Objective To evaluate the efficacy and safety of rabbit anti-human thymocyte immuneglobulin(rATG)induction therapy in kidney transplant recipients from donation after cardiac death in China.Methods This was a prospective,multicenter,single-arm and interventional study conducted in China(NCT03099122).Adult patients who underwent kidney transplantation from donation after cardiac death and received rATG induction therapy(cumulative dose of 5 mg/kg)were included.Univariate and multivariate logistic regression analyses were used to identify factors associated with acute rejection(AR),delayed graft function(DGF),graft failure and patient death.The occurrence of adverse events was also analyzed.Results A total of 115 adult patients were enrolled in the study,of whom 107 were evaluable for efficacy.The incidence of biopsy-proven acute rejection(BPAR)and acute rejection(AR)was 2.8%(95%confidence interval 0.6%-8.0%)and 4.7%(95%confidence interval 1.5%-10.6%),respectively.The incidence of delayed graft function(DGF)was 13.1%(95%confidence interval 7.3%-21.0%).Graft and patient survival rates were 97.2%(95%confidence interval 92.0%-99.4%)and 99.1%(95%confidence interval 94.9%-100%),respectively.Multivariate logistic regression analysis showed that donor serum creatinine and recipient panel reactive antibodies were risk factors for DGF(both P<0.05).Common treatment-emergent adverse events(incidence>5%)included anemia(8.7%),infectious pneumonia(8.7%),and urinary tract infection(8.7%).Conclusions Standard-dose rATG induction therapy demonstrates low incidences of BPAR,AR,and DGF,and good safety in kidney transplant recipients from donation after cardiac death in China.

Objective To evaluate the efficacy and safety of rabbit anti-human thymocyte immuneglobulin(rATG)induction therapy in kidney transplant recipients from donation after cardiac death in China.Methods This was a prospective,multicenter,single-arm and interventional study conducted in China(NCT03099122).Adult patients who underwent kidney transplantation from donation after cardiac death and received rATG induction therapy(cumulative dose of 5 mg/kg)were included.Univariate and multivariate logistic regression analyses were used to identify factors associated with acute rejection(AR),delayed graft function(DGF),graft failure and patient death.The occurrence of adverse events was also analyzed.Results A total of 115 adult patients were enrolled in the study,of whom 107 were evaluable for efficacy.The incidence of biopsy-proven acute rejection(BPAR)and acute rejection(AR)was 2.8%(95%confidence interval 0.6%-8.0%)and 4.7%(95%confidence interval 1.5%-10.6%),respectively.The incidence of delayed graft function(DGF)was 13.1%(95%confidence interval 7.3%-21.0%).Graft and patient survival rates were 97.2%(95%confidence interval 92.0%-99.4%)and 99.1%(95%confidence interval 94.9%-100%),respectively.Multivariate logistic regression analysis showed that donor serum creatinine and recipient panel reactive antibodies were risk factors for DGF(both P<0.05).Common treatment-emergent adverse events(incidence>5%)included anemia(8.7%),infectious pneumonia(8.7%),and urinary tract infection(8.7%).Conclusions Standard-dose rATG induction therapy demonstrates low incidences of BPAR,AR,and DGF,and good safety in kidney transplant recipients from donation after cardiac death in China.

