In recent years, the incidence of multiple primary lung cancer (MPLC) has been increasing, and it cannot be ignored in clinical practice. The treatment of MPLC is still controversial, but surgical treatment is recognized as the most important treatment. However, current studies have shown that the treatment of MPLC needs to develop multimodal treatment according to different patients. This review summarizes multiple treatment method for MPLC, including surgery, ablation, chemotherapy, radiotherapy, targeted therapy, and immunotherapy in order to enhance understanding of MPLC treatment.
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Humans ; Lung Neoplasms/surgery* ; Immunotherapy ; Combined Modality Therapy

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To investigate the effect of knockdown PRTN3 on polarization phenotype and anti-tumor function of macrophages in breast cancer.Methods A mouse monocyte/macrophage cell line(RAW264.7)with knockdown of PRTN3 was constructed.The mRNA and protein levels of PRTN3 were detected by RT-qPCR and flow cytometry.Macrophages were co-cultured with tumor cells,and the polarization phenotypes of macrophages were detected by flow cytometry,and the mRNA levels of polarization and cytokines related genes were detected by RT-qPCR.The tumor phagocytosis and tumor killing ability of macrophages were determined by in vitro phagocytosis assay and tumor killing assay.The effect of macrophages with PRTN3 knockdown on tumor progression and metasta-sis was compared in an orthotopic transplantation model of mouse breast cancer.Results The mRNA and protein levels of PRTN3 in the RAW264.7 cell line with stable knockdown of PRTN3 were significantly decreased(P＜0.01).Knockdown of PRTN3 in RAW264.7 cells upregulated the expression of M1 phenotype-related genes(CD80,CD86,iNOS,IL-1β,IL-6 and TNF-α)(P＜0.05).After macrophages co-culture with tumor cells,macrophages with knockdown of PRTN3 upregulated the expression of M1 phenotype-related genes(CD80,CD86,iNOS,IL-1β,IL-6 and TNF-α)(P＜0.01).Knockdown of PRTN3 enhanced the phagocyto-sis(P＜0.05)and tumor killing ability(P＜0.05)of macrophages in vitro.Adoptive transfusion of PRTN3-knockdown macrophages into tumor-bearing mice inhibited the growth of in situ breast cancer and reduced lung metastasis(P＜0.05).Conclusions PRTN3 regulates phenotypic polarization of macrophages,and knockdown of PRTN3 enhances the anti-tumor function of macrophages.

In CT examination,micro-offsets of±1-2 mm in CT laser-positioning systems may compromise clinical diag-nostic accuracy even when they remain below the equipment failure threshold.This paper analyzes the technical differences of CT laser positioning systems from different manufacturers and constructs a multidimensional micro-offsets detection system that com-bines phantom detection measurements,image backtracking analysis algorithm,and real-time monitoring technology.Integrating the clinical experience of multiple medical institutions,we proposed a brand-and anatomy-specific calibration strategy and explore the impact of micro-offsets on scanning accuracy and radiation dose.The strategy was verified in two clinical cases:in neurosur-gery,a Siemens CT positioning offset caused tumor residue,and after intervention the target deviation rate dropped to 0;in ortho-pedics,a GE CT offset forced a surgical plan revision,and post-intervention the plan-matching rate reached 100％.These results provide both a systematic theoretical foundation and standardized operating procedures for clinical practice.

Objective:To explore the application effects of the blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" in Medical Immunology. Methods:Eight-year program clinical medical students who were enrolled at Peking Union Medical College in 2016, 2017, and 2018 were selected as the research subjects. An anonymous questionnaire survey was used to analyze students' multidimensional evaluations of the new teaching methodology. The percentage of frontier hotspot topics in the "Immunology Forum" was used to analyze the students' mastery of cutting-edge knowledge in immunology. The number of "Immunology Forum" related "College Students Innovative Training Plan Program" from 2020 to 2023 was used to analyze the effectiveness of this new teaching method in cultivating students' scientific research and innovation abilities. Statistical analysis was conducted using SPSS 25.0 software, and the normality of all continuous variables was assessed using the Shapiro-Wilk test.Results:The questionnaire survey showed 100.00% satisfaction with the course and 95.90% recognition of the new teaching method. More than 90% of students agreed that the new teaching method improved their learning ability, research ability, innovation ability, internal drive, and academic communication ability. The average proportion of hotspot topics in the "Immunology Forum" was 90.37%±7.12%, which was significantly higher than the proportion of non-hotspot topics (5.67%±3.12%). The average number of topics related to "Immunology Forum" in the "College Students Innovative Training Plan Program" was 17.67±1.15 per session, which was significantly higher than the number of topics not related to "Immunology Forum" (8.00±1.73).Conclusions:The blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" can help students timely grasp the cutting-edge knowledge of immunology, cultivate their learning ability, internal drive, academic communication ability, innovation ability, and research ability, and lay a foundation for students to further explore their scientific research and innovation activities.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

In CT examination,micro-offsets of±1-2 mm in CT laser-positioning systems may compromise clinical diag-nostic accuracy even when they remain below the equipment failure threshold.This paper analyzes the technical differences of CT laser positioning systems from different manufacturers and constructs a multidimensional micro-offsets detection system that com-bines phantom detection measurements,image backtracking analysis algorithm,and real-time monitoring technology.Integrating the clinical experience of multiple medical institutions,we proposed a brand-and anatomy-specific calibration strategy and explore the impact of micro-offsets on scanning accuracy and radiation dose.The strategy was verified in two clinical cases:in neurosur-gery,a Siemens CT positioning offset caused tumor residue,and after intervention the target deviation rate dropped to 0;in ortho-pedics,a GE CT offset forced a surgical plan revision,and post-intervention the plan-matching rate reached 100％.These results provide both a systematic theoretical foundation and standardized operating procedures for clinical practice.

Objective:To explore the application effects of the blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" in Medical Immunology. Methods:Eight-year program clinical medical students who were enrolled at Peking Union Medical College in 2016, 2017, and 2018 were selected as the research subjects. An anonymous questionnaire survey was used to analyze students' multidimensional evaluations of the new teaching methodology. The percentage of frontier hotspot topics in the "Immunology Forum" was used to analyze the students' mastery of cutting-edge knowledge in immunology. The number of "Immunology Forum" related "College Students Innovative Training Plan Program" from 2020 to 2023 was used to analyze the effectiveness of this new teaching method in cultivating students' scientific research and innovation abilities. Statistical analysis was conducted using SPSS 25.0 software, and the normality of all continuous variables was assessed using the Shapiro-Wilk test.Results:The questionnaire survey showed 100.00% satisfaction with the course and 95.90% recognition of the new teaching method. More than 90% of students agreed that the new teaching method improved their learning ability, research ability, innovation ability, internal drive, and academic communication ability. The average proportion of hotspot topics in the "Immunology Forum" was 90.37%±7.12%, which was significantly higher than the proportion of non-hotspot topics (5.67%±3.12%). The average number of topics related to "Immunology Forum" in the "College Students Innovative Training Plan Program" was 17.67±1.15 per session, which was significantly higher than the number of topics not related to "Immunology Forum" (8.00±1.73).Conclusions:The blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" can help students timely grasp the cutting-edge knowledge of immunology, cultivate their learning ability, internal drive, academic communication ability, innovation ability, and research ability, and lay a foundation for students to further explore their scientific research and innovation activities.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.