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Cyclosporine A, a cyclic polypeptide, exhibits potent immunosuppressive activity and exerts its effects through various mechanisms including immunosuppression, anti-inflammatory, inhibition of apoptosis, promotion of epithelial healing and goblet cell function recovery, enhancement of tear secretion, and close association with ocular surface disease repair. Owing to its significant efficacy, inhibition of disease recurrence and few side effects, the clinical application of cyclosporine A in the management of ocular surface diseases, including dry eye, corneal graft rejection following penetrating keratoplasty, vernal keratoconjunctivitis, noninfective keratitis and herpes simplex virus keratitis, has witnessed a substantial rise in recent years. Nevertheless, variations exist in the management of ocular surface inflammatory diseases when utilizing distinct concentrations and dosage forms of cyclosporine A. Therefore, the paper provides an overview of impacts of cyclosporine A on ocular surface diseases.
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Objectives@#. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. @*Methods@#. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. @*Results@#. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. @*Conclusion@#. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
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Corneal refractive surgery and intraocular collamer lens(ICL)implantation are the mainstream refractive surgery methods at present. Many studies have proved that ICL implantation can effectively improve the postoperative visual acuity of patients. ICL implantation has gained favor among refractive doctors and patients because of its multiple advantages. Excellent postoperative visual acuity and visual quality are the key factors to improve patients' satisfaction. In order to evaluate the subjective and objective visual quality of patients after operation and avoid complications, this article reviews the visual quality and postoperative complications after ICL implantation.
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To explore the effect of doctor-patient relationship perception on work performance among medical staff in public hospitals and its mechanism. The convenient sampling method was used to select 380 medical staff working in four public tertiary hospitals in Sichuan Province, Zhejiang Province, and Fujian Province from August 2022 to October 2022 as the research objects, and the General Information Questionnaire, Doctor-Patient Relationship Scale, General Self-Efficacy Scale, Perceived Organizational Support Scale, Work Performance Questionnaire were used. This paper showed that the doctor-patient relationship perception of medical staff was negatively correlated with self-efficacy (r=-0.392, P<0.01) and work performance (r=-0.286, P<0.01), self-efficacy was positively correlated with perceived organizational support (r=0.538, P<0.01) and work performance (r=0.507, P<0.01), perceived organizational support was positively correlated with work performance (r=0.510, P<0.01). Self-efficacy played a partial mediating role between doctor-patient relationship perception and work performance, and its effect value was -0.241, accounting for 64.78% of the total effect. Perceived organizational support weakened the negative predictive effect of doctor-patient relationship perception on self-efficacy, which moderates the first half path of the mediating model that doctor-patient relationship perception affects work performance through self-efficacy. It indicated that the doctor-patient relationship perceived by medical staff in public hospitals is poor. Measures should be taken from the aspects of policy support, hospital and society levels to alleviate the doctor-patient relationship, play the mediating role of self-efficacy and the moderating role of organizational support, minimize the negative impact of doctor-patient relationship on the work performance among medical staff, and improve the work performance of medical staff, so as to improve the overall quality of medical services.
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OBJECTIVE@#To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology.@*METHODS@#The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn.@*RESULTS@#Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters.@*CONCLUSION@#Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.
