OBJECTIVE To evaluate the efficacy and safety of three aromatase inhibitors （exemestane， anastrozole， letrozole） for postmenopausal hormone receptor （HR）-positive early breast cancer. METHODS PubMed， the Cochrane Library， Embase， CNKI， Wanfang Data， VIP and SinoMed were searched to collect randomized controlled trials （RCTs） of the above three drugs in the treatment of postmenopausal HR-positive early breast cancer patients. The retrieval time limit was from the establishment of the database to October 25， 2024. After literature screening， data extraction and literature quality evaluation， network meta-analysis was performed by using RevMan 5.3 and Stata 18.0 software. RESULTS A total of 15 RCTs involving 44 055 patients were included. The results of network meta-analysis showed that the objective response rate of letrozole group was significantly higher than anastrozole group （P＜0.05）， and the order of surface under the cumulative ranking curve （SUCRA） from high to low was letrozole （85.6%）＞anastrozole （61.5%）＞exemestane （2.8%）. The disease-free survival rate of anastrozole group was significantly higher than exemestane and placebo groups （P＜0.05）， and the order of SUCRA from high to low was letrozole （85.8%）＞ anastrozole （67.3%）＞exemestane （41.4%）＞placebo （5.5%）. The total incidence of adverse reactions in anastrozole group was significantly higher than letrozole and placebo groups （P＜0.05）， and the order of SUCRA from high to low was exemestane （87.4%）＞letrozole （63.9%）＞anastrozole （47.0%）＞placebo （1.7%）. The results of subgroup analysis according to the course of treatment≥104 weeks were consistent with them. CONCLUSIONS Compared with anastrozole， letrozole has better efficacy and safety in the treatment of postmenopausal HR-positive early breast cancer， and the efficacy of exemestane is limited.

To ensure the rights and safety of the subjects and improve the quality of clinical trials, the author analyzed and discussed the deviation type and typical cases from 184 cases of protocol violation reviewed by the ethics committee in 56 clinical trials in a tertiary hospital in 2020. Among the 184 cases of violating the protocol, there were 29 major protocol violation cases and its proportion is 16%; 99 cases (54%) violated the GCP principle; 56 cases of other violations of the protocol that require to be reported, accounting for 30%. Through the case analysis of the researcher gave the wrong doses to subjects without following the protocol and drug administration did not conform to the rules, analyzed and discussed from the five perspectives of the research protocol design, the researcher, the clinical trial institution, the sponsor and the ethics committee, and put forward solutions and suggestions, so as to provide reference to improve the compliance of clinical trial protocol, reduce the risk of subjects and protect their rights and safety and ensure the successful progress of clinical trials.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

Objective The objective of this study is to investigate whether there is a correlation between a high TyG index(serum triglyceride glucose index)and higher mortality rates among patients undergoing peritoneal dialysis(PD).Methods This study utilized a single-center retrospective cohort as the basis for its methods..From January 1,2007 to December 31,2015,a total of 519 PD patients kept under observation until December 31,2018.There searchers employed the Kaplan-Meier method and Cox proportional hazards modelsto examine the cor-relation between TyG index levels and mortality.Results Over a period of 40.5 months,104(20.0%)individuals with Parkinson's disease passed away,with 55(52.9%)of these deaths attributed to cardiovascular disease(CVD).The serum median TyG index at baseline was 8.44(6.48,11.94).Through Cox regression analysis subject to the adjustments of such parameters as gender,age,body mass index(BMI),presence of cardiovascular disease,hypertension,diabetes mellitus,hemoglobin,serum albumin,serum Ferritin,total cholesterol,renal residual function(RRF),An increased risk of all-cause mortality(HR = 2.22,95%CI:1.43～3.44,P＜0.001)and CVD mortality(HR = 2.50,95%CI:1.34～4.65,P = 0.004)was observed with a higher baseline TyG index(8.44).A comparable impact was observed in the correlation between the average TyG index over time(TA-TyG index)and both all-cause mortality and CVD mortality.(HR = 1.90,95%CI:1.25～2.90,P = 0.003;HR = 2.05,95%CI:1.14～3.70,P = 0.017,respectively).Conclusion PD patients with a higher serum TyG index have a greater risk of all-cause mortality and mortality related to cardiovascular disease.

