BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

Objective:The impact of bystander CD8 + T cells (CD8 + Tbys) within the tumor microenvironment on the prognosis of early-stage non-small cell lung cancer (NSCLC) remains unclear, particularly concerning their infiltration differences at the invasive margin (IM) and tumor center (TC). Methods:We retrospectively collected postoperative specimens from 173 patients with primary early-stage NSCLC who underwent radical surgery at the Affiliated Tumor Hospital of Shandong First Medical University from 2014 to 2018. Tissue microarrays encompassing IM and TC regions were prepared and subjected to multicolor immunofluorescence staining (CK/CD8/CD103/DAPI). Image processing and phenotype recognition (CD8 + T cells, CK -CD8 +; CD8 + T bys, CK -CD8 +CD103 -) were performed using inFrom software, and automatic quantitative cell density analysis was conducted using R language. Differences in CD8 + T and CD8 + T bys densities at IM and TC were analyzed using the Mann-Whitney U test. The relationship between CD8 + T, CD8 + T bys and clinicopathological features was examined using the Kruskal-Wallis H test. The impact of CD8 + T and CD8 + T bys on recurrence-free survival (RFS) was evaluated using Kaplan-Meier, log-rank, and Cox proportional hazards models. Results:A total of 173 patients with stage ⅠA-ⅡA NSCLC were included, with a recurrence rate of 26.6% (46/173) and a median RFS of 62.3 months (range: 44.7-71.9 months). CD8 + T and CD8 + T bys densities (1/1 000) were significantly higher in the IM region than in the TC region [70(32, 155) vs. 37(18, 88), P＜0.001; 25(11, 46) vs. 18(7, 34), P=0.002]. No significant association was found between CD8 + T, CD8 + T bys and age, gender, smoking history, histological type, or pathological stage (all P＞0.05). Patients with low-density IM CD8 + T cells had lower RFS compared to those with high-density IM CD8 + T cells ( P=0.021; median RFS not reached), Further analysis revealed that patients with low-density IM CD8 + T bys cell had lower RFS compared to those with high-density IM CD8 + T bys ( P=0.047; median RFS not reached), and low-density IM CD8 + T cell was an independent risk factor for postoperative recurrence ( HR=1.836, 95% CI:1.007-3.347, P=0.048). Joint analysis of IM and TC revealed that patients with low IM CD8 + T bys and high TC CD8 + T bys had significantly lower RFS compared to the other three groups ( P=0.006), and this combination was an independent risk factor for postoperative recurrence in early-stage NSCLC ( HR=2.090, 95% CI:1.162-3.760, P=0.014). Conclusions:The spatial distribution of bystander CD8 + T cells within the primary tumor influences the prognosis of patients with early-stage NSCLC. Patients with low-density IM CD8 + T bys and high-density TC CD8 + T bys are more prone to recurrence after radical surgery.

Objective:The impact of bystander CD8 + T cells (CD8 + Tbys) within the tumor microenvironment on the prognosis of early-stage non-small cell lung cancer (NSCLC) remains unclear, particularly concerning their infiltration differences at the invasive margin (IM) and tumor center (TC). Methods:We retrospectively collected postoperative specimens from 173 patients with primary early-stage NSCLC who underwent radical surgery at the Affiliated Tumor Hospital of Shandong First Medical University from 2014 to 2018. Tissue microarrays encompassing IM and TC regions were prepared and subjected to multicolor immunofluorescence staining (CK/CD8/CD103/DAPI). Image processing and phenotype recognition (CD8 + T cells, CK -CD8 +; CD8 + T bys, CK -CD8 +CD103 -) were performed using inFrom software, and automatic quantitative cell density analysis was conducted using R language. Differences in CD8 + T and CD8 + T bys densities at IM and TC were analyzed using the Mann-Whitney U test. The relationship between CD8 + T, CD8 + T bys and clinicopathological features was examined using the Kruskal-Wallis H test. The impact of CD8 + T and CD8 + T bys on recurrence-free survival (RFS) was evaluated using Kaplan-Meier, log-rank, and Cox proportional hazards models. Results:A total of 173 patients with stage ⅠA-ⅡA NSCLC were included, with a recurrence rate of 26.6% (46/173) and a median RFS of 62.3 months (range: 44.7-71.9 months). CD8 + T and CD8 + T bys densities (1/1 000) were significantly higher in the IM region than in the TC region [70(32, 155) vs. 37(18, 88), P＜0.001; 25(11, 46) vs. 18(7, 34), P=0.002]. No significant association was found between CD8 + T, CD8 + T bys and age, gender, smoking history, histological type, or pathological stage (all P＞0.05). Patients with low-density IM CD8 + T cells had lower RFS compared to those with high-density IM CD8 + T cells ( P=0.021; median RFS not reached), Further analysis revealed that patients with low-density IM CD8 + T bys cell had lower RFS compared to those with high-density IM CD8 + T bys ( P=0.047; median RFS not reached), and low-density IM CD8 + T cell was an independent risk factor for postoperative recurrence ( HR=1.836, 95% CI:1.007-3.347, P=0.048). Joint analysis of IM and TC revealed that patients with low IM CD8 + T bys and high TC CD8 + T bys had significantly lower RFS compared to the other three groups ( P=0.006), and this combination was an independent risk factor for postoperative recurrence in early-stage NSCLC ( HR=2.090, 95% CI:1.162-3.760, P=0.014). Conclusions:The spatial distribution of bystander CD8 + T cells within the primary tumor influences the prognosis of patients with early-stage NSCLC. Patients with low-density IM CD8 + T bys and high-density TC CD8 + T bys are more prone to recurrence after radical surgery.