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Humanos , Moxibustión , Puntos de Acupuntura , Terapia por Acupuntura , Accidente Cerebrovascular/terapia , Minería de Datos , EpilepsiaRESUMEN
ObjectiveTo investigate the effect of Glycyrrhizae Radix et Rhizoma (GR)-containing serum on lipopolysaccharide (LPS)-induced inflammation in human colon epithelial adenocarcinoma cells (Caco2) based on inhibition of ferroptosis by the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. MethodCaco2 cells were divided into a normal group, a model group (LPS, 200 μg·L-1), low-, medium-, and high-dose GR-containing serum groups (5%, 10%, 20%), and a ferroptosis inhibitor group (3-amino-4-cyclohexylamino-benzoic acid ethyl ester, Fer-1, 10 μmol·L-1). The cells in the normal group were cultured normally, while those in other groups underwent the induction of an inflammation model. The cells in the low-, medium-, and high-dose GR-containing serum groups were treated with 5%, 10%, and 20% GR-containing serum for 24 hours, respectively, and the cells in the ferroptosis inhibitor group were treated with Fer-1 for 24 hours. Transmission electron microscopy was used to observe mitochondrial morphology in each group. Flow cytometry was used to detect intracellular Fe2+ levels. Microplate assays were performed to measure superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels. Enzyme-linked immunosorbent assay (ELISA) was used to measure interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor-α (TNF-α) levels. Western blot was used to measure the expression levels of Nrf2, HO-1, ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GSH-Px4) proteins. Small interfering RNA (siRNA) was used to investigate the role of Nrf2 in ferroptosis regulation. The cells after interference were divided into a negative control (NC) group, a Si-Nrf2 group, a GR-containing serum (20%) + Si-Nrf2 group, and a GR-containing serum (20%) + NC group. Microplate assays were performed to measure MDA, SOD, and GSH-Px levels, and Western blot was used to measure the expression levels of Nrf2, HO-1, FTH1, and GSH-Px4 proteins. ResultCompared with the normal group, the model group showed mitochondrial contraction, increased mitochondrial membrane thickness, and smaller mitochondrial morphology, increased Fe2+ content (P<0.01), blunted SOD activity (P<0.01), decreased GSH-Px expression (P<0.01), increased MDA content (P<0.01), reduced expression levels of Nrf2 and HO-1 (P<0.05), reduced FTH1 expression (P<0.01), and down-regulated GSH-Px4 expression (P<0.01). In the GR-containing serum groups, the medium- and high-dose groups showed a significant decrease in Fe2+ content (P<0.01), potentiated SOD and GSH-Px activities (P<0.01), and decreased MDA levels (P<0.01). The high-dose group showed a significant increase in Nrf2 expression (P<0.05), and the medium-dose group showed increased expression of HO-1 and GSH-Px4 proteins (P<0.05). The expression levels of FTH1 significantly increased in the low-, medium-, and high-dose groups (P<0.01). The study on mechanism revealed that compared with the NC group, the cells transfected with Nrf2 siRNA showed increased MDA content (P<0.01), blunted SOD activity (P<0.01), decreased GSH-Px activity (P<0.01), decreased expression of Nrf2 and HO-1 (P<0.01), and reduced levels of FTH1 and GSH-Px4 proteins (P<0.01). Compared with the Si-Nrf2 group, the cells treated with GR-containing serum showed a decrease in MDA content (P<0.01), an increase in SOD activity (P<0.01), an increase in GSH-Px activity (P<0.01), increased expression of Nrf2 and FTH1 proteins (P<0.05), and higher expression levels of HO-1 and GSH-Px4 proteins (P<0.01). ConclusionGR-containing serum can reduce the inflammatory cytokines and oxidative stress levels in LPS-induced Caco2 cells. Its mechanism is related to the promotion of Nrf2/HO-1 signaling pathway expression, alleviating intracellular lipid peroxidation and inhibiting ferroptosis.
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Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
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Masculino , Humanos , Glutamina/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológicoRESUMEN
Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh2(OCOCF3)4-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC50 value of 55.64 μmol·L-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC50 values of 13.8 and 12.3 μmol·L-1, respectively.
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Terpenos/farmacología , Viburnum/química , Estructura Molecular , Diterpenos/química , Hojas de la Planta/químicaRESUMEN
Objective:This paper mainly discusses the health policy of early life of pregnant women and infants in Beijing as an example,and to provide the basis for policy formulation and optimization.Methods:By using the content analysis method,149 policy texts are divided into two dimensions:policy objectives and policy instruments.The results are described by manual coding,cross analysis and trend analysis.Results:In regard to Policy Objectives,improvement of maternal and child health service levels accounts for the biggest proportion(61.7%),whereas improvement of research level accounts for the least(8.1%).In the four dimensions of policy instruments,mandatory,spontaneous,capacity-building,and incentive tools account for 90%,55%,48%and 42%respectively.According to the trend analysis,integrity of policy system has been continuously improved and the proportion of infant and child care has also increased.Both cross-analysis and trend analysis have showed the strong use of coercive and incentive tools by relevant policies;The use of spontaneous and capacity-building tools is low and decreases over time.Conclusion:Improving the level of maternal and child health services is the core concern of Beijing's early life health policy.However,relatively little attention is paid to the family,infant and child care,and scientific research construction.As for Policy Instruments,mandatory tools are widely used;Incentive Tools and Spontaneous Tools are mainly applied in well-being and soft guidance;insufficient use of Capacity-building Tools.Suggestions:In the future,the policy system should be further improved,which should be targeted and deficiency-mending.It is suggested that more resources should be increased for the family system,more attention should be paid to vulnerable groups early in life,and more financial support should be applied to scientific research on maternal and child health.
