In this comprehensive evidence-based analysis of ulcerative colitis(UC),a causal role is identified for colonic epithelial hydrogen peroxide(H_(2)O_(2))in both the pathogenesis and relapse of this debilitating inflamm...In this comprehensive evidence-based analysis of ulcerative colitis(UC),a causal role is identified for colonic epithelial hydrogen peroxide(H_(2)O_(2))in both the pathogenesis and relapse of this debilitating inflammatory bowel disease.Studies have shown that H_(2)O_(2) production is significantly increased in the non-inflamed colonic epithelium of individuals with UC.H_(2)O_(2) is a powerful neutrophilic chemo-tactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular“trail”that attracts adjacent intra-vascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC.A novel therapy aimed at removing the inappropriate H_(2)O_(2) mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one(biopsy-proven)histologic remission lasting 14 years to date.The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H_(2)O_(2) mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease.Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects.It is the aim of this paper to present experimental and clinical evidence that identifies H_(2)O_(2) produced by the colonic epithelium as the causal agent in the pathogenesis of UC.A detailed explanation of a novel therapeutic intervention to normalize colonic H_(2)O_(2),its rationale,components,and formulation is also provided.展开更多
Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge ex...Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that “avoid” control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.展开更多
Over the last few years,neuro-cardiology has grown the awareness of the relationship between the brain and the heart,contributing to developing a modern interdisciplinary field of neuro-cardiology.To enhance the aware...Over the last few years,neuro-cardiology has grown the awareness of the relationship between the brain and the heart,contributing to developing a modern interdisciplinary field of neuro-cardiology.To enhance the awareness of the relationship between the brain and the heart,we concentrate on the brain function disability that results from cardiac dysfunction and the brain function impairment that results from cardiac dysfunction.It is usual for patients with cerebral ischemia to be preceded by cardiac impairment.The main triggers of cerebral ischemia involve arrhythmia,atrial fibrillation,etc.,reflecting a strong connection between the heart and the brain.Cerebral ischemia is linked to how the heart and brain communicate and affect each other at the pathophysiological stage.The formation of the heart-brain axis mechanism is important in its incidence and growth.The analysis explores the etiology and pathogenesis of cerebral ischemia centered on the heart-brain axis neuronal pathway and the mechanism of the relationship between the heart and brain,which offers important enrichment to the hypothesis of combined care of brain and heart and is extremely useful for gaining new knowledge for research and production of multi-target drugs for the prevention and treatment of cerebral ischemia.展开更多
Introduction Overweight and obesity are usually measured using body mass index(BMI),with overweight classifying as a BMI of 25-29.9 kg/m^(2),obesity as a BMI of≥30 kg/m^(2),and morbid obesity as a BMI of≥40 kg/m^(2)...Introduction Overweight and obesity are usually measured using body mass index(BMI),with overweight classifying as a BMI of 25-29.9 kg/m^(2),obesity as a BMI of≥30 kg/m^(2),and morbid obesity as a BMI of≥40 kg/m^(2).1 Overweight and obesity are major health crises,posing a threat to the current global health progress.2 In 2021,3.71 million deaths and 129 million disability-adjusted life-years(DALYs)were attributable to overweight and obesity.展开更多
Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,de...Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.展开更多
Objective Diabetic kidney disease is a serious complication of diabetes,which is the leading cause of end-stage renal disease worldwide.Approximately 40%of individuals with diabetes develop diabetic kidney disease.At ...Objective Diabetic kidney disease is a serious complication of diabetes,which is the leading cause of end-stage renal disease worldwide.Approximately 40%of individuals with diabetes develop diabetic kidney disease.At present,the most important drugs for diabetic kidney disease include renin-angiotensin-aldosterone system inhibitors,angiotensin receptor blockers,sodium-glucose cotransporter-2 inhibitors,and newly approved aldosterone receptor antagonists.However,to date,there are still no effective drugs to prevent diabetic kidney disease from progressing to end-stage renal disease.Network pharmacology combined with bioinformatics and pharmacology provides a powerful tool for studying the mechanism of drug action.Traditional Chinese medicine has accumulated rich experience in the treatment of diabetic kidney disease,and its multi-target,multi-component,and multi-pathway characteristics provide new ideas for modern medicine.This article reviews the research progress of network pharmacology and drug therapy in diabetic kidney disease.展开更多
Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific...Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific animal models induced by inflammatory cytokines.This study introduces a novel mouse model of PD driven by the proinflammatory cytokine CXCL1,identified in our previous research.The involvement of CXCL1 in PD pathogenesis was validated using subacute and chronic MPTP-induced mouse models.Based on these findings,2-month-old C57BL/6J mice were intravenously administered CXCL1(20 ng/kg/day)for 2 weeks(5 days per week),successfully replicating motor deficits and pathological alterations in the substantia nigra observed in the chronic MPTP model.These results demonstrate the potential of CXCL1-induced inflammation as a mechanism for PD modeling.The model revealed activation of the PPAR signaling pathway in CXCL1-mediated neuronal damage by CXCL1.Linoleic acid,a PPAR-γactivator,significantly mitigated MPTPand CXCL1-induced toxicity and reduced serum CXCL1levels.In addition,the CXCL1-injected mouse model shortened the timeline for developing chronic PD mouse model to 2 weeks,offering an efficient platform for studying inflammation-driven processes in PD.The findings provide critical insights into the inflammatory mechanisms underlying PD and identify promising therapeutic targets for intervention.展开更多
Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory...Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.展开更多
Modern lifestyle and diet have increased the incidence rate of uric acid(UA)metabolism-related diseases like hyperuricemia(HUA)and gout,posing heavy economic burden to individual patients and their families and the so...Modern lifestyle and diet have increased the incidence rate of uric acid(UA)metabolism-related diseases like hyperuricemia(HUA)and gout,posing heavy economic burden to individual patients and their families and the society.UA metabolism is a complex physiological process involving the kidney,intestine,and other organs.A number of factors together regulate UA metabolism,including genetics,diet,hormones,and the gut microbiota.This review summaries the gut microbiota features in subjects with HUA and gout,and the therapeutic effects of implementing microecological therapies(probiotics,prebiotics,or fecal microbiota transplant)that target modulate the gut microbiota and its downstream metabolism on the disease.Current evidence shows that these strategies are safe and promising in alleviate inflammation,reduce UA,and restoring a healthy gut microbiota in subjects with UA metabolism-related diseases.However,most clinical data are generated by animal studies.Therefore,we propose that vigorous human intervention trials should be conducted in the future to evaluate the therapeutic effects of microecological therapies in managing HUA and gout.展开更多
Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic target...Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERαand ferroptosis.TXD activates the ERαsignaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treatment,particularly in older female patients who may benefit from its therapeutic outcomes.展开更多
Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an i...Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.展开更多
Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early sta...Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early stages often lacks noticeable symptoms, making it challenging to detect. Near-infrared II (NIR-II) fluorescence microscopic imaging obtains long wavelength, which enables reduced scattering, high spatial resolution and minimal autofluorescence, it is also a favorable imaging method for tumor diagnosis. PbS@CdS quantum dots (QDs) are one of the popular NIR-II fluorescence nanoprobes for well brightness. In this study, NIR-II emissive PbS@CdS QDs were utilized and further encapsulated with thiol-terminated poly(ethylene oxide) (SH-PEG, MW = 5000) to form PbS@CdS@PEG QDs nanoparticles (NPs). The obtained PbS@CdS@PEG QDs NPs were then