Objective To investigate the clinical phenotypic characteristics of a pedigree with congenital tooth agenesis(CTA)and identify the pathogenic gene using whole-exome sequencing(WES),aiming to confirm the disease-causing mutation site,explore its potential impact on protein structure and function,and provide new insights for the diagnosis of CTA.Methods The study focused on a pedigree with congenital absence of premolars.Blood samples were collected from pedigree members,and genomic DNA was extrac-ted.Potential pathogenic mutations were screened using WES and bioinformatics analysis.Candidate mutations were validated by Sanger sequencing.Gene Ontology(GO)functional annotation and KEGG pathway enrichment analysis were performed on co-expressed genes of the candidate gene.Results Clinical examination revealed that all four members of the family were patients with missing premolar teeth.WES identified two novel mutations in the TTN gene(c.94145G＞A and c.105406C＞T)in all affected family members.Sanger sequencing confirmed co-segregation of these mutations with the disease phenotype in the pedigree.Bioinformatics analysis indicated that Ttn was highly expressed during craniofacial development in mouse embryos.Enrichment analysis demonstrated that Ttn co-ex-pressed genes were significantly enriched in the extracellular matrix(ECM)receptor interaction and PI3K/Akt signaling pathway.Conclusion This study suggests that TTN is a potential pathogenic gene for congenital premolar agenesis in this pedigree.

Objective To investigate the clinical phenotypic characteristics of a pedigree with congenital tooth agenesis(CTA)and identify the pathogenic gene using whole-exome sequencing(WES),aiming to confirm the disease-causing mutation site,explore its potential impact on protein structure and function,and provide new insights for the diagnosis of CTA.Methods The study focused on a pedigree with congenital absence of premolars.Blood samples were collected from pedigree members,and genomic DNA was extrac-ted.Potential pathogenic mutations were screened using WES and bioinformatics analysis.Candidate mutations were validated by Sanger sequencing.Gene Ontology(GO)functional annotation and KEGG pathway enrichment analysis were performed on co-expressed genes of the candidate gene.Results Clinical examination revealed that all four members of the family were patients with missing premolar teeth.WES identified two novel mutations in the TTN gene(c.94145G＞A and c.105406C＞T)in all affected family members.Sanger sequencing confirmed co-segregation of these mutations with the disease phenotype in the pedigree.Bioinformatics analysis indicated that Ttn was highly expressed during craniofacial development in mouse embryos.Enrichment analysis demonstrated that Ttn co-ex-pressed genes were significantly enriched in the extracellular matrix(ECM)receptor interaction and PI3K/Akt signaling pathway.Conclusion This study suggests that TTN is a potential pathogenic gene for congenital premolar agenesis in this pedigree.

Objective:To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock,and to clarify its mechanism.Methods:A total of 54 healthy adult SD rats were randomly divided into normal group,blast injury complicated with hemorrhagic shock(model)group,and the fluid resuscitation(treatment)group,and there were 18 rats in each group.Among them,10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes.The average survival time(ST),24 h and 72 h survival rates of the rats in various groups were observed;the blood pressure(BP),heart rate(HR),and respiratory rate(RR)of the rats in various groups were observed;the levels of serum creatinine(Scr),blood urea nitrogen(BUN),lactate(LAC),glucose(GLU),iron ions,glutathione(GSH),and malondialdehyde(MDA)and the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in serum of the rats in various groups were detected;Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and heme oxygenase 1(HO-1)proteins in superior mesenteric artery tissue of the rats in various groups;the pathomorphology of the superior mesenteric artery of the rats in various groups was observed.Results:All the rats in normal group survived for 72 h,while the longest ST of the rats in model group did not exceed 9 h.Compared with model group,the ST and 24 h survival rate(SR)of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the BP,HR,and RR of the rats in model group were significantly decreased(P＜0.01).Compared with model group,the BP,HR,and RR of the rats in treatment group were significantly increased after fluid resuscitation(P＜0.05).Compared with normal group,the activities of AST and ALT,and the levels of Scr and BUN in serum of the rats in model group were significantly increased(P＜0.01).Compared with model group,the serum levels of LAC and GLU of the rats in treatment group were significantly decreased(P＜0.01).Compared with normal group,the concentration of iron ion,GSH level,MDA level,LDH activity in serum of the rats in model group were significantly increased(P＜0.05);compared with model group,the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased(P＜0.01).Compared with normal group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased(P＜0.05);compared with model group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased(P＜0.01);compared with model group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased(P＜0.01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered,the swelling was significant and the thickness was increased;the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated.The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact,and there was no swelling in the subendothelial matrix;the vascular endothelial cell membrane of the rats in model group was damaged,there were cytoplasmic dissolution and fragmentation,and the swelling of the subendothelial matrix was significant;the swelling of the vascular endothelial cells in treatment group was alleviated.Conclusion:Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock,and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.

