Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
RNA, Long Noncoding/physiology* ; Osteogenesis/physiology* ; Humans ; Neovascularization, Physiologic/genetics* ; Bone and Bones/metabolism* ; Animals ; Mesenchymal Stem Cells ; Signal Transduction ; Osteoblasts ; Osteoclasts ; Angiogenesis

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Objective:To comprehensively evaluate the changes in pulmonary artery hemodynamics in patients with repaired tetralogy of Fallot (rTOF) using four-dimensional flow (4D Flow) MRI, and to explore the value of viscous energy loss (EL) as an evaluation parameter of the right heart in patients with rTOF.Methods:A total of 30 rTOF patients who were prospectively admitted at Fuwai Hospital between October 2017 and November 2019, and 19 healthy controls who were prospectively recruited on March 2023, were enrolled in this study. All participants underwent a comprehensive 4D Flow MRI evaluation, and indicators of comparison between the two groups including quantitative flow analysis, wall shear stress (WSS) assessment, and EL evaluation in four planes: the right ventricular outflow tract (RVOT), main pulmonary artery (MPA), right pulmonary artery (RPA), and left pulmonary artery (LPA). The correlation between EL and traditional right ventricular (RV) function parameters, as well as WSS, was analyzed.Results:The RV function was generally decreased in rTOF patients, with an RV ejection fraction of 41.42 (35.85, 43.33) %. Compared with healthy controls, the volumes of backward flow, peak velocities, and both axial and circumferential WSS at the RVOT, MPA, RPA, and LPA were significantly increased in rTOF patients (all P<0.05). The EL in the pulmonary artery was extremely low in healthy controls, with the maximum EL values for the MPA-RPA and MPA-LPA segments during cardiac cycle being 0.51 (0.42, 0.73) and 0.68 (0.40, 0.94) mW, respectively. However, in rTOF patients, the EL values were as high as 63.63 (35.35, 82.15) and 56.41 (34.96, 88.76) mW, respectively. There was a significant moderate negative correlation between EL and RV ejection fraction, and a moderate to high positive correlation between EL with RV volume index, regurgitation fraction, as well as peak velocities (all P<0.05). Additionally, there was a significant positive correlation between EL and axial and circumferential WSS, with the correlation coefficients at MPA ranging from 0.67 to 0.88 (all P<0.05). Conclusions:Disordered flow in the pulmonary artery is common in patients with rTOF and should not be overlooked. The extensive viscous EL is closely associated with traditional RV function parameters and WSS. EL is expected to become an crucial parameter for evaluating right heart function in rTOF patients.