characterized and further studied in detail. The PbS@CdS@PEG QDs NPs had large absorption spectra, exhibited strong NIR-II fluorescence emission at approximately 1300nm, and possessed good NIR-II fluorescence properties. Then, the mice model of early-stage brain metastases of TNBC was established, and the PbS@CdS@PEG QDs NPs were injected into the tumor-bearing mice for NIR-II fluorescence microscopic bioimaging. The brain vessels and tumors of the living mice were detected with high spatial resolution under the NIR-II fluorescence microscopic imaging system with irradiation of 808nm laser. The tumor tissues were further restricted and prepared as thin slices. The NIR-II fluorescence signals were collected from the tumor slices with high spatial resolution and signal-to-background ratio (SBR). Thus, the PbS@CdS@PEG QDs NPs-assisted NIR-II fluorescence microscopic system can effectively achieve targeting brain metastases of TNBC imaging, offering a novel and promising approach for TNBC-specific diagnosis.展开更多
BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-assoc...BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.展开更多
BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has...BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.展开更多
Background and Aims:Multiple regulatory mechanisms play an important role in arsenic-induced liver injury.To investigate whether histone H3 lysine 4(H3K4)methyltransferase(SET7/9)and histone H3K4 demethyltransferase(L...Background and Aims:Multiple regulatory mechanisms play an important role in arsenic-induced liver injury.To investigate whether histone H3 lysine 4(H3K4)methyltransferase(SET7/9)and histone H3K4 demethyltransferase(LSD1/KDM1A)can regulate endoplasmic reticulum stress(ERS)-related apoptosis by modulating the changes of H3K4 methylations in liver cells treated with arsenic.Methods:Apoptosis,proliferation and cell cycles were quantified by flow cytometry and real-time cell analyzer.The expression of ERS-and epigenetic-related proteins was detected by Western blot analysis.The antisense SET7/9 expression vector and the overexpressed LSD1 plasmid were used for transient transfection of LO_(2) cells.The effects of NaAsO_(2) on the methylation of H3 in the promoter regions of 78 kDa glucose-regulated protein,activating transcription factor 4 and C/EBP-homologous protein were evaluated by chromatin immunoprecipitation assay.Results:The protein expression of LSD1(1.25±0.08 vs.1.77±0.08,p=0.02)was markedly decreased by treatment with 100μM NaAsO_(2),whereas the SET7/9(0.68±0.05 vs.1.10±0.13,p=0.002)expression level was notably increased,which resulted in increased H3K4me1/2(0.93±0.64,1.19±0.22 vs.0.71±0.13,0.84±0.13,p=0.03 and p=0.003).After silencing SET7/9 and overexpressing LSD1 by transfection,apoptosis rate(in percentage:3.26±0.34 vs.7.04±0.42,4.80±0.32 vs.7.52±0.38,p=0.004 and p=0.02)was significantly decreased and proliferation rate was notably increased,which is reversed after inhibiting LSD1(in percentage:9.31±0.40 vs.7.52±0.38,p=0.03).Furthermore,the methylation levels of H3 in the promoter regions of GRP78(20.80±2.40 vs.11.75±2.47,20.46±2.23 vs.14.37±0.91,p=0.03 and p=0.01)and CHOP(48.67±4.04 vs.16.67±7.02,59.33±4.51 vs.20.67±3.06,p=0.004 and p=0.001)were significantly increased in LO_(2) cells exposed to 100μM NaAsO_(2) for 24 h.Conclusions:Histone methyltransferase SET7/9 and histone demethyltransferase LSD1 jointly regulate the changes of H3K4me1/me2 levels in arsenic-induced apoptosis.NaAsO_(2) induces apoptosis in LO_(2) cells by activating the ERS-mediated apoptotic signaling pathway,at least partially by enhancing the methylation of H3 on the promoter regions of ERS-associated genes,including GRP78 and CHOP.展开更多
BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of gr...BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.展开更多
The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary...The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.展开更多
BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metas...BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.展开更多
