Collagen, a vital matrix protein for various tissue and functions in animals, is widely applied in biomaterials. In type Ⅰ collagen, missense mutations of glycine (Gly) in the Gly-Xaa-Yaa triplet of the triple helix are a major cause of osteogenesis imperfecta (OI). Clinical manifestations exhibit marked heterogeneity, spanning a broad disease spectrum from mild skeletal fragility (Type Ⅰ) to severe limb deformities (Type Ⅲ) and perinatal lethal forms (Type Ⅱ). This study utilized recombinant collagen as a model to further elucidate whether Gly→Ala/Val mutations at the N-terminus of the integrin-binding sequence GFPGER affect collagen structure and function, and to explore the underlying mechanisms by which missense mutations impact the biological function of collagen. By introducing Ala and Val substitutions at seven Gly positions N-terminal to the GFPGER sequence, we systematically assessed the effects of these amino acid replacements on the triple-helical structure, thermal stability, integrin-binding ability, and cell adhesion of recombinant collagen. All constructs formed a stable triple-helix structure, with slightly compromised thermal stability. Gly→Val substitutions increased the susceptibility of recombinant collagen to trypsin, which suggested local conformational perturbations in the triple helix. In addition, Gly→Val substitutions significantly reduced the integrin-binding affinity and decreased HT1080 cell adhesion, with the effects stronger than Gly→Ala substitutions. Compared with Gly→Ala substitutions, substitution of Gly with the larger residue Val had enhanced negative effects on the structure and function of recombinant collagen. These findings provide new insights into the molecular mechanisms of osteogenesis imperfecta and offer theoretical references and experimental foundations for the design of collagen sequences and the development of collagen-based biomaterials.
Recombinant Proteins/biosynthesis* ; Glycine/genetics* ; Humans ; Osteogenesis Imperfecta/genetics* ; Integrins/metabolism* ; Collagen/metabolism* ; Collagen Type I/metabolism* ; Amino Acid Substitution ; Mutation ; Mutation, Missense

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Status epilepticus is a neurological emergency with unknown pathogenesis, controversial treatment options, and poor prognosis. In recent years, with the development of 18F-flurodeoxyglucose positron emission tomography ( 18F-FDG PET) imaging technology, further studies on status epilepticus have been carried out from the perspective of molecular metabolism. This article reviews the current role of 18F-FDG PET in patients with status epilepticus on etiology, disease activity, electric activity, location of epileptogenic foci, and prognosis evaluation.

【Objective】 To explore the clinical efficacy of traditional Chinese medicine(TCM) therapy in patients with transfusion related iron overload diagnosed with chronic aplastic anemia (CAA). 【Methods】 A total of 115 patients with CAA and iron overload who had been admitted to Zhejiang Provincal Hospital of TCM from February 2015 to December 2016 were studied. They were assigned to treatment group(n=69), positive control group(n=16), and negative control group(n=30) according to different treatment plan designed in advance. Patients in the treatment group were treated with TCM of "Bushen Huoxue" recipe once a day, with the formula mixed with astragalus 40 g, rehmannia 12 g, cornus 12 g, deerhorn glue melting by heat 12 g, atractylodes 20 g, radix paeoniae alba 20 g, curculigo orchioides 10 g, herba epimedii 10 g, cistanche 12 g, cassia stem 10 g, dried orange peel 8 g, poria 10, gingembre 6 g, angelica sinensis 20 g, salvia miltiorrhiza 20 g, zedoary 9 g, leonurus 30 g, gromwell 15 g, and prepared liquorice root 6 g. Patients in positive control group were treated with desferrioxamine for more than 8 h per day, 5 to 7 days per week. Patients in negative control group were treated with basic treatment.The serum ferritin (SF) and cytokines of patients of the three groups before and 3 months after therapy were detected according to the blood-stasis of TCM symptom rating scale, and the correlation between the decrease of ferritin after treatment and the improvement of blood stasis syndrome score was analyzed. 【Results】 The level of SF of the treatment group, positive and negative control group before treatment were 1 881.63±1 386.81 vs 6 581.36±5 180.96 vs1 974.25±1 753.06, and were 2 040.14±1 484.27 vs 4 169.18±3 631.64(P<0.05)vs 2 699.80±2 352.34(P<0.05) 3 months after treatment. The treatment was effctive in 16 patients in treatment group, accounted for 23.19%(16/69). The score of blood stasis syndrome of the three groups before and after treatment were 4.26±1.45vs 6.88±1.31 vs 4.17±1.18 and 4.42±1.43 vs 5.00±0.89 vs 4.67±1.51(P<0.01), respectively. The effective rate of improving blood stasis syndrome score in the treatment group was up to 26.09%. The decrease of serum ferritin was positively correlated with the improvement of blood stasis score (P < 0.01). The levels of IL-6 and IL-10 in treatment group were 20.79±14.14 and 56.27±25.54 before treatment, 13.00±6.48 and 41.02±9.93(P<0.05)3 months after treatment, respectively. 【Conclusion】 "Bushen Huoxue" therapy can stabilize the the level of SF and improve the blood stasis syndrome in CAA patients with iron overload.

