Objective:To compare the therapeutic efficacy of intravenous pantoprazole and famotidine for the treatment of epigastric pain in patients presenting to the emergency department.Methods:In this triple-blind randomized ...Objective:To compare the therapeutic efficacy of intravenous pantoprazole and famotidine for the treatment of epigastric pain in patients presenting to the emergency department.Methods:In this triple-blind randomized clinical trial,eligible patients presenting with epigastric pain were randomly assigned to receive intravenous pantoprazole or famotidine.Block randomization was used,and patients,treating physicians,and outcome assessors were blinded to treatment allocation.Pain intensity was assessed at baseline and at 30 and 60 minutes after drug administration.Results:Eighty patients were enrolled,with a mean age of 36.6 years(SD,15.0),and 42.5%were male.Mean pain scores decreased significantly over time in both treatment groups.In the pantoprazole group,pain scores declined from 8.02±1.28 at baseline to 4.75±1.31 at 30 minutes and 1.62±1.29 at 60 minutes,whereas in the famotidine group scores decreased from 8.12±1.48 to 5.37±1.23 and 2.35±1.54,respectively.There was no significant difference in baseline pain scores between groups(P=.92).Pantoprazole resulted in greater pain reduction compared with famotidine at both 30 minutes(P=.04)and 60 minutes(P=.05).Conclusions:Both medications were effective in relieving epigastric pain;however,pantoprazole provided greater and more sustained pain reduction,supporting its preferential use in emergency settings.展开更多
Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA...Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.展开更多
Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological me...Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.展开更多
Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles ...Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid,multiplexed shunting and regulation of sensory signals.This specialized geometry enables separation,filtering,and feedback regulation of neuronal signals,thereby coordinating peripheral and central responses at multiple levels.Recent advances,including spatial transcriptomics,single-cell sequencing,super-resolution microscopy,organoid models,and novel electrophysiological methods,have permitted more precise dissection of the T-junction's molecular composition,ion-channel distribution,and electrophysiological properties.Here,we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks,and we detail its functional alterations in both physiological signaling and pathological pain states,with particular emphasis on ion-channel modulation,signal attenuation,and selective transmission mechanisms.Finally,we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies,aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.展开更多
Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with m...Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with meningitis symptoms at a referral hospital in Mersin,Turkey,between January 2019 and January 2022.Clinical findings and laboratory results,including leukocyte count,C-reactive protein(CRP),and procalcitonin levels in blood,were examined.Logistic regression,Chi square test,and receiver operating characteristics(ROC)curve analyses assessed the predictive value of these parameters.Results:A total of 199 participants were included in the study;99 patients were diagnosed with meningitis after lumbar puncture and 100 served as controls.Patients with meningitis exhibited significantly higher leukocyte counts(median:11890×10^(3)/μL vs.7905×10^(3)/μL,P<0.001)and CRP levels(median:6.00 mg/dL vs.0.95 mg/dL,P<0.001)compared to controls.Procalcitonin levels were significantly elevated in meningitis patients(median:0.21 ng/mL vs.0.10 ng/mL,P<0.001).Logistic regression identified albumin(OR=0.16,95%CI=0.06-0.40),and CRP(OR=1.18,95%CI=1.08-1.28)as independent predictors of meningitis.ROC analysis for CRP demonstrated a sensitivity of 80.6%and specificity of 70.0%at a cut-off value of 2.23 mg/dL(AUC=0.792).Conclusions:Elevated albumin levels and CRP contents in the blood were significant predictors of meningitis in emergency service.Early identification of predictive markers may aid in timely lumbar puncture and management of atypical cases.展开更多
We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As...We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As emergency medicine clinicians,we frequently encounter diverse and complex cases,and such rare conditions pose significant challenges in the diagnostic process.This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.展开更多
