1.Preoperative differentiation of vagal nerve cervical schwannomas from sympathetic chain cervical schwannomas based on diagnosis score and vascular displacement nomogram
Shiyu XIANG ; Qiao LI ; Changqing SHEN ; Yajia GU ; Bin WU
China Oncology 2025;35(7):695-701
Background and purpose:Accurate preoperative differentiation between vagal nerve cervical schwannomas(SCCS)and sympathetic chain cervical schwannomas(SCCS)in the neck is crucial because of their different postoperative complication.This study aimed to construct and validate a Diagnosis Score and vascular displacement nomogram for the preoperative differentiation of VNCS from SCCS in the neck.Methods:This cross-sectional study retrospectively analyzed patients with pathologically confirmed VNCS and SCCS at Fudan University Shanghai Cancer Center from January 2017 to April 2022.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:1612167-18).Inclusion criteria:① histopathological diagnosis of VNCS or SCCS through biopsy or surgical resection;② patients with complete clinic data;③availability of preoperative contrast-enhanced computed tomography(CT)or magnetic resonance imaging(MRI)examinations.Patients were excluded for:① contrast agent contraindications;② poor image quality;③ severe artifacts;④ non-standard scanning protocols.The cohort was randomly divided into training and validation sets in a 7∶3 ratio.Two radiologists(one resident and one attending physician)independently evaluated tumor characteristics(location,size and vascular displacement patterns)on preoperative imaging.Independent predictors were selected using LASSO regression analysis to construct a diagnostic scoring system and nomogram,with model performance evaluated by the receiver operating characteristic(ROC)curve.Results:A total of 110 patients were enrolled,with 77 cases allocated to the training set and 33 cases to the validation set.The age range was 24-78 years,and the mean age was(51.22±12.36)years.There were no statistically significant differences in baseline characteristics including age,gender,tumor location and size between the two patient groups(P>0.05).ICA/ECA splaying was significantly associated with SCCS(P<0.001),while the ICA/IJV splaying was significantly associated with VNCS(P<0.001).Lateral and posterior ICA displacement were significantly associated with SCCS(P<0.001),and medial and anterior ICA displacement were significantly associated with VNCS(P<0.001).Five features including tumor size,ICA displacement direction,IJV displacement direction,ICA/ECA splaying and ICA/IJV splaying were used to establish the Diagnosis Score and nomogram.The nomogram combined imaging features showed favorable preference value for differentiating VNCS from SCCS,with area under curve(AUC)values of 0.953(95%CI:0.912-0.994)and 0.939(95%CI:0.885-0.993)for the training and validation cohorts,respectively.Conclusion:The Diagnosis Score and vascular displacement nomogram showed favorable predictive efficacy for differentiating VNCS from SCCS in the neck,and might be useful for clinical decision-making.
2.Preoperative differentiation of vagal nerve cervical schwannomas from sympathetic chain cervical schwannomas based on diagnosis score and vascular displacement nomogram
Shiyu XIANG ; Qiao LI ; Changqing SHEN ; Yajia GU ; Bin WU
China Oncology 2025;35(7):695-701
Background and purpose:Accurate preoperative differentiation between vagal nerve cervical schwannomas(SCCS)and sympathetic chain cervical schwannomas(SCCS)in the neck is crucial because of their different postoperative complication.This study aimed to construct and validate a Diagnosis Score and vascular displacement nomogram for the preoperative differentiation of VNCS from SCCS in the neck.Methods:This cross-sectional study retrospectively analyzed patients with pathologically confirmed VNCS and SCCS at Fudan University Shanghai Cancer Center from January 2017 to April 2022.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:1612167-18).Inclusion criteria:① histopathological diagnosis of VNCS or SCCS through biopsy or surgical resection;② patients with complete clinic data;③availability of preoperative contrast-enhanced computed tomography(CT)or magnetic resonance imaging(MRI)examinations.Patients were excluded for:① contrast agent contraindications;② poor image quality;③ severe artifacts;④ non-standard scanning protocols.The cohort was randomly divided into training and validation sets in a 7∶3 ratio.Two radiologists(one resident and one attending physician)independently evaluated tumor characteristics(location,size and vascular displacement patterns)on preoperative imaging.Independent predictors were selected using LASSO regression analysis to construct a diagnostic scoring system and nomogram,with model performance evaluated by the receiver operating characteristic(ROC)curve.Results:A total of 110 patients were enrolled,with 77 cases allocated to the training set and 33 cases to the validation set.The age range was 24-78 years,and the mean age was(51.22±12.36)years.There were no statistically significant differences in baseline characteristics including age,gender,tumor location and size between the two patient groups(P>0.05).ICA/ECA splaying was significantly associated with SCCS(P<0.001),while the ICA/IJV splaying was significantly associated with VNCS(P<0.001).Lateral and posterior ICA displacement were significantly associated with SCCS(P<0.001),and medial and anterior ICA displacement were significantly associated with VNCS(P<0.001).Five features including tumor size,ICA displacement direction,IJV displacement direction,ICA/ECA splaying and ICA/IJV splaying were used to establish the Diagnosis Score and nomogram.The nomogram combined imaging features showed favorable preference value for differentiating VNCS from SCCS,with area under curve(AUC)values of 0.953(95%CI:0.912-0.994)and 0.939(95%CI:0.885-0.993)for the training and validation cohorts,respectively.Conclusion:The Diagnosis Score and vascular displacement nomogram showed favorable predictive efficacy for differentiating VNCS from SCCS in the neck,and might be useful for clinical decision-making.
