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Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.
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BACKGROUND:Previous studies have shown that N-methyl-D-aspartic acid receptor(NMDA)receptors are associated with fluorine,but the role in fluoride-induced endoplasmic reticulum stress remains unclear. OBJECTIVE:To observe the changes of excitatory neurotransmitter NMDA receptor and endoplasmic reticulum stress IRE1α-ASK1-JNK pathway protein expression in brain tissue of rats with experimental fluorosis,and to investigate the pathogenesis of neurological injury in fluorosis by giving NMDA receptor inhibitor to SH-SY5Y cells. METHODS:(1)Animal model:18 1-month-old SD rats were randomly divided into control group(drinking water fluoride content<0.5 mg/L),low fluoride group(drinking water fluoride content 10.0 mg/L)and high fluoride group(drinking water fluoride content 100.0 mg/L),with 6 rats in each group,half of each sex.After 6 months of fluoride intake,the rats were observed for the occurrence of dental fluorosis,and the 24-hour urinary fluoride content was measured.After anesthesia and euthanasia,the brain tissue of rats was taken to observe the pathological changes.Western blot assay was used to detect NMDA receptors and IRE1α,ASK1 and JNK protein expression in the brain tissue.(2)Cell model:SH-SY5Y cells were cultured in vitro and treated with sodium fluoride at final concentrations of 0.3 mmol/L and 3 mmol/L.The fluoride-stained cells were interfered with 10 μmol/L NMDA receptor antagonists Ifenprodil and MK-801 to observe the relevant protein changes. RESULTS AND CONCLUSION:(1)The incidence of dental fluorosis and urinary fluoride level in rats in the high fluoride group were significantly higher than that in the control and low fluoride groups(P<0.05).(2)Compared with the control group,the cytoplasm of neuronal cells in the CA3 area of the hippocampus in the low fluoride group was slightly more basophilic,while the neuronal cells in the CA3 area of the high fluoride group were disorganized,with increased basophilicity and some of the nuclei solidified.(3)In rat brain tissue,the expressions of NR2A in the high fluoride group and NR2B in the low fluoride group were significantly higher compared with the control group(P<0.05),and NR2B,IRE1,ASK1,and p-JNK protein expression levels were increased in the high fluoride group compared with the control and low fluoride groups(P<0.05).(4)In SH-SY5Y cells,NR1,NR2A and NR2B protein expressions were significantly increased in the high fluoride group compared to the control group(P<0.05).The protein levels of NR1 and NR2A were significantly reduced in the high fluorine + Ifenprodil group and high fluorine + MK-801 group compared with the high fluorine group(P<0.05).NR2B protein expression was significantly lower in the high fluorine + Ifenprodil group than that in the high fluorine group(P<0.05).(5)In SH-SY5Y cells,IRE1,ASK1,and p-JNK protein expression was significantly higher in the high fluoride group compared with the control group(P<0.05),while ASK1 and p-JNK protein expressions were significantly decreased in the high fluorine + Ifenprodil group and high fluorine + MK-801 group compared with the high fluorine group(P<0.05).IRE1 protein level was significantly lower in the high fluorine + Ifenprodil group than that in the high fluorine group(P<0.05).(6)It is concluded that excessive fluorine intake activates NMDA receptors in the central nervous system,causing increased expression of endoplasmic reticulum stress IRE1α,ASK1,and p-JNK proteins,and the use of NMDA receptor inhibitors has a mitigating effect on endoplasmic reticulum stress caused by fluorosis.
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Objective:To explore the effects of multi-disciplinary team (MDT) participation for residency training in bariatric and metabolic surgery.Methods:A questionnaire was designed considering patient benefits, doctor benefits, and interviewees' background and recognition of MDT. The questionnaire was used to survey 48 residents who rotated to the department of gastrointestinal surgery and participated in the management of patients undergoing bariatric and metabolic surgery in Peking University Third Hospital from February to October 2023. According to the frequency of MDT participation, the residents were divided into two groups (<5 times and ≥5 times). They were evaluated by five superior surgeons, and the scores of the two groups were compared using the independent samples t test. Results:All the 48 residents completed the questionnaire survey. Only 16 residents (33.33%) had been exposed to the knowledge of bariatric and metabolic surgery, and most of the respondents believed that participating in MDT could improve their professional competence ( n=42, 87.50%) and special English proficiency ( n=30, 62.50%). The group of MDT participation ≥5 times had significantly higher scores of knowledge of internal medicine [(7.42±1.09) vs. (5.16±1.28)], knowledge of anesthesia and critical care medicine [(7.11±0.85) vs. (4.93±0.99)], perioperative management [(7.08±0.67) vs. (4.97±1.21)], laparoscopic skills [(6.43±0.83) vs. (4.99±0.65)], and professional knowledge of general surgery [(6.46±0.86) vs. (5.87±0.51)] compared with the group of MDT participation <5 times (all P<0.05). Conclusions:MDT participation in bariatric and metabolic surgery can help residents quickly understand and master relevant knowledge, which is of great significance for increasing the personnel reserve of bariatric and metabolic surgery.
