1.Immunodynamic changes in a mouse model of malignant pleural effusion
Xiao-Lei WEI ; Xu GUO ; Chuang-Xin ZHANG ; Qi WANG ; Xiao-Fan LIU ; Ming-Ming SHAO ; Huan-Zhong SHI ; Kan ZHAI
Laboratory Animal Research 2026;42(1):59-67
Background:
Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression.
Results:
The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity.
Conclusions
Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.
2.Structure of myelin in the central nervous system and another possible driving force for its formation-myelin compaction.
Qi SHAO ; Simin CHEN ; Tian XU ; Yuyu SHI ; Zijin SUN ; Qingguo WANG ; Xueqian WANG ; Fafeng CHENG
Journal of Zhejiang University. Science. B 2025;26(4):303-316
Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism*
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Humans
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Central Nervous System/metabolism*
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Animals
3.Structural equation analysis and modeling of upper limb WMSDs and their adverse ergonomic factors
Siwu ZHONG ; Ning JIA ; Xin SUN ; Meibian ZHANG ; Qing XU ; Huadong ZHANG ; Ruijie LING ; Yimin LIU ; Gang LI ; Yan YIN ; Hua SHAO ; Jue LI ; Hengdong ZHANG ; Bing QIU ; Dayu WANG ; Qiang ZENG ; Rugang WANG ; Yan YE ; Bin XIAO ; Hua ZOU ; Jianchao CHEN ; Dongxia LI ; Yongquan LIU ; Qinghua SHI ; Jixiang LIU ; Enfei JIANG ; Jun QI ; Liangying MEI ; Xianfeng ZHAO ; Mimi YANG ; Xinwei GUO ; Zhi WANG ; Zhongxu WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(4):254-263
Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.
4.Structural equation analysis and modeling of upper limb WMSDs and their adverse ergonomic factors
Siwu ZHONG ; Ning JIA ; Xin SUN ; Meibian ZHANG ; Qing XU ; Huadong ZHANG ; Ruijie LING ; Yimin LIU ; Gang LI ; Yan YIN ; Hua SHAO ; Jue LI ; Hengdong ZHANG ; Bing QIU ; Dayu WANG ; Qiang ZENG ; Rugang WANG ; Yan YE ; Bin XIAO ; Hua ZOU ; Jianchao CHEN ; Dongxia LI ; Yongquan LIU ; Qinghua SHI ; Jixiang LIU ; Enfei JIANG ; Jun QI ; Liangying MEI ; Xianfeng ZHAO ; Mimi YANG ; Xinwei GUO ; Zhi WANG ; Zhongxu WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(4):254-263
Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.
5.Oxidative damage and epithelial barrier disruption of lung tissue mediated by PM2.5 at different doses
Yuyu SHI ; Qi SHAO ; Xueqian WANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(12):1565-1571
Objective To investigate the dose-dependence of inflammation,oxidative stress and epithelial barrier disruption in C57BL/6 mice using different concentrations of PM2.5.Methods A total of 36 male C57BL/6 mice were randomly divided into control group,PM2.5 5.0 group,PM2.5 7.5 group and PM2.5 10.0 group.The trachea of the control group was instilled with normal saline,and the animals were sacrificed after the last poisoning.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue.The ELISA kit was used to detect the levels of IL-4,IL-1β and TNF-α inflammatory cytokines in the serum of four groups of mice.Biochemical kits and ELISA kits were used to detect the levels of oxidative stress nitrogen monoxide(NO),malondialdehyde(MDA)and superoxide dismutase(SOD)in four groups of mice.Deoxyribonucleotide terminal transferase-mediated nick end labeling was used by TUNEL staining to observe the level of apoptosis of epithelial cells.Immunohistochemistry was used to detect the expression of epithelial barrier tight junction proteins.Results Acute exposure to PM2.5 led to widening of alveolar septum and exudation of inflammatory cells,increased serum levels of inflammatory cytokines IL-4,IL-1 β and TNF-α and NO and MDA in lung tissue,and decreased SOD(P<0.01 or P<0.05).increased apoptosis of epithelial cells;The expression of epithelial barrier tight junction protein was dose-dependent(P<0.01 or P<0.05).Conclusions Acute exposure to PM2.5 particulate matter can lead to acute lung injury in mice by promoting the release of inflammation in lung tissue and inducing oxidative and antioxidant imbalance.In addition,PM2.5 exposure led to epithelial cell apoptosis,especially at a modeled dose of 10 mg/kg,which disrupted the tight junctions of the epithelial barrier and further exacerbated lung injury in mice.
