BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

Objective:To explore the impact of National Metabolic Management Center (MMC) mode on the metabolic indexes in different age patients with type 2 diabetic mellitus (T2DM).Methods:A prospective study method was used. A total of 798 T2DM patients underwent the MMC mode management in Shanghai Punan Hospital of Pudong New District from May 2021 to August 2024 were selected. The patients followed the MMC one-stop diagnosis and treatment management service standards to enter the registration, treatment, examination and follow-up processes. The average follow-up time was 12.0 months. The glucose and lipid metabolism indexes, blood pressure and body mass index (BMI) before intervention and after receiving the intervention by MMC were measured. The glucose and lipid metabolism indexes included triacylglycerol, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin. The control rates of blood glucose, blood lipid, blood pressure and BMI were calculated after intervention.Results:The triacylglycerol, total cholesterol, LDL-C, fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin after intervention in patients with T2DM were significantly lower than those before intervention: (1.75 ± 1.63) mmol/L vs. (2.08 ± 1.74) mmol/L, (4.37 ± 1.11) mmol/L vs. (4.88 ± 1.24) mmol/L, (2.47 ± 0.92) mmol/L vs. (2.92 ± 0.98) mmol/L, (6.54 ± 1.71) mmol/L vs. (8.12 ± 3.05) mmol/L, (9.04 ± 3.49) mmol/L vs. (12.10 ± 5.28) mmol/L and (6.89 ± 1.23)% vs. (8.85 ± 2.31)%, the HDL-C after intervention was significantly higher than that before intervention: (1.21 ± 0.31) mmol/L vs. (1.13 ± 0.29) mmol/L, and there were statistical differences ( P<0.01). The control rates of blood lipid and blood glucose after intervention in patients with T2DM were significantly higher than those before intervention: 54.6% (436/798) vs. 37.3% (298/798) and 62.0% (495/798) vs. 26.1% (208/798), and there were statistical differences ( P<0.01); there were no statistical differences in the control rates of BMI and blood pressure before intervention and after intervention ( P>0.05). In T2DM patients with age <50 years and from 50 to 59 years, the triacylglycerol, total cholesterol, LDL-C, fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin after intervention were significantly lower than those before intervention, the HDL-C after intervention was significantly higher than that before intervention, and there were statistical differences ( P<0.05 or <0.01); the control rates of blood lipid and blood glucose after intervention were significantly higher than those before intervention, the patients with <50 years: 44.5% (114/256) vs. 27.7% (71/256) and 76.6% (196/256) vs. 28.9% (74/256), the patients with 50 to 59 years: 54.8% (86/157) vs. 28.0% (44/157) and 66.9% (105/157) vs. 24.8% (39/157), and there were statistical differences ( P<0.01); there were no statistical differences in the control rates of BMI and blood pressure between before intervention and after intervention ( P>0.05). In T2DM patients with age from 60 to 69 years, the triacylglycerol, total cholesterol, LDL-C, fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin after intervention were significantly lower than those before intervention, and there were statistical differences ( P<0.05 or <0.01); there was no statistical differences in HDL-C before intervention and after intervention ( P>0.05); the control rates of blood lipid and blood glucose after intervention were significantly higher than those before intervention: 59.0% (177/300) vs. 47.3% (142/300) and 53.3% (160/300) vs. 25.7% (77/300), and there were statistical differences ( P<0.01); there were no statistical differences in the control rates of BMI and blood pressure before intervention and after intervention ( P>0.05). In T2DM patients with aged ≥70 years, the total cholesterol, LDL-C, 2 h postprandial blood glucose and glycated hemoglobin after intervention were significantly lower than those before intervention, and there were statistical differences ( P<0.05 or <0.01); there were no statistical difference in triacylglycerol, HDL-C and fasting blood glucose between before intervention and after intervention ( P>0.05); the control rate of blood glucose after intervention was significantly higher than that before intervention: 48.2% (41/85) vs. 22.4% (19/85), and there was statistical difference ( P<0.01); there were no statistical differences in the control rates of BMI, blood pressure and blood lipid between before intervention and after intervention ( P>0.05). Conclusions:The intervention based on MMC mode management could effectively improve the glucose and lipid metabolism in patients with T2DM, especially for patients with aged <70 years. However, additional health guidance is needed for patients with aged ≥ 70 years to further enhance their health benefits.

