Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Effect of VEGFR 2 gene polymorphism V297I on clinical outcomes of advanced NSCLC patients treated with bevacizumab combining with chemotherapy as first line treatment / 中国肿瘤生物治疗杂志

@# Objective: To investigate the effect of VEGFR2 gene polymorphism V297I on the clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with bevacizumab combining with chemotherapy. Methods:Atotal of 135 patients with advanced NSCLC, who were treated by bevacizumab plus platinum-based chemotherapy for first-line regimen, were included in this study. PCR-RFLP assay was used to detect the VEGFR2 genotypes in peripheral blood of patients and qPCR was used to detect the VEGFR2 mRNA in the cancer tissues of NSCLC patients. Logistic regression analysis was used to analyze the correlation between gene polymorphism and other variants, Kaplan-Meier assay to analyze the correlation between genotype and prognosis, and Cox regression model to analyze the risk factors for patients’PFS. Results: Of the polymorphisms analyzed, only polymorphism V297I was found to be of clinical significance. V297I locates in the coding region of VEGFR2, and it’s prevalence in the study population was as follows: CC genotype in 99 cases (73.33%), CT genotype in 33 cases (24.44%) and TT genotype in 3 cases (2.23%); the frequency of minor allele was 0.14, and the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P>0.05). The overall objective remission rate (ORR) of the 135 patients was 45.93%, the median progression free survival (mPFS) was 8.2 months and the median overall survival (mOS) was 20.8 months. The ORR, mPFS and mOS of patients with CT/TT genotype and CC genotype were 41.67%, 6.2 months, 18.9 months and 47.47%, 8.9 months and 21.5 months, respectively (all P<0.05).Additionally, the mRNAexpression of VEGFR2 in cancer tissues of the patients with CT/TT genotype was significantly higher than those with CC genotype (P< 0.01). The risk factors for patients’PFS included V297I, gender and ECOG score. Conclusion:Among advanced NSCLC patients treated by bevacizumab plus platinum-based chemotherapy, the polymorphism V297I of VEGFR2 may impact the clinical outcomes and prognosis of NSCLC patients treated with bevacizumab first line treatment by influencing the mRNAexpression of VEGFR2.

Comparative analysis of endoscopic R0 resection followed by additional chemoradiotherapy for early stage esophageal cancer compared with esophagectomy: A multi-center study from ECETC / 中国胸心血管外科临床杂志

@#Objective    To evaluate the strategy of chemoradiotherapy following endoscopic R0 resection for esophageal cancer in M3-T1b stage. Methods    There were 45 esophageal cancer patients with M3-T1b stage with endoscopic R0 resection followed by additional chemoradiotherapy from ECETC (Esophageal Cancer Endoscopic Therapy Consortium) as a trial group with 34 males and 11 females at age of 61.37±7.14 years. There were 90 patients with esophagectomy from Fudan University Shanghai Cancer Center as a control group with 63 males and 27 females at age of 61.04±8.17 years. Propensity score match (1:2) was used to balance the factors: gender, age, position, depth of invasion and lymphovascular invasion (LVI), which may influence the outcomes. Overall survival (OS) rate, relapse free survival (RFS) rate, and local recurrence rate were compared between the two groups. Result    There was no statistical difference (HR=2.66 with 95%CI 0.87 to 8.11, P=0.179) in terms of OS rate between the two groups. One, two and three years overall survival rate of patients in the control group was 93%, 86%, and 84%, respectively. Nobody died in the trial group within 3 years after surgery. The RFS rate between the two groups didn’t significantly differ (HR=1.48, 95% CI 0.66 to 3.33, P=0.389). One, two and three years RFS rate of patients in the contorl group was 87%, 78%, and 76%, respectively, while 97%, 93%, and 73% in the trial group, respectively. The local recurrence rates between the two groups didn’t significantly differ either ( HR=0.53，95%CI 0.13 to 2.18, P=0.314). One, two and three years local recurrence rate of patients in the control group was 5%, 6% and 6%, respectively, while 0%, 0% and 21% in the trial group, respectively. Conclusion    Similar outcomes are found regarding OS, RFS and local recurrence rates between the two groups. The strategy of endoscopic R0 resection followed by additional chemoradiotherapy has prospect for the treatment of esophageal cancer in M3-T1b stage. And this kind of therapy may be provided for those with risk factors or can not tolerate surgery.

Feasibility of neoadjuvant therapy followed by minimally invasive esophagectomy for locally advanced esophageal cancer: A case control study / 中国胸心血管外科临床杂志

