1.Accuracy of Magnetic Resonance Spectroscopy–Detected Fumarate Peak for Diagnosing Fumarate Hydratase Deficiency in Uterine Leiomyomas: A Prospective Study
Guiqin LIU ; Wenxin YU ; Shihang PAN ; Yuansheng LUO ; Jingli CHEN ; Mengying ZHU ; Zaoyu WANG ; Yang SONG ; Jin ZHANG ; Jianrong XU ; Yan ZHOU ; Jun MA ; Guangyu WU
Korean Journal of Radiology 2026;27(5):440-451
Objective:
To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs.
Materials and Methods:
This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features.
Results:
The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002).
Conclusion
A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.
2.Construction of CD8+T cell-associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-cell RNA-seq Data
Xin-Tong ZHANG ; Jian-Jun ZHU ; Jin WU ; Hao WU ; Fan LU ; Wen-Tao ZHANG ; Jing-Jia CHANG ; Ting TANG ; Zhi-Gao OU ; Feng-Feng JIA ; Li LI ; Peng-Fei YU ; Ming LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1511-1528
Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8+T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
3.Analysis of age cut-off and prognosis of early-onset gastric cancer in young patients
Jun LU ; Chenbin LV ; Linyan TONG ; Jie CHEN ; Jianing WU ; Fenglin LIU
Chinese Journal of Gastrointestinal Surgery 2025;28(4):400-407
Objective:To explore the optimal age cutoff for diagnosis and the prognosis of early-onset gastric cancer in young patients.Methods:Clinicopathological data of patients with gastric adenocarcinoma aged ≤45 years who had undergone radical gastrectomy in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center from January 2013 to December 2018 were retrospectively collected. Patients with distant metastases, other malignant tumors, combined organ resection, gastric stump cancer, positive margin, and incomplete clinical or follow-up data were excluded. X-tile software analysis of the actual overall survival of the collected cases yielded an optimal cut-off of 32 years. Accordingly, the enrolled cases were divided into an early-onset young group (age ≤32 years) and young adult group (age >32 years). Clinicopathological characteristics, long-term survival, and postoperative recurrence were compared between the two groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify the factors affecting the prognosis of young patients with gastric cancer.Results:The study cohort comprised 462 patients, including 256 (55.4%) women, 419 (90.7%) with middle and lower gastric cancers, and 343 (74.2%) with poorly differentiated tumors. There were 101 patients in the early-onset young group and 361 in the young adult group. These groups did not differ significantly in terms of sex, body mass index, tumor location, tumor size, surgical procedure, neurovascular invasion, or tumor stage (all P>0.05). The proportion of patients with poorly differentiated tumors in the early-onset young group was significantly higher than that in the young adult group (89.1%[90/101] vs. 70.1%[253/361], χ 2=15.26, P<0.001). All study patients completed 5 years of follow-up, the median duration of which was 101 months (61-133 months). Death or tumor recurrence occurred in 151 patients (32.7%), in 118 of whom the sites of recurrence and metastasis could be identified, 38 in the early-onset young group and 80 in the young adult group. Fifty-five (46.6%) patients developed peritoneal metastases and 40 (33.9%) hematogenous metastases. In the early-onset young group, 20 patients developed peritoneal metastases, 11 hematogenous metastases, five distant lymph node metastases, and two local recurrence. In the young adult group, 35 patients developed peritoneal metastases, 29 hematogenous metastases, six local recurrences, and 10 distant lymph node metastases. The 5-year overall survival and disease-free survival rates were significantly higher in the young adult group than in the early-onset young group (73.7% vs. 57.4%, P=0.002 and 70.6% vs. 55.4%, P=0.004, respectively). Cox multivariate analysis showed that age >32 years (HR=0.63, 95%CI: 0.43-0.90, P=0.012) was an independent protective factor for overall survival, whereas later N stage (HR=1.67, 95%CI:1.09-2.57, P=0.018) was an independent risk factor for overall survival after surgery ( P<0.05). Age >32 years (HR=0.60, 95%CI: 0.41-0.86, P=0.006) was also an independent protective factor for disease-free survival, whereas later N stage was an independent risk factor (HR=1.69, 95%CI: 1.08-2.64, P=0.021). Conclusion:Young patients with early-onset gastric cancer aged ≤32 years have worse tumor differentiation and prognosis.
