ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

Promoting the high-quality development of the transformation of medical scientific research results has become an important content and development direction in China’s medical science and technology system reform. Various risks involved in medical scientific research need to be fully recognized and prevented， and strengthening science and technology insurance services is one of the important ways. Commercial insurance in the field of translational medicine in China is in a rapid development stage， and the main insurance products include drug research and development insurance， clinical trial liability insurance， genetic testing insurance， and other insurances. While commercial insurance intervenes in the innovation of medical science and technology， ethical and liability issues often raise concerns and controversies. Combined with the current practices of handling ethical issues related to commercial insurance for translational medicine in China， this paper reviewed the current development status of commercial insurance related to translational medicine from the perspective of the insurance industry， discussed the relevant ethical issues， and proposed coping strategies.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Background::Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening.Methods::We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial.Results::This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios.Conclusion::This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective The objective of this study was to investigate the effect of salinomycin on proliferation and autophagic flux of human melanoma M21 cells. Methods The cell survival rate was determined by MTS assay and IC50values( half inhibitory concentration)were calculated. The morphological changes of cells after salinomycin administration were observed under optical micro-scope. Flow cytometry was used to examine the apoptosis rate of M21 cells. Western blot was used to detect the expression of autophag-ic-related protein LC3B and p62 in M21 cells. The presence of autophagosomes in M21 cells after salinomycin administration was ob-served under transmission electron microscope. Western blot and immunofluorescence were used to detect the level of p62 protein and localizing changes in M21 cells. Results Salinomycin significantly inhibited proliferation of M21 cells, and the IC50values were (1. 38 ± 0. 18)μM. After salinomycin administration,the proliferation rate of M21 cells was slowed down,and obvious vacuoles ap-peared in the cells. Salinomycin could not only induce cell apoptosis,but it also increased the ratio of LC3B-Ⅱ/LC3B-Ⅰ in M21 cells. The increase and accumulation of autophagosomes were directly observed under transmission electron microscope. The level of p62 protein was slightly elevated after salinomycin treatment and gradually aggregated into the cytoplasm,indicating that autophagic flux was inhibited. Conclusion Salinomycin can inhibit the proliferation of human malignant melanoma M21 cells,and its mechanism may be related to the accumulation autophagosomes granules and inhibition of autophagic flux.

ObjectiveThe study is to investigate the predictive values of dosimetric parameters and patient related factors in severe acute radiation pneumonitis (SARP) after concurrent chemoradiotherapy in non-small cell lung cancer (NSCLC).Methods In all,147 NSCLC patients treated with concurrent chemotherapy and 3DCRT between 2006 and 2010 was collected.Independent sample t test was used to compare parameter values between patients with SARP and those without SARP.Logistic regression was used to identify significant determined factor.Predictive value of each parameter was tested by ROC analysis.Pearson correlation was used to analyze correlations between parameters.Represent factors were identified by factor analysis.ResultsThe incidence of SARP was 9.5％ ( 14/147 ).The means lung dose (MLD),V20,V30,V40,and V50 ( x2 =4.87 -6.84,P =0.009 -0.025,respectively ) were determining factors for SARP.Our datasets shows that for SARP ＜5％,MLD,V20,V30,V40 and V50 should be ≤16.77 Gy,V20≤34.15％,.V30 ≤23.62％,.V40 ≤ 18.57％,V50 ≤ 13.02％.ROC analysis show that areas under MLD,V20,V30,V40 and V50 curves was corresponding to 0.678,0.661,0.667,0.677,and 0.651,respectively.In addition,the sensitivity and specificity of each parameter at cutoff values are:78.0％ and 48.1％ for MLD;42.9％ and 82.0％ for V2o ;78.6％ and 52.9％ for V30 ;71.4％ and 61.7％ for V40,and 57.1％ and 67.7％ for V50.Factor analysis suggest that we can choose 1 or 2 parameters from MLD,V20,or V30,and another from V40 or V50 for predicting.The incidence of SARP was greater in patients with tumorsin right lower lung than other locations ( 22.2％ vs 6.7％,x2 =6.19,P =0.0 2 3 ).Conclusions The MLD,V20,V30,V40 and V50 are determining factors for SARP.As predictive value of each parameter alone is relatively week,using two or more parameters to predict SARP is recommended.

Objective To investigate the effects of 20 Hz repetitive transcranial magnetic stimulation (rTMS) with different intensities on neurobehavior and expression of glial fibrillary acidic protein (GFAP) in ischemic penumbra of rats with cerebral infarction,so as to explore the probable mechanism. Methods Forty-three rats were randomly divided into a blank control group( n =7 ),a model control group( n =7),a sham stimulation control group(n =8) and a rTMS group (n =21) ; the rTMS group was further subdivided into 3 subgroups:80％ MT subgroup,100％ MT subgroup and 120％ MT subgroup,with 7 rats in each subgroup.The cerebral infarction model was established by right middle cerebral artery occlusion (MCAO) in each group except the blank control group.The 3 rTMS subgroups were given 14 successive blocks of 20 Hz rTMS with corresponding intensity.The sham stimulation control group received sham treatment (without any output).The model control group was given no stimulation,and the blank control group did not receive any special treatment.Functional assessments were performed at 3 different time points.After 14-day treatment,the expression of GFAP proteins in ischemic penumbra were detected by immunohistochemistry technique. Results Functional outcome reflected from 3 behavioral tests in 100％ MT subgroup after 14-day stimulation was better than 1 day after operation,while in the other rTMS subgroups functional outcomes were just better in 2 behavioral tests.The expressions of GFAP in 3 rTMS subgroups were all less than that in model control group. Conclusions The 20 Hz rTMS with 80％ MT and 100％ MT might be safe and effective to improve the functional outcome in rats with acute cerebral infarction,especially 100％ MT.Decrease of expression of GFAP in ischemic penumbra might be one of the mechanisms of beneficial effects of rTMS in ischemia brain injury.