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Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.
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The community teaching bases play an important role in training of general practice talents. To raise the training quality, the development of their own capacity is crucial, but community medical institutions also need close cooperation with the departments of general practice in medical schools and the higher-level general hospitals. This article discusses the integration model of management, teaching and research in general practice talent training based on the cooperation of community teaching bases with relevant governmental departments, professional societies/associations, general hospitals and medical schools.
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Objective:To construct an evaluation system for clinical thinking ability of general practitioners in the treatment of multimorbidity.Methods:This was a cross-sectional study. The draft of evaluation indexes for clinical thinking ability of general practitioners in treatment of multimorbidity was preliminary developed through literature review, collation, analysis and discussion. Nineteen clinical and teaching experts of general practice were selected for consultation via anonymous convenient sampling. From January to June 2022, 2 rounds of expert consultation were conducted using the Delphi method. During the first round of consultation, according to the survey feedback, we modified and improved the evaluation system of general practitioners′ clinical thinking ability for multi-disease co-treatment. During the second round, experts were asked to assess the importance of each index, and to calculate the weight of each index accordingly. Questionnaires were sent to experts via letters. The content of the questionnaires encompasses the basic information of experts, evaluation for various indexes and relevant opinions. The mean value of importance assignment ≥3.5, coefficient of variation ≤0.25 and the full score frequency ≥30% were taken as the criteria. Indexes unsatisfying the criteria were removed, so that the final index system could be constructed.Results:The average age of 19 experts was 50.2 years old, 9 of them were male. A total of 2 rounds of expert consultation were conducted, 19 questionnaires were issued in each round, and 19 effective questionnaires were received afterwards. In the first round of consultation, 10 experts put forward revised opinions, and some indexes were adjusted according to the definition criteria and the discussion of the research group. In the second round of consultation, 3 experts put forward suggestions for modification. According to the definition criteria, no need to delete the indexes. After discussion by the research group, some indexes were adjusted, and finally an evaluation system of clinical thinking ability for multi-disease co-treatment of general practitioners was established, including 4 first-level indexes and 30 second-level indexes. The weights of the 4 first-level indexes in descending order were "overall thinking ability" (38.01%), "diagnostic thinking ability" (33.96%), "evidence-based thinking ability" (14.75%), and "critical thinking ability" (13.28%). Among the 30 secondary indexes, the top 5 were "ability to identify and handle priority emergency incidents" (5.04%), "risk assessment and critical illness identification ability" (4.63%), "emergency referral ability" (4.61%), "communication and expression ability" (4.57%), and "standardized diagnosis and treatment ability" (4.23%).Conclusion:This study successfully constructed an evaluation system for clinical thinking ability of general practitioners in the treatment of multimorbidity.
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Objective:To investigate the status quo of educational and teaching research in community bases for general practice standardized residency training in China.Methods:The studies related to education research in community bases for general practice standardized residency training were searched from Chinese Journal Full Text Database (CNKI), Wanfang Database and China Science and Technology Journal Database (VIP) from inception to November 30, 2023. The keywords of "standardized training of general practitioner residents" or "general practice standardized training" or "general practitioner standardized training" or "general practice training" and "community-based teaching " or "community training" "community base" or "community teaching" were used for search, and affiliations of authors should contain"community health service center". The literature was read and summarized using Endnote and Excel software.Results:A total of 171 articles were retrieved that met the criteria, and 130 articles were finally selected for analysis according to the quality review criteria of the literature. The authors of articles were distributed in 78 institutions of 17 provinces or regions, with 9 provinces or regions having a total of 123 articles (94.6%) with 2 published articles or more, of which the highest number was found in Beijing and Shanghai. Seventeen institutions published 2 or more articles with a total of 69 articles (53.1%), including 67 articles (51.5%) were co-authored by 2 units. The ranking top ten institutions in terms of the number of articles published were 5 community health service centers in Beijing, 4 in Shanghai (co-authored with Shanghai Zhongshan Hospital). There were 46 articles (35.4%) published in core journals and 55 articles (42.3%) with fund-supported projects. The studies presented teaching methods, teaching and training contents, teaching evaluation and effects, teacher training, teaching base construction and information technology application.Conclusion:The educational and teaching research in community bases for general practice standardized training in China has gradually received attention, the researches were mainly carried out by community medical institutions, but the overall quality of research needs to be further improved.
