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OBJECTIVES@#To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants.@*METHODS@#A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared.@*RESULTS@#The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively.@*CONCLUSIONS@#SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.
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Nouveau-né , Enfant , Nourrisson , Femelle , Humains , Enfant d'âge préscolaire , Prématuré , Âge gestationnel , Études longitudinales , Études rétrospectives , Nourrisson petit pour son âge gestationnelRésumé
Objective:To prepare rabbit polyclonal antibodies against respiratory syncytial virus (RSV) N protein and use them as the detection antibodies to establish a N-ELISA-based method for rapid detection of neutralizing antibodies.Methods:A plasmid of pET30a-N for the expression of RSV N protein was constructed. After purification, the protein was immunized into New Zealand rabbits to prepare polyclonal antibodies, which were used as the detection antibodies. Positive serum samples were diluted and used to neutralize RSV (100 TCID 50/well). Hep-2 cells were inoculated and cultured, and then the cells were fixed with 80% acetone. ELISA was performed to detect RSV N protein in infected cells. When the absorbance value of a well was below the cut-off value, it was regarded as the positive well in the neutralization test. The highest dilution of a positive well serum was the neutralizing antibody titer. After optimizting the antibody dilution, detection time, cell density and the duration of neutralization, the method for neutralizing antibody detection was established based on N-ELISA. The established method was verified by analyzing the influences of different cell generations and edge effects, and calculating the accuracy, repeatability and precision. The correlation between the established method and microneutralization method was analyzed by detecting human RSV IgG-positive serum. Results:The plasmid pET30a-N was successfully constructed, and the expressed N protein showed high purity and good specificity. After the third immunization, the antibody titer in rabbit serum was 1∶51 200, and the antibodies could specifically bind to RSV. The prepared rabbit anti-RSV N polyclonal antibodies had a titer of 1∶51 200, and showed good specificity. The neutralizing antibodies could be detected on day 4 with the established method, and the duration of neutralization was shortened to 30 min. Cell generations and the position of wells in the 96-well plate (edge well and non-edge well) had no significant effect on the method, and the repeatability, precision and accuracy of the method were good. In the detection of 64 RSV IgG-positive human serum samples by the established method and microneutralization method, the correlation coefficient was 0.929 6, indicating a good positive correlation between the two methods.Conclusions:A N-ELISA-based method for rapid neutralizing antibody detection is successfully established, which can be used to evaluate the serum antibody level after RSV vaccination.
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Objective:To observe the effects and explore the mechanism of Tuina(Chinese therapeutic massage)static training on vascular endothelial cell dysfunction and adiponectin(APN)in obese rats. Methods:Eight of 40 Sprague-Dawley rats were randomly selected as a normal group to be fed a common diet.The remaining rats were fed a high-fat diet to induce obesity models and randomly divided into a model group,an aerobic exercise group,and a static training group after successful modeling,with 8 rats in each group.During the entire experiment,rats in the normal group were fed a common diet without intervention.Rats in the model group were fed a high-fat diet without intervention.Rats in the aerobic exercise group were given moderate-intensity running exercises.Rats in the static training group were given 6-day/week static training for 8 weeks.The body mass and length of rats were recorded throughout the experiment,and the Lee's index was calculated.After the intervention,the perirenal and peri-epididymal fat weights of rats were measured,and the fat/body mass ratio was calculated.Four items of blood lipids were detected by biochemical methods[triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)];serum nitric oxide(NO),endothelin-1(ET-1),soluble thrombomodulin(sTM),and APN were detected by enzyme-linked immunosorbent assay.The morphological changes of the aorta in each group were observed under the microscope. Results:Compared with the normal group,the body mass,body length,Lee's index,perirenal fat mass,peri-epididymal fat mass,fat/body mass ratio,TG,TC,LDL,ET-1,and sTM in the model group were significantly increased(P<0.05),while the HDL,NO,and APN were significantly reduced(P<0.01).Compared with the model group,the body mass,Lee's index,perirenal fat mass,peri-epididymal mass,fat/body mass ratio,TC,LDL,ET-1,and sTM in the aerobic exercise group and the static training group were significantly reduced(P<0.05 or P<0.01),while the HDL,NO,and APN were significantly increased(P<0.05 or P<0.01).Compared with the aerobic exercise group,NO in the static training group was significantly higher(P<0.05).APN was positively correlated with NO(P<0.01),while APN was negatively correlated with ET-1 or sTM(P<0.01).Aortic morphological observation showed that the degree of endothelial injury in the aerobic exercise group and the static training group was less significant than that in the model group,and the improvement of endothelial cell morphology in the static training group was more notable than that in the aerobic exercise group. Conclusion:Tuina static training and aerobic exercise improved the aortic endothelial injury in obese rats,and the effect of Tuina static training was more significant.The mechanism of action may be related to regulating lipid metabolism and promoting APN secretion.