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There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the KD of which reached to 8.722×10-10 g·mL-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.
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Objective:To investigate the influence of abnormal blood pressure circadian rhythms and the morning surge on aortic stiffness in elderly patients with isolated systolic hypertension(ISH).Methods:A total of 300 untreated elderly(≥60 years)patients with ISH were enrolled.24-hour ambulatory blood pressure was measured by using a non-invasive portable ambulatory sphygmomanometer with an inflatable cuff.Brachial-ankle pulse wave velocity(baPWV)and the ankle-brachial pressure index(ABI)were measured by using an automated device.Patients were divided into the dipper(n=95), no-dipper(n=177)and extreme dipper(n=28)groups according to the rate of nocturnal blood pressure reduction.They were also divided into the morning surge(n=88)and no morning surge(n=212)groups according to the morning blood pressure surge(MBPS). Differences between the groups were compared.Correlations between the parameters were calculated by partial correlation analyses.The effects on baPWV and ABI were calculated by multiple linear regression analyses.Results:baPWV was higher in the extreme dipper group than in the dipper and no dipper groups[(1 402±234)cm/s vs.(1 467±114)cm/s vs.(1 538±140)cm/s, P<0.01], while ABI values were lower in the extreme dipper group than in the dipper group(0.98±0.10 vs.1.05±0.12, P<0.01)and the no dipper group(0.98±0.10 vs.1.03±0.12, P<0.05). Moreover, baPWV[(1 508±170)cm/s vs.(1 430±163)cm/s, P<0.01]was higher while ABI values(0.98±0.13 vs.1.06±0.11, P<0.01)were lower in the morning surge group than in the no morning surge group.baPWV was positively correlated with daytime Systolic blood pressure(dSBP)( r=0.169, P<0.01), 24 hSBPCV( r=0.143, P<0.05), and MBPS( r=0.157, P<0.01), while ABI was negatively correlated with dSBP( r=-0.146, P=0.011)and MBPS( r=-0.321, P<0.01). Age( P<0.01), dSBP( P<0.05)and 24 h systolic blood pressure variation coefficient( P<0.05)were independent factors for baPWV, while dSBP and MBPS were independent factors for ABI(all P<0.01). Conclusions:Abnormal blood pressure circadian rhythms and the morning surge are associated with increased aortic stiffness in elderly patients with ISH.
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Previously, we discovered that cells contain a 5-hydroxytryptamine (5-HT) degradation system (5DS), which includes 5-HT2A receptor (5-HT2AR), 5-HT synthase, and monoamine oxidase A (MAO-A). Among these, 5-HT2AR has the ability to regulate the expression of 5-HT synthase and MAO-A, and activation of 5DS causes upregulation of these proteins at the same time, resulting in the production of reactive oxygen species (ROS) in the mitochondria. In this study, we investigated the relationship between interstitial pneumonia (IP) and 5DS activation, as well as the therapeutic effect of inhibiting 5DS on IP. Animal models of bleomycin (BLM)-induced IP in mice and radiation (Rad)-induced IP in rats were established, and the models were treated with the 5-HT2AR antagonist sarpogrelate hydrochloride (SH), 5-HT synthesis inhibitor carbidopa (CDP), and their combination (SH∶CDP = 2∶1). The animal experiments were carried out in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. In the two IP models, immunohistochemistry staining and Western blot analysis showed that the expression of 5-HT synthase was significantly upregulated in all cells of lung tissue, while the expression of 5-HT2AR and MAO-A was most significantly upregulated in the macrophages. Treatment with SH or CDP significantly reduced pulmonary interstitial thickening, alveolar atrophy with collapse, massive macrophage infiltration and interstitial fibrosis in the two IP models, as measured by HE and Masson staining, and a combination of both almost eliminated the lung tissue lesions. Moreover, treatment with the combination of SH and CDP almost completely eliminated increased ROS and malondialdehyde levels, decreased superoxide dismutase activity, increased tumor necrosis factor-α and interleukin-1β levels, and upregulated nuclear factor-κB phosphorylation and α-smooth muscle actin, matrix metalloproteinase-2, and collagen expression. SH and CDP worked together to create a synergistic effect. The findings suggested that the activation of 5DS, as evidenced by increased 5-HT synthesis in all cells of lung tissue and increased 5-HT synthesis and degradation in macrophages, is probably related to the occurrence of IP and that inhibition of 5DS can effectively treat IP.
