Objective:This study aims to analyze the characteristics and current status of gene therapy drug policy documents and to provide recommendations for optimizing China's gene therapy drug policy system.Methods:A three-dimensional analytical framework of"policy instruments-interactive subjects-policy phases"was constructed using content analysis and word frequency analysis.This framework was applied to the relevant policy documents issued from March 2009 to March 2024,enabling multidimensional classification and cross-comparison.Results:Among the 37 national-level policy documents included,246 text items were identified under the dimension of policy instruments,with supply-based instruments(45.9%)and environmental instruments(41.5%)being more prevalent,while demand-based instruments(12.6%)were less represented.The distribution of policy instruments was skewed,and internal structural differences were observed.In the dimension of interactive subjects,195 text items were identified,with drug manufacturing and R&D enterprises(36.9%),drug regulatory and accreditation agencies(22.1%),patients and subjects(19.0%),medical institutions and healthcare professionals(11.8%),and other government departments(10.2%)playing uneven roles.In the dimension of policy phases,the policies were categorized into three stages:drug R&D,production,and usage,with some policies covering multiple phases.Conclusions and suggestions:The study suggests combining and optimizing policy instruments for balanced application,strengthening demand-oriented policies,considering the needs of different interacting entities to formulate comprehensive policies,promoting cross-subject collaboration for win-win outcomes,and enhancing phase-linkage efficiency to build a comprehensive chain ecosystem for gene therapy drug development.

Objective:To explore and stimulate the pathway mechanism for doctors from core hospitals,which are the high-quality medical resources in loose medical alliances,to sink to the grassroots level on their own initiative and continue to participate in the co-operation,so as to provide useful references for improving the effectiveness of cooperation within medical alliances.Methods:The fuzzy set Qualitative Comparative Analysis(fsQCA)method was used to investigate 205 doctors in the core hospitals of a loose medical alliance in District X of City B.This investigation was grounded in relationship commitment theory,motivation theory,social exchange theory,and cooperation reinforcement theory.Results:The level of relationship commitment of doctors in the core hospitals to proactively participate in cooperation was influenced by multiple factors,including doctors'perception of job significance,opportunity cost perception,organizational support,and teamwork experience.This resulted in the formation of three concurrent driving mechanism pathways:merger-driven effect,experience-enhancing effect,and altruistic trigger effect.Among these factors,the perception of work significance was a necessary condition,and cooperative experience played an important role in doctors'continuous participation.Conclusion:The level of relational commitment of doctors to participate in cooperative efforts is driven by a combination of various factors,with different incentive mechanisms exhibiting heterogeneity within loose medical alliances.Designing appropriate incentive and support strategies tailored to specific contexts can effectively drive the proactive downward flow of high-quality medical resources from core hospitals within loose medical alliances.

Blakeslea trispora CarRA has both lycopene cyclase and phytoene synthase activity. In order to analyze the double functional activity of CarRA proteins and to detect the active sites of lycopene cyclase, we constructed two detection systems in Escherichia coli by color complementary. Through PCR-driven overlap extension we got carRA gene cDNA, then constructed prokaryotes expression vector pET28a-carRA. pET28a-carRA with plasmid pAC-LYC carrying crtl/crtB/crtE gene clusters were co-transformed to BL21(DE3) to validate lycopene cyclase activity. We constructed the plasmid pAC-LYC delta (crtB) carrying crtl/crtE gene clusters, then co-transtormed them with pET28a-carRA to BL21(DE3) to validate phytoene synthase activity. Based on color complementary, and HPLC analysis of metabolites, we confirmed that the CarRA protein activity detection system was reliable. Our study provides a screening model for specific mutation of lycopene cyclase without affecting phytoene synthase activity.
Alkyl and Aryl Transferases ; genetics ; metabolism ; Carotenoids ; biosynthesis ; Cloning, Molecular ; DNA, Complementary ; genetics ; Escherichia coli ; genetics ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Genetic Vectors ; genetics ; Geranylgeranyl-Diphosphate Geranylgeranyltransferase ; Intramolecular Lyases ; genetics ; metabolism ; Mucorales ; enzymology ; genetics ; Mutation ; Polymerase Chain Reaction

OBJECTIVETo investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.

METHODSA total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.

RESULTSThe exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.

CONCLUSIONTDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

Case-Control Studies ; Erythrocyte Count ; Forced Expiratory Volume ; Humans ; Inflammation ; physiopathology ; L-Lactate Dehydrogenase ; blood ; metabolism ; Leukocyte Count ; Lung ; physiopathology ; Occupational Exposure ; adverse effects ; Pulmonary Ventilation ; Succinate Dehydrogenase ; blood ; metabolism ; Superoxide Dismutase ; metabolism ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity

Curcumae Rhizoma is a Chinese medicinal herb that is contraindicated during pregnancy. Cold-congelation and blood-stasis are corresponding syndromes to Curcumae Rhizoma. Whether syndrome-based treatment is associated with developmental neurotoxicity of Curcumae Rhizoma remains to be unclear. To verify the theory of traditional Chinese medicine of "syndrome-based treatment during pregnancy", the present study induced the mice blood stasis model by immersing mice in ice water. Pregnant C57 BL/6 wild type(WT) mice and pregnant Nrf2 knock out(KO) mice were randomly divided into control groups and Rhizoma Curcumae exposure groups. The mice were exposed to Rhizoma Curcumae during day 5 to day 18 after pregnancy. The neurodevelopment was examined to evaluate the differences of developmental neurotoxicity between normal and blood-stasis pregnant mice exposed to Rhizoma Curcumae. caspase-3 and caspase-9 activity in brain of the offspring were measured by colorimetric assays. Bcl-2 mRNA and protein expression in brain of the offspring were examined by Real-time RT-PCR and Western blot, respectively. According to the findings, C57 BL/6 mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) had a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring, compared with the normal control group, but with no significant change in those of blood-stasis pregnant mice offspring. However, mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) showed no change in Bcl-2 gene expression and p38 MAPK phosphorylation in brain of the offspring. Nrf2 gene knockout using CRISPR/Cas9 resulted in a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring. In conclusion, developmental neurotoxicity of the blood-stasis pregnant mice exposed to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Nrf2 activation involved in the phenomenon of Rhizoma Curcumae of "syndrome-based treatment during pregnancy", but the upstream signal pathway mechanism value shall be further investigated.
Animals ; Apoptosis ; Brain ; drug effects ; Caspases ; genetics ; Curcuma ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Maternal Exposure ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-E2-Related Factor 2 ; genetics ; Pregnancy ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Random Allocation ; Rhizome ; chemistry ; Signal Transduction

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective To investigate the effects of chronic exposure to monochloroacetic acid on the lung function and whole blood counts in occupational exposed workers,and provide new markers for occupational health surveillance.Methods We conducted a cross-sectional molecular epidemiology study of 121 workers who were occupationally exposed to monochloroacetic acid and 69 unexposed workers frequencymatched by age and smoking status from the same geographic region.The lung function was measured by portable lung function instrument,and the lymphocyte subsets were measured by flow eytometry.Linear regression was used to test for differences in the levels of each marker between exposed and control workers.Results FEV1.0/FVC was significantly decreased in both male and female workers exposed to monochloroacetic acid compared to unexposed workers (P＜0.01) after adjusting for potential confounders,which were highly consisteut when stratified by smoking status.Among male workers,monochloroacetic acid exposure was associated with significant decrease in the levels of CD8+ T cells (P＜0.05) and monocytes (P＜0.05),and these statistically significant differences were observed between exposure and control workers only among smokers,not among non-smokers.However,there were no significant differences in the levels of whule blood cells and lymphocyte subsets between two groups anong female workers.Conclusion The chronic monochloroacetic acid exposure was associated with pulmonary dysfunction and immunosuppression,which mainly occurred among nale workers and smokers.

Objective To investigate the effects of chronic exposure to monochloroacetic acid on the lung function and whole blood counts in occupational exposed workers,and provide new markers for occupational health surveillance.Methods We conducted a cross-sectional molecular epidemiology study of 121 workers who were occupationally exposed to monochloroacetic acid and 69 unexposed workers frequencymatched by age and smoking status from the same geographic region.The lung function was measured by portable lung function instrument,and the lymphocyte subsets were measured by flow eytometry.Linear regression was used to test for differences in the levels of each marker between exposed and control workers.Results FEV1.0/FVC was significantly decreased in both male and female workers exposed to monochloroacetic acid compared to unexposed workers (P＜0.01) after adjusting for potential confounders,which were highly consisteut when stratified by smoking status.Among male workers,monochloroacetic acid exposure was associated with significant decrease in the levels of CD8+ T cells (P＜0.05) and monocytes (P＜0.05),and these statistically significant differences were observed between exposure and control workers only among smokers,not among non-smokers.However,there were no significant differences in the levels of whule blood cells and lymphocyte subsets between two groups anong female workers.Conclusion The chronic monochloroacetic acid exposure was associated with pulmonary dysfunction and immunosuppression,which mainly occurred among nale workers and smokers.