Introduction: Uterine fibroids are benign tumors that develop from the connective and muscular tissues of the uterus. Common among African-American women, patients suffering from them often arrive late to the hospital...Introduction: Uterine fibroids are benign tumors that develop from the connective and muscular tissues of the uterus. Common among African-American women, patients suffering from them often arrive late to the hospital in our African regions. This study aimed to investigate the knowledge and perception of uterine fibroids among women who came to the gynecology-obstetrics department of the Regional Hospital Center (CHR) Tsévié. Methodology: It was a cross-sectional descriptive study, with data collection conducted from May 7th to 20th, 2024, using systematic sampling. The study included all women present in the Gynecology-Obstetrics Department of CHR Tsévié during the study period who willingly and informedly consented to participate in the survey. Results: 362 women participated in the study. Among them, 36.8% had a secondary level, and 72.9% were Christians. About 97.5% had heard of uterine fibroids. In 63.5% of cases, their entourage was the principal source of information. The diagnostic methods mentioned by the women were ultrasound in 94.6% of cases, while prayers and occultism were also cited in 28% and 33.3% of cases, respectively. While 91.9% of the women considered the hospital, the place for treatment, some indicated that treatment would require plant-based approaches (46.8%) and prayers (26%). The cost of treatment was an obstacle for 85.4% of women, and 61.3% expressed fear of dying during surgery. There was a statistically significant relationship between treatment choice and religion. Conclusion: The majority of women had heard of uterine fibroids but had incorrect information about the treatment.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Introduction: The therapeutic approach to benign prostatic hyperplasia (BPH) has evolved profoundly. Surgical treatment is reserved for complicated cases and the reference surgical technique is transurethral resection...Introduction: The therapeutic approach to benign prostatic hyperplasia (BPH) has evolved profoundly. Surgical treatment is reserved for complicated cases and the reference surgical technique is transurethral resection of the prostate (TURP). This work aims to study the epidemiological, clinical and therapeutic aspects of monopolar transurethral resection of the prostate in our department. Materials and Methods: We conducted a descriptive study with retrospective data collection over a 12-month period from November 1, 2023 to December 31, 2024. The urology unit, an integral part of the surgery department, of the Sino-Guinean Friendship Hospital in Conakry served as the setting for this study. It included 27 patients with benign prostatic hypertrophy treated surgically by monopolar transurethral resection and having a usable medical record. The parameters studied were epidemiological, clinics and therapeutic. Results: The mean age of the patients was 68.57 ± 5.7 years with extremes from 50 to 79 years. The peak frequency was observed between 70 and 79 years (48.15%). All our patients had lower urinary tract disorders, i.e. 100% of cases. On digital rectal examination, an increase in the volume of the prostate of benign appearance was observed in all cases. The mean prostate volume was 43.7 cc on ultrasound with extremes from 34 cc to 58 cc. The total PSA level was less than 4 ng/ml in the majority of cases. The postoperative course was generally uncomplicated (n = 26) with removal of the urinary catheter on the second postoperative day (D2). However, one peroperative complication was observed in one patient;it was a bladder breach, leading to the passage of glycine into the peritoneum. Conclusion: Transurethral resection of the prostate has reduced the length of hospital stay of our patients, as well as the comorbidities associated with the treatment. The complications associated with it are rare but potentially serious. Its performance requires in-depth mastery of the endoscopic anatomy of the lower urinary tract as well as technical operative expertise.展开更多
Introduction: Urethral prolapse, a rare benign lesion of the female urethra, is considered unusual in children, but it is far from exceptional in girls aged 18 to 24. African origin. The diagnosis is clinical but can ...Introduction: Urethral prolapse, a rare benign lesion of the female urethra, is considered unusual in children, but it is far from exceptional in girls aged 18 to 24. African origin. The diagnosis is clinical but can be overlooked or confused with other pathologies. Treatment remains controversial. The aim of this work is to study the epidemiological, clinical and therapeutic data of urethral mucosal prolapse in young girls in our department. Materials and methods: Retrospective and descriptive study on urethral mucosal prolapse in little girls identified from the hospitalization