3.Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing.
Xudong LI ; Hong HUANG ; Fang WANG ; Mengjia LI ; Binglei ZHANG ; Jianxiang SHI ; Yuke LIU ; Mengya GAO ; Mingxia SUN ; Haixia CAO ; Danfeng ZHANG ; Na SHEN ; Weijie CAO ; Zhilei BIAN ; Haizhou XING ; Wei LI ; Linping XU ; Shiyu ZUO ; Yongping SONG
Chinese Medical Journal 2025;138(15):1866-1881
BACKGROUND:
Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets.
METHODS:
In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis.
RESULTS:
In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment.
CONCLUSIONS
This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans
;
Lymphoma, Large B-Cell, Diffuse/therapy*
;
Tumor Microenvironment/genetics*
;
Antigens, CD19/metabolism*
;
Leukemia, Myelomonocytic, Chronic/genetics*
;
Immunotherapy, Adoptive/adverse effects*
;
Male
;
Single-Cell Analysis/methods*
;
Female
;
Sequence Analysis, RNA/methods*
;
Receptors, Chimeric Antigen
;
Middle Aged
4.Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy.
Chao CHEN ; Shiyu DU ; Qianglan LU ; Xueting SHEN ; Shuai DING ; Lihua QU ; Yamei GAO ; Zhiqiang YIN ; Zhe LI ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2025;15(10):5431-5443
Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C2P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn2+ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C2P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.
5.Study on effect of andrographolide for inhibiting proliferation of colon cancer cells by up-regulating BMP9
Shiyu WANG ; Xiaoli ZHOU ; Yanmei LI ; Baicheng HE ; Jun SHEN ; Zhenhua CHEN
Chongqing Medicine 2025;54(1):24-30
Objective To study the related molecular mechanism of andrographolide(AGP)in inhibi-ting the proliferation of human colon cancer LoVo cells and promoting their apoptosis.Methods The LoVo cells were set up as the control group and experimental group.The cells were treated with different concentra-tions of AGP(0,20,40,80 μmol/L).The cell viability was detected by CCK-8,the cellular cycle and apoptosis were detected by flow cytometery,and Western blot was used to detect protein level of PCNA,Bad and Bcl-2,and the effect of AGP of BMP9 overexpression or silencing AGP on PCNA,Bad and Bcl-2 protein levels;West-ern blot was used to analyze the effect of AGP on PTEN,Akt1/2/3 and p-Akt1/2/3 levels.Results AGP could inhibit the proliferation of LoVo cells,promoted their apoptosis and increased the BMP9 expression lev-el.The BMP9 overexpression could enhance the effect of AGP for inhibiting the proliferation and promoting the apoptosis,silencing BMP9 could weaken the above effects of AGP(P<0.05).AGP decreased the expres-sion level of p-Akt1/2/3 in the LoVo cells and increased the PTEN expression level(P<0.05).BMP9 over-expression enhanced AGP and decreased the p-Akt 1/2/3 expression level in the LoVo cells,and silencing BMP9 could weaken the above effects of AGP(P<0.05).Conclusion AGP could inhibit the proliferation of human colon cancer LoVo cells,its mechanism may be related with up-regulating BMP9 expression,thus in-crease PTEN protein level and inhibit P13K/Akt signal.
