1.Management of an imported family cluster of dengue fever cases in Shanghai, 2024
Lei SHEN ; Dongsheng REN ; Mingyi CAI ; Zhixiang TENG ; Qi SHEN ; Qingyuan XU ; Xiaofen NI
Shanghai Journal of Preventive Medicine 2026;38(2):170-174
ObjectiveTo investigate and manage an imported dengue fever (DF) outbreak in Shanghai in 2024, to summarize the experience and lessons learned from the on-site management, and to provide a reference basis for future prevention and control of DF. MethodsEpidemiological investigation and case search were carried out for an imported DF outbreak in Shanghai, 2024. Real-time fluorescence polymerase chain reaction (RT-PCR) was used to detect dengue virus nucleic acid in the serum samples from cases. Meanwhile, emergency vector surveillance and mosquito control measures were carried out in the affected areas, and the effectiveness of the management was evaluated. ResultsAccording to the epidemiological investigation, it was confirmed that this epidemic was a family cluster of imported DF, with both cases infected in Thailand and developed symptoms successively after returning to Shanghai. Laboratory testing identified the pathogens as dengue virus serotype-3 (DENV-3). In the core and precautionary area, ultra-low-volume space spraying and residual spraying were combined to kill adult mosquitoes, and at the same time, comprehensive cleaning and elimination of mosquito breeding sites was carried out. After 2 weeks, the Breteau Index (BI) in the core area decreased from 20 to 5, and the mosquito net trap index decreased from 2 mosquitoes (net·hour)-1 to 0.67 mosquitoes (net·hour)-1. Continuous implementation of mosquito control measures kept the BI and net trap index below the safety thresholds [BI<5 and mosquito net trap index <2 mosquitoes (net·hour)-1] both in the core and precautionary area. ConclusionEarly diagnosis and isolation of patients, combined with rapid suppression of the density of vector Aedes mosquitoes, are the key measures to prevent the transmission of imported DF cases.
2.Research on the effectiveness of health information dissemination via the “Shanghai CDC” WeChat public account
Ying GUO ; Xiaoxuan WANG ; Wen XIA ; Xiaoyan HUANG ; Xuanmeng HU ; Qi SHEN ; Chen DONG
Shanghai Journal of Preventive Medicine 2025;37(2):179-183
ObjectiveTo explore the effectiveness of health information dissemination and its influencing factors using the "Shanghai CDC" WeChat public account as a case study, providing references for public health institutions to optimize the use of official new media platforms for effective publicity. MethodsA total of 1 030 headline articles published on the "Shanghai CDC" WeChat public account between 2016 and 2019 were analyzed using content analysis and non-parametric tests to examine the impact of factors such as titles and content categories. ResultsFrom 2016 to 2019, the number of WeChat public account followers increased by 280 000, with the articles accumulating over 8.8 million views. The median (P25, P75) open rate of articles was 5.90% (3.69%, 10.31%), and the median (P25, P75) sharing and forwarding rate was 6.60% (4.25%, 9.17%). Factors such as the use of first- and second-person pronouns, degree adverbs, negative adverbs, explicit viewpoints, and title length all significantly affected the open rate of articles, with OR (95%CI) values of 0.175 (0.041‒0.756), 32.606 (2.350‒452.432), 4.079 (1.093‒15.230), 0.106 (0.028‒0.409), and 1.184 (1.063‒1.319),respectively (all P<0.05). In terms of content, statistical significant differences in dissemination effectiveness were observed across article categories and themes (P<0.05). In terms of article categories, articles related to news hotspots and service information had higher open rates of 9.58% and 14.00%, respectively. These two types of articles also obtained higher sharing and forwarding rates of 7.65% and 9.16%, respectively. In terms of article topics, compared with healthy life and health products, among the top four topics in terms of publication volume, the open rates of articles about infectious diseases and disease-causing biology and immunization programs were higher, accounting for 7.88% and 6.88%, respectively, with no significant difference in sharing and forwarding rates. ConclusionThe "Shanghai CDC" WeChat public account demonstrated good dissemination effectiveness. Enhancing article titles by increasing informational content and degree adverbs (e.g., "highly," "most," and "extremely") and negative adverbs (e.g., "no") can improve dissemination reach. Public health WeChat accounts should incorporate news hotspots or service information in their articles. While maintaining their strengths in disseminating knowledge on infectious diseases and immunization programs, they should also enhance public education in other professional fields within their scope of responsibility to improve the overall dissemination impact of health information.
