Objectives:To establish a comprehensive system of Cardiovascular Academic Performance Evaluation(CAPE)and rank global TOP100 medical institutions in the fields of cardiovascular diseases(CVD). Methods:CVD-related terms were extracted from Medical Subject Headings(MeSH),Embase thesaurus(EMtrees)and International Classification of Diseases(ICD)by CVD-related professionals,as well as by librarians and information professionals.Terminology databases(named as Fuwai Subject Headings)were established,and nine sub-disciplines were proposed,including ischemic heart diseases,hypertension,vascular diseases,arrhythmia,pulmonary vascular diseases,heart failure,congenital heart diseases,cardiomyopathy,and valvular heart diseases.The mapping patterns of sub-discipline,cardiovascular terminology and entry terms were pre-defined.The CVD-related research literature published from January 1,2016 to December 31,2022 were retrieved from Web of Science,PubMed and Scopus.Based on this,metadata were fused and duplicates were excluded.Fuwai Subject Headings were searched and matched into four respects for each literature,including subject words,titles,keywords,and abstracts,which was used to generate an information table of"Position—CVD terminology—Frequency",and to calculate CVD correlation scores and sub-discipline scores.We standardized the names of medical institutions and scholars,and make a ranking system for CAPE based on original articles with strong cardiovascular correlation(correlation score≥4).When evaluating the science and technological performance for Chinese hospitals in cardiovascular diseases,National Natural Science Foundation Projects,authorized invention patents,prize achievements,research platforms,and registered data of drug clinical trials in Center for Drug Evaluation(CDE)were considered besides research papers. Results:During 2016 and 2022,1 545 103 CVD research literatures were found worldwide.After excluding meeting abstracts,books,biographies,news,videos,audio texts,retracted publications,and corrections,1 178 019 CVD research literatures were further evaluated.518 058 literatures were indexed as"strongly correlated to CVD"using Fuwai Subject Headings.Besides papers,other data sources were also collected,including 11 143 CVD-related Natural Science Foundation Projects,19 382 CVD-related effective authorized invention patents,103 CVD-related national prize achievements,24 CVD-related national research platforms,and 2 084 CDE registered data of CVD-related drug clinical trials.Research teams from nine sub-disciplines reviewed and validated research literature in respective fields,and classification rules of corresponding sub-disciplines were created and improved based on their opinions.Finally,eleven individual indexes were chosen to construct CAPE system for ranking global TOP100 medical institutions in overall CVD field and TOP30 in nine sub-disciplines.From 2016 to 2022,the number of cardiovascular disease research papers published by Chinese institutes has increased by 123.5%,with a total of approximately 76.8 thousands papers published(about 30 papers per day on average),ranked the second under the United States(approximately 114.1 thousands papers).However,the proportion of papers published by the Chinese Journal Citation Reports(JCR)and the Chinese Academy of Sciences only ranked eighth in the world.In the comprehensive academic performance of original cardiovascular research papers in global hospitals from 2020 to 2022,only two Chinese medical institutions ranked in the TOP20 as evaluated by CAPE system. Conclusions:Based on multi-source data from 2016 to 2022,CAPE initiated to establish a cardiovascular academic performance evaluation system.

Objective:To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO 3) and its related mechanism. Methods:Sixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO 3 group, and ASA group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO 3 group and AS-A group were intraperitoneally injected with 100 μl NaIO 3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 ( Ccl2), interleukin-1 beta ( Il-1β), mixed lineage kinase domain-like protein ( Mlkl), receptor-interacting protein kinase 3 ( Ripk3), and tumor necrosis factor ( Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. Results:Fundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO 3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO 3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO 3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO 3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences ( t=2.66, P<0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO 3 group, with statistically significant differences ( F=39.18, 10.66, 53.51, 41.40, 24.13; P<0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO 3 group was significantly increased, and the difference was statistically significant ( F=9.62, P<0.05). Conclusion:AS-A antagonizes NaIO 3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO 3-triggered perturbation of retinal homeostasis.

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Carnosic acid (CA) is a natural phenolic diterpene compound found in rosemary (Rosmarinus officinalis) characterized as an ortho-dihydroquinone - type molecule. Multiple lines of studies have shown that CA has potent neuroprotective effects in vitro and in vivo in Parkinson's disease (PD). The aim of the present review is to summarize the pharmacological neuroprotective actions of CA, and provide a comprehensive review of the molecular mechanism by which CA exert neuroprotective effect in PD. The current review highlights CA is a therapeutic potential for PD.