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Background Bromadiolone is the second-generation anticoagulant rodenticide widely used all over the world. Exposure to bromadiolone in early life stage can lead to neurodevelopmental toxicity, but its toxic mechanism of neurodevelopment is not clear so far. Objective To investigate the developmental neurotoxicity and mechanism of bromadiolone to zebrafish embryos. Methods Zebrafish embryos were randomly divided into four groups: a solvent control group (dimethylsulphoxide) and three bromadiolone exposure groups (0.39, 0.78, and 1.18 mg·L−1). The exposure period was from 4 h to 120 h post-fertilization. The number of spontaneous movement per minute was recorded at 24 h post-treatment. The locomotor ability of zebrafish larvae and the activity of acetylcholinesterase (AChE) were tested at 120 h post-treatment. The relative expression levels of neurodevelopment-related genes (elavl3, gap43, mbp, and syn2a) were measured by fluorescence quantitative PCR. Results Compared with the control group, the number of spontaneous movement per minute at 24 h decreased significantly in the 1.18 mg·L−1 bromadiolone exposure group (P<0.05). Compared with the control group, the total distance travelled of the zebrafish larvae in the 0.78 and 1.18 mg·L−1 bromadiolone exposure groups decreased by 60% and 69% respectively (P<0.05, P<0.01), and the total movement time decreased by 34% and 65% respectively (P<0.05, P<0.01). The AChE activity in the 1.18 mg·L−1 bromadiolone exposure group increased by 36% when compared with the control group (P<0.05). The fluorescence quantitative PCR results showed that compared with the control group, the expression levels of neurodevelopment-related genes elavl3, syn2a, and mbp were significantly down-regulated by 66%, 69%, and 65% in the 1.18 mg·L−1 bromadiolone exposure group respectively (P<0.01), the expression level of gap43 was up-regulated by 56% in the 0.78 mg·L−1 bromadiolone exposure group (P<0.01) and down-regulated by 34% in the 1.18 mg·L−1 bromadiolone exposure group (P<0.05). Conclusion Bromadiolone exposure could inhibit spontaneous movement and locomotive behavior, down-regulate the expression levels of neurodevelopment-related genes, hinder the release of neurotransmitters, and result in neurodevelopmental toxicity in the early-staged zebrafish.
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The outpatient and emergency electronic medical record system is an important part of the hospital information system. By analyzing the current outpatient and emergency electronic medical record system in hospitals in China, this paper rounded up weaknesses in the development of the outpatient and emergency electronic medical record system in terms of management standards, support, technology bottleneck, data sharing and security. On such basis, the authors suggested to improve the policy standards, clarify the construction objectives, increase the support, optimize the system functions and strengthen the security management, which aimed at promoting the high-quality development of the construction of outpatient and emergency electronic medical record system in China′s hospitals.