BACKGROUND The optimal approach for managing hepatic hemangioma is controversial.AIM To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience.MET...BACKGROUND The optimal approach for managing hepatic hemangioma is controversial.AIM To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience.METHODS A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018.Patients were classified into four groups based on the clinical grading system and treatment:(1)Observation group with score<4(Obs score<4);(2)Surgical group with score<4(Sur score<4);(3)Observation group with score≥4(Obs score≥4);and(4)Surgical group with score≥4(Sur score≥4).The clinico-pathological index and outcomes were evaluated.RESULTS There were significantly fewer symptomatic patients in surgical groups(Sur score≥4 vs Obs score≥4,P<0.001;Sur score<4 vs Obs score<4,χ^(2)=8.60,P=0.004;Sur score≥4 vs Obs score<4,P<0.001).The patients in Sur score≥4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score≥4(P<0.001;P<0.001).Nevertheless,there was no significant difference in need for intervention and total patients with adverse event between the Sur score<4 and Obs score<4(P>0.05;χ^(2)=1.68,P>0.05).CONCLUSION This clinical grading system appeared as a practical tool for hepatic hemangioma.Surgery can be suggested for patients with a score≥4.For those with<4,follow-up should be proposed.展开更多
BACKGROUND The bacterium Eikenella,classified as a gram-negative member of the phylum Proteobacteria,is distinguished by its rarity,corrosive nature,facultative anaerobic properties,and conditional pathogenicity.It re...BACKGROUND The bacterium Eikenella,classified as a gram-negative member of the phylum Proteobacteria,is distinguished by its rarity,corrosive nature,facultative anaerobic properties,and conditional pathogenicity.It represents the sole species within its genus-Eikenella corrodens(E.corrodens)-and can be found colonizing both human and animal oral and nasopharyngeal regions.Additionally,it occasionally inhabits the gastrointestinal or urogenital tracts.However,its slow growth rate can be attributed to its high nutritional requirements.However,there is an uneven distribution of construction and diagnostic capacity in China which poses undeniable challenges for the clinical examination and analysis of this case,especially in the basic hospitals.CASE SUMMARY Here we presented a case of empyema associated with E.corrodens infection in a 67-year-old male patient without any previous history of infectious diseases in our primary hospital in Dongguan district of China.The patient was admitted due to recurrent worsening cough,sputum production,and dyspnea for 3 d,which had persisted for over 20 years.Moreover,the patient experienced a onehour episode of unconsciousness.Upon admission,immediate comprehensive examinations were conducted on the patient which subsequently led to his admission to the intensive care unit.Meanwhile,the patient presented with drowsiness and profuse sweating along with bilateral conjunctival edema observed during initiation of non-invasive ventilation,suggesting empyema.A significant amount of coffee-colored malodorous pleural fluid was drained during the procedure above and sent to the laboratory department for inspection.Finally,laboratory culture results confirmed the presence of E.corrodens infection in the pleural fluid sample.The patient received antimicrobial therapy until died on day 22 in the hospital.CONCLUSION In this report,we presented a case of empyema associated with E.corrodens infection.Multiple courses of morphological examination,viable culture analysis,and biochemical identification revealed its difficulties in detecting distinctive characteristics,as well as a detection model worth promoting.It’s just that there were still certain deficiencies in terms of morphological assessment,biochemical identification,and drug susceptibility testing.展开更多
文摘In this comprehensive evidence-based analysis of ulcerative colitis(UC),a causal role is identified for colonic epithelial hydrogen peroxide(H_(2)O_(2))in both the pathogenesis and relapse of this debilitating inflammatory bowel disease.Studies have shown that H_(2)O_(2) production is significantly increased in the non-inflamed colonic epithelium of individuals with UC.H_(2)O_(2) is a powerful neutrophilic chemo-tactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular“trail”that attracts adjacent intra-vascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC.A novel therapy aimed at removing the inappropriate H_(2)O_(2) mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one(biopsy-proven)histologic remission lasting 14 years to date.The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H_(2)O_(2) mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease.Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects.It is the aim of this paper to present experimental and clinical evidence that identifies H_(2)O_(2) produced by the colonic epithelium as the causal agent in the pathogenesis of UC.A detailed explanation of a novel therapeutic intervention to normalize colonic H_(2)O_(2),its rationale,components,and formulation is also provided.
