Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.

Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.

Objective:To investigate the relationship between carotid intraplaque hemorrhage (IPH) in CT angiography(CTA) and perivascular fat density (PFD).Methods:This study retrospectively analyzed 103 patients with carotid atherosclerosis, including 209 carotid plaques, who received carotid CTA and high-resolution magnetic resonance angiography in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2018 to July 2023. According to the evaluation of IPH by MRI, the plaques were divided into IPH group ( n=85) and non IPH group ( n=124). CTA was used to evaluate the plaque characteristics (calcification, lumen stenosis, maximum plaque thickness and plaque density) and PFD. Univariate and multivariate logistic analysis was used to evaluate the relationship between PFD and IPH. The diagnostic efficacy of multiple features was performed by receiver operating characteristic curve analysis. Results:Finally, 103 patients with 209 carotid plaques were collected. Multivariate logistic regression analysis showed that PFD ( OR=1.183, 95% CI 1.104-1.267, P<0.001) still showed a significant association with IPH after adjusting for age, hyperlipidemia, degree of luminal stenosis, plaque calcification, maximum plaque thickness, and plaque density. The area under the curve values, sensitivity, specificity, and accuracy of combined PFD, maximum plaque thickness, and plaque density were 0.980, 88.24%, 98.39%, and 94.26%, respectively. Conclusion:The changes of PFD in the carotid artery are closely related to the presence of carotid IPH in MRI and may become a new imaging indicator for high-risk plaque identification and cerebrovascular risk assessment.

Lung cancer is one of the most prevalent malignant tumors,which incidence and mortality rates increasing annually.Development of drug resistance is a primary factor contributing to treatment failure.Tumor-associated macrophages(TAMs),as key immune cells within tumor microenvironment(TME),play a significant role in the emergence and progression of drug resistance in tu-mors.TAMs can polarize into two distinct subtypes,M1 and M2,in response to diverse signaling stimuli.Research indicates that M2 TAMs are closely associated with poor prognoses in lung cancer,facilitating drug resistance through mechanisms such as promoting angiogenesis,enabling immune evasion,inducing stem cell-like characteristics in tumors,modulating relevant signaling pathways,and secreting cytokines.Traditional Chinese medicine(TCM)is characterized by its multi-target approach and minimal toxic side effects,it has been shown to enhance tumor sensitivity to drugs,slow malignant progression,and extend patient survival.This paper reviews the relationship between TAMs and lung cancer drug resistance while summarizing current research on TCM and their active components that regulate TAM activity to mitigate drug resistance in lung cancer,aiming to provide new insights for targeting TAMs in this context.

Lung cancer is one of the most prevalent malignant tumors,which incidence and mortality rates increasing annually.Development of drug resistance is a primary factor contributing to treatment failure.Tumor-associated macrophages(TAMs),as key immune cells within tumor microenvironment(TME),play a significant role in the emergence and progression of drug resistance in tu-mors.TAMs can polarize into two distinct subtypes,M1 and M2,in response to diverse signaling stimuli.Research indicates that M2 TAMs are closely associated with poor prognoses in lung cancer,facilitating drug resistance through mechanisms such as promoting angiogenesis,enabling immune evasion,inducing stem cell-like characteristics in tumors,modulating relevant signaling pathways,and secreting cytokines.Traditional Chinese medicine(TCM)is characterized by its multi-target approach and minimal toxic side effects,it has been shown to enhance tumor sensitivity to drugs,slow malignant progression,and extend patient survival.This paper reviews the relationship between TAMs and lung cancer drug resistance while summarizing current research on TCM and their active components that regulate TAM activity to mitigate drug resistance in lung cancer,aiming to provide new insights for targeting TAMs in this context.

Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.

