Objective: Serum from SSc patients was analyzed centrally to determine ANA patterns and extractable nuclear antigens (ENAs) between lcSSc and dcSSc and associations with organ involvement. Methods: 1145 SSc patients h...Objective: Serum from SSc patients was analyzed centrally to determine ANA patterns and extractable nuclear antigens (ENAs) between lcSSc and dcSSc and associations with organ involvement. Methods: 1145 SSc patients had ANA and ENA analyzed by indirect immunofluorescence on HEp-2 substrate at a screening serum dilution of 1/160. Most ENA antibodies [Sm. U1-RNP, Ro52, SS-A/Ro60, topoisomeraseI (Topo1), SS-B/La, chromatin, ribosomal P and Jo1] were measured by laser bead immunoassay;and RNA polymerase III (RNAP) by ELISA. Results: ANA was positive in 95% (same in lcSSc, and dcSSc). Centromere pattern was present in 34%, speckled 22%, nucleolar 18%, homogeneous and speckled (H&S) 16%, multiple nuclear dots 6%. Anti-centromere Ab (ACA) occurred in 46% of lcSSc and 11% of dcSSc (P = 0.0001). ENAs that differed between lcSSc and dcSSc subsets were Topo1 (OR 2.4, P = 0.0001) and RNAP (OR 5.6, P 0.0001) more common in dcSSc. Overall, 15% had positive Topo1;usually with a H&S pattern (67%);Topo1 was associated with ILD on CXR (OR 2.3;95% CI 1.5 - 3.5) and HRCT (OR 3.8;95% CI 1.8 - 8.2). RNAP occurred in 18.5% (35.4% in dcSSc vs. 8.9% in lcSSc). Scleroderma renal crisis (SRC) was 13 times more likely if RNAP positive;P = 0.0001. ACA was only weakly associated with sPAP > 50 mmHg (OR 1.8;95%CI 1.1 - 3.0). Conclusion: ANA homogeneous pattern alone is rare in SSc;ACA was significantly more common in lcSSc. Many ENAs are equal in lcSSc and dcSSc except RNAP and Topo1. RNAP has the highest OR of SRC. Topo1 is less strongly associated with ILD. Abstract word count: 249, Body word count 1246, Figures 2, Tables 2. Key Messages: 1) 95% of SSc has a positive ANA and ANA patterns in SSc include centromere, nucleolar, and homogeneous and speckled together;2) Most ENAs are equal in both dcSSc and lcSSc except anti RNA polymerase III and topoisomerase I;3) RNA polymerase III has the highest association (odds ratio) with scleroderma renal crisis, topoisomerase I is associated with interstitial lung disease;whereas anticentromere was not associated with elevated pulmonary arterial pressures on echocardiogram.展开更多
Aim: The aim of this study is to describe the clinical characteristics of patients with a diagnosis of systemic sclerosis who later suffer a stroke and to identify associations for this relationship. Background: Prior...Aim: The aim of this study is to describe the clinical characteristics of patients with a diagnosis of systemic sclerosis who later suffer a stroke and to identify associations for this relationship. Background: Prior studies have showed an increased risk of cardiovascular disease among patients with chronic inflammatory disorders, with chronic inflammation leading to atherosclerosis believed to be the culprit. Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by diffuse fibrosis of the skin and internal organs. Previous studies have suggested a possible link between systemic sclerosis and macrovascular complications such as stroke. Methods: This is a retrospective chart review of patients treated within the University of Pennsylvania Health System from October 2015 to April 2019 with a diagnosis of SSc. Using ICD10 codes, we identified a cohort of SSc patients who suffered a stroke. Information regarding demographics and stroke risk factors were gathered from the charts of patients with a diagnosis of both SSc plus stroke and compared to a control group of randomly selected patients with SSc who never suffered a stroke. Continuous variables were conveyed using a mean plus a standard deviation. A two-sample t-test was used to compare the two groups of patients. Qualitative variables were compared using a two-tailed Fisher’s exact test. Results: Based on a large cohort of SSc patients (n = 2080) followed between October 2015 and April 2019, we identified 36 SSc patients who developed a subsequent stroke (1.7% of cohort). When looking at risk factors for stroke in SSc patients, we identified hypertension and atrial fibrillation to be associated with the diagnosis of stroke in such patients. Specifically, 28 of the 36 patients with both SSc and stroke also had a diagnosis of hypertension while in the control group, only 17 of 36 patients had hypertension. Atrial fibrillation was seen in 9 of 36 patients with both SSc and CVA while it was seen in only 2 of 36 patients in the control group. Conclusions: This case control study demonstrated that the presence of hypertension and atrial fibrillation had a statistically significant association with the diagnosis of CVA in patients with SSc.展开更多
Objective: The aim of this study was to describe the epidemiological, clinical and therapeutic features of systemic scleroderma at Cocody UTH. Methodology: We conducted a retrospective and descriptive study over a per...Objective: The aim of this study was to describe the epidemiological, clinical and therapeutic features of systemic scleroderma at Cocody UTH. Methodology: We conducted a retrospective and descriptive study over a period of 10 years (September 15, 2008 to April 15, 2019) on the files of patients hospitalized for systemic scleroderma in the rheumatology unit of the UTH of Cocody. We used the classification criteria of the American Society of Rheumatology (1980) to retain the diagnosis. Results: Nineteen patients’ files had been collected, representing a hospital frequency of 0.32%. The average age was 37.25 ± 13.82 years old. There were 15 women and 4 men. The average consultation time was 26.44 months. The mode of revelation of the disease was mostly cutaneous and articular. All patients had cutaneous sclerosis (average Rodnan score = 27.63/11.61 (min = 4, max = 49).) Scleroderma was diffuse in 70.59% of cases;a Raynaud’s phenomenon was seen in 47.37%. The main clinical manifestations were: cutaneous (100%), articular (89.47%), pulmonary (57.89%) and digestive (63.16%). No renal damage was found. Pulmonary fibrosis (5 cases), pulmonary arterial hypertension (3 cases) and pericardial effusion (2 cases) were sometimes founded in explorations. The positivity of antinuclear antibodies (ANA) was seen in 72% of patients and anti scl70 antibodies in 42.85%. The treatment included corticosteroids and immunosuppressants, respectively used in 84.2% and 63.16% of cases. The outcome was marked by 5 cases of death attributed to respiratory distress. Conclusion: Systemic scleroderma seems to be a very rare condition in Ivorian rheumatology milieu. The main systemic manifestations were digestive and pulmonary. Treatment was very often symptomatic sometimes associated with D-penicillamine.展开更多
