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 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 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.

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 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.

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

This study was aimed at identifying species of ticks and investigating infections with tick-borne pathogens a-mong people in Yadong,Tibet.The total of 23 ticks(Ixodes and Haemaphysalis)collected from livestock in Yadong,Tibet in July 2021,the gene sequences of cytochrome oxidase subunitⅠ(COX Ⅰ),mitochondrial 16S ribosomal DNA(16S rDNA)and mitochondrial 12S ribosomal DNA(12S rDNA)were identi-fied on the basis of molecular biology classification.The gene sequences of spotted fever group rickettsia(SFGR),Borrelia burgdorferi,Francisella tularensis and Coxiella burnetii in ticks were amplified by PCR and sequenced,and phylogenetic ana-lyses were performed.In addition,184 serum samples collected from Yadong in 2021 were screened for antibodies to Lyme dis-ease,Q fever,spotted fever,and tularemia by ELISA,and infections with tick-borne pathogens in Yadong were comprehen-sively analyzed.The ticks(Ixodes)collected in Yadong,Tibet,were grouped into two categories.The COX Ⅰ,16S rDNA,and 12S rDNA gene sequences of the ticks had 99.5％,97.57％,and 99.12％ similarity,respectively,to those of Ixodes nuttallia-nus in GenBank.The similarities between the COX Ⅰ and 16S rDNA gene sequences of another Ixodes tick species and the COXⅠ and 16S rDNA gene sequences of Ixodes ovatus in GenBank were 88.29％ and 95.75％,respectively.The similarity between the COX Ⅰ,16S rDNA,and 12S rDNA gene sequences of Haemaphysalis ticks and those of Haemaphysalis Tibet in GenBank were 96.04％,96.17％,and 97.47％,respectively.The sequence amplification results for Borrelia burgdorferi,Francisella tularensis,and Coxsiella burnetii in 23 ticks were negative,whereas gltA gene amplification of spotted fever group Rickettsia in 23 ticks was positive.The similarity of gltA gene sequences with respect to those of Candidatus Rickettsia tarasevichiae,Rickettsia raoultii,Rickettsia canadensis,and a Rickettsia endosymbiont of Eucalyptus brunneri in GenBank was 96.77％,96.76％,95.35％,and 95.35％,respectively.Among 184 serum samples from Yadong,the positivity rates of Lyme disease,Q fever,spotted fever,and tularemia were 6.52％,12.50％,8.70％,and 10.87％,respectively.These results indicated that the 23 parasitic ticks collected in Yadong,Tibet,in July 2021 were Ixodes nuttallianus,Ixodes ovatus and Haemaphysalis ti-betensis,and 23 ticks were infected with SFGR.Lyme disease,Q fever,spotted fever,and tularemia infection were prevalent in the population of Yadong.Therefore,efforts to control tick-borne diseases must be strengthened.

Objective:To investigate the effect of early postoperative enteral nutrition(EN)on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer,in order to provide reference for postoperative rehabilitation of such patients.Methods:Patients who received laparoscopic assisted radical gastrectomy in Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2020 to December 2022 were included in the analysis.According to the different ways of postoperative nutritional treatment,patients were divided into the observation group(early postoperative EN group)and the control group(parenteral nutrition group),and indexes such as postoperative rehabilitation,abdominal drainage flow and the level of inflammatory mediators in drainage fluid were compared between the two groups.Results:A total of 81 patients were included,including 41 in the observation group and 40 in the control group.Interval of the first postoperative exhaust(t=3.806;P＜0.001)and resuming diet day(t=5.510;P＜0.001),and length of postoperative hospital stay(t=2.401;P=0.019)in the observation group were shorter than those in the control group.Levels of peripheral blood albumin(t=14.040;P＜0.001)and prealbumin(t=9.832;P＜0.001)of the observation group at postoperative day(POD)5 were significantly higher than those of the control group,but there was no significant difference in hemoglobin level(t=1.477;P=0.144).The level of CRP in peripheral blood of the observation group at POD 5(t=7.758;P＜0.001)and the incidence of postoperative SIRS[(12.2％,5/41)vs(32.5％,13/40),x2=4.830;P=0.028)]were significantly lower than those in the control group.The average drainage volume(t=6.858;P＜0.001),drainage removal time(t=5.016;P＜0.001),and TNF-α level(t=4.993;P＜0.001)and IL-6 level(t=20.640;P＜0.001)in postoperative drainage at POD 5 were significantly lower in the observation group than those in the control group.Conclusion:Early postoperative EN could accelerate the rehabilitation process after laparoscopic radical gastrectomy,improve postoperative nutritional status,and reduce abdominal inflammation.

Objective To explore the change of brain functional connectivity strength in patients with type 2 diabetes mellitus(T2DM)and its neuropathological mechanism.Methods Fifty-six T2DM patients who visited Gansu Provincial Hospital from October 2017 to March 2021 were selected as T2DM group,and 48 healthy controls were selected as control group.A prospective study was conducted on the changes in brain function in T2DM patients by analysis of resting state functional connectivity strength(FCS)and functional connectivity(FC)based on seed points.Brain functional magnetic resonance imaging,clinical variable collection,and neuropsychological testing of patients in two groups were performed.We calculate the FCS value,evaluate the brain function changes of the two groups in the resting state,take the brain regions with significant differences between the groups as the seed points and perform functional connectivity analysis with the whole brain.Correlation analysis was conducted between the FCS,FC values of the different brain regions and clinical variables such as fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),thyroid hormone(TSH)levels,as well as the scores of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),clock drawing test(CDT),Hamilton Depression Rating Scale(HAMD-24)and Hamilton Anxiety Scale(HAMA).Results Compared with control group,the HAMD-24 and HAMA scores in T2DM group significantly increased(P<0.01),while the MoCA scores decreased(P<0.05);In T2DM group,the FCS value of the right middle temporal gyrus increased(GRF correction,voxel level P<0.001,clustering level P<0.05),and the FC value of the right middle temporal gyrus-left anterior cingulate cortex decreased(GRF correction,voxel level P<0.001,clustering level P<0.05).Correlation analysis showed that the FC value of right middle temporal gyrus-left anterior cingulate cortex in T2DM patients was negatively correlated with HAMD-24 score(r=-0.395,P=0.003),HbA1c level(r=-0.303,P=0.023),and positively correlated with TSH level(r=0.324,P=0.017).Conclusions The increase of FCS value in the right middle temporal gyrus and the decrease of FC value in the right middle temporal gyrus-left anterior cingulate cortex may be important neuroimaging features of brain function damage in T2DM patients.HbA1c may play an important role in the process of brain damage in T2DM patients.