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Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of breast myofibroblastoma. Methods: The clinicopathological data and prognostic information of 15 patients with breast myofibroblastoma diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from 2014 to 2022 were collected. Their clinical characteristics, histological subtypes, immunophenotypes and molecular characteristics were analyzed. Results: There were 12 female and 3 male patients, ranging in age from 18 to 78 years, with a median and average age of 52 years. There were 6 cases in the left breast and 9 cases in the right breast, including 12 cases in outer upper quadrant, 2 cases in inner upper quadrant and 1 case in outer lower quadrant. Most of the cases showed a well-defined nodule grossly, including pushing growth under the microscope in 13 cases, being completely separated from the surrounding breast tissue in 1 case, and infiltrating growth in 1 case. Among them, 12 cases were classic subtype and composed of occasional spindle cells with varying intervals of collagen fiber bundles; eight cases had a small amount of fat; one case had focal cartilage differentiation; one case was epithelioid subtype, in which epithelioid tumor cells were scattered in single filing or small clusters; one case was schwannoma-like subtype, and the tumor cells were arranged in a significant palisade shape, resembling schwannoma, and one case was invasive leiomyoma-like subtype, in which the tumor cells had eosinophilic cytoplasm and were arranged in bundles, and infiltrating into the surrounding mammary lobules like leiomyoma. Immunohistochemical studies showed that the tumor cells expressed desmin (14/15) and CD34 (14/15), as well as ER (15/15) and PR (15/15). Three cases with histologic subtypes of epithelioid subtype, schwannoma-like subtype and infiltrating leiomyoma-like subtype showed RB1 negative immunohistochemistry. Then FISH was performed to detect RB1/13q14 gene deletion, and identified RB1 gene deletion in all three cases. Fifteen cases were followed up for 2-100 months, and no recurrence was noted. Conclusions: Myofibroblastoma is a rare benign mesenchymal tumor of the breast. In addition to the classic type, there are many histological variants, among which the epithelioid subtype is easily confused with invasive lobular carcinoma. The schwannoma-like subtype is similar to schwannoma, while the invasive subtype is easily misdiagnosed as fibromatosis-like or spindle cell metaplastic carcinoma. Therefore, it is important to recognize the various histological subtypes and clinicopathological features of the tumor for making correct pathological diagnosis and rational clinical treatment.
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Female , Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Aged , Antigens, CD34 , Biomarkers, Tumor/analysis , Leiomyoma/pathology , Neoplasms, Muscle Tissue/pathology , Neurilemmomaالملخص
ObjectiveTo investigate the value of percutaneous and intravenous contrast-enhanced ultrasound(P-Ⅳ-CEUS) in sentinel lymph nodes(SLNs) after resection of early-stage primary breast cancer. MethodsA retrospective analysis was done on the clinical and imaging data of 42 early breast cancer patients. Following primary tumor resection, all these patients underwent reoperation in our hospital. SLNs were examined by preoperative P-Ⅳ-CEUS and intraoperative sentinel lymph node biopsy(SLNB) was performed by using Methylene blue as a tracer. Then we analyzed the detection and false-negative rate in CEUS and SLNB respectively. By using the surgical pathological results as the gold standard, the diagnostic efficacy of CEUS for SLNs was explored. ResultsThe detection rate and false negative rate of SLNs in percutaneous contrast-enhanced ultrasound (P-CEUS) were 92.9% (39/42) and 7.1% (3/42), respectively. The detection rate in methylene blue staining was 100% (41/41) and one patient underwent neoadjuvant therapy due to biopsy-confirmed metastasis. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of P-Ⅳ-CEUS were 66.7% (2/3), 100% (37/37), 100% (2/2), 97.3% (36/37) and 97.4% (38/39), respectively. ConclusionsP-Ⅳ-CEUS after resection of early-stage primary breast cancer can accurately detect SLNs and characterize their status, which is a reliable clinical basis for reducing invasive SLNB.
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OBJECTIVES@#To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality.@*METHODS@#We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated.@*RESULTS@#The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission.@*CONCLUSIONS@#Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.
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Objective To investigate the effect of plateau hypoxia on the blood-brain barrier after subarachnoid hemorrhage (SAH) in rats. Methods Adult male SD rats (n = 78) were randomly divided into 4 groups: sham group (sham), SAH model group (SAH), plateau hypoxia sham group (Hp sham) and plateau hypoxia SAH model group (Hp SAH). The rat model of plateau hypoxia was established through low-pressure simulation chamber (altitude 5000 m), and the SAH model was established by endovascular perforation method. At 24 hours after SAH, neurobehavior score and SAH grade were assessed. The morphological changes of neurons and apoptosis of nerve cells in the CA1 region of hippocampal were observed by the staining of Nissl and TUNEL. The expression of phosphorylated PI3K (p-PI3K), PI3K, phosphorylated Akt (p-Akt), Akt, phosphorylated nuclear factor κB (p-NF-κB), NF-κB, matrix metalloproteinase-9 (MMP-9), occludin and claudin-5 in hippocampal were detected by the method of Western blotting. The expression of occludin and claudin-5 proteins in the CA1 region of hippocampal were observed by immunofluorescent staining. Results At 24 hours after SAH, the neurobehavior score decreased significantly and SAH grade increased significantly in the SAH and Hp SAH group (P< 0.05). Neurobehavior score decreased significantly in the Hp SAH group compared with the SAH group (P < 0.05). In the SAH group, neurons in the CA1 region of hippocampus were atrophied and deformed, the arrangement were disordered, the number of neurons decreased significantly, and the apoptosis of nerve cells increased significantly(P< 0.05). Plateau hypoxia could aggravate the morphological damage of neurons and apoptosis of nerve cells. The expression of p-PI3K/PI3K, p-Akt/Akt, occludin and claudin-5 proteins decreased significantly, while the expression of p-NF-κB/NF-κB and MMP-9 proteins increased significantly in the SAH and Hp SAH group (P< 0.05). The expression of p-PI3K/PI3K and MMP-9 proteins increased significantly in Hp SAH group compared with the SAH group. The expression of claudin-5 protein increased significantly in Hp sham group compared with the sham group (P < 0.05). Immunofluorescent staining showed that the expression of occludin and claudin-5 proteins in the CA1 region of hippocampus decreased in the SAH group. Plateau hypoxia could further decreased the expression of occludin and claudin-5 proteins. Conclusion Plateau hypoxia aggravates blood-brain barrier disruption after subarachnoid hemorrhage in rats through inhibiting PI3K/Akt/NF-κB pathway.