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Objective:To analyze the prenatal characteristics and pregnancy outcomes of fetuses with 17q12 microdeletion or microduplication.Methods:From January 2018 to December 2022, 14 fetuses diagnosed with 17q12 microdeletion and three with 17q12 microduplication by chromosomal microarray analysis folloning invasive prenatal diagnostic techniques at Nanjing Maternity and Child Health Care Hospital were retrospectively enrolled in this study. Relevant articles up to February 1, 2023, were retrieved from PubMed, Embase, China National Knowledge Infrastructure, Wanfang database, and Yiigle with the terms "17q12 microdeletion", "17q12 microduplication", "prenatal diagnosis", and "pregnancy outcome". Eighty-four 17q12 microdeletion cases and fourteen 17q12 microduplication cases were retrieved. Prenatal ultrasound features and pregnancy outcomes of those fetuses were analyzed and summarized.Results:In this study, ninety-eight 17q12 microdeletion cases and seventeen 17q12 microduplication cases were analyzed. (1) 17q12 microdeletion: The prenatal ultrasound showed all the 17q12 microdeletion cases had renal abnormalities (100.0%, 98/98), and renal hyperechogenicity was detected in 81.6% (80/98) of them; pedigree analysis suggested that 74.2% (49/66) mutations were de novo; 64.1% (41/64) of pregnant women chose to terminate the pregnancy and 35.9%(23/64) chose to continue pregnancy; eight out of 12 live births who were followed up had different degrees of abnormalities and four were normal during the follow-up period. (2) 17q12 microduplication: Among the 17 fetuses, 10 had upper gastrointestinal obstruction; pedigree analysis suggested that four were de novo mutations (4/13); nine out of 14 pregnant women with reported pregnancy outcomes chose to terminate the pregnancy, and five continued the pregnancy to delivery; follow up of the live births found that four neonates were normal and one had a good prognosis after surgery. Conclusions:Fetuses with 17q12 microdeletion often show renal hyperechogenicity in ultrasound images, and most mutations were de novo with poor prognosis. 17q12 microduplication in fetuses is often characterized by upper gastrointestinal obstruction, and most inherited from their parents.
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ObjectiveTo research the mechanism underlying the effect of raw and processed Aurantii Fructus Immaturus switched to Zhishi Shaoyaosan (ZSS) on constipation-predominant irritable bowel syndrome (C-IBS) rats via the brain-gut-microbiota axis. MethodEighty rats were randomly divided into the blank, model, positive drug (pinaverium bromide, 15.625 mg·kg-1), raw ZSS, stir-fried ZSS, bran-fried ZSS, charcoal-fried ZSS and finished ZSS groups (3.75 g·kg-1), with 10 rats in each group. Except for the blank group, which received intragastric administration of 0.9% sodium chloride solution at room temperature, all other groups were administered the ice solution at 0 to 4 ℃ (2 mL·d-1, for a total of 14 d) to establish the C-IBS rat model. The fecal water content and the propulsion rate of small intestine were detected after 14 d of continuous drug administration. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), neuro-peptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP), diamine oxidase (DAO) and D-lactic acid (D-LA) were detected by enzyme linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the changes in colonic pathological injury in each group. The expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) and aquaporin-3 (AQP3) mRNA in colon tissues were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and the protein expressions of VIP and AQP3 in colon tissues were detected by Western blot. The content of short chain fatty acids (SCFAs) was determined by gas chromatography-mass spectrometry. ResultCompared with the blank group, the fecal water content and intestinal propulsion rate of rat in the model group were significantly decreased (P<0.01), and the levels of 5-HT, VIP, CGRP and SP in serum were significantly increased. Simultaneously, the NPY levels significantly decreased (P<0.01), the levels of DAO and D-LA in plasma were significantly increased (P<0.01), and the mucosal epithelium of colon tissue was slightly damaged, with reduced goblet cells and significantly reduced luminal granules. The mRNA expression levels of AQP3, cAMP and PKA and the protein expression levels of AQP3 and VIP in colon tissue were significantly decreased (P<0.05, P<0.01). The total amount of SCFAs in feces showed an obvious decreasing trend, with the contents of acetic acid, isobutyric acid, isovaleric acid, valeric acid and caproic acid decreased significantly, while the contents of propionic acid and butyric acid increased significantly (P<0.05, P<0.01). Compared with the model group, the treatment groups increased the intestinal propulsion rate, improved the intestinal mucosal barrier function, and adjusted the level of serum brain-gut peptide in C-IBS rats (P<0.05, P<0.01). The expression levels of AQP3, cAMP, PKA mRNA and VIP, AQP3 protein in colon tissue of rats in all treatment groups were increased. All the treatment groups had a significant downregulation of the content of SCFAs except for isobutyric acid in rat feces, and the effect of ZSS prepared by the bran-fried Aurantii Fructus Immaturus was superior than that of other ZSS. ConclusionThe raw and processed Aurantii Fructus Immaturus switched to ZSS could influence the brain-gut-microbiota axis to treat C-IBS rats and it is more reasonable to use bran-fried Aurantii Fructus Immaturus in ZSS.