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Retinal vein occlusion(RVO)is the second most common cause of vision loss due to retinal vascular disease. Macular edema(ME)is a common complication of RVO and a major cause of central vision impairment. Optical coherence tomography(OCT)is a high-resolution imaging technique that can provide detailed cross-sectional images of the retina and choroid. OCT biomarkers play an important role in the early and accurate diagnosis of RVO-ME, prediction of disease progression, and assessment of visual prognosis. This article provides an overview of various OCT biomarkers for RVO-ME, including retinal thickness, disorganization of retinal inner layers, hyper-reflectivity of retinal inner layer, the integrity of external limiting membrane and ellipsoid zone, the third highest reflectance band of the fovea, hyperreflective dots, paracentral acute middle maculopathy, prominent middle limiting membrane sign, serous retinal detachment height, macular volume and choroidal thickness. These biomarkers serve as objective indicators for evaluating the severity of RVO-ME, guiding treatment decisions, and predicting visual outcomes.
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ObjectiveTo study the traditional Chinese medicine (TCM) syndromes of children with alopecia areata, and provide evidence for TCM differentiation and treatment in clinic. MethodsA retrospective analysis was conducted on the clinical data of 800 children with alopecia areata admitted to the Hair Medicine Center of the China-Japan Friendship Hospital from January 1, 2012 to December 31, 2021. The clinical data of the children were collected using a four-examination information questionnaire, including clinical characteristics (age of consultation, age of onset, course of disease, family history, severity grading), alopecia areata-related factors (triggers), and four-examination information (including sleep, diet, emotions, bladder and bowel function, etc.). Descriptive frequency analyses, rank sum tests, factor analyses and cluster analyses were performed, and the distribution of the major TCM syndromes was summarised with the clinical data. ResultsThere were 800 children with alopecia areata, including 449 males and 351 females; 8 cases (1.00%) were in infancy, 36 cases (4.50%) were in early childhood, 180 cases (22.50%) were in preschool, 380 cases (47.50%) were in school age, and 196 cases (24.50%) were in puberty at the time of consultation; the average age of consultation was 8.31±3.86 years, the average age of onset of disease was 5.40±3.82 years, and the average duration of disease was 2.94±2.77 years; 527 children (65.87%) with severe alopecia areata; 85 children (13.56%) had a family history of alopecia areata; 772 children (96.50%) had unknown triggers for their first alopecia areata, and 28 children (3.50%) reported the presence of obvious triggers, including fright (9 cases), high fever (5 cases), allergic reactions (4 cases), micronutrient (zinc, iron, etc.) deficiencies (4 cases), inappropriate diet (2 cases), environmental factors (1 case, new house renovation), atopic dermatitis (1 case), atopic asthma (1 case), and pneumonia (1 case). A total of 40 four-examination information items were collected, among which the frequency of kicking quilts was the highest with 380 cases (47.50%), followed by picky eating (369 cases, 46.13%), sleeplessness (334 cases, 41.75%), irritability (334 cases, 41.75%), partiality towards certain foods (306 cases, 38.25%), impulsiveness (297 cases, 37.13%), dry stools (233 cases, 29.13%), yellow urine (215 cases, 26.88%), nail biting (213 cases, 26.63%), bad breath (211 cases, 26.38%). According to factor analysis and cluster analysis, five types of TCM syndromes were obtained, in order as qi and blood deficiency syndrome (110 cases, 13.75%), spleen deficiency syndrome (114 cases, 14.25%), kidney essence deficiency syndrome (140 cases, 17.50%), dietary stagnation syndrome (150 cases, 18.75%), and liver depression and spleen deficiency syndrome (286 cases, 35.75%). Patients in each age group and SALT grading are mainly liver depression and spleen deficiency syndrome. ConclusionThe TCM symptoms of children with alopecia areata are mainly based on qi and blood deficiency syndrome, spleen deficiency syndrome, kidney essence deficiency syndrome, dietary stagnation syndrome, and liver depression and spleen deficiency syndrome, of which liver depression and spleen deficiency syndrome is the most common type at different ages and stages of the disease.
