Objective To establish a transgenic mouse model of facioscapulohumeral muscular dystrophy(FSHD)using tamoxifen induction and Myf6-CreERT2 and FLExDUX4 mice.Methods Dual transgenic(M6D4/+)mice were generated by crossbreeding Myf6-CreERT2 hemizygous and FLExDUX4 hemizygous mice.Full-length DUX4(DUX4-fl)expression was induced by tamoxifen starting at 3 weeks old.The disease model was evaluated at 9 weeks old by assessing changes in body mass,four-limb strength,inverted screen test,skeletal muscle weight ratio,hematoxylin/eosin,Picrosirius Red,and immunofluorescent staining of skeletal muscle paraffin sections,quantitative real-time polymerase chain reaction(RT-PCR),and RNA-sequencing(RNA-seq)of skeletal muscle.Results Dual transgenic heterozygous mice(M6D4/+)were successfully obtained.These mice exhibited significant physiological and pathological changes at 9 weeks,including delayed weight gain,reduced four-limb strength and endurance,decreased skeletal muscle weight ratio,and increases in centrally nucleated muscle fibers and fibrosis.Expression levels of DUX4 and its targeted genes were significantly up-regulated in skeletal muscle,as demonstrated by RT-PCR.RNA-seq revealed up-regulation of immune regulation-,interleukin-6,and tumor necrosis factor-related genes and down-regulation of skeletal muscle development-and differentiation-related genes.Conclusions M6D4/+mice effectively simulated the skeletal muscle phenotype of FSHD and thus provide a good animal model for research into the pathogenesis,intervention,and treatment of FSHD.

Objective To establish a transgenic mouse model of facioscapulohumeral muscular dystrophy(FSHD)using tamoxifen induction and Myf6-CreERT2 and FLExDUX4 mice.Methods Dual transgenic(M6D4/+)mice were generated by crossbreeding Myf6-CreERT2 hemizygous and FLExDUX4 hemizygous mice.Full-length DUX4(DUX4-fl)expression was induced by tamoxifen starting at 3 weeks old.The disease model was evaluated at 9 weeks old by assessing changes in body mass,four-limb strength,inverted screen test,skeletal muscle weight ratio,hematoxylin/eosin,Picrosirius Red,and immunofluorescent staining of skeletal muscle paraffin sections,quantitative real-time polymerase chain reaction(RT-PCR),and RNA-sequencing(RNA-seq)of skeletal muscle.Results Dual transgenic heterozygous mice(M6D4/+)were successfully obtained.These mice exhibited significant physiological and pathological changes at 9 weeks,including delayed weight gain,reduced four-limb strength and endurance,decreased skeletal muscle weight ratio,and increases in centrally nucleated muscle fibers and fibrosis.Expression levels of DUX4 and its targeted genes were significantly up-regulated in skeletal muscle,as demonstrated by RT-PCR.RNA-seq revealed up-regulation of immune regulation-,interleukin-6,and tumor necrosis factor-related genes and down-regulation of skeletal muscle development-and differentiation-related genes.Conclusions M6D4/+mice effectively simulated the skeletal muscle phenotype of FSHD and thus provide a good animal model for research into the pathogenesis,intervention,and treatment of FSHD.

Objective:To investigate the status of medical care seeking delay and diagnosis delay of pulmonary tuberculosis (PTB) patients in Tongzhou District and Changping District of Beijing, analyze the related factors and put forward suggestions for early detection and scientific management of PTB patients.Methods:A retrospective epidemiological survey was conducted to collect the incidence data of PTB registered in Tongzhou and Changping from January 1 to December 31, 2021 by using the Chinese Tuberculosis Information Management System, and telephone interview were used for information supplement. Multivariate logistic regression model and decision tree model were used to analyze the influencing factors of medical care seeking delay and diagnosis delay of PTB patients.Results:In 2021, the medical care seeking delay time M( Q1, Q3) in the PTB patients in Tongzhou and Changping was 11 (5, 26) days, with a delay rate of 41.71%. Results from multivariate logistic regression model analysis revealed that factors influencing the medical care seeking delay included regular health check-up ( OR=0.033, 95% CI: 0.008-0.147), coughing for less than 2 weeks or showing any symptom of PTB before medical care seeking ( OR=0.378, 95% CI: 0.215-0.665), showing other symptoms before medical care seeking( OR=2.791, 95% CI: 1.710-4.555), no work or school in medical care seeking ( OR=2.990, 95% CI: 1.419-6.298). The diagnosis delay time M( Q1, Q3) in the PTB patients was 8 (0, 18) days, with a delay rate of 35.20%. Multivariate logistic regression model analysis revealed that the factors influencing the diagnosis delay of PTB included being diagnosed at a specialized tuberculosis hospital ( OR=0.426, 95% CI: 0.236-0.767) or a tuberculosis prevention and control institution ( OR=1.843, 95% CI: 1.061-3.202) and being traced as a source of infection ( OR=2.632, 95% CI: 1.062-6.521). The overall performance of the multivariate logistic regression model was comparable to that of the decision tree model, with the decision tree model exhibiting higher sensitivity but lower specificity. Conclusions:The medical care seeking delay rate and diagnosis delay rate of tuberculosis in Tongzhou and Changping were at low levels in 2021. However, it is still necessary to strengthen the health education and active screening, improve the public awareness of PTB prevention and control, and further improve the level of medical services and medical access to reduce the medical care seeking delay and diagnosis delay of PTB patients.