We hereby present a case of anaemia in a 73 years old patient with known past medical history of diffuse systemic scleroderma, who presented with acute onset of dizziness and haemetemesis. Blood tests revealed sudden ...We hereby present a case of anaemia in a 73 years old patient with known past medical history of diffuse systemic scleroderma, who presented with acute onset of dizziness and haemetemesis. Blood tests revealed sudden drop of haemoglobin and an urgent gastroscopy revealed gastric antral vascular ectasia (GAVE) or “watermelon stomach”. GAVE is a rare but well recognised cause of acute bleeding in systemic scleroderma patients and should be kept as a differential diagnosis in the work up of anaemia in these patients.展开更多
Objective: To determine the efficacy of immunesuppressive treatment over 1 year in early diffuse cutaneous systemic sclerosis (dcSSc). Methods: dcSSc patients with less than 3 years disease duration and at least one y...Objective: To determine the efficacy of immunesuppressive treatment over 1 year in early diffuse cutaneous systemic sclerosis (dcSSc). Methods: dcSSc patients with less than 3 years disease duration and at least one year of data enrolled in the CSRG database were included. Regression analyses for achieving at least minimal important differences (MID) for 5 outcomes over one year were done to determine baseline predictors of change and if immunesuppressive treatment yielded the attainment of the MID. Results: 124 patients (mean age 52.3 years;79.2% female) were included. Variables associated with MID at one year were often the baseline variable and for some outcomes, age, sex, smoking, restrictive lung disease and treatment type. Treatment with immunesuppressive was not found to be associated with achieving MIDs in multivariate analyses. Conclusion: Treatment was associated with achieving a MID change at 1 year using univariate statistics, but not in multivariate models. These observational data do not support improvement with immunesuppressives over one year but there could be confounding or biases comparing with those prescribed immunesuppressives vs. those who don’t.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
BACKGROUND Not all neuropsychiatric(NP)manifestations in patients with systemic lupus erythematosus(SLE)are secondary to lupus.The clarification of the cause of NP symptoms influences therapeutic strategies for SLE.AI...BACKGROUND Not all neuropsychiatric(NP)manifestations in patients with systemic lupus erythematosus(SLE)are secondary to lupus.The clarification of the cause of NP symptoms influences therapeutic strategies for SLE.AIM To understand the attribution of psychiatric manifestations in a cohort of Chinese patients with SLE.METHODS This retrospective single-center study analyzed 160 inpatient medical records.Clinical diagnosis,which is considered the gold standard,was used to divide the subjects into a psychiatric SLE(PSLE)group(G1)and a secondary psychiatric symptoms group(G2).Clinical features were compared between these two groups.The sensitivity and specificity of the Italian attribution model were explored.RESULTS A total of 171 psychiatric syndromes were recorded in 138 patients,including 87 cases of acute confusional state,40 cases of cognitive dysfunction,18 cases of psychosis,and 13 cases each of depressive disorder and mania or hypomania.A total of 141(82.5%)syndromes were attributed to SLE.In contrast to G2 patients,G1 patients had higher SLE Disease Activity Index-2000 scores(21 vs 12,P=0.001),a lower prevalence of anti-beta-2-glycoprotein 1 antibodies(8.6%vs 25.9%,P=0.036),and a higher prevalence of anti-ribosomal ribonucleoprotein particle(rRNP)antibodies(39.0%vs 22.2%,P=0.045).The Italian attribution model exhibited a sensitivity of 95.0%and a specificity of 70.0%when the threshold value was set at 7.CONCLUSION Patients with PSLE exhibited increased disease activity.There is a correlation between PSLE and anti-rRNP antibodies.The Italian model effectively assesses multiple psychiatric manifestations in Chinese SLE patients who present with NP symptoms.展开更多
Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biologic...Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biological functions as nutritional interventions.Despite the interest in organic acids and monoglycerides,few studies have examined the effects of the combination of these acid-based additives in weaned pigs under disease challenge conditions.Therefore,this study aimed to investigate the effects of dietary supplementation with blend of organic acids and/or medium-chain fatty acid monoglycerides on intestinal health and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC)F18 at 4-week of age.Results Dietary supplementation of organic acids,monoglycerides,or both organic acids and monoglycerides(combination)reduced(P<0.05)the diarrhea frequency of ETEC F18-infected pigs throughout the experimental period(d−7 to 21 post-inoculation).This is consistent with the reduced(P<0.05)proportion ofβ-hemolytic coliforms in feces observed for the organic acid and combination treatments on d 10 post-inoculation.Supplementation of organic acids,monoglycerides,or combination also reduced(P<0.05)bacterial translocation in mesenteric lymph nodes on d 21 post-inoculation.Pigs fed with monoglycerides or combination had lower(P<0.05)white blood cells on d 5 post-inoculation,and pigs fed the combination also had lower(P<0.05)lymphocytes than pigs in control group.Monoglyceride supplementation increased(P<0.05)white blood cells and neutrophils compared with control group on d 14 post-inoculation.However,supplementation with organic acid blend,monoglyceride blend,or combination did not affect growth performance in this experiment.Conclusions Supplementation with monoglycerides or organic acids alone or in combination improves the detrimental effects of ETEC F18 infection in weaned pigs,as indicated by reduced diarrhea,fecal shedding ofβ-hemolytic coliforms,and bacterial translocation,and thus enhancing disease resistance.Monoglycerides reduced the inflammatory response during peak infection,but their immunomodulatory and possible synergistic effects with organic acids need to be further investigated.展开更多
