1.Clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver in children
Jinyue ZHENG ; Chang ZHAO ; Jing LIANG ; Yuhang PAN ; Wen HU ; Luying TANG ; Chunkui SHAO ; Jianning CHEN
Chinese Journal of Pathology 2025;54(11):1156-1162
Objective:To investigate the clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Three cases of UESL diagnosed in the Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University from 2020 to 2023 were retrospectively collected. The clinical, histomorphological, immunohistochemical, and genetic profiles were reviewed and analyzed.Results:The cohort comprised of three patients, including one male and two females, aged 7, 9, and 15 years, respectively. Tumor locations were in the right lobe of the liver in two cases, and in both the right and left lobes in one case. One case exhibited tumor rupture with hemorrhage. Gross examination revealed solid tumors in gray-red fleshy appearance, with areas of hemorrhage and necrosis. Microscopically, the tumor was composed of irregularly shaped spindle and polygonal cells arranged in bundles or sheets with varying density, scattered within a myxoid matrix containing giant tumor cells and eosinophilic globules. The tumor cells were positive for Vimentin, CD56, CD68, and bcl-2, with a Ki-67 index of 30%-80%. INI1 expression was retained, while p53 exhibited a mutant pattern. CKpan, CK7, CK19, EMA, HepPar-1, Arginase-1, AFP, CD34, S-100, Myogenin, and MyoD1 were negative. All three cases harbored TP53 missense mutations. Case 1 also showed MDM2 copy number amplification (class Ⅰ mutation), and case 2 exhibited a frameshift mutation in exon 10 of TSC2 (class Ⅱ mutation). Additionally, several class Ⅲ mutations were identified in all three cases. Germline testing for tumor-related genetic variants in case 2 revealed a missense mutation in exon 12 of DICER1, an in-frame insertion mutation in exon 8 of MSH2, and a missense mutation in exon 30 of TSC2.Conclusion:UESL is a rare malignant mesenchymal tumor of the liver, predominantly affecting children, with distinctive clinicopathological features and genetic alterations. TP53 mutations may play a key role in the pathogenesis of this tumor.
2.Hematopoietic stem cell and kidney transplantation from the same donor in a patient with acute myeloid leukemia and literature review
Yan YIN ; Zilin QUAN ; Li SONG ; Zhonglin FENG ; Dongmei CUI ; Liyan ZHAO ; Yuhang HU ; Qinghua ZHOU ; Xiaoli KANG ; Junjie LIAO ; Qizhen LIANG ; Suijin WU ; Hongmei WU ; Shuangxin LIU
Chinese Journal of Nephrology 2025;41(9):691-695
The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.
3.Identification of unknown pollutants in drinking water based on solid-phase extraction and supramolecular solvent extraction
Zixin QIAN ; Yuhang CHEN ; Chao FENG ; Yuanjie LIN ; Qian XU ; Ziwei LIANG ; Xinyu WANG ; Dasheng LU ; Ping XIAO ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2025;42(7):854-861
Background With the progression of industrialization, an increasing number of emerging contaminants are entering aquatic environments, posing significant threats to the safety of drinking water. Therefore, establishing a system for identifying unknown hazardous factors and implementing safety warning mechanisms for drinking water is of paramount importance. Among these efforts, non-target screening plays a critical role, but its effectiveness is largely constrained by the scope of coverage of sample pre-treatment methods. Objective To integrate modern chromatography/mass spectrometry techniques with advanced data mining methods to develop a non-discriminatory sample pre-treatment method for comprehensive enrichment of unknown contaminants in drinking water, laying a technical foundation for the discovery and identification of unknown organic hazardous factors in drinking water. Methods A non-discriminatory pre-treatment method based on supramolecular and solid-phase extraction was developed. The final target compounds including 333 pesticides, 194 pharmaceuticals and personal care products (PPCPs), and 59 per- and polyfluoroalkyl substances (PFASs) were used for optimizing the pre-treatment method, confirming its coverage. The impacts of different eluents on the absolute recovery rates of target compounds were compared to select the conditions with the highest recovery for sample pre-treatment. The effects of different supramolecular solvents and salt concentrations on target compound recovery were also evaluated to determine the most suitable solvent and salt concentration. Results The solid-phase extraction elution solvents, supramolecular extraction solvents, and salt concentrations were optimized based on the target compound recovery rates. The optimal recovery conditions were achieved using 2 mL methanol, 2 mL methanol (containing 1% formic acid), 2 mL ethyl acetate, 2 mL dichloromethane, hexanediol supramolecular solvent, and 426 mg salt. The detection method developed based on these conditions showed a good linear relationship for all target compounds in the range of 0.1-100.0 ng·mL−1, with R² > 0.99. The method’s limit of detection ranged from 0.01 ng−1 to 0.95 ng−1, and 95% of target compounds were recovered in the range of 20%-120%, with relative standard deviation (RSD) less than 30%, indicating good precision. Conclusion The combined pre-treatment method of solid-phase extraction and supramolecular solvent extraction can effectively enrich contaminants in drinking water across low, medium, and high polarities, enabling broad-spectrum enrichment of diverse trace contaminants in drinking water. It provides technical support for broad-spectrum, high-throughput screening and identification of organic pollutants in drinking water, and also serves as a reference for establishing urban drinking water public safety warning systems.
