1.Current situation, challenges, and countermeasures on the construction of scientific and technological ethical governance capacity of innovation entities
Ting XIA ; Liqi WANG ; Haitao GE
Chinese Medical Ethics 2026;39(1):36-43
Innovation entities bear primary responsibility for the management of scientific and technological ethics. Understanding the current construction status of the scientific and technological ethical governance capacity among Chinese innovation entities is conducive to grasping effectiveness and shortcomings of scientific and technological ethical governance of innovation entities, providing a scientific basis and practical guidance for innovation entities to fulfill their primary responsibilities better. Based on a questionnaire survey targeting 313 innovation entities, this paper investigated and analyzed the current status and existing challenges of scientific and technological ethical governance capacity among Chinese innovation entities from five aspects. It was found that China has made certain achievements in scientific and technological ethical governance, yet there were still issues such as incomplete construction of regulatory systems, low efficiency of ethical review, unestablished regular education and training systems, and imperfect dynamic monitoring systems for ethical risks. Among these issues, the scientific and technological ethical governance capacity of enterprises was identified as requiring urgent improvement. Additionally, strengthening multi-stakeholder collaboration remained a key challenge in building a collaborative and co-governance system for scientific and technological ethics. Based on these issues identified in the survey, countermeasures and suggestions were proposed from five perspectives, that is, enhancing the capacity in institutional construction, ethical review, value transmission, risk early warning, and collaborative governance of innovation entities on scientific and technological ethical governance. The aim was to provide references for accelerating the construction of the scientific and technological ethical governance system and improving the scientific and technological ethical governance capacity of innovation entities.
2.Seasonal variation of adult mosquitoes in Yantai, Shandong Province, China: a study based on the circular distribution method
Chun-hui LI ; Cheng-juan LIU ; Ting WANG ; Xiao-ge ZHOU ; Pei-Jun GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):108-113
Objective This study aimed to investigate the seasonal variation of mosquitoes in Yantai, Shandong Province, and provide a scientific basis for mosquito and mosquito-borne disease control. Methods From March to November for each of the years between 2020 and 2023, adult mosquitoes were collected from different habitats, including parks, hospitals, urban residential areas, rural households and livestock sheds, in 13 counties of Yantai City using a mosquito trap lamp method, among which, female mosquitoes were separated and identified, and the numbers were counted. We used the circular distribution method to analyze the temporal distribution characteristics of mosquito density. Results The γ values obtained for mosquitoes in Yantai from 2020 to 2023, the distribution of mosquitoes in different habitats, and dominant mosquito species in different months showed strong seasonality, with values ranging from 0.7461 to 0.8531(P < 0.05). The peak period of seasonal variation in mosquitoes occurred from June 28thto September 13th, with August 5thbeing identified as the peak day. The peak periods of seasonal variation in mosquitoes in residential areas, parks, hospitals, peasant households, and animals sheds were observed from June 24thto September 14th, June 25thto September 10th, June 22ndto September 12th, July 1stto September 9th, and July 2ndto September 17th, respectively, with corresponding peak days on August 4th,3rd, 2nd, 5th, and 9th, respectively. The peak periods of Culex pipiens pallens, Aedes albopictus, and Anopheles sinensis were from June 26thto September 11th, June 28thto September 17th, and July 12thto September 17th, respectively, with corresponding peak days on August 3rd,7th, and 14th, respectively. Conclusions Our findings in this study revealed that the peak of mosquito activity in Yantai was concentrated in early August, with a peak period extending from June 28thto September 13th, and there were differences between different habitats(with peak periods for rural households and livestock sheds occurring later than those in residential areas, parks, and hospitals). Moreover, with respect to the mosquito species, populations of Cx. pipiens pallens and Ae. albopictus peaked earlier than those of An. sinensis. Based on these findings, we recommend that city-wide mosquito control work should commence in late June, and include appropriate early prevention and control measures for key habitats, such as livestock sheds, and dominant mosquito species, such as Cx. pipiens pallens, to minimize the density of mosquito vectors and the risk of disease transmission.
3.Effect of electroacupuncture on intestinal function after gastric cancer surgery.
Junjie GUAN ; Miaomiao GE ; Yuling CAI ; Ting WANG ; Zhiwei JIANG ; Jianhua SUN ; Gang WANG
Chinese Acupuncture & Moxibustion 2025;45(6):751-756
OBJECTIVE:
To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery.
METHODS:
Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups.
RESULTS:
The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05).
CONCLUSION
Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult
;
Aged
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Female
;
Humans
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Male
;
Middle Aged
;
Acupuncture Points
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C-Reactive Protein/metabolism*
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Electroacupuncture
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Gastrectomy
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Interleukin-10
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Interleukin-6
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Intestines/physiopathology*
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Stomach Neoplasms/therapy*
4.Regulation of apoptosis and autophagy in hepatoblastoma cells by Ganoderma lucidum polysaccharides through Akt/mTOR pathway.