BACKGROUND The diagnosis of gastric carcinoma(GC)is essential for improving clinical outcomes.However,the biomarkers currently used for GC screening are not ideal.AIM To explore the diagnostic implications of the neut...BACKGROUND The diagnosis of gastric carcinoma(GC)is essential for improving clinical outcomes.However,the biomarkers currently used for GC screening are not ideal.AIM To explore the diagnostic implications of the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammatory index(SII)for GC.METHODS The baseline data of 133 patients with GC and 134 patients with precancerous gastric conditions admitted between January 2022 and December 2023 were retrospectively analyzed.The information on peripheral blood platelet,neutrophil,and lymphocyte counts in each patient was collected,and the NLR,PLR,and SII levels of both groups were calculated.Additionally,multivariate logistic regression analysis was conducted,and the diagnostic implications of NLR,PLR,and SII in differentiating patients with precancerous gastric conditions,compared with those with GC,were analyzed through receiver operating characteristic(ROC)curves.RESULTS The data indicated that NLR,PLR,and SII had abnormally increased levels in the patients with GC.Gender and body mass index were risk factors for the occurrence of GC.ROC data revealed that the areas under the curve of three patients with precancerous gastric conditions,who were differentiated from those with GC,were 0.824,0.787,and 0.842,respectively.CONCLUSION NLR,PLR,and SII are all abnormally expressed in GC and have diagnostic implications,especially when used as joint indicators,in distinguishing patients with precancerous gastric conditions from those with GC.展开更多
Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evalua...Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.展开更多
OBJECTIVE:To explore the mechanisms by which Huoxue Chubi decoction(活血除痹汤,HXCB) affects the protein kinase B(Akt)-mammalian target of rapamycin(mTOR) autophagy pathway in scleroderma Balb/c model mice.METHODS:A s...OBJECTIVE:To explore the mechanisms by which Huoxue Chubi decoction(活血除痹汤,HXCB) affects the protein kinase B(Akt)-mammalian target of rapamycin(mTOR) autophagy pathway in scleroderma Balb/c model mice.METHODS:A scleroderma model was established in male Balb/c mice,followed by daily administration of HXCB(4.6,2.3 and 1.15 g·kg^(-1)·d^(-1)) for 4 weeks.Bodyweight,epidermal and dermal thickness,dermal collagen levels,cutaneous reactive oxygen species(ROS) levels,Akt,Phosphorylated Akt(p-Akt),m TOR,Phosphorylated mTOR(p-mTOR),B-celllymphoma-2-interacting myosin-like coiled-coil protein 1(Beclin-1) and microtubule-associated protein A/B-light chain 3(LC3) protein and messenger ribonucleic acid(mRNA) expression were assessed.RESULTS:HXCB treatment significantly reduced epidermal and dermal thickness,dermal collagen levels,ROS levels and the mRNA and protein expression of factors in the Akt-mTOR signaling pathway compared to the scleroderma model group.Conversely,mice body weight and autophagy factors Beclin-1 and LC3 were significantly increased in mice receiving HXCB treatment.Moreover,finally,ROS expression positively correlated with skin thickness,collagen contents and the mRNA expression levels of Akt,while the protein and mRNA expression levels of Akt-mTOR pathway-related factors were inversely correlated with the protein and mRNA expression of Beclin-1 and LC3.CONCLUSION:HXCB can regulate autophagy by invigorating Qi and promoting blood circulation,thereby reducing blood stasis,facilitating new tissue generation,and contributing to scleroderma treatment.This effect may be attributed to the promotion of autophagy and enhancement of collagen degradation through the reduction of tissue oxidative stress elicited by HXCB.展开更多
Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereo...Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).展开更多
BACKGROUND Chronic psychological stress(CPS)is increasingly recognized for its detrimental effects on systemic and oral health,yet its impact on peri-implantitis remains underexplored.AIM To evaluate the evidence link...BACKGROUND Chronic psychological stress(CPS)is increasingly recognized for its detrimental effects on systemic and oral health,yet its impact on peri-implantitis remains underexplored.AIM To evaluate the evidence linking CPS to peri-implantitis.METHODS This systematic review was conducted according to the PRISMA guidelines.Publications searching PubMed,EMBASE,MEDLINE,Cochrane Library,and ClinicalTrials.gov for human studies published in English from 1983 to December 2024.Additionally,quality assessment of selected full-text articles were performed using the modified Newcastle–Ottawa Scale.RESULTS From an initial total of 3964 studies,4 cross-sectional studies comprising 432 participants met the inclusion criteria and consistently demonstrated a positive association between CPS and peri-implantitis.However,the findings are compromised by small sample sizes,study design limitations,methodological heterogeneity,and inadequate adjustment for critical confounders such as smoking and prior periodontitis.CONCLUSION Cortisol levels in peri-implant sulcus fluid were linearly correlated with probing depth,with evidence suggesting this relationship may be independent of hyperglycemia.Depression emerged as the most significant CPS subtype associated with peri-implantitis.Additionally,CPS may amplify peri-implantitis inflammation by modulating cytokine expression effects.Long-term studies with larger,more diverse patient populations and careful control of confounding variables are needed to establish causality and understand the underlying mechanisms.Including psychological evaluations and stress management techniques in peri-implant care protocols could improve treatment outcomes and patient health.展开更多
Objective The systemic immune-inflammation index(SII)has recently attracted significant interest as a new biomarker for predicting the prognosis of patients with glioblastoma(GBM).However,the predictive significance o...Objective The systemic immune-inflammation index(SII)has recently attracted significant interest as a new biomarker for predicting the prognosis of patients with glioblastoma(GBM).However,the predictive significance of it is still a subject of debate.This study intended to assess the clinical effectiveness of the SII in GBM and establish a nomogram.Methods Receiver operating characteristic(ROC)curves were utilized to determine the optimal cut-off values of the SII.Kaplan–Meier(KM)survival curves were used to analyze the median overall survival(OS).Cox regression analysis was carried out to evaluate the associations between OS and different clinical factors.Based on the SII and clinical characteristics,a nomogram was constructed,and its value in clinical application was evaluated by means of decision curve analysis.Results The optimal SII cut-off value was 610.13.KM analysis revealed that GBM patients with higher SII values had shorter OS(15.0 vs.34.0 months,P=0.044).Multivariate analysis demonstrated that a high SII was an independent predictor of poor outcome in GBM(HR=1.79,P=0.029).The nomogram incorporating the preoperative SII showed good predictive accuracy for GBM patient prognosis(C-index=0.691).Conclusions The SII is an independent predictive indicator for GBM.Patients with elevated SII levels tend to have a poorer prognosis.A nomogram combining the SII with clinical and molecular pathological features can assist clinicians in assessing the risk of death in GBM patients,providing a basis for individualized treatment decisions.展开更多
Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse ef...Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse effects.In recent decades,novel systemic therapies such as immunotherapy and targeted therapy have profoundly transformed HCC management.Although some patients with advanced HCC exhibit dramatically improved outcomes,the efficacy of immunotherapy and targeted therapy,either asmonotherapy or in combina-tion,remains limited.Numerous trials have indicated that locoregional therapies,including transarterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),and transarterial radioembolization(TARE),may synergize with systemic therapies to enhance ad-vanced HCC treatment.However,further studies are required to optimize these combination regimens.In contrast,curative treatments,such as surgical resection,liver transplantation,or local ablation,are typically recommended for patients with early-stage HCC.Although these treatments have achieved an impressivemedian overall survival(OS)exceeding 60months,more than half of the patients experience recurrence within 5 years.Consequently,the development of effective perioperative neoadjuvant or adjuvant therapies is urgently needed to reduce the incidence of recurrence and metastasis.It provides a comprehensive overview of recent advances in systemic therapies for advanced HCC,as well as adjuvant or neoadjuvant immunotherapies for early HCC.Additionally,emerging clinical trials and trial designs for future investigations into systemic therapies for HCC management are critically analyzed.展开更多
BACKGROUND Systemic lupus erythematosus(SLE)can affect multiple organs or systems.The involvement of the central nervous system can result in the manifestation of epilepsy,an acute confusional state,and other rare neu...BACKGROUND Systemic lupus erythematosus(SLE)can affect multiple organs or systems.The involvement of the central nervous system can result in the manifestation of epilepsy,an acute confusional state,and other rare neuropsychiatric presentations,such as catatonia.CASE SUMMARY We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and delirium.The initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia,which was mitigated by discontinuing olanzapine and supplementing with lorazepam.In this case,whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential diagnosis.CONCLUSION Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.展开更多
Portal hypertension and cirrhosis are associated with severe hemodynamic changes in hepatic and systemic circulation in the adult population.During cirrhosis progression,circulation becomes hyperdynamic,with cardiac,p...Portal hypertension and cirrhosis are associated with severe hemodynamic changes in hepatic and systemic circulation in the adult population.During cirrhosis progression,circulation becomes hyperdynamic,with cardiac,pulmonary and renal consequences.Cirrhotic adults also present with cirrhotic cardiomyopathy,with systolic and diastolic dysfunction and electrophysiological abnormalities.This article provides an update on normal liver hemodynamics,a brief reminder of the liver and systemic hemodynamics in cirrhotic adults,and a description of liver and systemic hemodynamics in cirrhotic children.This review attempts to clarify whether liver and systemic hemodynamics are altered in cirrhotic children like they are in adults.The characterization of these hemodynamic disturbances could contribute to a better understanding of hepatic and systemic physiopathology in pediatric cirrhosis.展开更多
Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cel...Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cells,cancer-associated fibroblasts,adipocytes,and the extracellular matrix.All of these TME components interact via soluble factors,such as growth factors,cytokines,and chemokines.These interactions remodel the TME and drive inflammation and tumor progression.Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME.This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition,migration,and invasion.Chronic inflammation causes inflammatory mediators to enter the circulation over time,as evidenced by systemic biomarkers,such as the systemic immune-inflammation index,which links inflammation to disease severity.Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation.Inflammation in the prostate gland confers resistance to therapy,primes distant metastatic niches,and promotes metastatic spread,resulting in poor clinical outcomes.Therapeutic strategies,such as anti-inflammatory agents and immunotherapies,hold promise in mitigating disease burden.This review explored the immune landscape of systemic inflammation in prostate cancer,discussed the role of the immune landscape in resistance to therapy and metastasis,and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.展开更多
Liver cancer presents unique challenges due to its systemic impact and complex treatment modalities.Patients often experience a range of complications,including cardiovascular,renal,hematological,and metabolic abnorma...Liver cancer presents unique challenges due to its systemic impact and complex treatment modalities.Patients often experience a range of complications,including cardiovascular,renal,hematological,and metabolic abnormalities,which can significantly affect treatment outcomes and quality of life.This article emphasizes the integration of multidisciplinary strategies and artificial intelligence-driven diagnostics,which have the potential to improve patient outcomes by optimizing early detection and targeted management of these complications.A recent study on 60 liver cancer patients undergoing interventional therapy highlighted the importance of recognizing and managing these complications.This article offers an overview of systemic complications in liver cancer,focusing on pathophysiological mechanisms,risk factors,and strategies to improve care.By addressing gaps in the existing literature and proposing future research directions,it underscores the importance of comprehensive,patient-centered approaches to refine therapeutic strategies.展开更多
Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and l...Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.展开更多
文摘Objective: Serum from SSc patients was analyzed centrally to determine ANA patterns and extractable nuclear antigens (ENAs) between lcSSc and dcSSc and associations with organ involvement. Methods: 1145 SSc patients had ANA and ENA analyzed by indirect immunofluorescence on HEp-2 substrate at a screening serum dilution of 1/160. Most ENA antibodies [Sm. U1-RNP, Ro52, SS-A/Ro60, topoisomeraseI (Topo1), SS-B/La, chromatin, ribosomal P and Jo1] were measured by laser bead immunoassay;and RNA polymerase III (RNAP) by ELISA. Results: ANA was positive in 95% (same in lcSSc, and dcSSc). Centromere pattern was present in 34%, speckled 22%, nucleolar 18%, homogeneous and speckled (H&S) 16%, multiple nuclear dots 6%. Anti-centromere Ab (ACA) occurred in 46% of lcSSc and 11% of dcSSc (P = 0.0001). ENAs that differed between lcSSc and dcSSc subsets were Topo1 (OR 2.4, P = 0.0001) and RNAP (OR 5.6, P 0.0001) more common in dcSSc. Overall, 15% had positive Topo1;usually with a H&S pattern (67%);Topo1 was associated with ILD on CXR (OR 2.3;95% CI 1.5 - 3.5) and HRCT (OR 3.8;95% CI 1.8 - 8.2). RNAP occurred in 18.5% (35.4% in dcSSc vs. 8.9% in lcSSc). Scleroderma renal crisis (SRC) was 13 times more likely if RNAP positive;P = 0.0001. ACA was only weakly associated with sPAP > 50 mmHg (OR 1.8;95%CI 1.1 - 3.0). Conclusion: ANA homogeneous pattern alone is rare in SSc;ACA was significantly more common in lcSSc. Many ENAs are equal in lcSSc and dcSSc except RNAP and Topo1. RNAP has the highest OR of SRC. Topo1 is less strongly associated with ILD. Abstract word count: 249, Body word count 1246, Figures 2, Tables 2. Key Messages: 1) 95% of SSc has a positive ANA and ANA patterns in SSc include centromere, nucleolar, and homogeneous and speckled together;2) Most ENAs are equal in both dcSSc and lcSSc except anti RNA polymerase III and topoisomerase I;3) RNA polymerase III has the highest association (odds ratio) with scleroderma renal crisis, topoisomerase I is associated with interstitial lung disease;whereas anticentromere was not associated with elevated pulmonary arterial pressures on echocardiogram.
文摘Aim: The aim of this study is to describe the clinical characteristics of patients with a diagnosis of systemic sclerosis who later suffer a stroke and to identify associations for this relationship. Background: Prior studies have showed an increased risk of cardiovascular disease among patients with chronic inflammatory disorders, with chronic inflammation leading to atherosclerosis believed to be the culprit. Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by diffuse fibrosis of the skin and internal organs. Previous studies have suggested a possible link between systemic sclerosis and macrovascular complications such as stroke. Methods: This is a retrospective chart review of patients treated within the University of Pennsylvania Health System from October 2015 to April 2019 with a diagnosis of SSc. Using ICD10 codes, we identified a cohort of SSc patients who suffered a stroke. Information regarding demographics and stroke risk factors were gathered from the charts of patients with a diagnosis of both SSc plus stroke and compared to a control group of randomly selected patients with SSc who never suffered a stroke. Continuous variables were conveyed using a mean plus a standard deviation. A two-sample t-test was used to compare the two groups of patients. Qualitative variables were compared using a two-tailed Fisher’s exact test. Results: Based on a large cohort of SSc patients (n = 2080) followed between October 2015 and April 2019, we identified 36 SSc patients who developed a subsequent stroke (1.7% of cohort). When looking at risk factors for stroke in SSc patients, we identified hypertension and atrial fibrillation to be associated with the diagnosis of stroke in such patients. Specifically, 28 of the 36 patients with both SSc and stroke also had a diagnosis of hypertension while in the control group, only 17 of 36 patients had hypertension. Atrial fibrillation was seen in 9 of 36 patients with both SSc and CVA while it was seen in only 2 of 36 patients in the control group. Conclusions: This case control study demonstrated that the presence of hypertension and atrial fibrillation had a statistically significant association with the diagnosis of CVA in patients with SSc.
文摘Objective: The aim of this study was to describe the epidemiological, clinical and therapeutic features of systemic scleroderma at Cocody UTH. Methodology: We conducted a retrospective and descriptive study over a period of 10 years (September 15, 2008 to April 15, 2019) on the files of patients hospitalized for systemic scleroderma in the rheumatology unit of the UTH of Cocody. We used the classification criteria of the American Society of Rheumatology (1980) to retain the diagnosis. Results: Nineteen patients’ files had been collected, representing a hospital frequency of 0.32%. The average age was 37.25 ± 13.82 years old. There were 15 women and 4 men. The average consultation time was 26.44 months. The mode of revelation of the disease was mostly cutaneous and articular. All patients had cutaneous sclerosis (average Rodnan score = 27.63/11.61 (min = 4, max = 49).) Scleroderma was diffuse in 70.59% of cases;a Raynaud’s phenomenon was seen in 47.37%. The main clinical manifestations were: cutaneous (100%), articular (89.47%), pulmonary (57.89%) and digestive (63.16%). No renal damage was found. Pulmonary fibrosis (5 cases), pulmonary arterial hypertension (3 cases) and pericardial effusion (2 cases) were sometimes founded in explorations. The positivity of antinuclear antibodies (ANA) was seen in 72% of patients and anti scl70 antibodies in 42.85%. The treatment included corticosteroids and immunosuppressants, respectively used in 84.2% and 63.16% of cases. The outcome was marked by 5 cases of death attributed to respiratory distress. Conclusion: Systemic scleroderma seems to be a very rare condition in Ivorian rheumatology milieu. The main systemic manifestations were digestive and pulmonary. Treatment was very often symptomatic sometimes associated with D-penicillamine.
