1.Analysis of Clinical Diagnosis and Traditional Chinese Medicine Medication Rule of Children with Nephrotic Syndrome in Single Center
Tingting XU ; Xia ZHANG ; Ying DING ; Long WANG ; Shanshan XU ; Yijin WANG ; Yue WANG ; Feiyu YAO ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):176-184
ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine (TCM) medication rule of children with primary nephrotic syndrome (PNS) in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected, and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria, an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting, association rule analysis, and cluster analysis were carried out on TCM in the prescription, and the high-frequent drugs were analyzed. Results(1) General information: A total of 711 children were included, consisting of 522 males (73.42%) and 189 females (26.58%). The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age, and the average age of onset was (4.74 ± 3.48) years old. (2) Clinical treatment plan and use of immunosuppressive agents: Of the 711 children with PNS, 237 were treated with hormone alone (32.33%), and 474 (66.67%) received immunosuppressive agents combined with hormones. In the initial treatment, hormone combined with Tacrolimus (TAC) was the preferred treatment (32.91%). For children with refractory PNS who exhibited poor clinical efficacy, Rituximab (RTX) was mostly used for treatment, with a ratio of up to 23.63%. (3) TCM syndrome and medication rule: In PNS syndrome differentiation, Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases, accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases, accounting for 16.60%. A total of 711 children were included, of which 706 children were treated with TCM. This involved a total of 706 prescriptions, 226 TCM, and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae (81.16%), Radix Astragali (71.81%), Poria (68.84%), Rhizoma Atractylodis Macrocephalae (63.60%), and Fructus Corni (57.37%). The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest, and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children, TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS, RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali, Poria, Rhizoma Atractylodis Macrocephalae, and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.
2.Analysis of Clinical Diagnosis and Traditional Chinese Medicine Medication Rule of Children with Nephrotic Syndrome in Single Center
Tingting XU ; Xia ZHANG ; Ying DING ; Long WANG ; Shanshan XU ; Yijin WANG ; Yue WANG ; Feiyu YAO ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):176-184
ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine (TCM) medication rule of children with primary nephrotic syndrome (PNS) in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected, and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria, an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting, association rule analysis, and cluster analysis were carried out on TCM in the prescription, and the high-frequent drugs were analyzed. Results(1) General information: A total of 711 children were included, consisting of 522 males (73.42%) and 189 females (26.58%). The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age, and the average age of onset was (4.74 ± 3.48) years old. (2) Clinical treatment plan and use of immunosuppressive agents: Of the 711 children with PNS, 237 were treated with hormone alone (32.33%), and 474 (66.67%) received immunosuppressive agents combined with hormones. In the initial treatment, hormone combined with Tacrolimus (TAC) was the preferred treatment (32.91%). For children with refractory PNS who exhibited poor clinical efficacy, Rituximab (RTX) was mostly used for treatment, with a ratio of up to 23.63%. (3) TCM syndrome and medication rule: In PNS syndrome differentiation, Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases, accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases, accounting for 16.60%. A total of 711 children were included, of which 706 children were treated with TCM. This involved a total of 706 prescriptions, 226 TCM, and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae (81.16%), Radix Astragali (71.81%), Poria (68.84%), Rhizoma Atractylodis Macrocephalae (63.60%), and Fructus Corni (57.37%). The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest, and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children, TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS, RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali, Poria, Rhizoma Atractylodis Macrocephalae, and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.
