1.A Case of Multidisciplinary Treatment for Inflammatory Myofibroblastic Tumor Complicated by ANCA-Associated Vasculitis
Shaoying WANG ; Linyi PENG ; Ke ZHENG ; Zhiwei WANG ; Dachun ZHAO ; Xia ZHANG ; Lin ZHAO ; Wenhui WANG ; Weiqing WANG ; Zhenzhen ZHU ; Jin XU ; Min SHEN
JOURNAL OF RARE DISEASES 2026;5(1):43-51
A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.
2.Analyses of serotypes and antibiotic resistance of Salmonella in diarrheal diseases in Baoshan District of Shanghai from 2023 to 2024
Fangdian LIN ; Xu ZHANG ; Junqing SHEN ; Min JIN
Shanghai Journal of Preventive Medicine 2026;38(4):289-295
ObjectiveTo retrospectively analyze the correlation among serotypes, antimicrobial resistance phenotypes, and resistance genotypes of Salmonella isolates from diarrheal cases in Baoshan District of Shanghai from 2023 to 2024, and to provide a reference for the prevention and control of Salmonella infections and the rational use of antibiotics in clinical practice. MethodsSalmonella isolates collected from diarrheal cases under surveillance in Baoshan District from 2023 to 2024 were serotyped. Antimicrobial resistance phenotypes were determined using the broth microdilution method, and whole-genome sequencing was performed to identify resistance genes. Positive predictive value and Kappa were calculated to evaluate the agreement between phenotypic and genotypic resistance profiles of Salmonella. ResultsA total of 64 Salmonella isolates belonged to 17 serotypes, with the predominant ones being Salmonella Typhimurium (25.00%) and Salmonella Enteritidis (18.75%). The tested strains exhibited high resistance rates to ampicillin (60.94%), streptomycin (59.38%), and ampicillin/sulbactam (45.31%). All isolates remained susceptible to ceftiofur and ceftazidime/avibactam. Forty different resistance profiles were identified, and 39 isolates accounting for 60.94%, were multidrug-resistant. Overall, 80 resistance genes belonging to 13 categories were detected, with the most prevalent being blaTEM-1 (57.81%), aac(6')⁃Iy (54.69%), and aph(6)⁃Id (46.88%). No carbapenem or polymyxin resistance genes were found. The types and numbers of resistance genes varied significantly across serotypes. A high concordance was observed between genotype and phenotype for penicillins (positive predictive value: 94.59%, Kappa: 0.81), cephalosporins (90.91%, 0.46), cephamycins (100.00%, 0.65), macrolides (77.78%, 0.86), tetracyclines (100.00%, 0.93), and chloramphenicol (95.83%, 0.93). ConclusionSalmonella isolates from diarrheal diseases in Baoshan District exhibit high antimicrobial resistance. Whole-genome sequencing provides valuable support for resistance surveillance, however, it still needs to be integrated with phenotypic susceptibility testing for comprehensive assessment. Further studies are warranted to elucidate the mechanisms and transmission patterns of resistance in Salmonella.
3.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
5.Development and validation of a prediction score for subtype diagnosis of primary aldosteronism.
Ping LIU ; Wei ZHANG ; Jiao WANG ; Hongfei JI ; Haibin WANG ; Lin ZHAO ; Jinbo HU ; Hang SHEN ; Yi LI ; Chunhua SONG ; Feng GUO ; Xiaojun MA ; Qingzhu WANG ; Zhankui JIA ; Xuepei ZHANG ; Mingwei SHAO ; Yi SONG ; Xunjie FAN ; Yuanyuan LUO ; Fangyi WEI ; Xiaotong WANG ; Yanyan ZHAO ; Guijun QIN
Chinese Medical Journal 2025;138(23):3206-3208
6.Associations between statins and all-cause mortality and cardiovascular events among peritoneal dialysis patients: A multi-center large-scale cohort study.