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
Angiogenic Proteins/therapeutic use* ; Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Endothelial Cells ; Humans ; Nanoparticles ; Nucleic Acids/therapeutic use*

Objective:To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis (AD).Methods:Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group,whole formula group (WF),exterior-releasing formula group (ERF),interior-clearing for-mula group (ICF),and positive control group (PC).A mouse model of AD was established using the semi-antigen 2,4-dinitrofluorobenzene induction method.The lesion scores,transepidermal water loss and pH,and skin histopathology of mice in each group were observed.The expressions of filaggrin,loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting,and their mRNA expressions were detected by quantitative polymerase chain reaction.Results:Mice in the WF,ERF,ICF,and PC groups showed reduced skin lesion performance,improved histopathology,decreased skin lesion score,transepidermal water loss and pH,and upregulated ex-pressions of proteins including filaggrin,loricrin,and involucrin,and their mRNAs.The most obvious regulatory effect was observed in the WF group,followed by the ICF,ERF,and PC groups,accordingly.Conclusions:Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin,loricrin,and involucrin,and their mRNA expressions,and the most optimal effect was noted in the WF group,followed by the ICF and ERF groups,which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Endo-β-N-acetylglucosaminidase is used widely in the glycobiology studies and industries. In this study, a new endo-β-N-acetylglucosaminidase, designated as Endo SA, was cloned from Streptomyces alfalfae ACCC 40021 and expressed in Escherichia coli BL21 (DE3). The purified recombinant Endo SA exhibited the maximum activity at 35 ºC and pH 6.0, good thermo/pH stability and high specific activity (1.0×10⁶ U/mg). It displayed deglycosylation activity towards different protein substrates. These good properties make EndoSA a potential tool enzyme and industrial biocatalyst.
Cloning, Molecular ; Enzyme Stability ; Escherichia coli ; genetics ; Gene Expression ; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Streptomyces ; enzymology ; genetics

Objective:To evaluate the clinical significance of endoscopic vidian neurectomy (EVN) on outcomes in patients with coexisting refractory allergic rhinitis (AR) and bronchial asthma, and to analyze its influence factor.Methods:Clinical data of 109 patients with moderate to severe persistent intractable AR and bronchial asthma who were allocated to the bilateral EVN group (surgery group, 70 cases) or conservative medication group (drug group, 39 cases) from 1 May 2008 to 30 April 2013 in Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University were retrospectively analyzed, including 47 cases of male and 62 cases of female aged (32.7±6.8) years.Ninety-five patients were followed up for at least 3 years. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Visual Analog Scale (VAS), Asthma Quality of Life Questionnaire (AQLQ), Total Asthma Symptom Score (TASS), forced expiratory volume in 1 second of predicted (FEV1) and medication scores were evaluated at 6 months, 1 year and 3 years after undergoing the initial treatments in the two groups. Multiple factor analysis was used to determine the factors influencing the improvement after EVN.Results:Postoperative scores of RQLQ were significantly lower than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 2.39±0.61 ( ± s), 0.81±0.43, 0.89±0.32, 1.06±0.24, respectively, all P<0.001). Postoperative scores of VAS were significantly lower than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year,3 years after operation was 7.13±1.04, 2.52±1.47, 2.70±1.42, 2.85±1.64, respectively, all P<0.05). Scores of RQLQ and VAS in surgery group were significantly lower than those of drug group. Postoperative scores of AQLQ were significantly higher than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 3.78±0.81, 4.99±0.45, 4.75±0.71, 4.62±0.64, respectively, all P<0.05), and were significantly higher than those of drug group. The TASS and FEV1 were not significantly changed in surgery group. The postoperative medication scores for AR were gradually reduced after surgery (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 0.99±0.21, 0.37±0.12, 0.39±0.26, 0.45±0.11, respectively, all P<0.05), and the postoperative medication scores for Asthma were gradually reduced after surgery too (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 1.27±0.31, 0.82±0.29, 0.85±0.23, 0.96±0.19, respectively, all P<0.05), and all the postoperative medication scores were significantly lower than those of drug group. At the end of the follow-up, the improvement rates for AR and asthma were 90.6% (58/64) and 45.3% (29/64), respectively. Asthma outcomes were significantly improved by controlling rhinitis symptoms in patients whose asthma attacks were induced by "rhinitis onset" or "climate change" . Conclusion:For patients with AR and bronchial asthma, EVN can significantly control AR symptoms, and improve asthma outcomes in patients whose asthma attacks are induced by rhinitis onset and/or climate change.

Objective:To explore the application of games combined with speech training in rehabilitation care for language development retardation in high-risk children aged 2 to 5 years.Methods:Totally 190 high-risk children aged 2 to 5 years with language development retardation admitted from January 2016 to December 2018 in Luzhou People's Hospital were selected by convenient sampling, and divided into observation group ( n=95) and control group ( n=95) according to the random number table. Children in the control group received conventional speech training, while children in the observation group received speech training combined with games for 6 months. The effects of rehabilitation training were observed in the two groups, and the speech development quotient of the children was evaluated using the Gesell Developmental Schedules (GDS) . The satisfaction rate to rehabilitation of parents of two groups were compared. Results:After 6 months of training, the effective rates of rehabilitation training were 86.32% (82/95) in the observation group and 73.68% (70/95) in the control group, and the difference was statistically significant ( P<0.05) . The GDS scores were (60.36±8.25) in the observation group and (56.67 ± 7.84) in the control group, and the difference was statistically significant ( P<0.05) . The satisfaction rate of parents of children in the observation group on rehabilitation effect, service attitude, professional skills, and humane care were higher than those in the control group, and the differences between the two groups were statistically significant ( P<0.05) . Conclusions:In high-risk children aged 2 to 5 years with language development retardation, speech training combined with games can improve children's speech development quotient and promote their rehabilitation.