1.Application of optimized hippocampus-avoidance prophylactic cranial irradiation in limited-stage small cell lung cancer
Tianyou ZHAN ; Lei DENG ; Wenqing WANG ; Tao ZHANG ; Nan BI ; Jianyang WANG ; Xin WANG ; Wenyang LIU ; Yirui ZHAI ; Zefen XIAO ; Jima LYU ; Qinfu FENG ; Dongfu CHEN ; Ye-Xiong LI ; Zongmei ZHOU
Chinese Journal of Radiation Oncology 2024;33(3):205-211
Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.
2.Clinical characteristics of eosinophilic gastroenteritis in children under six years old
Jing LI ; Jin ZHOU ; Yan ZHAO ; Jie WU ; Tianyou WANG
Chinese Pediatric Emergency Medicine 2024;31(1):41-46
Objective:To analyze the clinical characteristics of eosinophilic gastroenteritis in children under 6 years old.Methods:The clinical data,laboratory examinations,imaging examinations,gastrointestinal endoscopy,histopathology,treatment,and prognosis of patients under 6 years old with eosinophilic gastroenteritis who were hospitalized in the Department of Gastroenterology,Beijing Children's Hospital from January 1,2016 to December 31,2022 were collected and analyzed.Results:A total of 31 children under 6 years of age with eosinophilic gastroenteritis were enrolled in the study,including 14 cases≤3 years old and 17 cases>3 years old, and 38.71% (12/31) of them had multiple sites involved. The main clinical manifestations were abdominal pain(20/31,64.52%),vomiting(11/31,35.48%),hematochezia(7/31,22.58%),and diarrhea(7/31,22.58%).The children with eosinophilic duodenitis and eosinophilic colitis were more likely to have abdominal pain, with an incidence of 83.33%(10/12)( P<0.05). Eosinophilia increased in 70.97%(22/31)of children,which was more common in children >3 years of age(88.24% vs. 50.00%, P<0.05).Anemia was seen in 29.03%(9/31)of the patients,and it was more common in children under 3 years of age(50.00% vs. 11.76%, P<0.05).Hypoalbuminemia was found in 22.58%(7/31)of patients. Specific IgE(sIgE)was positive in 73.33%(22/30)of children. Milk,egg,and wheat were the most common allergens. Gastrointestinal endoscopy showed mucosal edema(29/31,93.55%),erythema(26/31,83.87%),roughness(12/31,38.71%),ulcer(10/31,32.26%),et al.All children were treated with the elimination diet. Besides,10 cases were treated with omeprazole, 16 cases were treated with montelukast, and 17 cases were treated with glucocorticoid. The incidence of relapse or steroid resistance was 32.26%(10/31),and 70.00%(7/10)of them occurred within one year of treatment. Conclusion:Eosinophilic gastroenteritis in children under 6 years of age may involve single or multiple sites.Abdominal pain is the most common clinical manifestation. Children may have elevated peripheral blood eosinophils,anemia,or hypoalbuminemia.Most children have food allergens. Nearly one-third of children experience relapse or steroid resistance.
3.Clinical characteristics of eosinophilic esophagitis in children
Jing LI ; Jin ZHOU ; Jing GUO ; Yongli FANG ; Jie WU ; Tianyou WANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(2):104-108
Objective:To summarize the clinical characteristics of eosinophilic esophagitis (EoE) in children.Methods:Clinical data of children with EoE who were hospitalized in the Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University from January 1, 2017, to December 31, 2022, were retrospectively analyzed.Results:A total of 18 children with EoE were included in the study, including 13 males and 5 females, with the age of 11.96 (4.96, 12.81) years.Vomiting was more common in preschool children (4/5), while abdominal pain was the main symptom in school-age and adolescent children (11/13). There were 22.22% (4/18) of the children with EoE had an increased white blood cell count, and 33.33%(6/18) had an increased eosinophil count.Allergic history in the first-degree relatives was detected in 55.56%(10/18) of the children with EoE.Total immunoglobulin E (IgE) level was elevated in 68.75% (11/16) of the children.Food-specific IgE was positive in 66.67% (12/18) of the children with EoE.Milk, eggs, and wheat were the most common allergens.Esophageal mucosal hyperemia and erythema, rough, erosion, linear ulcers, annular changes, furrow or wrinkled paper changes, granular changes, polypoid or relaxation of the cardia were seen under endoscopy, whereas 27.78% (5/18) of the children showed normal esophageal mucosa.The histopathology showed chronic inflammation of the esophagus and increased eosinophil count.Three patients were lost of follow-up, and the remaining 15 were followed up for 6-24 months.All children with EoE were treated with the elimination diet.Nine children treated with glucocorticoids experienced clinical remission in a short period of time, involving 1 case with recurrence after withdrawal and being effectively treated by hormone therapy, and 2 cases of repeated digestive system symptoms or increased eosinophil count after withdrawal and being effectively relieved by the elimination diet.Conclusions:EoE is more common in elderly children and boys.Vomiting is the main symptom in pre-school aged children, whereas abdominal pain is the main symptom in school-aged children and adolescents.Increased peripheral white blood cell count and eosinophil count can be detected in some cases, and most of them are positive for food allergen tests.Gastrointestinal endoscopy and histopathology are important in the diagnosis of EoE.Elimination diet may be effective in some patients.Glucocorticoids are of great significance in the treatment of EoE, but a few children are steroid-dependent.