4.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
5.Genomic evolutionary characteristics of 69 Legionella pneumophila strains in Fujian Province
Junjie MAO ; Rui JIN ; Xuechen LIANG ; Yuhang DENG ; Yadong GAO ; Quwen LI
Chinese Journal of Zoonoses 2025;41(7):691-696
Legionella pneumophila is an important pathogen responsible for legionellosis.Understanding the genetic diversity,evo-lutionary traits,and potential pathogenicity of L.pneumophila in Fujian Province is crucial for the implementation of effective public health interventions.This study was aimed at investigating these aspects through the analysis of environmental isolates collected from 2019 to 2024.A total of 69 environmental isolates of L.pneumophila were collected,and serotypes were determined with agglutination methods.The predominant serotypes were LP1 and LP5,identified in 23 isolates(33.33%)and 15 isolates(18.84%),respectively.Whole-genome sequencing was conducted to assess the genomic characteristics of these isolates.The genomic sizes ranged from 3.26 Mb to 3.81 Mb,and the GC content ranged from 38.0%to 38.3%.Sequence type(ST)1 880 emerged as the dominant strain among the isolates.All isolates carried several virulence-associated genes,including mip,iraA,htpB,LPG_RS03055,and lspM,thus indicat-ing strong potential for pathogenicity.The prevalence of the multidrug resistance genes lpeA and lpeB was 23.2%,thereby suggesting a concerning level of antibiotic resistance.Various mobile genetic elements,such as genomic islands,insertion sequences,phages,and CRISPR/Cas systems,were also detected.In conclusion,our findings emphasize the importance of continued research and surveil-lance of L.pneumophila,particularly the ST1880 clone,to gain a deeper understanding of its transmission mechanisms and to imple-ment control measures effectively.These insights should aid in enhancing public health responses to legionellosis in Fujian Province.
6.Surgical efficacy of transanal anaplasty for the treatment of rectovestibular fistulae
Dazhi REN ; Yan LI ; Heying YANG ; Yuhang YUAN ; Daokui DING ; Beibei SUN ; Xueer LI ; Chunxiao YAN ; Haodi LIANG ; Yali JIN ; Kun SONG
Chinese Journal of General Surgery 2025;40(2):139-143
Objective:To evaluate the clinical efficacy and the mid- and long-term follow-up outcomes of transanal anaplasty for treating rectovestibular fistula.Methods:The clinical data of 68 female infants diagnosed with rectovestibular fistula undergoing transanal anoplasty at the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from Oct 2014 to Dec 2023 was collected. Postoperative complications, perineal and anal appearances, and defecation function of postoperative children aged 3 years or older were recorded.Results:After surgery 68 children followed-up for 6 months of recent with short-term complications in 6 cases, including 3 cases of incision infection, 2 cases of rectal mucosal prolapse, and 1 case of anal stenosis. Rintala score was (18.65±1.99). Twenty-five children underwent anorectal manometry, no significant differences were observed in the maximal systolic pressure of the anal canal( t=-0.596, P=0.563) and the maximum systolic time( t=-0.183, P=0.854). The resting pressure( t=-3.050, P=0.005), functional length( t=2.696, P=0.012), and positive rate of rectal anal inhibitory reflex( χ2=6.382, P=0.012) of the anal canal were significantly lower than those of the normal group( P<0.05). Conclusions:Transanal anaplasty for the treatment of rectovestibular fistula in girls has a low incidence of complications. It results in a normal perineal body appearance, good anal bowel control, and high quality of life.