Objective:To analyze the relationship between health belief and the stages of parental decision-making on childhood 13-valent pneumococcal conjugate vaccine (PCV13) immunization in China.Methods:Cross-sectional multistage survey sampling method was used to select study subjects. The study subjects were parents who were aged 20-45 years and had one and more children ≤5 years old in three cities in China. A self-administered questionnaire designed based on health belief model was used to collect the information. Multinomial logistic regression analysis was used to assess the relationships between perceived susceptibility, perceived severity of illness, perceived effect of PCV13 and stages of parental decision-making on childhood PCV13 immunization.Results:A total of 1 716 valid questionnaires were returned (89.33%). The average age of the study subjects was (35.33±4.95) years, and 79.60% of them were women. In the study subjects, 48.31% had in action, 21.79% were in contemplation and 29.90% were in pre-contemplation. The multinominal logistic regression analysis indicated that high perceived susceptibility ( OR=0.14, 95% CI:0.09-0.22; OR=0.54, 95% CI:0.39-0.76), high perceived severity of illness ( OR=0.55, 95% CI:0.42-0.73), and high perceived effect of PCV13 ( OR=0.27, 95% CI:0.18-0.40; OR=0.51, 95% CI:0.32-0.81) were significantly lower in those who were in contemplation or pre-compared with those who had in action. For study subjects with low perceived susceptibility, high perceived effect of PCV13 might decrease the probabilities of contemplation ( OR=0.53, 95% CI:0.32-0.87) and pre-contemplation ( OR=0.27, 95% CI:0.18-0.41). For those with high perceived susceptibility, perceived severity of illness might decrease the probability of contemplation ( OR=0.43, 95% CI:0.23-0.82). Conclusions:Childhood PCV13 vaccination willingness and level is low in China. It is important to pay greater attention to the intervention on health belief in child parents, such as perceived effect of PCV13, perceived severity of illness, and perceived susceptibility, in health policy development and health promotion.

Exosomes are extracellular vesicles with a diameter of 40-100 nm, which contain a variety of functionally active substances such as proteins, microRNAs, and they are transported into the cell via different pathways. Studies have confirmed that exosomes slow down the progression of diabetic retinopathy by modifying changes in the levels of cell proliferation/apoptosis factors, antioxidant regulatory factors, inflammatory factors, and vascular endothelial growth factor in different ways, including direct regulation and delivery of different miRNAs, long-chained noncoding RNAs, which in turn inhibit high-glucose-induced retinal inflammation, neovascularization, microvascular damage, and vascular leakage and other retinal injuries caused by high glucose. This review summarizes the basic characteristics of exosomes and their research progress in diabetic retinopathy.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

Objective To evaluate the efficacy of Gateway balloon dilation in the treatment of symptomatic severe stenosis of middle cerebral artery.Methods The clinical data and imaging materials of 98 patients with severe symptomatic stenosis of the middle cerebral artery,who were admitted to the Second Affiliated Hospital of Nanchang University of China from May 2019 to August 2022 to receive Gateway balloon dilation,were retrospectively analyzed.The diameter of the narrowed artery before and after Gateway balloon dilation treatment,peak systolic blood flow velocity(PSV),end-diastolic blood flow velocity(EDV),Mori classification of stenosis lesion,operation-related complications,imaging manifestations and clinical follow-up results were analyzed.Results Of the 98 patients,Mori type A was seen in 83(84.69％)and Mori type Bin 15(15.31％).Successful Gateway balloon dilation procedure was accomplished in all patients.After surgery,the symptoms were improved or stabilized to varying degrees.The mean residual lumen diameter of the stenosis lesion was significantly increased from preoperative(2.01±0.13)mm to postoperative(2.33±0.25)mm,the stenosis ratio was remarkably decreased from preoperative(81.28±15.17)％to postoperative(50.24±12.83)％,the PSV and EDV were strikingly decreased from preoperative(251.01±60.13)cm/s and(104.28±32.25)cm/s to postoperative(155.33±53.28)cm/s and(70.24±36.33)cm/s respectively,the differences were statistically significant(all P＜0.05).Seven patients developed surgical complications,which were improved in short time.The patients were followed up for 10 months,modified Rankin Scale(mRS)score of ≤2 points was obtained in 88 patients(89.79％),indicating that the patients had a good quality of life as well as a good functional recovery.Conclusion For the treatment of symptomatic severe stenosis of middle cerebral artery,Gateway balloon dilation carries a significant long-term therapeutic effect with fewer surgical complications.Therefore,Gateway balloon dilation is an effective treatment for this type of disease.