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Objective:To explore the protective effect and the mechanism of Danggui Shaoyaosan(DSS) on angiotensin Ⅱ (AngⅡ)/transient receptor potential cation channel 6 (TRPC6) pathway in nephrotic syndrome (NS) rats. Method:In animal experiments, doxorubicin (4 mg·kg<sup>-1</sup> for the 1<sup>st</sup> week and 2 mg·kg<sup>-1</sup> for the 2<sup>nd</sup> week) was injected twice to the tail vein of rats to induce NS model in 160 rats, which were then randomly divided into model group (normal saline), losartan group (30 mg·kg<sup>-1</sup>·d<sup>-1</sup>), and low-(4.3 g·kg<sup>-1</sup>·d<sup>-1</sup>), medium-(8.6 g·kg<sup>-1</sup>·d<sup>-1</sup>), and high-dose (17.2 g·kg<sup>-1</sup>·d<sup>-1</sup>) DSS groups. Besides, a normal group was also set. After intervention for four weeks, ultrastructure changes of the kidney were identified by transmission electron microscopy (TEM). The 24-hour urine protein was detected by kits. Radioimmunoassay was used to detect the content of AngⅡ and Calcineurin (CaN) in plasma. Western blot was used to detect the protein expression of TRPC6, angiotensin Ⅱ type 1 receptor (AT1R), podocyte slit diaphragm-specific protein (Nephrin), and cysteine-aspartic acid protease-3 (Caspase-3) in the renal cortex. Immunohistochemistry was used to detect the expression of TRPC6 and AT1R in the slit diaphragm. In cell experiments, AngⅡ stimulated MPC5 podocytes. The cells were randomly divided into a normal group, an AngⅡ group, an AngⅡ+SAR7334 (TRPC6-specific inhibitor) group, an AngⅡ+5%DSS group, an AngⅡ+10%DSS group, and an AngⅡ+15%DSS group. Western blot was used to detect the protein expression of TRPC6, AT1R, Nephrin, and Caspase-3 in podocytes. Result:Compared with the normal group, the model group showed increased 24-hour urine protein content (<italic>P</italic><0.01) and AngⅡ and CaN in plasma (<italic>P</italic><0.01), incomplete glomerular structure, the extensive fusion of podocyte process with elevated fusion rate (<italic>P</italic><0.01), increased expression distribution of AT1R and TRPC6 in the renal cortex, and up-regulated protein expression of AT1R, TRPC6, and Caspase-3 in renal tissues (<italic>P</italic><0.01), and reduced Nephrin protein expression (<italic>P</italic><0.01). Compared with model group, the losartan group and the high-dose DSS group exhibited decreased 24-hour urine protein content (<italic>P</italic><0.01) and the content of AngⅡ and CaN in plasma (<italic>P</italic><0.01), improved glomerular structure, reduced fusion rate of podocyte process (<italic>P</italic><0.01), diminished expression distribution of TRPC6 and AT1R in the renal cortex, declining protein expression of AT1R, TRPC6 and Caspase-3 in renal tissues (<italic>P</italic><0.01), and elevated Nephrin protein expression (<italic>P</italic><0.01). Additionally, compared with the normal podocytes, AngⅡ-stimulated podocytes showed increased protein expression of AT1R, TRPC6 and Caspase-3 (<italic>P</italic><0.01), and decreased expression of Nephrin (<italic>P</italic><0.01). Compared with the AngⅡ group, the AngⅡ+SAR7334 group displayed reduced protein expression of AT1R, TRPC6, and Caspase-3 (<italic>P</italic><0.01) and increased protein expression of Nephrin (<italic>P</italic><0.01). Conclusion:DSS can improve the pathological characteristics of NS presumedly by inhibiting the interaction between AngⅡ and TRPC6 in podocytes and improving the structural integrity of podocytes to repair the damage of glomerular molecular barrier and slow down the progression of NS-induced proteinuria.
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Hyperglycemic kidney injury (HKI) is a common complication of diabetic patients. We examined the relationship between HKI and the abnormal expression of 5-hydroxytryptamine (5-HT) system induced by hyperglycemia in type 2 diabetes mellitus (T2DM). In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (respectively or in combination). In cell culture experiments, human glomerular mesangial cells (HMC) were stimulated with D-glucose (D-Glu), and 5-HT2AR, 5-HT synthesis, and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor clorgyline. Periodic acid-Schiff (PAS) staining and Masson staining, immunohistochemistry and Western blot, fluorescent probe, and enzyme linked immunosorbent assay (ELISA) and enzyme reagent were respectively used to detect histopathology, protein expression, intracellular reactive oxygen species (ROS), and biochemical indexes. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT2AR, 5-HT synthases, and MAO-A were expressed in glomerular basement membrane and kidney tubular epithelial cells of mouse kidney and HMC. The expression of these proteins was significantly up-regulated in T2DM mice or when HMC cells were exposed to high concentration of D-Glu. HKI, characterized by abnormal renal function, glomerular swelling, and glomerular basement membrane thickening and fibrosis, is closely associated with an increase in kidney 5-HT2AR, 5-HT synthesis, and 5-HT degradation. Among them, 5-HT2AR can mediate the expression of 5-HT synthases and MAO-A; MAO-A can catalyze the degradation of 5-HT to increase the production of mitochondrial ROS, leading to the phosphorylation of nuclear factor kappa B (NF-κB) with the production of inflammatory cytokines, and the up-regulation of matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) with the production of collagens. SH and CDP can effectively treat HKI, and the combination of SH and CDP has a clear synergistic effect.
