Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.05,P<0.01),the expression of p62 mRNA and protein decreased(P<0.05,P<0.01),the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 protein increased(P<0.05,P<0.01).16S rDNA sequencing results showed that the diversity and evenness of the intestinal flora in the model group mice decreased,with a decrease in the relative abundance of Firmicutes,Actinobacteria and Patescibacteria(P<0.05),and an increase in the relative abundance of Bacteroidota,Verrucomicrobiota and Proteobacteria(P<0.05);the relative abundance of Bacilli and Coriobacteriia decreased(P<0.05),the relative abundance of Bacteroidia,Clostridia and Verrucomicrobiae increased(P<0.05);the relative abundance of Ligilactobacillus and Dubosiella decreased(P<0.05),the relative abundance of unclassified Muribaculaceae,Lachnospiraceae NK4A136_group,Akkermansia and unclassified Lachnospiraceae increased(P<0.05).Compared with the model group,the diversity and evenness of intestinal flora increased in Kuijie Ankang Decoction group and SASP group,with an increase in the relative abundance of Firmicutes(P<0.05),a decrease in the relative abundance of Bacteroidota and Verrucomicrobiota(P<0.05),the relative abundance of Bacteroidia and Bacilli increased(P<0.05),the relative abundance of Verrucomicrobiae decreased(P<0.05);the relative abundance of unclassified Muribaculaceae and Ligilactobacillus increased(P<0.05),while the relative abundance of Lachnospiraceae NK4A136_group and Akkermansia decreased(P<0.05).Conclusion Kuijie Ankang Decoction can significantly improve the intestinal mucosal injury of UC mice,and the mechanism may be related to the regulation of colon autophagy level and intestinal flora disorder.

Objective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.05,P<0.01),the expression of p62 mRNA and protein decreased(P<0.05,P<0.01),the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 protein increased(P<0.05,P<0.01).16S rDNA sequencing results showed that the diversity and evenness of the intestinal flora in the model group mice decreased,with a decrease in the relative abundance of Firmicutes,Actinobacteria and Patescibacteria(P<0.05),and an increase in the relative abundance of Bacteroidota,Verrucomicrobiota and Proteobacteria(P<0.05);the relative abundance of Bacilli and Coriobacteriia decreased(P<0.05),the relative abundance of Bacteroidia,Clostridia and Verrucomicrobiae increased(P<0.05);the relative abundance of Ligilactobacillus and Dubosiella decreased(P<0.05),the relative abundance of unclassified Muribaculaceae,Lachnospiraceae NK4A136_group,Akkermansia and unclassified Lachnospiraceae increased(P<0.05).Compared with the model group,the diversity and evenness of intestinal flora increased in Kuijie Ankang Decoction group and SASP group,with an increase in the relative abundance of Firmicutes(P<0.05),a decrease in the relative abundance of Bacteroidota and Verrucomicrobiota(P<0.05),the relative abundance of Bacteroidia and Bacilli increased(P<0.05),the relative abundance of Verrucomicrobiae decreased(P<0.05);the relative abundance of unclassified Muribaculaceae and Ligilactobacillus increased(P<0.05),while the relative abundance of Lachnospiraceae NK4A136_group and Akkermansia decreased(P<0.05).Conclusion Kuijie Ankang Decoction can significantly improve the intestinal mucosal injury of UC mice,and the mechanism may be related to the regulation of colon autophagy level and intestinal flora disorder.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma (NSCLC).
 Methods: A total of 865 NSCLC patients were screened for the risk factors, including age, gender, address, tumor/lymph nodes/metastasis (TNM) stage, and cancer awareness. Survival of the patients was calculated by Kaplan-Meier method and Cox regression analysis.
 Results: After an average observation time of 304 d (ranging from 0 to 4 718 d), 62 of the 394 patients in the cancer awareness group survived, whereas 26 of the 471 patients in the cancer concealment group survived. Cancer-specific and all-cause survival was poorer in the cancer concealment group (P<0.001 for each, log-rank test). Cox multivariate regression analysis showed that cancer concealment displayed significantly lower cancer-specific survival [hazard ratio (HR)=1.534, 95% confidence interval (CI) 1.320 to 1.784, P<0.001] and all-cause survival (HR=1.558, 95% CI 1.346 to 1.803, P<0.001).
 Conclusion: Cancer concealment is associated with a poor survival of NSCLC patients, which may prohibit the patients from obtaining the real "right to survival".
Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms ; Lymphatic Metastasis ; Prognosis ; Proportional Hazards Models

OBJECTIVE: To investigate the expression pattern of adapter protein with a Src-homology 2 domain (SH2B1), the suppressor of cytokine signaling-3 (SOCS3), protein-tyrosine phosphatase 1B (PTP1B) and neturopetide Y (NPY) in obese and normal mice hypothalamus and its relation with serum leptin and insulin levels. METHODS: The obesity animal model was prepared with healthy C57/bl6 mice. Lee's index and Homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. The mRNA levels of SH2B1, SOCS3, PTP1B and NPY were measured by fluorescent quantitation RT-PCR. The SH2B1 and NPY protein expressions were detected by Western blot. RESULTS: Compared with the normal mice of the same age, SH2B1 mRNA expression in the obese mice hypothalamus decreased. SOCS3 and PTP1B mRNA expression increased. Western blot showed that SH2B1 protein expression decreased, while NPY protein expression increased in the obese mice. Linear correlation analysis showed that the serum leptin and fasting insulin levels were negatively correlated with SH2B1mRNA expression and positively correlated with SOCS3 and PTP1B mRNA expression. CONCLUSION SH2B1, SOCS3, PTP1B and NPY are key factors for obesity development.
Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Hypothalamus ; metabolism ; Insulin ; blood ; Insulin Resistance ; Leptin ; blood ; Mice ; Mice, Inbred C57BL ; Neuropeptide Y ; metabolism ; Obesity ; metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; metabolism ; RNA, Messenger ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism

OBJECTIVE: To explore the protective effects of ischemic postconditioning on non-heart-beating donor (NHBD) in rat NHBD lung transplantation model. METHODS: Forty Sprague-Dawley rats were randomized into the ischemic postconditioning group (IPO group) and the control group (C group), 10 pairs in each group in which left lung orthotopic transplantations from NHBDs were done with " two-cuff-one-stent technique". In the C group, perfusion was resumed by declamping pulmonary artery immediately after transplantation, whereas in the IPO group, 5 cycles of 1-min reperfusion and 1-min reocclusion of pulmonary artery were applied as postcontioning before full recovery of perfusion. RESULTS: Compared with the C group, water content of donor lungs was lower and pathological changes were milder in the IPO group, meanwhile compliance, structure and function of donor lungs were better preserved. Furthermore, the expression of cell apoptosis and MDA content in donor lungs were lower in the IPO group, while SOD content was higher. CONCLUSION Ischemic postconditioning can reduce ischemic reperfusion injury of NHBD lung transplantation and preserve the structure and function of donor lungs. It can inhibit lipid peroxidation and cell apoptosis in NHBD lungs after transplantation.
Animals ; Heart Arrest ; Ischemic Postconditioning ; Lung ; metabolism ; pathology ; surgery ; Lung Transplantation ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Superoxide Dismutase ; metabolism