Objective:To understand the effect of a new tracheal tube fixation device in the "double fixation" of oral tracheal intubation for critically ill patients in adult emergency department.Methods:A retrospective analysis of patients with oral tracheal intubation admitted to our EICU from January 2016 to June 2017 was performed using traditional tape and inch band fixation as a control group; the experience of treatment from July 2017 to December 2018 for patients with oral tracheal intubation, the new double-fixation method of tracheal tube fixation device was used as the observation group. The degree of displacement, oral cleanliness, facial skin allergies and injuries, and comfort of the two groups of patients was compared.Results:The rate of tracheal displacement in the experimental group was mildly 11.2% (11/98), moderately 5.1% (5/98), and the control group was mildly 24.2% (15/62), moderately 14.5% (9/62) and severe 6.5% (4/62). The incidence of facial skin allergy and skin damage was 6.1% (6/98), 0, and the control group was 24.2% (15/62), 11.3% (7/62), the difference was statistically significant ( Z value was -4.021, χ2 value was 24.48, P<0.05). The comfort score of the test group was (1.05±1.01) points, which was significantly higher than (2.10±1.71) points of the control group ( t value was 4.920, P<0.01). Conclusions:The new type of tracheal tube fixation device "dual fixation" for critically ill patients with mechanical ventilation through oral endotracheal intubation is visually beautiful, and has good firmness and comfort. It can effectively reduce the occurrence of adverse events and has good application value.

Objective:To analyze the effects of noise exposure on the hearing at different frequencies in workers from the automobile manufacturing industry.Methods:A total of 4723 noise workers in a large automobile manufacturing company in Guangzhou were chosen as the research object by using judgment sampling method between April and July, 2018, and carried out 0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 kHz pure tone audiometry threshold to analyze the characteristics of the status of hearing loss at different frequencies and its relationship with the noise exposure time.Results:The detection rate of hearing loss in noise-exposed workers was 29.8% (1406/4723) . Among them, the binaural hearing loss was 21.2% (999/4723) , and single unilateral hearing loss accounted for 8.6% (407/4723) . The hearing loss detection rate of right ear was higher than that of the left ear ( P<0.05) , especially in the 6.0 kHz ( P<0.001) . The detection rate of increased speech frequency hearing threshold was 1.9% (90/4723) , and the detection rate of increased high-frequency hearing threshold was 28.9% (1366/4723) . The detection rate of increased threshold in both the left and the right ear increased with the increase of frequency ( P<0.001) , the increased hearing threshold was the highest at the frequency of 6.0 kHz. The auditory threshold of left ear in 0.5 kHz were higher than that of right ear at the same frequency ( P<0.05) . The detection rate of hearing loss increased with the increase of noise exposure time ( P<0.001) , and the increased threshold of 3.0, 4.0 and 6.0 kHz from workers increased with the increase of noise exposure time ( P<0.001) . Conclusion:There is a significant increased threshold in workers exposed to noise frequency of 6.0 kHz, right ear is more easily damaged than left ear, there is a dose-response relationship for the noise exposure time and high-frequency hearing loss.