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Objective To analyze the drug consumption of the joint logistics support force during field training in Yunnan, summarize the drug use characteristics of medical staff, and analyze the drug use rules, so as to provide the basis for modular drug support. Methods The basic information and drug use of the personnel in an institution of the joint logistics support force during the resident training period from April to June 2020 were collected and sorted out. The drug use indicators were calculated by using the defined daily dose (DDD) as the unit, including: daily drug dose (DDDs), daily drug dose cost (DDDc), drug use intensity (DUI), drug utilization rate (DUR) and drug ranking ratio (R) were used to describe drug use characteristics. Results During the resident training period, the amount of musculoskeletal system drugs was large, and the number of users was large. The dosage of cardiovascular system drugs, digestive system drugs and hormone drugs was large, but the number of users was small. Sensory organ drugs, dermatological drugs, heat-clearing agents (Chinese patent medicine) and respiratory system drugs were small in dosages, but the number of users was large. Ranked by DDDs, the top 3 drugs with the highest dosage were Yunnan Baiyao plaster, Yunnan Baiyao Band-Aid and Loratadine Tablets. Ranked by DDDc, the largest daily cost was Budesonide and Formoterol Fumarate Powder for Inhalation. As age increases, the intensity of drug use increased; The intensity of drug use in women was greater than that in men. The intensity of drug use was different for different categories personnel. Conclusion Musculoskeletal system drugs are important drugs for field training. The task personnel should formulate a list of medicines for basic diseases based on their own medication for basic diseases and the duration of the task, and submit it to the medicinal material guarantee department to ensure the carrying drugs. The factors affecting modular drug support in field training include: task type, region, solar term, duration and personnel composition, etc.
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Objective:To investigate the differences in incidence of deep vein thrombosis (DVT) after closed fracture of lower extremity between patients with different blood types ABO.Methods:A retrospective study was conducted in the 1, 951 patients who had been admitted to Department of Orthopaedics Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University for lower extremity fractures from August 2014 to June 2018. They were 924 males and 1,027 females with a mean age of 63 (46, 78) years (range, from 16 to 102 years). Of them, 572 were type O, 564 type A, 609 type B and 206 type AB. Venous ultrasonography was performed on both lower extremities within 12 hours after admission. The incidences of DVT after fracture were compared between different blood types in all the patients, patients with proximal fracture of the knee, peri-knee fracture and distal fracture of the knee, and patients<60 years old and ≥60 years old.Results:The incidences of DVT were, respectively, 26.75% (153/572), 28.72% (162/564), 34.32% (209/609) and 29.61% (61/206) for patients with blood type O, type A, type B and type AB. The DVT incidence for type B was significantly higher than that for type O ( P< 0.008). The incidences of DVT were, respectively, 28.74% (98/341), 28.99% (100/345), 39.45% (144/365) and 30.97% (35/113) for blood type O, type A, type B and type AB in the patients with proximal fracture of the knee. The DVT incidence for blood type B was significantly higher than those for blood type O and blood type A ( P< 0.008). There were no significant differences in the DVT incidence between different blood types ABO in the patients with peri-knee fracture, distal fracture of the knee,<60 years old or ≥60 years old( P>0.05). The incidences of DVT were, respectively, 30.99% (97/313), 33.33% (108/324), 45.22% (156/345), 34.74% (33/95) for blood type O, type A, type B and type AB in the patients ≥60 years old. The DVT incidence for blood type B was significantly higher than those for blood type O and blood type A ( P< 0.008). Conclusions:The incidence of DVT varied with different blood types ABO after lower extremity fracture. The highest DVT incidence was found in patients with blood type B. The impact of blood type on the DVT incidence after lower extremity fracture was mainly observed in the patients with proximal fracture of the knee or an age of ≥ 60 years old.
