Stroke is one of the most serious complications of transcatheter aortic valve replacement(TAVR),tremendously increasing mortality and the loss of neurocognitive function.Since TAVR is expected to further spread into lower-risk patient groups,there will be greater emphasis to obviate such serious complications.One possible technique for preventing stroke is using cerebral embolic protection devices(CEPDs).CEPDs are designed for capturing or deflecting emboli that are enter route to the brain and hence to protect the brain from embolism.Since this is a rapidly growing field with recent advances,and the impact of CEPD on preventing neurological events is still limited,there is an urgent need for understanding the role of CEPD in preventing clinically significant strokes.Although their clinical utilization is increasing,the risk factors for stroke related to TAVR and evidence for using CEPDs are not yet clear.In this review,we present an overview of the available literature on TAVR related stroke and CEPD,and outline recent advances within this field.

The current production of Chinese herbal decoction pieces faces several issues including strong subjectivity,unstable quality,low production efficiency,and a lack of intelligent systems.In order to expedite the intelligent transformation and upgrading of Chinese medicine processing,this paper delves deeply into the problems and challenges encountered in establishing a digital and intel-ligent production model for Chinese herbal pieces.Addressing the slow progress in fundamental research on traditional Chinese medi-cine processing mechanisms,the absence of online digital quality characterization techniques,the low level of production equipment in-telligence,and the lack of evaluation standards for high-quality decoction pieces,this paper proposes a"New Quality Productive Forces"formation approach driven by technological innovation.Through interdisciplinary integration methods,the paper explores the mechanisms of Chinese medicine processing in depth,clarifies the correlation between the processing procedures and the"medicinal properties-quality"relationship,and employs bionic sensing and artificial intelligence to achieve a holistic quality characterization of decoction pieces.Additionally,the use of cloud-edge collaborative big data systems is proposed to enhance intelligent upgrades of the production lines.The paper also aims to establish a high-quality decoction piece evaluation system integrating"physical-chemical-bio-logical"multimodal data fusion.This approach aims to steer the Chinese medicine processing towards becoming more efficient,precise,and sustainable,thereby promoting high-quality sustainable development of the Chinese herbal decoction industry and providing both theoretical and practical support for the modernization of traditional Chinese medicine.

Objective To understand the distribution and antimicrobial resistance changes of bacteria isolated from pleural and peritoneal effusion in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Provincial Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacteria antimicrobial resistance surveillance method was imple-mented according to technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),and WHO-NET 5.6 software was used to analyze the data of bacteria isolated from pleural and peritoneal effusion as well as antimicrobial susceptibility testing results.Results From 2012 to 2021,a total of 28 934 bacterial strains were iso-lated from specimens of pleural and peritoneal effusions from member units of Hunan Provincial Antimicrobial Re-sistance Surveillance System,with 5 752 strains from pleural effusion and 23 182 from peritoneal effusion.The top five bacteria isolated from pleural effusion were Escherichia coli(n=907,15.8％),Staphylococcus aureus(n=535,9.3％),Klebsiella pneumoniae(n=369,6.4％),Staphylococcus epidermidis(n=452,7.9％),and Staphy-lococcus haemolyticus(n=285,5.0％).The detection rate of methicillin-resistant Staphylococcus aureus(MR-SA)from pleural effusion was 24.3％-39.2％,and that of methicillin-resistant coagulase negative Staphylococcus(MRCNS)was 58.8％-77.1％.The top five bacteria isolated from peritoneal effusion were Escherichia coli(n=8 264,35.6％),Klebsiella pneumoniae(n=2 074,9.0％),Enterococcus faecium(n=1 458,6.3％),Staphylo-coccus epidermidis(n=1 383,6.0％),and Pseudomonas aeruginosa(n=1 152,5.0％).The detection rate of MRSA from peritoneal effusion was 22.1％-52.4％,which presented a decreasing trend(P=0.004).The detec-tion rate of MRCNS was 60.4％-79.4％.The resistance rates of Enterobacterales from peritoneal effusion to ce-fazolin,cefuroxime,ceftriaxone and cefepime all showed decreasing trends(all P＜0.05).Vancomycin-,linezo-lid-,and teicoplanin-resistant Staphylococcus strains were not found in pleural and peritoneal effusions.The resis-tance rates of Enterococcus faecium to most tested antimicrobial agents were higher than those of Enterococcus fae-calis.The resistance rates of Enterobacterales to imipenem and meropenem were ≤8.5％.The resistance rates of non-fermentative Gram-negative bacilli to imipenem and meropenem were ≤43.3％.Conclusion The data structure of Hunan Antimicrobial Resistance Surveillance System for pleural and peritoneal effusions from 2012 to 2021 is relatively complete.The constituent and antimicrobial susceptibility of isolated pathogenic bacteria vary in different years.

