This study investigates the genetic diversity and evolutionary relationships of different Artemisia argyi germplasm resources to provide a basis for germplasm identification, variety selection, and resource protection. A total of 192 germplasm resources of A. argyi were studied, and EST-based simple sequence repeat(EST-SSR) primers were designed based on transcriptomic data of A. argyi. Polymerase chain reaction(PCR) amplification was performed on these resources, followed by fluorescence capillary electrophoresis to detect genetic diversity and construct DNA fingerprints. From 197 pairs of primers designed, 28 pairs with polymorphic and clear bands were selected. A total of 278 alleles were detected, with an average of 9.900 0 alleles per primer pair and an average effective number of alleles of 1.407 2. The Shannon's diversity index(I) for the A. argyi germplasm resources ranged from 0.148 1 to 0.418 0, with an average of 0.255 7. The polymorphism information content(PIC) ranged from 0.454 5 to 0.878 0, with an average of 0.766 9, showing high polymorphism. Cluster analysis divided the A. argyi germplasm resources into three major groups: Group Ⅰ contained 136 germplasm samples, Group Ⅱ contained 45, and Group Ⅲ contained 11. Principal component analysis also divided the resources into three groups, which was generally consistent with the clustering results. Mantel test results showed that the genetic variation in A. argyi populations was to some extent influenced by geographic distance, but the effect was minimal. Structure analysis showed that 190 germplasm materials had Q≥ 0.6, indicating that these germplasm materials had a relatively homogeneous genetic origin. Furthermore, 8 core primer pairs were selected from the 28 designed primers, which could distinguish various germplasm types. Using these 8 core primers, DNA fingerprints for the 192 A. argyi germplasm resources were successfully constructed. EST-SSR molecular markers can be used to study the genetic diversity and phylogenetic relationships of A. argyi, providing theoretical support for the identification and molecular-assisted breeding of A. argyi germplasm resources.
Artemisia/classification* ; Microsatellite Repeats ; Genetic Variation ; Expressed Sequence Tags ; DNA Fingerprinting ; Phylogeny ; Polymorphism, Genetic ; DNA, Plant/genetics* ; Genetic Markers

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

ObjectiveTo investigate the mechanism of astragaloside-Ⅳ （AS-Ⅳ） in regulating pyroptosis to alleviate intestinal ischemia-reperfusion injury （IRI） by combining network pharmacology and in vivo experiments. MethodFirstly， the corresponding target genes of AS-Ⅳ were obtained from TraditionalChineseMedicineSystemsPharmacology（TCMSP） database and Swiss Target Prediction database， and the target genes related to intestinal IRI and Pyroptosis were obtained from GeneCards database， and the common target genes of the three were obtained by drawing Venn diagrams through unspiralized website. Protein-protein interaction （PPI） network was constructed by STRING database and Cytoscape software to screen common target genes and imported into Cytoscape software to obtain core target genes. Microbiotics platform was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis and prediction of the mechanism of action of AS-Ⅳ in regulating Pyroptosis to alleviate intestinal IRI. Then C57/BL6J mice were randomly divided into 5 groups normal group， model group（IR）， drug administration group （IR+AS-Ⅳ）， nucleotide-binding oligomerization structural domain-like receptor protein 3 （NLRP3） agonist NSS group （IR+AS-Ⅳ+NSS）， and NLRP3 inhibitor MCC950 group （IR+AS-Ⅳ+MCC950） by using a randomized numerical table method. The intestinal IRI model was established by clamping the superior mesenteric artery for 45 min and resuming perfusion for 2 h in the model group， the drug administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group， and the normal group was only separated from the vessels without clamping. The administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group were gavaged with astragaloside dissolved in 0.1% dimethylsulfoxide （50 mg·kg^-1） for 3 consecutive days before modeling， with the last gavage 2 h before modeling， and the remaining two groups were gavaged with equal amounts of saline. The NLRP3 agonist NSS group was injected intraperitoneally with 4 mg·kg^-1 of NSS 1 h before modeling， and the NLRP3 inhibitor MCC950 group was injected intraperitoneally with 10 mg·kg^-1 of MCC950 1 h before modeling.The mice were put to death by reperfusion for 2 h， and intestinal tissues were obtained. The levels of IL-18 and IL-1β were detected by enzyme linked immunosorbent assay（ELISA）， and the protein expression of thioredoxin-binding protein （TXNIP）， NLRP3， Caspase-1 and pyrocatechin D （GSDMD） were detected by Western blot， and the pathological changes of intestinal tissues were evaluated by Chiu's score. ResultNetwork pharmacological analysis showed that there were 1599 targets of intestinal IRI， 199 targets of AS-Ⅳ action， 197 targets of pyroptosis， and 20 targets common to all three. There were 10 core targets， including NLRP3， TXNIP， silencing information regulator 1 （SIRT1）， high mobility group protein 1 （HMGB1）， interleukin-18 （IL-18）， GSDMD， and metallo matrix protease-9 （MMP-9），et al. The results of in vivo experiments showed that compared with the normal group， Chiu's score was elevated in the model group， the levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of TXNIP， NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the model group，Chiu's score was decreased in the administered group and NLRP3 inhibitor MCC950 group，the level of IL-18，IL-1β inflammatory factors in the intestinal tissue of mice was decreased（P<0.05）， and the level of TXNIP，NLRP3，Caspase-1，GSDMD protein expression was decreased（P<0.05）. Compared with the administered group， Chiu's score was elevated in the NLRP3 agonist NSS group， the levels of IL-18， IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the NLRP3 inhibitor MCC950 group， the NLRP3 agonist NSS group had elevated Chiu's scores， elevated levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues （P<0.05）， and elevated levels of TXNIP，NLRP3， Caspase-1， and GSDMD protein expression （P<0.05）. ConclusionNetwork pharmacological predictions were consistent with the results of in vivo experiments， and astragaloside attenuated intestinal ischemia-reperfusion injury by inhibiting cellular pyroptosis through the TXNIP-NLRP3 signaling pathway.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P＜0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)