records of the Sino-Guinean Friendship Hospital in Conakry. The study period was 5 years. Patients were selected randomly. Outcome assessment focused on the occurrence of recurrences and urinary incontinence. The mean follow-up duration was 24 months. The parameters studied were: Age, clinical and histological findings, therapeutic data and patient outcomes. Results: The incidence of urethral mucosal prolapse in girls in the urology department was 2.2 cases/year. The mean age of the patients was 6.7 years (with extremes of 5 months and 10 years). The age group of 7 to 10 years was the most represented, observed in 63.63% of patients. The most frequent reason for consultation was vulvar bleeding in 7 patients, or 63.63%. Malpighian hyperplasia with a congested chorion was the most observed histological type, in 4 patients. Surgical treatment consisting of complete excision of the prolapsed part had given excellent results. Conclusion: Urethral prolapse is a rare pathology, observed mainly in young black girls. Its diagnosis is based mainly on clinical examination. Surgical treatment gives satisfactory results, both clinically and aesthetically.展开更多
Introduction: Diabetic ketoacidosis (DKA) is the most common metabolic complication of diabetes. Although historically reported in children, it is increasingly observed in adults. Short-term outcomes and prognosis var...Introduction: Diabetic ketoacidosis (DKA) is the most common metabolic complication of diabetes. Although historically reported in children, it is increasingly observed in adults. Short-term outcomes and prognosis vary widely across healthcare settings. Therefore, we aimed to determine the prevalence, diagnostic characteristics, and outcomes of newly diagnosed diabetic ketoacidosis in a hospital setting in Dakar. Methodology: We conducted a descriptive and analytical cross-sectional study from January 1, 2020, to January 31, 2021, in the Endocrinology-Metabolism Department of the Pikine National Hospital Center. All diabetic patients hospitalized for newly diagnosed diabetic ketoacidosis during this period were included. Results: A total of 54 patients were enrolled in the study. The prevalence of newly diagnosed DKA in the facility was 17.1%. The mean age was 38.54 years, with a male predominance and a sex ratio of 1.16. Thirty-five patients had a family history of diabetes. Upon admission, 14.9% of patients had altered consciousness, and 92.4% exhibited cardinal symptoms, with an average duration of 14.2 days. Kussmaul breathing and gastrointestinal symptoms were observed in 13% and 33% of cases, respectively. The mean capillary blood glucose level at admission was 3.43 g/L. Infection was identified as the precipitating factor in half of the cases, while no triggering factor was found in the remaining cases. The mean BMI was 25.27 kg/m², and the average glycated hemoglobin (HbA1c) level was 12.2%. We recorded the diabetes classification for all patients. Nine had type 1 diabetes, twelve had type 1b diabetes, thirty-one had type 2 diabetes, and two had diabetes secondary to corticosteroid therapy. All patients received continuous intravenous insulin therapy via a syringe pump. The mean time to ketosis resolution was 34.6 hours. The average total dose of regular insulin administered was 442.3 IU. The mean duration of hospitalization was 7.6 days. One patient died, and fifty-one were discharged while continuing insulin therapy, with an average dose of 53 IU. Conclusion: The prevalence of newly diagnosed DKA remains high. With proper management, the prognosis is generally favorable. Diabetes classification is crucial, as it determines subsequent treatment strategies.展开更多
Laser wakefield accelerators(LWFAs)offer acceleration gradients up to 1000 times higher than those of conventional radio-frequency accelerators,offering a pathway to significantly more compact and cost-effective accel...Laser wakefield accelerators(LWFAs)offer acceleration gradients up to 1000 times higher than those of conventional radio-frequency accelerators,offering a pathway to significantly more compact and cost-effective accelerator systems.This breakthrough opens up new possibilities for laboratory-scale light sources.All-optical inverse Compton scattering(AOCS)sources driven by LWFAs produce high-brightness,quasimonochromatic X rays with micrometer-scale source sizes,delivering the spatial coherence and resolution required for X-ray phase-contrast imaging(XPCI).These features position AOCS X-ray sources as promising tools for applications in biology,medicine,physics,and materials science.However,previous AOCS-based imaging studies have primarily focused on X-ray absorption imaging.In this work,we report successful experimental demonstrations of edge-enhanced in-line XPCI using energy-tunable,quasi-monochromatic AOCS X rays.With a spatial resolution of~20μm,our results clearly show the potential of high-resolution,AOCS-based XPCI applications.展开更多