Objective To explore the effect of exercise under cold exposure on hepatic protein ki-nase B(AKT)/forkhead box O1(FoxO1)expression in obese rats.Methods Among rats successfully induced nutritional obesity by high-fat diet,forty were selected and randomly divided into a normal-temperature control group(NC,n=10),a normal-temperature exercise group(NE,n=10),a sus-tained-cold control group(SC,n=10),and a sustained-cold exercise group(SE,n=10).The normal temperature was kept at 25°C±1°C,while the low temperature remained at 4°C±1°C,with 50%to 60%relative humidity.The exercise protocol was every other day at a speed of 25 m/min for 2 sets of 30 min each,with an interval of 10 minutes.After 5 weeks,glucose and insulin tolerance were tested by oral glucose tolerance test(OGTT)and insulin tolerance test insulin tolerance test(ITT).Then,all rats were weighed and sacrificed,then taken blood from the abdominal aorta to sepa-rate serum,followed by detection of serum alanine aminotransferase(ALT)and aspartate aminotransfer-ase(AST)levels using fully automatic biochemical analyzer.Moreover,livers were weighed to calcu-late the liver index.Meanwhile,the mRNA expressions of hepatic AKT,FoxO1 and PEPCK were de-tected using RT-qPCR,while the protein expressions of AKT,phosphorylated protein kinase B(p-AKT),and FoxO1 in the liver were measured using Western blotting.Results(1)The average body weights of the NE,SC and SE groups were significantly lower than the NC group(P<0.01),with that of the SC and SE groups significantly lower than the NE group(P<0.01).(2)Compared with the NC group,the area under the OGTT curve of the SC group decreased(P<0.01).Moreover,the area under the ITT curve of the SE group was significantly lower than the other 3 groups(P<0.01,P<0.01,P<0.05),with that of the NE and SC groups significantly lower than the NC group(P<0.05,P<0.01).(3)The liver indices of the NE,SC and SE groups were all significantly lower than the NC group(P<0.01),while the serum ALT level of the NE group was significantly lower than the NC and SE groups(P<0.05),with that of the SC group significantly lower than the NC group(P<0.01).(4)Compared with the NC group,hepatic AKT mRNA expression increased significantly in the SE group(P<0.05),while the hepatic FoxO1 and PEPCK mRNA expression decreased significantly in the other three groups(P<0.01).(5)Compared with the NC group,the liver AKT protein phosphorylation levels were significantly higher in the other three groups(P<0.05,P<0.05,P<0.01),while the FoxO1 protein expression decreased significantly(P<0.05,P<0.01,P<0.01).(6)Body mass,liver FoxO1,PEPCK mRNA expression,AKT protein phosphorylation level and FoxO1 protein expression level of obese rats were affected by cold exposure,exercise and cold exposure+exercise,and the liver index and serum ALT level were done by exercise and cold exposure+exercise.However,the area un-der the ITT curve and liver AKT mRNA content were impacted by cold exposure and exercise,while that under the OGTT curve was influenced by cold exposure and cold exposure+exercise.Conclu-sion Exercise under cold exposure can activate hepatic AKT/FoxO1 signaling pathway,protect liver function,increase insulin sensitivity,and effectively improve glucose metabolism in obese rats.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Objective To explore the effect of exercise under cold exposure on hepatic protein ki-nase B(AKT)/forkhead box O1(FoxO1)expression in obese rats.Methods Among rats successfully induced nutritional obesity by high-fat diet,forty were selected and randomly divided into a normal-temperature control group(NC,n=10),a normal-temperature exercise group(NE,n=10),a sus-tained-cold control group(SC,n=10),and a sustained-cold exercise group(SE,n=10).The normal temperature was kept at 25°C±1°C,while the low temperature remained at 4°C±1°C,with 50%to 60%relative humidity.The exercise protocol was every other day at a speed of 25 m/min for 2 sets of 30 min each,with an interval of 10 minutes.After 5 weeks,glucose and insulin tolerance were tested by oral glucose tolerance test(OGTT)and insulin tolerance test insulin tolerance test(ITT).Then,all rats were weighed and sacrificed,then taken blood from the abdominal aorta to sepa-rate serum,followed by detection of serum alanine aminotransferase(ALT)and aspartate aminotransfer-ase(AST)levels using fully automatic biochemical analyzer.Moreover,livers were weighed to calcu-late the liver index.Meanwhile,the mRNA expressions of hepatic AKT,FoxO1 and PEPCK were de-tected using RT-qPCR,while the protein expressions of AKT,phosphorylated protein kinase B(p-AKT),and FoxO1 in the liver were measured using Western blotting.Results(1)The average body weights of the NE,SC and SE groups were significantly lower than the NC group(P<0.01),with that of the SC and SE groups significantly lower than the NE group(P<0.01).(2)Compared with the NC group,the area under the OGTT curve of the SC group decreased(P<0.01).Moreover,the area under the ITT curve of the SE group was significantly lower than the other 3 groups(P<0.01,P<0.01,P<0.05),with that of the NE and SC groups significantly lower than the NC group(P<0.05,P<0.01).(3)The liver indices of the NE,SC and SE groups were all significantly lower than the NC group(P<0.01),while the serum ALT level of the NE group was significantly lower than the NC and SE groups(P<0.05),with that of the SC group significantly lower than the NC group(P<0.01).(4)Compared with the NC group,hepatic AKT mRNA expression increased significantly in the SE group(P<0.05),while the hepatic FoxO1 and PEPCK mRNA expression decreased significantly in the other three groups(P<0.01).(5)Compared with the NC group,the liver AKT protein phosphorylation levels were significantly higher in the other three groups(P<0.05,P<0.05,P<0.01),while the FoxO1 protein expression decreased significantly(P<0.05,P<0.01,P<0.01).(6)Body mass,liver FoxO1,PEPCK mRNA expression,AKT protein phosphorylation level and FoxO1 protein expression level of obese rats were affected by cold exposure,exercise and cold exposure+exercise,and the liver index and serum ALT level were done by exercise and cold exposure+exercise.However,the area un-der the ITT curve and liver AKT mRNA content were impacted by cold exposure and exercise,while that under the OGTT curve was influenced by cold exposure and cold exposure+exercise.Conclu-sion Exercise under cold exposure can activate hepatic AKT/FoxO1 signaling pathway,protect liver function,increase insulin sensitivity,and effectively improve glucose metabolism in obese rats.

