OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of tirzepatide for diabetes mellitus type 2 （T2DM） and long-term weight management， and provide evidence-based basis for clinical drug treatment and health insurance policy formulation. METHODS Computer searches were conducted in Embase， PubMed， the Cochrane Library， CNKI and health technology assessment （HTA） official website from their inception to October 1st 2024 to collect HTA report， systematic review/ meta-analysis and pharmacoeconomic study on tirzepatide for the treatment of T2DM or for weight management. After data extraction and quality evaluation， descriptive analysis was performed on the research results. RESULTS Totally 18 papers were included， including 14 systematic reviews/meta-analyses and 4 pharmacoeconomics studies， and no HTA report was retrieved. In terms of efficacy， most results showed that the tirzepatide 10 mg and 15 mg were significantly better than other glucagon-like peptide-1 （GLP-1） receptor agonists in reducing glycosylated hemoglobin， body weight， and waist circumference （P＜0.05）. In terms of safety， compared with other GLP-1 receptor agonists， tirzepatide did not increase the incidence of gastrointestinal-related adverse events （AE）， the incidence of AE of grade ≥3， or the incidence of severe hypoglycemia （P＞0.05）. However， tirzepatide 15 mg may significantly increased the incidence of hypoglycemia and the rate of discontinuation due to adverse reactions （P＜ 0.05）. In terms of cost-effectiveness， based on the background of foreign pharmacoeconomic studies， tirzepatide was more cost- effective compared to semaglutide and liraglutide in the treatment of T2DM or for weight management. CONCLUSIONS Tirzepatide at doses of 10 mg and 15 mg has good efficacy and safety for the treatment of T2DM and for long-term weight management. However， when using the 15 mg dose of tirzepatide， close monitoring is required due to the risk of hypoglycemia and discontinuation due to adverse reactions it may pose. Based on pharmacoeconomic studies conducted abroad results， tirzepatide exhibits economic advantages.

Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

Objective　This study aimed to investigate the epidemiological characteristics, recombination patterns, and mutation variations of Coxsackievirus A6 (CV-A6) based on whole-genome sequences of CV-A6 collected from Anhui Province from 2022 to 2023, to understand the relationship between recombination and evolution in CV-A6. Methods　CV-A6-positive samples collected from different regions of Anhui Province during 2022-2023 were subjected to whole-genome sequencing. Genome sequence alignment, phylogenetic analysis, and similarity analysis were conducted using software tools such as MEGA11, SimPlot, and DNAstar. Amino acid mutation sites in the P1-P3 coding regions were also analyzed. Results　A total of 10 CV-A6 isolates were sequenced in this study. The nucleotide and amino acid sequence similarity among the 10 isolates ranged from 94.0% to 99.7% and 98.3% to 99.9%, respectively. Compared with the prototype strain, their nucleotide and amino acid sequence similarity ranged from 79.6% to 80.1% and 94.8% to 95.1%, respectively. The VP1 phylogenetic tree revealed that all 10 isolates belonged to the D3a subtype, consistent with the genotypic trends observed in recent years in China. Recombination analysis showed that the P1 coding region was relatively conserved, whereas certain levels of recombination events occurred between CV-A6 and other enteroviruses in the P2 and P3 coding regions. Recombination evolution analysis of the 3D region indicated that the CV-A6 strains were divided into two recombinant branches, RF-A and RF-K, with 4 isolates classified as RF-A and 6 as RF-K. Amino acid mutation site analysis showed varying degrees of mutations in the P1-P3 regions. Specifically, in the 3D region, RF-A and RF-K recombinant branches displayed different mutation patterns, with 13 unique amino acid mutations observed in the RF-A branch and 6 unique mutations in the RF-K branch. Conclusions　The D3a subtype is the predominant epidemic genotype of CV-A6 in Anhui Province during 2022-2023, and no evidence of emergent new sub-genotypes was observed. However, some mutations may have occurred in the 3D region, indicating potential genetic changes.

BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

Objective:To understand the genome-wide sequence variation and molecular evolution of coxsackievirus A4 (CV-A4) strain in Anhui province, so as to provide a theoretical basis for the pathogenic monitoring and scientific prevention and treatment of hand, foot and mouth disease in the future.Methods:Five CVA4 isolates of 2020 were sequenced by first-generation sequencing method. MEGA11.0 was used to construct a phylogenetic tree based on VP1 region for 5 CV-A4 isolates, 32 CV-A4 strains and Enterovirus A71(EV-A71) prototype strain BrCr, and the isolates and enterovirus A (EV-A) prototype strains based on P1, P2 and P3 regions respectively, and DNAStar was used for amino acid sequence comparison in VP1 region. BioEdit7.2 was used for amino acid displacement entropy analysis and amino acid site entropy mapping. SimPlot3.5 and RDP4 were used for recombination analysis of CV-A4 isolate and EV-A prototype representative strains, and DnaSP6 software was used for selection pressure analysis of isolates and reference representative strains.Results:The phylogenetic tree showed that the isolates belonged to the C2 subtype, which belonged to the same clade as the CV-A4 strain circulating in Chinese mainland, and the amino acid sequence homology of the C2 subtype branch was 97.3%-100%, and the isolates had 6 amino acid variation sites compared with the prototype. The selection pressure analysis showed that the CV-A4 strain of the C2 subtype was affected by negative selection pressure, and there were 25 mutagenic sites in the amino acid sequence in the coding region of the displacement entropy analysis, accounting for 1.14%, and the evolution of the strain mainly depended on recombination. Recombination analysis showed that the isolates recombined with a variety of EV-A prototype strains in the P2 and P3 regions, and the recombination section with the CV-A5 prototype strain was longer, especially in the 3A-3C section, and P1 was a relatively conserved region.Conclusions:CV-A4 has frequent recombination events with other EV-A prototype strains in P2 and P3, and the molecular evolution of CV-A4 in Anhui should continue to be closely monitored.

Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Hyperandrogenism is a common endocrine pathological state in women, and polycystic ovary syndrome is the main cause. Studies have shown that in addition to affecting reproductive function, hyperandrogenism in women can also interfere with vascular endothelial function, and directly or indirectly increases the risk of atherosclerotic disease by affecting risk factors such as blood pressure, lipids, and glucose. This article reviews the impact of hyperandrogenism on the cardiovascular system of women, aiming at a deeper understanding of the role of androgens in women′s health.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Objective:To analyze the selection status of randomized controlled trial (RCT) outcome indicators of TCM for the treatment of adenomyosis (AM) in the past five years; To provide suggestions for the future studies in this field.Methods:The RCTs of TCM for the treatment of AM were retrieved from the databases of CNKI, Wanfang Data, VIP, CBM, PubMed, Embase, the Cochrane Library, Web of Science, Chinese Clinical Trial Register and ClinicalTrials from the establishment of the database to February 28, 2022. The risk of bias was assessed, and the outcome indicators were classified, described and analyzed, and compared with the international core outcome set (COS) studies.Results:A total of 48 studies were included, of which 47 were from published literature and 1 was from registered clinical trials, involving 4 544 patients and 77 outcome indicators. Among the 47 literatures, the total clinical efficacy rate (63.83%) was the most frequently reported outcome indicator, followed by uterine volume (61.70%). Ultrasound examination was the main outcome index in 1 registered trial. Compared with the international COS study, it was found that the included studies paid attention to the outcome report of pain degree, menstrual status and hematological indicators, the reporting rate of quality of life and economic indicators was low, and the urinary system symptoms and fertility outcome indicators were not reported.Conclusion:In the selection of outcome indicators, RCTs of TCM treatment of AM pay attention to the symptoms and signs outcomes, physical and chemical examination outcomes. However, there were still several problems of the selection of outcome measures: unclear primary and secondary outcome indicator, the use of unreasonable composite outcomes, lack of measurement blindness, insufficient attention to endpoint criteria, and ignoring economic evaluation.

Objective:To analyze the current level and dynamic change of the salary and income satisfaction rate of doctors in Chinese tertiary public hospitals in recent years.Methods:In January 2018, March 2019 and March 2021, the project team of " the third party evaluation of the China Healthcare Improvement Initiative" conducted a questionnaire survey among doctors of 136 tertiary public hospitals in 31 provinces. The first-line clinicians were investigated by stratified sampling method. The salary level and satisfaction of doctors were investigated by questionnaire. Chi square test was used for comparison between groups.Results:The sample size of the three surveys was 20 786, 23 289 and 22 836 respectively. The median value of doctors′ actual income after tax in 2017, 2018 and 2020 was 100 800 yuan, 120 000 yuan, 150 000 yuan respectively, and the median expected annual income after tax was 196 000 yuan, 250 000 yuan and 250 000 yuan. The proportion of doctors satisfied with the current income was 16.5%, 17.8% and 26.9% respectively. The salary and satisfaction rate of doctors had an upward trend, but the overall level was still low.Conclusions:In recent years, the salary of doctors in tertiary public hospitals in China has been improved to a certain extent, but on the whole, it is at a low level, and there is still much room for improvement. In the future, the government needs to improve the hospital salary system and increase the salary of doctors continuously, especially needs to pay attention to the doctors with high education level and intermediate titles.