6.Effects of MOTOmed intelligent training combined with standing balance training on recovery of lower limb motor function and balance in patients with post-stroke hemiplegia
Jia SUN ; Haiye SHEN ; Shiyu WANG
Journal of Navy Medicine 2025;46(10):1006-1011
Objective To explore the effects of MOTOmed intelligent training combined with standing balance training on the recovery of lower limb motor function and balance in stroke patients with hemiplegia.Methods A total of 124 patients with post-stroke hemiplegia who received rehabilitation care in the Sixth People's Hospital of Nantong from May 2022 to May 2024 were selected as research objects.They were assigned to observation group(62 cases)or control group(62 cases)using a random number table.The control group received MOTOmed intelligent training,and the observation group received MOTOmed intelligent training combined with standing balance training.After 2 months of rehabilitation,the lower limb motor function(Fugl-Meyer assessment lower extremity subscale[FMA-LE]score,time up and go test[TUGT],balance function,postural stability[length and area of center of gravity movement,average trajectory error,completion time],quality of life(stroke specific quality of life[SS-QOL]),and self-care ability(Barthel index[BI])were compared between the two groups.Results After interventions,the FMA-LE scores of the observation group and control group were 19.41±5.72 and 16.08±4.41,respectively;the TUGT result was(40.06±12.35)s and(45.13±10.97)s;the station balance scores were 2.83±0.71 and 2.57±0.63;the walking function balance scores were 2.91±0.43 and 2.75±0.41;the lengths of center of gravity movement were(246.05±45.63)mm and(279.61±42.01)mm;the area of center of gravity movement was(92.75±22.16)mm2 and(102.36±27.84)mm2;the average trajectory error was(21.14±5.06)%and(25.78±5.42)%;the completion time of the tests was(79.24±5.06)s and(82.87±6.73)s;the SS-QOL scores were 138.91±32.05 and 125.65±34.83;BI was 51.24±7.91 and 46.05±6.63.There were significant differences in these indexes between the two groups(all P<0.05).Conclusion MOTOmed intelligent training combined with standing balance training can promote the recovery of lower limb motor function,improve lower limb motor balance,and enhance the quality of life of stroke patients with hemiplegia.
7.Unilateral chronic ankle instability affects bilateral postural stability,proprioception,plantar tactile sensation and muscle strength
Yanhao LIU ; Shiyu DONG ; Ziyin LIU ; Qipeng SONG ; Peixin SHEN
Chinese Journal of Tissue Engineering Research 2025;29(17):3572-3578
BACKGROUND:Unilateral chronic ankle instability has adverse effects on the affected limb,and evidence has shown that the nonaffected side may be similarly involved,but direct evidence is currently lacking.OBJECTIVE:To investigate the effects of unilateral chronic ankle instability on bilateral postural stability,proprioception,plantar tactile sensation,and muscle strength.METHODS:A total of 122 participants were recruited in this study,including 67 individuals with unilateral chronic ankle instability and 55 individuals without chronic ankle instability.Postural stability,proprioception,plantar tactile sensation and muscle strength were tested bilaterally in individuals with unilateral chronic ankle instability,as well as in those without chronic ankle instability.One-way analysis of variance or Kruskal-Wallis test was used for intergroup comparisons.RESULTS AND CONCLUSION:(1)Compared with individuals without chronic ankle instability,individuals with chronic ankle instability had longer time to stability in the anterior-posterior direction bilaterally(P=0.001-0.012),and longer time to stability in the medial-lateral direction on the affected side(P=0.012-0.025);had higher proprioception thresholds of plantarflexion,dorsiflexion,inversion,and eversion of the bilateral ankles(P=0.000-0.035);showed lower tactile sensation sensitivities of the bilateral great toe,first metatarsal head,fifth metatarsal head,arch,and heel(P=0.000-0.008);and had weaker muscle strength for inversion and eversion of the bilateral ankles(P=0.000-0.019).(2)Individuals with unilateral chronic ankle instability have bilateral deficits in postural stability,proprioception,plantar tactile sensation,and muscle strength.Therefore,the rehabilitation needs of both limbs should be fully considered when treating chronic ankle instability.