文摘Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that “avoid” control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.
基金supported by NSFC Projects of International Cooperation and Exchanges(NO.81720108004)National Natural Science Foundation of China(NO.81974019)+5 种基金The Research Team Project of Natural Science Foundation of Guangdong Province of China(NO.2017A030312007)Science and Technology Planning Project of Guangdong Province(NO.2022B1212010010)The key program of guangzhou science research plan(NO.201904020047)The Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(NO.DFJH201812NO.KJ012019119NO.KJ012019423.)
文摘Over the last few years,neuro-cardiology has grown the awareness of the relationship between the brain and the heart,contributing to developing a modern interdisciplinary field of neuro-cardiology.To enhance the awareness of the relationship between the brain and the heart,we concentrate on the brain function disability that results from cardiac dysfunction and the brain function impairment that results from cardiac dysfunction.It is usual for patients with cerebral ischemia to be preceded by cardiac impairment.The main triggers of cerebral ischemia involve arrhythmia,atrial fibrillation,etc.,reflecting a strong connection between the heart and the brain.Cerebral ischemia is linked to how the heart and brain communicate and affect each other at the pathophysiological stage.The formation of the heart-brain axis mechanism is important in its incidence and growth.The analysis explores the etiology and pathogenesis of cerebral ischemia centered on the heart-brain axis neuronal pathway and the mechanism of the relationship between the heart and brain,which offers important enrichment to the hypothesis of combined care of brain and heart and is extremely useful for gaining new knowledge for research and production of multi-target drugs for the prevention and treatment of cerebral ischemia.
文摘Introduction Overweight and obesity are usually measured using body mass index(BMI),with overweight classifying as a BMI of 25-29.9 kg/m^(2),obesity as a BMI of≥30 kg/m^(2),and morbid obesity as a BMI of≥40 kg/m^(2).1 Overweight and obesity are major health crises,posing a threat to the current global health progress.2 In 2021,3.71 million deaths and 129 million disability-adjusted life-years(DALYs)were attributable to overweight and obesity.
文摘Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.
文摘Objective Diabetic kidney disease is a serious complication of diabetes,which is the leading cause of end-stage renal disease worldwide.Approximately 40%of individuals with diabetes develop diabetic kidney disease.At present,the most important drugs for diabetic kidney disease include renin-angiotensin-aldosterone system inhibitors,angiotensin receptor blockers,sodium-glucose cotransporter-2 inhibitors,and newly approved aldosterone receptor antagonists.However,to date,there are still no effective drugs to prevent diabetic kidney disease from progressing to end-stage renal disease.Network pharmacology combined with bioinformatics and pharmacology provides a powerful tool for studying the mechanism of drug action.Traditional Chinese medicine has accumulated rich experience in the treatment of diabetic kidney disease,and its multi-target,multi-component,and multi-pathway characteristics provide new ideas for modern medicine.This article reviews the research progress of network pharmacology and drug therapy in diabetic kidney disease.
基金supported by the National Natural Science Foundation of China (32471049,32170984,32471188,32200802)Natural Science Foundation of Shandong Province (ZR2023QH110)。
文摘Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific animal models induced by inflammatory cytokines.This study introduces a novel mouse model of PD driven by the proinflammatory cytokine CXCL1,identified in our previous research.The involvement of CXCL1 in PD pathogenesis was validated using subacute and chronic MPTP-induced mouse models.Based on these findings,2-month-old C57BL/6J mice were intravenously administered CXCL1(20 ng/kg/day)for 2 weeks(5 days per week),successfully replicating motor deficits and pathological alterations in the substantia nigra observed in the chronic MPTP model.These results demonstrate the potential of CXCL1-induced inflammation as a mechanism for PD modeling.The model revealed activation of the PPAR signaling pathway in CXCL1-mediated neuronal damage by CXCL1.Linoleic acid,a PPAR-γactivator,significantly mitigated MPTPand CXCL1-induced toxicity and reduced serum CXCL1levels.In addition,the CXCL1-injected mouse model shortened the timeline for developing chronic PD mouse model to 2 weeks,offering an efficient platform for studying inflammation-driven processes in PD.The findings provide critical insights into the inflammatory mechanisms underlying PD and identify promising therapeutic targets for intervention.
