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

Objective:To evaluate the relationship of early tumor shrinkage and depth of tumor response with the clinical efficacy and pro-gnosis of programmed death-1(PD-1)inhibitor combined with trastuzumab and first-line chemotherapy in the treatment of HER-2-positive advanced gastric cancer.Methods:We retrospectively analyzed data from 40 patients treated with this combination at Nanjing Drum Tower Hospital,The Affliated Hospital of Nanjing University Medical School from June 2018 to March 2023.Key metrics included early tumor shrinkage(ETS),depth of response(DpR),objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse reactions.Survival analysis using Log-rank test and Kaplan-Meier method,and plot PFS and OS survival curves.COX regression analysis for correlation testing.Results:The patient's ORR was 77.5%,DCR was 100%,complete response rate was 15.0%,medi-an PFS(mPFS)was 11.10 months,and median OS(mOS)was 30.77 months.COX univariate analysis showed that tumor differentiation,liver metastasis,distant lymph node metastasis,DpR were related to PFS and OS(all P<0.05),ETS was only related to PFS(P=0.010),and PD-L1 ex-pression was not related to PFS and OS.There was a significant difference in mPFS between patients with ETS≥35%and ETS<35%(P=0.008),while there was no significant difference in mOS(P=0.076);There were significant differences in mPFS and mOS between patients with DpR≥40%and DpR<40%(P=0.001).COX multivariate analysis showed that DpR is an independent factor affecting PFS and OS,and distant lymph node metastasis is an independent factor affecting OS.The overall tolerance to treatment of the patients was good,with no grade 4 or above treatment-related adverse reactions or death.Conclusions:ETS and DpR may be predictive indicators of the efficacy and prognosis of PD-1 inhibitors combined with trastuzumab and first-line chemotherapy for HER-2 positive advanced gastric cancer.

To investigate the effects of Sangen Decoction, a compound Chinese herbal medicine, on osteoclastogenesis and bone resorption function of osteoclasts induced by polymethylmethacrylate particles in vitro.

Objective:To study the distributing characteristics of digestive malignancy in patients with type 2 diabetes mellitus.Methods:We reviewed the complete data of 201 dead patients with type 2 diabetes mellitus from 2000 to 2005,sifted those complicated by cancer and those by digestive malignancy,and then analyzed the distributing characteristics and morbidity of the tumor.Results:The patients(126 males and 75 females) died at the average age of(73.53?9.03) years.Of the total number,57 cases(44 males and 13 females) were complicated by cancer and 25(22 males and 3 females) by digestive malignancy,the latter constituting the largest proportion of the diabetic patients(12.44%),followed by malignancy of the blood system,the lung and the urinary system.The pancreas was involved in 4.48% of the cases,while the stomach,esophagus,gallbladder and other digestive organs in only 0.498% of them.Of all the patients,those complicated by pancreatic cancer ran a shortest disease course of about 3 years,while those with the colon involved a longest course of about 11 years.Conclusion:Patients with type 2 diabetes mellitus are liable to cancer,particularly to digestive malignancy,and males are more susceptible than females.The cancerous characteristics,including morbidity and disease course,vary in different digestive organs.