Objective:To evaluate the therapeutic value of radiotherapy in combined immunotherapy and chemotherapy as first-line treatment for patients with oligometastatic non-small cell lung cancer (NSCLC).Methods:A retrospective analysis was conducted on data from 195 NSCLC patients who lacked epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations and were treated at the Anyang Tumor Hospital and the Fourth Hospital of Hebei Medical University from January 2019 to December 2021. These patients consisted of 166 male and 29 female cases, aged from 28 to 85 years, with an average age of (61.4 ± 9.3) years. These patients were divided into two groups, with each group receiving the radiotherapy and combined immunotherapy and chemotherapy (the radiotherapy and combination group, n = 60) and combined immunotherapy and chemotherapy only (the combination group, n = 135). Then, propensity score matching (PSM) was performed to analyze the differences in prognosis between both groups before and after PSM, as well as the short-term efficacy and adverse reactions after PSM. Results:For the 195 NSCLC patients, the median follow-up time was 31.8 months, with median overall survival (OS) and median progression-free survival (PFS) recorded at 23.8 months and 9.2 months, respectively. The radiotherapy and combination group exhibited enhanced 1-, 2-, and 3-year survival rates of 78.5%, 55.9%, and 45.1%, respectively, significantly higher than the combination group (48.3%, 35.6%, and 26.6%, respectively, χ2 = 14.65, P < 0.001). Similarly, the radiotherapy and combination group displayed 1-, 2-, and 3-year PFS rates of 51.9%, 29.5%, and 22.7%, respectively, exceeding those of the combination group (30.0%, 24.5%, and 16.9%, respectively, χ2=6.09, P=0.014). After PSM, the radiotherapy and combination group manifested an objective response rate (ORR) of 60.0% (33/55) and a disease control rate (DCR) of 89.1% (49/55), which were 16.4% (9/55) and 56.4% (31/55), respectively for the combination group. These results suggested that the radiotherapy and combination group demonstrated significantly higher ORR and DCR ( χ2 = 22.18, 14.85, P<0.001). After PSM, the radiotherapy and combination group yielded 1-, 2-, and 3-year survival rates of 70.9%, 52.3%, and 41.9%, respectively, significantly than the combination group (43.6%, 29.8%, and 27.1%, respectively, χ2=8.95, P=0.003). The radiotherapy and combination group exhibited 1-, 2-, and 3-year PFS rates of 47.3%, 27.3%, and 18.7%, respectively, significantly higher than the combination group (23.6%, 17.6%, and 15.4%, respectively, χ2 = 6.71, P = 0.010). Multivariate Cox regression analysis revealed that independent factors affecting OS included clinical stage, treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.88, 2.11, 0.23, 1.79, P < 0.05). Similarly, independent factors affecting PFS consisted of treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.62, 0.37, 3.42, P <0.05). There were no statistical differences in the incidence of grade ≥ 2 bone marrow suppression (18.2% vs. 12.7%) and grade ≥ 2 pneumonia (21.8% vs. 14.5%) between both groups ( P>0.05). Conclusions:Introducing radiotherapy into combined immunotherapy and chemotherapy as first-line treatment for oligometastatic NSCLC can optimize both local and systemic disease control and significantly improve patient prognosis without increasing treatment-related adverse reactions.

Objective To discuss the application of multi-parameters of coronary CT angiography(CTA)in diagnosing coronary heart disease(CHD)and predicting major adverse cardiovascular events(MACE)after percutaneous coronary intervention(PCI).Methods A total of 350 patients with CHD,who received PCI at the Affiliated Beijing Rehabilitation Hospital of Capital Medical University of China from January 2021 to January 2024,were enrolled in this study as observation group.Other 180 patients with suspected CHD,who underwent coronary CTA and coronary angiography(CAG)to exclude coronary artery lesion in the same period as in the observation group,were collected and used as control group.According to whether MACE occurred or not within 6 months after PCI,the patients of observation group were further divided into MACE group and non-MACE group.The CTA parameters,including total plaque volume(TPV),plaque burden(PB),remodeling index(RI),fat attenuation index(FAI)around coronary artery,spot calcification and napkin-ring sign,were compared between the observation group and the control group as well as between MACE group and non-MACE group.Logistic regression analysis was used to analyze the independent factors influencing the occurrence of MACE after PCI.Area under receiver operating characteristic curve(AUC)was adopted to assess the value of each parameter in predicting the occurrence of MACE within 6 months after PCI.Results The TPV,PB,RI,FAI,and the detection rate of spot calcification and napkin-ring sign in the observation group were significantly higher than those in the control group(P＜0.05).Of the 350 patients in the observation group,54(15.43％)developed MACE within 6 months after PCI,including cardiac death(n=5,1.43％),non-fatal myocardial infarction(n=22,6.29％),target vessel reconstruction due to in-stent restenosis(n=15,4.29％),and hospitalization due to heart failure(n=12,3.43％),all the 54 patients were classified in MACE group.The non-MACE group had 296 patients.The TPV,PB,RI,FAI,and the detection rate of napkin-ring sign in MACE group were higher than those in non-MACE group(P＜0.05).Logistic multivariate analysis showed that TPV,PB and FAI were the independent factors influencing the occurrence of MACE in CHD patients after PCI(P＜0.05).ROC curve analysis indicated that in predicting the occurrence of MACE within 6 months after PCI the sensitivity of TPV,PB and FAI were 65.40％,76.90％and 76.90％respectively,and the specificity of TPV,PB and FAI were 63.80％,72.50％and 73.80％respectively.The sensitivity and specificity of the combined detection were 96.20％and 71.80％respectively,with an AUC of 0.896.Conclusion Multi-parameters of coronary CT A have important application value in diagnosing CHD and in predicting the occurrence of MACE after PCI.The combined detection of TPV,PB and FAI can provide important reference for making clinical decision.

