Objective To investigate the protective effect of mitochondrial fission inhibitor 1(Mdivi-1),on organ function in rats with explosive blast injury combined with hemorrhagic shock.Methods A total of 192 SD rats(half male and half female,12 weeks old,weighing about 220 g)were randomly divided into 6 groups:Sham group(only surgical incision along the midline of the abdomen),model group(ESH group,thermal radiation and shock wave injury followed by femoral artery hemorrhage),lactated Ringer's solution resuscitation group(ESH+LR group,LR solution infusion in the femoral vein for resuscitation),and low-,middle-and high-dose Mdivi-1 groups(0.1,0.5 and 1.0 mg/kg Mdivi-1 intervention after infusion of LR solution).Fluorescent protein tracing was used to determine the leakage amount of fluorescent protein in the lung and kidney tissues to evaluate the vascular permeability.Evans blue dye staining was employed to observe the intestinal permeability and pulmonary vascular permeability.Laser Doppler flowmetry was applied to monitor the tissue blood perfusion in the liver,kidneys,and intestine.Serum levels of cardiac injury marker troponin I(TNI),liver function markers aspartate aminotransferase(AST)and alanine aminotransferase(ALT),and renal function markers serum creatinine(Scr)and blood urea nitrogen(BUN)were detected to evaluate the functions of corresponding organs.The water contents of the lungs and brain were calculated by measuring wet weight and dry weight of the lung and brain tissues.Blood pressure,heart rate,and respiratory rate were monitored.The survival time and 72-hour survival rate were recorded and calculated.Results Compared with the Sham group,the ESH group exhibited significantly increased vascular permeability in the lungs and kidneys as well as intestinal tissue(P<0.05),along with obviously elevated water contents in the lungs and brain(P<0.05),and decreased blood perfusion in the liver,kidneys,and intestine by 57.1%,39.2%,and 43.2%of the Sham group,respectively(P<0.05),elevated levels of TNI,AST,ALT,Scr and BUN(P<0.05),mean survival time of 3.8±1.1 h,and a 72-hour survival rate of 0(P<0.05).Although LR solution resuscitation reduced vascular permeability and alleviated organ injury in rats with explosive injury combined with hemorrhagic shock,there were no significant differences compared to the ESH group(P>0.05).Mdivi-1 treatment notably decreased vascular permeability in the lungs and kidneys and intestine,and water contents in the lungs and brain when compared with the LR group(P<0.05),with the dose of 0.5 mg/kg demonstrating the most significant effect.Additionally,Mdivi-1 treatment also significantly enhanced organ perfusion,improved organ functions,prolonged survival time,and increased survival rate.The 0.5 mg/kg treatment resulted in a 72-hour average survival time 55.64 h and a survival rate of 62.5%.Conclusion Mitochondrial fission inhibitor Mdivi-1 can reduce the permeabilities in the lungs,kidneys and intestine,improve tissue blood perfusion,protect the organ functions of the heart,liver and kidneys,and finally prolong survival time and increase survival rate in rats with concomitant explosive blast injury and hemorrhagic shock.

BACKGROUND:Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose,infection and inflammation.It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors,and has great application prospect in bone tissue engineering. OBJECTIVE:To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine,especially its osteogenic potential under high glucose,infection and inflammation conditions,and its biological safety,so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS:PubMed,WanFang,and CNKI were searched for relevant literature using the keywords of"berberine,bone defects,bone repair,bone regeneration,osteoinductive,osteoporosis,osteoblast,osteoclast,bone tissue engineering,bone,high glucose,diabetes,inflam*,infect*"in English and Chinese,respectively.A total of 105 literatures were selected for review. RESULTS AND CONCLUSION:Berberine can be used to treat multiple diseases including bone diseases,and it has the ability to promote bone regeneration.This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies.Studies have shown that it can play a role in bone repair by promoting osteogenesis,inhibiting osteoclast formation and activity,and preventing osteoporosis.It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin,PI3K/AKT,EGFR/MEK/p38MAPK,cAMP/PKA/CREB,ERK and other signaling pathways.Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose,infection and inflammation,which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site.Berberine also has the advantages of low toxicity,low price,easy access(currently it can be synthesized),which is a relatively ideal bone induction potential drug.In recent years,the application of berberine in the treatment of bone defect tends to be localized,mainly through the combination with bone tissue engineering technology to improve bioavailability,and has shown good bone repair effect and excellent biological safety in animal experiments.In addition,preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes,local infection and inflammation.In the future,more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine,and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength,efficacy and biological safety.

Bones possess metabolic activity, with their homeostasis maintained by bone resorption and bone formation mediated by osteoclasts and osteoblasts. By measuring bone metabolism markers, the overall state of bone metabolism and dynamic changes in systemic bone tissue can be reflected. Traditional bone turnover markers, including alkaline phosphatase, bonespecific alkaline phosphatase, procollagen type 1 N-terminal propeptide, procollagen type 1 C-terminal propeptide, osteocalcin, c-terminal telopeptides of type 1 collagen(CTX) and its subtype β-CTX, n-terminal telopeptides of type 1 collagen, have been widely used in clinical practice but still have limitations in terms of stability, diagnostic reliability, and specific reflection of bone sites. Recently, novel bone turnover markers like microRNA, C-X-C chemokine ligand 12, Gelsolin, Annexin A2, sclerostin, Dickkopf-related protein 1, and citrate have garnered significant attention. This article endeavors to conduct a review of the production, mechanism of action, detection methods, diagnostic value, and application prospects of new bone turnover markers in osteoporosis, thereby offering novel ideas for the prevention, diagnosis, and treatment of osteoporosis.

Bones possess metabolic activity, with their homeostasis maintained by bone resorption and bone formation mediated by osteoclasts and osteoblasts. By measuring bone metabolism markers, the overall state of bone metabolism and dynamic changes in systemic bone tissue can be reflected. Traditional bone turnover markers, including alkaline phosphatase, bonespecific alkaline phosphatase, procollagen type 1 N-terminal propeptide, procollagen type 1 C-terminal propeptide, osteocalcin, c-terminal telopeptides of type 1 collagen(CTX) and its subtype β-CTX, n-terminal telopeptides of type 1 collagen, have been widely used in clinical practice but still have limitations in terms of stability, diagnostic reliability, and specific reflection of bone sites. Recently, novel bone turnover markers like microRNA, C-X-C chemokine ligand 12, Gelsolin, Annexin A2, sclerostin, Dickkopf-related protein 1, and citrate have garnered significant attention. This article endeavors to conduct a review of the production, mechanism of action, detection methods, diagnostic value, and application prospects of new bone turnover markers in osteoporosis, thereby offering novel ideas for the prevention, diagnosis, and treatment of osteoporosis.

Gene mutation (e.g. substitution, insertion and deletion) and related phenotype information are important biomedical knowledge. Many biomedical databases (e.g. OMIM) incorporate such data. However, few studies have examined the quality of this data. In the current study, we examined the quality of protein single-point mutations in the OMIM and identified whether the corresponding reference sequences align with the mutation positions. Our results show that close to 20% of mutation data cannot be mapped to a single reference sequence. The failed mappings are caused by position conflict, site shifting (peptide, N-terminal methionine) and other types of data error. We propose a preliminary model to resolve such inconsistency in the OMIM database.
Amino Acid Sequence ; Consensus Sequence ; Databases, Genetic ; Molecular Sequence Data ; Point Mutation ; Sequence Alignment