@#bjective    To evaluate the safety and efficacy of neoadjuvant therapy followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal cancer. Methods    We retrospectively analyzed clinical data of 56 consecutive patients with locally advanced esophageal cancer treated by neoadjuvant therapy followed by surgery in our hospital between January 2015 and December 2016. There were 51 males and 5 females. The patients were divided into 2 groups. Neoadjuvant therapy followed by open surgery esophagectomy group was as an OE group with 25 patients aged 61 (50-73) years. And neoadjuvant therapy followed by MIE was as a MIE group with 31 patients aged 60 (55-79) years. Results    The pathologic complete response (pCR) rate of 28 patients with neoadjuvant concurrent chemoradiotherapy was significantly higher than that of 28 patients with neoadjuvant chemotherapy (21.4% vs. 10.7%, P<0.05). The operation time, intraoperative blood loss, R2 rate and the number of lymph nodes dissection in the MIE group were obviously better than those of the OE group with statistical differences (P<0.05). However, there was no significant difference in the number of resected lymph nodes along the bilateral recurrent laryngeal nerves and lymph node metastasis rate (P>0.05) between the two groups. The incidence of postoperative respiratory complications in the MIE group was lower than that of the OE group (P=0.041). There was no significant difference between the two groups in the incidence of other complications, re-operation, re-entry to ICU, median length of stay or perioperative deaths (P>0.05). There was only one patient with neoadjuvant concurrent chemoradiotherapy in the OE group died due to gastric fluid asphyxia caused by  trachea-esophageal fistula. Conclusion    Neoadjuvant therapy followed by MIE for locally advanced esophageal cancer is safe and feasible. The oncological outcomes seem comparable regardless of OE.

Effect of retrosternal versus posterior mediastinum approach for tubular stomach reconstruction on early surgical complications and short-term quality of life in patients with McKeown esophagectomy: A case control study / 中国胸心血管外科临床杂志

@#Objective     To compare short-term quality of life and postoperative complications in esophageal squamous cell carcinoma patients with different routes reconstruction after McKeown esophagectomy. Methods     The clinical data of 144 patients with esophageal squamous cell carcinoma who received McKeown esophagectomy in Shanghai Chest Hospital from January 2016 to October 2016 were retrospectively reviewed. Among them 93 patients accepted retrosternal approach (a RR group, 71 males and 22 females at an average age of 63.5±7.7 years) and 51 patients accepted posterior mediastinal approach (a PR group, 39 males and 12 females at an average age of 62.3±8.0 years). Short-term surgical outcomes were compared and a Quality of Life Questionnaire of Patients Underwent Esophagectomy 1.0   was performed at postoperative 1st and 3rd month. Results     There was no difference in two groups in sex, age, Body Mass Index (BMI), and location and clinical stage of tumors (P>0.05). The neoadjuvant therapy was more performed in the RR group (16.1% vs. 5.9%, P=0.075). There were more robot-assisted esophagecctomy operations performed in the PR group (52.9% vs. 45.2%, P=0.020). No significant difference was noted in operation duration, intraoperative blood loss or length of ICU stay between the RR and PR groups (251.3±59.1 min vs. 253.1±27.7 min, P=0.862; 223.7±75.1 ml vs. 240.0±75.1 ml, P=0.276; 3.7±6.6 d vs. 2.3±2.1 d, P=0.139). The patients in the PR group had more lymph nodes dissected and shorter hospital stay (P<0.001). Rate of R1/2 resection was higher in the RR group (12.9% vs. 5.9%, P=0.187). No surgery-related mortality was observed in both groups. The anastomotic leak and the anastomotic stricture was higher in the RR group than that in the PR group (25.8% vs. 5.9%, P=0.003). No significant difference was found between the two groups in the quality of life at postoperative 1st and 3rd month. However, the quality of life at postoperative 3rd month significantly improved in both groups (P<0.001). Compared with the PR group, the dysphagia was more severe in the RR group at postoperative 1st month (3.3±1.5 vs. 2.6±1.1, P=0.007), while the reflux symptom was lighter at postoperative 3rd month (3.0±1.8 vs. 3.6±1.6, P=0.045). Conclusion     The two different routes reconstruction after McKeown esophagectomy are both safe and feasible. The anterior mediastinal approach increases the risk of anastomotic leak, but with low incidence of reflux symptom.

Consideration about the application of robotic surgical system in minimally invasive esophagectomy under multidisciplinary treatment concept / 中国胸心血管外科临床杂志

@#Nowadays, thoracoscopic laparoscopic esophagectomy (TLE) has been widely used in the treatment of esophageal cancer. In recent years, robot assisted minimally invasive esophagectomy (RAMIE) has been developing vigorously. According to the research progress and practical experience in the world, RAMIE has the same safety and effectiveness as TLE. In this paper, several aspects on this novel operation were demonstrated, including the safety evaluation, lymph node dissection, prognosis of RAMIE, comparison of RAMIE and TLE, and the role of RAMIE in multidisciplinary treatment of esophageal cancer, in order to promote the rational application of RAMIE in esophagectomy.

Clinical Study of Cyclosporin A for Psoriasis in China

BACKGROUND: The efficacy of Cyclosporin A(CyA) in the treatment of psoriasis is well recongized, the dosage less than 5mg/kg per day(mg/kg/d) is recommended. OBJECTIVE: The purpose of this study is to evaluate the indication, dose, course and side-effects of CyA therapy for psoriasis, especially in China. METHODS: Forty patients with psoriasis were treated with doses of CyA 5mg/kg/d, compared with 20 patients treated with Tigason lmg/kg/d by Global PAST. RESULTS: 1. Of 40 patients 33 patients (82.5%)were cured clinically in 4-5weeks and all the patients(100%) had responses to the therapy. 2. The efficacy and the Global PASI reduction of CyA therapy were significantly better than that of Tigason therapy. 3. During the CyA therapy, no severe side-effects and obvious laboratory changes were found. CONCLUSION: CyA(5mg/kg/d) was satisfactory for psoriasis, especially for psoriasis pustulosa, arthropathica and erythroderma. CyA was found to be superior to Tigason. The therapy course and side-effects seemed to be related to the dosage.