ABSTRACT
BACKGROUND@#Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China.@*METHODS@#In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells.@*RESULTS@#A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS.@*CONCLUSIONS@#FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.
ABSTRACT
Objective To investigate the effects of elemene combined with chemotherapy on S100A4 and MMP-9 protein expression in Lewis lung carcinoma mice and to explore the possible mechanism. Methods Twenty-four mice inoculated with Lewis cells were randomly divided into 4 groups,including lung carcinoma model group,chemotherapy group,elemene group,and combination group,6 mice in each group. On day 11 after inoculation, the mice in chemotherapy group were given intraperitoneal injection of etoposide (3 mg·kg-1·d-1)and cisplatin (3 mg·kg-1·d-1),the mice in elemene group were given intraperitoneal injection of elemene (100 mg·kg-1·d-1), the mice in the combination group were given intraperitoneal injection of elemene (100 mg·kg-1·d-1),etoposide (3 mg·kg-1·d-1),and cisplatin (3 mg·kg-1·d-1). After 7-day continuous treatment,the tumor body mass, spleen index, thoracic gland index, growth-inhibition rate, and metastasis-inhibition rate in various groups were measured,the contents of protein S100A4 and matrix metalloproteinase 9 (MMP-9)in tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA),and the protein expression levels of S100A4 and MMP-9 were detected by immunohistochemical staining. Results In the combination group, the growth-inhibition rate and the inhibitory rate of metastases were increased obviously, the spleen index and thoracic gland index were also increased, the contents of S100A4 and MMP-9 were decreased, and the protein expression rates of S100A4 and MMP-9 were reduced(P < 0.05 or P < 0.01 compared with the chemotherapy group). Conclusion Elemene combined with chemotherapy could inhibit the Lewis lung carcinoma growth and metastasis in mice, and the possible mechanism might be associated with the decrease of S100A4 and MMP-9 protein expression in the tumor tissues.
ABSTRACT
Objective A new type of tibial femoral force balancing telemetry device was developed for measuring force balance on the tibial femoral contact surface in knee joint. MethodThe force balance telemetry device was designed imitating the configuration of tibial part of total knee prosthesis, in which force sensors and telemetry circuit were embedded. During total knee arthroplasty(TKA), this device was implanted as a tibial prosthesis to measure tibial femoral force while the knee joint was being placed at different angles. The tension balance was adjusted by releasing soft tissue around knee joint. ResultsThe results indicat that this device has advantage of high accuracy for force measurement (r>0.98，RMS= 65 g), which is sufficient to meet clinical demand. ConclusionsThe measurement of force balance on the tibial femoral contact surface with telemetry device can provide new insight into the estimation of optimal knee prosthesis position and selection of appropriate polyethylene insert.