1.Clinical features and immunotherapy for children with loss-of-function/gain-of-function mutations in the STAT gene: an analysis of 10 cases.
Hong-Wei LI ; Yan-Hong WANG ; Shang-Zhi WU ; Bi-Yun ZHANG ; Shi-Hui XU ; Jia-Xing XU ; Zhan-Hang HUANG ; Cheng-Yu LU ; De-Hui CHEN
Chinese Journal of Contemporary Pediatrics 2025;27(8):951-958
OBJECTIVES:
To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies.
METHODS:
A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment.
RESULTS:
For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms.
CONCLUSIONS
STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans
;
Male
;
Immunotherapy
;
Female
;
Child, Preschool
;
Child
;
Gain of Function Mutation
;
Retrospective Studies
;
Infant
;
Loss of Function Mutation
;
STAT Transcription Factors/genetics*
2.PROTAC-loaded nanocapsules degrading BRD4 for radio-chemotherapy sensitization in glioblastoma.
Yun GUO ; Mingzhu FANG ; Shilin ZHANG ; Zheng ZHOU ; Zonghua TIAN ; Haoyu YOU ; Yun CHEN ; Jingyi ZHOU ; Xiaobao YANG ; Yunke BI ; Chen JIANG ; Tao SUN
Acta Pharmaceutica Sinica B 2025;15(10):5050-5070
Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.
3.Research on ST-T change recognition algorithm based on lead attention network
Liang WEI ; Yun-chi LI ; Jun XIE ; Tong XU ; Feng ZUO ; Yong-qin LI ; Bi-hua CHEN ; Mi HE ; Yu-shun GONG
Chinese Medical Equipment Journal 2025;46(7):1-11
Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]
4.Retrospecitve study on clinical treatment of 214 children with high altitude pulmonary edema
Xueyue WANG ; Yu ZHANG ; Henghai NIE ; Chao CHEN ; Jing WANG ; Yifan LE ; Kaixiong LAN ; Xianjin BI ; Xiaoyang HONG ; Yun HAO ; Xiuping XU ; Liuxin DU
Chinese Pediatric Emergency Medicine 2025;32(7):504-508
Objective:To analyse the clinical characteristics of 214 cases of paediatric high altitude pulmonary edema(HAPE)and the efficacy of dexamethasone in adjunctive therapy.Methods:This retrospective study analyzed 214 pediatric cases of HAPE admitted to the Department of Paediatrics of the General Hospital of Tibetan Military between June 2015 to June 2017 and June 2019 to June 2021.Patients were divided into dexamethasone-treated group and dexamethasone-untreated group.Baseline data,clinical characteristics were collected to evaluate the treatment efficacy and drug side effects.Results:There were 107 children in each of the two groups with a median age of 8(5,11)years. The median age of the dexamethasone-treated group was 9(6,12)years and the mean age of the dexamethasone-untreated group was 7(3,10)years. The proportion of male children was 69.60%(149/214);the onset of illness was mostly concentrated within 72 hours,accounting for 97.20%(208/214)of the cases;83.18%(178/214)of the cases had symptoms of combined upper respiratory tract infection before entering the plateau. The most important clinical symptoms of the children were cough(86.92%,186/214),cyanosis(70.09%,150/214),and shortness of breath(66.36%,142/214). The proportion of auscultatory rhonchi was 83.18%(178/214),and all cases showed positive findings on chest radiography. After the dexamethasone regimen,the overall cure rate of the children was 94.39%,the average disappearance time of the symptoms and signs was(40.52±7.85)h,and the average hospital stay was(3.60±1.90)d. After treatment with the dexamethasone-free regimen,the overall cure rate was 92.52%,the mean time to disappearance of symptoms and signs was(42.10±7.62)h,and the mean length of stay in the hospital was(3.84±2.08)d. There was no significant difference in the cure rate,the disappearance time of symptoms and signs,and the average hospitalisation days between the two groups( P>0.05),but a total of 11 children in the dexamethasone-treated group experienced adverse drug reactions,and no children in the dexamethasone-untreated group experienced adverse drug reactions. Conclusion:Han Chinese male children,particularly those with upper respiratory infections,should be closely monitored for HAPE risk within three days of ascending to high altitudes. This study does not recommend the use of dexamethasone for pediatric HAPE due to the lack of therapeutic benefits and potential adverse effects.
