BACKGROUND:Due to the treatment of cervical spondylosis,the Zero-P system of the anterior cervical interbody fusion system will have problems such as screw loosening and fracture after operation,so a novel Low-P system has been developed. OBJECTIVE:To compare the effects of the novel Low-P and Zero-P anterior cervical intervertebral fusion systems on the biomechanical properties of adjacent segments of the cervical spine and to perform stress analysis on the internal fixation system,so as to provide a theoretical reference for clinical treatment. METHODS:A complete model of the C1-C7 segment of the cervical spine was established.Based on the effectiveness of the model,a finite element model of Low-P(type Z Low-P and type H Low-P)and Zero-P system implanted in C4-C5 segments was established.The stress distribution of implanted devices and adjacent vertebral nucleus pulposus,fibrous rings and end plates was analyzed under the conditions of forward flexion,posterior extension,lateral bending and rotation. RESULTS AND CONCLUSION:(1)After implantation of Low-P and Zero-P internal fixation devices,the range of motion of the type H Low-P system was large;the maximum stress value of type Z Low-P system was small;the maximum stress of Zero-P on the nucleus pulposus of adjacent segments was large;the maximum stress of end plate was small.(2)The influence of three internal fixation systems on adjacent segment fiber rings was close.(3)The screw stress of the Zero-P internal fixation system was much greater than that of the Low-P system.(4)It is indicated that compared with Zero-P type internal fixation system,the novel Low-P system reduces the stress value of steel plate and screw,which can reduce screw loosening and internal fixation system failure.The Low-P system has less stress on the nucleus pulposus of adjacent discs and reduces disc degeneration in adjacent segments.This paper provides a theoretical basis for the clinical study of a Low-P type internal fixation system.

The aim of this study was to investigate the effect of amentoflavone(AF)on airway inflammation in asthmatic young rats and its mechanism.The asthmatic model of young SD rats was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).The rats were randomly grouped into asthma model(M)group,dexamethasone(DXMS)group,AF low(AF L),AF medium(AF M),AF high(AF H)dose group and normal control group(CT)group.After administration,the airway reactivity was detected with non-invasive lung function instrument and the inflammatory cell types in bronchoalveolar lavage fluid(BALF)were analyzed and counted by Giemsa staining.Furthermore,hematoxylin-eosin(HE)staining was applied to evaluate the pathological morphology of lung and bronchial tissues,enzyme-linked immunosorbent assay(ELISA)kits were used to detect the content of inflammatory factors in serum,Western blot was applied to detect the protein expression of GMP-AMP synthase(cGAS),interferon gene stimulator(STING),phosphorylated interferon regulatory factor 3(p-IRF3)and interferon regulatory factor 3(IRF3)in lung tissue of rats.Compared with the CT group,the asthma model group showed obvious pathological damage of bronchial tissue and lung tissue,higher level of airway reactivity,higher pathological scores of lung tissue and bronchial tissue,increased total number of inflammatory cells and the number of monocytes,eosinophils,neutrophils and lymphocytes in BALF,higher levels of inflammatory factors in serum,and higher expression levels of cGAS,STING and p-IRF3/IRF3 proteins in lung tissue(P<0.05).Compared with the M group,the pathological damage of lung and bronchus tissue in asthmatic rats was relieved after treatment with DXMS and high-dose AF,the airway reactivity,pathological score of lung tissue and bronchial tissue,total number and classification of inflammatory cells in BALF,inflammatory factors in serum and expression of cGAS,STING,p-IRF3/IRF3 proteins in lung tissue were obviously lower(P<0.05).In conclusion,AF can alleviate airway inflammation in asthmatic young rats,possibly by inhibiting cGAS-STING signal pathway.