4.Study on the impact of ultrasound-guided bedside hyperthermic intraperitoneal chemotherapy after laparoscopic gastric cancer surgery on the prognosis of patients with positive peritoneal lavage fluid cytology
Linyan TONG ; Jun LU ; Chenbin LV ; Lisheng CAI ; Yonghe WU
Chinese Journal of Gastrointestinal Surgery 2025;28(5):528-535
Objective:To investigate the impact of bedside ultrasound-guided hyperthermic intraperitoneal chemotherapy (HIPEC) after laparoscopic gastric cancer surgery on the prognosis of patients with only positive peritoneal lavage cytology (CY+) and no other distant metastases.Methods:The clinicopathological data of 49 patients with only positive peritoneal lavage cytology who underwent laparoscopic gastrectomy and D2 lymph node dissection from December 2017 to December 2022 were retrospectively analyzed. The patients were divided into the HIPEC group (27 cases) and the non-HIPEC group (22 cases) based on whether they received postoperative bedside ultrasound-guided HIPEC. The patterns of postoperative recurrence and metastasis and the 3-year survival rates were compared between the two groups. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to determine the prognostic factors.Results:There was no statistically significant difference in all baseline clinicopathological data between the two groups ( P>0.05); the median follow-up time for all patients was 31 months (ranging from 13 to 73 months), and the overall recurrence rate for all patients was 55.1% (27/49). Among them, 12 cases (24.5%) had peritoneal metastasis, 7 cases (14.3%) had hematogenous recurrence, 5 cases (10.2%) had distant lymph node metastasis, and 3 cases (6.1%) had local recurrence. The overall recurrence rates of patients in the HIPEC group and the non-HIPEC group were 51.8% (14/27) and 59.1% (13/22), respectively. There was no statistically significant difference (χ 2=0.26, P=0.612). The peritoneal metastasis rate of patients in the HIPEC group was 18.5% (5/27), which was lower than that of the non-HIPEC group at 31.8% (7/22). However, there was no statistically significant difference (χ 2=1.16, P=0.282). The proportions of local recurrence, hematogenous metastasis, and distant lymph node metastasis were comparable between the two groups (all P>0.05). The cumulative 3-year recurrence rates of the two groups were similar (70.7% vs. 71.3%, P=0.266). In the HIPEC group, the 3-year overall survival rate was 61.1%, which was significantly higher than that of the non-HIPEC group (31.5%). The difference was statistically significant ( P=0.014). The disease-free progression survival rates of the two groups were 29.3% and 28.7% respectively, and there was no statistically significant difference between them ( P=0.266). Cox multivariate analysis showed that no postoperative HIPEC (HR=5.21, 95%CI:1.90-14.31, P=0.001), poor tumor differentiation (HR=3.78, 95%CI:1.07-13.26, P=0.038), and later N stage (HR=6.18, 95%CI:1.39-7.59, P=0.017) were independent risk factors for the overall survival rate after surgery ( P<0.05). Later N stage (HR=3.67, 95%CI:1.07-12.55, P=0.038) was an independent risk factor for the disease-free progression survival rate after surgery ( P<0.05). Conclusion:Bedside ultrasound-guided HIPEC after laparoscopic gastrectomy and D2 lymph node dissection can improve the overall survival of CY+ gastric cancer patients.
5.Calcium imaging in C2C12 cells and RAW264.7 cells post co-culture and changes induced by sodium palmitate
Li-jun SONG ; Shuang WU ; Qin SHA ; Chuan-xin YANG ; Xing-yu TONG ; Hui JIANG
Fudan University Journal of Medical Sciences 2025;52(6):877-882
Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.