3.Analysis of discordant results between multiplex fluorescence PCR-capillary electrophoresis for microsatellite instability (MSI) detection and immunohistochemistry (IHC) for mismatch repair (MMR) protein expression in gastrointestinal adenocarcinoma
Yijin GU ; Haimin XU ; Qiyun LI ; Fei YUAN ; Lei DONG ; Chaofu WANG
Chinese Journal of Oncology 2025;47(8):715-725
Objective:This study investigated the underlying causes of discordance between multiplex fluorescence polymerase chain reaction (PCR)-capillary electrophoresis in determining MSI and immunohistochemistry (IHC) for mismatch repair (MMR) protein evaluation in gastrointestinal adenocarcinomas, aiming to improve interpretation accuracy and guide clinical precision treatment strategies.Methods:A retrospective analysis was conducted on 511 surgically resected or biopsied specimens (161 gastric adenocarcinomas and 350 colorectal adenocarcinomas) diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to June 2024. MMR protein expression of tumors was evaluated by IHC, while MSI status was assessed using the 2B3D National Cancer Institute (NCI) Panel through multiplex fluorescence PCR-capillary electrophoresis on tumor DNA and matched normal DNA. The concordance between the two methods was analyzed, and factors contributing to the discordance were investigated. Cases with unstable dinucleotide loci only in the 2B3D NCI Panel, focal MMR protein loss, or unexplained discrepancies underwent validation using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis markers or next-generation sequencing (NGS).Results:In the 511 gastrointestinal adenocarcinomas, the results of the two methods were discordant in 15 cases (2.9%), with a significantly higher discordantrate in gastric cancers (7.5%, 12/161) compared to colorectal cancers (0.9%, 3/350; P<0.001). Key contributors to the discordance included: sampling limitations (6 cases), 2B3D NCI Panel design constraints (3 cases),tumor heterogeneity (3 cases),isolated MSH6 deficiency (1 case),and unexplained discrepancies (2 cases).Validation studies demonstrated that cases with dinucleotide-only instability showed concordance with IHC after using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis and NGS verifications. Specimens with focal MMR protein loss and unexplained discrepancies aligned with initial PCR results upon NGS validation. Unexplained cases harbored Kirsten rat sarcoma class Ⅰ variants and multiple class Ⅱ genetic alterations. Conclusions:Colorectal adenocarcinoma demonstrated higher concordance between PCR-capillary electrophoresis and IHC than gastric adenocarcinoma.Discordant results require systematic evaluation including technical review, specimen quality control, and supplemental NGS analysis to resolve discrepancies.
4.Summary of the best evidence for cognitive function improvement in Alzheimer's disease patients
Yijin WANG ; Yanxuan ZHANG ; Ruihan LI ; Li QI ; Weixin ZHANG ; Yin GAO
Chinese Journal of Modern Nursing 2025;31(30):4152-4158
Objective:To retrieve and summarize the best evidence for cognitive function improvement in Alzheimer's disease patients, so as to provide reference for clinical practice.Methods:Following the "6S" evidence model, guidelines, expert consensus, clinical decision, and systematic reviews on cognitive function improvement in Alzheimer's disease patients were systematically retrieved from domestic and foreign databases and websites. The search keywords included "Alzheimer's disease, cognitive function, improvement". Evidence-based nursing methods were used to evaluate the quality of literature and extract evidence. The search period was from July 1, 2000 to July 31, 2024.Results:A total of 15 articles were included, including five guidelines, four expert consensus, two clinical decision, and four systematic reviews. Sixteen pieces of best evidence were summarized from four aspects of evaluation and identification, pharmacological intervention, non-pharmacological intervention, and caregiver support.Conclusions:Patients with Alzheimer's disease require timely identification of symptoms related to cognitive impairment and assessment using standardized scales. Multiple intervention methods, such as pharmacological intervention, non-pharmacological intervention, and caregiver support, should be used to enhance patients' quality of life. Evidence application should be tailored to each patient's specific circumstances through individualized selection and adjustment to ensure the effectiveness and scientific rigor of cognitive function improvement strategies, thereby facilitating the translation of optimal evidence into clinical practice.