Objective:To systematically review the association between delivery mode and exclusive breastfeeding rate during hospitalization and within the first six months of life.Methods:Observational studies on the association between delivery mode and feeding pattern were searched from PubMed, Web of Science, Cochrane Library, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database, and VIP Database from inception to October 2022. Two independent reviewers screened the literature, extracted data, and assessed the quality of included studies using Critical Appraisal Tools published by Joanna Briggs Institute or Newcastle-Ottawa Quality Scale (NOS). This meta-analysis was performed using R 4.1.0 software. Fixed-effect or random-effect models were used to pool data. Egger test and funnel plot were used to assess publication bias.Results:A total of 34 studies involving 597 203 subjects were included, including 22 cross-sectional studies and 12 cohort studies. All of the 22 cross-sectional studies were B-level quality, and eleven out of the 12 included cohort studies scored 7 points or above on the NOS scale with high quality. The results of meta-analysis showed that the likelihood of exclusive breastfeeding during hospitalization of women who had cesarean section was lower than those who delivered vaginally ( OR=0.33, 95% CI: 0.22-0.50, P<0.001); and so was the likelihood of exclusive breastfeeding at six months postpartum ( OR=0.61, 95% CI: 0.47-0.79, P<0.001). Conclusion:Current evidence suggests that cesarean section is a disadvantage to exclusive breastfeeding during hospitalization and within six months after delivery.

OBJECTIVE: To explore the clinical features, lysosomal enzymatic [acid α-glucosidase (GAA)] activities and genetic variants in a child with late-onset Pompe disease (LOPD). METHODS: Clinical data of a child who had presented at the Genetic Counseling Clinic of West China Second University Hospital in August 2020 was retrospectively analyzed. Blood samples were collected from the patient and her parents for the isolation of leukocytes and lymphocytes as well as DNA extraction. The activity of lysosomal enzyme GAA in leukocytes and lymphocytes was analyzed with or without addition of inhibitor of GAA isozyme. Potential variants in genes associated with neuromuscular disorders were analyzed, in addition with conservation of the variant sites and protein structure. The remaining samples from 20 individuals undergoing peripheral blood lymphocyte chromosomal karyotyping were mixed and used as the normal reference for the enzymatic activities. RESULTS: The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months. Physical examination revealed unstable walking, difficulty in going upstairs and obvious scoliosis. Her serum creatine kinase was significantly increased, along with abnormal electromyography, whilst no abnormality was found by cardiac ultrasound. Genetic testing revealed that she has harbored compound heterozygous variants of the GAA gene, namely c.1996dupG (p.A666Gfs*71) (maternal) and c.701C>T (p.T234M) (paternal). Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1996dupG (p.A666Gfs*71) was rated as pathogenic (PVS1+PM2_Supporting+PM3), whilst the c.701C>T (p.T234M) was rated as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3). The GAA in the leukocytes from the patient, her father and mother were respectively 76.1%, 91.3% and 95.6% of the normal value without the inhibitor, and 70.8%, 112.9% and 128.2% of the normal value with the inhibitor, whilst the activity of GAA in their leukocytes had decreased by 6 ~ 9 times after adding the inhibitor. GAA in lymphocytes of the patient, her father and mother were 68.3%, 59.0% and 59.5% of the normal value without the inhibitor, and 41.0%, 89.5% and 57.7% of the normal value with the inhibitor, the activity of GAA in lymphocytes has decreased by 2 ~ 5 times after adding the inhibitor. CONCLUSION The child was diagnosed with LOPD due to the c.1996dupG and c.701C>T compound heterozygous variants of the GAA gene. The residual activity of GAA among LOPD patients can range widely and the changes may be atypical. The diagnosis of LOPD should not be based solely on the results of enzymatic activity but combined clinical manifestation, genetic testing and measurement of enzymatic activity.
Humans ; Child ; Male ; Female ; Glycogen Storage Disease Type II/pathology* ; Retrospective Studies ; alpha-Glucosidases/genetics* ; Mothers ; Lysosomes/pathology* ; Mutation

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

Objective To compare biomechanical properties of the traditional and novel locking compression plate （LCP） for treating femoral shaft fracture, so as to provide theoretical basis for selecting more effective bone plate. Methods The bending strength and fatigue tests on the plate were performed, and the finite element analysis on deformation, stress and life of the plate were conducted by using ANSYS Workbench. Results The average bending yield load and bending strength of the novel LCP were 1.4 times of that of the traditional LCP, and the average cycle times of the novel and traditional LCP were 106 and 47 091, respectively. The difference of service life for two LCPs was 33.8%. ConclusionsThe failure probability of the novel LCP is smaller than that of the traditional LCP, and the novel LCP has more effective biomechanical stability.

Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both

Objective To study the effects of different doses of T-2 toxin on organs and bones of BALB/c pregnant mice and their offspring mice.Methods Sixty female SPF BALB/c mice at the age of 6-weeks were mated with 30 6-week-old male SPF BALB/c mice.Female mice were divided into control,low dose,medium dose and high dose groups according to body weight via the random digital table method,with 15 mice in each group.After mating with male mice,the pregnant mice in each group were 14,10,9 and 15,respectively.Nutritional interventions (feed:the doses of T-2 toxin were 0,600,1 200 and 2 400 ng/g,respectively) were initiated from the gestation day 0 until the first generation mice were grown up (6-weeks-old).The growth status and organ coefficient (heart,liver,kidney,thymus,spleen and brain) of the two generations in each period were recorded.Skeletal X-ray photographs of the two generations were taken by digital radiography.The histopathological changes in the organs (liver,thymus,spleen and epiphyseal cartilage) of the two generations were observed under light microscope.Results Among the pregnant mice,there were no significant differences in organ coefficients (P ＞ 0.05).No abnormalities were observed in each group of skeletal X-ray photographs.In the female generation mice,there were no significant differences in the coefficients of heart,liver and kidney (F =0.233,2.196,0.430,P ＞ 0.05),while there were significant differences in the coefficients of thymus,spleen and brain (F=3.683,3.148,4.498,P ＜ 0.05),and the thymus coefficient of medium dose group was higher than that of control group;the thymus coefficient of high dose group was lower than that of other three groups;the spleen coefficients of the three dose groups were higher than that of control group;the brain coefficients of the three dose groups were lower than that of control group (P ＜ 0.05).In the male generation mice,there were no significant differences in the coefficients of thymus and brain (F =2.447,1.620,P ＞ 0.05),while there were significant differences in the coefficients of heart,liver,kidney and spleen (F =5.339,2.738,11.435,2.872,P ＜ 0.05),and the heart coefficient of high dose group was lower than that of control group and low dose group;the coefficients of liver and kidney in medium dose and high dose groups were lower than those in control and low dose groups;the spleen coefficients of the three dose groups were higher than that of control group (P ＜ 0.05).The pathological changes of liver,thymus,spleen and epiphyseal cartilage were found in dose exposure groups;epiphyseal hyperplasia was found in the skeletal X-ray photographs of medium and high dose groups.Conclusion T-2 toxin has no significant effects on pregnant mice,but it could cause damage to the organs and epiphyseal plate cartilage of the first generation,and the location of the injury is related to gender.

OBJECTIVE:To explore losses and gains (L&G) and L&G ratio induced by Essential Medicine System in a county. METHODS:By choosing a county in western China as sample area,field investigation was used to collect outpatient and inpatient visits,outpatient and inpatient income,drug income,total length of stay and medical insurance reimbursement criteria in primary medical institutions (township health centers,village health rooms) of the county during 2009-2015. By setting the year 2009 as the baseline year,the drug cost reimbursed by medical insurance was simulated and calculated when Essential Medicine System were not implemented;L&G and L&G ratio of medical insurance were calculated by comparing with actual drug cost reimbursed by medical insurance. RESULTS:The year 2012,in which the sample county fully implemented the Essential Medicine System was the turning year. Medical insurance funds lost in primary medical institutions of the county during 2010-2011(lost 437000,915000 yuan,respectively),but gained during 2012 to 2015(gained 199000,494000,858000,1290000 yuan, respectively);the L&G ratio increased from -0.67％ to 1.21％. For reimbursed outpatient drug cost and inpatient cost,L&G of medical insurance were different. For reimbursed drug cost of village health room and township health center,L&G of medical insurance were also different. CONCLUSIONS:The implementation of Essential Medicine System benefits to medical insurance within the county and Medical insurance funds can be saved.

