Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective To explore the correlation of baseline CCL19+dendritic cell(CCL19+DC)infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+T cell infiltration.Methods We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January,2020 to December,2023,and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+DC and CD8+T cell infiltration using immunofluorescence assay.We evaluated the predictive value of baseline CCL19+DCs for patient responses to immunotherapy using receiver-operating characteristics(ROC)curves and analyzed the correlations of baseline CCL19+DC expression with immunotherapy efficacy and CD8+T cell and cytotoxic T lymphocyte(CTL)infiltrations.In co-culture systems of lung adenocarcinoma PC9 cells,CD8+T cells and DCs(overexpressing CCL19 with or without anti PD-1 antibody treatment),the expressions of granzyme B,perforin,IFN-γ,and Ki-67 in T cells were analyzed using flow cytometry.Results The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+DC infiltration level in lung adenocarcinoma tissues than those with poor responses.CCL19+DC infiltration had an area under ROC curve of 0.785,a sensitivity of 75.6%,and a specificity of 62.8%for predicting immunotherapy efficacy.The expression of CD8+T cell surface molecules Granzyme B(P<0.01),Perforin(P<0.01),IFN-γ(P<0.01)and Ki-67(P<0.001)in patients with high expression of CCL19+DC were higher than those in patients with low expression of CCL19+DC.The baseline CCL19+DC infiltration level was positively correlated with immunotherapy efficacy(P=0.003),CTL infiltration of(r=0.6657,P<0.001)and CD8+T cell infiltration(P=0.007).In the co-cultured cells,CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+T lymphocytes than either of the single treatments(P<0.01 or 0.001).Conclusion The baseline CCL19+DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

Objective: To establish aNBR1-knockout lung cancer mouse model through CRISPR-Cas9 technology by using adeno-associated virus(AAV) as a vector to specifically inhibitNBR1expression and to investigate the impact ofNBR1knockout on tumor growth and immune cell infiltration and regulation. Methods: sgRNAs targeting mouseNBR1(Gene ID: 17966) was designed using the online tool CRISPOR(http://crispor.tefor.net/crispor.py). AAV6 was utilized as the vector for sgRNA delivery, and the efficiency of gene knockout was confirmed using PCR and DNA sequencing methods. To determine the best AAV infection approach in mice, 6 C57BL/6J mice were randomly divided into intranasal and endotracheal groups. After 28 days, lung tissue sections were assessed for enhanced green fluorescent protein expression to identify the more efficient infection method for subsequent experiments. Lung tumor growth, as well as immune cell infiltration and activation status in tumor tissues, were detected using methods including HE staining, immunohistochemistry, immunofluorescence, and flow cytometry. Results: DNA sequencing and immunofluorescence results indicated successful construction of the AAV6-U6-sgNBR1-CAG-Cre-GFP vector with stable knockout efficiency. Fluorescence microscopy showed higher efficiency of lung infection in mice through intratracheal administration(P<0.05). HE staining revealed reduced tumor area in mouse lungs after targetedNBR1knockout compared to the control group(P<0.01). Immunofluorescence and flow cytometry results demonstrated enhanced functional activity of CD8+T lymphocytes in lung cancer tissues of mice with targetedNBR1knockout, characterized by increased effector T lymphocytes and decreased exhausted T lymphocytes(P<0.01). Conclusion Using CRISPR/Cas9 technology, we construct a lung cancer mouse model with targetedNBR1knockout. We verify that targeted inhibition of NBR1 expression significantly enhances the functional activity of CD8+T lymphocytes in lung tissues, resulting in suppressed tumor growth, reduced tumor burden, and extended survival in lung cancer mice. This study lays an experimental foundation for investigations into the mechanisms and functions ofNBR1and other genes in lung adenocarcinoma cells.

Objective To explore the correlation of baseline CCL19+dendritic cell(CCL19+DC)infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+T cell infiltration.Methods We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January,2020 to December,2023,and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+DC and CD8+T cell infiltration using immunofluorescence assay.We evaluated the predictive value of baseline CCL19+DCs for patient responses to immunotherapy using receiver-operating characteristics(ROC)curves and analyzed the correlations of baseline CCL19+DC expression with immunotherapy efficacy and CD8+T cell and cytotoxic T lymphocyte(CTL)infiltrations.In co-culture systems of lung adenocarcinoma PC9 cells,CD8+T cells and DCs(overexpressing CCL19 with or without anti PD-1 antibody treatment),the expressions of granzyme B,perforin,IFN-γ,and Ki-67 in T cells were analyzed using flow cytometry.Results The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+DC infiltration level in lung adenocarcinoma tissues than those with poor responses.CCL19+DC infiltration had an area under ROC curve of 0.785,a sensitivity of 75.6%,and a specificity of 62.8%for predicting immunotherapy efficacy.The expression of CD8+T cell surface molecules Granzyme B(P<0.01),Perforin(P<0.01),IFN-γ(P<0.01)and Ki-67(P<0.001)in patients with high expression of CCL19+DC were higher than those in patients with low expression of CCL19+DC.The baseline CCL19+DC infiltration level was positively correlated with immunotherapy efficacy(P=0.003),CTL infiltration of(r=0.6657,P<0.001)and CD8+T cell infiltration(P=0.007).In the co-cultured cells,CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+T lymphocytes than either of the single treatments(P<0.01 or 0.001).Conclusion The baseline CCL19+DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