5.Retrospecitve study on clinical treatment of 214 children with high altitude pulmonary edema
Xueyue WANG ; Yu ZHANG ; Henghai NIE ; Chao CHEN ; Jing WANG ; Yifan LE ; Kaixiong LAN ; Xianjin BI ; Xiaoyang HONG ; Yun HAO ; Xiuping XU ; Liuxin DU
Chinese Pediatric Emergency Medicine 2025;32(7):504-508
Objective:To analyse the clinical characteristics of 214 cases of paediatric high altitude pulmonary edema(HAPE)and the efficacy of dexamethasone in adjunctive therapy.Methods:This retrospective study analyzed 214 pediatric cases of HAPE admitted to the Department of Paediatrics of the General Hospital of Tibetan Military between June 2015 to June 2017 and June 2019 to June 2021.Patients were divided into dexamethasone-treated group and dexamethasone-untreated group.Baseline data,clinical characteristics were collected to evaluate the treatment efficacy and drug side effects.Results:There were 107 children in each of the two groups with a median age of 8(5,11)years. The median age of the dexamethasone-treated group was 9(6,12)years and the mean age of the dexamethasone-untreated group was 7(3,10)years. The proportion of male children was 69.60%(149/214);the onset of illness was mostly concentrated within 72 hours,accounting for 97.20%(208/214)of the cases;83.18%(178/214)of the cases had symptoms of combined upper respiratory tract infection before entering the plateau. The most important clinical symptoms of the children were cough(86.92%,186/214),cyanosis(70.09%,150/214),and shortness of breath(66.36%,142/214). The proportion of auscultatory rhonchi was 83.18%(178/214),and all cases showed positive findings on chest radiography. After the dexamethasone regimen,the overall cure rate of the children was 94.39%,the average disappearance time of the symptoms and signs was(40.52±7.85)h,and the average hospital stay was(3.60±1.90)d. After treatment with the dexamethasone-free regimen,the overall cure rate was 92.52%,the mean time to disappearance of symptoms and signs was(42.10±7.62)h,and the mean length of stay in the hospital was(3.84±2.08)d. There was no significant difference in the cure rate,the disappearance time of symptoms and signs,and the average hospitalisation days between the two groups( P>0.05),but a total of 11 children in the dexamethasone-treated group experienced adverse drug reactions,and no children in the dexamethasone-untreated group experienced adverse drug reactions. Conclusion:Han Chinese male children,particularly those with upper respiratory infections,should be closely monitored for HAPE risk within three days of ascending to high altitudes. This study does not recommend the use of dexamethasone for pediatric HAPE due to the lack of therapeutic benefits and potential adverse effects.
6.Research on ST-T change recognition algorithm based on lead attention network
Liang WEI ; Yun-chi LI ; Jun XIE ; Tong XU ; Feng ZUO ; Yong-qin LI ; Bi-hua CHEN ; Mi HE ; Yu-shun GONG
Chinese Medical Equipment Journal 2025;46(7):1-11
Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]
7.Clinical guideline for the diagnosis and treatment of open skin avulsion injuries of the lower leg (version 2024)
Hao ZHANG ; Wenjun LI ; Xianyou ZHENG ; Qingtang ZHU ; Wei CHEN ; Xiangjun BAI ; Sheng LU ; Yun XIE ; Hua CHEN ; Gang LUO ; Xin WANG ; Xiaoqing HE ; Tengbo YU ; Aixi YU ; Jianzheng ZHANG ; Zhao XIE ; Juyu TANG ; Zhenbing CHEN ; Guangyue ZHAO ; Jiacan SU ; Long BI ; Tianbing WANG ; Zhenyu PAN
Chinese Journal of Trauma 2024;40(12):1071-1081
Skin avulsion injuries of the lower leg are common in clinical practice, which can easily lead to skin necrosis and infection of the lower leg, and have a significant impact on the appearance and function of the lower limb. Among them, the open avulsion injury has the highest incidence and is often accompanied by multiple tissue injuries. Therefore, improper diagnosis and treatment may cause skin and soft tissue defects of the lower leg combined with bone exposure or even bone defects, seriously impairing patients′ life and health. In order to have a better understanding of the open skin avulsion injury of the lower leg, achieve precise diagnosis and treatment and improve prognosis, the Chinese Society of Traumatology of Chinese Medical Association and the Chinese Association of Microsurgeons of Chinese Medical Doctor Association organized experts in the related fields to formulate Clinical guideline for the diagnosis and treatment of open skin avulsion injuries of the lower leg ( version 2024) based on evidence-based medicine principles. A total of 16 recommendations were proposed on the diagnosis, treatment, postoperative rehabilitation of open lower leg skin avulsion injury, so as to provide a reference for its diagnosis and treatment.