Objective To investigate the effects of different doses of T-2 toxin on the expression of cytokines cytokines and pathological changes in parental mice and their offspring. Methods One hundred female mice and 25 male mice (CD-1, SPF) were adapted for one week. After regular random mating, observation of vaginal suppository within the first 24 hours was as the 0th day of pregnancy. The pregnant rats were divided into high dose, medium dose, low dose and control groups according to body weight by a random number table(Feed: the doses of T-2 toxin were 1 200, 600, 300, and 0 μg/kg, respectively), with 16 - 18 rats in each group. The high, middle and low dose groups began to consume the poisoned feed on the 0th day of pregnancy, while the control group consumed the standard feed. After natural delivery, their offspring were continually treated the same way as their mother until the offspring reached adulthood. Serum levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), organ coefficient and pathological changes of articular cartilage were determined. Results The levels of IL-1β,IL-6 and TNF-α in the control, low, middle and high T-2 toxin groups during the pro-pregnancy of the middle-aged mice were [(219.56 ± 19.32), (136.89 ± 20.41), (210.49 ± 21.23), (207.41 ± 21.23); (192.73 ± 22.43), (136.25 ± 29.55), (187.43 ± 39.32), (232.48 ± 39.32); (1 303.02 ± 142.10), (1 072.60 ± 78.30), (1 065.03 ± 37.44), and (1 169.72 ± 104.18) ng/L], respectively. The differences between control and T-2 toxin treated groups were statistically significant (F = 17.124, 6.237, 7.670, P < 0.05). For further pairwise comparison,IL-1β and IL-6 in low dose group were significantly lower than those in control, middle and high dose groups (P < 0.05); TNF-α content in control group was significantly higher than those in low,middle and high dose groups(P<0.05).There were significant differences in the levels of IL-1β,IL-6 and TNF-α between the control group and the low,middle and high dose groups of offspring weanling mice[(142.36 ± 13.36),(113.01 ± 8.65), (102.13 ± 8.31), (123.42 ± 10.41); (109.92 ± 9.76), (100.26 ± 15.60), (85.25 ± 9.97), (100.21 ± 16.46);(1 308.45 ± 204.90), (1 248.60 ± 96.85), (1 081.09 ± 105.51), (1 204.87 ± 153.96) ng/L, F = 49.823, 10.530, 7.490, P < 0.05]. The levels of IL-1β and IL-6 in the control group were significantly higher than those in the low, middle and high dose groups(P < 0.05).The levels of TNF-α in the control group were significantly higher than those in the medium and high dose groups(P < 0.05).The levels of the three cytokines IL-1β, IL-6 and TNF-α in adult filial mice were significantly different [(69.71 ± 9.61), (61.31 ± 10.07), (63.07 ± 10.39), (58.56 ± 9.69); (172.55 ± 24.55),(146.91 ± 13.47),(151.02 ± 24.93), (157.21 ± 17.86); (1 136.87 ± 137.39), (1 002.22 ± 86.52), (987.12 ± 130.80),(1 047.21 ± 171.64)ng/L, F=4.670,5.636, 4.775, P < 0.05], the contents of the three cytokines in the poisoning groups were significantly lower than that of the control group (P < 0.05). The organ coefficients of thymus, spleen and liver in the second trimester were significantly different [(0.14 ± 0.03), (0.20 ± 0.06), (0.15 ± 0.02), (0.12 ± 0.03); (0.71 ± 0.16), (0.78 ± 0.14), (0.77 ± 0.15), (0.38 ± 0.10); (6.19 ± 0.43), (5.57 ± 0.57), (6.04 ± 0.32), (5.11 ± 0.29), F = 4.056, 11.064, 8.312, P < 0.05], and the thymus index was significantly increased in low dose group (P<0.05),spleen coefficient decreased significantly in high dose group (P < 0.05), and liver coefficients in low and high dose group were significantly decreased (P < 0.05). In the offspring, the midbrain coefficient of viscera showed significant changes [(3.45 ± 0.73), (3.11 ± 0.31), (2.98 ± 0.45), (3.04 ± 0.22), F = 7.529, P < 0.05], which was significantly decreased in the exposed rats(P<0.05).Both the mid-pregnant mice and filial mice showed varying degrees of changes in epiphyseal cartilage injury. The degree of epiphyseal cartilage injury became higher with increasing dosages of T-2 toxin in mid-pregnancy and post-weaning parental mice, and the injury was more serious in post-weaning mice. Conclusions Exposure to T-2 toxin can cause decrease of cytokines IL-1β, IL-6 and TNF-α in the blood of CD-1 pregnant and filial mice, and also cause the cartilage damage in mice, which are aggravated following increased doses of T-2 toxin and extension of exposure time.