The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide associa...The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat...Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.展开更多
intramolecular tandem rearrangement for the synthesis of bicyclic furans is reported.The reaction was initiated by an intramolecular cross-coupling of the built-in alkynyl sulfoxide and alkynyl sulfide motifs in the p...intramolecular tandem rearrangement for the synthesis of bicyclic furans is reported.The reaction was initiated by an intramolecular cross-coupling of the built-in alkynyl sulfoxide and alkynyl sulfide motifs in the presence of BF_(3)·Et_(2)O,followed by a[3,3]-sigmatropic sulfonium rearrangement and 5-exo-dig cyclization,affording cycloalkano[c]furans as final products in moderate yields with 100% atom economy.The synthetic utility of the resulting furans has been demonstrated through late-stage diversification by utilizing the alkylthio groups or the furan rings.展开更多
Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading a...Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.展开更多
The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion...The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.展开更多
In order to explore the reduction pathways of zinc oxide in LiCl molten salt and the optimal process,experiments were conducted in an alumina crucible using metallic lithium as the reducing agent and lithium chloride ...In order to explore the reduction pathways of zinc oxide in LiCl molten salt and the optimal process,experiments were conducted in an alumina crucible using metallic lithium as the reducing agent and lithium chloride molten salt as the reaction medium at 923 K.The study assessed the effects of lithium thermochemical reduction and electrolytic reduction of ZnO.The volatilization behavior of metal oxides in molten salts,the equivalent of a reducing agent,reduction time,amount of molten salt,stirring time,and the method of reduction feed were investigated for their impacts on the reduction yield and product composition.X-ray powder diffraction(XRD)analysis of the products showed that lithium reduction of ZnO not only produced metallic Zn but also formed a LiZn alloy.Electrolytic reduction can be used to obtain the metallic Zn product by controlling the potential below-2.2 V(vs Ag/Ag^(+)).Moreover,sintered oxides and higher electrode potentials could enhance the efficiency of electrolysis.Under the optimal reaction conditions determined experimentally,the lithium reduction experiment achieved a yield of 77.2%after a 12-h test,and the electrolytic reduction reached a yield of 85.4%after a 6-h test.展开更多
Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Method...Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.展开更多
文摘Objective:To compare the therapeutic efficacy of intravenous pantoprazole and famotidine for the treatment of epigastric pain in patients presenting to the emergency department.Methods:In this triple-blind randomized clinical trial,eligible patients presenting with epigastric pain were randomly assigned to receive intravenous pantoprazole or famotidine.Block randomization was used,and patients,treating physicians,and outcome assessors were blinded to treatment allocation.Pain intensity was assessed at baseline and at 30 and 60 minutes after drug administration.Results:Eighty patients were enrolled,with a mean age of 36.6 years(SD,15.0),and 42.5%were male.Mean pain scores decreased significantly over time in both treatment groups.In the pantoprazole group,pain scores declined from 8.02±1.28 at baseline to 4.75±1.31 at 30 minutes and 1.62±1.29 at 60 minutes,whereas in the famotidine group scores decreased from 8.12±1.48 to 5.37±1.23 and 2.35±1.54,respectively.There was no significant difference in baseline pain scores between groups(P=.92).Pantoprazole resulted in greater pain reduction compared with famotidine at both 30 minutes(P=.04)and 60 minutes(P=.05).Conclusions:Both medications were effective in relieving epigastric pain;however,pantoprazole provided greater and more sustained pain reduction,supporting its preferential use in emergency settings.
基金supported by the Natural Science Foundation of Beijing Municipality(No.F252065)the National Natural Science Foundation of China(No.32271190,32571323)the STI 2030 Major Project(No.2021ZD0203202)。
文摘Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.
基金supported by the National Natural Science Foundation of China,No.82274304(to YH)the Major Clinical Study Projects of Shanghai Shenkang Hospital Development Center,No.SHDC2020CR2046B(to YH)Shanghai Municipal Health Commission Talent Plan,No.2022LJ010(to YH).
文摘Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.
