Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective:The classification model of prognosis of elderly cancer patients in rural areas of Shaanxi province was constructed based on machine learning algorithm, and its effectiveness was verified, providing reference for early prognosis recognition and intervention treatment.Methods:Using a multicenter, cross-sectional survey method and convenience sampling method, 597 elderly cancer patients in rural areas hospitalized in 9 different medical institutions (Shaanxi Cancer Hospital and its member units of specialty alliance) in Shaanxi Province from July to August 2022 were selected as the research objects, and a variable database of "basic information", "self-care ability", "symptoms", "comprehensive needs" and "quality of life" of elderly cancer patients in rural areas was established. Machine learning and statistical analysis were carried out to explore the important prognostic characteristics of elderly cancer patients in rural areas, and a prognostic classification model for elderly cancer patients in rural areas was constructed and verified.Results:The 597 valid questionnaires were ultimately collected.Among the 597 elderly cancer patients in rural areas, 207 were males and 390 were females, aged (69.56 ± 8.84) years. The results of cluster exploration showed that the prognosis of elderly cancer patients in rural areas was divided into three categories: good, medium and poor. The areas under the working characteristic curves of the subjects in good, medium and poor were 0.84, 0.79 and 0.69, respectively. The results of characteristic exploration showed that 10 indicators of "whether accompanied by metastasis", "distress", "sadness", "numbness", "eating", "walking", "fatigue", "forgetfulness", "fun of life" and "relationship with others" were important characteristic indicators of prognosis evaluation of elderly cancer patients in rural areas. There were statistically significant differences among the 10 important characteristic indicators in the three categories of prognosis of rural elderly cancer patients ( χ2=21.07, H values were 18.51-144.38, all P<0.01). There were statistically significant differences in the three categories of "comprehensive needs", "quality of life", "self-care ability" and "symptoms" ( H values were 519.40, 40.80, 103.69, all P<0.01). Conclusions:The construction and verification of a prognostic classification model for elderly cancer patients in rural areas based on machine learning algorithm can effectively explore the important characteristic indicators and prognostic classification of elderly cancer patients in rural areas, and provide basis and guidance for clinical medical staff to make individualized plans.

Objective To investigate current status in knowledge,attitude and practice(KAP)of transitional care among the nurses in Shaanxi province,identify the influencing factors that hinder the transitional care and carry out training of transitional care for the nurses in different specialties in order to provide a theoretical basis for establishing a transitional care model for discharged patients.Methods A total of 2 288 nurses were selected to participate the survey from 41 hospitals in Shaanxi province by the stratified two-stage random sampling method.A self-designed questionnaire for general information,an obstacle factor scale,and a KAP of transitional care questionnaire were used as the survey instruments.The data acquired from the survey were processed by Cluster analysis to identify potential categories and the influencing factors.Results Totally 2085 nurses finished the study.Total score of KAP of transitional care among the nurses in Shaanxi province was found at(134.96±23.75),which was at a medium level.The scores of knowledge,attitude and practice were 77.24%,80.64%and 76.98%respectively.Cluster analysis showed that all the nurses could be categorised into either a lower scored group(n=1 596,76.5%)or a higher scored group(489,23.5%),with a best potential category number of 2 for the 2 085 nurses who participated the survey.There were statistically significant differences between the groups in terms of care training,telephone follow-up,network platform,outpatient service of nursing experts,family visits,patient club and hospital categories(all P＜0.05).Logistic regression analysis on even factors above showed that care training,telephone follow-up,network platform and patient club could significantly affect the potential categorisation of KAP of the nurses in transitional care(all P＜0.05).The main factors that hindered the transitional care included insufficient human resources(93.81%),insufficient supply of community services(93.57%)and lack of a standardised flowchart for transitional care(93.09%).Conclusions Levels of KAP about the transitional care are at a medium level among the nurses of 41 hospitals in Shaanxi province,which indicates that the nurses are active in attitude,but the knowledge and practice are required to be further improved and standardised.The results of cluster analysis indicate that it is necessary for nursing managers to carry out targeted trainings in transitional care for the nurses in different categories.This study provides a theoretical basis to establish a diversified transitional care mode for discharged patients in Shaanxi province.

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

Objective To investigate the effect of ursolic acid (UA) on the colorectal tumor and microenvironment in mice,and to provide a theoretical basis for the clinical application of UA.Methods The models of subcutaneous transplanted tumor of mouse CT26 cells was established.The models were divided into four groups:control group,tumor bearing group,tumor beating dimethyl sulfoxide (DMSO) group and tumor beating UA group.Tbe serum levels of interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA).The number and percentage of myeloid-derived suppressor cell (MDSC) in the spleen of mice were analyzed by flow cytometry.The mRNA levels of IL-6 and signal transducer and activator of transcription 3 (STAT3) in tumor were examined by real-time quantitative polymerase chain reaction (RT-PCR).The protein levels of STAT3 and p-STAT3 in tumor were detected by Western blotting.Results The results showed that UA could significantly decrease the number of spleen MDSC.The accounts of spleen MDSC of tumor bearing UA group (249.60 ± 17.12) was lower than that of tumor beating DMSO group (366.40 ± 34.08),and the difference was statistically significant (P =0.021).The serum level of IL-6 in tumor bearing UA group [(46.40 ± 17.05) pg/ml] was decreased than that in tumor bearing DMSO group [(94.27 ±21.51) pg/ml],and the difference was statistically significant (P =0.012).The expression levels of IL-6 and STAT3 mRNA in tumor tissues of tumor bearing UA group (0.12 ±0.01,0.21 ±0.08) were lower than those of tumor bearing DMSO group (0.69 ± 0.14,0.79 ± 0.06),and the differences were statistically significant (P =0.008;P =0.003).The protein expression levels of STAT3 and p-STAT3 in tumor tissues of tumor bearing UA group (0.81 ±0.02,0.28 ±0.04) were lower than those of tumor bearing DMS0 group (0.98 ±0.02,0.91 ±0.22),and the differences were statistically significant (P =0.027;P =0.029).Conclusion UA may inhibit the activation of STAT3 signaling pathway and the amplification of MDSC in microenvironment by reducing IL-6,thus to enhance the function of immune-killing tumor cells to regulate tumor immune microenvironment and inhibit the immune escape of mouse colorectal cancer cells.