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Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data(including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography), imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
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Humans , Connexins/genetics , Connexin 26/genetics , Hearing Loss, Central/genetics , Deafness/genetics , MutationABSTRACT
Objective:To investigate the effect of high-intensity interval training on cognitive weakness in elderly patients with coronary heart disease.Methods:A randomized controlled study was used. A total of 70 elderly patients with coronary heart disease after discharge from the Cardiology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from June 2020 to June 2021 were selected and divided into the control group (35 cases) and the observation group (35 cases) by random digits table method. The control group received conventional treatment, and the observation group received high-intensity interval training on the basis of conventional treatment. The changes of peak oxygen intake (PeakVO 2), anaerobic threshold oxygen uptake (ATVO 2), Fried phenotype score, Montreal Cognitive Assessment score, and SF-36 quality of life assessment score before and after 12 weeks of intervention were compared between the two groups. Results:During the intervention, 2 cases fell off in the control group and 2 cases in the observation group. After 12 weeks of intervention, PeakVO 2 and ATVO 2 in the observation group were (23.91 ± 5.88), (20.79 ± 5.19) ml·min -1·kg -1, respectively, higher than those in the control group(20.56 ± 5.81), (17.29 ± 5.36) ml·min -1·kg -1, and the differences were statistically significant ( t = 2.38, 2.69, both P<0.05). The scores of SF-36 quality of life assessment and Montreal Cognitive Assessment in the observation group were (85.33 ± 6.43), (22.64 ± 3.81) points, which were significantly higher than those in the control group (78.72 ± 8.14), (20.67 ± 3.04) points, and the differences were statistically significant ( t = 3.66, 2.32, both P<0.05); the Fried phenotype score in the observation group was (1.36 ± 0.99) points, which was significantly lower than that in the control group (3.03 ± 1.08) points, and the difference was statistically significant ( t = 6.54, P<0.05). Conclusions:High-intensity interval training can improve cardiopulmonary function, aerobic exercise ability, cognitive weakness and quality of life in elderly patients with coronary heart disease.
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Objective To investigate the risk factors of coronary microvascular disease(CMVD)in elderly female patients.Methods Clinical data of 109 consecutive female elderly patients who re-ceived coronary angiography and coronary flow reserve(CFR)in our hospital from September 2020 to June 2022 were retrospectively collected in this study.According to CFR value,they were divided into CMVD group(CFR<2.0,n=55)and non-CMVD group(CFR ≥2.0,n=54).The basic clinical data were compared between the two groups,and influencing factors associated with CMVD were analyzed.Results Significantly higher BMI and elevated UA,hs-CRP,TG,LDL and Lp-PLA2 levels,while lower HDL level was observed in the CMVD group than the non-CMVD group(P<0.05,P<0.01).Lp-PLA2 and hs-CRP were negatively correlated with CFR(r=-0.816;r=-0.399,P<0.01).Spearman correlation analysis indicated that CRV value was nega-tively correlated with Lp-PLA2 and hs-CRP levels(r=-0.816,-0.399,P<0.01).Logistic re-gression analysis showed that hs-CRP and Lp-PLA2 were independent risk factors for CMVD in elderly female patients(P<0.05).ROC curve analysis revealed that the AUC value of Lp-PLA2 for diagnosing CMVD in elderly female patients was 0.745(95%CI:0.655-0.836),with a sensi-tivity of 69.1%and a specificity of 67.0%.And,the AUC value of hs-CRP was 0.752(95%CI:0.661-0.844).Conclusion Lp-PLA2 and hs-CRP levels are quite higher in elderly female CMVD patients,and can predict the occurrence of CMVD in elderly female patients.