6.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.
8.Construction and validation of a risk prediction model for sarcopenia in colorectal cancer patients
Xue-Jing ZHANG ; Qi-Hong GU ; Meng-Yao CHENG ; Yan SHAO ; Shi-Yu LIU ; Jian YANG ; Li-Li TONG
Parenteral & Enteral Nutrition 2024;31(6):346-352
Objective:To investigate the incidence of sarcopenia in postoperative colorectal cancer patients and its influencing factors,to construct a prediction model for sarcopenia and to complete the validation.Methods:A total of 450 colorectal cancer patients admitted between January 2022 and December 2023 were prospectively enrolled in this study.The incidence and influencing factors of sarcopenia were analyzed statistically.A risk prediction model for sarcopenia was constructed using logistic regression,displayed and validated with a nomogram.Results:In this study,a total of 315 colorectal cancer patients were included in the modeling group,ranging in age from 37 to 89 years old,with an average age of(67.09±9.06)years old.Among these,144 were females(45.71%)and 171 were males(54.29%).Sarcopenia was present in 72 patients(22.86%).Univariate analysis identified tumor stage,smoking history,drinking history,combined diabetes,nutritional status and physical exercise as independent risk factors for sarcopenia in colorectal cancer patients(P<0.05).Logistic regression analysis confirmed that Tumor stage,smoking history,drinking history and diabetes mellitus were risk factors for sarcopenia in colorectal cancer patients(P<0.05),while nutritional status and physical exercise were protective factors for sarcopenia in colorectal cancer patients(P<0.05).In the verification group,the area under the curve(AUC)was 0.880(95%CI:0.823,0.933),Yoden index was 0.613,and sensitivity and specificity were 87.4%and 73.9%,respectively.Hosmer-Lemeshow goodness of fit test indicated χ2=4.664,P=0.795.Conclusion:This study established a risk prediction model for sarcopenia in colorectal cancer patients.Tumor stage,smoking history,drinking history,diabetes mellitus,nutritional status and physical exercise were influencing factors for sarcopenia in colorectal cancer patients.The predictive model can assist clinical nurses in identifying high-risk patients and implementing timely interventions.
9.Study on the epidemiological characteristics of work-related musculoskeletal disorders among 29 industries or occupational groups in China
Ning JIA ; Meibian ZHANG ; Qing XU ; Huadong ZHANG ; Ruijie LING ; Yimin LIU ; Zhi WANG ; Gang LI ; Yan YIN ; Hua SHAO ; Jue LI ; Hengdong ZHANG ; Bing QIU ; Dayu WANG ; Qiang ZENG ; Rugang WANG ; Yan YE ; Bin XIAO ; Hua ZOU ; Jianchao CHEN ; Dongxia LI ; Yongquan LIU ; Qinghua SHI ; Jixiang LIU ; Enfei JIANG ; Jun QI ; Liangying MEI ; Xianfeng ZHAO ; Mimi YANG ; Xinwei GUO ; Xin SUN ; Zhongxu WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(12):884-895
Objective:To analyze the distribution characteristics of work-related musculoskeletal disorders (WMSDs) among the occupational population in China's key industries during the period from 2018 to 2023, and to provide data support for the formulation of targeted prevention strategies.Methods:Between January 1, 2018, and December 31, 2023, a cross-sectional epidemiological survey and a retrospective investigation were conducted in seven geographical regions of North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China, using a combination of epidemiological cross-sectional and retrospective surveys. The industries were stratified according to the degree of closeness to WMSDs, the size of the occupational population, and the importance of the national economy, and then cluster sampling was conducted according to the size of the enterprises (large, medium, and small) within each stratum. Representative enterprises were selected, and workers who had been employed for more than one year and met the inclusion criteria were selected as the study subjects. The survey subjects completed the Chinese version of the Musculoskeletal Disorders Survey Questionnaire online by scanning a QR code. A total of 88, 609 valid questionnaires were collected. Continuous data were described by means and standard deviations, and the standardized incidence rates of WMSDs were evaluated using chi-square tests to compare the standardized incidence rates of different body parts.Results:The standardized prevalence rate of WMSDs among the frontline working population in China was 36.7%, with the top three being the neck (21.37%), shoulders (18.23%), and lower back (14.92%). There was a statistically significant difference in the standardized prevalence rate of WMSDs between different body parts (χ 2=47577.82, P<0.05). The lowest standardized prevalence rate of WMSDs was found in the southeast coastal region of China (32.54%), while the highest was in the northwest (49.70%) and northeast regions (46.16%). The