Objective To evaluate the diagnostic value of contrast-enhanced ultrasound in breast precancerous lesions . Methods Retrospectively analyzed the contrast-enhanced ultrasound model and angiographic predictive model of 465 cases of the A prospective multicenter study of breast nodules contrast-enhanced ultrasound" that led the Sichuan Provincial People′s Hospital from January 2016 to April 2017 ,which included 69 cases of breast precancerous lesions and 396 other types benign lesions ,and the sensitivity ,specificity and accuracy of the diagnosis of breast precancerous lesions were calculated . Results The sensitivity of ultrasound predictive model for the diagnosis of precancerous lesions was 60 .9％ and AUC was 0 .681 . Precancerous lesions mainly showed non-concentricity , increased homogeneity , and increased lesions;other types of benign lesions mainly showed non-centripetal ,high uniformity enhancement and lesion size unchanged . Conclusions Contrast-enhanced ultrasound shows a potential value in the differential diagnosis of precancerous lesions and other types of benign lesions ,that can help clinicians to take early intervention measures for breast precancerous lesions ,but there are still many problems to be solved .

Objective To observe the effect of EGFR‐TKI combined with chemotherapy on the changes of serum insulin‐like growth factor1(IGF‐1)and anterior gradient‐2(AGR2)levels in the patients with advanced non‐small cell lung cancer(NSCLC) ,and to investigate whether IGF‐1 and AGR2 can serve as a potential indicator of the prognosis and efficacy of chemotherapy in NSCLC . Methods Sixty‐eight patients with advanced NSCLC were selected as the experimental group treated by EGFR‐TKI combined chemotherapy and 30 healthy people served as the healthy control group .(treatment group) .The levels of serum IGF‐1 and AGR2 before chemotherapy and at 3 weeks after chemotherapy were detected by ELISA .The influence of serum IGF‐1 and AGR2 levels on the prognosis was analyzed by using Kanplan‐Meier method .Results (1)The disease control rate(DCR)in the EGFR‐TKI com‐bined chemotherapy was 52 .9% ;(2)the level of serum IGF‐1 before treatment in the experimental group was (329 .35 ± 88 .13)μg/L ,which was significantly higher than (146 .36 ± 41 .27)μg/L in the healthy control group(P<0 .01);the level of serum AGR2 in experimental group was(16 .72 ± 6 .23)ng/mL ,which was significantly higher than (4 .38 ± 2 .17)ng/mL in the healthy control group(P<0 .01);serum levels of IGF‐1 and AGR2 after treatment were(211 .53 ± 52 .31)μg/L and (9 .72 ± 3 .56)ng/mL respec‐tively ,which were significantly lower than those before treatment (P<0 .01);serum IGF‐1 and AGR2 in NSCLC patients were pos‐itively correlated(r=0 .489 ,P<0 .01);(3)serum levels of IGF‐1 and AGR2 after chemotherapy were(128 .62 ± 48 .24)μg/L and (7 .22 ± 4 .27)ng/mL respectively ,which were obviously lower than(334 .23 ± 82 .11)μg/L and(18 .43 ± 6 .17)ng/mL before chem‐otherapy(all P<0 .01) .The Kanplan‐Meier analysis revealed that serum IGF‐1 and AGR2 levels in advanced NSCLC had an obvi‐ous influence on the prognosis .Conclusion Serum IGF‐l and AGR2 levels may have a potential clinical value to assess the therapeu‐tic efficacy of EGFR‐TKI combined chemotherapy and prognosis in advanced NSCLC .

Objective:To investigate effects of viola on macrophage TOLL-like receptor expression ,and tentatively explore the partial mechanism of viola intervention on macrophage function.Methods: Using viola water decoction lavage intervention in clean grade SD rats of conventional preparation containing serum ,In a certain concentration coculture with mouse peritoneal macrophages in 96-well plates.After 24 hours,cell phagocytosis activity was determined by neutral red uptake assay ,changes in expression levels of TLR-1,TLR-2,TLR-3,TLR-4,TLR-5 mRNAs were determined by RT-PCR.Results:Compared with the same concentration of normal serum group :(1 ) viola-containing serum group macrophage activity was significantly increased ( P<0.01 );( 2 ) Within certain concentration,viola containing serum group with increased or decreased expression levels of TLR -1,TLR-2,TLR-3 mRNA(P<0.05 or P<0.01 ) ,the expression level of TLR-4 was not significantly altered in each group ( P>0.05 ) ,and the expression level of TLR-5 was significantly increased in each group ( P<0.01 ).Conclusion:Viola-containing serum has obvious promoting effect on macrophage phag-ocytosis,the mechanism of which may be related to that this drug regulates and controls part of macrophage TOLL -like receptor expres-sion.