7.Optimization of 90Y PET/CT imaging based on the block-sequential regularized expectation maximization reconstruction algorithm
Tiantian ZHANG ; Ziwei LIANG ; Zhongbin HANG ; Yan ZHANG ; Deqing LIU ; Yuhang SHAN ; Yong LIAO ; Xin HUANG ; Bin LIANG ; Lin ZHANG ; Xiaobin FENG ; Zuoxiang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):335-340
Objective:To optimize the image quality of PET/CT following 90Y-selective internal radiation therapy ( 90Y-SIRT) using block-sequential regularized expectation maximization (BSREM) reconstruction algorithm, and to evaluate its impact of different β values on image quality and quantitative analysis. Methods:A retrospective study was conducted on 8 male patients with hepatic tumors (age: 62(52, 71) years) treated at Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine Tsinghua University, between June 2024 and January 2025. All patients were treated with 90Y resin microspheres (2.6(0.9, 3.6)GBq) and underwent post-treatment 90Y PET/CT liver imaging. Imaging data were reconstructed using BSREM with different noise penalty weighting factors ( β values: 0, 300, 1000, 1500, 2500, 3500, 4000, 6000, 8000, 10000). Visual assessment was independently performed by two nuclear medicine physicians, using a 4-point scale (1=worst, 4=best). The mean score was considered as the final score. The consistency of the 2 reviewers was calculated and analyzed by Kappa test. Visual scores of different β value groups were compared by Friedman test. The β value demonstrating highest mean score and optimal consistency was selected as the optimal. Quantitative analysis was performed using MIM software to calculate the maximum absorbed dose ( Dmax) and the mean absorbed dose ( Dmean) for tumor, normal liver, and whole liver regions, and the CV was used to evaluate the impact of β values. Results:The visual assessment consistency of reviewers in 3 β value groups (0, 3500, 6000) were the highest (7/8) (all kappa=0.88, all P<0.05). Visual scores of the 10 β value groups were significantly different ( χ2=28.74, P<0.001), and the visual scores of 2 β value groups (3500, 4000) were the highest, both of which were 4.0(4.0, 4.0). Overall, visual assessment identified β=3500 as the optimal. Quantitative analysis revealed that, (1) Dmax in all regions (tumor, normal liver, whole liver) decreased with the increasing β values, stabilizing when β>1000 ( CV 56%-67%); (2) Dmean remained stable across different β values ( CV 0.04%-5.00%). Conclusions:In BSREM reconstruction, β=3500 is the optimal parameter for improving 90Y-PET image quality. β values significantly affect Dmax (stabilizing at β > 1000), but have no significant impact on Dmean, suggesting that reconstruction parameters primarily influence dose distribution morphology rather than average dose assessments.
8.Genomic evolutionary characteristics of 69 Legionella pneumophila strains in Fujian Province
Junjie MAO ; Rui JIN ; Xuechen LIANG ; Yuhang DENG ; Yadong GAO ; Quwen LI
Chinese Journal of Zoonoses 2025;41(7):691-696
Legionella pneumophila is an important pathogen responsible for legionellosis.Understanding the genetic diversity,evo-lutionary traits,and potential pathogenicity of L.pneumophila in Fujian Province is crucial for the implementation of effective public health interventions.This study was aimed at investigating these aspects through the analysis of environmental isolates collected from 2019 to 2024.A total of 69 environmental isolates of L.pneumophila were collected,and serotypes were determined with agglutination methods.The predominant serotypes were LP1 and LP5,identified in 23 isolates(33.33%)and 15 isolates(18.84%),respectively.Whole-genome sequencing was conducted to assess the genomic characteristics of these isolates.The genomic sizes ranged from 3.26 Mb to 3.81 Mb,and the GC content ranged from 38.0%to 38.3%.Sequence type(ST)1 880 emerged as the dominant strain among the isolates.All isolates carried several virulence-associated genes,including mip,iraA,htpB,LPG_RS03055,and lspM,thus indicat-ing strong potential for pathogenicity.The prevalence of the multidrug resistance genes lpeA and lpeB was 23.2%,thereby suggesting a concerning level of antibiotic resistance.Various mobile genetic elements,such as genomic islands,insertion sequences,phages,and CRISPR/Cas systems,were also detected.In conclusion,our findings emphasize the importance of continued research and surveil-lance of L.pneumophila,particularly the ST1880 clone,to gain a deeper understanding of its transmission mechanisms and to imple-ment control measures effectively.These insights should aid in enhancing public health responses to legionellosis in Fujian Province.