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

BACKGROUND: Gait impairment is closely related to quality of life in patients with Parkinson's disease (PD). This study aimed to explore alterations in brain microstructure in PD patients and healthy controls (HCs) and to identify the correlation of gait impairment in the ON and OFF states of patients with PD, respectively. METHODS: We enrolled 24 PD patients and 29 HCs from the Movement Disorders Program at Beijing Friendship Hospital Capital Medical University between 2019 and 2020. We acquired magnetic resonance imaging (MRI) scans and processed the diffusion kurtosis imaging (DKI) images. Preprocessing of diffusion-weighted data was performed with Mrtrix3 software, using a directional distribution function to track participants' main white matter fiber bundles. Demographic and clinical characteristics were recorded. Quantitative gait and clinical scales were used to assess the status of medication ON and OFF in PD patients. RESULTS: The axial kurtosis (AK), mean kurtosis (MK), and radial kurtosis (RK) of five specific white matter fiber tracts, the bilateral corticospinal tract, left superior longitudinal fasciculus, left anterior thalamic radiation, forceps minor, and forceps major were significantly higher in PD patients compared to HCs. Additionally, the MK values were negatively correlated with Timed Up and Go Test (TUG) scores in both the ON and OFF in PD patients. Within the PD group, higher AK, MK, and RK values, whether the patients were ON or OFF, were associated with better gait performance (i.e., higher velocity and stride length). CONCLUSIONS PD exhibits characteristic regional patterns of white matter microstructural degradation. Correlations between objective gait parameters and DKI values suggest that dopamine-responsive gait function depends on preserved white matter microstructure. DKI-based Tract-Based Spatial Statistics (TBSS) analysis may serve as a tool for evaluating PD-related motor impairments (e.g., gait impairment) and could yield potential neuroimaging biomarkers.
Humans ; Parkinson Disease/diagnostic imaging* ; White Matter/physiopathology* ; Male ; Female ; Middle Aged ; Aged ; Gait/physiology* ; Diffusion Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods*

Blood-bi-syndrome is primarily characterized by localized numbness and mild pain in the limbs.Records about the diagnosis and treatment of blood-bi-syndrome are scattered throughout classical medical literature.According to the theory of Yindan and Yangdan formulas in the classical prescription system,when the body's ascending function of qi movement is insufficiency,Yangdan formulas which contain Astragali Radix can be used for warming and uplifting yang qi.Conversely,when the descending function of qi movement is insufficiency,Yindan formulas which contain containing Bupleuri Radix can be used for astringing,descending,clearing and purging.This article,based on the principles of Yindan and Yangdan formulas,analyzed the fundamental pathogenesis of blood-bi-syndrome developing from the transmission of superficial syndromes,as well as its clinical manifestations during the transmission and change between taiyin disease and yangming disease.And the therapeutic strategies for blood-bi-syndrome were also summarized.It is proposed that taiyin blood-bi-syndrome arises in individuals with constitutionally deficient cold after the attack of pathogenic factors,resulting from fluid depletion,blood insufficiency,and stomach deficiency,which should be treated by Yangdan Formulas with pungent-sweet-warm properties for warming and uplifting yang qi.For the treatment of patients with taiyin blood-bi-syndrome characterized by exterior syndrome,Astragali Radix-containing classical prescriptions like Astragali Radix and Cinnamomi Ramulus Five-Component Decoction(Huangqi Guizhi Wuwu Decoction)can be chosen;for the treatment of patients with taiyin blood-bi-syndrome characterized by interior syndrome,Zingiberis Rhizoma Recens-containing classical prescriptions like Citri Reticulatae Pericarpium and Bambusae Caulis in Taenia Decoction(Jupi Zhuru Decoction)is adopted.Conversely,yangming blood-bi-syndrome occurs in individuals with constitutionally excessive heat after the attack of pathogenic factors,resulting from the internal accumulation of blood stasis and heat and the impairment of the fluid and blood,which should be treated by Yindan Formulas with pungent-sweet-cold or sour-cold properties for astringing,descending,clearing and purging.For the treatment of patients with yangming blood-bi-syndrome characterized by exterior syndrome,Puerariae Lobatae Radix-containing classical prescriptions like Phyllostachydis Henonis Folium and Puerariae Lobatae Radix Decoction(Zhuye Gegen Decoction)can be used;for the treatment of patients with yangming blood-bi-syndrome characterized by interior syndrome,Paeoniae Radix Alba-containing classical prescriptions like Rhei Radix et Rhizoma and Eupolyphaga seu Steleophaga Decoction(Dahuang Zhechong Wan)is recommended.