Organoids are a novel disease model that is self-assembled from stem cells or malignant tumors and is used in clinical research.They are similar to tissues and organs in the body and have partially functional 3D cell structures.There are two types of traditional models for liver cancer research,i.e.,in vivo models(animal models of liver cancer established by induction)and in vitro cell experiments using corresponding cell lines.Organoids have the advantages of the two types of traditional models and show unique advantages in tumor research.Traditional models cannot fully reflect the microenvironment of cells,which often leads to the inconsistency with clinical research findings,and the emergence of new research models provides a new direction for the research on liver cancer.This article reviews the research advances in liver cancer organoids,in order to provide a new perspective for future research on liver cancer.

Brucellosis is a zoonotic infectious disease caused by Brucella infection. So far, animal to animal Brucellosis has not been eradicated, and there is a lack of safe and effective human vaccine. Therefore, "early, combined, sufficient, and full course" drug treatment remains an important strategy in the management of human Brucellosis. The goal of treating brucellosis is to alleviate and shorten the symptom period, reduce complications, relapses, and chronicity. At present, although antibiotic treatment is effective for most patients, there are still some patients who experience treatment failure or later recurrence, so the treatment strategy for brucellosis urgently needs to be optimized. This article elaborates on the treatment principles, clinical treatment status, and future development trends of brucellosis, in order to provide references for optimizing drug treatment methods for brucellosis.

Acute lung injury (ALI), in which various factors inside and outside the lung lead to hypoxemic respiratory insufficiency and even the development of acute respiratory distress syndrome, has a high morbidity and mortality rate, and its pathogenesis is characterized by complex signaling pathways and limited therapeutic options. A large number of studies have reported that nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), vascular endothelial growth factors (VEGF) and JAK/signal transducer and activator of transcription (STAT) signaling pathways are all related to the inflammatory response of ALI, and they are involved in regulating the inflammatory response process of ALI individually or cooperatively. Therefore, this article reviews the research progress on the pathogenesis-related signaling pathways and the drug interventions, aiming to provide a reference for early intervention in lung injury, optimizing the donor pool to increase the proportion of donation after cardiac death and providing quality donor protection conditions.

Objective:To discuss the alleviative effect of ginsenoside Rg1 on chronic intermittent hypoxia(CIH)-induced brain injury in the mice,and to clarify its possible mechanism.Methods:Forty male C57BL/6 mice were randomly divided into control group,model group,inhibitor group(treated with calpain-1 inhibitor),low dose of ginsenoside Rg1 group(treated with 10 mg·kg-1 ginsenoside Rg1),and high dose of ginsenoside Rg1 group(treated with 20 mg·kg-1 ginsenoside Rg1).Except for the control group,the mice in all other groups were placed in a hypoxic chamber with automatically regulated oxygen concentration to induce hypoxic brain injury.The peripheral blood oxygen saturation(SpO2)of tail of the mice in various groups was detected;the escape latencies and path lengths and the frequency of swimming route crossing the target quadrant of the mice in various groups were determined by Morris water maze test;the levels of blood urea nitrogen(BUN),lactate(LA),malondialdehyde(MDA),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and the activities of superoxide dismutase(SOD)and lactate dehydrogenase(LDH)in serum of the mice in various groups were detected by kits;the degrees of brain tissue injury of the mice in various groups were observed by HE staining.The levels of reactive oxygen species(ROS)in CA1 region of hippocampus tissue of the mice in various groups were detected by dihydroethidium(DHE)probe;the expression levels of calpain-1,IL-6,and TNF-α proteins in brain tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the SpO2 of the mice in model group was significantly decreased(P＜0.01),indicating that the model was successfully established.Compared with model group,the SpO2 of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly increased(P＜0.01).The Morris water maze test results showed that compared with control group,the escape latency and path length of the mice in model group were significantly prolonged(P＜0.01),and the frequency of swimming route of crossing the target quadrant was significantly decreased;compared with model group,the escape latencies and path lengths of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly shortened(P＜0.01),and the frequency of swimming route of crossing the target quadrant was significantly increased.Compared with control group,the levels of BUN,LA,MDA,IL-6,and TNF-α in serum of the mice in model group were significantly increased(P＜0.01),while the activity of LDH was significantly increased(P＜0.01),and the activity of SOD was significantly decreased(P＜0.01);compared with model group,the levels of BUN,LA,MDA,IL-6,and TNF-α in serum of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly decreased(P＜0.01),while the activities of LDH were significantly decreased(P＜0.01),and the activities of SOD were significantly increased(P＜0.01).The HE staining results showed that compared with control group,the pyramidal neurons in CA1 region of hippocampus tissue of the mice in model group were loosely arranged,while some neurons were triangular,with nuclear pyknosis,cytoplasmic hyperchromasia,and a few neurons were lost,indicating obvious hypoxic neuronal injury;compared with model group,the hypoxic neuronal injury in CA1 region in hippocampus tissue of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group was effectively alleviated.The DHE probe detection showed that compared with control group,the level of ROS in CA1 region in hippocampus tissue of the mice in model group was significantly increased(P＜0.01);compared with model group,the levels of ROS in CA1 region in hippocampus tissue of the mice in inhibitor group,low dose of ginsenoside Rg1 group and high dose of ginsenoside Rg1 group were significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of calpain-1,TNF-α,and IL-6 proteins in hippocampus tissue of the mice in model group were significantly increased(P＜0.01);compared with model group,the expression levels of calpain-1,TNF-α,and IL-6 proteins in hippocampus tissue of the mice in inhibitor group,low dose of GRg1 group and high dose of GRg1 group were significantly decreased(P＜0.01).Conclusion:Ginsenoside Rg1 can alleviate brain tissue injury of the mice induced by CIH;its mechanism may be related to the inhibition of brain tissue inflammatory response and oxidative stress,and the downregulation of calpain-1 expression.