基金supported by grant from the National Key Technology Support Program of the Ministry of Science and Technology of China(No.2021ZD0203204)。
文摘Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid,multiplexed shunting and regulation of sensory signals.This specialized geometry enables separation,filtering,and feedback regulation of neuronal signals,thereby coordinating peripheral and central responses at multiple levels.Recent advances,including spatial transcriptomics,single-cell sequencing,super-resolution microscopy,organoid models,and novel electrophysiological methods,have permitted more precise dissection of the T-junction's molecular composition,ion-channel distribution,and electrophysiological properties.Here,we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks,and we detail its functional alterations in both physiological signaling and pathological pain states,with particular emphasis on ion-channel modulation,signal attenuation,and selective transmission mechanisms.Finally,we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies,aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.
文摘Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with meningitis symptoms at a referral hospital in Mersin,Turkey,between January 2019 and January 2022.Clinical findings and laboratory results,including leukocyte count,C-reactive protein(CRP),and procalcitonin levels in blood,were examined.Logistic regression,Chi square test,and receiver operating characteristics(ROC)curve analyses assessed the predictive value of these parameters.Results:A total of 199 participants were included in the study;99 patients were diagnosed with meningitis after lumbar puncture and 100 served as controls.Patients with meningitis exhibited significantly higher leukocyte counts(median:11890×10^(3)/μL vs.7905×10^(3)/μL,P<0.001)and CRP levels(median:6.00 mg/dL vs.0.95 mg/dL,P<0.001)compared to controls.Procalcitonin levels were significantly elevated in meningitis patients(median:0.21 ng/mL vs.0.10 ng/mL,P<0.001).Logistic regression identified albumin(OR=0.16,95%CI=0.06-0.40),and CRP(OR=1.18,95%CI=1.08-1.28)as independent predictors of meningitis.ROC analysis for CRP demonstrated a sensitivity of 80.6%and specificity of 70.0%at a cut-off value of 2.23 mg/dL(AUC=0.792).Conclusions:Elevated albumin levels and CRP contents in the blood were significant predictors of meningitis in emergency service.Early identification of predictive markers may aid in timely lumbar puncture and management of atypical cases.
文摘We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As emergency medicine clinicians,we frequently encounter diverse and complex cases,and such rare conditions pose significant challenges in the diagnostic process.This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.
文摘Introduction: Uterine fibroids are benign tumors that develop from the connective and muscular tissues of the uterus. Common among African-American women, patients suffering from them often arrive late to the hospital in our African regions. This study aimed to investigate the knowledge and perception of uterine fibroids among women who came to the gynecology-obstetrics department of the Regional Hospital Center (CHR) Tsévié. Methodology: It was a cross-sectional descriptive study, with data collection conducted from May 7th to 20th, 2024, using systematic sampling. The study included all women present in the Gynecology-Obstetrics Department of CHR Tsévié during the study period who willingly and informedly consented to participate in the survey. Results: 362 women participated in the study. Among them, 36.8% had a secondary level, and 72.9% were Christians. About 97.5% had heard of uterine fibroids. In 63.5% of cases, their entourage was the principal source of information. The diagnostic methods mentioned by the women were ultrasound in 94.6% of cases, while prayers and occultism were also cited in 28% and 33.3% of cases, respectively. While 91.9% of the women considered the hospital, the place for treatment, some indicated that treatment would require plant-based approaches (46.8%) and prayers (26%). The cost of treatment was an obstacle for 85.4% of women, and 61.3% expressed fear of dying during surgery. There was a statistically significant relationship between treatment choice and religion. Conclusion: The majority of women had heard of uterine fibroids but had incorrect information about the treatment.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
文摘Introduction: The therapeutic approach to benign prostatic hyperplasia (BPH) has evolved profoundly. Surgical treatment is reserved for complicated cases and the reference surgical technique is transurethral resection of the prostate (TURP). This work aims to study the epidemiological, clinical and therapeutic aspects of monopolar transurethral resection of the prostate in our department. Materials and Methods: We conducted a descriptive study with retrospective data collection over a 12-month period from November 1, 2023 to December 31, 2024. The urology unit, an integral part of the surgery department, of the Sino-Guinean Friendship Hospital in Conakry served as the setting for this study. It included 27 patients with benign prostatic hypertrophy treated surgically by monopolar transurethral resection and having a usable medical record. The parameters studied were