Shuang GAO ; Lei NAN ; Xinqiu LI ; Shaomei LI ; Huaying PEI ; Jinghong ZHAO ; Ying ZHANG ; Zibo XIONG ; Yumei LIAO ; Ying LI ; Qiongzhen LIN ; Wenbo HU ; Yulin LI ; Liping DUAN ; Zhaoxia ZHENG ; Gang FU ; Shanshan GUO ; Beiru ZHANG ; Rui YU ; Fuyun SUN ; Xiaoying MA ; Li HAO ; Guiling LIU ; Zhanzheng ZHAO ; Jing XIAO ; Yulan SHEN ; Yong ZHANG ; Xuanyi DU ; Tianrong JI ; Yingli YUE ; Shanshan CHEN ; Zhigang MA ; Yingping LI ; Li ZUO ; Huiping ZHAO ; Xianchao ZHANG ; Xuejian WANG ; Yirong LIU ; Xinying GAO ; Xiaoli CHEN ; Hongyi LI ; Shutong DU ; Cui ZHAO ; Zhonggao XU ; Li ZHANG ; Hongyu CHEN ; Li LI ; Lihua WANG ; Yan YAN ; Yingchun MA ; Yuanyuan WEI ; Jingwei ZHOU ; Yan LI ; Caili WANG ; Jie DONG
Chinese Medical Journal 2025;138(21):2856-2858
7.Research progress of the interaction between RAAS and clock genes in cardiovascular diseases.
Rui-Ling MA ; Yi-Yuan WANG ; Yu-Shun KOU ; Lu-Fan SHEN ; Hong WANG ; Ling-Na ZHANG ; Jiao TIAN ; Lin YI
Acta Physiologica Sinica 2025;77(4):669-677
The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans
;
Renin-Angiotensin System/genetics*
;
Cardiovascular Diseases/genetics*
;
CLOCK Proteins/physiology*
;
Animals
8.Clinical Application and Pharmacological Mechanism of Sishenwan in Treatment of Ulcerative Colitis: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Sifeng JIA ; Yuyu DUAN ; Zixing QIAN ; Yifan CAI ; Junyi SHEN ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):261-270
Ulcerative colitis (UC), a chronic, non-specific inflammatory bowel disease with typical symptoms such as abdominal pain, diarrhea, and bloody stools, demonstrates a high relapse rate and difficulty in curing. Sishenwan, first recorded in Internal Medicine Abstract (Nei Ke Zhai Yao), are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney, and astringing the intestine and stopping diarrhea. In recent years, Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors, including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term, its side effects, high relapse rate, and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan, used alone or in combination with Western medicine or other Chinese medicine compound prescriptions, significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus, pus, and blood in stools, and persistent abdominal pain, reduce Mayo scores and the relapse rate, and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen, isopsoralen, and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level, Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future, a full-chain system covering syndrome differentiation, targeting, and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics, providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.
9.Clinical Application and Pharmacological Mechanism of Sishenwan in Treatment of Ulcerative Colitis: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Sifeng JIA ; Yuyu DUAN ; Zixing QIAN ; Yifan CAI ; Junyi SHEN ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):261-270
Ulcerative colitis (UC), a chronic, non-specific inflammatory bowel disease with typical symptoms such as abdominal pain, diarrhea, and bloody stools, demonstrates a high relapse rate and difficulty in curing. Sishenwan, first recorded in Internal Medicine Abstract (Nei Ke Zhai Yao), are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney, and astringing the intestine and stopping diarrhea. In recent years, Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors, including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term, its side effects, high relapse rate, and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan, used alone or in combination with Western medicine or other Chinese medicine compound prescriptions, significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus, pus, and blood in stools, and persistent abdominal pain, reduce Mayo scores and the relapse rate, and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen, isopsoralen, and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level, Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future, a full-chain system covering syndrome differentiation, targeting, and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics, providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.
10.Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma.
Yumeng LIN ; Yibo HUANG ; Bowen YANG ; You ZHANG ; Ning JI ; Jing LI ; Yu ZHOU ; Ying-Qiang SHEN ; Qianming CHEN
Chinese Medical Journal 2025;138(15):1853-1865
BACKGROUND:
Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.
METHODS:
To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated.
RESULTS:
OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression.
CONCLUSION
Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans
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ErbB Receptors/metabolism*
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Mouth Neoplasms/metabolism*
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Cell Line, Tumor
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Animals
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Drug Resistance, Neoplasm/genetics*
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Cadherins/metabolism*
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Carcinoma, Squamous Cell/metabolism*
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Mice
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Mutation/genetics*
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Mice, Nude
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Protein Kinase Inhibitors/therapeutic use*
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Cetuximab/pharmacology*
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Afatinib/therapeutic use*
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Cell Proliferation/drug effects*
;
Signal Transduction/drug effects*

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