3.Survey results analysis of death cognition and hospice attitude among healthcare providers in hematology department
Zhimin YAN ; Yanquan LIU ; Minjuan ZENG ; Xiaojun CHEN ; Jiankai ZHANG ; Yue YIN ; Jianzhen SHEN ; Zhanghua QI
Journal of Leukemia & Lymphoma 2025;34(3):159-166
Objective:To investigate the current state of death cognition among healthcare providers in hematology department and their attitudes toward hospice care for patients with hematologic malignancies.Methods:A cross-sectional investigation study was conducted. A total of 198 medical staff in hematology department of 4 teaching hospitals, including the First School of Clinical Medicine of Guangdong Medical University, Fujian Medical University Union Hospital, the Affiliated Hospital of Putian University and the First Affiliated Hospital of Gannan Medical University from March 2024 to June 2024 were selected as the investigation subjects. The general situation and background of medical staff in hematology department were investigated by using the "General Sociological Questionnaire". "Death Attitude Description Scale (Chinese version)" was used to investigate the status of death cognition among medical staff in hematology department. "Frommelt Attitudes Toward Care of the Dying Scale Form B (Chinese version)" was used to investigate the hospice care attitude of medical staff in hematology department. The survey results of doctors and nurses were compared.Results:There were 105 doctors and 93 nurses in hematology department included in this study. A total of 198 qualified "General Sociology Questionnaires" were collected. After excluding 6 unqualified questionnaires, 192 copies of "Death Attitude Description Scale (Chinese version)" and "Frommelt Attitudes Toward Care of the Dying Scale Form B (Chinese version)" were collected. There were statistically significant differences in gender, educational background, political status and experience of taking care of terminally ill patients between doctors and nurses (all P < 0.05). The scores of approaching acceptance, neutral acceptance, death escape, death fear and flight acceptance were (4.35±0.37), (4.03±0.51), (2.98±0.62), (2.54±0.29) and (2.19±0.42) points, respectively in the doctor group; the corresponding scores were (3.12±0.41), (3.89±0.46), (2.66±0.63), (2.81±0.57) and (2.37±0.65) points, respectively in the nurse group, and the differences between the 2 groups were statistically significant (all P < 0.05). The total score of hospice care attitude of doctors in hematology department was (108±15) points, and that of nurses was (116±13) points, and the difference was statistically significant ( t = -3.61, P < 0.001). The hospice care attitude of doctors and nurses towards patients with hematologic malignancies is generally between positive and neutral. The nurse group showed more recognition of the positive role of the patient's family members in the process of hospice care, and the doctor group showed more recognition of the promoting role of medical staff in hospice care. There were statistically significant differences in hospice care attitude scores of medical staff in hematology department to patients with different occupational background, gender, age, place of residence, family discussion about death, whether the only child, whether they had the experience of taking care of terminally ill patients, and whether they suffered from serious illness and religious belief (all P < 0.05). Conclusions:The death cognition of medical staff in hematology department is neutral, and they show a certain sense of hospice care.
4.Cytotoxic effects of the novel photosensitizer PEG-MTPABZ-PyC-mediated photodynamic therapy on gastric cancer cells.
Lingjuan CHEN ; Qi WANG ; Lu WANG ; Yifei SHEN ; Haibin WANG ; Hengxin WANG ; Xuejie SU ; Meixu LEI ; Xianxia CHEN ; Chengjin AI ; Yifan LI ; Yali ZHOU
Journal of Central South University(Medical Sciences) 2025;50(7):1137-1144
OBJECTIVES:
The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells.
METHODS:
Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA).
RESULTS:
PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS.