Objective:To analyze the effects of noise exposure on the hearing at different frequencies in workers from the automobile manufacturing industry.Methods:A total of 4723 noise workers in a large automobile manufacturing company in Guangzhou were chosen as the research object by using judgment sampling method between April and July, 2018, and carried out 0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 kHz pure tone audiometry threshold to analyze the characteristics of the status of hearing loss at different frequencies and its relationship with the noise exposure time.Results:The detection rate of hearing loss in noise-exposed workers was 29.8% (1406/4723) . Among them, the binaural hearing loss was 21.2% (999/4723) , and single unilateral hearing loss accounted for 8.6% (407/4723) . The hearing loss detection rate of right ear was higher than that of the left ear ( P<0.05) , especially in the 6.0 kHz ( P<0.001) . The detection rate of increased speech frequency hearing threshold was 1.9% (90/4723) , and the detection rate of increased high-frequency hearing threshold was 28.9% (1366/4723) . The detection rate of increased threshold in both the left and the right ear increased with the increase of frequency ( P<0.001) , the increased hearing threshold was the highest at the frequency of 6.0 kHz. The auditory threshold of left ear in 0.5 kHz were higher than that of right ear at the same frequency ( P<0.05) . The detection rate of hearing loss increased with the increase of noise exposure time ( P<0.001) , and the increased threshold of 3.0, 4.0 and 6.0 kHz from workers increased with the increase of noise exposure time ( P<0.001) . Conclusion:There is a significant increased threshold in workers exposed to noise frequency of 6.0 kHz, right ear is more easily damaged than left ear, there is a dose-response relationship for the noise exposure time and high-frequency hearing loss.

Objective:To investigate the effects of long-term ionizing radiation on peripheral blood cells of nuclear power workers.Methods:In March 2019, a total of 530 radiation exposed workers in the nuclear power industry who underwent in-service radiation occupational health examination in Guangzhou occupational disease prevention and control hospital in 2018 and with service age ≥1 year were selected as the radiation group. At the same time, 545 workers in nuclear power industry were selected as control group. According to the methods and requirements of GBZ 235-2011 ＂technical specification for occupational health monitoring of radiation workers＂ and GBZ 98-2017 ＂health requirements for radiation workers＂, the occupational health monitoring data were collected, and the change rules of peripheral blood cells in the two groups were analyzed.Results:Compared with the control group, the total number of WBC, NEUT, LYMP, Hb, MCV and MCHC in radiation group were lower than those in control group ( P<0.05) , and the difference was statistically significant ( P<0.05) . The MPV increased significantly ( P<0.05) . Compared with the control group, the abnormal rate of WBC and Hb in the radiation group was higher than that in the control group ( P<0.01) , but there was no significant difference in the abnormal rate of RBC and PLT ( P>0.05) . Conclusion:Low dose ionizing radiation has a certain cumulative damage effect on peripheral blood cells of radiation workers in nuclear power industry. The change rules of different cell subtypes are different, and the changes of WBC and PLT appear earlier.

Objective:To investigate the effects of long-term ionizing radiation on peripheral blood cells of nuclear power workers.Methods:In March 2019, a total of 530 radiation exposed workers in the nuclear power industry who underwent in-service radiation occupational health examination in Guangzhou occupational disease prevention and control hospital in 2018 and with service age ≥1 year were selected as the radiation group. At the same time, 545 workers in nuclear power industry were selected as control group. According to the methods and requirements of GBZ 235-2011 ＂technical specification for occupational health monitoring of radiation workers＂ and GBZ 98-2017 ＂health requirements for radiation workers＂, the occupational health monitoring data were collected, and the change rules of peripheral blood cells in the two groups were analyzed.Results:Compared with the control group, the total number of WBC, NEUT, LYMP, Hb, MCV and MCHC in radiation group were lower than those in control group ( P<0.05) , and the difference was statistically significant ( P<0.05) . The MPV increased significantly ( P<0.05) . Compared with the control group, the abnormal rate of WBC and Hb in the radiation group was higher than that in the control group ( P<0.01) , but there was no significant difference in the abnormal rate of RBC and PLT ( P>0.05) . Conclusion:Low dose ionizing radiation has a certain cumulative damage effect on peripheral blood cells of radiation workers in nuclear power industry. The change rules of different cell subtypes are different, and the changes of WBC and PLT appear earlier.