BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Objective:To explore the differences in clinical efficacy between Co-Cr-Mo guided multidirectional sliding growing rod technology (CMSG) and traditional growing rod in the treatment of neurofibromatosis type 1 dysplastic early-onset scoliosis.Methods:A retrospective analysis was conducted on the data of 20 patients with neurofibromatosis type 1 dysplastic early-onset scoliosis who underwent surgical treatment in the Scoliosis Department of Zhengzhou Orthopaedic Hospital Affiliated to Henan University from January 2010 to July 2022. There were 10 patients in the traditional rod group (treated with traditional growing rod surgery) and 10 patients in the CMSG group (treated with CMSG technology). All patients were ≤10 years old and had a Cobb angle ≥45°. The number of surgeries and the occurrence of complications were recorded. The Cobb angle of the main scoliotic curve, the Cobb angle of kyphosis from T 5 to T 12, and the height from T 1 to S 1 were measured from the imaging data to evaluate the correction of deformity and spinal growth. Results:There were no significant differences in age, gender, follow - up time, preoperative Cobb angle, and preoperative Cobb angle of kyphosis from T 5-T 12 between the CMSG group and the TGR group ( P>0.05). The number of surgeries 1.3±0.67 and the total medical cost 91, 100±34, 700 yuan in the CMSG group were lower than those in the TGR group (5.3±1.77 times and 155, 800±45, 900 yuan], and the differences were statistically significant ( t=6.687, P<0.001; t=3.558, P=0.002). The Cobb angles of the main curve before surgery, after the first surgery, and at the last follow - up in the CMSG group were 69.7°±17.8°, 19.8°±9.7°, and 24.4°±9.0° respectively, while those in the TGR group were 62.0°±11.1°, 32.1°±11.4°, and 33.3°±11.6° respectively. The differences in Cobb angles after the first surgery and at the last follow-up between the two groups were statistically significant ( t=2.633, P=0.017; t=2.313, P=0.033). The Cobb angles of kyphosis from T 5 to T 12 before surgery, after the first surgery, and at the last follow - up in the CMSG group were 40.0°±24.2°, 21.0°±6.0°, and 33.6°±9.3° respectively, while those in the TGR group were 31.3°±14.5°, 26.3°±10.5°, and 32.3°±17.2° respectively. There were no significant differences in the Cobb angles of kyphosis from T 5 to T 12 after the first surgery and at the last follow-up between the two groups ( t=1.383, P=0.184; t=0.243, P=0.811). The heights from T 1 to S 1 before surgery, after the first surgery, and at the last follow-up in the CMSG group were 30.5±3.4 cm, 33.7±3.3 cm, and 37.9±4.8 cm respectively, with an annual increase of 1.18±0.39 cm. The heights from T 1 to S 1 in the TGR group were 29.1±3.0 cm, 31.4±2.9 cm, and 36.3±3.5 cm respectively, with an annual increase of 1.25±0.23 cm. There was no significant difference in the annual growth height of T 1-S 1 between the two groups ( t=1.367, P=0.189). During the follow-up period, 3 patients in the CMSG group had 3 complications: 1 case of coronal plane trunk decompensation, 1 case of rod fracture, and 1 case of distal junctional kyphosis. In the TGR group, 7 patients had 8 complications: 2 cases of wound rupture, 3 cases of screw loosening, 1 case of distal addition phenomenon, 1 case of proximal addition phenomenon, and 1 case of rod fracture. Conclusion:The Co-Cr-Mo guided multidirectional sliding growing rod technique is safe and effective in treating type 1 neurofibromatosis with malnutrition type early-onset scoliosis. It can effectively control the progression of spinal deformities,preserve the growth ability of the spine, and have a low overall incidence of complications.

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P＜0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P＜0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.

OBJECTIVE To retrospectively investigate the incidence of surgical site infection(SSI),distribution and drug resistance of pathogens in 53 hospitals of Suzhou area from 2020 to 2023 so as to provide strategies for pre-vention and control of the hospital-associated infections in Suzhou area.METHODS The data regarding the SSI,distribution and drug resistance of pathogens were statistically analyzed through Suzhou City Regional Hospital In-fection Surveillance Platform.RESULTS The incidence of SSI was 0.24％among the 53 hospitals from 2020 to 2023.Staphylococcus aureus,Enterococcus faecalis,Staphylococcus epidermidis,Enterococcus faecium and Staphylococcus haemolyticus ranked the top 5 species of gram-positive bacteria;Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Enterobacter cloacae and Acinetobacter baumannii ranked the top 5 spe-cies of gram-negative bacteria.There were significant differences in the distributions of S.aureus,K.pneumoniae and A.baumannii in the superficial,deep and organ cavities(P＜0.05).The isolation rate of carbapenem-resistant Acinetobacter baumannii(CRAB)was 69.23％,and the isolation rate of methicillin-resistant Staphylococcus au-reus(MRSA)was 42.14％.The drug resistance rate of the S.aureus strains to oxacillin reached up to 40.24％;the drug resistance rates of the A.baumannii to imipenem and meropenem reached up 63.00％and 65.80％,re-spectively.The drug resistance rates of the K.pneumoniae strains to imipenem and meropenem approximated to 30％,and the drug resistance rate to tigecycline was 19.84％.CONCLUSIONS The total incidence of SSI shows a downward trend in the 53 hospitals of Suzhou area.The S.aureus is the major species of pathogens,and some of the pathogens show high drug resistance rates.

Objective To understand the current status of the job competency of full-time healthcare-associated in-fection(HAI)management professionals in all levels and types of medical institutions across China,and provide in-formation and basis for professional training,competency improvement,and career planning.Methods The strati-fied sampling method was adopted to select HAI management professionals from medical institutions in 31 provin-cial-level administrative regions across the country as the research subjects.The designed content of questionnaire involved four parts,including the surveyed personnel's basic information,daily job competency assessment,satis-faction level towards the job,as well as opinions and suggestions on the management of full-time HAI management professionals.The assessment on daily job competency was divided into 13 dimensions,ranging from very incompe-tent to very competent in 5 levels.The scores of HAI management professionals with different professional back-grounds were compared and analyzed.Results A total of 8 709 valid questionnaires were collected,with 3 475 and 3 697 surveyed personnel from tertiary and secondary medical institutions,respectively,and 1 537 from primary or unclassified medical institutions.The overall average score for the competency assessment of full-time HAI manage-ment professionals was(4.17±0.80)points.The scores of professionals with different professional backgrounds,from high to low,were as follows:nursing([4.12±0.81]points),clinical medicine([4.07±0.86]points),pre-ventive medicine([3.93±0.92]points),laboratory medicine([3.88±0.93]points),pharmacy([3.86±0.94]points),and health management([3.85±0.95]points).For the core competency of HAI management professio-nals,such as monitoring and analyzing HAI cases,identifying and investigating HAI outbreaks,the assessment scores for professionals with medical backgrounds were the highest(both P＜0.05).For the basic work of HAI prevention and control,such as checking and guiding the implementation of rules and regulations,guiding occupa-tional protection,management and communication,and implementing HAI management training,professionals with a nursing background had the highest assessment scores(all P＜0.05).Full-time HAI management professionals were relatively satisfied with their training,while those with a background in preventive medicine had lower satisfac-tion with their training,career development,and job benefits(all P＜0.05).Conclusion There are significant differences in the competency of HAI management professionals with different professional backgrounds.It is nece-ssary to optimize division of labor and leverage the strengths,providing ideas and models for promoting the construction of a specialized and professional HAI management team.