Objective:To investigate the relationship between carotid intraplaque hemorrhage (IPH) in CT angiography(CTA) and perivascular fat density (PFD).Methods:This study retrospectively analyzed 103 patients with carotid atherosclerosis, including 209 carotid plaques, who received carotid CTA and high-resolution magnetic resonance angiography in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2018 to July 2023. According to the evaluation of IPH by MRI, the plaques were divided into IPH group ( n=85) and non IPH group ( n=124). CTA was used to evaluate the plaque characteristics (calcification, lumen stenosis, maximum plaque thickness and plaque density) and PFD. Univariate and multivariate logistic analysis was used to evaluate the relationship between PFD and IPH. The diagnostic efficacy of multiple features was performed by receiver operating characteristic curve analysis. Results:Finally, 103 patients with 209 carotid plaques were collected. Multivariate logistic regression analysis showed that PFD ( OR=1.183, 95% CI 1.104-1.267, P<0.001) still showed a significant association with IPH after adjusting for age, hyperlipidemia, degree of luminal stenosis, plaque calcification, maximum plaque thickness, and plaque density. The area under the curve values, sensitivity, specificity, and accuracy of combined PFD, maximum plaque thickness, and plaque density were 0.980, 88.24%, 98.39%, and 94.26%, respectively. Conclusion:The changes of PFD in the carotid artery are closely related to the presence of carotid IPH in MRI and may become a new imaging indicator for high-risk plaque identification and cerebrovascular risk assessment.

Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

Background and purpose:Tumor-associated macrophages(TAM)as the main stromal cells in the tumor microenvironment play an important role in tumor progression.This study aimed to explore the clinical significance of M1 type TAM infiltration in hepatocellular carcinoma(HCC).Methods:We collected tissue paraffin samples from 320 HCC patients who underwent surgery at the Affiliated Nantong Hospital Three of Nantong University from January 2012 to December 2020.Immunohistochemical methods were used to detect the distribution of CD86 labeled M1 type TAM in HCC tissues,and positive cell density was calculated.Groups were established according to cell density,high-density group had cells with greater than average density(29 cells/mm2),and low-density group had cells with less than or equal to average density.The correlation and prognostic significance of M1 TAM density with clinicopathologic features and tumor infiltrating CD8+T lymphocytes of HCC were analyzed.Using immunohistochemistry to detect the expression of programmed death ligand-1(PD-L1),the cases were divided into four groups based on the cell density of CD86 and PD-L1.In the CD86+high-density group,PD-L1 high-density(CD86highPD-L1high)and PD-L1 low-density(CD86highPD-L1low)groups were included.In the CD86+low-density group,the PD-L1 high-density(CD86lowPD-L1high)and PD-L1 low-density(CD86lowPD-L1low)groups were included.We analyzed the prognostic significance of CD86+M1 type TAM density combined with PD-L1 expression.This study was approved by the Ethics Committee of Affiliated Nantong Hospital Three of Nantong University(ethics number:EK2022005).Results:CD86+M1 type TAM was mainly distributed in the tumor stroma.Its high-density rate was 44.7%(143/320).The density of CD86+M1 type TAM was positively correlated with tumor infiltrating CD8+T lymphocyte density(P＜0.001)and negatively correlated with hepatitis B virus surface antigen(HBsAg)positivity(P=0.003),and had no significant correlation with clinical and pathological features such as patient age,gender,cirrhosis,tumor size,histological grading and microvascular invasion.The CD86+M1 type TAM high-density group had better overall survival(OS)and disease-free survival(DFS)than the low-density group,and the differences were statistically significant(all P＜0.001).Multivariate Cox proportional hazards regression model analysis showed that low-density CD86+M1 type TAM was an independent risk factor for evaluating OS and DFS(OS:HR=1.468,P=0.022;DFS:HR=2.233,P＜0.001).The CD86highPD-L1high group had poor OS and DFS than the CD86highPD-L1low group,and the differences were statistically significant(both P＜0.05).The CD86lowPD-L1high group had poor OS and DFS than the CD86lowPD-L1low group.The difference in OS between the two groups was statistically significant(P＜0.05),while the difference in DFS was not statistically significant.Conclusion:The presence of high-density CD86+M1 type TAM in HCC tissue suggests a good prognosis and is an independent prognostic factor.Expression of PD-L1 in HCC tissue suggests increased invasiveness and poorer prognosis.