5.Construction and efficacy evaluation of artificial intelligence-based automatic grading model for neurological severity at acute phase of patients with traumatic cervical spinal cord injury
Yijin WANG ; Zhenzhen GUAN ; Liang WANG ; Xuhua LU
Chinese Journal of Trauma 2025;41(5):449-455
Objective:To construct an artificial intelligence (AI)-based automatic grading model for neurological severity at acute phase of patients with traumatic cervical spinal cord injury (TCSCI) and evaluate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 315 patients with TCSCI admitted to the Second Affiliated Hospital of Naval Medical University from January 2019 to December 2023, including 243 males and 72 females, aged 30-75 years [(57.6±7.0)years]. Injured segments involved C 1-C 4 in 143 patients and C 5-C 8 in 172. According to the American Spinal Injury Association (ASIA) scale, the injuries were classified as Grade A in 15 patients, Grade B in 53, Grade C in 74, and Grade D in 173. The patients were randomly divided into training group ( n=252) and test group ( n=63) with a ratio of 8∶2. The patients′ sensory and motor functions were assessed according to the ASIA scale within 48 hours after injury. The cervical spine MRI instance segmentation model was used to extract injury severity features of TCSCI patients in sagittal T2-weighted images. The grading model consisted of a two-layer cascade network. The first layer involved gradient boosting, Gaussian naive bayes, K-nearest neighbors, decision tree, random forest and support vector machine classifier. In the training group, the 6 machine learning models were trained separately. In the second layer, the performance of the six models was optimized to obtain the corresponding optimal grading models, so as to match the models with the best grading performance for each feature. In the test group, the performance of each model was evaluated by calculating accuracy, recall, precision, average precision, and F1 score. Results:A total of 138 clinical and imaging features were included to construct an automatic grading model for neurological severity of TCSCI patients at acute phase, comprising 132 clinical neurological features (including 56 light touch sensory scores, 56 pinprick sensory scores, and 20 key muscle scores) and 6 MRI imaging features. In the test group, the accuracy, recall, precision, average precision and F1 score of the six models, including gradient boosting, Gaussian naive bayes, K-nearest neighbors, decision tree, random forest and support vector machine classifier in the first layer of the automatic grading model for neurological severity at acute phase of TCSCI patients, in the overall grading of light touch, pinprick sensory and key muscle motor function were all above 0.86. In terms of the overall light touch function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were K-nearest neighbors (0.90), gradient boosting (0.99), Gaussian naive bayes (0.98), random forest (0.96), and gradient boosting (0.96), respectively. In terms of the overall pinprick sensory function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were gradient boosting (0.98), Gaussian naive bayes (0.98), gradient boosting (0.99), decision tree (0.99), and gradient boosting (0.95), respectively. In terms of the overall key muscle motor function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were K-nearest neighbors (0.97), gradient boosting and support vector machine classifier (0.97), decision tree (0.95), random forest (0.95), and support vector machine classifier (0.96), respectively. In terms of sensory function, gradient boosting had the highest number of superior performances in the overall light touch and pinprick sensory function grading. In terms of motor function, the support vector machine classifier had the highest number of superior performances in the overall key muscle motor function grading.Conclusion:The automatic grading model for neurological severity at acute phase of patients with TCSCI that is constructed based on machine learning models and two-layer cascade networks can achieve the optimization of the grading performance of each feature and exhibit a strong grading ability for the sensory and motor function severity.
6.Correlation between lncRNA HCG11 mRNA and miR-4465 Expression Levels and Clinicopathological Features and Prognosis in Triple-negative Breast Cancer Tissues
Ling ZHANG ; Haiyan XU ; Qiangli WANG ; Yijin YANG ; Bin CHEN
Journal of Modern Laboratory Medicine 2025;40(1):84-89
Objective To investigate the expression and clinical significance of long non-codingRNA HCG11 (lncRNA HCG11) mRNA and microRNA (miR)-4465 in patients with triple-negative breast cancer(TNBC). Methods The clinicopathological data of 110 TNBC patients hospitalized in Jiulong Hospital of Suzhou from June 2017 to June 2020 were collected,and the clinical significance of the expression of lncRNA HCG11mRNA and miR-4465 was analyzed. Results The expression of lncRNA HCG11 mRNA (1.81±0.53) in cancer tissues was higher than that in adjacent tissues (0.87±0.13),while the expression of miR-4465 (0.68±0.14) was lower than that in adjacent tissues (1.09±0.18),and the differences were statistically significant(t=18.066,18.857,all P<0.05). The results of Pearson analysis showed that lncRNA HCG11mRNA was negatively correlated with the expression of miR-4465 (r=-0.443,P<0.001). The proportion of patients with high expression of lncRNA HCG11mRNA and low expression of miR-4465 in cancer tissues with lymph node metastasis in TNM stage Ⅲ+Ⅳ was higher than that in TNM stage Ⅰ+Ⅱ,and the proportion of patients without lymph node metastasis was higher (x2=6.614,18.510;8.093,22.976,all P<0.05) The 3-year survival rate of lncRNA HCG11mRNA patients with high expression was lower than that of lncRNA HCG11mRNA patients with low expression,and the 3-year survival rate of patients with high expression of miR-4465 was higher than that of patients with low expression of miR-4465 (Log-rank x2=14.45,13.39,all P<0.05). The proportion of patients with clinical stage Ⅲ+Ⅳ in death group was higher than that in survival group (x2=12.667,18.026,all P<0.05). LncRNA HCG11mRNA(HR=2.623,95%CI:1.344~5.118) was risk factors for 3-year death in TNBC patients,while miR-4465(HR=0.891,95%CI:0.821~0.967) was a protective factor (P<0.05). Conclusion The high expression of lncRNA HCG11 mRNA and the low expression of miR-4465 in triple negatire breast cancer were related to the clinicopathological characteristics and prognosis of patients,and are expected to become prognostic marker for TNBC.