Objective:To evaluate the therapeutic value of radiotherapy in combined immunotherapy and chemotherapy as first-line treatment for patients with oligometastatic non-small cell lung cancer (NSCLC).Methods:A retrospective analysis was conducted on data from 195 NSCLC patients who lacked epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations and were treated at the Anyang Tumor Hospital and the Fourth Hospital of Hebei Medical University from January 2019 to December 2021. These patients consisted of 166 male and 29 female cases, aged from 28 to 85 years, with an average age of (61.4 ± 9.3) years. These patients were divided into two groups, with each group receiving the radiotherapy and combined immunotherapy and chemotherapy (the radiotherapy and combination group, n = 60) and combined immunotherapy and chemotherapy only (the combination group, n = 135). Then, propensity score matching (PSM) was performed to analyze the differences in prognosis between both groups before and after PSM, as well as the short-term efficacy and adverse reactions after PSM. Results:For the 195 NSCLC patients, the median follow-up time was 31.8 months, with median overall survival (OS) and median progression-free survival (PFS) recorded at 23.8 months and 9.2 months, respectively. The radiotherapy and combination group exhibited enhanced 1-, 2-, and 3-year survival rates of 78.5%, 55.9%, and 45.1%, respectively, significantly higher than the combination group (48.3%, 35.6%, and 26.6%, respectively, χ2 = 14.65, P < 0.001). Similarly, the radiotherapy and combination group displayed 1-, 2-, and 3-year PFS rates of 51.9%, 29.5%, and 22.7%, respectively, exceeding those of the combination group (30.0%, 24.5%, and 16.9%, respectively, χ2=6.09, P=0.014). After PSM, the radiotherapy and combination group manifested an objective response rate (ORR) of 60.0% (33/55) and a disease control rate (DCR) of 89.1% (49/55), which were 16.4% (9/55) and 56.4% (31/55), respectively for the combination group. These results suggested that the radiotherapy and combination group demonstrated significantly higher ORR and DCR ( χ2 = 22.18, 14.85, P<0.001). After PSM, the radiotherapy and combination group yielded 1-, 2-, and 3-year survival rates of 70.9%, 52.3%, and 41.9%, respectively, significantly than the combination group (43.6%, 29.8%, and 27.1%, respectively, χ2=8.95, P=0.003). The radiotherapy and combination group exhibited 1-, 2-, and 3-year PFS rates of 47.3%, 27.3%, and 18.7%, respectively, significantly higher than the combination group (23.6%, 17.6%, and 15.4%, respectively, χ2 = 6.71, P = 0.010). Multivariate Cox regression analysis revealed that independent factors affecting OS included clinical stage, treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.88, 2.11, 0.23, 1.79, P < 0.05). Similarly, independent factors affecting PFS consisted of treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.62, 0.37, 3.42, P <0.05). There were no statistical differences in the incidence of grade ≥ 2 bone marrow suppression (18.2% vs. 12.7%) and grade ≥ 2 pneumonia (21.8% vs. 14.5%) between both groups ( P>0.05). Conclusions:Introducing radiotherapy into combined immunotherapy and chemotherapy as first-line treatment for oligometastatic NSCLC can optimize both local and systemic disease control and significantly improve patient prognosis without increasing treatment-related adverse reactions.