4.Prognostic value of CDKN3 and analysis of immune cell infiltration in oral squamous cell carcinoma
Hui ZHU ; Huanping LU ; Tianyou LI ; Jing CHEN
International Journal of Laboratory Medicine 2024;45(11):1302-1307
Objective To analyze the predictive value of cyclin-dependent activator 3(CDKN3)in the prog-nosis of oral squamous cell carcinoma(OSCC)and its relationship with immune cell infiltration,and to ex-plore the biological function of CDKN3 in the occurrence and development of OSCC.Methods RNAseq data related to OSCC were obtained from the Cancer Genome Atlas and Gene Expression Omnibus database.The expression level of CDKN3,prognostic value,clinicopathological features and immune cell infiltration were an-alyzed by R language and statistical methods.Gene enrichment analysis was used to analyze the biological role of CDKN3 in OSCC.Results Compared with normal tissues,CDKN3 was highly expressed in OSCC tumor tissues(P<0.01),and the area under curve for the receiver operating characteristic curve was 0.955.The pa-tients with high expression of CDKN3 had a poor prognosis(P=0.024).The expression of CDKN3 was cor-related with pathological stage(P<0.05)and histological grade(P<0.001).There was a significant differ-ence in the level of immune cell infiltration between the CDKN3 high and low expression groups(P<0.05).Functional enrichment analysis showed that CDKN3 was closely related to cell cycle.Conclusion CDKN3 may be a potential carcinogenic risk factor of OSCC,which is related to the clinicopathological characteristics,prog-nosis and immune cell infiltration of patients.CDKN3 may be a diagnostic biomarker and a potential therapeu-tic target for OSCC.
5.Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma
Huixia GAO ; Ying LI ; Nan LI ; Shuang HUANG ; Meng ZHANG ; Chunju ZHOU ; Ningning ZHANG ; Yiming ZHANG ; Jing YANG ; Ling JIN ; Xiaoling WANG ; Tianyou WANG ; Yanlong DUAN
Chinese Journal of Pediatrics 2024;62(11):1097-1102
Objective:To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL).Methods:A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% (20/23) in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×10 6/L and was 12 (0, 25)×10 6/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion:BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.
6.Analysis of clinical, pathological and CT features of epidermal growth factor receptor exon 19 and 21 mutations in lung adenocarcinoma
Jiwen HUO ; Qi LI ; Tianyou LUO ; Fajin LYU
Chinese Journal of Radiology 2023;57(2):142-149
Objective:To investigate the clinical, pathological and CT characteristics of lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) 19 and 21 exon mutations.Methods:Clinical, pathological and imaging data of 683 patients with lung adenocarcinoma in the First Affiliated Hospital of Chongqing Medical University from December 2012 to December 2020 were retrospectively analyzed. According to the gene mutation status, patients were divided into EGFR common loci mutation group (exons 19 or 21) with 382 cases (mutation group), including 19 exon mutation in 165 cases (exon 19 mutation subgroup) and 21 exon mutation in 217 cases (exon 21 mutation subgroup), and EGFR negative mutation group with 301 cases (negative mutation group). Independent sample t-test and χ 2 test were used to compare those features between mutation group and negative mutation group, exon 19 mutation subgroup and exon 21 mutation subgroup. The indicators with statistically significant differences in univariate analysis were included in binary logistic regression analysis to screen out independent predictors and establish the model. Receiver operating characteristic curve and area under curve (AUC) were used to evaluate the predictive performance of the model or index. Results:There were significant differences between mutation group and negative mutation group in gender distribution, smoking history, the proportion of solid-dominated growth pattern, peripheral distribution, tumor maximum diameter (3 cm as the cut-off point) distribution, spiculation, ground-glass opacity (GGO), air bronchogram, vascular convergence sign, pleural retraction, the number of lung metastases (10 as the cut-off point), pleural effusion, necrosis, and lymph node metastasis in lung adenocarcinoma patients ( P<0.05). The logistic regression showed that female (OR=5.230,95%CI 3.534-7.740, P<0.001), non-smoking history (OR=2.970, 95%CI 1.986-4.443, P<0.001), GGO (OR=3.092, 95%CI 1.746-5.477, P<0.001), absence of necrosis (OR=1.754, 95%CI 1.047-2.939, P=0.033), vascular convergence sign (OR=3.129, 95%CI 1.971-4.969, P<0.001), pleural retraction (OR=2.434, 95%CI 1.680-3.526, P<0.001), and the number of lung metastases≥10 (OR=2.242, 95%CI 1.284-3.915, P=0.005) were independent predictors of EGFR exon 19 and 21 mutations, and the AUC of the logistic model based on these predictors in predicting EGFR exon 21 and 19 mutations in lung adenocarcinoma was 0.804. There were significant differences between EGFR exon 19 mutation subgroup and EGFR 21 mutation subgroup in gender distribution, the proportion of acinar-dominated growth pattern, peripheral distribution, vascular convergence sign, pleural retraction ( P<0.05). The logistic regression showed that vascular convergence sign (OR=1.833, 95%CI 1.187-2.831, P=0.006) was independent predictor of EGFR exon 21, the AUC of vascular convergence sign for distinguishing EGFR exon 19 and EGFR 21 mutation was 0.604. Conclusions:There are some differences in the clinical, pathological, and CT features of patients between EGFR common loci mutation and EGFR negative mutations, EGFR exon 19 and exon 21 mutations in lung adenocarcinoma. Familiarity with these differences is helpful for the individualized treatment of patients with unknown gene mutation status of lung adenocarcinoma.
