Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective:To investigate the protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-28 3 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were mea-sured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P<0.05),while expressions of IL-6,JAK1,STAT3 mRNAs and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue were further increased(P<0.05);LMT-28,an inhibitor of IL-6/STAT3 signaling pathway,attenuated the liver protective effect of ASD on NAFLD rats.Conclusion:ASD can protect liver of NAFLD rats by activating IL-6/STAT3 signaling pathway.

Objective:To investigate the protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-28 3 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were mea-sured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P<0.05),while expressions of IL-6,JAK1,STAT3 mRNAs and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue were further increased(P<0.05);LMT-28,an inhibitor of IL-6/STAT3 signaling pathway,attenuated the liver protective effect of ASD on NAFLD rats.Conclusion:ASD can protect liver of NAFLD rats by activating IL-6/STAT3 signaling pathway.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective To establish the UPLC fingerprint chromatogram combined with chemometric analysis for the quality evaluation of classical formula Linggui Zhugan Decoction.Methods SHIMADZU Shim-Pack GIST C18 column(100 mm×2.1 mm,2.0 μm)was used with acetonitrile-0.1%phosphoric acid aqueous solution as mobile phase,gradient elution;flow rate was 0.2 mL/min;the detection wavelength was 266 nm for the first 30 minutes and 235 nm for the last 36 minutes;the column temperature was 30℃.The UPLC fingerprint of Linggui Zhugan Decoction was established by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012.130723 version),and the common peak was determined and the similarity evaluation was carried out.Based on the peak area determination results of the common peak of the fingerprint,the quality of different batches of Linggui Zhugan Decoction was evaluated by chemometrics such as clustering analysis and principal component analysis.Results A total of 24 common peaks were confirmed and 14 components were identified by using reference substances.The similarity of 10 batches of Linggui Zhugan Decoction samples was greater than 0.950,which could be divided into two categories by chemometrics,and the principal component 1-4 were the main factors affecting its quality evaluation.OPLS-DA identified 6 differential markers.Conclusion The fingerprint research method established in the study is simple,reliable and reproducible.Through the method of fingerprint combined with chemometrics analysis,the differences between Linggui Zhugan Decoction from different origins of medicinal materials are identified,which provides a reference for the internal quality evaluation of Linggui Zhugan Decoction.

This paper discusses the necessity of artificial intelligence(AI)technology empowering the field of traditional Chinese medicine(TCM)in the context of the intelligent era,the connotation and tasks of smart TCM,and the progress of related research and transformation.It closely follows the national orientation,rigid needs and problems,conducts top-level design,and proposes popular AI technologies that can be used in the field of TCM in the future and the research directions that smart TCM will focus on in the fu-ture,in order to further promote the integration of multidisciplinary cross-innovation and help realize the modernization,inheritance and innovation of TCM and lay the foundation.

This paper discusses the necessity of artificial intelligence(AI)technology empowering the field of traditional Chinese medicine(TCM)in the context of the intelligent era,the connotation and tasks of smart TCM,and the progress of related research and transformation.It closely follows the national orientation,rigid needs and problems,conducts top-level design,and proposes popular AI technologies that can be used in the field of TCM in the future and the research directions that smart TCM will focus on in the fu-ture,in order to further promote the integration of multidisciplinary cross-innovation and help realize the modernization,inheritance and innovation of TCM and lay the foundation.