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AIM: To compare the clinical effectiveness of using multifocal defocus spectacle lenses, orthokeratology lenses, and single-vision spectacle lenses in patients with myopia and small-angle intermittent exotropia.METHODS: This retrospective study included 150 patients aged 8-15 years with basic intermittent exotropia, strabismus of -10△ to -20△ prism diopters(D)(block lenses), and spherical equivalents of -1.00 to -5.50 D, who visited our hospital from June 2021 to September 2022. They were selected and divided into three groups on a voluntary basis: the HAL group(50 patients with multifocal myopia defocus spectacle lenses), the OK lens group(50 patients with nighttime orthokeratology lenses), and the SVL group(50 patients with regular single-vision spectacle lenses). After wearing the lenses consistently, changes in axial length, prism diopters with the naked eye and lenses(prism at 33 cm), positive fusional vergence of blurred points, and near stereopsis were observed and compared among groups before intervention and after 1 a. The Newcastle control score(NCS)was used to evaluate the eye position control ability of the patients in the three groups.RESULTS: Before the intervention, the axial lengths of the HAL, OK lens, and SVL groups were 24.83±0.91, 24.93±0.97, and 24.98±0.68 mm, respectively(P>0.05). After 1 a, the axial lengths of the three groups were 25.02±0.90, 25.18±0.97, and 25.45±0.65, respectively(P<0.05). Compared with an increase of 0.47±0.30 mm in the SVL group after 1 a, the axial length of the HAL and OK lens groups increased by 0.19±0.06 and 0.25±0.21 mm, respectively(both P<0.05). Before intervention, the prism diopters of the HAL, OK lens, and SVL groups measured using the prism were -15.00△±3.12△, -14.34△±3.00△ and -14.06△±3.22△, respectively. After 1 a, the prism diopters of the three groups with lenses were -9.34△±3.84△, -18.42△±4.41△, and -19.58△±5.21△, respectively, which increased by 5.66△±2.13△, -4.08△±3.34△, and -5.52△±3.70△, respectively, compared with the preintervention values(P<0.05). Before intervention, the near stereopsis in the HAL, OK lens, and SVL groups were 89.20″±54.65″, 93.00″±52.54″, and 88.40″±55.31″, respectively(P>0.05). After 1 year, near stereopsis in the groups were 76.00″±20.40″, 81.20″±18.91″, and 100.60″±51.41″, respectively(P<0.05). The positive fusional vergence(fuzzy point)of the three groups was 15.04±1.97, 15.14±1.67, and 14.62±1.47, respectively, before intervention(P>0.05), and it was 17.10±2.02, 13.12±1.41, and 13.26±2.45, respectively, after 1 a(P<0.05). In addition, the eye position control in the HAL group was significantly better than that in the OK lens and SVL groups after wearing lenses for 1 a(P<0.05).CONCLUSION: For patients with myopia and small-angle intermittent exotropia, wearing HAL can effectively control changes in strabismus and axial length compared with OK lenses and SVL, particularly for better control of strabismus, whereas wearing OK lenses or SVL would result in exotropic drifts. Stereopsis and positive fusional vergence were significantly improved in the HAL group.