文摘We hereby present a case of anaemia in a 73 years old patient with known past medical history of diffuse systemic scleroderma, who presented with acute onset of dizziness and haemetemesis. Blood tests revealed sudden drop of haemoglobin and an urgent gastroscopy revealed gastric antral vascular ectasia (GAVE) or “watermelon stomach”. GAVE is a rare but well recognised cause of acute bleeding in systemic scleroderma patients and should be kept as a differential diagnosis in the work up of anaemia in these patients.
文摘Objective: To determine the efficacy of immunesuppressive treatment over 1 year in early diffuse cutaneous systemic sclerosis (dcSSc). Methods: dcSSc patients with less than 3 years disease duration and at least one year of data enrolled in the CSRG database were included. Regression analyses for achieving at least minimal important differences (MID) for 5 outcomes over one year were done to determine baseline predictors of change and if immunesuppressive treatment yielded the attainment of the MID. Results: 124 patients (mean age 52.3 years;79.2% female) were included. Variables associated with MID at one year were often the baseline variable and for some outcomes, age, sex, smoking, restrictive lung disease and treatment type. Treatment with immunesuppressive was not found to be associated with achieving MIDs in multivariate analyses. Conclusion: Treatment was associated with achieving a MID change at 1 year using univariate statistics, but not in multivariate models. These observational data do not support improvement with immunesuppressives over one year but there could be confounding or biases comparing with those prescribed immunesuppressives vs. those who don’t.
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
基金Supported by STI2030-Major Projects,No.2021ZD0202001National Natural Science Foundation of China,No.T2341003Capital Funds for Health Improvement and Research,No.CFH 2022-2-4012.
文摘BACKGROUND Not all neuropsychiatric(NP)manifestations in patients with systemic lupus erythematosus(SLE)are secondary to lupus.The clarification of the cause of NP symptoms influences therapeutic strategies for SLE.AIM To understand the attribution of psychiatric manifestations in a cohort of Chinese patients with SLE.METHODS This retrospective single-center study analyzed 160 inpatient medical records.Clinical diagnosis,which is considered the gold standard,was used to divide the subjects into a psychiatric SLE(PSLE)group(G1)and a secondary psychiatric symptoms group(G2).Clinical features were compared between these two groups.The sensitivity and specificity of the Italian attribution model were explored.RESULTS A total of 171 psychiatric syndromes were recorded in 138 patients,including 87 cases of acute confusional state,40 cases of cognitive dysfunction,18 cases of psychosis,and 13 cases each of depressive disorder and mania or hypomania.A total of 141(82.5%)syndromes were attributed to SLE.In contrast to G2 patients,G1 patients had higher SLE Disease Activity Index-2000 scores(21 vs 12,P=0.001),a lower prevalence of anti-beta-2-glycoprotein 1 antibodies(8.6%vs 25.9%,P=0.036),and a higher prevalence of anti-ribosomal ribonucleoprotein particle(rRNP)antibodies(39.0%vs 22.2%,P=0.045).The Italian attribution model exhibited a sensitivity of 95.0%and a specificity of 70.0%when the threshold value was set at 7.CONCLUSION Patients with PSLE exhibited increased disease activity.There is a correlation between PSLE and anti-rRNP antibodies.The Italian model effectively assesses multiple psychiatric manifestations in Chinese SLE patients who present with NP symptoms.
基金supported by Animal Nutrition,Eastman Chemical Company,Kingsport,TN,USA.
文摘Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biological functions as nutritional interventions.Despite the interest in organic acids and monoglycerides,few studies have examined the effects of the combination of these acid-based additives in weaned pigs under disease challenge conditions.Therefore,this study aimed to investigate the effects of dietary supplementation with blend of organic acids and/or medium-chain fatty acid monoglycerides on intestinal health and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC)F18 at 4-week of age.Results Dietary supplementation of organic acids,monoglycerides,or both organic acids and monoglycerides(combination)reduced(P<0.05)the diarrhea frequency of ETEC F18-infected pigs throughout the experimental period(d−7 to 21 post-inoculation).This is consistent with the reduced(P<0.05)proportion ofβ-hemolytic coliforms in feces observed for the organic acid and combination treatments on d 10 post-inoculation.Supplementation of organic acids,monoglycerides,or combination also reduced(P<0.05)bacterial translocation in mesenteric lymph nodes on d 21 post-inoculation.Pigs fed with monoglycerides or combination had lower(P<0.05)white blood cells on d 5 post-inoculation,and pigs fed the combination also had lower(P<0.05)lymphocytes than pigs in control group.Monoglyceride supplementation increased(P<0.05)white blood cells and neutrophils compared with control group on d 14 post-inoculation.However,supplementation with organic acid blend,monoglyceride blend,or combination did not affect growth performance in this experiment.Conclusions Supplementation with monoglycerides or organic acids alone or in combination improves the detrimental effects of ETEC F18 infection in weaned pigs,as indicated by reduced diarrhea,fecal shedding ofβ-hemolytic coliforms,and bacterial translocation,and thus enhancing disease resistance.Monoglycerides reduced the inflammatory response during peak infection,but their immunomodulatory and possible synergistic effects with organic acids need to be further investigated.