Programmed cell death 1 (PD-1) inhibitor therapy for lung adenocarcinoma may induce rare but severe hematologic adverse events, including severe anemia. Although glucocorticoids are recommended for managing immune-related adverse events, therapeutic experience with PD-1 inhibitor-induced severe anemia remains limited, and its efficacy and safety have not been fully validated. This article reports a case of advanced lung adenocarcinoma in which severe anemia developed following combination therapy with chemotherapy and PD-1 inhibitor. After comprehensive evaluation, the patient was diagnosed with anemia of inflammation (AI) and achieved significant hemoglobin recovery following high-dose glucocorticoid treatment. These findings may provide new insights into the recognition and management of this rare hematologic toxicity in clinical practice.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Anemia/etiology* ; Immunotherapy/adverse effects* ; Lung Neoplasms/immunology* ; Male ; Antibodies, Monoclonal/therapeutic use* ; Middle Aged

Objective:To investigate the efficacy of different types of neoadjuvant therapy for esophageal cancer.Methods:The clinical data of 542 patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant therapy in Anyang Tumor Hospital of Science and Technology from January 2015 to May 2022 were retrospectively analyzed. These patients, consisting of 198 females and 344 males, with 289 cases aging ≤ 65 and 253 cases aging >65, were divided into a neoadjuvant chemoradiotherapy (NCRT) group (137 cases), a neoadjuvant chemotherapy (NCT) group (241 cases), and a neoadjuvant immunotherapy plus chemotherapy (NICT) group (164 cases). In this study, primary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, and secondary endpoints comprised overall survival (OS), progression-free survival (PFS), and safety. Survival analysis was performed using the Kaplan-Meier method, and inter-group comparisons were made using the Log-rank test. Furthermore, prognostic factors were analyzed based on the Cox proportional hazards regression model.Results:The NCRT, NCT, and NICT groups exhibited MPR and pCR rates of 66.4% (91/137) and 35.3% (85/241), 63.4% (104/164) and 35.8% (49/137), and 6.6% (16/241) and 31.1% (51/164), respectively ( χ2=1.67, P < 0.001). These groups displayed 1-, 2-, and 3-year OS rates of 89.8%, 85.9%, and 91.9%; 82.3%, 71.4%, and 81.5%; and 72.3%, 61.4%, and 77.8%, respectively, with significant differences ( χ2=9.20, P < 0.01). Furthermore, they exhibited 1-, 2-, and 3-year PFS rates of 81.5%, 75.9%, and 80.1%; 67.9%, 61.0%, and 65.5%; and 66.6%, 53.5%, and 65.3%, respectively, with significant differences ( χ2=4.62, P < 0.05). Multivariate analysis showed that therapeutic modality, T stage, and N stage were independent prognostic factors for OS ( P < 0.05). Additionally, there was no difference in adverse reactions and postoperative complications among the three groups. Conclusions:Compared to NCT, NICT and NCRT feature higher pCR and MPR rates, along with more survival benefits. Therefore, neoadjuvant immunotherapy has the potential to serve as a preoperative therapeutic modality for esophageal cancer, yet large-scale randomized controlled trials are still required for confirmation.

Objective:To evaluate the efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC).Methods:A retrospective analysis was conducted on the data of 75 patients with R/M ESCC treated with sintilimab at Anyang Tumor Hospital from January 2020 to October 2021. The patients were divided into the radiotherapy (RT) group ( n=37) and non-radiotherapy (NRT) group ( n=38) based on whether they received radiotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse effects were compared between two groups. Count data were expressed as composition ratios and analyzed using Chi-square test or Fisher's exact test. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:There was no statistically significant difference in ORR and DCR between the RT and NRT groups (70% vs. 61%, P=0.375; 95% vs. 89%, P=0.414). However, the complete response (CR) rate in the RT group was higher compared to that in the NRT group (19% vs. 3%, P=0.022). The median follow-up duration was 25.4 months. There was no statistically significant difference in the median PFS and OS between the RT and NRT groups (13.8 months vs. 9.9 months, P=0.221; 20.2 months vs. 18.9 months, P=0.214). Subgroup analysis demonstrated that among patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes, there was no statistically significant difference in the median PFS between the RT and NRT groups (15.1 months vs. 8.4 months, P=0.115), but the median OS in the RT group was better than that in the NRT group (not reached vs. 12.3 months, P=0.036). Compared to the NRT group, besides an increase in grade 1-2 pneumonitis (41% vs. 18%, P=0.035), no significant increase in treatment-related toxicity was observed in the RT group. Conclusion:Immunotherapy combined with radiotherapy is safe in patients with R/M ESCC, and shows survival benefit in patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes.