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To investigate the effect of irbesartan on hypoxia reoxygenation(HR)induced myocardial cell pyropto-sis by regulating the cGAS-STING signaling pathway.Methods:H9c2 myocardial cells were cultured in vitro and grouped into control group,HR group,low-dose irbesartan group,high-dose irbesartan group,high-dose irbesartan+RocA(cGAS-STING signaling path-way activator)group,and RU.521(cGAS-STING signaling pathway inhibitor)group.Cell viability was detected by CCK-8;ELISA was applied to detect levels of lactate dehydrogenase(LDH),IL-6,IL-18 and IL-1β;propidium iodide(PI)staining method was applied to detect the formation of cell membrane pores;RT-qPCR method was applied to detect the expressions of cGAS and STING mRNA in cells;Western blot method was applied to detect the expressions of NLRP3,Caspase-1,GSDMD,cGAS and STING pro-teins.Results:Compared with the control group,the A450 values(24 h,48 h)of H9c2 cells in the HR group were obviously reduced,the levels of LDH,IL-6,IL-18,IL-1β,PI staining positive rate,the expressions of cGAS,STING mRNA,the expressions of NLRP3,Caspase-1,GSDMD,cGAS,STING proteins were obviously increased(P<0.05);compared with the HR group,the A450 values(24 h,48 h)of H9c2 cells in the low and high dose irbesartan groups and the RU.521 group were obviously increased,the levels of LDH,IL-6,IL-18,IL-1β,PI staining positive rate,the expressions of cGAS,STING mRNA,the expressions of NLRP3,Caspase-1,GSDMD,cGAS,STING proteins were obviously reduced(P<0.05);RocA was able to partially reverse the protective effect of irbe-sartan on HR-induced myocardial cells(P<0.05);the detection indicators of H9c2 cells in the RU.521 group were at the same level as those in the high-dose irbesartan group(P>0.05).Conclusion:Irbesartan can inhibit HR-induced myocardial cell pyrop-tosis by inhibi-ting the cGAS-STING signaling pathway.

Objective:To investigate the effect of irbesartan on hypoxia reoxygenation(HR)induced myocardial cell pyropto-sis by regulating the cGAS-STING signaling pathway.Methods:H9c2 myocardial cells were cultured in vitro and grouped into control group,HR group,low-dose irbesartan group,high-dose irbesartan group,high-dose irbesartan+RocA(cGAS-STING signaling path-way activator)group,and RU.521(cGAS-STING signaling pathway inhibitor)group.Cell viability was detected by CCK-8;ELISA was applied to detect levels of lactate dehydrogenase(LDH),IL-6,IL-18 and IL-1β;propidium iodide(PI)staining method was applied to detect the formation of cell membrane pores;RT-qPCR method was applied to detect the expressions of cGAS and STING mRNA in cells;Western blot method was applied to detect the expressions of NLRP3,Caspase-1,GSDMD,cGAS and STING pro-teins.Results:Compared with the control group,the A450 values(24 h,48 h)of H9c2 cells in the HR group were obviously reduced,the levels of LDH,IL-6,IL-18,IL-1β,PI staining positive rate,the expressions of cGAS,STING mRNA,the expressions of NLRP3,Caspase-1,GSDMD,cGAS,STING proteins were obviously increased(P<0.05);compared with the HR group,the A450 values(24 h,48 h)of H9c2 cells in the low and high dose irbesartan groups and the RU.521 group were obviously increased,the levels of LDH,IL-6,IL-18,IL-1β,PI staining positive rate,the expressions of cGAS,STING mRNA,the expressions of NLRP3,Caspase-1,GSDMD,cGAS,STING proteins were obviously reduced(P<0.05);RocA was able to partially reverse the protective effect of irbe-sartan on HR-induced myocardial cells(P<0.05);the detection indicators of H9c2 cells in the RU.521 group were at the same level as those in the high-dose irbesartan group(P>0.05).Conclusion:Irbesartan can inhibit HR-induced myocardial cell pyrop-tosis by inhibi-ting the cGAS-STING signaling pathway.