Objective:To investigate the clinical application of Grunenwald incision in cervicothoracic junction surgery.Methods:The clinical data of 25 patients with cervicothoracic junction tumor and 1 patient with cervicothoracic junction trauma in the single treatment group of Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2011 to September 2021 were analyzed retrospectively, including 19 males and 7 females, aged 9-73 years old. Among the 26 patients, there were 9 cases of upper mediastinal tumor, 6 cases of superior sulcus tumor, 4 cases of thyroid tumor invading the upper mediastinal, 4 cases of chest wall tumor, 2 cases of esophageal cancer combined with supraclavicular lymph node metastasis, and 1 case of foreign body penetrating injury at the cervicothoracic junction. Grunenwald incision or additional posterolateral thoracic incision, median sternal incision, neck collar incision were used in all patients. The degree of tumor resection was evaluated. The operation time, intraoperative blood loss, length of hospital stay were observed, and the postoperative follow-up was analyzed.Results:There was no perioperative death in the whole group. 14 cases were treated with Grunenwald incision alone, 6 cases with additional posterolateral chest incision, 4 cases with additional neck collar incision, and 2 cases with additional median sternal incision. The tumors were completely resection in 22 cases, palliative tumor resection in 3 cases, and complete foreign body removal in 1 case. Postoperative pathology included 4 cases of schwannoma; 3 cases of lung adenocarcinoma, thyroid cancer and myofibroblastoma, respectively; 2 cases of supraclavicular lymph node metastasis of esophageal cancer and lung squamous carcinoma, respectively; 1 case of large cell neuroendocrine carcinoma, metastatic carcinoma of the first rib after lung squamous cell carcinoma, ganglioneuroma, nodular goiter, hemangioma, well differentiated liposarcoma, vascular endothelial tumor and cavernous angioma, respectively. The operation time was 120-430 min, with a mean of(226.92±88.40)min. The intraoperative blood loss was 100-1 000 ml, with a mean of(273.46±196.34)ml. The length of hospital stay was 6-26 days, with a mean of(12.73±4.46 )days. 26 patients were followed up for 6-130 months, with a mean of(57.88±43.64) months. During the follow-up period, 6 patients died.Conclusion:Grunenwald incision can provide good exposure of the structures near the cervicothoracic junction, preserve the integrity of sternoclavicular joint, reduce shoulder deformity, and has advantages for patients with cervicothoracic junction tumors, high rib resection, and cervicothoracic junction trauma.

This study was aimed at identifying the bioactive components of the crude and stir-baked hawthorn for invigorating spleen and promoting digestion, respectively, to clarify the processing mechanism of hawthorn by applying the partial least squares(PLS) algorithm to build the spectrum-effect relationship model. Firstly, different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions were prepared, respectively. Then, the contents of 24 chemical components were determined by ultra-high performance liquid chromatography-mass spectrometry. The effects of different polar fractions of crude hawthorn and stir-baked hawthorn aqueous extracts and combinations of different fractions were evaluated by measuring the gastric emptying rate and small intestinal propulsion rate. Finally, the PLS algorithm was used to establish the spectrum-effect relationship model. The results showed that there were significant differences in the contents of 24 chemical components for different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions, and the gastric emptying rate and small intestinal propulsion rate of model rats were improved by administration of different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions. The bioactive components of crude hawthorn identified by PLS models were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, neochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, malic acid, quinic acid and fumaric acid, while neochlorogenic acid, cryptochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, quinic acid and fumaric acid were the bioactive components of stir-baked hawthorn. This study provided data support and scientific basis for identifying the bioactive components of crude and stir-baked hawthorn, and clarifying the processing mechanism of hawthorn.
Animals ; Rats ; Spleen ; Crataegus ; Quinic Acid ; Least-Squares Analysis ; Vanillic Acid ; Algorithms ; Digestion