OBJECTIVE To evaluate the efficacy and safety of guideline-directed medical therapy （GDMT） combined with vericiguat in treating heart failure with reduced ejection fraction （HFrEF）. METHODS A retrospective study was conducted on 346 patients with HFrEF who received standardized diagnosis and treatment at the First People’s Hospital of Changzhou from January 2023 to May 2024. They were divided into standard treatment group （n＝215） and vericiguat group （n＝131）. Patients in the standard treatment group received GDMT， while patients in the vericiguat group received GDMT combined with vericiguat. Propensity score matching （PSM） was used to balance confounding factors between two groups， and the effectiveness （including outcome and prognostic indicators） and safety （occurrence of adverse events） of both groups were evaluated. Kaplan-Meier survival curves for primary and secondary outcome events were drawn， and the influential factors of primary outcome events were screened through univariate and multivariate Cox regression analysis. RESULTS After PSM， there were 100 patients in the standard treatment group and 100 patients in the vericiguat group， and there was no statistically significant differences in baseline data between two groups （P＞0.05）. During a 1-year follow-up， there were statistically significant differences in the cumulative incidence of major outcome events between the standard treatment group and the vericiguat group， cumulative incidence of hospitalization events due to heart failure， changes in N-terminal pro-B-type natriuretic peptide levels before and after treatment between the standard treatment group and the vericiguat group （P＜0.05）. There was no statistically significant difference in the incidence of adverse events between the two groups （P＞0.05）. Multivariate Cox regression analysis results showed that left ventricular ejection fraction ≤35% was a risk factor for the occurrence of major outcome events within 1 year [hazard ratio （HR）＝ 2.090， 95% confidence interval （CI）： 1.175-3.718， P＝0.012]， while the use of vericiguat was a protective factor for the occurrence of major outcome events within 1 year （HR＝0.505， 95%CI： 0.284-0.899， P＝0.020）. CONCLUSIONS Compared with GDMT， GDMT combined with vericiguat can improve the clinical symptoms and prognosis of HFrEF patients， and has good safety.

Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.

Objective:To investigate the difference of condylar bone density,volume and surface area in adult female patients with different vertical skeletal features of skeletal Class Ⅱ.Methods:This study was a retrospective case-control study.150 female patients aged 18-30 years were included as the subjects.Lateral cephalic radiographs were measured and the cases with high angle,average an-gle and low angle of skeletal Class Ⅱ were included and respectively grouped(n=50),the CBCT images were collected,the condyles were reconstructed by Mimics Reseach 20.0 software,the bone density,volume and surface area of the condyles were measured.Univa-riate analysis of variance(ANOVA)was used to compare the difference of condyle measurements among the 3 groups.Results:The overall difference of condylar bone density,volume and surface area among the 3 groups were statistically significant(P＜0.05).Pair-wise comparison showed that the condyle bone mineral density in high angle group was lower than that in average angle group(P＜0.05),in average angle group was lower than that in low angle group(P＜0.05),in high angle group was lower than that in low angle group(P＜0.001).Condyle volume and surface area in high angle group were lower than those in low angle group(P＜0.05),in aver-age angle group was lower than those in low angle group(P＜0.001),in high angle group was lower than those in average angle group(P＞0.05).Conclusion:The condyle bone density,volume and surface area of the different vertical skeletal features of skeletal class Ⅱ in adult female patients are different.

A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.

The essence of clinical practice guidelines lies in their recommendations. It is common to find strong recommendations supported by low-quality evidence in current published guidelines. There is a typical misunderstanding among medical professionals that without high-quality evidence, it is impossible to develop high-quality guidelines or only expert consensus can be developed. Based on the GRADE approach, this paper explains the concept and clinical significance of low-quality evidence, and introduces the methods for formulating recommendations based on low-quality evidence in guidelines, with the aim to provide reference for guideline developers and users in China.

Objective:This study constructs a strategic model for healthy city construction using Hubei Province as a case study,aiming to provide a reference for advancing healthy city initiatives.Methods:Utilizing grounded theory,we analyzed interview data from 9 cities in Hubei.Through open coding,principal axis coding,and selective coding,we identified and refined the strategic components for healthy city construction.Results:The strategies for healthy city construction in Hubei encompasses 30 initial categories,11 main categories,and 3 core categories:government initiative-led,departmental cooperation,and social co-construction and co-governance.This framework culminates in a theoretical model centered on sustainable construction,with the long-term improvement of population health as the ultimate goal.Conclusion:The strategies of government initiative-led,departmental cooperation,and social co-construction and co-governance function synergistically as guiding,implementing,and mobilizing frameworks for healthy city construction.By integrating these strategies,we can promote the sustainability of healthy cities and ultimately achieve long-term improvement of population health level.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.

  Objective  To promote the development of high-quality health standards in China and summarize the characteristics of global health standards management systems and development processes.  Methods  We conducted a systematic search of relevant databases and the websites of standardization institutions. A descriptive method was used to analyze the basic characteristics of the standard management systems and development processes.  Results  The majority of the investigated countries and organizations primarily implement voluntary standards, with the exception of Chinese and the European Committee for Standardization that enforce compulsory standards. All countries and organizations have health standards at the national, group, and enterprise levels. In China and Japan, standards authorities are subordinate to the government, while in other countries or organizations, they operate as independent civil societies. The development process for health standards generally involves five stages: "Project/Proposal → Draft → Enquiry → Review → Publication". However, the specific steps in the development of health standards vary across different countries and organizations. Furthermore, China ranks high in the number of both standards and health standards issued, but the proportion of health standards is only 2.06%.  Conclusions  There are significant differences between China and other countries in terms of the management system and development process of health standards. To promote the management and development of high-quality health standards in China, we recommend promoting the coordination mechanism for standard development, increasing efforts to publicize standards and evaluate the implementation effect, strengthening the construction of personnel for the development of health standards, optimizing the efficiency of standard development and improving the internationalization level of health standards.

With the development of the Scientific, Transparent and Applicable Rankings tool for clinical practice guidelines(STAR), the publication of evaluation and ranking for scientificity, transparency and applicability of Chinese guidelines and consensus published in the medical journals in 2021and 2022, as well as the publication of the STAR evaluation and ranking for some specialities, the STAR evaluation and ranking has received widespread attention in the medical community. In order to further enhance its scientificity and transparency, Methodology and Technology Specialization Committee of the STAR Working Group presents this article to introduce sample identification and speciality assignment in the evaluation and ranking process.