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Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.
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ObjectiveThe active ingredients, action targets, and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques, and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP), Swiss Target Prediction, Pharmmapper, and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases, and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction (PPI). The gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group, a model group, a Cuscutae Semen group, and an estradiol valerate group, and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline, and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks, samples were collected, and hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), Muller's tube inhibitor/anti-Muller's tube hormone (AMH), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of extracellular regulatory protein kinase (ERK), nuclear transcription factor-κB p65 (NF-κB p65), nuclear transcription factor-κB suppressor α (IκBα), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened, mainly including tumor protein p53 (TP53), protein kinase B1 (Akt1), sarcoma (SRC), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis, TNF signaling pathway, and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group, the Cuscutae Semen group can significantly upregulate AMH, E2, and HDL-C (P<0.05, P<0.01), significantly downregulate LH, TC, and LDL-C (P<0.01), greatly reduce IL-1β, IL-6, and TNF-α protein levels, as well as ERK, NF-κB p65, and their phosphorylation levels (P<0.01). ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component, multi-target, and multi-pathway approach, and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.
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BACKGROUND:In recent years,many studies have confirmed that assembloids can make up for the shortcomings of organoids,which cannot fully reproduce the interaction between cell and cell and between cell and matrix.Since the assembloids construction methods are in the early stage of development,there is no unified standard. OBJECTIVE:To review the current construction methods,applications,advantages,and disadvantages of assembloids,guide the development and improvement of vitro cell models. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"assembloids,organoids,tumor microenvironment,organoids AND assemble,organoids AND microenvironment"and Chinese search terms"assembloids,organoids,tumor microenvironment,organoid reorganization,multicellular model".Totally 94 articles were screened out for review after excluding irrelevant articles and deduplication. RESULTS AND CONCLUSION:(1)According to the different sources of cells,the construction of assembloids can be divided into three methods:self-assembly,direct-assembly,and mixed-assembly.According to the differences of cell culture methods,it can be divided into suspension culture method,matrix culture method,organ chip culture method,and 3D bio-printing.(2)The process of self-assembly covers early stages of cell and tissue development,so it has broad prospects in the fields of organ development and developmental disorders.The function of differentiated mature cells is relatively perfect,and the assembloids directly assembled by them have more potential in the study of functional disorders and cell-damaging diseases.Self-assembly may be better in organ transplantation,and direct-assembly will be more suitable for the repair of tissue damage.Mixed-assembly combines the advantages of the former two and is mostly used to explore the physiological and pathological mechanisms of cells in the microenvironment,as well as drug screening.(3)Although different assembloids have their own advantages,they all face the problem of imperfect vasculature system,then,each method has its own limitations,for example,the degree of cell differentiation in self-assembly assembloids may still be different from that in vivo,and the fixed cell types in direct-assembly models cannot simulate complex microenvironments in vivo.These are urgent problems to be solved.(4)In the future,with the continuous improvement of assembloids culture technology,scientists can assemble biomimetic organoids with more complex tissues in vitro,providing infinitely realistic models for the study of physiological and pathological processes of human tissue and organ.