Objective:To comprehensively evaluate the changes in pulmonary artery hemodynamics in patients with repaired tetralogy of Fallot (rTOF) using four-dimensional flow (4D Flow) MRI, and to explore the value of viscous energy loss (EL) as an evaluation parameter of the right heart in patients with rTOF.Methods:A total of 30 rTOF patients who were prospectively admitted at Fuwai Hospital between October 2017 and November 2019, and 19 healthy controls who were prospectively recruited on March 2023, were enrolled in this study. All participants underwent a comprehensive 4D Flow MRI evaluation, and indicators of comparison between the two groups including quantitative flow analysis, wall shear stress (WSS) assessment, and EL evaluation in four planes: the right ventricular outflow tract (RVOT), main pulmonary artery (MPA), right pulmonary artery (RPA), and left pulmonary artery (LPA). The correlation between EL and traditional right ventricular (RV) function parameters, as well as WSS, was analyzed.Results:The RV function was generally decreased in rTOF patients, with an RV ejection fraction of 41.42 (35.85, 43.33) %. Compared with healthy controls, the volumes of backward flow, peak velocities, and both axial and circumferential WSS at the RVOT, MPA, RPA, and LPA were significantly increased in rTOF patients (all P<0.05). The EL in the pulmonary artery was extremely low in healthy controls, with the maximum EL values for the MPA-RPA and MPA-LPA segments during cardiac cycle being 0.51 (0.42, 0.73) and 0.68 (0.40, 0.94) mW, respectively. However, in rTOF patients, the EL values were as high as 63.63 (35.35, 82.15) and 56.41 (34.96, 88.76) mW, respectively. There was a significant moderate negative correlation between EL and RV ejection fraction, and a moderate to high positive correlation between EL with RV volume index, regurgitation fraction, as well as peak velocities (all P<0.05). Additionally, there was a significant positive correlation between EL and axial and circumferential WSS, with the correlation coefficients at MPA ranging from 0.67 to 0.88 (all P<0.05). Conclusions:Disordered flow in the pulmonary artery is common in patients with rTOF and should not be overlooked. The extensive viscous EL is closely associated with traditional RV function parameters and WSS. EL is expected to become an crucial parameter for evaluating right heart function in rTOF patients.

This paper analyzed the "non-standardization" phenomenon of syndrome differentiation in traditional Chinese medicine （TCM） from the diagnosis process. It is proposed that the symptoms and signs collected by the four examinations of inspection， listening/smelling， inquiry， and palpation naturally have a certain "ambiguity"， which can be reduced by the comparison and comprehensive condensation （comprehensive analysis of the four examinations） of a large amount of multi-dimensional clinical data， thereby realizing the sublimation of TCM diagnosis from "ambiguity" of four examinations to "accuracy" of diagnostic conclusion. Based on the above assumptions， this paper further proposed that a research idea of intelligent syndrome differentiation in TCM， that is， by taking the clinical thinking ability of TCM physicians as the core， adopting artificial intelligence technology based on knowledge graph visualization， integrating the complex network association and reasoning method of "symptom-pathogenesis-syndrome" linked by pathogenesis， and through the automatic analysis and reasoning process of a large amount of multi-dimensional and ambiguous clinical data， the intelligent TCM diagnosis based on syndrome differentiation can be realized.

Objective:To investigate the clinical and cardiac magnetic resonance (CMR) characteristics of heart involvement in patients with Fabry disease (AFD).Methods:From January 2018 to March 2021, eight AFD patients [3 males and 5 females, mean age (50±11) years old, range 26-60 years old] confirmed by genetic testing or pathology in Fuwai Hospital were retrospectively included in this study. At the same time, sixteen patients with hypertrophic cardiomyopathy (HCM) [6 males and 10 females, mean age (46±15) years old] and 16 healthy individuals [6 males and 10 females, mean age (51±11) years old] were included as controls. The clinical baseline data and CMR data of the patients were collected and analyzed. The CMR data were analyzed using the software CVI42, with the corresponding parameters automatically generated. One-way ANOVA or Kruskal-Wallis test was used to compare the differences in the parameters among the three groups. Independent-samples t test, Fisher precise test or Mann-Whitney U test were used for the comparison between each two groups. Results:Statistically significant difference was found in renal insufficiency between the HCM group and the AFD group; No other significant difference was found in other clinical factors and ECG results (all P>0.05). CMR results showed that in the AFD group, there were 5 cases with symmetric or roughly symmetric hypertrophy, and 3 with asymmetric hypertrophy. The late gadolinium enhancement (LGE) showed myocardial enhancement in 5 patients, mainly presenting as multiple intermural enhancement, and partially as local subendocardial enhancement. In the HCM group, fourteen cases suffered mainly asymmetric ventricular septal thickening, with or without thickening of other parts of left ventricular wall; and 2 cases had thickening of middle and distal part of the left ventricle. The LGE showed myocardial enhancement in 14 patients, which manifested as focal or patchy enhancement in hypertrophic myocardium, including focal enhancement in the right ventricular insertion of ventricular septum (more common) and subendocardial enhancement in the middle and far segments of left ventricle. Statistically significant difference was found in the differences between the left atrial anterior posterior diameter, the maximum wall thickness of left ventricular, the left ventricular myocardial mass index (LVMI) and the native T 1 value among the three groups (all P<0.001). However, there was no statistically significant difference in the left atrial anterior posterior diameter and the maximum wall thickness of left ventricular between AFD group and HCM group ( P>0.05). The LVMI in AFD group was higher than that in healthy group and HCM group (all P<0.05). Significant difference was found in the native T 1 value among the three groups, with the native T 1 value of the AFD group [(1 177.4±46.0) ms] was significantly lower than that of the healthy group [(1 244.5±34.3) ms] and the HCM group [(1 278.8±41.6) ms], with ( F=13.10, P<0.001). Conclusions:The clinical characteristics of AFD and HCM are quite similar. When AFD is suspected, CMR imaging should be the first choice for imaging examination. Especially, T 1 mapping imaging can provide important information for the diagnosis of AFD.