Objective To investigate the mechanism of regulation of neurogenic cell function by pancreatic cancer cell-derived ex-osomes.Methods After TrkA inhibitor GW441756 was added,the effect of pancreatic cancer cell-derived exosomes on nerve growth factor/tropomyosin receptor kinase A(NGF/TrkA)expression level of neurogenic cells was detected by Western blot.The effects of pan-creatic cancer cell-derived exosomes and NGF/TrkA on the proliferation capacity of neurogenic cells were investigated by CCK-8 assay and clonal formation assay,and the effects of pancreatic cancer cell-derived exosomes and NGF/TrkA on the migration capacity of neuro-genic cells were investigated by Transwell assay.Results Pancreatic cancer cell-derived exosomes could up-regulate the expression of NGF/TrkA in neurogenic cells,and its effect can be inhibited by TrkA inhibitor GW441756.After the addition of TrkA inhibitor GW441756,the proliferation and migration ability of neurogenic cells were inhibited,and the inhibition effect could be reversed after co-culture with exosomes.Conclusion Pancreatic cancer cell-derived exosomes affect the function of neurogenic cells by up-regulating NGF/TrkA levels in neurogenic cells.

Objective To investigate the mechanism of regulation of neurogenic cell function by pancreatic cancer cell-derived ex-osomes.Methods After TrkA inhibitor GW441756 was added,the effect of pancreatic cancer cell-derived exosomes on nerve growth factor/tropomyosin receptor kinase A(NGF/TrkA)expression level of neurogenic cells was detected by Western blot.The effects of pan-creatic cancer cell-derived exosomes and NGF/TrkA on the proliferation capacity of neurogenic cells were investigated by CCK-8 assay and clonal formation assay,and the effects of pancreatic cancer cell-derived exosomes and NGF/TrkA on the migration capacity of neuro-genic cells were investigated by Transwell assay.Results Pancreatic cancer cell-derived exosomes could up-regulate the expression of NGF/TrkA in neurogenic cells,and its effect can be inhibited by TrkA inhibitor GW441756.After the addition of TrkA inhibitor GW441756,the proliferation and migration ability of neurogenic cells were inhibited,and the inhibition effect could be reversed after co-culture with exosomes.Conclusion Pancreatic cancer cell-derived exosomes affect the function of neurogenic cells by up-regulating NGF/TrkA levels in neurogenic cells.

OBJECTIVE To study the secondary metabolites of the endophytic fungus Fusarium sp. HSL-3 isolated from Hainan Mangrove and screen their anti-inflammatory and anti-tumor activities. METHODS This fungus was fermented statically by using rice medium, and the secondary metabolites of the fungus were isolated and purified by column chromatography and HPLC. Structures indentification of the ortained compounds was carried out through MS and NMR. RESULTS Eight compounds were respectively isolated and identified as follows:lateritin(1), 4-carbomethoxy-6-hydroxy- 2-quinolone(2), 3,5-dimethoxydihydro-fusarubin D(3), anhydrofusarbin(4), 3,3'-methylene-bis(4-hydroxybenzaldehyde)(5), crypticin B(6), vanillyl alcohol(7) and 3,4-dihydroxyphenylaceticacid(8), among which, compounds 2 and 5 were isolated from the genus Fusarium for the first time. Compounds 3 and 5 showed good anti-inflammatory activity on RAW264.7 cells with the inhibition rate of NO at 50 µmol·L-1 were 87% for compound 3 and 71% for compound 5, while compound 1 showed significant cytotoxic activity against human non-small cell lung cancer cell line A549, among which the IC50 value was (7.92±0.27) µmol·L-1. CONCLUSION Compounds 3 and 5 isolated from endophytic fungus Fusarium sp. HSL-3 isolated from Hainan Mangrove show strong anti-inflammatory activity, while compound 1 shows significant anti-tumor activity.