epidemiological, clinics and therapeutic. Results: The mean age of the patients was 68.57 ± 5.7 years with extremes from 50 to 79 years. The peak frequency was observed between 70 and 79 years (48.15%). All our patients had lower urinary tract disorders, i.e. 100% of cases. On digital rectal examination, an increase in the volume of the prostate of benign appearance was observed in all cases. The mean prostate volume was 43.7 cc on ultrasound with extremes from 34 cc to 58 cc. The total PSA level was less than 4 ng/ml in the majority of cases. The postoperative course was generally uncomplicated (n = 26) with removal of the urinary catheter on the second postoperative day (D2). However, one peroperative complication was observed in one patient;it was a bladder breach, leading to the passage of glycine into the peritoneum. Conclusion: Transurethral resection of the prostate has reduced the length of hospital stay of our patients, as well as the comorbidities associated with the treatment. The complications associated with it are rare but potentially serious. Its performance requires in-depth mastery of the endoscopic anatomy of the lower urinary tract as well as technical operative expertise.
文摘Introduction: Urethral prolapse, a rare benign lesion of the female urethra, is considered unusual in children, but it is far from exceptional in girls aged 18 to 24. African origin. The diagnosis is clinical but can be overlooked or confused with other pathologies. Treatment remains controversial. The aim of this work is to study the epidemiological, clinical and therapeutic data of urethral mucosal prolapse in young girls in our department. Materials and methods: Retrospective and descriptive study on urethral mucosal prolapse in little girls identified from the hospitalization records of the Sino-Guinean Friendship Hospital in Conakry. The study period was 5 years. Patients were selected randomly. Outcome assessment focused on the occurrence of recurrences and urinary incontinence. The mean follow-up duration was 24 months. The parameters studied were: Age, clinical and histological findings, therapeutic data and patient outcomes. Results: The incidence of urethral mucosal prolapse in girls in the urology department was 2.2 cases/year. The mean age of the patients was 6.7 years (with extremes of 5 months and 10 years). The age group of 7 to 10 years was the most represented, observed in 63.63% of patients. The most frequent reason for consultation was vulvar bleeding in 7 patients, or 63.63%. Malpighian hyperplasia with a congested chorion was the most observed histological type, in 4 patients. Surgical treatment consisting of complete excision of the prolapsed part had given excellent results. Conclusion: Urethral prolapse is a rare pathology, observed mainly in young black girls. Its diagnosis is based mainly on clinical examination. Surgical treatment gives satisfactory results, both clinically and aesthetically.
文摘Introduction: Diabetic ketoacidosis (DKA) is the most common metabolic complication of diabetes. Although historically reported in children, it is increasingly observed in adults. Short-term outcomes and prognosis vary widely across healthcare settings. Therefore, we aimed to determine the prevalence, diagnostic characteristics, and outcomes of newly diagnosed diabetic ketoacidosis in a hospital setting in Dakar. Methodology: We conducted a descriptive and analytical cross-sectional study from January 1, 2020, to January 31, 2021, in the Endocrinology-Metabolism Department of the Pikine National Hospital Center. All diabetic patients hospitalized for newly diagnosed diabetic ketoacidosis during this period were included. Results: A total of 54 patients were enrolled in the study. The prevalence of newly diagnosed DKA in the facility was 17.1%. The mean age was 38.54 years, with a male predominance and a sex ratio of 1.16. Thirty-five patients had a family history of diabetes. Upon admission, 14.9% of patients had altered consciousness, and 92.4% exhibited cardinal symptoms, with an average duration of 14.2 days. Kussmaul breathing and gastrointestinal symptoms were observed in 13% and 33% of cases, respectively. The mean capillary blood glucose level at admission was 3.43 g/L. Infection was identified as the precipitating factor in half of the cases, while no triggering factor was found in the remaining cases. The mean BMI was 25.27 kg/m², and the average glycated hemoglobin (HbA1c) level was 12.2%. We recorded the diabetes classification for all patients. Nine had type 1 diabetes, twelve had type 1b diabetes, thirty-one had type 2 diabetes, and two had diabetes secondary to corticosteroid therapy. All patients received continuous intravenous insulin therapy via a syringe pump. The mean time to ketosis resolution was 34.6 hours. The average total dose of regular insulin administered was 442.3 IU. The mean duration of hospitalization was 7.6 days. One patient died, and fifty-one were discharged while continuing insulin therapy, with an average dose of 53 IU. Conclusion: The prevalence of newly diagnosed DKA remains high. With proper management, the prognosis is generally favorable. Diabetes classification is crucial, as it determines subsequent treatment strategies.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0530000)the Discipline Construction Foundation of“Double World-class Project”.
