Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

OBJECTIVES: To study the role of microRNA (miR)-30d-5p in high glucose-induced podocyte injury. METHODS: Podocytes were hyperglycated with 30 mmol/L glucose, transfected with miR-30d-5p inhibitor and mimic, and then treated with 1 mg/mL 3-methyladenine (3-MA). The transfection efficiency of miR-30d-5p was quantified by reverse transcription PCR. Apoptosis was detected by flow cytometry. The expressions of nephrin, microtubule-associated protein light chain (LC) 3Ⅱ/LC3Ⅰ, P62, autophagy-related gene (ATG) 5, PTEN induced putative kinase (PINK) 1 and Parkin gene (PARK2) were detected by Western blotting. The mito-chondrial membrane potential was detected by JC-1 fluorescent probe, and adenosine triphosphate (ATP) content in cells was detected by relevant kits. RESULTS: Under high glucose induction, podocyte apoptosis increased, miR-30d-5p and P62 expressions were upregulated, while nephrin, ATG5, PINK1, PARK2 and LC3Ⅱ/LC3Ⅰ expressions decreased (all P<0.01). MiR-30d-5p inhibitor reversed the effect of high glucose on apoptosis, and the expression of ATG5, PINK1, PARK2, nephrin, LC3Ⅱ/LC3Ⅰ and P62 (all P<0.01). High glucose induced loss of mitochondrial membrane potential and ATP content in podocytes, while inhibition of miR-30d-5p increased them. Autophagy inhibitors 3-MA and miR-30d-5p mimics reversed the effects of miR-30d-5p inhibition on apoptosis, autophagy and mitochondrial function of podocytes induced by high glucose (all P<0.05). CONCLUSIONS Inhibition of miR-30d-5p may promote mitochondrial autophagy (mitophagy) by promoting the expression of ATG5, PINK1, PARK2 and alleviating high glucose-induced podocyte damage.
Podocytes/drug effects* ; MicroRNAs/metabolism* ; Glucose/adverse effects* ; Autophagy/drug effects* ; Animals ; Mice ; Autophagy-Related Protein 5/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Membrane Proteins/genetics* ; Membrane Potential, Mitochondrial/drug effects* ; Microtubule-Associated Proteins/genetics* ; Protein Kinases

Background: There is no standard cut-off value of serum IgG4 concentration and serum IgG4/total IgG ratio for the diagnosis of IgG4-related disease (IgG4-RD) or as a marker of treatment responses. We aimed to explore this issue through a retrospective cohort analysis of adults in southwest China. Methods: The diagnostic performance of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD was evaluated in a retrospective analysis of 177 adults newly diagnosed as having IgG4-RD and 877 adults without IgG4-RD. Dynamic analysis was performed to evaluate the significance of serum IgG4 concentration on IgG4-RD treatment responses. Results: The serum IgG4 concentration differed according to sex. The optimal cut-off values of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD diagnosis were 1.92 g/L and 0.12 in males and 1.83 g/L and 0.11 in females, respectively. For patients with serum IgG4 concentration >2.01 g/L, the cut-off values in the total population were >3.00 g/L and 0.19, respectively. The median serum IgG4 concentration decreased over time, and the decrease rate increased over time. The serum IgG4 concentration significantly decreased at >1 week post-treatment (P=0.004), and the median decrease rate was close to 50% at >4 weeks post-treatment. Conclusions Serum IgG4 can be a good indicator for IgG4-RD diagnosis; however, different diagnostic cut-off values should be determined according to sex. The decreasing rate is more conducive than the serum IgG4 concentration to monitor treatment efficacy. The IgG4/IgG ratio did not improve the diagnostic efficacy for IgG4-RD.