Objective:To explore the biomarkers of radiochemotherapy sensitivity and potential mechanisms in esophageal squamous cell carcinoma (ESCC), and validate the screened biomarkers at human tissue, animal and cellular levels.Methods:Based on bioinformatics system, clinical and transcriptome data of ESCC were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. HUB genes related to chemoradiotherapy sensitivity were identified by weighted correlation network analysis (WGCNA) and cytoscape software and survival differences were analyzed. CellMiner database was used to predict and screen drugs with strong correlation with HUB genes. The expression levels of HUB genes in clinical tissues was detected by real-time reverse transcription PCR (qRT-PCR). Then, oe-AKR1C1 mouse model, cisplatin-resistant cells and radiation-resistant cells were constructed, and the effects of HUB genes on tumor size and mass, and cell proliferation ability were analyzed.Results:A total of 5 HUB genes were identified, among which NAD(P)H quinone dehydrogenase 1 (NQO1), AKR1C1 and NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) were significantly correlated with ESCC survival (all P<0.05). Dacarbazine, alectinib and obatoclax were the anti-tumor drugs predicted to have a strong correlation with HUB genes in this study. Human tissue test results showed that the expression levels of NQO1, AKR1C1 and NDUFS2 were up-regulated in patients with chemoradiotherapy resistance, and AKR1C1 and NDUFS2 had statistical significance (both P<0.05). The results of mouse tumor bearing experiment showed that the tumor volume and mass of oe-AKR1C1 mice after radiotherapy and chemotherapy were significantly higher than those in the control group (both P<0.05). The cell experiment results showed that the expression levels of AKR1C1 and NDUFS2 in radiation-resistant cells and cisplatin-resistant cells were significantly higher than those in control cells ( P<0.05), while there was no statistically significant difference in the relative expression level of NQO1. Conclusion:NQO1, AKR1C1 and NDUFS2 are HUB genes significantly related to the survival of ESCC, which can be used as important therapeutic tumor targets for ESCC.

ObjectiveTo observe the effect of gastrodin on the steroid regulatory element-binding protein 1c （SREBP1c） signaling pathway in high-fat high-cholesterol diet （HFHC）-induced mice and explore the mechanism of gastrodin in the treatment of non-alcoholic fatty liver disease （NAFLD）. MethodEight-week-old male C57BL/6J mice were used in vivo and divided into the following four groups， with six mice in each group： normal group， gastrodin group （50 mg·kg^-1）， model group， and model + gastrodin group （50 mg·kg^-1）. NAFLD model was established by feeding mice with HFHC for four weeks， and the mice were euthanized and the liver tissues were collected after four weeks. In vitro experiments were performed using Huh7 cells which were divided into five groups， and induced with free fatty acids （FFA， 200 μmol·L^-1， oleic acid-palmitic acid 2∶1） to establish an NAFLD cell model. After 24 h， different concentrations of gastrodin （0， 5， 10， 20， and 40 μmol·L^-1） were added to each group and cultured for another 24 h. Oil red O staining was used to detect lipid accumulation in mouse liver and Huh7 cells. Hematoxylin-eosin （HE） staining was used to observe pathological changes in liver tissue. Levels of serum total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and triglycerides （TG） were measured using an automatic biochemical analyzer. Relevant assay kits were used to detect liver TC， TG， and FFA levels. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of lipid synthesis-related proteins fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）， and stearoyl-CoA desaturase 1 （SCD1）. ResultCompared with the normal group， the model group showed significantly increased serum TC， LDL-C， and TG levels （P<0.01）， liver TC， TG， and FFA levels （P<0.01）， increased lipid accumulation in Huh7 cells （P<0.01）， and significantly increased expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells （P<0.01）. Compared with the model group， after gastrodin treatment， the serum TC， LDL-C， and TG levels in mice significantly decreased （P<0.05， P<0.01）， the severity of fatty liver disease improved significantly， liver TC， TG， and FFA levels decreased significantly （P<0.05， P<0.01）， lipid accumulation in Huh7 cells decreased significantly （P<0.05， P<0.01）， the expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells decreased significantly （P<0.05， P<0.01）. ConclusionGastrodin can reduce hepatic lipid accumulation and blood lipid levels， improve HFHC-induced NAFLD， and its mechanism of action may be related to the regulation of the SREBP1c lipid synthesis-related signaling pathway.