8.Unilateral chronic ankle instability affects bilateral postural stability,proprioception,plantar tactile sensation and muscle strength
Yanhao LIU ; Shiyu DONG ; Ziyin LIU ; Qipeng SONG ; Peixin SHEN
Chinese Journal of Tissue Engineering Research 2025;29(17):3572-3578
BACKGROUND:Unilateral chronic ankle instability has adverse effects on the affected limb,and evidence has shown that the nonaffected side may be similarly involved,but direct evidence is currently lacking.OBJECTIVE:To investigate the effects of unilateral chronic ankle instability on bilateral postural stability,proprioception,plantar tactile sensation,and muscle strength.METHODS:A total of 122 participants were recruited in this study,including 67 individuals with unilateral chronic ankle instability and 55 individuals without chronic ankle instability.Postural stability,proprioception,plantar tactile sensation and muscle strength were tested bilaterally in individuals with unilateral chronic ankle instability,as well as in those without chronic ankle instability.One-way analysis of variance or Kruskal-Wallis test was used for intergroup comparisons.RESULTS AND CONCLUSION:(1)Compared with individuals without chronic ankle instability,individuals with chronic ankle instability had longer time to stability in the anterior-posterior direction bilaterally(P=0.001-0.012),and longer time to stability in the medial-lateral direction on the affected side(P=0.012-0.025);had higher proprioception thresholds of plantarflexion,dorsiflexion,inversion,and eversion of the bilateral ankles(P=0.000-0.035);showed lower tactile sensation sensitivities of the bilateral great toe,first metatarsal head,fifth metatarsal head,arch,and heel(P=0.000-0.008);and had weaker muscle strength for inversion and eversion of the bilateral ankles(P=0.000-0.019).(2)Individuals with unilateral chronic ankle instability have bilateral deficits in postural stability,proprioception,plantar tactile sensation,and muscle strength.Therefore,the rehabilitation needs of both limbs should be fully considered when treating chronic ankle instability.
9.Clinical characteristics of 23 children with epilepsia partialis continua
Wenwen SHEN ; Shiyu WANG ; Ting LI
Journal of Apoplexy and Nervous Diseases 2024;41(9):811-815
Objective To study the clinical manifestations of children with epilepsia partialis continua(EPC),and to improve the understanding of the treatment and prognosis of this disease.Methods We retrospectively analyzed the data of 23 patients with EPC at the Department of Pediatrics of Xuanwu Hospital of Capital Medical University from July 2017 to July 2022.The data included general information,clinical manifestations,electroencephalography(EEG)re-sults,and surgical and prognostic information.Results A total of 23 patients(15 males and 8 females)were included,with a mean age of onset of(5.1±3.0)years and a mean age of epileptic exposure of(6.0±3.5)years.Twenty-one pa-tients(91.3%)developed motor seizures of focal origin as the initial presentation.Eleven patients(47.8%)presented with hemiparesis at 0.3 to 3 years after disease onset.All the patients showed a slow rhythm of the affected hemisphere on EEG;and cerebral hemiatrophy was found in 11 cases,and hippocampal abnormalities were found in 13 cases.The me-tabolism of the affected hemisphere was decreased in all the 7 examinees.All the 9 examinees had decreased perfusion in different brain regions.Among 10 cases undergoing surgery,the mean age at the time of the operation was(7.7±3.4)years,and the mean duration of the disease at the time of the operation was(3.6±3.6)years;after surgery,7 cases were free from seizures;2 cases had remission,and 1 had no improvement.Conclusion EPC is common in preschool-age and school-age children,manifesting as slower rhythms and interictal epileptiform discharges in the affected hemisphere on EEG.The decreased perfusion of the brain may be linked to the development of EPC.Surgical treatment can alleviate sei-zures for patients with EPC.
10.The best evidence summary for blood glucose management in patients with end-stage diabetic kidney disease undergoing hemodialysis
Hongmei ZHANG ; Ning ZHANG ; Yujiao SUN ; Lili SHEN ; Yi LU ; Shiyu HAN
Chinese Journal of Practical Nursing 2024;40(1):43-50
Objective:To retrieve, evaluate and integrate the best evidence of blood glucose management in hemodialysis patients with end-stage diabetic kidney disease, so as to provide a basis for clinical evidence-based nursing practice.Methods:BMJ Best Clinical Practice, Cochrane, OVID, Scopus, UpToDate, CNKI, Wanfang Database, Medical Pulse database, and other guideline networks and professional association websites and databases were searched for blood glucose management in hemodialysis patients with end-stage diabetic kidney disease. The search time limit was from the establishment of the database to May 10, 2023.Results:A total of 14 articles were included, including 1 clinical decision, 5 guidelines, 6 systematic reviews, 1 randomized controlled trial, and 1 expert consensus. The best evidences for blood glucose management in hemodialysis patients were summarized, including 8 aspects of pre-dialysis assessment, pre-dialysis blood glucose management, blood glucose management during dialysis, blood glucose management during dialysis interval, diet and nutrition, exercise management, lifestyle intervention and health education, with 25 pieces of evidence.Conclusions:This study summarizes the best evidence of blood glucose management in hemodialysis patients with end-stage diabetic kidney disease, and provides evidence-based basis for clinical practice for medical staff.

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