7.Relationship between the expression of SUCNR1 and YBX1 in tissues of patients with colorectal cancer liver metastases and their clinicopathological characteristics and prognosis
Yi WANG ; Qiangli WANG ; Jia ZHANG ; Yijin YANG ; Sheng WANG
Journal of International Oncology 2025;52(3):152-157
Objective:To explore the relationship between the expression levels of succinate receptor 1 (SUCNR1) and Y-box binding protein 1 (YBX1) in colorectal cancer tissues of patients with colorectal cancer liver metastases (CRLM) and their clinicopathological characteristics and prognosis.Methods:One hundred and five CRLM patients who underwent surgical treatment in Suzhou Kowloon Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to May 2020 were taken as the study subjects. The high expression rates of SUCNR1 and YBX1 in cancer tissues and adjacent tissues were compared. Clinicopathological characteristics and prognosis of patients with high and low SUCNR1 and YBX1 expression were compared. Univariate and multivariate Cox proportional risk regression models were applied to analyze prognostic influencing factors.Results:SUCNR1 staining was mainly located on the cell membrane in colorectal cancer tissues, and positive staining showed yellow or brownish yellow; YBX1 was mainly located in the cytoplasm of colorectal cancer tissues, and positive staining showed yellow or brownish yellow. The high expression rate of SUCNR1 in cancer tissues (74.29%, 78/105) of CRLM patients was obviously higher than that in adjacent tissues (27.62%, 29/105), and the high expression rate of YBX1 in cancer tissues (84.76%, 89/105) was obviously higher than that in adjacent tissues (32.38%, 34/105), with statistically significant differences ( χ2=45.75, P<0.001; χ2=59.36, P<0.001). There were statistically significant differences in histological grade ( χ2=7.43, P=0.006) and the time from colorectal cancer diagnosis to liver metastasis ( χ2=9.19, P=0.002) between patients with high and low expression of SUCNR1; there was a statistically significant difference in time from colorectal cancer diagnosis to liver metastasis ( χ2=13.08, P<0.001) between patients with high and low expression of YBX1. The 3-year overall survival (OS) rates of patients with high and low expression of SUCNR1 were 52.56% and 77.78%, respectively, with a statistically significant difference ( χ2=6.10, P=0.014) ; the 3-year OS rates of patients with high and low expression of YBX1 were 53.93% and 87.50%, respectively, with a statistically significant difference ( χ2=6.02, P=0.014). Univariate analysis showed that, histological grade ( HR=4.69, 95% CI: 1.14-19.36, P=0.033), time from colorectal cancer diagnosis to liver metastasis ( HR=4.05, 95% CI: 1.02-16.62, P=0.048), cancer tissues SUCNR1 ( HR=5.12, 95% CI: 1.17-22.34, P=0.030), and YBX1 expression ( HR=6.29, 95% CI: 1.55-25.47, P=0.010) were all influencing factors for OS in CRLM patients. Multivariate analysis showed that, histological grade ( HR=4.16, 95% CI: 1.12-15.54, P=0.034), time from colorectal cancer diagnosis to liver metastasis ( HR=5.59, 95% CI: 1.25-24.99, P=0.024), expression of SUCNR1 in cancer tissues ( HR=3.68, 95% CI: 1.28-10.54, P=0.015), and expression of YBX1 in cancer tissues ( HR=3.42, 95% CI: 1.56-7.52, P=0.002) were all independent influencing factors for OS in CRLM patients. Conclusions:The high expression rates of SUCNR1 and YBX1 in cancer tissues of CRLM patients are higher than those in adjacent tissues. Patients with high and low SUCNR1 expression have differences in tumor histological grade, time from colorectal cancer diagnosis to liver metastasis, patients with high and low YBX1 expression has a difference in time from colorectal cancer diagnosis to liver metastasis. The 3-year OS rates of patients with low expression of SUCNR1 and YBX1 are higher than those of patients with high expression. The histological grade, the time from colorectal cancer diagnosis to liver metastasis, and the expression of SUCNR1 and YBX1 in cancer tissues are all independent influencing factors for OS in CRLM patients.