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Diet can be both a trigger and a treatment for migraine. The effects of alcohol, dairy products and pickled foods on migraine have been highly recognized. The effects of plant foods and caffeine on migraine currently have 2 sides. Ketogenic diet (KD), modified Atkins diet (MAD), and high n-3 fatty acid/low n-6 fatty acid diet can improve migraine through protecting nerves, improving mitochondrial function and energy metabolism, reducing calcitonin gene-related peptide (CGRP) levels, and inhibiting neuroinflammation. In this paper, the recent advance in the above content is summarized as follows.
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Human platelet lysates(HPL), as a new type of biomaterial, can promote tissue repair, cell proliferation and inflammation control. This paper introduced the development of HPL in the field of regenerative medicine and cell therapy and summarizes their application. The potential of HPL to promote cell proliferation was used as an entry point to show its advantages as a supplement of cell culture medium. Since there is currently no standard procedure for HPL preparation, this paper sorts out the standardization elements such as raw materials source, donor variability and preparation technology, in order to provide reference for the establishment of standards of relevant industry in the future.
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Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.
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Objective:To investigate the value of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and texture analysis for predicting BRAF gene mutation in rectal cancer.Methods:The clinical diagnositic trial was conducted. The clinicopathological data of 36 rectal cancer patients who were admitted to the First People's Hospital of Shangqiu from January 2016 to June 2021 were collected. There were 28 males and 8 females, aged (50±4)years. All the 36 patients were confirmed by pathological examination. After genetic testing, 12 patients with BRAF mutant type of BRAF V600E mutation were allocated into the mutation group, and 24 patients with BRAF wild type were allocated into the non-mutation group. All patients underwent MRI scan before surgery, and IVIM related post-processing images were received by Function Tool post-processing software. Observation indicators: (1) consistency test between observers of IVIM para-meters and texture parameters; (2) comparison of IVIM parameters on MRI between the two groups; (3) comparison of texture parameters on MRI between the two groups; (4) diagnostic efficacy of IVIM and texture parameters. The intraclass correlation coefficient (ICC) was used to evaluate the consistency between observers, with ICC >0.80 as good consistency. The average values of para-meters with ICC >0.80 were included for further analysis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed by the indepen-dent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The texture parameters were combined using the Logistic regression model. Receiver operating charac-teristic curve was used to analyze the predictive performance and calculate the sensitivity and specificity. Results:(1) Consistency test between observers of IVIM parameters and texture parameters: the ICCs between two observers of IVIM parameters including apparent diffusion coefficient, diffusion related coefficient, perfusion-related diffusion coefficient and perfusion-related parameter were 0.91, 0.90, 0.91, 0.89, respectively. The ICCs of texture parameters including the minimum value, the maximum value, the 10th percentile and the 25th percentile between two observers were <0.80 while the ICCs of texture parameters including mean value, the 50th percentile, the 75th percentile, the 90th percentile, energy, entropy, skewness and kurtosis between two observers were >0.80. (2) Comparison of IVIM parameters on MRI between the two groups: IVIM parameters of diffusion related coefficient and perfusion-related parameter on MRI were (0.70±0.13)×10 -3 mm 2/s and 0.39±0.30 for the mutation group, versus (0.79±0.12)×10 -3 mm 2/s and 0.17±0.10 for the non-mutation group, showing significant differences between the two groups ( t=-2.17, 2.46, P<0.05). (3) Comparison of texture parameters on MRI between the two groups: the texture parameters of mean value and energy on diffusion related coefficient image were 0.54±0.23 and 0.00(0.00,0.01) for the mutation group, versus 0.77±0.34 and 0.01(0.00,0.01) for the non-mutation group, showing significant differences between the two groups ( t=-2.12, Z=-1.35, P<0.05). (4) Diagnostic efficacy of IVIM and texture parameters: the areas under the curve (AUCs) of diffusion related coefficient, perfusion-related parameter, IVIM parameters combination, mean value of diffu-sion related coefficient image, energy value of diffusion related coefficient image, texture parameters combination were 0.69[95% confidence interval ( CI) as 0.52-0.84], 0.76(95% CI as 0.59-0.88), 0.79(95% CI as 0.62-0.91), 0.71(95% CI as 0.52-0.85), 0.79(95% CI as 0.62-0.91), 0.84(95% CI as 0.68-0.94), which were all lower than the AUC of IVIM and texture parameters combination as 0.92(95% CI as 0.79-0.99). Conclusions:IVIM parameters and texture parameters of MRI can non-invasively predict the mutation status of BRAF gene in rectal cancer. The combination of IVIM and texture parameters has a better predictive efficacy.