文摘BACKGROUND The diagnosis of gastric carcinoma(GC)is essential for improving clinical outcomes.However,the biomarkers currently used for GC screening are not ideal.AIM To explore the diagnostic implications of the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammatory index(SII)for GC.METHODS The baseline data of 133 patients with GC and 134 patients with precancerous gastric conditions admitted between January 2022 and December 2023 were retrospectively analyzed.The information on peripheral blood platelet,neutrophil,and lymphocyte counts in each patient was collected,and the NLR,PLR,and SII levels of both groups were calculated.Additionally,multivariate logistic regression analysis was conducted,and the diagnostic implications of NLR,PLR,and SII in differentiating patients with precancerous gastric conditions,compared with those with GC,were analyzed through receiver operating characteristic(ROC)curves.RESULTS The data indicated that NLR,PLR,and SII had abnormally increased levels in the patients with GC.Gender and body mass index were risk factors for the occurrence of GC.ROC data revealed that the areas under the curve of three patients with precancerous gastric conditions,who were differentiated from those with GC,were 0.824,0.787,and 0.842,respectively.CONCLUSION NLR,PLR,and SII are all abnormally expressed in GC and have diagnostic implications,especially when used as joint indicators,in distinguishing patients with precancerous gastric conditions from those with GC.
文摘Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.
基金Natural Science Foundation-funded Project:Exploration the Mechanism of Yiqi Huoxue Therapy in Treating Scleroderma Fibrosis based on Phosphatidylinositol 3-Kinase (PI3K)-Protein Kinase B (Akt)-Mammalian Target of Rapamycin (mTOR) Signal Pathway about Autophagy (No.81804106)the 2023 Science and Technology Innovation Project Dongzhimen Hospital Beijing University of Chinese Medicine:Exploration the Mechanism of Radix Salviae Miltiorrhizae Components in Treating Scleroderma Fibrosis Based on PI3K-Akt-mTOR Signal Pathway about Autophagy (No.DZMKJCX-2023-009)。
文摘OBJECTIVE:To explore the mechanisms by which Huoxue Chubi decoction(活血除痹汤,HXCB) affects the protein kinase B(Akt)-mammalian target of rapamycin(mTOR) autophagy pathway in scleroderma Balb/c model mice.METHODS:A scleroderma model was established in male Balb/c mice,followed by daily administration of HXCB(4.6,2.3 and 1.15 g·kg^(-1)·d^(-1)) for 4 weeks.Bodyweight,epidermal and dermal thickness,dermal collagen levels,cutaneous reactive oxygen species(ROS) levels,Akt,Phosphorylated Akt(p-Akt),m TOR,Phosphorylated mTOR(p-mTOR),B-celllymphoma-2-interacting myosin-like coiled-coil protein 1(Beclin-1) and microtubule-associated protein A/B-light chain 3(LC3) protein and messenger ribonucleic acid(mRNA) expression were assessed.RESULTS:HXCB treatment significantly reduced epidermal and dermal thickness,dermal collagen levels,ROS levels and the mRNA and protein expression of factors in the Akt-mTOR signaling pathway compared to the scleroderma model group.Conversely,mice body weight and autophagy factors Beclin-1 and LC3 were significantly increased in mice receiving HXCB treatment.Moreover,finally,ROS expression positively correlated with skin thickness,collagen contents and the mRNA expression levels of Akt,while the protein and mRNA expression levels of Akt-mTOR pathway-related factors were inversely correlated with the protein and mRNA expression of Beclin-1 and LC3.CONCLUSION:HXCB can regulate autophagy by invigorating Qi and promoting blood circulation,thereby reducing blood stasis,facilitating new tissue generation,and contributing to scleroderma treatment.This effect may be attributed to the promotion of autophagy and enhancement of collagen degradation through the reduction of tissue oxidative stress elicited by HXCB.
基金supported by the Shenzhen Science and Technology Program(grant number:KQTD20180411185028798).
文摘Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).
文摘BACKGROUND Chronic psychological stress(CPS)is increasingly recognized for its detrimental effects on systemic and oral health,yet its impact on peri-implantitis remains underexplored.AIM To evaluate the evidence linking CPS to peri-implantitis.METHODS This systematic review was conducted according to the PRISMA guidelines.Publications searching PubMed,EMBASE,MEDLINE,Cochrane Library,and ClinicalTrials.gov for human studies published in English from 1983 to December 2024.Additionally,quality assessment of selected full-text articles were performed using the modified Newcastle–Ottawa Scale.RESULTS From an initial total of 3964 studies,4 cross-sectional studies comprising 432 participants met the inclusion criteria and consistently demonstrated a positive association between CPS and peri-implantitis.However,the findings are compromised by small sample sizes,study design limitations,methodological heterogeneity,and inadequate adjustment for critical confounders such as smoking and prior periodontitis.CONCLUSION Cortisol levels in peri-implant sulcus fluid were linearly correlated with probing depth,with evidence suggesting this relationship may be independent of hyperglycemia.Depression emerged as the most significant CPS subtype associated with peri-implantitis.Additionally,CPS may amplify peri-implantitis inflammation by modulating cytokine expression effects.Long-term studies with larger,more diverse patient populations and careful control of confounding variables are needed to establish causality and understand the underlying mechanisms.Including psychological evaluations and stress management techniques in peri-implant care protocols could improve treatment outcomes and patient health.
基金funded by National Natural Science Foundation of China,grant number 82203007.
