OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Objective To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty(PKP)of vertebrae following local anesthesia.Methods From August 2019 to June 2021,118 patients with thora-co lumbar osteoporotic fractures were treated and divided into observation group and control group,with 59 patients in each gruop.In observation group,there were 26 males and 33 females,aged from 57 to 80 years old with an average of(67.69±4.75)years old;14 patients on T11,12 patients on T12,18 patients on L1,15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group.In control group,there were 24 males and 35 females,aged from 55 to 77 years old with an average of(68.00±4.43)years old;19 patients on T11,11 patients on T12,17patients on L1,12 patients on L2;the same amount of normal saline was injected intramuscularly in control group.Observation indicators included operation time,intraoperative bleeding,visual analogue scale(VAS)evaluation and recording of preoperative(T0),intraoper-ative puncture(T1),and working cannula placement(T2)between two groups of patients,at the time of balloon dilation(T3),when the bone cement was injected into the vertebral body(T4),2 hours after the operation(T5),and the pain degree at the time of discharge(T6);adverse reactions such as dizziness,nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery.Results All patients were successfully completed PKP via bilateral pedicle ap-proach,and no intravenous sedative and analgesic drugs were used during the operation.There was no significant difference in preoperative general data and VAS(T0)between two groups(P＞0.05).There was no significant difference in operation time and intraoperative blood loss between the two groups(P＞0.05).VAS of T1,T2,T3,T4 and T5 in observation group were all lower than those in control group(P＜0.05),and there was no significant difference in T6 VAS(P＞0.05).T6 VAS between two groups were significantly lower than those of T0,and the difference was statistically significant(P＜0.05).There was no signifi-cant difference in incidence of total adverse reactions between two groups(P＞0.05).There was a statistically significant differ-ence in the acceptance of repeat PKP surgery(P＜0.05).Conclusion Half an hour before operation,intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia,which could increase the comfort of patients during operation and 2 hours after operation,and improve patients satisfaction with surgery.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective: To explore the prevalence of elevated blood pressure and overweight/obesity and their comorbidities among Tibetan middle school students in Lhasa, and to analyze their association with lifestyle and other factors, so as to provide a basis for the intervention measures targeting elevated blood pressure, overweight and obesity among middle school students in high altitude area. Methods: Using a stratified cluster random sampling method in September 2021, a total of 1 488 Tibetan junior and high students from Lhasa City were investigated with blood pressure measurement, physical examination and questionnaire survey. The influencing factors of elevated blood pressure, overweight and obesity and their comorbidities association were analyzed by multivariate Logistic regression. Results: The prevalence of elevated blood pressure, overweight/obesity and their comorbidities were 17.8%, 17.4% , 5.0% respectively. Multivariate Logistic regression analysis showed that age( OR =0.81), residence, body mass inex(BMI) and gender were the influencing factors of elevated blood pressure; and the risks of elevated blood pressure in female students were higher than male students ( OR =1.89), suburban students were higher than urban students ( OR =8.06), overweight and obesity groups were higher than normal groups ( OR =2.55, 2.87) ( P <0.05). Adjusting for confounding factors such as gender, residence and school, and BMI (only for elevated blood pressure), daily screen time ≥2 h was positively correlated with elevated blood pressure, overweight/obesity and its comorbidities ( OR =1.56, 1.59 , 2.51) ( P <0.05). Conclusions The prevalence of elevated blood pressure, overweight/obesity are relatively high in Lhasa. Longer screen time is a common factor affecting with elevated blood pressure, overweight/obesity and comorbidities among Tibetan students. Measures should be taken intervene in the lifestyle of Tibetan students, in order to reduce elevated blood pressure and overweight/obesity.

Objective To study the mechanism of polyene phosphatidylcholine in improving metabolic disorders and fatty liver induced by high fat diet.Methods Thirty-two C57BL/6 mice were randomly divided into blank group,control group,model group and experimental group.The blank group was fed with low-fat diet and intraperitoneal injection of 10％glucose 200 μL twice a week.Control group was fed with low-fat diet twice a week and intraperitoneally injected 10％glucose solution 200 μL containing polyene phosphatidylcholine(PPC)20 μg.Model group was fed with high-fat diet and intraperitoneal injection of 10％glucose 200 μL twice a week.Experimental group was fed with high-fat diet twice a week and intraperitoneally injected 10％glucose solution 200 μL containing PPC 20 μg.The body weight of the mice was measured,blood glucose test strips and insulin resistance was analyzed.The levels of triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),glutamic oxalic aminotransferase(GOT)and glutamic pyruvic aminotransferase(GPT)in serum and liver were analyzed by biochemical method.The levels of tumor necrosis factor-α(TNF-α),interleukin-6 and IL-8 were detected by enzyme-linked immunosorbent assay(ELISA).Results The serum TG levels of blank group,control group,model group and experimental group were(0.15±0.01),(0.11±0.01),(0.21±0.01)and(0.12±0.01)mmol·L-1;LDL levels were(0.41±0.01),(0.25±0.01),(0.71±0.02)and(0.49±0.01)mmol·L-1;GOT levels were(30.30±0.89),(31.39±1.18),(43.04±2.82)and(25.64±0.72)mmol·L-1;GPT levels were(9.15±0.45),(7.39±1.88),(12.87±1.81)and(7.96±1.64)mmol·L-1;fasting blood glucose levels were(4.97±0.08),(6.08±0.18),(8.12±0.20)and(7.29±0.02)mmol·L-1;fasting insulin levels were(6.52±1.11),(5.45±0.28),(54.83±4.32)and(30.55±2.73)mU·L-1;the levels of TNF-α in liver tissues were(3.98±0.63),(3.95±0.98),(20.55±4.71)and(15.28±1.73)pg·g-1;IL-6 levels were(18.93±8.56),(17.64±3.29),(59.40±4.63)and(37.54±7.33)pg·g-1;IL-8 levels were(67.16±12.37),(59.44±3.58),(198.40±9.27)and(132.10±7.04)pg·g-1.The difference of above indicatory between experimental group and model group was statistically significant(all P＜0.05).Conclusion Polyene phosphatidylcholine may inhibit the expression of TNF-α,IL-6 and IL-8 inflammatory factors by mediating the inhibition of inflammation on liver tissue and then improve metabolic disorders.

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.
Cannabinoid Receptor Modulators/pharmacology* ; Cannabinoid Receptor Agonists/pharmacology* ; Receptors, Cannabinoid ; Cannabinoids/pharmacology* ; Anti-Inflammatory Agents/pharmacology*

Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.