Science Foundation,USA(Grant Nos.DMS2052983,DMS-1761320,and IIS-1900473)+3 种基金National Aero-nautics and Space Administration(NASA),USA(Grant No.:80NSSC21M0023)Michigan State University(MSU)Foundation,USA,Bristol-Myers Squibb(Grant No.:65109)USA,and Pfizer,USAsupported by the National Natural Science Foundation of China(Grant Nos.:11971367,12271416,and 11972266).
文摘Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data,these models showcase remarkable efficacy across various tasks,including new drug design and drug target identification.The adaptability of pre-trained trans-former-based models renders them indispensable assets for driving data-centric advancements in drug discovery,chemistry,and biology,furnishing a robust framework that expedites innovation and dis-covery within these domains.Beyond their technical prowess,the success of transformer-based models in drug discovery,chemistry,and biology extends to their interdisciplinary potential,seamlessly combining biological,physical,chemical,and pharmacological insights to bridge gaps across diverse disciplines.This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields.In our review,we elucidate the myriad applications of transformers in drug discovery,as well as chemistry and biology,spanning from protein design and protein engineering,to molecular dynamics(MD),drug target iden-tification,transformer-enabled drug virtual screening(VS),drug lead optimization,drug addiction,small data set challenges,chemical and biological image analysis,chemical language understanding,and single cell data.Finally,we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.
基金supported by the Atatürk University Scientific Research Projects Coordinator(Project No:2020/8737)。
文摘Objective:To investigate the protective effects of naringin on doxorubicin(DOX)-induced liver injury.Methods:A total of 50 male rats were allocated into five groups:the control group,the DOX group,the DOX groups treated with 50 mg/kg and 100 mg/kg of naringin by gastric lavage for 10 days,as well as the group treated with 100 mg/kg of naringin alone.Liver and serum samples were collected for biochemical,histopathological,and molecular analyses,including liver enzyme activity,oxidative stress markers,inflammation,apoptosis-related proteins,and DNA damage indicators.Results:Naringin attenuated DOX-induced elevation in liver enzyme activity and inflammation markers while enhancing antioxidant activities.Naringin also activated the Nrf2-HO-1 signaling pathway,with the most pronounced effect in the high-dose naringin group.In addition,naringin modulated apoptotic signaling by downregulating the expression of PI3K-AKT and BAX,and upregulating Bcl-2,as well as reduced the level of 8-OHdG.Histopathological evaluation showed that DOX-induced structural liver alterations,such as cellular degeneration and necrosis,were notably attenuated by naringin treatment.Conclusions:Naringin treatment exerts protective effects against DOX-induced liver injury through its antioxidative,anti-inflammatory,and anti-apoptotic effects.
文摘BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on the knowledge,attitudes,and preventive practices regarding breast cancer and the associated factors among females in Wollo,Ethiopia,remain limited.AIM To assess the impact of family history(FH)of breast disease on knowledge,attitudes,and breast cancer preventive practices among reproductive-age females.METHODS A community-based cross-sectional study was conducted in May and June 2022 in Northeast Ethiopia and involved 143 reproductive-age females with FH of breast diseases and 209 without such a history.We selected participants using the systematic random sampling technique.We analyzed the data using Statistical Package for Social Science version 25 software,and logistic regression analysis was employed to determine odds ratios for variable associations,with statistical significance set at P<0.05.RESULTS Among participants with FH of breast diseases,the levels of knowledge,attitudes,and preventive practices were found to be 83.9%[95%confidence interval(CI):77.9-89.9],49.0%(95%CI:40.8-57.1),and 74.1%(95%CI:66.9-81.3),respectively.In contrast,among those without FH of breast diseases,these levels were significantly decreased to 10.5%(95%CI:6.4-14.7),32.1%(95%CI:25.7-38.4),and 16.7%(95%CI:11.7-21.8),respectively.This study also indicated that knowledge,attitudes,and preventive practices related to breast cancer are significantly higher among participants with FH of breast diseases compared to those without HF breast diseases.CONCLUSION Educational status,monthly income,and community health insurance were identified as significant factors associated with the levels of knowledge,attitudes,and preventive practices regarding breast cancer among reproductive-age females.
文摘BACKGROUND Various stone factors can affect the net results of shock wave lithotripsy(SWL).Recently a new factor called variation coefficient of stone density(VCSD)is being considered to have an impact on stone free rates.AIM To assess the role of VCSD in determining success of SWL in urinary calculi.METHODS Charts review was utilized for collection of data variables.The patients were subjected to SWL,using an electromagnetic lithotripter.Mean stone density(MSD),stone heterogeneity index(SHI),and VCSD were calculated by generating regions of interest on computed tomography(CT)images.Role of these factors were determined by applying the relevant statistical tests for continuous and categorical variables and a P value of<0.05 was gauged to be statistically significant.RESULTS There were a total of 407 patients included in the analysis.The mean age of the subjects in this study was 38.89±14.61 years.In total,165 out of the 407 patients could not achieve stone free status.The successful group had a significantly lower stone volume as compared to the unsuccessful group(P<0.0001).Skin to stone distance was not dissimilar among the two groups(P=0.47).MSD was significantly lower in the successful group(P<0.0001).SHI and VCSD were both significantly higher in the successful group(P<0.0001).CONCLUSION VCSD,a useful CT based parameter,can be utilized to gauge stone fragility and hence the prediction of SWL outcomes.
文摘Introduction: The Six Sigma methodology is an opportunity for a better understanding of the performance of analytical methods and for a better adaptation of the quality control management policy of the medical biology laboratory. Using the sigma metric, this study assessed the performance of the Biochemistry analytical system of a medical biology laboratory in Côte d'Ivoire. Methods: Six Sigma methodology was applied to 3 analytes (alanine aminotransferase, glucose and creatinine). Performance indicators such as measurement imprecision and bias were determined based on the results of internal and external quality controls. The sigma number was calculated using the total allowable error values proposed by Ricos et al. Results: For both control levels, ALT had a sigma number greater than 6 (7.6 for normal control and 7.9 for pathological control). However, low sigma numbers, less than or equal to 2 for creatinine (1.4 for normal control and 2 for pathological control) and less than 1 for glucose were found. Conclusion: This study revealed good analytical performance of ALT from the point of view of 6 sigma analysis. However, modifications to the overall quality control procedure for glucose and creatinine are needed to improve their analytical performance. The study should be extended to the entire laboratory’s analytes in order to modify the strategies of quality control procedures based on metric analysis for an overall improvement in analytical performance.
基金supported by the National Natural Science Foundation of China(Grant No.32170738)the National Medical Research Council of Singapore(Grant No.NMRC/CBRG/0013/2012).
文摘Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.
文摘This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.
文摘This manuscript features the promising findings of a study conducted by Ju et al,who used graphene nanocomposites for air disinfection in dental clinics.Their study demonstrated that,compared with conventional filters,graphene nanocom-posites substantially improved air quality and reduced microbial contamination.This manuscript highlights the innovative application of graphene materials,emphasizing their potential to enhance dental clinic environments by minimizing secondary pollution.On the basis of the unique antimicrobial properties of gra-phene and the original study’s rigorous methodology,we recommend using gra-phene nanocomposites in clinical settings to control airborne infections.
文摘Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.