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Objective:To investigate the expression and significance of endoplasmic reticulum stress apoptosis pathway related proteins in renal cortex of rats with chronic fluorosis.Methods:Twenty four healthy SD rats were divided into 4 groups (6 rats/group, half male and half female) according to their body mass (100 - 120 g) by random number table method, rats in control group drank tap water (fluoride content < 0.5 mg/L), and in low, medium and high fluoride groups drank tap water with fluoride content (sodium fluoride) of 10, 50 and 100 mg/L, respectively. After 180 days of feeding, dental fluorosis was examined, 24-hour urine sample was collected and the content of fluoride in urine was detected by fluoride ion selective electrode method. Renal tissue was taken after anesthesia, and the pathological changes of renal cortex were observed by hematoxylin-eosin (HE) staining. The expressions of endoplasmic reticulum stress apoptosis pathway related proteins [inositol-requiring enzyme 1α (IRE1α), apoptosis signal-regulating kinase 1 (ASK1), C-Jun N-terminal kinase (JNK) and phosphorylated JNK (P-JNK)] were determined by immunohistochemical staining in rat renal cortex.Results:No dental fluorosis was found in control group. The incidence of dental fluorosis in low, medium and high fluoride groups were 2/6, 5/6 and 6/6, respectively. Compared with control group [(5.707 ± 1.190) mg/L], the urinary fluoride in low, medium and high fluoride groups [(17.028 ± 3.006), (34.378 ± 12.045), (94.759 ± 31.773) mg/L] was significantly higher ( P < 0.05), and the urinary fluoride in high fluoride group was higher than that in low and medium fluoride groups ( P < 0.05). HE staining showed that, compared with control group, the cell volume of renal tubules and glomeruli in medium and high fluoride groups increased, the cells arranged closely, and the eosinophilia of the cytoplasm increased. The immunohistochemical staining results showed that there was no significant difference in the expression of JNK protein in rat renal cortex between control group and low, medium and high fluoride groups ( F = 0.07, P > 0.05). The expressions of IRE1α, ASK1 and P-JNK proteins in rat renal cortex in high fluoride group were higher than those of control, low and medium fluoride groups ( P < 0.05), and the expressions of IRE1α and ASK1 proteins in medium fluoride group were significantly higher than those in control and low fluoride groups ( P < 0.05). Conclusion:Long-term excessive fluoride intake can lead to renal cortex injury in rats, and the mechanism of injury may be related to the activation of IRE1α-ASK1-JNK endoplasmic reticulum stress apoptosis pathway.
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Objective:To investigate the correlation between serum cystatin C (Cys C) and left ventricular geometry in patients with obstructive sleep apnea syndrome (OSAS) complicated with prehypertension(PH).Methods:A total of 408 patients with PH and OSAS diagnosed by polysonogram monitoring in the sleep monitoring room of Respiratory Department, the First Hospital of Shanxi Medical University from July 2018 to June 2021 were collected. Serum Cys C concentration and echocardiography were performed in all patients. According to the classification of left ventricular geometry, all patients were divided into four groups: normal configuration (NG) group( n=297), concentric remodeling (CR) group( n=49), eccentric hypertrophy (EH) group( n=33), and concentric hypertrophy (CH) group( n=29). General clinical data, sleep parameters, blood biochemical parameters, Cys C concentration and echocardiographic parameters were compared among the four groups, and the correlation between serum Cys C and left ventricular geometry was analyzed. Results:①The serum Cys C concentration increased successively from NG group, CR group, EH group to CH group, and the increase in CH group was the most obvious ( P<0.05). In addition, there were statistically significant differences in body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), severity of OSAS, the percentage of the time that the blood oxygen saturation was less than 90% of the total sleep time (T90), lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), left ventricular end diastolic diameter (LVEDD), inter-ventricular septal diameter (IVST), left ventricular posterior wall thickness diameter (LVPWT), left ventricular mass index (LVMI), relative wall thickness (RWT), left ventricular ejection fraction (LVEF) and E/A among all groups (all P<0.05). ②Multivariate Logistic regression analysis showed that Cys C was independently correlated with CR (β=0.721, OR=2.057, P=0.047), EH(β=0.961, OR=2.614, P=0.017) and CH (β=1.180, OR=3.254, P=0.010). Conclusions:There is a correlation between serum Cys C and left ventricular geometry in OSAS patients with PH, suggesting that serum Cys C might be involved in the change of left ventricular geometry.
