Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Eleven compounds were isolated and purified from the ethyl acetate part of 80% ethanol extract of Ferula feruloides root by a combination of normal-phase silica gel column chromatography, Sephadex LH-20 dextran gel column chromatography and semi-preparative liquid chromatography and then modern wave spectrometry methods (NMR, MS, UV, IR) were used to identify the structures of the compounds, which were identified as baigene D (1), baigene E (2), baigene F (3), β-kirialovin (4), α-kirialovin (5), falcarindiol (6), ammoresinol (7), dshamirone (8), 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-3-[4-methyl-5-(4-methy1-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin (9), 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadi-enyl]-furo[3,2-c]coumarin (10), and baigene C (11). Compounds 1-3 are new coumarin analogues, and compounds 4-6 are firstly isolated from F. feruloides. The anti-proliferative activity of compounds 5, 7-11 against human gastric cancer (MKN-45) cells was evaluated using MTT assay, which showed that compounds 7-11 exhibited strong inhibitory activity, and compound 5 exhibited weak inhibitory activity.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

【Objective】 To understand the obesity status of Kazakh children and adolescents in the agricultural and pastoral areas of Xinjiang and its association with lifestyle, so as to provide reference and help for maintaining good body shape and health intervention for Kazakh children and adolescents in agricultural and pastoral areas. 【Methods】 From April to June 2022, 6 242 Kazakh children and adolescents aged 10 - 20 years were tested for obesity and surveyed by lifestyle questionnaires using stratified whole-group sampling in the farming and herding areas of Yili Kazakh Autonomous Prefecture and Altay Region, Xinjiang. χ² test and Logistic regression analysis were used to analyze data. 【Results】 The obesity detection rate of Kazakh children and adolescents in Xinjiang farming and herding areas was 18.71%, with higher rates in boys (22.24%) compared to girls (15.12%), and the difference was statistically significant (χ² =52.04, P<0.01). Significant differences were observed in the obesity rates based on grade level, fruit consumption frequency, screen time of television, feeling hopeful for the future, fatigue, loneliness, and sadness (χ² =24.29, 4.61, 694.51, 7.15, 10.33, 6.51, 8.07, P<0.01). Logistic regression analysis showed that female students (OR=0.63, 95%CI: 0.56 - 0.69) and students who felt hopeful about the future (OR=0.96, 95%CI: 0.94 - 0.99) were protective factors against obesity (P<0.05); while high school and lower grades (senior high school OR=1.38, 95%CI: 1.24 - 1.57; junior high school OR=1.82, 95%CI: 1.58 - 2.06; primary school OR=2.67, 95%CI: 2.33 - 2.99), fruit consumption ≥1time/d (OR=1.07, 95%CI: 1.03 - 1.16), watching TV ≥2h/d (OR=1.07, 95%CI: 1.02 - 1.17), frequent feeling of fatigue (OR=1.07, 95%CI: 1.03 - 1.12), loneliness (OR=1.08, 95%CI: 1.02~1.19) and sadness (OR= 1.09, 95%CI: 1.04 - 1.14) of students were risk factors for the development of obesity (P<0.05). 【Conclusions】 The obesity rate of Kazakh children and adolescents in the agricultural and pastoral areas of Xinjiang is high and closely associated with lifestyle. Therefore, it is crucial to improve unhealthy lifestyles in order to reduce obesity and promote the physical and mental well-being of this population.

BACKGROUND:Bibliometrics and visual analyses based on thematic literature are particularly important for understanding the foundation and frontiers of postmenopausal osteoporosis research. OBJECTIVE:To perform bibliometric,citation,and visualization analyses of highly cited SCI papers in postmenopausal osteoporosis research over the last 20 years. METHODS:The top 100 highly cited papers on postmenopausal osteoporosis published between 2003 and 2022 included in SCI-EXPANDED catalog of the Web of Science database were obtained for bibliometric measure and visual analysis using CiteSpace software. RESULTS AND CONCLUSION:The top 100 highly cited papers have a total of 67 377 citations in the Web of Science Core Collection,with an annual average of 49.17 citations per paper.Postmenopausal osteoporosis research primarily involves medical,engineering,biological,and multidisciplinary fields.The subcategories are dominated by endocrinology and metabolism,and medicine:internal medicine.Stable and close cooperative network relationships have been formed globally.United States,University of California System,Cummings,and Steven R are the country,research institution,and author,respectively,with the most highly-cited publications.The frontiers of postmenopausal osteoporosis research mainly include calcium and vitamin D supplementation and fracture risk,clinical studies of bisphosphonates in the treatment of postmenopausal osteoporosis,atypical femur fracture,clinical studies of new drugs and sequential treatment of postmenopausal osteoporosis,predictors of fracture risk,mid-and long-term follow-up of osteoporotic vertebral compression fractures,genetic polymorphisms and hereditary factors,formulation and updating of clinical practice guidelines for postmenopausal osteoporosis.Large cohort studies,high-quality randomized controlled trials,systematic reviews,meta-analyses,and clinical practice guidelines are the great engines that drive the development of clinical research in postmenopausal osteoporosis.We should make efforts in the above areas to improve China's international influence in the field of osteoporosis.

