ObjectiveTo investigate whether anti-programmed death-1 （PD-1） monoclonal antibody can enhance the efficacy and safety of argon-helium cryoablation combined with targeted therapy in patients with unresectable hepatocellular carcinoma （uHCC） aged 60 years or older. MethodsA retrospective analysis was performed for the clinical data of 124 patients with advanced uHCC aged 60 years or older who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to September 2024. After propensity score matching， 57 patients received cryoablation combined with targeted therapy （double combination group）， while 57 received cryoablation combined with targeted therapy and anti-PD-1 monoclonal antibody （triple combination group）. The indicators for efficacy assessment included objective response rate （ORR）， disease control rate （DCR）， progression-free survival （PFS）， overall survival （OS）， and the incidence rate of adverse events. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the influencing factors for survival prognosis. ResultsThe triple combination group had a significantly higher ORR than the double combination group （59.6% vs 29.8%， χ²=9.083， P=0.003）， while there was no significant difference in DCR between the two groups （87.7% vs 77.2%， χ²=1.516， P=0.218）， and compared with the double combination group， the triple combination group had significantly longer median PFS （9.1 months vs 4.8 months， χ²=7.813， P=0.005） and median OS （26.1 months vs 13.6 months， χ²=14.199， P<0.001）. The multivariate Cox proportional-hazards regression model analysis showed that triple combination treatment was an independent influencing factor for PFS （hazard ratio ［HR］=0.52， 95% confidence interval ［CI］： 0.35 — 0.78， P=0.001） and OS （HR=0.32， 95%CI： 0.20 — 0.51， P<0.001）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）. ConclusionTriple combination treatment with argon-helium cryoablation， targeted therapy， and anti-PD-1 monoclonal antibody can significantly improve survival benefits in uHCC patients aged 60 years or older， with a controllable safety profile.

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective To investigate the application value of pan-immune-inflammation value(PIV),hypersensitive C-reactive protein(hs-CRP)/albumin(ALB)ratio(HCAR)and procalcitonin/platelet count ratio(PCT/PLT)in pulmonary infection in elderly patients with chronic obstructive pulmonary disease(COPD).Methods A total of 143 elderly patients with COPD and pulmonary bacterial infection were selected as the infected group.Meanwhile,143 elderly patients with COPD and without pulmonary infection were selected as the uninfected group.Patients in the infected group were furthrer divided into the mild group(47 cases),the moderate group(51 cases)and the severe group(45 cases)according to the degree of pulmonary infection.They were divided into the favorable prognosis group(112 cases)and the poor prognosis group(31 cases)according to the prognosis.Blood biochemical indicators,PIV,HCAR and PCT/PLT were compared between groups.The relationship between above indicators and pulmonary infection,infection degree and the prognosis was analyzed.Results Compared with the uninfected group,neutrophil(NEU),monocyte(MON),hs-CRP and PCT levels were higher,while lymphocyte(LYM)and ALB levels were lower in the infected group(P＜0.05).PIV,HCAR and PCT/PLT were higher in the infected group and the poor prognosis group than those in the uninfected group and the favorable prognosis group,respectively(P＜0.05).PIV,HCAR and PCT/PLT in the mild group,the moderate group and the severe group increased in sequence(P＜0.05).Spearman correlation analysis showed that PIV,HCAR and PCT/PLT were positively correlated with the degree of pulmonary infection(P＜0.05).Multivariate Logistic regression analysis showed that high levels of PIV,HCAR and PCT/PLT were independent risk factors for pulmonary infection in elderly patients with COPD(P＜0.05),and also independent risk factors for poor prognosis in patients with pulmonary infection(P＜0.05).The areas under the curve(AUC)of PIV combined with HCAR and PCT/PLT for diagnosing pulmonary infection in elderly patients with COPD and predicting poor prognosis in patients with pulmonary infection were 0.980 and 0.910(P＜0.05).Conclusion PIV,HCAR and PCT/PLT are related to COPD with pulmonary infection in the elderly.They can help to identify pulmonary infection,judge the condition of pulmonary infection and evaluate the prognosis in patients with pulmonary infection.

AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P＜0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P＜0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P＜0.05 or P＜0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P＜0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P＜0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.

AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P＜0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P＜0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P＜0.05 or P＜0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P＜0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P＜0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.