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Objective:To examine the effects of heart rate control during hospitalization on short-term prognosis of heart failure in elderly patients.Methods:As a prospective study, 150 elderly patients with heart failure were selected from the Department of Geriatrics, Qilu Hospital of Shandong University.The subjects were divided into an experimental group and a control group by digitally generated random numbers, with 75 individuals in each group.Both groups received conventional anti-heart failure therapy during hospitalization, but patients from the control group had doses of heart rate control drugs adjusted every 2-4 weeks, with no special requirement for the heart rate before hospital discharge.In contrast, patients from the experimental group were given heart rate control drugs with timely dose adjustment to achieve more proactive heart rate control, aiming for a rate <70 beat/min, as long as heart failure symptom improvement and good volume management could be maintained.Values of cardiac function indexes were compared between the two groups at discharge and 6 months after discharge.Heart failure readmission rates within 6 months, cardiovascular disease mortality rates and the incidences of composite endpoint events after readmission due to heart failure aggravation were compared between the two groups.Treatment safety was also evaluated.Results:There was no statistical difference in blood pressure, heart rate, N-terminal pro-B-type natriuretic peptide(NT-pro-BNP), left ventricular ejection fraction(LVEF), left ventricular end systolic diameter(LVESD), or left ventricular end diastolic diameter(LVEDD)between the two groups at admission( P>0.05), and there was no statistical difference in the average length of hospitalization between the two groups( P>0.05). The experimental group had a lower average heart rate and diastolic pressure than the control group at discharge and 6 months latter[at discharge: (61.6±4.2)beat/min(1 mmHg=0.133 kPa) vs.(78.0±7.1)beat/min, (62.1±10.4)mmHg vs.(66.1±10.2)mmHg; at 6 months: (64.7±12.1)beat/min vs.(71.8±11.2)beat/min, (62.8±11.2)mmHg vs.(68.6±10.2)mmHg; P<0.05 or P<0.01]. NT-pro-BNP in the experimental group was significantly lower than that in the control group at discharge[(1 706±1 408)ng/L vs.(2 806±3 812)ng/L, P<0.05]. The absolute values of changes in LVEF(ΔLVEF), LVESD(ΔLVESD)and LVEDD(ΔLVEDD)after 6 months in the experimental group were significantly higher than those in the control group[ΔLVEF: (0.08±0.09) vs.(0.02±0.09), P<0.05; ΔLVESD: (-5.82±7.44)mm vs.(-1.63±6.07)mm, P<0.01; ΔLVEDD: (-2.76±5.52)mm vs.(-0.86±4.44)mm, P<0.05]. The rate of readmission and the incidence of composite endpoint events within 6 months in the experimental group were significantly lower than those in the control group[21.3%(16 cases) vs.36.0%(27 cases), P<0.05]; 25.3%(19 cases) vs.44.0%(33 cases), P<0.05.There was no significant difference in all-cause mortality between the two groups( P>0.05). Conclusions:For elderly patients with heart failure, proactive active heart rate control during hospitalization and a rate <70 beat/min before discharge will improve cardiac function indexes and lower the rate of readmission with exacerbation of heart failure, cardiovascular disease mortality and the incidence of composite end-point events after readmission.This strategy has good safety and is beneficial for short-term prognosis.
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OBJECTIVE@#To investigate the drug resistant related FOXO3/Bcl-6 signaling pathway in K562/G cell line and its related microRNA(miRNA) mechanisms.@*METHODS@#The drug resistance potency of imatinib on K562/G was detected by MTT assay. The expression of FOXO3 and Bcl-6 proteins in K562 and K562/G cells was detected by Western blot. Real-time PCR (RT-PCR) was used to detect the expression of FOXO3 and Bcl-6 mRNA. The miRNA expression profiling in K562 and K562/G cells was analyzed by microarray technique, and the miRNA targeted to FOXO/Bcl-6 signaling pathway was identified.@*RESULTS@#The expression of FOXO3 and Bcl-6 protein was significantly increased in K562/G cells as compared with that in K562 cells (P<0.01), the expression level of Bcl-6 mRNA showed no increase in K562/G cells. However, FOXO3 mRNA was up-regulated in K562/G cells (P<0.05). MiRNA microarray results showed that 109 miRNAs were expressed differentially in K562 and K562/G cells. The expression of 81 miRNAs were up-regulated while 28 miRNAs were down-regulated. Through reverse prediction by bioinformatics, miR-6718-5p, miR-5195-5p, miR-4711-3p, miR-4763-5p, miR-4664-5p and miR-3176 were related to FOXO/Bcl-6 signaling pathway.@*CONCLUSION@#The FOXO3/Bcl-6 signaling pathway contributes to imatinib resistance in K562/G cell line, and the miRNA expression profiles showed significant differences between K562/G and K562 cells.