8.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
9.Different Prophylaxis Strategies for Central Nervous System Recurrence of Diffuse Large B-Cell Lymphoma
Shuang QU ; Li-Sheng LIAO ; Yan-Bin ZHENG ; Jie-Song WANG ; Hong-Ming HE ; Bi-Yun CHEN ; Hong SUN
Journal of Experimental Hematology 2024;32(5):1401-1406
Objective:To analyze the effects of highdose methotrexate(HD-MTX)and lenalidomide as central nervous system(CNS)prophylaxis strategies in patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively.The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies.Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement.The CNS relapse-free survival(CRFS)rate,adverse effects,and the effects of different prophylaxis strategies on overall survival(OS)rate and progression-free survival(PFS)rate were evaluated in different groups and subgroups.Results:There were 200 patients enrolled in this study,80 cases in lenalidomide group and 120 cases in HD-MTX group.According to the delivery timing of prophylactic HD-MTX,the patients in HD-MTX group were further divided into two groups:80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval.At a median follow-up of 48(14-133)months,the 4-year CRFS rate,4-year PFS rate,and 4-year OS rate of the HD-MTX group was 93.6%,57.2%,and 68.8%,respectively,while that of the lenalidomide group was 90.4%,69.4%and 75.6%.There were no significant differences in 4-year CRFS rate,4-year PFS rate,and 4-year OS rate between HD-MTX group and lenalidomide group(all P>0.05),but lenalidomide group showed a trend of improvement in PFS.Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups(91.7%vs 83.4%,P>0.05),while 4-year PFS rate showed difference(49.5%vs 64.2%,P<0.05).A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group,and 25 cycles occurred neutropenia accompanied with infection(10.1%),while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection(8.3%).Both the two groups had no treatment-related deaths.Conclusion:Compared with HD-MTX,lenalidomide combined with immunochemotherapy can prevent CNS relapse,at the same time,improve prognosis,which is a safe and well tolerated central prophylaxis strategy.
10.YANG Zhi-Min's Experience in Differentiating and Treating Insomnia Based on the Generation,Dispersion,Divergence and Aggregation of Nutritive qi and Defensive qi
Xiao-Xuan ZHANG ; Jin-Xiu CHEN ; Shi-Ya HUANG ; Hua-Hua GUAN ; Bi-Yun XU ; Fu-Ping XU ; Jia-Min YUAN ; Zhi-Min YANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2179-2183
Disharmony between nutritive qi(ying)and defensive qi(wei)is the core pathogenesis of insomnia.The normal function of ying-wei in the generation,dispersion,divergence and aggregation is the precondition for the realization of the coordination between ying and wei.The disordered function of ying-wei in the generation,dispersion,divergence and aggregation will cause the disharmony between ying and wei,and then the insomnia occurs.For the treatment of insomnia caused by the disordered function of ying-wei in the generation,Guizhi Decoction associated prescriptions are used for strengthening middle energizer and nourishing ying and wei.For the treatment of insomnia caused by the disordered function of ying-wei in the dispersion,Mahuang Decoction associated prescriptions are used to relieve the exterior and eliminate the pathogen for insomnia patients with the manifestations of the attack of exopathogens,and Xiao Chaihu Decoction associated prescriptions are used to dredge the triple energizer for insomnia patients with the dysfunction of the triple energizer.For the treatment of insomnia caused by the disordered function of ying-wei in the divergence,Rhei Radix et Rhizoma associated bitter-cold prescriptions are used to purge the interior heat for insomnia patients with abundant interior heat syndrome,Gypsum Fibrosum associated pungent-cold prescriptions are used to release muscles and clear heat for insomnia patients with the interior heat complicated by exterior syndrome,Natrii Sulfas Exsiccatus associated salty-cold prescriptions are used to clear heat,moisten dryness and dissipate the masses for insomnia patients with interior heat complicated by dryness syndrome,sour-cold medicines are used to clear heat and remove retained water,supplement deficiency and relieve exterior for insomnia patients with interior heat complicated by water-retention syndrome,deficiency syndrome and exterior syndrome,and Ophiopogonis Radix associated prescriptions and Lillli Bulbus associated prescriptions are used to clear heat and nourish ying for insomnia patients with the consumption of ying and yin.For the treatment of insomnia caused by the disordered function of ying-wei in the aggregation,the compatibility of Poria and Cinnamomi Ramulus is used for warming yang and resolving fluid retention in patients with fluid retention,Taohong Siwu Decoction associated prescriptions are used to activate blood and remove stasis in patients with predominance of blood stasis syndrome,the compatibility of Poria and Paeoniae Radix Alba are used to treat retained water and blood stasis in patients with water-blood co-morbidity.Treating insomnia caused by disharmony between ying and wei from the perspective of the function of ying-wei in the generation,dispersion,divergence and aggregation is aimed at the core pathogenesis of insomnia,which makes the treatment easy to be carried out,and can provide reference for clinical differentiation and treatment of insomnia.

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