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BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.Static exercise can effectively improve skeletal muscle insulin resistance,but the mechanism remains unclear. OBJECTIVE:To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase(PI3K)/protein kinase B(AKT)/glucose transporter(GLUT4)signaling pathway. METHODS:After 1 week of adaptive feeding,7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet,while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection.Twenty-four mice were successfully modeled and they were randomly divided into model group(n=8),metformin group(n=8)and static exercise group(n=8),which continued to be fed high-fat diet.The metformin group was given 200 mg/kg metformin dissolved in normal saline(2 ml/kg)by gavage,once a day,for 6 weeks.The static exercise group was given normal saline daily by gavage and carried out static exercise,30 minutes a day,6 days per week.The model group was given the same dose of normal saline daily by gavage without exercise intervention.After the intervention,the fasting blood glucose of each group was detected,the intraperitoneal glucose tolerance test was performed,and the area under the glycemic curve was calculated.Glycosylated hemoglobin,serum insulin,insulin resistance index were detected by ELISA.Total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein were detected using biochemical methods.The mRNA expression levels of PI3K,AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR.Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining,and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION:Compared with the blank group,fasting blood glucose,glycosylated hemoglobin,area under the glycemic curve,insulin resistance index,total cholesterol,triglyceride and low-density lipoprotein levels were significantly increased in the model group(P<0.01,P<0.05).Whereas,these indicators were significantly lower in the static exercise and metformin group than the model group(P<0.01,P<0.05).Compared with the blank group,serum insulin and high-density lipoprotein levels were significantly declined in the model group(P<0.01)and the mRNA expression of PI3K,AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced(P<0.01).These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group(P<0.01).Compared with the blank group,the muscle fibers in the model group were disordered,and the muscle cells atrophied and the muscle fiber gap widened.The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group(P<0.01).Compared with the model group,atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group,and the cross-sectional area of muscle fiber was significantly increased in both groups(P<0.01).These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K,AKT and GLUT4 mRNA in skeletal muscle tissue,thereby improving the morphology and function of skeletal muscle tissue,alleviating insulin resistance and regulating glucose homeostasis.
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Objective:To investigate the clinical characteristics, muscle pathological features and treatment in patients with Juvenile idiopathic inflammatory myopathy (JIIM) with positive anti-nuclear matrix protein 2 (NXP2) antibody.Methods:The clinical data of 8 IMM patients with positive anti-NXP2 antibody were collected and the clinical manifestations, auxiliary examinations, muscle pathological changes and therapeutic effects were retrospectively analyzed.Results:The ratio of male to female was 1:3. The median age of disease onset was (6.1±3.8) years. Eight cases had proximal muscle weakness, 7 had dermatomyositis-like rash, 5 had myalgia,4 had calcinosis,3 had skin ulcer, 2 had edema and 1 had abdominal pain. Five cases had elevated serum creatine kinase. Eight cases with lower limb muscle MRI showed abnormal signals in muscle, space between muscles and fat tissue, 3 cases with chest high-resolution CT (HRCT) showed interstitial lung disease. Abdominal CT of 1 case showed irregular thickening, edema and peripheral inflammatory exudation in ascending colon and proximal transverse colon. Pathological biopsy of skeletal muscle showed perifascicular atrophy, inflammatory cell infiltration in fascicular membrane and around small vessels and muscle fiber space. Edema, hyperplasia could be seen in interstitium; but dissolved necrosis, and regenerated muscle fibers were rarely seen. Treatments included glucocorticoids, immunosuppressive agents and biological agents (1 case). After 6 months of follow-up, 5 cases had good outcomes and 3 cases had poor outcomes.Conclusion:Dermatomyositis is the major clinical manifestation of idiopathic inflammatory myopathy with positive anti-NXP2 antibody.It is associated with myasthenia, calcinosis, skin ulcers and intestinal vasculitis. The pathological changes in skeletal muscle are relatively slightmild. Glucocorticoids combined with immunosuppressive agents are effective in most cases.