Objective To investigate the application value of pan-immune-inflammation value(PIV),hypersensitive C-reactive protein(hs-CRP)/albumin(ALB)ratio(HCAR)and procalcitonin/platelet count ratio(PCT/PLT)in pulmonary infection in elderly patients with chronic obstructive pulmonary disease(COPD).Methods A total of 143 elderly patients with COPD and pulmonary bacterial infection were selected as the infected group.Meanwhile,143 elderly patients with COPD and without pulmonary infection were selected as the uninfected group.Patients in the infected group were furthrer divided into the mild group(47 cases),the moderate group(51 cases)and the severe group(45 cases)according to the degree of pulmonary infection.They were divided into the favorable prognosis group(112 cases)and the poor prognosis group(31 cases)according to the prognosis.Blood biochemical indicators,PIV,HCAR and PCT/PLT were compared between groups.The relationship between above indicators and pulmonary infection,infection degree and the prognosis was analyzed.Results Compared with the uninfected group,neutrophil(NEU),monocyte(MON),hs-CRP and PCT levels were higher,while lymphocyte(LYM)and ALB levels were lower in the infected group(P＜0.05).PIV,HCAR and PCT/PLT were higher in the infected group and the poor prognosis group than those in the uninfected group and the favorable prognosis group,respectively(P＜0.05).PIV,HCAR and PCT/PLT in the mild group,the moderate group and the severe group increased in sequence(P＜0.05).Spearman correlation analysis showed that PIV,HCAR and PCT/PLT were positively correlated with the degree of pulmonary infection(P＜0.05).Multivariate Logistic regression analysis showed that high levels of PIV,HCAR and PCT/PLT were independent risk factors for pulmonary infection in elderly patients with COPD(P＜0.05),and also independent risk factors for poor prognosis in patients with pulmonary infection(P＜0.05).The areas under the curve(AUC)of PIV combined with HCAR and PCT/PLT for diagnosing pulmonary infection in elderly patients with COPD and predicting poor prognosis in patients with pulmonary infection were 0.980 and 0.910(P＜0.05).Conclusion PIV,HCAR and PCT/PLT are related to COPD with pulmonary infection in the elderly.They can help to identify pulmonary infection,judge the condition of pulmonary infection and evaluate the prognosis in patients with pulmonary infection.

Objective To analyze levels of pan-immune-inflammation value(PIV),interleukin-6(IL-6),heparin-binding protein(HBP)and prealbumin(PAB)in patients with severe community-acquired pneumonia(CAP),and their values in evaluating the therapeutic effect at 72 h after admission.Methods According to the initial(72 h)treatment outcome,120 patients with severe CAP(the severe group)were divided into the effective group(n=87)and the failed group(n=33).Meanwhile,120 patients with non-severe CAP admitted in the same period were selected as the non-severe group.PIV,IL-6,HBP and PAB levels on the day after admission were compared between the severe group,the non-severe group,the failed group and the effective group.The value of above indicators in evaluating the condition of CAP and the therapeutic effect at 72 h after admission separately and in combination were analyzed using receiver operating characteristic(ROC)curves.Results Compared with the non-severe group,there were higher PIV,IL-6 and HBP levels,and lower PAB levels in the servere grouop(P＜0.05).ROC curves indicated that for evaluating severe CAP using a single indicator,the area under the curve(AUC)of PIV was the highest[0.830(95%CI:0.780-0.881)].The AUC of PIV combined with IL-6,HBP and PAB for evaluating severe CAP was 0.929(95%CI:0.892-0.967),which was higher than that of evaluation using a single indicator(P＜0.05).Compared with the effective group,there were higher PIV,IL-6 and HBP levels,and lower PAB level in the failed group(P＜0.05).ROC curves indicated that for evaluating the therapeutic effect on severe CAP at 72 h after admission using a single indicator the AUC of PIV was the highest[0.777(95%CI:0.692-0.862)].The AUC of PIV combined with IL-6,HBP and PAB for evaluating the therapeutic effect on severe CAP at 72 h after admission was 0.916(95%CI:0.846-0.986),which was higher than that of evaluation using a single indicator(P＜0.05).Conclusion Detection of PIV combined with IL-6,HBP and PAB has a good value in evaluating the condition of patients with CAP and the therapeutic effect on severe CAP at 72 h after admission.

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*

Objective:To compare the differences in the delineation of the gross tumor volume (GTV) and lymph nodes of nasopharyngeal carcinoma (NPC) patients using computerized tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT), and to investigate the optimal standard uptake value (SUV; relative to the MRI-based delineation) for the automatic delineation of GTV using PET. Methods:A total of 53 NPC patients proposing to receive radiotherapy were selected for this study. The CT, MRI, and PET images of each patient were obtained before radiotherapy. Then GTV and positive lymph nodes were delineated on these three types of images. They were individually named GTV MRI, GTV CT, GTV PET2.5 (SUV=2.5), Lymph MRI, Lymph CT, and Lymph PET2.5 and compared. The GTV ∩2.5 (overlapped GTV) was obtained through the alignment of MRI and PET/CT images. Meanwhile, GTV was delineated on PET images using thresholds of SUV=4.0, 4.5, 5.0, and 5.6, obtaining GTV PET4.0, GTV PET4.5, GTV PET5.0, and GTV PET5.6. Then their volume and Dice similarity coefficients (DSCs) were compared. Results:Compared to GTV MRI, GTV CT decreased by 1.73% ( P>0.05) and GTV PET2.5 increased by 21.34% ( t=-3.52, P < 0.05) in the three types of images. The volume of Lymph PET2.5 was 1.61 and 1.87 times the volume of Lymph MRI and Lymph CT, respectively ( t=-4.12, -5.18; P< 0.05). The volume of high-SUV lymph nodes was 4.07 times the volume of lymph nodes with low SUVs or SUV=0 ( t=5.50, P< 0.05) on PET images. The DSC between GTV PET4.0and GTV MRI was 0.78 ± 0.27, which was lower than that between GTV PET2.5 and GTV MRI (0.84 ± 0.18). However, GTV PET4.0 approximated to GTV ∩2.5 ( P>0.05). Conclusions:Compared to CT and 18F-FDG PET/CT, MRI shows more accurate boundaries of GTV and lymph nodes. When 18F-FDG PET/CT was adopted to automatically delineate GTV, the GTV delineated using SUV=4.0 was closer to GTV MRI.