1.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
2.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
3.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
4.Research progress in hydrogels in tissue engineering trachea
Wenxuan CHEN ; Yibo SHAN ; Fei SUN ; Zhiming SHEN ; Yi LU ; Jianwei ZHU ; Lei YUAN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1195-1199
In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.
5.Integration strategy for chronic disease screening indicators in occupational medical examinations
Tianyang SHEN ; Jiming ZHANG ; Tengxiao SHAN ; Zhijun ZHOU
China Occupational Medicine 2025;52(3):336-340
As the prevalence of chronic diseases increases among occupational populations in China, the focus of occupational health management has shifted from ″occupational disease prevention and control″ to ″occupational disease and chronic disease prevention and control″. At present, occupational medical examinations (OME) are mainly focused on occupational disease prevention and control, and generally lack of chronic disease indicators such as blood lipids and blood glucose, limiting the role of OME in life-cycle health management of workers. To address this gap, it is necessary to incorporate chronic disease screening indicators into OME. Integrating OME and chronic disease screening faces bottlenecks, including concerns about increased operating costs in small- and medium-sized enterprises, and the risk of employment discrimination caused by the leakage of employee health privacy. A tiered strategy is recommended. Incorporating low-cost indicators such as blood lipids, waist circumference into routine examinations, and customizing advanced screening for elder or high-risk position workers. The prioritization of screening indicators can be determined by expert consultation and employer-employee discussions. Meanwhile, the results of chronic disease screening indicators should not be included in occupational health surveillance records to protect workers′ privacy. In summary, expanding OME to cover more chronic disease indicators provides valuable economic and social benefits. In the long run, common chronic disease screening indicators should be included in the regular medical examination indicators of OME, thereby reducing the burden of chronic diseases on occupational populations and promoting the health management of occupational populations.
6.Saltwater stir-fried Plantaginis Semen alleviates renal fibrosis by regulating epithelial-mesenchymal transition in renal tubular cells.
Xin-Lei SHEN ; Qing-Ru ZHU ; Wen-Kai YU ; Li ZHOU ; Qi-Yuan SHAN ; Yi-Hang ZHANG ; Yi-Ni BAO ; Gang CAO
China Journal of Chinese Materia Medica 2025;50(5):1195-1208
This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals
;
Epithelial-Mesenchymal Transition/drug effects*
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Fibrosis/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Kidney Diseases/pathology*
;
Kidney Tubules/pathology*
;
Humans
7.CFAP300 loss-of-function variant causes primary ciliary dyskinesia and male infertility via disrupting sperm flagellar assembly and acrosome formation.
Hua-Yan YIN ; Yu-Qi ZHOU ; Qun-Shan SHEN ; Zi-Wen CHEN ; Jie-Ru LI ; Huan WU ; Yun-Xia CAO ; Rui GUO ; Bing SONG
Asian Journal of Andrology 2025;27(6):743-750
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans
;
Male
;
Infertility, Male/pathology*
;
Acrosome/pathology*
;
Sperm Tail/pathology*
;
Pedigree
;
Spermatozoa
;
Adult
;
Loss of Function Mutation
;
Ciliary Motility Disorders/genetics*
;
Spermatogenesis/genetics*
;
Female
8.Analysis of burden and equality of lower extremity peripheral artery disease in people aged 40 and above in the Belt and Road partner countries from 1990 to 2021.
Guangdian SHEN ; Longzhu ZHU ; Jiayao YING ; Shiyi SHAN ; Zeyu LUO ; Denan JIANG ; Jing WU ; Yuefeng ZHU
Journal of Zhejiang University. Medical sciences 2025;54(1):10-20
OBJECTIVES:
To analyze the disease burden and inequalities of lower extremity peripheral artery disease (LEPAD) among people aged 40 and above in the Belt and Road partner countries from 1990 to 2021.
METHODS:
Data were retrieved from the Global Burden of Disease 2021 database. The age-standardized prevalence rates, mortality rates, and the annual rate of years lived with disability (YLDs) of LEPAD were analyzed. Trends were measured using the estimated annual percentage change (EAPC), and the slope index of inequality (SII) and concentration index were used to quantify the absolute and relative inequalities.