6.Review of application scope of mobile medical devices combined with EMA method for lung cancer patient caring
Zi-dan WANG ; Hong-yue WU ; Bing LI ; Xin-tong ZHENG ; Jun-ling LIU ; Ying-nan ZHAO ; Yan LI
Chinese Medical Equipment Journal 2025;46(10):71-77
Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]
7.Efficacy and safety of a facilitated percutaneous coronary intervention with half-dose recombinant staphylokinase in ST-segment elevation myocardial infarction
Tian-yu WU ; Wen-hao ZHANG ; Peng-sheng CHEN ; Chen LI ; Tian WU ; Zhan LÜ ; Tong WANG ; Kun LIU ; Zhi-wen TAO ; Xiao-xuan GONG ; Liang YUAN ; Yong LI ; Bo CHEN ; Xin CHEN ; Zeng-guang CHEN ; Nai-quan YANG ; Yuan-yuan SANG ; Xiao-yan WANG ; Bai-hong LI ; Li ZHU ; Guo-yu WANG ; Xin ZHAO ; Chuan LU ; Jun JIANG ; Rui-na HAO ; Chun-jian LI
Chinese Journal of Interventional Cardiology 2025;33(8):431-438
Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P<0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P>0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.
8.Effects of Zhuanggu Zhitong Prescription on osteoporosis in castrated rats based on Notch signaling pathway
Jun YANG ; Jie QU ; Liming CHEN ; Tong WU
International Journal of Traditional Chinese Medicine 2025;47(1):58-63
Objective:To explore the mechanism of Zhuanggu Zhitong Prescription in preventing and treating postmenopausal osteoporosis.Methods:Rats were randomly divided into blank group, model group, Zhuanggu Zhitong Prescription high-, medium-, and low-dosage groups, and an estradiol group, with 10 rats in each group. Except for the blank group, all other groups of rats underwent bilateral oophorectomy to remove the ovaries, in order to prepare a postmenopausal osteoporosis rat model. On the 5th day after modeling, the blank group and model group were orally administered with 0.9% NaCl physiological saline, Zhuanggu Zhitong Prescription high-, medium-, and low-dosage groups were orally administered with 13.2, 8.2, and 3.3 g/kg of Zhuanggu Zhitong Prescription, and the estradiol group was orally administered with 0.016 7 g/100 g estradiol aqueous solution once a day for 12 consecutive weeks. The bone density of the lumbar spine in rats was measured; immunohistochemistry and Western blot were used to detect the expressions of Notch1, Jagged1, and Hes1 proteins; PCR was used to detect the mRNA levels of Notch1, Jagged1, and Hes1 in rats.Results:Compared with the model group, the bone density of rats in each group significantly increased ( P<0.01), the protein and mRNA levels of Notch1 and Jagged1 increased ( P<0.01), and the protein and mRNA levels of Hes1 decreased ( P<0.01). Conclusions:Zhuanggu Zhitong Prescription can improve bone mineral density in castrated osteoporosis rats, promote the increase and thickening of trabeculae of femoral bone in rats, promote bone formation, and further prevent osteoporosis. The mechanism may be related to the activation of Notch signaling pathway, up-regulation of Notch1 and Jagged1 proteins, and decrease of Hes1 protein expression, thus promoting bone differentiation.
9.Exploration on the mechanism of the Zhuanggu Zhitong Prescription in preventing and treating osteoporosis in ovariectomized rats based on the Wnt/β-catenin signaling pathway
International Journal of Traditional Chinese Medicine 2025;47(7):946-951
Objective:To explore the mechanism of Zhuanggu Zhitong Prescription in preventing and treating postmenopausal osteoporosis.Methods:SD female rats were randomly divided into six groups using the random number table method: blank group, model group, estradiol group, and Zhuanggu Zhitong Prescription low-, medium-, and high-dosage groups. Except for the blank group, all other groups underwent ovariectomy to induce a postmenopausal osteoporosis model over a 3-month period. After successful modeling, the Zhuanggu Zhitong Prescription low-, medium-, and high-dosage groups received intragastric administration of Zhuanggu Zhitong aqueous solution at dosages of 3.3 g/kg, 8.2 g/kg, and 13.2 g/kg, respectively. The estradiol group received intragastric administration of an estradiol solution at a dosage of 0.167 mg/kg. Both the blank group and the model group received intragastric administration of an equal volume of normal saline once daily for 12 weeks. The bone density of rat femur tissue was detected. Immunohistochemistry, real-time fluorescence quantitative PCR, and Western blot were used to detect the protein or mRNA levels of Wnt3a, β-catenin, and short stature related transcription factor 2 (Runx2).Results:Compared with the model group, the bone mineral density of lumbar vertebrae increased in the estradiol group and the Zhuanggu Zhitong Prescription low-, medium-, and high-dosage groups ( P<0.01). Additionally, the mean optical density, as well as the mRNA and protein expression levels of Wnt3a, β-catenin, and Runx2 in femur tissue also increased ( P<0.01). Conclusions:Zhuanggu Zhitong Prescription can improve bone mineral density in castrated osteoporosis rats, promote the increase and thickening of femoral bone trabeculae, promote bone formation, and prevent osteoporosis. The mechanism may be related to the activation of Wnt/β-catenin signaling pathway to up-regulate the expressions of Wnt3a and Runx2, thus promoting bone differentiation.