Objective To investigate the anesthetic effects and adverse effects of cypropofol and propofol combined with alfentanil,respectively,for gastroenteroscopy.Methods A total of 162 patients who underwent elective gastroenteroscopy at the Gastrointestinal Endoscopy Center of the First Hospital of Lanzhou University from January to February 2024 were enrolled,including 86 males and 76 females,at an age of 18～65 years old,with a BMI value of 18～30 kg/m2,and ASA grade ≤ Ⅱ.They were randomly divided into propofol group(Group P)and cypropofol group(Group C),with 81 cases in each group.All patients were sedated with 0.7 μg/kg alfentanil,and in 30 s later,2 mg/kg propofol and 0.4 mg/kg cypropofol was intravenously dripped into Group P and Group C,respectively.When the modified alertness/sedation score(MOAA/S)≤1,a gastroscope was started to insert.The related indicators,including total procedure time,successful cases of sedation,induction time and awakening time,heart rate,blood pressure,and pulse oximetry saturation were recorded,occurrence of adverse reactions such as hypotension,respiratory depression,injection pain,intraoperative body movement,nausea and vomiting were observed,and the satisfaction of endoscopists and of patients to anesthesia were recorded and compared between the 2 groups.Results There were no statistical differences in the success rate of sedation,induction time and awakening time between the 2 groups.The patients of the Group C had more stable intraoperative vital signs,statistically lower incidences of injection pain,respiratory depression and hypotension(P＜0.05),and increased satisfaction for anesthesia(P＜0.05)when compared with those in Group P.No obvious difference were observed in the satisfaction of endoscopist to anesthesia between the 2 groups.Conclusion In combination with small-dose alfentanil,0.4 mg/kg cypropofol shows similar sedation effect as 2 mg/kg propofol in gastroenteroscopy,with comparable induction and awakening time.Cypropofol has more advantages in stable intraoperative vital signs,less adverse effects such as low blood pressure,respiratory depression and injection pain,higher the patient satisfaction,which is worthy of clinical promotion.

Objective To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation(MPR),and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population.Methods The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected.Volume reconstruction(VR)and MPR were performed on the skull,and 160 cranial suture tomography images were generated for each sample.Then the MPR images of cranial sutures were scored according to the closure grading criteria,and the mean closure grades of sagittal suture,coronal sutures(both left and right)and lambdoid sutures(both left and right)were calculated respectively.Finally taking the above grades as independent variables,the linear regression model and four machine learning models for age estimation(gradient boosting regression,support vector regression,decision tree regression and Bayesian ridge regression)were established for northern Chinese Han adults age estimation.The accu-racy of each model was evaluated.Results Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest.All four machine learning models had higher age estimation accuracy than linear regression model.The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years.Conclusion The combination of skull CT-MPR and machine learning model can be used for age esti-mation in northern Chinese Han adults,but it is still necessary to combine with other adult age estima-tion indicators in forensic practice.