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Objective:To explore the effect of Toll-like receptor 9 (TLR9) signaling pathway activation on the transcriptome in the renal tubular cells.Methods:Mouse primary renal tubular epithelial cells were extracted and cultured. When the degree of cell fusion reached 80%, they were divided into two groups, which were added with 10 μL phosphate buffered saline (PBS, PBS control group) and TLR9 activator cytosine phosphate guanidine oligodeoxynucleotide (CpG-ODN) with a final concentration of 5 μmol/L (CpG-ODN treatment group). The RNA sequencing was performed on the Illumina platform after extraction. DEGseq software was used to analyze the differential expression of genes between the two groups. Goatools and KOBAS online software were used to analyze the differential genes involved signal pathways. Homer software was used to predict transcription factors.Results:Compared with the PBS control group, there were a total of 584 differentially expressed genes in the CpG-ODN treatment group, of which 102 were up-regulated and 482 were down-regulated. The most significantly enriched gene ontology (GO) terms of differentially expressed genes included response to interferon-β, defense response to virus and other inflammatory pathway. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways included 2'-5'-oligoadenylate synthase activity, regulation of ribonuclease activity, negative regulation of virus life cycle, cellular response to interferon-βand defense response to protozoan. The results of transcription factor prediction showed that interferon regulatory factor 3 (IRF3) was the most significantly enriched transcription factor in the promoter sequence of differential genes; the most significant transcription factor downstream of TLR9 was IRF3, and other predicted transcription factors such as transcription factor 21 (TCF21), zinc finger protein 135 (ZNF135), and PR domain containing 4 (PRDM4) might be new candidates for TLR9 signaling pathway.Conclusion:CpG-ODN activates TLR9 signaling pathway, and primary renal tubular epithelial cells can directly respond to CpG-ODN stimulation and undergo transcriptome changes, which provides a basis for further research on the molecular mechanism of TLR9 pathway in sepsis induced acute kidney injury.
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Objective:To investigate the effect of somatostatin receptor ligands (SRLs) on bone metabolism in patients with acromegaly.Methods:Retrospective analysis of clinical data of acromegaly patients( n=100) received surgery or SRLs alone for 3 months. The changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), osteocalcin (OC), N-mid fragment of osteocalcin (N-MID), amino-terminal peptide of type I procollagen (P1NP) and C-terminal peptide degradation product of type I collagen(CTX) were compared before and after treatment. Patients were divided into drug treatment group and surgical group according to treatment methods. According to the decline of GH after medication, patients in the drug treatment group were further divided into drug sensitive group and drug insensitive group. Results:The average dynamic GH and IGF-1 indexes in the drug treatment group were significantly decreased after treatment compared with before treatment (both P<0.05), and CTX was also significantly decreased after treatment [1.25 (0.67, 1.40) ng/mL vs 1.34 (0.57, 1.68) ng/mL, P<0.05]. The mean dynamic GH, IGF-1 index, OC, N-MID, P1NP, and CTX in surgical group were significantly decreased after treatment compared with before treatment (all P<0.01). In the surgical group, there was a positive correlation between GH difference (ΔGH) and N-mid difference (ΔN-MID; r=0.454, P=0.026), and there was a positive correlation between IGF-1 index difference (ΔIGF-1 index) and CTX difference (ΔCTX; r=0.339, P=0.036). After treatment, the mean dynamic GH, IGF-1 index, CTX, P1NP, and N-MID in drug treatment group were significantly higher than those in surgical group (all P<0.001). CTX and N-MID decreased significantly after treatment in drug sensitive group compared with drug insensitive group (35.3% vs 7.2%, P<0.001; 24.1% vs 11.8%, P<0.05), and ΔGH was positively correlated with ΔCTX ( r=0.328, P=0.004). Conclusion:SRLs treatment can reduce bone formation marker N-MID and bone resorption marker CTX, improving the high turnover state of bone metabolism in patients with acromegaly, which may attribute to the reduction of GH and IGF-1 levels.