基金supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。
文摘Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.
基金the National Natural Science Foundation of China(32325040)the Research Fund for the National Key R&D Program of China(2022YFD2100700).
文摘Modern lifestyle and diet have increased the incidence rate of uric acid(UA)metabolism-related diseases like hyperuricemia(HUA)and gout,posing heavy economic burden to individual patients and their families and the society.UA metabolism is a complex physiological process involving the kidney,intestine,and other organs.A number of factors together regulate UA metabolism,including genetics,diet,hormones,and the gut microbiota.This review summaries the gut microbiota features in subjects with HUA and gout,and the therapeutic effects of implementing microecological therapies(probiotics,prebiotics,or fecal microbiota transplant)that target modulate the gut microbiota and its downstream metabolism on the disease.Current evidence shows that these strategies are safe and promising in alleviate inflammation,reduce UA,and restoring a healthy gut microbiota in subjects with UA metabolism-related diseases.However,most clinical data are generated by animal studies.Therefore,we propose that vigorous human intervention trials should be conducted in the future to evaluate the therapeutic effects of microecological therapies in managing HUA and gout.
基金supported by the National Natural Science Foundation of China (No. 8196140154)the Natural Science Foundation of Xinjiang Uygur Autonomous Region (Nos.2023D01C139 and 2023D01C63)the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund (No. SKL-HIDCA-2020-8)。
文摘Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERαand ferroptosis.TXD activates the ERαsignaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treatment,particularly in older female patients who may benefit from its therapeutic outcomes.
基金supported by the National Natural Science Foundation of China(32171131,32371013,82071429,82471274,and 32371181)Shandong Province Natural Science Foundation(2021ZDSYS11,ZR2019ZD31,and ZR2022MC098)the Taishan Scholars Construction Project.
文摘Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
基金supported by the National Natural Science Foundation of China(NSFC)under Grant Nos.62035011,82202220 and 82060326State Key Laboratory of Pathogenesis,Prevention and treat ment of High Incident Diseases in central Asia(Nos.SKL-HIDCA-2022-3 and SKL-HIDCA-2022-GJ1)+3 种基金the Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Program(No.2022E02130)Xinjiang Uygur Autonomous Region Natural Sci ence Foundation Key Project(No.2022D01D40)Outstanding Youth Project(2023D01E06)Y.Gao and C.Zhang authors contributed equally to this work.
文摘Triple-negative breast cancer (TNBC) is an aggressive and often fatal disease, especially since the brain metastasis of TNBC has been a particularly severe manifestation. However, brain metastasis in TNBC at early stages often lacks noticeable symptoms, making it challenging to detect. Near-infrared II (NIR-II) fluorescence microscopic imaging obtains long wavelength, which enables reduced scattering, high spatial resolution and minimal autofluorescence, it is also a favorable imaging method for tumor diagnosis. PbS@CdS quantum dots (QDs) are one of the popular NIR-II fluorescence nanoprobes for well brightness. In this study, NIR-II emissive PbS@CdS QDs were utilized and further encapsulated with thiol-terminated poly(ethylene oxide) (SH-PEG, MW = 5000) to form PbS@CdS@PEG QDs nanoparticles (NPs). The obtained PbS@CdS@PEG QDs NPs were then characterized and further studied in detail. The PbS@CdS@PEG QDs NPs had large absorption spectra, exhibited strong NIR-II fluorescence emission at approximately 1300nm, and possessed good NIR-II fluorescence properties. Then, the mice model of early-stage brain metastases of TNBC was established, and the PbS@CdS@PEG QDs NPs were injected into the tumor-bearing mice for NIR-II fluorescence microscopic bioimaging. The brain vessels and tumors of the living mice were detected with high spatial resolution under the NIR-II fluorescence microscopic imaging system with irradiation of 808nm laser. The tumor tissues were further restricted and prepared as thin slices. The NIR-II fluorescence signals were collected from the tumor slices with high spatial resolution and signal-to-background ratio (SBR). Thus, the PbS@CdS@PEG QDs NPs-assisted NIR-II fluorescence microscopic system can effectively achieve targeting brain metastases of TNBC imaging, offering a novel and promising approach for TNBC-specific diagnosis.