الموضوعات
Humans , Forkhead Box Protein O3/genetics , Imatinib Mesylate/pharmacology , K562 Cells , MicroRNAs/genetics , RNA, Messenger , Signal Transductionالملخص
OBJECTIVE:To study the m echanism of Liangfu pil ls in the tre atment of gastric ulcer. METHODS :Based on network pharmacology ,the active ingredients ,targets and gastric ulcer related targets of Liangfu pill were screened by searching TCMSP,GeneCards,OMIM and DisGeNET databases ,and the common targets of Liangfu pill and gastric ulcer were screened by Venny 2.1 software. The protein interaction network of Liangfu pill in the treatment of gastric ulcer was constructed by STRING database. Cytoscape 3.7.2 software was used to construct topological analysis of the network.The function of GO and the enrichment of KEGG pathway were analyzed by DAVID database. Active component-gastric ulcer target-KEGG pathway network was constructed for Liangfu pill. In animal experiment ,mice were randomly divided into blank group ,model group ,ranitidine group (positive control ,39 mg/kg),Liangfu pill low- ,medium- and high- dose groups (0.78,1.56,3.12 g/kg),and were given corresponding drugs intragastrically ,once a day ,for consecutive 7 days. After last administration ,except for blank group ,the other groups were given absolute ethanol (0.01 mL/g)intragastrically to induce the gastric ulcer model. After modeling ,the pathological changes of gastric tissue were observed and the gastric ulcer index was calculated ;the expression of TP 53,c-Jun,p38 MAPK,Akt,p-Akt and TNF-α protein in gastric tissues of mice were detected. RESULTS:A total of 9 active ingredients (i.g. isorhamnetin ,β-gsterol,kaempferol)and 166 common targets were screened in Liangfu pills. Liangfu pill can treat gastric ulcer through GO functions such as cell response to chemical stimulation ,protein binding and extracellular space ,and KEGG pathways such as cancer signaling pathway , hepatitis B , Δ 基金项目:国家自然科学基金资助项目(No.81660649);贵州省 bladder cancer ,pancreatic cancer ,TNF signaling pathway and 优秀青年科技人才项目(No.黔科合平台人才〔2019〕5658);贵州中医 prostate. The results of animal experiments showed that 药大学博士启动基金项目 (No.2019-38);贵州中医药大学科研项目 compared with model group ,Liangfu pills could significantly (No.贵中医科院内〔2019〕39号) *讲师,博士。研究方向:中药药效物质基础及作用机理。电话: reduce the pathological changes of gastric tissue and gastric 0851-88308060。E-mail:997845460@qq.com ulcer index ,as well as the protein expression of TP 53, # 通信作者:教授,博士。研究方向:中药药效物质基础及作用机 c-Jun,p38 MAPK,Akt,p-Akt and TNF-α(P<0.05 or P< 理。E-mail:weina-0613@163.com 0.01). CONCLUSIONS :The 9 active components and 166 中国药房 2021年第32卷第9期 China Pharmacy 2021Vol. 32 No. 9 ·1063· targets of Liangfu pill were screened out. Liangfu pill can inhibit the expression of inflammatory factors by inhibiting MAPK ,NF-κ B,TNF and PI 3K/Akt signaling pathway ,and thus play an important role in improving gastric ulcer.
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Objective:To observe the improving effect of Danggui Shaoyaosan on diminished ovarian reserve (DOR) in rats triggered by Tripterygia wilfordii polyglycoside tablet combined with stress, and to explore the role of transforming growth factor-<italic>β</italic><sub>1 </sub>(TGF-<italic>β</italic><sub>1</sub>)/Smads signaling pathway in such improvement. Method:Forty-eight female SD rats with normal sexual cycle were selected and randomly divided into a normal group (<italic>n</italic>=8) and a modeling group (<italic>n</italic>=40), and the ones in the modeling group were given Tripterygium wilfordii polyglycoside tablets (50 mg·kg<sup>-1</sup>) combined with random stress for 15 d. After successful modeling, the rats were randomized into the model group, low-, medium-, and high-dose (3.96, 7.92, 15.84 g·kg<sup>-1</sup>) Danggui Shaoyaosan groups, and estradiol valerate group (0.09 mg·kg<sup>-1</sup>), with eight in each group. Under the premise of stress exposure, they were separately gavaged with the normal saline, low-, medium- and high-dose Danggui Shaoyaosan, and estradiol valerate for 15 successive days. The estrous cycle of rats in each group was observed daily. After intervention, the rats were sacrificed and the ovarian visceral index was calculated. The pathological changes in ovarian tissues were observed by hematoxylin eosin (HE) staining. The protein expression levels of TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1 </sub>receptor (TGF-<italic>β</italic><sub>1</sub>R) in the ovarian tissues of rats were measured by immunohistochemistry (IHC), and the mRNA expression levels of Smad2, Smad3, and Smad7 in the ovarian tissues by real-time polymerase chain reaction (Real-time PCR). Result:Compared with the normal group, the model group exhibited disordered estrus cycle (<italic>P</italic><0.05), reduced visceral index (<italic>P</italic><0.01), and down-regulated TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1</sub>R protein and Smad2 and Smad3 mRNA expression in the ovarian tissues (<italic>P</italic><0.01), and up-regulated Smad7 mRNA expression (<italic>P</italic><0.01). Compared with the model group, Danggui Shaoyaosan at the low, medium, and high doses and estradiol valerate improved the estrus cycle of rats to varying degrees (<italic>P</italic><0.05) and increased the visceral index, with better effects observed in the medium-group and high-dose Danggui Shaoyaosan groups (<italic>P</italic><0.05,<italic>P</italic><0.01). Besides, the protein expression levels of TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1</sub>R and the mRNA expression levels of Smad2 and Smad3 in the ovarian tissues were elevated to varying degrees (<italic>P</italic><0.01), and the Smad7 mRNA expression declined (<italic>P</italic><0.01). The improvements in TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1</sub>R protein expression of the medium-dose Danggui Shaoyaosan group and estradiol valerate group were more obvious. Conclusion:Danggui Shaoyaosan significantly improves ovarian reserve in DOR rats, which is closely related to the regulation of TGF-<italic>β</italic><sub>1</sub>/Smads signaling pathway.