In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.
Acetic Acid ; Drugs, Chinese Herbal/analysis* ; Rhizome/chemistry* ; Quality Control ; Electronics

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC₅₀ = 0.33 μmol·L^-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L^-1, 21.2% inhibition at 1 μmol·L^-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group (n=3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups (n=6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups (n=3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group (P<0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased (P<0.01), myocardial fibrosis and hypertrophy were aggravated (P<0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased (P<0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group (P<0.01), myocardial fibrosis and hypertrophy were reduced (P<0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased (P<0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased (P<0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.05), the apoptosis level was decreased (P<0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased (P<0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.

OBJECTIVE: To investigate the clinicopathological features of intestinal diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical features, pathological morphology, immunophenotype, and EBER in situ hybridization of 136 DLBCL patients diagnosed in Jinan People's Hospital Affiliated to Shandong First Medical University from January 2007 to October 2014 were analyzed retrospectively. A total of 136 DLBCL samples were obtained, the DLBCL sites were categorized as: duodenum (n=23), ileocecal region (n=63), other small intestine (n=29), rectum (n=7), and other large intestine (n=14). Survival curves for the DLBCL patients were plotted using the Kaplan-Meier method and judged by the Log-rank test. RESULTS: Patients with DLBCL of the ileocecal region and other small intestine except duodenum were mainly male (P=0.042), and had a higher proportion of limited-stage tumors(P=0.015), and lower International Prognostic Index (IPI) (P=0.001). Patients with DLBCL of ileocecal region had higher incidence of lactate dehydrogenase elevation (P=0.007), and higher incidence of intestinal obstruction or perforation (P<0.001) than those with DLBCL of other regions. The 5-year overall survival and 5-year progression-free survival of patients with DLBCL in ileocecal and other small intestine sites were higher than those in other sites, but the differences were not statistically significant (P=0.135, 0.459). Fifty percent of intestinal DLBCL were germinal center B cell-like (GCB) subtypes. A low-grade B-cell lymphoma was found in 21% of 136 tumor samples. In ileocecal and other small intestinal specimens, the proportion of low-grade B-cell lymphoma was 29%, and the difference was statistically significant(P=0.025). About 16% of 136 DLBCL samples expressed follicular lymphoma while no mucosa-associated lymphoid tissue lymphoma . The Epstein-Barr virus-encoded RNA-1 (EBER1) positive rate of duodenal DLBCL was significantly higher than that of other sites (5/23, 22% vs 2/63, 3%, P=0.001). CONCLUSION The intestinal DLBCL is commonly observed in male, and ileocecal is the most primary site. Patients with DLBCL of the ileocecal region and small intestine except duodenum have low IPI, high proportion of limited-stage tumors, low level of lactate dehydrogenase, high incidence of intestinal obstruction or perforation, and low incidence of inert lymphoma. The EBER1 positive rate of DLBCL in duodenal is higher.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Prognosis ; Retrospective Studies

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Anticoagulants/therapeutic use* ; Atrial Fibrillation/therapy* ; China/epidemiology* ; Humans ; Registries ; Risk Factors ; Stroke