8.Protein phosphatase 2A promotes mitophagy to alleviate fructose-induced mitochondrial oxidative damage in M2-type macrophages
Xiaoman LI ; Li LAN ; Yijin LONG ; Huilian LI ; Minghong WANG ; Xinhan WANG ; Xiyi LI ; Shen TANG
Journal of Army Medical University 2025;47(18):2186-2196
Objective To investigate the effects of fructose exposure on mitochondrial oxidative damage in M2-type macrophages and elucidate the regulatory role of protein phosphatase 2A(PP2A)in the process using its specific activator ABL127,an inhibitor of protein phosphatase methylesterase-1(PPME-1).Methods ① Immortalized mouse bone marrow-derived macrophages Ana-1 were subjected and grouped into M0(conventional culture),M2(treated with 20 ng/mL IL-4 for 24 h),and M2+Fru groups(IL-4 plus 0.04,0.20,1.00,or 5.00 mmol/L fructose).Cell viability was assessed with CCK-8 assay.Number of mitochondria,total and mitochondrial levels of reactive oxygen species(ROS),and mitochondrial membrane potential(ΔΨM)were measured using fluorescent probes.Total and demethylated PP2Ac protein levels were detected by Western blotting.② Ana-1 cells were also divided into M0,M2,M2+Fru(20 ng/mL IL-4+5.00 mmol/L fructose,24 h),and M2+Fru+ABL127(20 ng/mL IL-4+5.00 mmol/L fructose+1.00 μmol/L ABL127,24 h)to investigate PP2A-mediated mechanisms.Numbers of mitochondria and lysosomes,ROS level,and ΔΨM were detected via fluorescence assays.Expression of mitophagy-related proteins,PTEN induced putative kinase 1(PINK1),P62,microtubule-associated protein light chain 3(LC3),and voltage-dependent anion channel(VDAC)was evaluated by Western blotting,and the mRNA levels of M2 markers,found in inflammatory zone 1(Fizz1),arginase-1(Arg-1),and TGF-β were measured using RT-qPCR.Results ① Compared with the M2 group,fructose treatment at a concentration ranging from 0.04 to 5.00 mmol/L showed no effect on cell viability in M2 macrophages,but increased total ROS level in a dose-dependent manner(P<0.05).Fructose of 5.00 mmol/L resulted in significantly elevated mitochondrial ROS and mitochondrial quantity(P<0.05),reduced ΔΨM(P<0.05),up-regulated demethylated-PP2Ac(P<0.05),and no changed total-PP2Ac protein level.② Compared with the M2+Fru group,the addition of ABL127 led to decreased number of mitochondria but increased number of lysosomes(P<0.01),up-regulation of PINK1,LC3Ⅱ and VDAC proteins,down-regulation of P62(P<0.05),reduced total and mitochondrial ROS levels,and enhanced ΔΨM(P<0.01).The mRNA expression of Fizz1,Arg-1,and TGF-β was notably decreased in the M2+Fru group than the M2 group(P<0.05),and the levels were rescued by ABL127 treatment(P<0.05).Conclusion Fructose induces PP2Ac demethylation and then mitochondrial oxidative damage in M2-type macrophages.PP2A activation promotes mitophagy and reverses fructose-induced damage.
9.Preliminary efficacy and safety analysis of modified SIOPEL-4 protocol for newly diagnosed pediatric hepatoblastoma with lung metastases
Jiaxin PENG ; Can HUANG ; An'an ZHANG ; Yali HAN ; Haishan RUAN ; Xiaoxia WANG ; Min XU ; Yuan XIN ; Liting YU ; Zhibao LYU ; Mingxuan FENG ; Shayi JIANG ; Yijin GAO
Chinese Journal of Pediatrics 2025;63(12):1343-1348
Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.
10.Clinical characteristics and molecular function of ubiquitin-like containing PHD and RING finger domains 1 in soft tissue sarcoma
Yijin YAN ; Huan WANG ; Yifan DING ; Haoran XU ; Weihua HU ; Huang FANG
Journal of Clinical Surgery 2025;33(7):735-740
Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2%,synovial sarcoma 3.8%,leiomyosarcoma 40.7%,malignant peripheral nerve sheath tumor 3.8%,myxofibrosarcoma 9.6%,pleomorphic sarcoma 19.9%,P=0.001),tumor necrosis(none 38.8%,focal necrosis 20.8%,moderate necrosis 33.8%,extensive necrosis 6.6%,P=0.010),and tumor metastasis(no metastasis 67%,metastasis 33%,P<0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P<0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P<0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|>1.0 and adjusted P value<0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|>2.0 and adjusted P value<0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

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