PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67% in the TXA group and 47.95% in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.
Humans ; Tranexamic Acid/administration & dosage* ; Hip Fractures/surgery* ; Male ; Aged ; Female ; Fracture Fixation, Intramedullary/adverse effects* ; Blood Loss, Surgical/prevention & control* ; Antifibrinolytic Agents/administration & dosage* ; Aged, 80 and over ; Bone Nails ; Middle Aged ; Blood Transfusion/statistics & numerical data*

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

Objective To observe the influence of dapagliflozin tablets on myocardial enzymes,mitral valve blood flow and major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI)complicated with type 2 diabetes mellitus(T2DM)after interventional therapy.Methods AMI patients with T2DM were divided into control group and treatment group by cohort method.The control group was given aspirin tablets 300 mg and ticagrelor 180 mg orally,qd,until the day of interventional treatment.After interventional therapy,aspirin tablets 100 mg,qd,oral ticagrelor tablets 90 mg each time,once in the morning and once in the evening.On the basis of the treatment in the control group,the patients in the treatment group were given dapagliflozin tablets 5-10 mg,qd,every morning after admission.After 3 months of continuous treatment,the clinical efficacy,blood glucose control effect[fasting plasma glucose(FPG),2 hour postprandial blood glucose(2 h PG)],myocardial enzymes indicators[creatine kinase(CK),creatine kinase isoenzyme-MB(CK-MB)],ventricular remodeling indicators[left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVESD)],adverse drug reactions and MACE were compared between the two groups.Results There were 55 cases in the control group and 59 cases in the treatment group.After treatment,the total effective rates of the treatment group and the control group were 88.14％(52 cases/59 cases)and 72.73％(40 cases/55 cases),respectively,the difference was statistically significant(P＜0.05).After treatment,the FPG of the treatment group and the control group were(7.29±0.71)and(7.81±0.75)mmol·L-1,respectively;the 2 h PG were(8.66±1.33)and(9.59±1.38)mmol·L-1,respectively;the CK were(145.68±29.82)and(163.68±42.16)U·L-1,respectively;the CK-MB were(8.21±2.37)and(10.33±3.08)U·L-1,respectively;the LVEF were(57.63±8.74)％and(51.41±6.49)％,respectively;LVESD were(33.26±5.33)and(39.51±5.38)mm,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P＜0.05).During the treatment,the adverse drug reactions in the treatment group mainly included nausea and vomiting,diarrhea,constipation.The adverse drug reactions in the control group mainly included hypoglycemia,diarrhea,headache.The total incidence of adverse drug reactions in the treatment group and the control group was 6.68％(4 cases/59 cases)and 9.09％(5 cases/55 cases),respectively,and the difference was not statistically significant(P＞0.05).After 3 months of follow-up,the total incidence of MACE in the treatment group and the control group was 5.08％and 18.18％,respectively,the difference was statistically significant(P＜0.05).Conclusion Dapagliflozin has a significant efficacy in the treatment of AMI patients with T2DM,and it can enhance the effect of blood glucose control,reduce the myocardial injury,inhibit the ventricular remodeling,and reduce the risk of MACE,with high safety.

As the second largest cofactor after ATP in body, S-adenosyl-L-methionine (SAM) is responsible for methyl donor in SAM-dependent methyltransferases (MTases). The methylation of essential ingredients (e.g., DNA, RNA, protein) plays a critical role in epigenetic regulation, cellular signal transduction and metabolic cycles, which is closely related to different kinds of diseases. Therefore, SAM-dependent methyltransferases are considered as promising drug targets. Currently, a growing number of nucleoside analogues have been developed as SAM-competitive inhibitors, blocking the downstream signaling pathways to cure diseases. In the review, we outline the design strategy and optimization process of methyltransferase inhibitors, analyze the shortcomings and solutions of developing nucleoside derivatives as MTase inhibitors, to provide guidance and broad direction to the development of nucleoside MTase inhibitors.

Objective To assess the impact of ultrasound-guided fascia iliaca compartment block on major cardiovascular events and postoperative prognosis in patients with lower limb aortoiliac occlusive disease(ASO).Methods This study was a retrospective study including 353 patients with lower limb arterial reconstruction surgery for ASO at Xiamen Hospital Affiliated to Zhongshan Hospital of Fudan University from January 2018 to January 2022.Patients were divided into two groups based on different anesthesia:the group receiving ultrasound-guided fascia iliaca block combined with sciatic nerve block(Group B)and the group receiving monitored anesthesia care(MAC)(Group M).The primary outcome was the occurrence of major adverse cardiovascular events after lower limb arterial reconstruction surgery in ASO patients.The secondary outcomes included the incidence of non-cardiac postoperative myocardial injury,postoperative amputation,and other adverse reactions such as postoperative delirium,nausea,and vomiting as well as postoperative laboratory indicators.By using propensity score matching to balance baseline characteristics before surgery,the impact of different anesthesia methods on the occurrence of MACE and prognosis after surgery in ASO patients was analyzed.Results After propensity score matching,the incidence of MACE in Group B was lower compared with Group M(10%vs.3.4%,P=0.038);The incidence of MINS in Group B(33%vs.25%,P=0.200);The amputation rate of Group B(4.2%vs.3.4%,P＞0.99);The incidence of complications in Group B was(6.8%vs.4.2%,P=0.39);There was no statistically significant differ-ence in postoperative laboratory indicators between the two groups(P＞0.05).Multivariate analysis showed that nerve block(OR=0.25,95%CI:0.05～0.93),postoperative HBG(OR=0.95,95%CI:0.91～0.99)were in-dependent factors in reducing the incidence of MACE.Conclusion Ultrasound-guidance fascia iliaca compartment block and sciatic nerve block could reduce the risk of major adverse cardiovascular events in patients undergoing lower limb arterial revascularization surgery.