Objective:To explore the clinical efficacy of the San Diego osteotomy in treating developmental dysplasia of the hip (DDH) in children.Methods:A retrospective analysis was conducted on 33 pediatric cases of posterolateral acetabular dysplasia treated with the San Diego osteotomy at the 920th Hospital of the People's Liberation Army Joint Logistics Support Force in China from August 2018 to August 2022. The cohort included 3 males (4 hips) and 30 females (36 hips), with an average age of 4.9±1.4 years (range, 2-8 years). Among these, 32 cases (38 hips) were diagnosed with DDH, and 1 case (2 hips) with paralytic dislocation of the hip. According to the T?nnis classification, 3 hips were classified as type II, 25 hips as type III, and 12 hips as type IV. The San Diego osteotomy technique was utilized to enhance the posterior lateral acetabular coverage, combined with femoral osteotomy to adjust the hip abduction, flexion, and adduction angles. Postoperative outcomes were assessed using the modified Severin radiographic classification and the McKay grading system.Results:All 33 patients were followed up for an average of 37.70±18.44 months (range, 12-74 months). No cases of postoperative hip redislocation or residual acetabular underdevelopment were observed. The hip abduction angle improved from 24.98°±3.48° at 6 weeks postoperatively to 37.28°±4.63° at the 3-month follow-up, and 64.05°±3.82° at the 6-month follow-up, with a statistically significant difference ( F=77.327, P<0.001). The hip flexion angle increased from 26.34°±5.05° at 6 weeks postoperatively to 76.53°±4.38° at 3 months, and 106.47°±2.29° at 6 months, also showing a statistically significant difference ( F=54.377, P<0.001). The hip adduction angle progressed from 1.73°±1.18° at 6 weeks postoperatively to 12.33°±1.97° at 3 months, and 29.03°±4.17° at 6 months, with a significant difference ( F=45.162, P<0.001). The McKay hip joint grading system indicated 11 excellent, 20 good, and 9 acceptable outcomes, yielding an overall excellent and good rate of 78%. The Severin radiographic grading revealed 16 hips at grade I and 24 hips at grade II. Five patients (5 hips) experienced transient vascular compromise of the femoral head at 3 months postoperatively, which resolved after a 1-month non-weight-bearing period. At the final follow-up, one patient had residual femoral head enlargement in the right hip, while the remaining 32 cases showed satisfactory ossification and remodeling of the femoral head. Conclusion:The San Diego osteotomy significantly enhances hip joint range of motion and results in satisfactory hip joint function in children with developmental dysplasia of the hip

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.