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The study explored the effect of acteoside on renal fibrosis in rats with unilateral ureteral obstruction. Twenty-four healthy adult male SD rats were randomly divided into sham (CON) group, unilateral ureteral obstruction (UUO) group, UUO+acteoside (ACT) group, UUO+benazepril (BZ) group by random number table method. The animal model of renal fibrosis was established by unilateral ureteral ligation. The pathological changes of renal tissues in each group of rats were observed by HE staining and Masson staining. Immunohistochemical method was used to detect the protein expression levels of collagenⅢ, heat shock protein (HSP)-47, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), β-catenin, Bcl-2, and caspase-3. Western blotting was used to detect the protein expression of glucose-regulated protein 78 (GRP78) in renal tissue. Compared with CON group, UUO group had renal tubular dilation and significantly increased interstitial collagen fiber deposition; The degree of renal tubular dilation and interstitial collagen fibers in UUO+ACT group and UUO+BZ group were significantly reduced compared to UUO group, but still significantly heavier than CON group. Compared with CON group, the protein expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78 in renal tissues of UUO group were significantly higher, while the protein expression level of Bcl-2 was significantly lower (all P<0.05). In comparison with UUO group, the expression levels of Bcl-2 in UUO+ACT group and UUO+BZ group were significantly higher, while the expression levels of other proteins were all significantly lower (all P<0.05). The study shows that acteoside may improve renal fibrosis by decreasing the expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78, and upregulating the expression level of Bcl-2 in renal tissues.
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This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1β, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1β, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.
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Humains , Facteur de nécrose tumorale alpha , Ginsénosides , Caspase-3 , Matrix metalloproteinase 9 , Interleukine-6 , Simulation de docking moléculaire , Pharmacologie des réseaux , Espèces réactives de l'oxygène , Spectrométrie de masse en tandem , Lésion pulmonaire aigüe/génétique , Capsules , ARN messager , Médicaments issus de plantes chinoises/pharmacologieRésumé
OBJECTIVE@#To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients.@*METHODS@#Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP).@*RESULTS@#The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05).@*CONCLUSION@#For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
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Humains , Sujet âgé , Méthotrexate/effets indésirables , Études rétrospectives , Témozolomide/usage thérapeutique , Tumeurs du système nerveux central/traitement médicamenteux , Protocoles de polychimiothérapie antinéoplasique , Lymphome B diffus à grandes cellules/traitement médicamenteux , Système nerveux centralRésumé
Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.
Sujets)
Mâle , Humains , Femelle , Adulte , Adulte d'âge moyen , Cancer du nasopharynx , Chine , Microscopie , Organoïdes , Tumeurs du rhinopharynxRésumé
Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.
Résumé
This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.
Sujets)
Humains , Glycémie , Neuropathies diabétiques/traitement médicamenteux , Médicaments issus de plantes chinoises/usage thérapeutique , Hémoglobine glyquée , Hypoesthésie/traitement médicamenteux , Études multicentriques comme sujet , Douleur/étiologie , Résultat thérapeutique , Neuropathies périphériques/étiologieRésumé
OBJECTIVES@#To investigate the concentration and change characteristics of 1, 5-anhydroglucitol (1, 5-AG) in the vitreous humor of rabbit cadavers with hyperglycemic metabolism, and to explore the value of 1, 5-AG in forensic pathology identification of death caused by hyperglycemic metabolism disorders.@*METHODS@#A diabetic hyperglycemic rabbit model was established by using alloxan. Eighteen rabbits with fasting glucose concentration ≥13.80 mmol/L (experimental group) and 18 healthy rabbits with fasting glucose concentration ≤6.10 mmol/L (control group) were selected. After death from air embolism. The blood samples were collected immediately, and vitreous humor samples were collected at 0 h, 12 h, 24 h and 36 h after death. The concentration of 1, 5-AG in the blood and vitreous humor of rabbits was determined.@*RESULTS@#The blood glucose concentration in the experimental group was (25.10±3.14) mmol/L. At the time of death, there was no significant difference in the concentration of 1, 5-AG in the blood [(0.94±0.20) μg/mL] and in the vitreous humor (0.99±0.05 μg/mL, P>0.05). The concentration of 1, 5-AG in the vitreous humor of the experimental group was lower than that of the corresponding control group at all time points (P<0.05), and there was no significant difference betwwen 1, 5-AG concentration in vitreous humor between earch time point in the experimental group and the control group (P>0.05). Correlation analysis showed that the concentration of 1,5-AG in blood was negatively correlated with blood glucose in both control group and experimental group (control group: r=-0.79, P<0.05; experimental group: r=-0.97, P<0.05).@*CONCLUSIONS@#Vitreous humor can replace blood as an effective test sample for 1,5-AG detection. The concentration of 1, 5-AG in rabbit vitreous humor remains stable within 36 hours after death and is not affected by the change of postmortem interval. If the concentration of 1, 5-AG decreases significantly, it indicates the existence of hyperglycemia in rabbits before death.