文摘Objective The systemic immune-inflammation index(SII)has recently attracted significant interest as a new biomarker for predicting the prognosis of patients with glioblastoma(GBM).However,the predictive significance of it is still a subject of debate.This study intended to assess the clinical effectiveness of the SII in GBM and establish a nomogram.Methods Receiver operating characteristic(ROC)curves were utilized to determine the optimal cut-off values of the SII.Kaplan–Meier(KM)survival curves were used to analyze the median overall survival(OS).Cox regression analysis was carried out to evaluate the associations between OS and different clinical factors.Based on the SII and clinical characteristics,a nomogram was constructed,and its value in clinical application was evaluated by means of decision curve analysis.Results The optimal SII cut-off value was 610.13.KM analysis revealed that GBM patients with higher SII values had shorter OS(15.0 vs.34.0 months,P=0.044).Multivariate analysis demonstrated that a high SII was an independent predictor of poor outcome in GBM(HR=1.79,P=0.029).The nomogram incorporating the preoperative SII showed good predictive accuracy for GBM patient prognosis(C-index=0.691).Conclusions The SII is an independent predictive indicator for GBM.Patients with elevated SII levels tend to have a poorer prognosis.A nomogram combining the SII with clinical and molecular pathological features can assist clinicians in assessing the risk of death in GBM patients,providing a basis for individualized treatment decisions.
基金work was supported by grants from the National Natural Science Foundation of China(No.82073346)Doctoral Through Train Scien-tific Research Project of Chongqing(No.CSTB2022BSXM-JCX0004)+1 种基金Famous Teachers section of the Chongqing Talents Program(No.4246ZP112)Special Projects of Army Medical University for Improving Scientific and Technological Innovation Capabilities(No.2019XLC1009).
文摘Hepatocellular carcinoma(HCC)is a lethalmalignancy.Formany years,chemotherapeutic regimens have served as the foundation of sys-temic therapies for advanced HCCdespite their limited efficacy and significant adverse effects.In recent decades,novel systemic therapies such as immunotherapy and targeted therapy have profoundly transformed HCC management.Although some patients with advanced HCC exhibit dramatically improved outcomes,the efficacy of immunotherapy and targeted therapy,either asmonotherapy or in combina-tion,remains limited.Numerous trials have indicated that locoregional therapies,including transarterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),and transarterial radioembolization(TARE),may synergize with systemic therapies to enhance ad-vanced HCC treatment.However,further studies are required to optimize these combination regimens.In contrast,curative treatments,such as surgical resection,liver transplantation,or local ablation,are typically recommended for patients with early-stage HCC.Although these treatments have achieved an impressivemedian overall survival(OS)exceeding 60months,more than half of the patients experience recurrence within 5 years.Consequently,the development of effective perioperative neoadjuvant or adjuvant therapies is urgently needed to reduce the incidence of recurrence and metastasis.It provides a comprehensive overview of recent advances in systemic therapies for advanced HCC,as well as adjuvant or neoadjuvant immunotherapies for early HCC.Additionally,emerging clinical trials and trial designs for future investigations into systemic therapies for HCC management are critically analyzed.
基金Supported by STI2030-Major Projects,No.2021ZD0202001Capital Funds for Health Improvement and Research,No.CFH 2022-2-4012.
文摘BACKGROUND Systemic lupus erythematosus(SLE)can affect multiple organs or systems.The involvement of the central nervous system can result in the manifestation of epilepsy,an acute confusional state,and other rare neuropsychiatric presentations,such as catatonia.CASE SUMMARY We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and delirium.The initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia,which was mitigated by discontinuing olanzapine and supplementing with lorazepam.In this case,whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential diagnosis.CONCLUSION Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.
文摘Portal hypertension and cirrhosis are associated with severe hemodynamic changes in hepatic and systemic circulation in the adult population.During cirrhosis progression,circulation becomes hyperdynamic,with cardiac,pulmonary and renal consequences.Cirrhotic adults also present with cirrhotic cardiomyopathy,with systolic and diastolic dysfunction and electrophysiological abnormalities.This article provides an update on normal liver hemodynamics,a brief reminder of the liver and systemic hemodynamics in cirrhotic adults,and a description of liver and systemic hemodynamics in cirrhotic children.This review attempts to clarify whether liver and systemic hemodynamics are altered in cirrhotic children like they are in adults.The characterization of these hemodynamic disturbances could contribute to a better understanding of hepatic and systemic physiopathology in pediatric cirrhosis.
文摘Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cells,cancer-associated fibroblasts,adipocytes,and the extracellular matrix.All of these TME components interact via soluble factors,such as growth factors,cytokines,and chemokines.These interactions remodel the TME and drive inflammation and tumor progression.Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME.This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition,migration,and invasion.Chronic inflammation causes inflammatory mediators to enter the circulation over time,as evidenced by systemic biomarkers,such as the systemic immune-inflammation index,which links inflammation to disease severity.Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation.Inflammation in the prostate gland confers resistance to therapy,primes distant metastatic niches,and promotes metastatic spread,resulting in poor clinical outcomes.Therapeutic strategies,such as anti-inflammatory agents and immunotherapies,hold promise in mitigating disease burden.This review explored the immune landscape of systemic inflammation in prostate cancer,discussed the role of the immune landscape in resistance to therapy and metastasis,and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.
文摘Liver cancer presents unique challenges due to its systemic impact and complex treatment modalities.Patients often experience a range of complications,including cardiovascular,renal,hematological,and metabolic abnormalities,which can significantly affect treatment outcomes and quality of life.This article emphasizes the integration of multidisciplinary strategies and artificial intelligence-driven diagnostics,which have the potential to improve patient outcomes by optimizing early detection and targeted management of these complications.A recent study on 60 liver cancer patients undergoing interventional therapy highlighted the importance of recognizing and managing these complications.This article offers an overview of systemic complications in liver cancer,focusing on pathophysiological mechanisms,risk factors,and strategies to improve care.By addressing gaps in the existing literature and proposing future research directions,it underscores the importance of comprehensive,patient-centered approaches to refine therapeutic strategies.
基金funded by National Natural Science Foundation of China to Ping Yang with Grant number No.82202600by Nanjing Drum Tower Hospital to Ping Yang with Grant number No.2024-LCYJ-MS-11then to Shou-bin Zhan with Grant number No.2023-JCYJ-QP-25.
文摘Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.