基金National Natural Science Foundation of China,No.32260089Science and Technology Research Foundation of Guizhou Province,No.QKHJC-ZK(2022)YB642+3 种基金Science and Technology Research Foundation of Hubei Province,No.2022BCE030Science and Technology Research Foundation of Changzhou City,No.CE20225040Science and Technology Research Foundation of Zunyi City,No.ZSKHHZ(2022)344 and No.ZSKHHZ(2022)360WBE Liver Fibrosis Foundation,No.CFHPC2025028.
文摘BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.
基金Supported by Baoding Science and Technology Plan Project,No.2272P011Hebei Province Scientific Research Project,No.20241734Hebei Natural Science Foundation Project,No.H2024104011.
文摘BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.
基金The present study was supported by the National Natural Science Foundation of China(Grant No.81100284)Guizhou Science and Technology Cooperation Platform Personnel[2018](Grant No.5779-10,5779-19)Science and Technology Foundation of Guizhou Province(Grant No.ZK[2021]-364)。
文摘Background and Aims:Multiple regulatory mechanisms play an important role in arsenic-induced liver injury.To investigate whether histone H3 lysine 4(H3K4)methyltransferase(SET7/9)and histone H3K4 demethyltransferase(LSD1/KDM1A)can regulate endoplasmic reticulum stress(ERS)-related apoptosis by modulating the changes of H3K4 methylations in liver cells treated with arsenic.Methods:Apoptosis,proliferation and cell cycles were quantified by flow cytometry and real-time cell analyzer.The expression of ERS-and epigenetic-related proteins was detected by Western blot analysis.The antisense SET7/9 expression vector and the overexpressed LSD1 plasmid were used for transient transfection of LO_(2) cells.The effects of NaAsO_(2) on the methylation of H3 in the promoter regions of 78 kDa glucose-regulated protein,activating transcription factor 4 and C/EBP-homologous protein were evaluated by chromatin immunoprecipitation assay.Results:The protein expression of LSD1(1.25±0.08 vs.1.77±0.08,p=0.02)was markedly decreased by treatment with 100μM NaAsO_(2),whereas the SET7/9(0.68±0.05 vs.1.10±0.13,p=0.002)expression level was notably increased,which resulted in increased H3K4me1/2(0.93±0.64,1.19±0.22 vs.0.71±0.13,0.84±0.13,p=0.03 and p=0.003).After silencing SET7/9 and overexpressing LSD1 by transfection,apoptosis rate(in percentage:3.26±0.34 vs.7.04±0.42,4.80±0.32 vs.7.52±0.38,p=0.004 and p=0.02)was significantly decreased and proliferation rate was notably increased,which is reversed after inhibiting LSD1(in percentage:9.31±0.40 vs.7.52±0.38,p=0.03).Furthermore,the methylation levels of H3 in the promoter regions of GRP78(20.80±2.40 vs.11.75±2.47,20.46±2.23 vs.14.37±0.91,p=0.03 and p=0.01)and CHOP(48.67±4.04 vs.16.67±7.02,59.33±4.51 vs.20.67±3.06,p=0.004 and p=0.001)were significantly increased in LO_(2) cells exposed to 100μM NaAsO_(2) for 24 h.Conclusions:Histone methyltransferase SET7/9 and histone demethyltransferase LSD1 jointly regulate the changes of H3K4me1/me2 levels in arsenic-induced apoptosis.NaAsO_(2) induces apoptosis in LO_(2) cells by activating the ERS-mediated apoptotic signaling pathway,at least partially by enhancing the methylation of H3 on the promoter regions of ERS-associated genes,including GRP78 and CHOP.