Sujets)
Animaux , Lapins , Glycémie/métabolisme , Modifications postmortem , Corps vitré/métabolisme , Cadavre , AutopsieRésumé
Estimation of postmortem interval (PMI) is one of the important research contents in forensic pathology, and it has always been the focus and hot spot of research work. In recent years, scholars at home and abroad have made some research progress in estimating PMI by using ocular tissue. After death, the changes of cornea, aqueous humor, iris, lens, vitreous humor and retina all show time sequence change rule highly related to PMI. This paper reviews the research progress of PMI estimation based on the morphological, biochemical, molecular and genetic material changes of different ocular tissue structures after death, and discusses the existing problems and development trends.
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Humains , Modifications postmortem , Facteurs temps , Autopsie , Corps vitré , Anatomopathologie légaleRésumé
Objective:To evaluate the value of non-injection mucosal resection for Paris type 0-Ⅰ colon polyps with a long diameter less than 2 cm.Methods:At the Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, patients with type 0-Ⅰcolonic polyps of a long diameter less than 2 cm who underwent non-submucosal injection resection from January 2019 to December 2019 were enrolled as the non-injection group, and those who received endoscopic mucosal resection (EMR) in the same period were enrolled as the control (EMR group). The differences in complete resection rate, operation time, complication incidence and 1-year follow-up polyp detection rate between the two groups were compared.Results:A total of 373 patients were treated with non-injection mucosal resection and 743 patients with conventional EMR. There was no significant difference in gender [68.6% (256/373) VS 64.6% (480/743) for male, χ2=1.796], age (56.2±11.8 years VS 57.4±11.2 years, t=-1.984), number of polyps (1.5±0.9 VS 1.4±0.8, t=1.776), polyp distribution [48.0% (269/561) VS 34.6% (362/1 045) in right colon, χ2=3.364], lesion diameter less than 1 cm [80.0% (449/561) VS 76.9% (804/1 045), χ2=2.043] between the two groups ( P>0.05). The operation time in the non-injection group was 2.82±1.70 min, which was shorter than that in the EMR group (4.94±2.54 min) with significant difference ( t=-16.489, P<0.001). The number of metal clips used in the non-injection group was 0.90±0.68, which was less than that in the EMR group (1.30±0.73, t=-8.971, P<0.001). The en bloc resection rates of lesions in non-injection group and EMR group were both 100.0%. The complete resection rate of non-injection group was 97.3% (546/561), which was not significantly different from that of EMR group [98.1% (1 025/1 045), χ2=0.749, P=0.387]. There was no significant difference in the incidences of delayed bleeding in the two groups [0.0% (0/373) VS 0.8% (6/743), P=0.187]. No intraoperative or delayed perforation in either group occurred. There was no significant difference in the incidence of electrocoagulation syndrome between the two groups [0.8% (3/373) VS 0.7% (5/743), P=0.534]. A total of 63 patients in the non-injection group underwent colonoscopy review within the set period, and the polyp detection rate was 41.2% (26/63). A total of 178 patients in the EMR group also underwent colonoscopy review, and the polyp detection rate was 53.9% (96/178). There was no significant difference in the polyp detection rate between the two groups ( χ2=2.985, P>0.05). Conclusion:Non-submucosal injection resection is safe and effective for Paris type 0-Ⅰ colon polyps with a long diameter less than 2 cm, which can significantly shorten the operation time and is worth of clinical promotion.