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Background/Aims@#Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). @*Methods@#Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. @*Results@#A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. @*Conclusions@#Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.
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Objective:To describe the prevalence and clinical characteristics of macroprolactinemia in hyperprolactinemia patients.Methods:Consecutive 111 outpatients diagnosed with hyperprolactinemia were included in this study. Macroprolactin was routinely screened using the polyethylene glycol(PEG) precipitation method. Recovery of monomeric prolactin less than 40% was defined as macroprolactinemia. Clinical characteristics were analyzed in this study.Results:Among the 111 cases included, 99 were female and 12 were male, with an average age of(32.2±7.9) years. There were 32 cases(28.8%) of macroprolactinemia and 28 of them with normal monomeric prolactin levels(simple macroprolactinemia). prolactin levels before precipitation in simple macroprolactinemia were significantly lower than those with true hyperprolactinemia[(49.81±23.58 vs 83.56±65.82) ng/mL, P<0.05]. No amenorrhea and infertility were observed in patients with simple macroprolactinemia. The clinical manifestations of prolonged menstruation, oligomenorrhea and galactorrhea in female patients accounted for 25.9%, 37.0%, and 7.4%, respectively. Imaging data were obtained in 92 cases. The prevalence of pituitary adenomas in simple macroprolactinemia and true hyperprolactinemia was 42.9% and 66.0%, respectively. Fifteen(46.8%) of the macroprolactinemia cases were receiving or had received bromocriptine treatment, and 66.7% of them failed to achieve normal prolactin levels during therapy. Conclusion:Macroprolactinemia might be common in clinical practice. Macroprolactin should be screened in hyperprolactinemia patients lack of amenorrhea and infertility, and with poor response to dopamine agonist therapy.
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Objective To investigate the changing trend and correlation of platelet count and spleen diameter in patients with digestive system malignancy receiving oxaliplatin-based chemotherapy. Methods We retrospectively analyzed clinical data of 72 patients with digestive system cancer, recorded and analyzed platelet count and spleen diameter during and after oxaliplatin-based chemotherapy. Results The incidence of thrombocytopenia in all patients was 65.3%. The median time of thrombocytopenia after the beginning of chemotherapy was 2.53±0.49 months, and the median cumulative dose of oxaliplatin was 520±35.81 mg/m2; the median time of lowest platelet count after the beginning of chemotherapy was 4.03±0.49 months, and the median cumulative dose of oxaliplatin was 780±36.32 mg/m2. Splenomegaly occurred in 52(72.2%) patients during the follow-up. The median increase rate was (18.82±0.01)%. The median time of splenomegaly after the beginning of chemotherapy was 2.15±0.19 months, the median time for the largest spleen diameter was 4.68±2.89 months; after the end of chemotherapy, the median time for spleen contraction was 3.28±0.44 months, and the median time for spleen recovery was 8.80±1.05 months. Conclusion Oxaliplatin-based chemotherapy can cause thrombocytopenia and splenomegaly, and it is difficult to recover to baseline for a long time after the end of chemotherapy. The increase of spleen diameter was positively correlated with splenomegaly and thrombocytosis.
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To establish an intelligent cervical vertebra maturity assessment system, and to evaluate the reliability and clinical value of the system. Sixty children aged were recruited in the study. Lateral cephalometric radiograph and cone beam CT (CBCT) were taken at the same period. Based on the CBCT data, the system automatically extracted the patient's facial area through Otsu's method, intercepted the sagittal plane by three-dimensional least squares method, captured the second to fourth cervical vertebrae by superpixel segmentation. And then selected points were marked automatically through morphological algorithm and manual method. Consistency test was performed on the two sets of data to compare the reliability of automated cervical morphology capture. According to the parameters of morphological identification, positioning and staging algorithms were designed to form the intelligent cervical vertebra maturity assessment system. The cervical vertebra maturity was also judged manually on the lateral cephalometric radiograph. The weighted Kappa test and the Gamma correlation coefficient were subsequently applied to evaluate the consistency and correlation. The results showed that the cervical vertebra features automatically captured based on CBCT data had a high accuracy on the overall morphological recognition. In the prediction of 8 inflection points out of 13 points, there was no significant difference between automatic and manual method on both X and Y axes (all >0.05). The assessment results of the cervical vertebra maturity of the intelligent system had strong consistency and correlation with the manual recognition results (weighted Kappa value=0.877, Gamma value=0.991, both <0.05). The intelligent cervical vertebrae maturity assessment system based on CBCT data established in this study presents reliable outcome and high degree of automation, indicating that the system may be used clinically.