7.Progress in the pathogenesis of eosinophilic gastrointestinal diseases
Jing LI ; Jie WU ; Tianyou WANG
International Journal of Pediatrics 2023;50(3):190-194
Eosinophilic gastrointestinal diseases are a group of diseases with repeated or persistent gastrointestinal symptoms and the increase of eosinophils in gastrointestinal mucosa.Pathology shows an increase in the number of eosinophils in gastrointestinal mucosa.Fibrosis can be seen in the lamina propria of esophageal mucosa in patients with eosinophilic esophagitis.A variety of cytokines may be chemotactic to the aggregation of eosinophils, including Th2 cytokines, eotaxin, thymic stromal lymphopoietin, macrophage migration inhibitory factor, sialic acid-binding immunoglobulin-like lectin, integrin and extracellular matrix protein.The intestinal tissue injury of eosinophilic gastrointestinal diseases may be related to eosinophil degranulation and secretion of specific products, inflammatory response, oxidative damage, fibrosis, tissue remodeling and impaired barrier function.
8.Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fifth Edition)updated for the Omicron variant
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Yunxiao SHANG ; Baoping XU ; Zhisheng LIU ; Gen LU ; Jikui DENG ; Guanghua LIU ; Xiaochuan WANG ; Jianshe WANG ; Luzhao FENG ; Wei LIU ; Yi ZHENG ; Sainan SHU ; Min LU ; Wanjun LUO ; Miao LIU ; Yuxia CUI ; Leping YE ; Adong SHEN ; Gang LIU ; Liwei GAO ; Lijuan XIONG ; Yan BAI ; Likai LIN ; Zhuang WEI ; Fengxia XUE ; Tianyou WANG ; Dongchi ZHAO ; Zhengyan ZHAO ; Jianbo SHAO ; Wong Wing-kin GARY ; Yanxia HE ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(1):20-30
China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.
9.Matrix Stiffness Affects Mitochondrial Heterogeneity of Tibial Plateau Chondrocytes in Knee Osteoarthritis
Tianyou KAN ; Lingli HOU ; Hanjun LI ; Junqi CUI ; Yao WANG ; Lin SUN ; Liao WANG ; Zhifeng YU ; Mengning YAN
Journal of Medical Biomechanics 2023;38(3):E521-E527
Objective To investigate the difference of matrix stiffness in different regions of tibial plateau in osteoarthritis (OA) and its effects on morphology of the cartilage and mitochondria. Methods The tibial plateau cartilage specimens of OA were obtained for nanoindentation test, transmission electron microscopy and histological analysis. The stiffness of cartilage matrix in different regions of OA tibial plateau was detected by nano-indentation. The morphology of cartilage mitochondria in different regions was observed by transmission electron microscopy, and the changes of mitochondrial plane area, shape and ridge volume density were quantitatively analyzed. Cartilage injury in different regions of OA tibial plateau was observed by histological staining. Results The cartilage of OA tibial plateau showed regional heterogeneity, and the cartilage and mitochondria on medial side of varus knee OA were more severe, and the matrix stiffness was higher. The OA scores were positively correlated with matrix stiffness. There was also a significant correlation between OA scores and mitochondrial morphology: the higher OA scores, the larger and rounder mitochondrial plane area, and the lower cristae volume density. Conclusions The differences of tibial plateau revealed the correlation between cartilage matrix stiffness, OA scores and mitochondrial morphological parameters. The increased cartilage matrix stiffness may be the main cause of chondrocyte mitochondrial injury, and further aggravate the progression of OA.
10.Effect of CKIP-1 on hepatocyte apoptosis in nonalcoholic fatty liver disease
Li LI ; Ping XIE ; Chunshan BI ; Tianyou WANG ; Ning WANG ; Wenjun LIN ; Chuan ZHANG ; Wei AN ; Yutao ZHAN
Chinese Journal of Internal Medicine 2023;62(1):43-48
Objective:To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD).Methods:Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG 2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG 2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results:After CKIP-1 was transfected into HepG 2 cells, the degree of OA induced cell liposis was significantly reduced ( P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax ( P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 ( P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice ( P<0.01, P<0.05), and further decrease the expression of Bcl-2/Bax ( P<0.05). Conclusion:CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.

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