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Objective:To observe the protective effect of Huangqi Guizhi Wuwutang combined with Shengmaiyin on the heart function in patients with diabetic cardiomyopathy and explore its anti-myocardial fibrosis and anti-inflammatory effects. Method:The 96 patients were randomly divided into observation group (48 cases) and control group (48 cases). Both groups were given comprehensive measures to control blood sugar, blood lipids, blood pressure and heart failure. Patients in control group took Tongmai Jiangtang capsule, 3 granules/time, 3 times/day. Patients in observation group took Huangqi Guizhi Wuwutang combined with modified Shengmaiyin, 1 dose/day. The treatment courses were three months in both groups. Left ventricular ejection fraction (LVEF), early diastolic peak velocity E peak/late diastolic peak velocity A peak (E/A), left ventricular end diastolic diameter (LVEDd) and cardiac output per stroke (SV) through echocardiography were recorded before and after therapy. Cardiac troponin-I (cTn I), troponin T (cTn-T), creatine kinase isoenzyme -MB (CK-MB), lactate dehydrogenase (LDH), transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>) before and after treatment , matrix metalloproteinase-2 (MMP-2), insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), IL-1, tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2) and galectin-3 (Gal-3) levels were detected. Symptom of cardiac insufficiency and traditional Chinese medicine (TCM) syndrome score were evaluated before and after treatment. Result:The LVEF and E/A data in observation group were higher than those in control group (<italic>P</italic><0.01). The levels of cTn-I, cTn-T, LDH and CK-MB in the observation group were lower than those in the control group (<italic>P</italic><0.01). After treatment, the levels of TGF-<italic>β</italic><sub>1</sub>, MMP-2, IGF-1, IL-6, IL-1, TNF-<italic>α</italic>, NT-proBNP, sST2 and Gal-3 in the observation group decreased and were lower than those in the control group (<italic>P</italic><0.01). The clinical efficacy of the observation group was better than that of the control group (<italic>Z</italic>=1.974,<italic>P</italic><0.05). Conclusion:On the basis of conventional intervention of western medicine, Huangqi Guizhi Wuwutang combined with modified Shengmaiyin has anti-inflammatory and anti-myocardial fibrosis effects, with inhibitory effect on myocardial remodeling, and can reduce myocardial tissue damage to improve ventricular diastolic function and protect heart function. With such high clinical efficacy, it is worthy of clinical use.
الملخص
Objective:To get a general information about the occupational hazards status of nursing students between China and Sweden, to provide effective basis for reducing occupational exposure rate.Methods:Questionnaire survey. Design and develop an occupational hazards questionnaire and translate the questionnaire into Swedish.Results:The correct rate of occupational hazard in Chinese nursing students including mechanical, chemical, biological and physical hazards was 94.4% (1 024/1 085) and 89.8% (557/620), respectively. 81.6% (1 898/2 325), 90.7% (703/775), both higher than Swedish nursing students 58.4% (756/1295), 48.8% (361/740), 60.2% (1 671/2 775) 86.7% (802/925), the difference was statistically significant ( χ 2 =259.196-1 259.183, P<0.05). Only "operating posture is not standard will lead to the occurrence of low back pain" "Women need to wear gloves when intravenously injecting patients" "Women need to wear gloves when changing medicines for patients" "Women need to wear gloves when drawing blood for patients" 4 questions correct answer rate Sweden Nursing students were higher than Chinese nursing students ( χ 2=11.738-16.990, P<0.01), and the remaining questions of Chinese nursing students were higher than Swedish nursing students ( χ 2=11.738-45.464, P<0.01). Conclusions:Nursing students in China and Sweden generally have the awareness of occupational hazard cognition, and Chinese nursing students have a better grasp of the knowledge of occupational hazard cognition, but there are still weak links, which need to be improved from the aspect of education, managers should also consider reducing the occupational exposure of nursing students and even nurses from the management level, improve the employment quality of nursing students and nurses.