Subject(s)
Child , Humans , Cephalometry , Cervical Vertebrae/diagnostic imaging , Cone-Beam Computed Tomography , Radiography , Reproducibility of ResultsABSTRACT
Objective:To investigate the prognostic value of preoperative red blood cell distribution width (RDW) for hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 025 HCC patients who were admitted to three medical centers (586 in the First Affiliated Hospital of Xi'an Jiaotong University, 248 in the Second Affiliated Hospital of Xi'an Jiaotong University and 191 in the Qinghai University Affiliated Hospital) between April 2002 and August 2017 were collected. There were 809 males and 216 females, aged (54±11)years, with a range from 16 to 83 years. The average coefficient of variation of RDW (RDW-CV) of 1 025 patients was 14.3%. Of 1 025 patients, 347 cases had high RDW of RDW-CV >14.3%, and 678 had low RDW of RDW-CV ≤14.3%. Observation indicators: (1) clinico-pathological data of HCC patients; (2) influencing factors for prognosis of HCC patients; (3) follow-up and survival. (4) stratified analysis of independent influencing factors. Follow-up was performed by outpatient examination, telephone interview or internet interview to detect postoperative survival of patients up to October 2017. Measurment data with normal distribution were represented as Mean±SD, and measurment data with skewed distribution were described as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The Graphpad Prism 7.0 was used to draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard model. Results:(1) Clinicopathological data of HCC patients: cases with age ≤70 years or >70 years, cases without cirhhosis or with cirhhosis , cases of Child-Pugh grade A or Child-Pugh grade B or C, cases with the level of alpha fetoprotein (AFP) ≤200 μg/L or >200 μg/L, cases with single tumor or multiple tumors were 313, 34, 152, 186, 161, 53, 158, 143, 186, 109 for high RDW patients, versus 641, 37, 359, 310, 415, 48, 367, 227, 547, 131 for low RDW patients, respectively, showing significant differences in above indicators between the two groups ( χ2=6.709, 6.787, 23.906, 7.114, 34.375, P<0.05). (2) Influencing factors for prognosis of HCC patients: results of univariate analysis showed that age, Child-Pugh grade, AFP, RDW-CV, tumor diameter, the number of tumors were related factors for prognosis of patients ( hazard ratio=1.388, 1.432, 1.534, 1.455, 2.813, 1.505, 95% confidence interval as 1.004-1.920, 1.086-1.887, 1.263-1.864, 1.211-1.748, 2.293-3.450, 1.173-1.932, P<0.05 ). Results of multivariate analysis showed that age, RDW-CV, tumor diameter and the number of tumors were independent factors for prognosis of patients ( hazard ratio=1.020, 1.340, 2.427, 1.438, 95% confidence interval as 1.007-1.032, 1.027-1.749, 1.801-3.272, 1.057-1.956, P<0.05). (3) Follow-up and survival: 1 025 patients were followed up for 1-124 months, with a median follow-up time of 25 months. The median survival time was 23 months for high RDW patients, versus 44 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=11.640, P<0.05). (4) Stratified analysis of independent influencing factors: the results of stratified analysis of 3 independent influencing factors including age, tumor diameter and the number of tumors showed that in the 954 patients with age ≤70 years, the median survival time was 25 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=14.030, P<0.05). In the 71 patients with age >70 years, the median survival time was 11 months for high RDW patients, versus 29 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=0.933, P>0.05). In the 459 patients with tumor diameter ≤5 cm, the median survival time was 44 months for high RDW patients, versus 76 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=8.660, P<0.05). In the 487 patients with tumor diameter >5 cm, the median survival time was 14 months for high RDW patients, versus 18 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=2.950, P>0.05). In the 733 patients with single tumor, the median survival time was 20 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=13.530, P<0.05). In the 240 patients with multiple tumors, the median survival time was 15 months for high RDW patients, versus 20 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=6.820, P<0.05). Conclusions:Preoperative RDW can be used as a predictive index for prognosis of HCC patients, and patients with high RDW have poorer prognosis. RDW have better predictive value in patients with age ≤70 years or tumor diameter ≤5 cm.