Objective To establish a model of combined injury of thermal radiation and blast wave of gas explosion in closed pipeline,and investigate the characteristics of important organ injury induced by burn-blast combined injury in rats.Methods A total of 72 male SD rats(aged 8～10 weeks,weighing 200～10 g)were randomly divided into control group and mild and severe injured groups.After the model rats were inflicted with blast wave and thermal radiation,their physical parameters were detected and measured.The respiratory function of the survival rats was tested.In 24 h later,arterial blood gas analysis,blood biochemical tests,and detection for serum inflammatory factors and lung injury related protein levels were performed,and the pathological changes in the lung tissue and trachea were observed.Results The peak range of explosive blast wave overpressure was 209～493 kPa,and the temperature was 152～258 ℃.The mortality rate was 8.3％in the mild group and 53.1％in the severe group.Compared with the control group,longer inspiratory time(Ti)and relaxation time(Tr)and larger tidal volume(TV)(P＜0.05),while lower respiratory frequency(f)were observed in the 2 injured groups within 6 h after injury(P＜0.05).At 24 h after injury,the values of partial pressure of carbon dioxide(PaCO2),residual base value(BE)and bicarbonate(HCO3-)were increased significantly(P＜0.05),while partial pressure of oxygen(PaO2)was decreased(P＜0.05).The serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBI)and total bile acid(TBA)were notably elevated(P＜0.05).So were the levels of IL-1 β,TNF-α and IL-6(P＜0.01).Various severities of hyperemia foci and inflammation in the tracheal mucosa were observed in the injured rats.The incidence of lung injury was high,and the pathological manifestations were dot-shaped hemorrhage to diffuse hemorrhage of the whole lobe,rupture of alveolar septum,thickening of septum,and infiltration of red blood cells and inflammatory cells.The levels of serum lung injury-related proteins were significantly increased(P＜0.05).Conclusion A rat model which can highly simulate mild to severe burn-blast combined injury is constructed,which can meet the needs for rat model in study of explosive burn-blast compound injury.The main characteristics of the injury are lung injury,respiratory dysfunction,liver damage and secondary infection.

Objective To analyze prognostic relative factors in treatment by evaluating the surgical results of tibial pilon fracture retrospectively. Methods 32 cases with unilateral tibial pilon fracture were treated operatively between January 1997 and December 1999. Among them, 16 cases were found with unsatisfied results due to incisional complications, degenerative changes and stiffness of the ankle joint. Of 16 cases, there were 13 males and 3 females. The average age was 36.5 years (range, 25 to 55 years). The mechanisms of injury were fall in 7 cases, traffic accident in 5 cases, crash in 3 cases and other cause in 1 case. 6 cases with open fracture were treated in emergency. However, 10 cases with closed fracture were operated with an average interval of 8.1 days from injury to surgery(range, 2 to 25 days). According to the Ruedi-Allgower classification, there were type Ⅱ fracture in 7 cases and type Ⅲ fracture in 9 cases. Furthermore, there were 14 cases associated with fibular fracture. During operation, 7 cases were treated with open reduction and internal fixation with plates and screws, and 9 cases were treated with open reduced minimally and external fixation with a cast. Results The average period of follow-up was 24 months (range, 12 to 36 months). According to Mazurs criterion, the result of the treatment was evaluated as fair in 6 cases, 4 cases of which were type Ⅱ fracture, and 2 cases type Ⅲ fracture; poor in 10 cases, 3 cases of which were type Ⅱ fracture, and 7 cases type Ⅲ fracture. Complications included wound dehiscence in 1 case; infection in 4 cases, 2 of which with open fracture were superficial infection, and 2 cases with closed fracture were deep infection; posttraumatic arthritis of the ankle joint in 9 cases; and severe varus deformity in 2 cases.11 cases suffered from ankle stiffness. Conclusion Discouraged results of pilon fractures are significantly related to fracture type, reduction status and time of operation, reduction and fixation of fibular fracture, and bone grafting.