Warthin tumor is a benign salivary gland tumor comprising ductal epithelium and lymphoid stroma. To date, reports about the malignant transformations of intraepithelial and lymphoid components in Warthin tumor are extremely rare; lymphoid malignant transformation into B-cell lymphoma is particularly rare in combination with T-cell lymphoma. The case of Warthin tumor complicated with T-lymphoblastic lymphoma is reported to emphasize the importance of a careful light microscopic evaluation of lymphoid tissue in Warthin tumor for identifying occult lymphoma presence, reducing misdiagnosis and missed diagnosis, and determining a timely treatment.
Humans ; Adenolymphoma/pathology* ; Parotid Neoplasms/pathology* ; Salivary Gland Neoplasms ; Epithelium/pathology* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*

Objective To investigate the effect of Kuanxiong Lifei decoction on inflammatory factors in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and turbid phlegm obstructing lung syndrome. Methods Two hundred patients with AECOPD and turbid phlegm obstructing lung syndrome diagnosed by traditional Chinese medicine (TCM) differentiation visiting four hospitals of Longhua Hospital Affiliated to Shanghai University of TCM, Shanghai Seventh People's Hospital, Punan Hospital of Shanghai Pudong New Area, Gongli Hospital of Shanghai Pudong New Area were selected from May 2017 to March 2018, and they were divided into a test group and a control group by a random number table, 100 cases per group. The patients in the two groups were treated with routine western medicine according to the guidelines, and in the test group, additionally Kuanxiong Lifei decoction (components: pinellia ternate 15 g, allium macrostemon 12 g, ephedra 9 g, trichosanthes 30 g, poria cocos 15 g, almond 12 g, lumbricus 12 g, citrus peels 12 g, peach kernel 12 g , roasted licorice 6 g) was used for 10 days, the decoction was uniformly made by Chinese Medicine Pharmacy of Longhua Hospital, 1 dose daily, 2 times a day orally taken, warm 200 mL each time, 0.5 hours before or after meal. The efficacy was evaluated after treatment for 10 days. The level changes of white blood cell count (WBC), neutrophils (N), C-reactive protein (CRP), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) before and after treatment and the improvement of TCM syndrome scores and clinical efficacy were observed in two groups. Results After treatment, the levels of WBC, N, CRP, IL-8, TNF-α, TCM syndrome score of the patients in the two group were significantly decreased compared with those before treatment in the two groups (P < 0.05), and the above indexes in the test group were all significantly lower than those in the control group after treatment [WBC (×109/L): 6.58±1.41 vs.7.44±1.85, N: 0.58±0.08 vs. 0.64±0.08, CRP (mg/L): 7.3±1.8 vs. 9.6±1.7, IL-8 (ng/L): 23.5±6.2 vs. 27.8±9.8, TNF-α (ng/L): 9.45±2.18 vs. 10.25±1.67, TCM syndrome total score: 4.0 (3.0, 8.0) vs. 8.0 (5.0, 10.0), all P < 0.05]. The total effective rate of the test group was significantly higher than that of the control group [88% (88/100) vs. 84% (84/100), P < 0.05]. Conclusion Kuanxiong Lifei decoction can significantly reduce lung inflammatory factors, ameliorate overall symptoms and improve the prognosis of AECOPD patients with turbid phlegm obstructing lung syndrome.

Objective To investigate the relationship of c erbB2 with endocrine therapy and prognosis, to investigate the rapid and effective method to detect c erbB2 alteration in breast carcinoma(BC).Metheds Semi quantitative PCR was used to detect the amplification of c erbB2, and immunohistochemistry was used to detect the expression of protein of c erbB2. 58 cases of BC were followed up .Results There was significant relationship between c erbB2 protein overexpression and gene amplification(P