文摘Laser wakefield accelerators(LWFAs)offer acceleration gradients up to 1000 times higher than those of conventional radio-frequency accelerators,offering a pathway to significantly more compact and cost-effective accelerator systems.This breakthrough opens up new possibilities for laboratory-scale light sources.All-optical inverse Compton scattering(AOCS)sources driven by LWFAs produce high-brightness,quasimonochromatic X rays with micrometer-scale source sizes,delivering the spatial coherence and resolution required for X-ray phase-contrast imaging(XPCI).These features position AOCS X-ray sources as promising tools for applications in biology,medicine,physics,and materials science.However,previous AOCS-based imaging studies have primarily focused on X-ray absorption imaging.In this work,we report successful experimental demonstrations of edge-enhanced in-line XPCI using energy-tunable,quasi-monochromatic AOCS X rays.With a spatial resolution of~20μm,our results clearly show the potential of high-resolution,AOCS-based XPCI applications.
基金supported by grants from the National Natural Science Foundation of China(Grant No.32470658)the National Key Research and Development Program of China(Grant Nos.2022YFC2502400 and 2022YFC2502402).
文摘The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by the Natural Science Foundation of Hunan Province (2022JJ30987)the Key Research and Development Project of Hunan Province (2024JK2107),China。
文摘Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.
基金Project supported by the National Natural Science Foundation of China(No.21971042)。
文摘intramolecular tandem rearrangement for the synthesis of bicyclic furans is reported.The reaction was initiated by an intramolecular cross-coupling of the built-in alkynyl sulfoxide and alkynyl sulfide motifs in the presence of BF_(3)·Et_(2)O,followed by a[3,3]-sigmatropic sulfonium rearrangement and 5-exo-dig cyclization,affording cycloalkano[c]furans as final products in moderate yields with 100% atom economy.The synthetic utility of the resulting furans has been demonstrated through late-stage diversification by utilizing the alkylthio groups or the furan rings.
文摘Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.
基金supported by the Russian Science Foundation(Grant No.24-25-20087 to V.K.)。
文摘The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.
文摘In order to explore the reduction pathways of zinc oxide in LiCl molten salt and the optimal process,experiments were conducted in an alumina crucible using metallic lithium as the reducing agent and lithium chloride molten salt as the reaction medium at 923 K.The study assessed the effects of lithium thermochemical reduction and electrolytic reduction of ZnO.The volatilization behavior of metal oxides in molten salts,the equivalent of a reducing agent,reduction time,amount of molten salt,stirring time,and the method of reduction feed were investigated for their impacts on the reduction yield and product composition.X-ray powder diffraction(XRD)analysis of the products showed that lithium reduction of ZnO not only produced metallic Zn but also formed a LiZn alloy.Electrolytic reduction can be used to obtain the metallic Zn product by controlling the potential below-2.2 V(vs Ag/Ag^(+)).Moreover,sintered oxides and higher electrode potentials could enhance the efficiency of electrolysis.Under the optimal reaction conditions determined experimentally,the lithium reduction experiment achieved a yield of 77.2%after a 12-h test,and the electrolytic reduction reached a yield of 85.4%after a 6-h test.
文摘Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.