Humans ; Whooping Cough/prevention & control* ; Vaccines, Acellular ; China

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE

Objective: To analyze the safety and efficacy of combined left atrial appendage (LAA) and patent foramen ovale (PFO) closure in adult atrial fibrillation (AF) patients complicating with PFO. Methods: This study is a retrospective and cross-sectional study. Seven patients with AF complicated with PFO diagnosed by transesophageal echocardiography (TEE) in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to October 2020 were selected. Basic data such as age, gender and medical history were collected. The atrial septal defect or PFO occluder and LAA occluder were selected according to the size of PFO, the ostia width and depth of LAA. Four patients underwent left atrial appendage closure(LAAC) and PFO closure at the same time. PFO closure was performed during a one-stop procedure of cryoablation combined with LAAC in 2 patients. One patient underwent PFO closure at 10 weeks after one-stop procedure because of recurrent transient ischemic attack (TIA). All patients continued to take oral anticoagulants. TEE was repeated 8-12 weeks after intervention. In case of device related thrombus(DRT), TEE shall be rechecked 6 months after adjusting anticoagulant and antiplatelet drug treatment. Patients were follow-up at 1, 3, 6, 12, 24 months by telephone call, and the occurrence of cardio-cerebrovascular events was recorded. Results: Among the 7 patients with AF, 2 were male, aged (68.0±9.4) years, and 3 had a history of recurrent cerebral infarction and TIA. Average PFO diameter was (3.5±0.8)mm. Three patients were implanted with Watchman LAA occluder (30, 30, 33 mm) and atrial septal defect occluder (8, 9, 16 mm). 2 patients were implanted with LAmbre LAA occluder (34/38, 18/32 mm) and PFO occluder (PF1825, PF2525). 2 patients were implanted with LACbes LAA occluder (24, 28 mm) and PFO occluder (PF2525, PF1825) respectively. The patients were followed up for 12 (11, 24) months after operation. TEE reexamination showed that the position of LAA occluder and atrial septal defect occluder or PFO occluder was normal in all patients. DRT was detected in 1 patient, and anticoagulant therapy was adjusted in this patient. 6 months later, TEE showed that DRT disappeared. No cardiovascular and cerebrovascular events occurred in all patients with AF during follow-up. Conclusions: In AF patients complicated with PFO, LAAC combined with PFO closure may have good safety and effectiveness.
Adult ; Aged ; Atrial Appendage/surgery* ; Atrial Fibrillation/surgery* ; Cardiac Catheterization/methods* ; China ; Cross-Sectional Studies ; Foramen Ovale, Patent/surgery* ; Humans ; Male ; Middle Aged ; Retrospective Studies

Objective: To evaluate the effectiveness and safety of Pul-Stent as the treatment of postoperative branch pulmonary artery stenosis in children with congenital heart disease. Methods: This was a retrospective study. Thirty-three patients who underwent Pul-Stent implantation in Shanghai Children's Medical Center due to postoperative residual pulmonary artery stenosis from August 2014 to June 2015 were included. The immediate curative effect, follow-up and complications of Pul-Stent implantation were assessed. Comparisons between groups were performed with unpaired Student t test. Results: Pul-Stent implantation of 33 patients (19 males and 14 females) were performed successfully. Thirty-one patients underwent percutaneous stenting, and 2 patients underwent hybrid stenting. A total of 35 Pul-Stents were implanted (19 of model small, 15 of model medium and one of model large), 23 stents were planted in the proximal left pulmonary artery and 12 stents were in the proximal right pulmonary artery. The initial diameter of dilation balloon ranged from 6 to 16 mm, and the long sheath of percutaneous implantation ranged from 8 to 10 F in 29 patients (29/31, 94%). After stenting, the diameter of the narrowest segment of pulmonary artery increased from (4.0±1.7) mm to (9.1±2.1) mm in all patients (t=-21.60, P<0.001). The pressure gradient at the stenosis in 26 patients after biventricular correction decreased from (30.5±12.3) mmHg (1 mmHg=0.133 kPa) to (9.9±9.6) mmHg (t=12.92, P<0.001), and the right ventricular to aortic pressure ratio decreased from 0.57±0.14 to 0.44±0.12 (t=7.44, P<0.001). The pressure of the superior vena cava after stenting in 5 patients after cavopulmonary anastomosis decreased from (17.0±1.9) mmHg to (14.0±0.7) mmHg (t=2.86, P=0.046). Two patients died during reoperation for repairing other cardiac malformations. The remaining 31 patients were clinically stable during the follow-up period of (5.3±1.6) years, and one stent fracture was found on chest X-ray. Cardiac catheterization reexaminations in 16 patients showed that restenosis was found in one stent, while stent position and patency were satisfactory in the remaining stents. Nine children underwent post-dilation without stent fracture, displacement or aneurysm formation. Cardiac tomography showed no stent stenosis, fracture observed, or significant change in diameter of the stent in 8 patients. The inner diameter and pulmonary blood perfusion could not be accurately evaluated due to artifacts by cardiac magnetic resonance imaging in 4 patients. Conclusions: Pul-Stent has good compliance and adequate radial strength, and can dilate further over time to accommodate for somatic growth. It performs safely and effectively in treating post-operative branch pulmonary artery stenosis in children.
Child ; China ; Female ; Follow-Up Studies ; Heart Defects, Congenital/surgery* ; Humans ; Male ; Pulmonary Artery/surgery* ; Retrospective Studies ; Stenosis, Pulmonary Artery/surgery* ; Stents ; Treatment Outcome ; Vena Cava, Superior