Objective:To investigate the effect of circulating plasma cell(CPC)on the prognosis of multiple myeloma(MM),and to es-tablish and validate a modified CPC-RISS staging system based on CPC and RISS.Methods:A retrospective analysis was performed for the clinical data of 639 treatment-na?ve patients with MM who were treated in Department of Hematology,Xijing Hospital,from January 2006 to June 2023.Peripheral blood smear was used to calculate the percentage of CPC in patients,and the impact of CPC and other related factors on the prognosis of MM patients was analyzed.A CPC-RISS staging system was established based on RISS stage and the percentage of CPC,and the differences in survival and prognosis were analyzed between patients with different stages.Results:Compared with the patients without CPC,detectable CPC was significantly associated with various high-risk factors for MM,and the MM patients with CPC had a lower complete remission rate and shorter overall survival time and progression-free survival time.The modified CPC-RISS staging system was used to classify the patients with MM into four stages,and there were significant differences in median survival time and progression-free survival time between the patients with different stages of MM.Conclusion:The MM pa-tients with the presence of CPC exhibit more aggressive features,worse response to treatment,and a reduction in long-term survival rate.The modified CPC-RISS staging system can effectively predict the prognosis of treatment-na?ve MM patients.

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)and homocysteine(Hcy)combined with white matter hyperintensities(WMH)for cognitive impairment in patients with cerebral small vessel disease(CSVD).Methods A total of 240 patients with CSVD were selected.According to the Montreal Cognitive Assessment(MoCA)scale,all subjects were divided into the non-cognitive impairment group(MoCA≥26 points,120 cases)and the cognitive impairment group(MoCA＜26 points,120 cases).Paraventricular white matter high signal(PWMHs)and deep white matter high signal(DWMHs)were scored by Fazekas scale.The sum of the two parts was the total score,and the severity of DWMHs was graded by the score.The basic information,serum Lp-PLA2,Hcy level and severity of WMH were compared between the two groups.Logistic regression was applied to analyze influencing factors of cognitive impairment in CSVD patients.The predictive value of serum level of Lp-PLA2 and Hcy and WMH for cognitive impairment in CSVD patients was analyzed by receiver operating characteristic(ROC)curve.Results Compared with the non-cognitive impairment group,patients of the cognitive impairment group were older,had higher serum levels of Lp-PLA2 and Hcy,and had more severe of WMH(P＜0.05).Results of Logistic regression analysis showed that serum Lp-PLA2,Hcy levels and severity of WMH were influencing factors for cognitive impairment of patients with CSVD(P＜0.05).The results of ROC curve analysis showed that the area under the curve of serum Lp-PLA2,Hcy level combined with severity of WMH predicting cognitive impairment in patents with CSVD was 0.812,the sensitivity was 81.7%and the specificity was 71.7%(P＜0.05).Conclusion Patients with cognitive impairment caused by CSVD have higher serum levels of Lp-PLA2 and Hcy,and more severe WMH.The combination of the three has a relatively high predictive value for cognitive impairment in patents with CSVD.

The intervertebral disc is a complex structure composed of the central nucleus pulposus, the peripheral annulus fibrosus, and the cartilaginous endplates located at the top and bottom. This unique arrangement effectively isolates the nucleus pulposus from the host’s immune system. Additionally, specific substances within the intervertebral disc exhibit inhibitory effects on the infiltration of immune cells and cytokines, which has led to the recognition of the intervertebral disc as an immune-privileged tissue. However, during intervertebral disc degeneration (IDD), the physical barriers that maintain this immune privilege are compromised. As a result, the nucleus pulposus may be perceived as a foreign antigen by the immune system. Simultaneously, inflammatory cytokines released by the degenerating disc attract a significant influx of immune cells, disrupting the delicate immunological balance within the nucleus pulposus and exacerbating the progression of IDD. Recent studies have confirmed the infiltration of immune cells such as macrophages and mast cells into the degenerative intervertebral disc, and the phenotypic characteristics and quantitative changes of these immune cells are closely related to the process of IDD. In terms of treatment strategies, biological agents such as mesenchymal stem cell therapy, gene therapy and growth factors that regulate the immune microenvironment of degenerative intervertebral discs have entered the stage of animal experiments. At the same time, small molecule drugs have shown unique regulatory potential in restoring the immune-privileged status of intervertebral discs.