Objective To observe and compare the changes of vertebral bone mineral density(BMD)in the early stages of spinal Mycobacterium tuberculosis infection.Methods Patients who underwent spinal surgery at Xiangya Hospital,Central South University from January 1 to December 31,2023 were continuously enrolled(spinal tuber-culosis group),based on gender matching,non-spinal tuberculosis surgical patients treated for spinal stenosis were selected as the control group.Dual-energy X-ray scans were performed on the enrolled patients,difference in verte-bral BMD between two groups of patients was compared.An animal model of spinal Mycobacterium tuberculosis in-fection(referred to as the animal model)was constructed,differences in microstructure of trabecular bone between spinal tuberculosis group and control group was compared,and the bone volume/tissue volume(BV/TV),the thickness of trabecular bone(Tb.Th),the number of trabecular bone(Tb.N),and sparse density of trabecular(Tb.Sp)were used as evaluation indexes to further analyze the bone quality differences between the diseased verte-brae and the neighboring vertebrae.Results 69 patients were included in the spinal tuberculosis group and the con-trol group,respectively.The BMD of patients in the spinal tuberculosis group(0.793[0.712,0.869]g/cm2)was lower than that of the control group(0.907[0.800,1.020]g/cm2),difference was statistically significant(P＜0.05).Microstructure of trabecular bone BV/TV([18.4±5.4]％),Tb.Th([0.124±0.010]mm)in the spinal tuberculosis group of animal model were significantly altered compared with BV/TV([22.6±3.2]％),Tb.Th([0.160±0.017]mm)in the control group(both P＜0.05).In the spinal tuberculosis group,microstructure of diseased vetebral trabecular bone BV/TV([25.5±6.7]％)and Tb.N([1.871±0.443]/mm)were significantly lower than BV/TV([26.6±6.8]％)and Tb.N([1.969±0.454]/mm)in the neighboring vertebrae,both with statistically difference(both P＜0.05).Conclusion In the early stages of spinal Mycobacterium tuberculosis infec-tion,microstructure of vertebral trabecular bone can be altered,leading to a decrease in BMD.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To investigate the efficacy of different approaches for screw internal fixation in the treatment of posterior ankle fractures in trimalleolar fracture,and the complications was analyzed.Methods A prospective study was conducted on 80 patients with Haraguchi type Ⅰ posterior ankle fracture who admitted to our hospital from May 2019 to October 2020,they were randomly divided into group A and group B according to a random number table method,with 40 cases in each group.Patients in group A were treated with percutaneous anterior to posterior screw internal fixation for posterior ankle fractures,while patients in group B were treated with percutaneous posterolateral approach limited exposure and reduction screw internal fixation for posterior ankle fractures.The surgical indicators,postoperative recovery,American Orthopaedic Foot and Ankle Society(AOFAS)score,ROM score of ankle joint at the last follow-up,postoperative evaluation,and postoperative complications of patients between the two groups were compared.Results There was no statistically significant difference in operation time,complete weight-bearing time,or fracture healing time of patients between the two groups(P>0.05),but the fluoroscopy times of patients in group A was less than that in group B,the intraoperative bleeding volume and fibular incision length were less/shorter than those in group B(P<0.05).The AOFAS scores of patients 6 months after surgery and at the last follow-up in both groups increased compared with those 3 months after surgery,and the AOFAS scores at the last follow-up were higher than those 6 months after surgery,the differences were statistically significant(P<0.05).The AOFAS scores of patients 6 months after surgery and at the last follow-up in group B were higher than those in group A(P<0.05).There was no statistically significant difference in ROM score of ankle joints(plantar flexion,valgus,varus,dorsiflexion)of patients between the two groups at the last follow-up(P>0.05).There was no statistically significant difference in poor screw position,degree of pain,walking condition,or squatting condition of patients between the two groups(P>0.05).However,the reduction quality of posterior ankle fractures of patients in group B was better than that in group A(Z=4.248,P<0.05).No complications such as loosening of internal fixation or loss of fracture reduction occurred in both groups.Conclusion Both percutaneous anterior to posterior screw internal fixation and percutaneous posterolateral approach limited exposure and reduction screw internal fixation have good efficacy for posterior ankle fractures in trimalleolar fracture,with high safty.The former has more fluoroscopy times and less intraoperative bleeding,while the latter is better in improving ankle joint function and fracture reduction.

Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells(VSMCs)induced by homocysteine(Hcy).Methods Human VSMCs were cultured in vitro and divided into a Control group(0 μmol/L Hey)and a Hey group(100 μmol/L Hey).After intervention,expression levels of pro Caspase-1,gasdermin D(GSDMD),N-GSDMD,and NLR family pyrin domain containing 3(NLRP3)were detected by Western blot.MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction.Interleukin(IL)-1 β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay.Cells were also transfected with control miR-22-3p(miR-22-3p-NC),miR-22-3p-mimic,and miR-22-3p-inhibitor,to observe the effects on VSMC pyroptosis induced by Hcy.Results Expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs were increased(P＜0.05),IL-1 β and IL-18 levels were increased(P＜0.01),and the relative expression level of miR-22-3p was reduced(P＜0.01)in the Hcy group compared with the Control group.Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01),and significantly decreased levels of IL-1β and IL-18(P＜0.01),while transfection with miR-22-3p-inhibitor significantly increased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01)and significantly increased the levels of IL-1β and IL-18(P＜0.05).Conclusions MiR-22-3p may delay Hcy-induced VSMC pyroptosis.