9.Optimization of 90Y PET/CT imaging based on the block-sequential regularized expectation maximization reconstruction algorithm
Tiantian ZHANG ; Ziwei LIANG ; Zhongbin HANG ; Yan ZHANG ; Deqing LIU ; Yuhang SHAN ; Yong LIAO ; Xin HUANG ; Bin LIANG ; Lin ZHANG ; Xiaobin FENG ; Zuoxiang HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):335-340
Objective:To optimize the image quality of PET/CT following 90Y-selective internal radiation therapy ( 90Y-SIRT) using block-sequential regularized expectation maximization (BSREM) reconstruction algorithm, and to evaluate its impact of different β values on image quality and quantitative analysis. Methods:A retrospective study was conducted on 8 male patients with hepatic tumors (age: 62(52, 71) years) treated at Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine Tsinghua University, between June 2024 and January 2025. All patients were treated with 90Y resin microspheres (2.6(0.9, 3.6)GBq) and underwent post-treatment 90Y PET/CT liver imaging. Imaging data were reconstructed using BSREM with different noise penalty weighting factors ( β values: 0, 300, 1000, 1500, 2500, 3500, 4000, 6000, 8000, 10000). Visual assessment was independently performed by two nuclear medicine physicians, using a 4-point scale (1=worst, 4=best). The mean score was considered as the final score. The consistency of the 2 reviewers was calculated and analyzed by Kappa test. Visual scores of different β value groups were compared by Friedman test. The β value demonstrating highest mean score and optimal consistency was selected as the optimal. Quantitative analysis was performed using MIM software to calculate the maximum absorbed dose ( Dmax) and the mean absorbed dose ( Dmean) for tumor, normal liver, and whole liver regions, and the CV was used to evaluate the impact of β values. Results:The visual assessment consistency of reviewers in 3 β value groups (0, 3500, 6000) were the highest (7/8) (all kappa=0.88, all P<0.05). Visual scores of the 10 β value groups were significantly different ( χ2=28.74, P<0.001), and the visual scores of 2 β value groups (3500, 4000) were the highest, both of which were 4.0(4.0, 4.0). Overall, visual assessment identified β=3500 as the optimal. Quantitative analysis revealed that, (1) Dmax in all regions (tumor, normal liver, whole liver) decreased with the increasing β values, stabilizing when β>1000 ( CV 56%-67%); (2) Dmean remained stable across different β values ( CV 0.04%-5.00%). Conclusions:In BSREM reconstruction, β=3500 is the optimal parameter for improving 90Y-PET image quality. β values significantly affect Dmax (stabilizing at β > 1000), but have no significant impact on Dmean, suggesting that reconstruction parameters primarily influence dose distribution morphology rather than average dose assessments.
10.Hematopoietic stem cell and kidney transplantation from the same donor in a patient with acute myeloid leukemia and literature review
Yan YIN ; Zilin QUAN ; Li SONG ; Zhonglin FENG ; Dongmei CUI ; Liyan ZHAO ; Yuhang HU ; Qinghua ZHOU ; Xiaoli KANG ; Junjie LIAO ; Qizhen LIANG ; Suijin WU ; Hongmei WU ; Shuangxin LIU
Chinese Journal of Nephrology 2025;41(9):691-695
The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

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