Objective:To explore the impact of National Metabolic Management Center (MMC) mode on the metabolic indexes in different age patients with type 2 diabetic mellitus (T2DM).Methods:A prospective study method was used. A total of 798 T2DM patients underwent the MMC mode management in Shanghai Punan Hospital of Pudong New District from May 2021 to August 2024 were selected. The patients followed the MMC one-stop diagnosis and treatment management service standards to enter the registration, treatment, examination and follow-up processes. The average follow-up time was 12.0 months. The glucose and lipid metabolism indexes, blood pressure and body mass index (BMI) before intervention and after receiving the intervention by MMC were measured. The glucose and lipid metabolism indexes included triacylglycerol, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin. The control rates of blood glucose, blood lipid, blood pressure and BMI were calculated after intervention.Results:The triacylglycerol, total cholesterol, LDL-C, fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin after intervention in patients with T2DM were significantly lower than those before intervention: (1.75 ± 1.63) mmol/L vs. (2.08 ± 1.74) mmol/L, (4.37 ± 1.11) mmol/L vs. (4.88 ± 1.24) mmol/L, (2.47 ± 0.92) mmol/L vs. (2.92 ± 0.98) mmol/L, (6.54 ± 1.71) mmol/L vs. (8.12 ± 3.05) mmol/L, (9.04 ± 3.49) mmol/L vs. (12.10 ± 5.28) mmol/L and (6.89 ± 1.23)% vs. (8.85 ± 2.31)%, the HDL-C after intervention was significantly higher than that before intervention: (1.21 ± 0.31) mmol/L vs. (1.13 ± 0.29) mmol/L, and there were statistical differences ( P<0.01). The control rates of blood lipid and blood glucose after intervention in patients with T2DM were significantly higher than those before intervention: 54.6% (436/798) vs. 37.3% (298/798) and 62.0% (495/798) vs. 26.1% (208/798), and there were statistical differences ( P<0.01); there were no statistical differences in the control rates of BMI and blood pressure before intervention and after intervention ( P>0.05). In T2DM patients with age <50 years and from 50 to 59 years, the triacylglycerol, total cholesterol, LDL-C, fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin after intervention were significantly lower than those before intervention, the HDL-C after intervention was significantly higher than that before intervention, and there were statistical differences ( P<0.05 or <0.01); the control rates of blood lipid and blood glucose after intervention were significantly higher than those before intervention, the patients with <50 years: 44.5% (114/256) vs. 27.7% (71/256) and 76.6% (196/256) vs. 28.9% (74/256), the patients with 50 to 59 years: 54.8% (86/157) vs. 28.0% (44/157) and 66.9% (105/157) vs. 24.8% (39/157), and there were statistical differences ( P<0.01); there were no statistical differences in the control rates of BMI and blood pressure between before intervention and after intervention ( P>0.05). In T2DM patients with age from 60 to 69 years, the triacylglycerol, total cholesterol, LDL-C, fasting blood glucose, 2 h postprandial blood glucose and glycated hemoglobin after intervention were significantly lower than those before intervention, and there were statistical differences ( P<0.05 or <0.01); there was no statistical differences in HDL-C before intervention and after intervention ( P>0.05); the control rates of blood lipid and blood glucose after intervention were significantly higher than those before intervention: 59.0% (177/300) vs. 47.3% (142/300) and 53.3% (160/300) vs. 25.7% (77/300), and there were statistical differences ( P<0.01); there were no statistical differences in the control rates of BMI and blood pressure before intervention and after intervention ( P>0.05). In T2DM patients with aged ≥70 years, the total cholesterol, LDL-C, 2 h postprandial blood glucose and glycated hemoglobin after intervention were significantly lower than those before intervention, and there were statistical differences ( P<0.05 or <0.01); there were no statistical difference in triacylglycerol, HDL-C and fasting blood glucose between before intervention and after intervention ( P>0.05); the control rate of blood glucose after intervention was significantly higher than that before intervention: 48.2% (41/85) vs. 22.4% (19/85), and there was statistical difference ( P<0.01); there were no statistical differences in the control rates of BMI, blood pressure and blood lipid between before intervention and after intervention ( P>0.05). Conclusions:The intervention based on MMC mode management could effectively improve the glucose and lipid metabolism in patients with T2DM, especially for patients with aged <70 years. However, additional health guidance is needed for patients with aged ≥ 70 years to further enhance their health benefits.