Yang GE ; Hang GAO ; Yun-Peng QIN ; Rui SHEN ; Hua-Zhang WU ; Ting YE ; Hang SONG
China Journal of Chinese Materia Medica 2025;50(9):2432-2441
This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals
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Humans
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Autophagy/drug effects*
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Reishi/chemistry*
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Mice
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Apoptosis/drug effects*
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TOR Serine-Threonine Kinases/genetics*
;
Proto-Oncogene Proteins c-akt/genetics*
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Liver Neoplasms/genetics*
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Hepatoblastoma/genetics*
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Polysaccharides/pharmacology*
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Cell Line, Tumor
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Signal Transduction/drug effects*
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Male
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Cell Proliferation/drug effects*
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Hep G2 Cells
5.Identification and expression analysis of seed dehydration tolerance and PLD gene family in Panax medicinal plants.
Chao-Lin LI ; Min HUANG ; Na GE ; Qing-Yan WANG ; Jin-Shan JIA ; Ting LUO ; Jin-Yan ZHANG ; Ping ZHOU ; Jun-Wen CHEN
China Journal of Chinese Materia Medica 2025;50(12):3307-3321
Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism*
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Panax/physiology*
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Plant Proteins/metabolism*
;
Gene Expression Regulation, Plant
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Phospholipase D/metabolism*
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Plants, Medicinal/enzymology*
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Germination
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Multigene Family
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Water/metabolism*
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Dehydration
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Phylogeny
6.Development and Initial Validation of the Multi-Dimensional Attention Rating Scale in Highly Educated Adults.
Xin-Yang ZHANG ; Karen SPRUYT ; Jia-Yue SI ; Lin-Lin ZHANG ; Ting-Ting WU ; Yan-Nan LIU ; Di-Ga GAN ; Yu-Xin HU ; Si-Yu LIU ; Teng GAO ; Yi ZHONG ; Yao GE ; Zhe LI ; Zi-Yan LIN ; Yan-Ping BAO ; Xue-Qin WANG ; Yu-Feng WANG ; Lin LU
Chinese Medical Sciences Journal 2025;40(2):100-110
OBJECTIVES:
To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels.
METHODS:
The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT).
RESULTS:
The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049).
CONCLUSIONS
The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans
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Adult
;
Male
;
Attention/physiology*
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Female
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Middle Aged
;
Reproducibility of Results
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Young Adult
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Psychometrics
7.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
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Drug Monitoring/methods*
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Humans
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Organ Transplantation
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Immunosuppressive Agents/administration & dosage*
;
Delphi Technique
8.Analysis of common non-bacterial pathogens in hospitalized children with acute respiratory infections: a multicenter study in four regions of Fujian Province in 2023
Lin CAI ; Xiaoman GAO ; Fucun ZHU ; Xiuhua LIU ; Wenlong ZHOU ; Shaohua GE ; Lijuan ZHUANG ; Guanglin ZHANG ; Xiaoping LAI ; Ting LIU
Chinese Journal of Preventive Medicine 2025;59(10):1665-1675
Objective:To analyze the distribution and epidemiological characteristics of common non-bacterial pathogens in hospitalized children with acute respiratory tract infections(ARTI)from a multi-center study covering 4 regions in Fujian Province in 2023.Methods:A retrospective cohort study was conducted using medical record analysis.A total of 22 769 hospitalized children with ARTI were enrolled from January to December 2023 across seven regional pediatric medical centers in Fujian Province (covering four major geographical divisions of Fuzhou, Nanping, Sanming and Longyan; all selected hospitals were regional children′s medical centers).Using single-tube multiplex PCR with fragment analysis on a Sanger sequencing platform, the nucleic acids of 11 common non-bacterial respiratory pathogens were tested in nasopharyngeal swabs collected from 22 769 children. These pathogens included influenza A virus(FluA), influenza B virus(FluB), parainfluenza virus(PIV), respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus(HMPV), Mycoplasma pneumoniae(MP), and Chlamydia (Ch). Count data were described as [ n(%)], and the chi-square test/Fisher′s exact test was used