الملخص
Objective@#To get a general information about the occupational hazards status of nursing students between China and Sweden, to provide effective basis for reducing occupational exposure rate.@*Methods@#Questionnaire survey. Design and develop an occupational hazards questionnaire and translate the questionnaire into Swedish.@*Results@#The correct rate of occupational hazard in Chinese nursing students including mechanical, chemical, biological and physical hazards was 94.4% (1 024/1 085) and 89.8% (557/620), respectively. 81.6% (1 898/2 325), 90.7% (703/775), both higher than Swedish nursing students 58.4% (756/1295), 48.8% (361/740), 60.2% (1 671/2 775) 86.7% (802/925), the difference was statistically significant (χ2 =259.196-1 259.183, P<0.05). Only "operating posture is not standard will lead to the occurrence of low back pain" "Women need to wear gloves when intravenously injecting patients" "Women need to wear gloves when changing medicines for patients" "Women need to wear gloves when drawing blood for patients" 4 questions correct answer rate Sweden Nursing students were higher than Chinese nursing students (χ2=11.738-16.990, P<0.01), and the remaining questions of Chinese nursing students were higher than Swedish nursing students (χ2=11.738-45.464, P<0.01).@*Conclusions@#Nursing students in China and Sweden generally have the awareness of occupational hazard cognition, and Chinese nursing students have a better grasp of the knowledge of occupational hazard cognition, but there are still weak links, which need to be improved from the aspect of education, managers should also consider reducing the occupational exposure of nursing students and even nurses from the management level, improve the employment quality of nursing students and nurses.
الملخص
OBJECTIVE:To explore the protective effect of Alpinia zerumbet extract on acute gastric ulcer model mice. METHODS:Totally 48 mice were collected and randomly divided into blank group ,model group ,positive group (Sanjiu weitai granules,20 mg/kg),A. zerumbet extract high-dose ,medium-dose and low-dose groups (2.34,1.17,0.59 g/kg,by crude drug ), with 8 mice in each group. They were given normal saline or relevant medicine intragastrically ,once a day ,for consecutive 7 d. Then,except for blank group ,other groups were given disposable intragastric administration of absolute ethanol 0.1 mL/10 g to establish acute gastric ulcer model. Another 48 mice were collected and grouped with same method ,and then given relevant medicine for consecutive 15 d. From the 10th day of administration ,except for blank group ,other groups were given intragastric administration of aspirin (20 mg/kg) for consecutive 6 d to establish acute gastric ulcer model. In ethanol induction model experiment,the formation of gastric ulcer and the index of gastric ulcer were observed in each group ;HE staining was used to observe the pathological changes of gastric tissue ;the levels of gastrin (GAS)in serum ,and the levels of SOD ,MDA and NO in gastric tissue were determined by ELISA. In the aspirin induced model experiment ,the formation of gastric ulcer and the index of gastric ulcer were observed and measured by the same method ;the levels of GAS ,TNF-α,IL-1β in serum,and the levels of PGE2 and COX- 2 in gastric tissue were determined by ELISA. RESULTS :Compared with model group ,obvious ulcer lesions were found in gastric tissue of rats in model group ;the levels of GAS ,TNF-α,IL-1β in serum,and MDA ,NO in gastric tissue were increased significantly , while the levels of SOD , PGE2, (No.QZYY-2019- COX-2 in gastric tissue were decreased si gnificantly(P<0.05 063). Compared with model group ,the degree of gastric lesions in administration groups was alleviated to some extent;gastric ulcer index was decreased to some extent , mail:997845460@qq.com while the levels of the above indexes in serum and gastric tissue were improved in varying degrees , with statistical 制。E-mail:672863283@qq.com significance in most indexes (P<0.05 or P<0.01). CONCLUSIONS:A. zerumbet extract exerts its protective effect on absolute ethanol and a spirin-induced acute gastric ulcer model mice,the mechanism of which may be relieving gastric mucosal injury through inhibiting oxidative stress and inflammatory response.
الملخص
Cervical cancer is the second most common malignant tumor in women worldwide.The burden of cervical cancer is particularly heavy in less developed countries as the malignancy brings huge pain to the patients and their family members and causes huge losses to social development and global health.However,cervical cancer is a preventable and curable disease.While screening and human papillomavirus vaccination in developed countries have remarkably lowered the incidence and mortality of cervical cancer,there is still a far way to go to achieve the prevention and treatment of this disease.The multidisciplinary prevention and control programs slightly differ in different countries due to diverse economic and health conditions.The general principle is to vaccinate the young females and to implement a comprehensive strategy including human papillomavirus vaccine vaccination,screening,early diagnosis,and early treatment in adults.