Bronchiectasis is one of the most common and refractory lower respiratory tract diseases in clinic practice.Pseudomonas aeruginosa is the most common frequently isolated pathogen in adults with bronchiectasis complicated by infection.The complex relationship among inflammation,immunity,infection and structural damage in the airway of patients has been described as a"vicious circle"model,but the specific mechanism of different pathological links in this model and their intricate interactions are still not fully understood.The theory of"Strengthening fire eating qi"first appeared in Su Wen·Yin Yang Ying Xiang Da Lun,and provides simply explain the"qi"damage to"shape"damage of patients'airway from the perspective of"fire"and"qi"in traditional Chinese medicine,and provide new ideas for explaining the pathological mechanism connotation of bronchiectasis combined with Pseudomonas aeruginosa infection.The exploration of pathological mechanism is the fundamental source of understanding disease progression and discovering new treatment ideas.At present,the clinical treatment of Western medicine for patients with bronchiectasis mainly focuses on anti-infection and symptomatic treatment.Although etiological targeted therapies and targeted drugs are constantly explored and developed,they are still rarely applied in clinical practice.As a treasure of Chinese culture,traditional Chinese medicine has the advantage of taking both specimens into consideration,and its clinical efficacy and pharmacological value are worthy of further study.Based on the classical theory of"Strengthening fire eating qi",this review aims to understand and summarize the modern pathological mechanism of bronchiectasis combined with Pseudomonas aeruginosa infection and highlights current research hotspots in both Chinese and Western medicine treatment,in order to provide clinical thinking.

The incidence of tumors among the elderly is notably high, presenting significant challenges in terms of harm, complexity, and treatment.The processes of diagnosis and treatment often lack a precise clinical foundation and robust experimental evidence, resulting in numerous difficulties and dilemmas.A collaborative approach that integrates traditional Chinese and Western medicine, leveraging the strengths of both, can substantially alleviate these challenges and ensure that elderly cancer patients can undergo systematic, comprehensive, and intensive cancer treatments.Traditional Chinese medicine can play a vital role throughout the entire continuum of diagnosis and treatment for elderly cancer patients, whether by leading, assisting, or complementing other treatment modalities.This article employs the concepts of ′righteousness′and ′evil′from traditional Chinese medicine, where ′righteousness′signifies the ′state of a person′and ′evil ′denotes the ′state of a tumor′.We systematically explore collaborative diagnosis and treatment strategies that integrate traditional Chinese and Western medicine for tumor management in the elderly, categorizing the approaches into four conditions: strong righteousness with strong evil, strong righteousness with weak evil, weak righteousness with strong evil, and weak righteousness with weak evil.In cases where both righteousness and evil are strong, the treatment strategy is primarily dominated by Western medicine, with support from traditional Chinese medicine.Conversely, when righteousness is strong and evil is weak, the strategy entails a combination of both Chinese and Western medicine.In situations characterized by weak righteousness and strong evil, the treatment approach is largely guided by traditional Chinese medicine, while also considering equal attention to both modalities.Finally, when both righteousness and evil are weak, the coordinated diagnosis and treatment strategy is primarily based on Chinese medicine, with Western medicine adapting to the circumstances and intervening appropriately throughout the process.By accurately assessing the concepts of ′righteousness′and ′evil′and implementing collaborative diagnostic and treatment strategies that integrate both traditional Chinese and Western medicine, we can significantly enhance the physical condition of elderly cancer patients.This comprehensive approach not only boosts immunity and improves organ function but also increases tolerance to tumor treatments, alleviates complications, reduces adverse reactions, and ensures that elderly cancer patients can undergo systemic cancer treatment to its fullest extent.Ultimately, this strategy aims to improve prognosis, enhance quality of life, and extend the effective survival period.

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.

In the past, aortic dissection, aortic aneurysm, and other aortic diseases, primarily rely on surgical intervention. In recent years, due to breakthroughs in materials science, endovascular therapy has become the first choice for the surgical treatment of most aortic diseases. However, traditional endovascular repair cannot fully meet the clinical needs for certain complex lesions involving the aortic arch and the originations of visceral arteries. The emergence of physician-modified stent technology has brought new hope for the treatment of complex aortic diseases. This article provides a detailed introduction to the concept, development, technical characteristics, and applications of physician-modified stents in the treatment of aortic diseases, analyzing their advantages and limitations. Physician-modified stents serve as a powerful complement to traditional endovascular interventions and commercial branched stents, yet further research and refinement are still required.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.