Objective To explore the feasibility and accuracy of neutrophil-to-lymphocyte ratio(NLR)in the prediction of testicular torsion(TT)in children with acute scrotal pain.Methods A retrospective case-control study was performed on 158 pediatric patients with ultrasound suspicion of TT who underwent surgical testicular examination during Jan.2017 and Jan.2024.The patients were divided into TT group and non-TT group.Clinical data and laboratory data at admission were analyzed.Sensitivity and specificity of NLR to TT were determined with the area under the curve(AUC)represented on the receiver operating characteristic(ROC)curves.Results There were with no statistically significant differences in clinical data between the two groups(P＞0.05).The NLR was significantly higher in the TT group than in the non-TT group[(4.82±2.37)vs.(2.85±0.75),P＜0.05].The optimal cut-off value of TT predicted by NLR was 2.07,the AUC was 0.809(95％CI:0.709-0.909),and the sensitivity and specificity were 97.9％and 93.3％,respectively,which were significantly higher than other factors.Conclusion For suspicious ultrasound diagnosis of pediatric acute scrotal pain cases,NLR can be used to predict the possibility of TT and may help to evaluate the urgent surgical treatment in these patients.

[Objective]To evaluate the changes in cardiac structure and ventricular function in patients with Ander-son-Fabry Disease(AFD)by two-dimensional speckle tracking echocardiography(2D-STE)and to explore the character-istics of their early cardiac involvement.[Methods]All 45 patients diagnosed with AFD in this observational study under-went routine ultrasonic cardiogram(UCG)examination and 2D-STE.The patients were divided into 2 groups based on UCG measurements:with left ventricular hypertrophy(interventricular septum or posterior left ventricular wall thickness≥12 mm)and without left ventricular hypertrophy.TomTec software was used to analyze the echocardiographic images,then the baseline data,UCG routine parameters and myocardial strain of the two groups were compared.[Results]The study in-cluded 27 males(60.0%)and 18 females(40.0%),with an average age of(32.33±16.11),17 cases(37.78%)with left ventricular hypertrophy and 28 cases(62.22%)without left ventricular hypertrophy.All patients had normal left ventricu-lar ejection fraction(LVEF)(>50%).Compared with those without left ventricular hypertrophy,patients with left ventric-ular hypertrophy had significantly more target organ involvement,significantly higher E/A and average E/E' ratios(P<0.05).No statistical difference was found in global and segmental longitudinal strain(LS),circumferential strain(CS)and radial strain(RS)of the endocardium and myocardium between the two groups(all P>0.05).There were lower abso-lute values of global and segmental LS and CS in the myocardium than in the endocardium(all P<0.05),and higher abso-lute values of LS and RS in the mid segment than in the basal and apical segments(all P<0.05).[Conclusions]There is no significant association between early systolic dysfunction and left ventricular wall thickness.2D-STE strain can be used to detect AFD in the early stage.Ventricular wall myocardium exhibits more serious involvement than endocardium and mid segment was less involved than the apical and basal segments.

Objective: To analyze the trends in disease burden of tuberculosis among children under 5 years of age in China from 1990 to 2021, so as to provide insights for future tuberculosis control measures among children in China. Methods: Based on the Global Burden of Disease (GBD) 2021 datasets, the incidence, prevalence, mortality and disability adjusted life year(DALY) of tuberculosis of children under 5 years of age in China and globally were collected from 1990 to 2021. The incidence, prevalence, mortality and DALY rate of tuberculosis were compared by genders and types. In addition,the annual percent change(APC) and the average annual percent change(AAPC) of children s tuberculosis burden in China and globally from 1990 to 2021 were calculated by using the Joinpoint regression model, and the changing trends were analyzed. Results: The numbers of incident, prevalent and dead tuberculosis cases were 9 700, 8 477 800 and 200 among children under 5 years of age in China in 2021, and the DALY due to tuberculosis were 27 100 person years. There were significant reductions in incidence, prevalence, mortality and DALY rate of tuberculosis among children under 5 years of age in China ( AAPC =-5.45%, -1.14%, -12.37%, -11.34 %) and globally( AAPC =-2.38%, -1.41%, -4.66%, -4.56%), and the reductions in the incidence, mortality and DALY rate were more significant in China than globally ( P <0.05).In 1992 and later, the numbers of incident, prevalent and dead tuberculosis cases and the DALY of tuberculosis were higher among male than among female. In addition, the disease burden of drug susceptible tuberculosis appeared a tendency of downward in China from 1990 to 2021, while the incidence and prevalence of extensively drug resistant tuberculosis rose since 2015. Conclusions The disease burden of tuberculosis remarkably reduced among children under 5 years of age in China from 1990 to 2021. However, the burden of disease due to multidrug resistant tuberculosis appeared an upward trend recently. Increased attention is required to be paid to the prevention and control of tuberculosis among children and improved diagnosis and treatment of drug resistant tuberculosis are recommended.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.