to compare the differences in rates between groups. Epidemiological features, including positive detection rates, pathogen profiles, and correlations with region, sex, age and month, were analyzed. Results:Among 22 769 children with ARTI, pathogens were detected in 16 213 cases (71.21%), including 13 340 single infections (58.59%).The detection rates of single pathogens in descending order were human rhinovirus (HRV, 12.95%), Mycoplasma pneumoniae(MP, 12.27%), respiratory syncytial virus(RSV, 11.12%), influenza A virus (Flu-A, 7.98%), parainfluenza virus(PIV, 4.66%), human metapneumovirus(HMPV, 4.60%), adenovirus(ADV, 2.70%), human bocavirus(HBoV, 0.84%), human coronavirus(HCoV, 0.82%), influenza B virus(Flu-B, 0.47%) and Chlamydia(Ch, 0.18%).Mixed infections occurred in 2 873 cases(12.62%), primarily dual infections(2 679 cases).Regional analysis revealed significant disparities:Luoyuan County Hospital (Fuzhou) exhibited the highest total detection rate(86.59%, 1 414/1 633)and mixed infection rate(23.27%, 380/1 633)(both P<0.001), with notably elevated MP (26.39%, 431/1 633);Jian′ou City Hospital(Nanping) ranked second for Flu-A(14.21%, 409/2 879), RSV(13.20%, 380/2 879) and mixed infections(17.12%, 493/2 879);Lianjiang County Hospital(Fuzhou) showed distinct prevalence of Flu-A(10.68%, 130/1 217), PIV(6.00%, 73/1 217), and HBoV(1.73%, 21/1 217); Yong′an City Hospital (Sanming) reported high MP (26.07%, 238/913) and RSV(12.38%, 113/913);Shaowu City Hospital(Nanping) was dominated by MP (18.60%, 407/2 188) and HRV(13.39%, 293/2 188); Tingzhou Hospital(Longyan) had the highest HRV (17.88%, 407/2 276) and Flu-B (0.75%, 17/2 276); and Fuzhou Children′s Hospital showed elevated ADV(3.38%, 394/11 663) and HCoV(1.08%, 126/11 663). Except for Flu-B(0.47%, 108/22 769; P=0.054) and Ch(0.18%, 40/22769; P=0.900), all pathogens and mixed infections exhibited significant regional variations ( P<0.05).Gender analysis indicated higher detection rates of HRV, RSV, Flu-A, ADV, PIV, HBoV and mixed infections in males, while MP, HMPV, Flu-B, HCoV, and Ch were more prevalent in females, with statistically significant differences for HRV and MP (both P<0.001). Age stratification showed the highest overall detection rate in the 3-<6 years group (75.48%; P<0.001): RSV and Ch peaked in infants (<1 year), HRV, PIV, ADV and HBoV in toddlers (1-<3 years), HMPV, HCoV, and mixed infections in preschool children (3-<6 years), and MP, Flu-A and Flu-B in older children (6-<18 years).Analyzing the prevalent months, the monthly prevalence trends of pathogens in various regions are similar.Seasonal trends demonstrated year-round HRV activity (peaking in spring/autumn), MP prevalence in autumn/winter, RSV surges in spring-summer (April-June) and late summer-autumn (August-October), and Flu-A predominanced in winter-spring. Conclusion:Multiplex PCR with fragment analysis demonstrated high diagnostic efficacy. The top 4 non-bacterial pathogens in Fujian Province′s ARTI-hospitalized children in 2023 were HRV, MP, RSV and Flu-A. Pathogen distribution exhibited significant regional, age and seasonal variations, emphasizing the need for targeted prevention strategies.
9.The crucial function of IDO1 in pulmonary fibrosis: From the perspective of mitochondrial fusion in lung fibroblasts and targeted molecular inhibition.
Lei WANG ; Shanchun GE ; Ye ZHANG ; Deqin FENG ; Ting ZHU ; Louqian ZHANG ; Chaofeng ZHANG
Acta Pharmaceutica Sinica B 2025;15(6):3125-3148
The pathogenesis of pulmonary fibrosis (PF) is complex. It is characterized by myofibroblast hyperplasia and deposition of collagen protein. Indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in lung fibroblasts and epithelial cells, but its functions in lung homeostasis and diseases remain elusive. Here, we characterize the critical role of IDO1 in PF patients and bleomycin (BLM)-induced PF mouse models. We find that IDO1 is significantly upregulated in the fibrotic lungs of patients and mice, showing a positive correlation with genes characteristic of fibrosis. Functionally, IDO1 knockout inhibits lung fibroblast proliferation, differentiation, mitochondrial biogenesis, and mitochondrial oxidative phosphorylation. Conversely, IDO1 overexpression and accumulation of kynurenine (Kyn) exacerbate progressive lung fibrosis. Mechanistically, IDO1-deletion activated profound mitochondrial fusion-enhanced potentially the capacity for fatty acid oxidation, along with activation of de novo glycolytic serine/glycine synthesis pathways and mitochondrial one-carbon metabolism. Wedelolactone (WEL), a small molecule IKK inhibitor, is found to strongly bind to IDO1 and effectively protect mice from PF in an IDO1-dependent manner. Collectively, this study characterizes a promotor role for IDO1 in PF and suggests a potential avenue of targeting IDO1 to treat lung diseases.
10.Discovery of Yersinia LcrV as a novel biased agonist of formyl peptide receptor 1 to bi-directionally modulate intracellular kinases in triple-negative breast cancer.
Yunjun GE ; Huiwen GUAN ; Ting LI ; Jie WANG ; Liang YING ; Shuhui GUO ; Jinjian LU ; Richard D YE ; Guosheng WU
Acta Pharmaceutica Sinica B 2025;15(7):3646-3662
G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.


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