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Objective:To explore the use of internet-based continuous visual recognition task (MemTrax test, MTX) as a rapid screening tool for amnestic mild cognitive impairment (aMCI).Methods:Sixty-four patients with aMCI and 64 individuals with normal cognition as healthy controls were enrolled respectively from Department of Neurology and Health Examination Center of the First Affiliated Hospital of Kunming Medical University from August 2018 to December 2019. Montreal Cognitive Assessment (MoCA) scale and MTX were adopted to assess the cognitive function of all subjects. The total adjusted MoCA scale score, correct rate of MTX, reaction time of MTX and MTX score were obtained and statistically analyzed.Results:The adjusted MoCA scale scores of aMCI patients and healthy controls were 19 (14, 24) and 26 (24, 27; Z=6.795), the correct rate of MTX of aMCI patients and healthy controls were 74% (60%, 80%) and 88% (84%, 94%; Z=8.359), and the MTX score of aMCI patients and healthy controls were 51.11±14.07 and 70.56±14.91 ( t=7.590), respectively, all with statistically significant difference ( P<0.001). Reaction time of MTX of aMCI patients and healthy controls was 1.401 (1.253, 1.590) s and 1.277 (1.163, 1.410) s, respectively ( Z=3.083, P<0.01). After adjustment for age, physical or mental occupation, exercise, hypertension, hyperlipidemia, stroke, sleep time, as well as smoke, the linear regression showed that the aMCI patients had a significant decrease of adjusted MoCA score, correct rate of MTX and MTX score ( P<0.001), and an extension of reaction time of MTX ( P=0.071), compared with the controls. By MTX and MoCA scale assessment, the best cutoff value was 81% for correct rate of MTX and 23 for adjusted MoCA scale score respectively for the prediction of aMCI (with sensitivity of 79.7%, 93.8% respectively, and specificity of 68.8%, 82.8% respectively). The area under the curve (AUC) of correct rate of MTX was 0.93 (95% CI 0.89-0.97, P<0.001), and the AUC of adjusted MoCA score was 0.85 (95% CI 0.78-0.91, P<0.001). There was a statistically significant difference in paired comparison of the two AUCs (χ2=4.620, P<0.05). Conclusion:MTX acts better for the detection of aMCI than MoCA scale, and correct rate of MTX<81% can be considered as the existence of MCI.
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OBJECTIVE:To dev elop and apply a parenteral nutrition prescription decision support system for medical institutions and provide theoretical basis for improving clinical parenteral nutrition precision treatment. METHODS :Based on the review points of parenteral nutrition prescription ,the parenteral nutrition prescription decision support system was designed ;the function points and prescription review logic of each module of the system were discussed ,and the system was also used to review 100 pieces of clinical parenteral nutrition prescriptions. RESULTS :Information-based parenteral nutrition prescription decision support system included evaluation index management module ,drug management module ,index knowledge management module , index calculation and evaluation module ,feedback and tracking module. The logic of parenteral nutrition prescription review were based on the evaluation indexes ,and rationality knowledge base ,safety knowledge base and drug attribute base were constructed. Based on the above knowledge bases ,patient information and prescription information call and calculation ,the evaluation result set of safety and rationality of the prescription was finally formed. Based on this design concept ,the parenteral nutrition prescription decision support system realized the automatic review and warning of various indicators in TNA prescription ,and can quickly and efficiently review the safety and rationality of parenteral nutrition prescription. Through manual judgment ,the audit results of 100 prescriptions by the system were all correct. CONCLUSIONS :The basis of parenteral nutrition prescription review is the formulation of evaluation indexes ,and the technical difficulty lies in considering the individuality and rationality as well as the safety and stability of parenteral nutrition solution at the same time. The application of a well-structured information system will promote the precise and reasonable medication of parenteral nutrition and improve work efficiency of medical personnel.