RESULTS:
In 2021, the age-standardized prevalence and mortality rates of LEPAD were 3168.26/105 and 3.09/105, increasing by 4.30% and 19.31% compared to 1990, while YLDs rates decreased by 4.00%. Females had higher age-standardized prevalence and YLDs rates, while males had higher mortality rates. The EAPC for prevalence rates was slightly higher in males (0.22%) than in females (0.17%); while the EAPC of age-standardized mortality rate was 2.02% for females, compared to 1.45% for males. From 1990 to 2021, the age-standardized YLDs rates decreased from 16.23/105 to 15.58/105, with a faster decline in females (-0.12%) than in males (-0.06%). LEPAD prevalence varied across countries, with higher burden in Europe and faster growth in Gulf states. Higher socio-demographic index countries had higher prevalence. Inequity improved, with the SII at 52.90/105 and concentration index at 0.038 in 2021. Gender disparities persisted, with concentration index increased to 0.058 in females and reduced to -0.026 in males.
CONCLUSIONS
LEPAD prevalence and mortality among people aged 40 and above in the Belt and Road partner countries increased, while YLDs rates decreased from 1990 to 2021. Significant differences among people exist depending on gender and country, highlighting the need for enhanced screening, health education, and shared public health strategies across the Belt and Road partner countries.
Humans
;
Peripheral Arterial Disease/mortality*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Aged
;
Prevalence
;
Lower Extremity/blood supply*
;
Global Burden of Disease
;
Cost of Illness
9.Clinical Characteristics and Prognosis Analysis of Patients with Extranasal NK/T-Cell Lymphoma: A Multicenter Retrospective Study of Huaihai Lymphoma Working Group.
Hui-Rong SHAN ; Qing ZHANG ; Ling WANG ; Yu-Ye SHI ; Yu-Qing MIAO ; Tai-Gang ZHU ; Jing-Jing YE ; Xu-Dong ZHANG ; Liang WANG ; Zi-Yuan SHEN ; Wei SANG
Journal of Experimental Hematology 2025;33(1):93-100
OBJECTIVE:
To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL).
METHODS:
The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis.
RESULTS:
A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005).
CONCLUSION
The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Asparaginase/therapeutic use*
;
Lymphoma, Extranodal NK-T-Cell/pathology*
;
Prognosis
;
Retrospective Studies
;
Survival Rate
;
Polyethylene Glycols
10.Detection and Transfusion Strategy of Mimicking Antibodies.
Hui ZHANG ; Jie-Wei ZHENG ; Sha JIN ; Wei SHEN ; Shan-Shan LI ; Xiao-Wen CHENG ; Dong XIANG
Journal of Experimental Hematology 2025;33(4):1168-1172
OBJECTIVE:
To explore serological detection and blood transfusion strategies of mimicking antibodies, so as to provide appropriate transfusion strategies.
METHODS:
Detailed serological tests, including ABO blood group, Rh typing, antibody specificity, etc,were performed on two patients with autoimmune hemolytic anemia(AIHA). Meanwhile, the references about blood transfusion from mimicking antibody patients published from 1977 to 2024 in China and abroad were retrospectively summarized and analyzed.
RESULTS:
The patient 1 blood type was AB,CCDee and the antibody is mimicking anti-e, transfusion the e-negative red blood cells (RBCs) was effective. After two transfusions of e-RBCs, hemoglobin levels significantly increased from 48 g/L to 91 g/L, with complete resolution of hemolytic symptoms. The patient 2 blood type was O,CcDee, and the antibody was mimicking anti-c, the patient was diagnosed with AIHA and treated with hormone. No blood products were transfused during hospitalization, and his hemolysis was relieved.
CONCLUSION
Strictly grasping the indication of blood transfusion, blood transfusion should not be performed in the unnecessary conditions, and the corresponding antigen-negative RBC should be screened for transfusion in the necessay conditions.
Humans
;
Blood Transfusion
;
Anemia, Hemolytic, Autoimmune/therapy*
;
ABO Blood-Group System
;
Retrospective Studies
;
Antibodies
;
Male
;
Blood Grouping and Crossmatching

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