CONCLUSIONS
The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans
;
Stomach Neoplasms/drug therapy*
;
Photochemotherapy/methods*
;
Photosensitizing Agents/pharmacology*
;
Cell Line, Tumor
;
Polyethylene Glycols/chemistry*
;
Reactive Oxygen Species/metabolism*
;
Mesoporphyrins/pharmacology*
5.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
6.Scientific analysis and usage reassessment of suspected medicinal cinnabar unearthed from Mawangdui Tomb No.3 of the Han Dynasty.
Ning-Ning XU ; Ting-Yan REN ; Ming-Jie LI ; Pan XIAO ; Guo-Hui SHEN ; Ji-Qing BAI ; Qi LIU
China Journal of Chinese Materia Medica 2025;50(11):2915-2923
Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient
;
China
;
Humans
;
Medicine, Chinese Traditional/history*
;
Archaeology
;
Drugs, Chinese Herbal/history*
;
Spectroscopy, Fourier Transform Infrared
;
Spectrum Analysis, Raman
;
Mercury Compounds
7.Effects and mechanisms of total flavones of Abelmoschus manihot combined with empagliflozin in attenuating diabetic tubulopathy through multiple targets based on mitochondrial homeostasis and ZBP1-mediated PANoptosis.
Si-Yu CHA ; Meng WANG ; Yi-Gang WAN ; Si-Ping DING ; Yu WANG ; Shi-Yu SHEN ; Wei WU ; Ying-Lu LIU ; Qi-Jun FANG ; Yue TU ; Hai-Tao TANG
China Journal of Chinese Materia Medica 2025;50(13):3738-3753
This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals
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Rats
;
Mitochondria/metabolism*
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Benzhydryl Compounds/administration & dosage*
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Glucosides/administration & dosage*
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Abelmoschus/chemistry*
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Male
;
Homeostasis/drug effects*
;
Flavones/administration & dosage*
;
Rats, Sprague-Dawley
;
Diabetic Nephropathies/physiopathology*
;
Drugs, Chinese Herbal/administration & dosage*
;
DNA-Binding Proteins/genetics*
;
Humans
;
Apoptosis/drug effects*
8.Preparation of baicalin-berberine complex nanocrystal enteric microspheres and pharmacodynamic evaluation of ulcerative colitis treatment in rats.
Xiao-Chao HUANG ; Yi-Wen HU ; Peng-Yu SHEN ; Rui-Hong JIAN ; Dong-Li QI ; Zhi-Dong LIU ; Jia-Xin PI
China Journal of Chinese Materia Medica 2025;50(15):4263-4274
To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals
;
Colitis, Ulcerative/metabolism*
;
Rats
;
Nanoparticles/chemistry*
;
Microspheres
;
Male
;
Berberine/administration & dosage*
;
Flavonoids/administration & dosage*
;
Rats, Sprague-Dawley
;
Drugs, Chinese Herbal/administration & dosage*
;
Humans
;
Particle Size
;
Tumor Necrosis Factor-alpha/immunology*
;
Drug Liberation
;
Drug Compounding
9.Protective mechanism of Chaihu Shugan San against CORT-induced damage in PC12 cells based on mitochondrial dynamics.
Ling-Yuan ZHANG ; Qi-Qi ZHENG ; Jia-Li SHI ; Pei-Fang WANG ; Jia-Li LU ; Jian-Ying SHEN
China Journal of Chinese Materia Medica 2025;50(16):4546-4554
In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals
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PC12 Cells
;
Rats
;
Mitochondrial Dynamics/drug effects*
;
Mitochondria/metabolism*
;
Corticosterone/adverse effects*
;
Membrane Potential, Mitochondrial/drug effects*
;
Drugs, Chinese Herbal/pharmacology*
;
Protective Agents/pharmacology*
;
Cell Survival/drug effects*
10.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
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Male
;
Infertility, Male/pathology*
;
Acrosome/pathology*
;
Sperm Tail/pathology*
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Pedigree
;
Spermatozoa
;
Adult
;
Loss of Function Mutation
;
Ciliary Motility Disorders/genetics*
;
Spermatogenesis/genetics*
;
Female

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