standardized prevalence rate of WMSDs decreased from 42.88% in 2018 to 29.94% in 2023. The micro-enterprise observation group had a higher concentration of WMSDs in the neck (20.66%), lower back (17.95%), and shoulders (17.79%), while the large enterprise observation group had a higher concentration in the neck (20.54%), shoulders (17.52%), and lower back (14.65%). Among the industries surveyed, the highest standardized prevalence rate of WMSDs was found in the healthcare industry (53.18%), followed by the toy manufacturing industry (50.54%), the automotive manufacturing industry (43.39%), general aviation services (42.71%), and the ship and related equipment manufacturing industry (40.56%). The standardized prevalence rate of WMSDs among women was significantly higher than that of men ( OR value=1.44, P<0.05). In addition, the standardized prevalence rate of WMSDs with multiple affected body parts (four or more body parts affected simultaneously) was higher, and the risk of WMSDs increased with subjective fatigue, showing a significant "S-shaped" trend (the OR value was 2.19, 3.16, 4.71, 5.49, and 3.97 when the RPE was 13, 15, 17, 19, and 20, respectively. χ 2trend=17.23, P<0.001) . Conclusion:The distribution characteristics of WMSDs in key industries in China show obvious differences in different parts, regions, time, enterprise scale, industry and population attributes. Agriculture, pharmaceutical manufacturing, packaging and decoration and other printing industries have a high proportion of WMSDs in multiple parts at the same time and in a single site. It is necessary to study and implement precise preventive measures according to specific regions, industries and enterprise scales, as well as the characteristics of multi-site WMSDs, so as to effectively protect the health and well-being of the working population.
10.Study on the relationship between occupational exposure characteristics and musculoskeletal disorders in 29 industries or workforce groups in China
Ning JIA ; Meibian ZHANG ; Qing XU ; Huadong ZHANG ; Ruijie LING ; Yimin LIU ; Zhi WANG ; Gang LI ; Yan YIN ; Hua SHAO ; Jue LI ; Hengdong ZHANG ; Bing QIU ; Dayu WANG ; Qiang ZENG ; Rugang WANG ; Yan YE ; Bin XIAO ; Hua ZOU ; Jianchao CHEN ; Dongxia LI ; Yongquan LIU ; Qinghua SHI ; Jixiang LIU ; Enfei JIANG ; Jun QI ; Liangying MEI ; Xianfng ZHAO ; Mimi YANG ; Xinwei GUO ; Xin SUN ; Zhongxu WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(12):896-910
Objective:To explore the occupational contact characteristics of work-related musculoskeletal disorders (WMSDs) among key occupational groups in China, assess the impact of occupational factors on the occurrence of WMSDs, and propose corresponding preventive strategies.Methods:Between January 1, 2018, and December 31, 2023, a cross-sectional epidemiological survey method was employed to retrospectively investigate the occurrence of WMSDs and related occupational factors. Valid questionnaire data from 88609 on-the-job workers in 441 enterprises across 29 industries or job types in seven regions of China were collected, and the relationship between WMSDs and various occupational factors was discussed using multifactorial logistic regression analysis. Odds ratios ( OR) and their 95% confidence intervals ( CI) were calculated to assess the impact of different factors on the risk of WMSDs occurrence, with all statistical tests performed as two-tailed tests, using P<0.05 as the criterion for statistical significance. Results:Among the surveyed subjects, 59989 were male, accounting for 67.7% (59989/88609) ; 28620 women, accounting for 32.3% (28620/88609). The standardized incidence rate of work related musculoskeletal disorders (WMSDs) in 9 parts of the body was statistically significant ( P<0.05) among different working age groups without considering specific parts. The average length of service for onset of WMSDs (regardless of location) is (4.52±2.67) years, and there is a statistically significant difference in the length of service for onset of WMSDs in different locations ( P<0.05). As the frequency of heavy object handling increases, the standardization rate and OR value of WMSDs in various parts show a significant increase trend. The incidence of WMSDs is significantly correlated with maintaining poor work posture for a long time, frequent repetitive operations, and heavy object handling ( OR=1.52, 1.45, 1.63, P<0.01) . Conclusion:This study reveals that the risk of WMSDs in China's occupational population shows a non-linear change with increasing length of service, especially with a significant increase in 10 to 25 years of service. Poor work posture, frequent repetitive operations, and heavy object handling are significantly correlated with WMSDs, providing a scientific basis for developing more accurate and effective prevention strategies for WMSDs.

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