10.Clinical characteristics and prognosis of childhood-onset Takayasu arteritis involving pulmonary artery
Yingjie XU ; Gaixiu SU ; Dan ZHANG ; Min KANG ; Jia ZHU ; Tong YUE ; Ming LI ; Min WEN ; Feifei WU ; Jun HOU ; Shengnan LI ; Jianming LAI
Chinese Journal of Pediatrics 2025;63(11):1218-1223
Objective:To investigate the clinical characteristics, imaging features, risk factors, and prognosis of childhood-onset Takayasu arteritis (TAK) with pulmonary artery involvement.Methods:A retrospective cohort study was conducted in 107 pediatric patients who were initially diagnosed with childhood-onset TAK at Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical Universiy, from January 2010 to December 2024. Clinical data, including demographic information, imaging features, treatment regimens, and prognosis were collected. Patients were divided into with and without pulmonary artery involvement groups. Intergroup comparisons were performed. Multivariate logistic regression was used to identify risk factors for pulmonary artery involvement. Kaplan-Meier analysis with Log-Rank testing was used for survival analyze.Results:Among 107 children with TAK, 26 were male, 81 were female, with a diagnosis age of 88 (5, 137) months. Sixteen cases were in the pulmonary artery involvement group and 91 cases in the non-pulmonary artery involvement group. The pulmonary artery involvement group was predominantly female (14 cases), with a diagnosis age of 39 (4, 104) months. The pulmonary artery involvement group had higher incidence rates of fatigue,pulmonary hypertension, right heart failure,superior mesenteric artery involvement,as well as higher neutrophil counts, C-reactive protein (CRP) levels (all P<0.05). Hemoglobin was lower in the pulmonary artery involvement group ( P<0.05). Imaging findings revealed that all 16 children in the pulmonary artery involvement group showed signs of pulmonary arterial wall thickening. Other manifestations included dilation in 2 cases, stenosis in 2 cases, and occlusion in 1 case. Unilateral involvement (12 cases) was more common, and the right pulmonary artery (10 cases) was more frequently affected. Independent risk factors for pulmonary artery involvement in childhood-onset TAK patients included superior mesenteric artery involvement ( OR=5.58, 95% CI 1.41-22.10, P=0.014) and elevated CRP levels ( OR=1.02, 95% CI 1.00-1.03, P=0.027). During a follow-up of 3.9 (1.4,8.1) years, 2 patients with pulmonary artery involvement (all with pulmonary hypertension), among the survivors in the pulmonary artery involvement group, 2 cases still exhibited persistent pulmonary artery dilation, and one case had pulmonary artery occlusion; and 6 patients (6.6%) without pulmonary artery involvement died. Patients with pulmonary artery involvement had significantly lower survival rates compared to those without involvement ( P=0.024). Conclusions:Childhood-onset TAK with pulmonary artery involvement has an insidious clinical presentation, and can progress to pulmonary hypertension, pulmonary artery occlusion, and a significantly reduced survival rate. Patients with mesenteric artery involvement or elevated CRP have higher risks of pulmonary artery involvement, requiring close pulmonary vascular monitoring and early intervention to improve prognosis.

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