The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVE To evaluate the cost-effectiveness of using Bacillus Calmette-Guérin （BCG） versus epirubicin for intravesical perfusion after transurethral resection of bladder tumor （TUR-BT） in patients with intermediate- to high-risk non-muscle- invasive bladder cancer （NMIBC）. METHODS From the perspective of China’s health system， a Markov cohort model was constructed based on the ChiCTR-IIR-16008357 study. Quality-adjusted life years （QALYs） were used as the health outcome measure， with the willingness-to-pay（WTP） threshold set at one time the per capita gross domestic product of China in 2023 （89 358 yuan/QALY）. A cost-utility analysis was used to compare the incremental cost-effectiveness ratio （ICER） of the BCG regimen relative to the epirubicin regimen for intravesical perfusion after TUR-BT in patients with intermediate- to high-risk NMIBC in China. In addition， sensitivity analysis was performed. RESULTS The incremental cost of the BCG regimen compared to the epirubicin regimen was 34 309.51 yuan， with an incremental utility of 0.800 QALYs， resulting in an ICER of 42 871.33 yuan/QALY， which is below the WTP threshold. When the WTP threshold was 89 358 yuan/QALY， the probability that the BCG regimen would be acceptable was 77.70% in the probabilistic sensitivity analysis， higher than that of the epirubicin regimen， and the acceptability of the BCG regimen increased with increasing in the WTP threshold. CONCLUSIONS When the WTP threshold was set at one time the per capita gross domestic product of China in 2023， compared to epirubicin， BCG used for intravesical perfusion after TUR-BT in patients with intermediate- to high-risk NMIBC demonstrated better cost-effectiveness.

Objective:To explore genes related to costimulatory molecule related to the prognosis of bladder cancer,and to construct and evaluate prognosis model based on costimulatory molecule-based signature(CMS).Methods:Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database(GSE31684),and costimulatory molecule-related genes were retrieved from the literature.The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model.Forecast accuracy of model was verified in TCGA training group,TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve(ROC).Considering risk score and clinical characteristics,we constructed a nomogram and evaluated its performance by consistency analysis and ROC.CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration,and gene set enrichment analysis(GSEA)was performed to explore the potential mechanism.Results:Four prognostic-related CMSs were found:TNFRSF14,CD276,ICOS and TMIGD2,of which three were included in the risk score construction.Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients.Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy.Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state.GSEA results suggested that genes in high risk group were enriched in extracel-lular matrix(ECM)receptors interaction,cell cycle and other pathways.Conclusion:TNFRSF14,CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients.CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment.

Cardial troponin I(cTnI)is the preferred serological marker for the diagnosis of myocardial injury.cTnI detection is based on antibody sandwich immunoassay.The epitopes of cTnI antigen targeted by detecting and capturing antibodies in different detection reagents are inconsistent,which easily leads to the heterogeneity of cTnI detection results.Endogenous interfering factors such as cTnI autoantibody,heterophile antibody,rheumatoid factor,ect,which can seriously interfere with the results of cTnI detection,and affecting the clinical diagnosis,treatment and prognosis of myocardial injury diseases.In this paper,the research progress of antibody sandwich immunoassay for cTnI and interference of endogenous factors on cTnI detection and solutions are reviewed to provide theoretical basis for differential diagnosis of abnormal cTnI detection results in clinical practice.

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

The outbreak of novel coronavirus (SARS-CoV-2) infection has brought great harm to people's life and social development. Although SARS-CoV-2 infection is more common in mild patients at present, considering the characteristics of crtical disease, rapid progress and high mortality, the treatment of critical patients are the focus of clinical attention. Immune imbalance which is characterized by cytokine storm plays a vital role in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), extrapulmonary multiple organ failure and even death. Therefore, the application of immunosuppressive agent in crtical coronavirus disease patients has a promising prospect. In this paper, different immunosuppressive agents and their application in crtical SARS-CoV-2 infection are reviewed, so as to provide reference for crtical coronavirus disease therapy.

Objective:To systematically evaluate the efficacy and safety of iGlarLixi in the treatment of type 2 diabetes, providing evidence-based support for rational clinical medication.Methods:A systematic review was conducted by retrieving articles from PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang, and VIP databases to collect randomized controlled trials comparing the efficacy and safety of iGlarLixi(intervention group) with placebo or other anti-hyperglycemic drugs(control group) in the treatment of type 2 diabetes. The search was conducted from the inception of the databases up to August 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using RevMan 5.4 software. Results:A total of 11 studies with 6 392 patients were included in the meta-analysis. The results of the meta-analysis showed that in terms of efficacy, compared to insulin and GLP-1RAs, iGlarLixi demonstrated better reduction in patients′ HbA 1C levels(Insulin group WMD=-0.40, 95% CI -0.54--0.27, P<0.001; GLP-1RAs group WMD=-0.86, 95% CI -1.05--0.68, P<0.001), increased HbA 1C target rate(Insulin group OR=2.83, 95% CI 2.00-3.99, P<0.001; GLP-1RAs group OR=6.45, 95% CI 4.81-8.64, P<0.001), increased HbA 1C control rate without weight gain(Insulin group OR=3.00, 95% CI 2.43-3.71, P<0.001; GLP-1RAs group OR=2.67, 95% CI 1.76-4.06, P<0.001). Furthermore, iGlarLixi showed an advantage in weight reduction compared to the insulin group and demonstrated superior reduction in fasting plasma glucose compared to the GLP-1RAs group. In terms of safety, the incidence of hypoglycemic events in the iGlarLixi group was similar to that in the insulin group, but the incidence of gastrointestinal adverse events was higher than that in the insulin group. There was no difference in the incidence of gastrointestinal adverse events compared with GLP-1RAs, but the incidence of hypoglycemic events was higher in the iGlarLixi group. The incidence of serious adverse events was similar to that in the insulin and GLP-1RAs groups(Insulin group OR=0.94, 95% CI 0.71-1.23, P=0.640; GLP-1RAs group OR=0.97, 95% CI 0.61-1.52, P=0.880). Conclusion:iGlarLixi is superior to insulin but inferior to GLP-1RAs in reducing body weight, and the overall incidence of adverse events is not significantly different from that of insulin and GLP-1RAs, indicating that iGlarLixi is well tolerated and safe, and has a good clinical application prospect.