文摘BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.
基金supported by the National Key Research and Development Program of China(2022YFC2303401,2022YFC2304100,2016YFD0500301,2021YFC0863300)the Beijing Science and Technology Plan(Z211100002521017)the National Natural Science Foundation of China(82241080)。
文摘The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.
文摘BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.
文摘BACKGROUND The optimal approach for managing hepatic hemangioma is controversial.AIM To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience.METHODS A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018.Patients were classified into four groups based on the clinical grading system and treatment:(1)Observation group with score<4(Obs score<4);(2)Surgical group with score<4(Sur score<4);(3)Observation group with score≥4(Obs score≥4);and(4)Surgical group with score≥4(Sur score≥4).The clinico-pathological index and outcomes were evaluated.RESULTS There were significantly fewer symptomatic patients in surgical groups(Sur score≥4 vs Obs score≥4,P<0.001;Sur score<4 vs Obs score<4,χ^(2)=8.60,P=0.004;Sur score≥4 vs Obs score<4,P<0.001).The patients in Sur score≥4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score≥4(P<0.001;P<0.001).Nevertheless,there was no significant difference in need for intervention and total patients with adverse event between the Sur score<4 and Obs score<4(P>0.05;χ^(2)=1.68,P>0.05).CONCLUSION This clinical grading system appeared as a practical tool for hepatic hemangioma.Surgery can be suggested for patients with a score≥4.For those with<4,follow-up should be proposed.
基金Supported by the National Science Foundation of China(NSFC),No.81703846Dongguan Science and Technology of Social Development Program,No.20231800940062,No.20231800937142,No.20231800904242,No.20231800904232+1 种基金Doctoral Research Foundation of Binhaiwan Central Hospital in Dongguan,No.BS2023001First Batch of Young Medical Professionals award by the 2018 Tianjin Health Commission.
文摘BACKGROUND The bacterium Eikenella,classified as a gram-negative member of the phylum Proteobacteria,is distinguished by its rarity,corrosive nature,facultative anaerobic properties,and conditional pathogenicity.It represents the sole species within its genus-Eikenella corrodens(E.corrodens)-and can be found colonizing both human and animal oral and nasopharyngeal regions.Additionally,it occasionally inhabits the gastrointestinal or urogenital tracts.However,its slow growth rate can be attributed to its high nutritional requirements.However,there is an uneven distribution of construction and diagnostic capacity in China which poses undeniable challenges for the clinical examination and analysis of this case,especially in the basic hospitals.CASE SUMMARY Here we presented a case of empyema associated with E.corrodens infection in a 67-year-old male patient without any previous history of infectious diseases in our primary hospital in Dongguan district of China.The patient was admitted due to recurrent worsening cough,sputum production,and dyspnea for 3 d,which had persisted for over 20 years.Moreover,the patient experienced a onehour episode of unconsciousness.Upon admission,immediate comprehensive examinations were conducted on the patient which subsequently led to his admission to the intensive care unit.Meanwhile,the patient presented with drowsiness and profuse sweating along with bilateral conjunctival edema observed during initiation of non-invasive ventilation,suggesting empyema.A significant amount of coffee-colored malodorous pleural fluid was drained during the procedure above and sent to the laboratory department for inspection.Finally,laboratory culture results confirmed the presence of E.corrodens infection in the pleural fluid sample.The patient received antimicrobial therapy until died on day 22 in the hospital.CONCLUSION In this report,we presented a case of empyema associated with E.corrodens infection.Multiple courses of morphological examination,viable culture analysis,and biochemical identification revealed its difficulties in detecting distinctive characteristics,as well as a detection model worth promoting.It’s just that there were still certain deficiencies in terms of morphological assessment,biochemical identification,and drug susceptibility testing.