الموضوعات
Female , Humans , Early Detection of Cancer , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Vaccinationالملخص
Objective:To observe the change of growth and development, learning and memory, and oxidative stress in serum of offspring rats with fluorosis, and to explore the mechanism of fluoride on neurobehavioral development of offspring rats.Methods:Seventy-two SD rats (female and male ratio 3 ∶ 1) were fed adaptively for one week. According to their body mass [(80 ± 20) g], they were divided into control group (drinking tap water, containing less than 0.5 mg/L fluoride), low fluorine group (drinking water containing 10.0 mg/L of fluoride), and high fluorine group (drinking water containing 100.0 mg/L of fluoride) with random number table. After six months of feeding, they mated freely and gave birth in each group (24 rats with 18 females and 6 males). The rats in each group continued to be exposed to fluoride after giving birth, and the offspring rats were exposed to fluoride through breast milk feeding until the 28th day after birth. Body and brain weight, growth and development indicators (auricle separation, eyes opening, teeth eruption and hair growth) and neurobehavioral development indicators (cliff avoidance, auditory startle, surface righting and vibrissa positioning) were recorded. On the 28th day after birth, the learning and memory abilities (escape latency) of offspring rats were tested by Morris water maze; blood samples were taken from eyeballs to detect the content of nitric oxide (NO), the activity of nitric oxide synthase (NOS) and inducible nitric oxide synthase (iNOS).Results:On the 21st day and 28th day after birth, the differences of body weight among control group, low fluorine group and high fluorine group [21st day: (54.70 ± 3.02), (52.30 ± 2.58), (51.30 ± 2.71) g, 28th day: (91.70 ± 5.03), (90.40 ± 4.76), (86.00 ± 4.55) g] were statistically significant ( F = 3.96, 3.70, P < 0.05); on the 21st day, the body weight of high fluorine group was lower than that of control group ( P < 0.05); on the 28th day, the body weight of the high fluorine group was lower than those of control group and low fluorine group ( P < 0.05). On the 28th day, the difference of brain weight of control group, low fluorine group and high fluorine group was statistically significant ( F = 6.19, P < 0.05); and the low fluorine group and high fluorine group were lower than that of control group ( P < 0.05). Among the growth development indicators, the difference of time of completing eyes opening in control group, low fluorine group and high fluorine group was statistically significant ( F = 3.64, P < 0.05); and the high fluorine group was higher than that of control group ( P < 0.05). In neurobehavioral development indicators, the differences of time of completing cliff avoidance, surface righting between the control group, low fluorine group and high fluorine group were statistically significant ( F = 8.29, 7.69, P < 0.05); and the time of completing cliff avoidance in high fluorine group was higher than those of control group and low fluorine group ( P < 0.05), the time of completing surface righting was higher than that of control group ( P < 0.05). In Morris water maze, on the 4th day, the escape latencies of low fluorine group and high fluorine group were higher than that of control group ( P < 0.05). The results of oxidative stress in serum showed that there were statistically significant differences in serum NO content, NOS and iNOS activitives between the control group, low fluorine group and high fluorine group ( F = 4.86, 66.48, 70.95, P < 0.05); and the NO content of the high fluoirne group was higher than that of the control group ( P < 0.05), the activities of NOS and iNOS of the high fluoirne group were higher than those of control group and the low fluorine group ( P < 0.05). Conclusion:Excessive fluoride can increase the level of oxidative stress in serum, which may be closely related to the neurobehavioral retardation and the decline of learning and memory ability of offspring rats.
الملخص
Objective:To observe the changes of phosphorylated N-methyl-D-aspartate receptor (P-NMDAR) subunit and calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) protein expression in the brain tissue of rats with chronic fluorosis, and to explore the molecular pathogenesis of chronic fluorosis nerve injury.Methods:Eighteen one-month-old SD rats (half male and half female), weighing (100 ± 20) g, were randomly divided into three groups after adaptive feeding for 1 week: control group (drinking tap water, fluoride content < 0.5 mg/L), low fluoride group (drinking water fluoride content was 10.0 mg/L) and high fluoride group (drinking water fluoride content was 100.0 mg/L), with 6 rats in each group (half male and half female). Brain tissue was harvested after 180 days of feeding. HE staining was used to observe the morphological changes of rat brain tissue, Nissl staining was used to observe the changes of Nissl bodies in nerve cells, and immunohistochemical staining was used to observe the expressions of P-NMDAR subunits (P-NMDAR1, P-NMDAR2A) and CaMK Ⅱ protein in rat brain tissue.Results:Under light microscope, HE staining showed disordered arrangement of hippocampal neurons, nuclear hyperstaining and basophilic enhancement in the high fluoride group. The results of Nissl staining showed that the average optical density of Nissl bodies in nerve cells in the hippocampus of rats in the control group, low fluoride group, and high fluoride group were 0.024 4 ± 0.009 7, 0.024 0 ± 0.003 1, and 0.023 9 ± 0.013 8, respectively. There was no statistically significant difference between the groups ( F = 0.010, P > 0.05). Compared with the control group (0.011 8 ± 0.006 5, 0.065 6 ± 0.011 1, 0.143 8 ± 0.029 9) and low fluoride group (0.017 2 ± 0.006 8, 0.062 6 ± 0.017 8, 0.135 6 ± 0.029 6), the protein expressions of P-NMDAR1, P-NMDAR2A and CaMK Ⅱ in high fluoride group were significantly increased (0.026 3 ± 0.005 7, 0.086 3 ± 0.009 0, 0.210 9 ± 0.048 7, P < 0.05); and the protein expression of P-NMDAR1 in low fluoride group was higher than that in the control group ( P < 0.05). Conclusion:Long-term excessive fluoride intake can lead to nerve cell injury in rats, and the mechanism of injury maybe related to the excitotoxicity induced by calcium ion (Ca 2+) overload caused by overactivation of NMDAR subunits.