OBJECTIVES: To investigate the effects of PLK1 inhibitors on osimertinib-resistant non-small cell lung carcinoma (NSCLC) cells and the anti-tumor effect combined with osimertinib. METHODS: An osimertinib resistant NCI-H1975 cell line was induced by exposure to gradually increasing drug concentrations. Osimertinib-resistant cells were co-treated with compounds from classical tumor pathway inhibitor library and osimertinib to screen for compounds with synergistic effects with osimertinib. The Gene Set Enrichment Analysis (GSEA) was used to investigate the activated signaling pathways in osimertinib-resistant cells; sulforhodamine B (SRB) staining was used to investigate the effect of PLK1 inhibitors on osimertinib-resistant cells and the synergistic effect of PLK1 inhibitors combined with osimertinib. RESULTS: Osimertinib-resistance in NCI-H1975 cell (resistance index=43.45) was successfully established. The PLK1 inhibitors GSK 461364 and BI 2536 had synergistic effect with osimertinib. Compared with osimertinib-sensitive cells, PLK1 regulatory pathway and cell cycle pathway were significantly activated in osimertinib-resistant cells. In NSCLC patients with epidermal growth factor receptor mutations treated with osimertinib, PLK1 mRNA levels were negatively correlated with progression free survival of patients (R=－0.62, P<0.05), indicating that excessive activation of PLK1 in NSCLC cells may cause cell resistant to osimertinib. Further in vitro experiments showed that IC₅₀ of PLK1 inhibitors BI 6727 and GSK 461364 in osimertinib-resistant cells were lower than those in sensitive ones. Compared with the mono treatment of osimertinib, PLK1 inhibitors combined with osimertinib behaved significantly stronger effect on the proliferation of osimertinib-resistant cells. CONCLUSIONS PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; ErbB Receptors/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; Mutation ; Cell Line, Tumor

Wu Liande’s spirit was formed during the development of modern public health in China. It is a unity of the spirit of patriotism, humanitarianism, scientific exploration, and dedication, and a valuable resource and vivid textbook for medical students to carry out professional spirit education. Promoting Wu Liande’s spirit in the new era is not only conducive to inspiring the patriotism of medical students, bravely undertaking the mission of the times, and devoting themselves to the cause of human health, but also conducive to guiding medical students to refine benevolence and skill, and fulfill the sacred oath of medical students. To cultivate the professional spirit of medical students with Wu Liande’s spirit, it is necessary to achieve the "integration of specialized courses and ideological and political education" , promote the collaborative development of ideological and political courses and curriculum ideological and political education, innovate teaching methods and use modern information technology to empower Wu Liande’s spirit to be visualized and expressed, and take discipline practice as the starting point to expand the new path of professional spirit practice education for medical students.

Objective:To investigate the correlation between serum miR-122-5p and FOXO3 levels and osteoporosis (OP) in postmenopausal women with non-alcoholic fatty liver disease (NAFLD) .Methods:The clinical data and serum of 30 postmenopausal women with NAFLD and 48 postmenopausal women with no-NAFLD were collected. The levels of miR-122-5p and FOXO3 in serum were detected by qRT-PCR. Triglycerides, high-density lipoproteins, and low-density lipoproteins were detected by biochemical autoanalyzer. The bone mineral density of lumbar vertebrae 1-4, Wards triangular bone, femoral neck, greater trochanter and total hip was detected by bone mineral density analyzer. The correlation between the above clinical indicators and OP was analyzed.Results:The expression of miR-122-5p in postmenopausal female NAFLD patients (0.76±0.28) was lower than that in non-NAFLD patients (1±0.31) ( t=3.43, P=0.001) . The downstream target gene FOXO3 of miR-122-5p was identified by bioinformatics website analysis. The expression of FOXO3 in postmenopausal female NAFLD patients (1.31±0.30) was higher than that in non-NAFLD patients (1±0.27) ( t=4.73, P<0.001) . Student’ s t test and Logistic regression analysis showed that triglyceride, miR-122-5p and FOXO3 levels were risk factors for NAFLD (all P<0.05) . Pearson correlation coefficient showed that miR-122-5p level was significantly positively correlated with BMD of femoral neck ( r=0.488, P=0.006) , greater trochanter ( r=0.367, P=0.046) and whole hip ( r=0.404, P=0.027) . FOXO3 level was negatively correlated with bone mineral density of femoral neck ( r=-0.445, P=0.014) and whole hip ( r=-0.507, P=0.004) , while other indexes were not significantly correlated (all P>0.05) . Conclusion:Decreased serum miR-122-5p level and increased FOXO3 level in postmenopausal women with NAFLD may increase the risk of OP.