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BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.
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Adult , Humans , Dermatitis, Atopic/drug therapy , Treatment Outcome , Severity of Illness Index , Antibodies, Monoclonal, Humanized/therapeutic use , Injections, Subcutaneous , Double-Blind MethodABSTRACT
As a commonly used traditional Chinese medicine in clinical practice， Tripterygium wilfordii has the functions of dispelling wind and removing dampness， detoxicating and destroying parasites， detumescence， pain relief， promoting blood circulation， and dredging collateral. Modern pharmacological studies show that it also has other functions such as anticancer， anti-inflammation， and immunosuppression. It has been widely used to treat autoimmune diseases， renal diseases， and tumors. T. wilfordii contains a variety of chemical components， among which triptolide （TP） can cause varying degrees of damage to human digestive， circulatory， reproductive， and other systems， with liver injury being the most common one， which greatly limits the development of TP in new drug research and industrial application. Therefore， the authors focused on the research hotspot of TP-induced liver injury and summarized relevant Chinese and international literature regarding the clinical manifestations， injury mechanisms， and detoxification strategies of TP-induced liver injury. This helps to provide a scientific basis for the clinical drug safety and scientific drug supervision of TP. The clinical manifestations of TP-induced liver injury are mostly abnormal transaminases， loss of appetite， nausea and vomiting， anorexia， yellow staining of skin and sclera， and yellow urine. The mechanisms of the above clinical manifestations involve apoptosis， oxidative stress， influence on cytochrome P450 superfamily， macrophage polarization， regulation of biological clock gene Clock， etc. Among them， cell apoptosis is related to neurogenic locus notch homolog protein 1 （Notch1）， dynamin-related protein 1 （Drp1）-cytochrome C （Cyt C）， phosphatidylinositide 3-kinases （PI3K）/protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， tumor suppressor protein 53 （p53）， Fas cell surface death receptor （Fas）/Caspase-8， and other signaling pathways. Oxidative stress is related to inhibition of nuclear factor-erythroid 2-related factor 2 （NRF2） signaling pathway， promotion of cytochrome P450 2E1 （CYP2E1） expression， and excessive accumulation of reactive oxygen （ROS）. The influence of the cytochrome P450 superfamily is manifested as reducing the substrate affinity， activity， and expression of cytochrome P450 3A （CYP3A）， cytochrome P450 2C9 （CYP2C9）， cytochrome P450 2C19 （CYP2C19）， and cytochrome P450 1A2 （CYP1A2）. Promoting the transformation of macrophages into the M1 type is related to the secretion of inflammatory factors and the accumulation of endotoxin， and the internal rhythmic regulation of the biological clock gene Clock， is related to the expression of cytochrome P450 3A11 （CYP3A11） metabolic enzyme. The detoxification strategies in the clinical application include herbs-processing detoxification strategy and drug-pairing detoxification. The traditional Chinese medicines and monomers that are helpful for detoxification include Glycyrrhiza uralensis， Paeonia lactiflora， Lysimachia christinae， Rehmannia glutinosa， saffron， and paeoniflorin. The reviews and discussion about these topics can help to provide more references for related research and clinical application of TP.
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OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of generic drugs and original drugs of voriconazole. METHODS The information of patients who used voriconazole generic drugs selected in National Centralized Drug Procurement （generic drug group） or non-selected original drugs （original drug group） in the treatment of fungal infection was collected from the our hospital. The propensity score matching was carried out to eliminate bias. The comprehensive efficacy was evaluated according to clinical efficacy， image findings and microbiological test， and stratified analysis of different populations was conducted based on fungal species， underlying diseases， etc.， the efficacy of different stratifications was evaluated. Evaluation of safety was performed by using the incidence of adverse reactions. The total cost， defined daily doses （DDDs） and defined daily dose cost （DDDc） were used to evaluate the cost-effectiveness. RESULTS A total of 436 patients were included， and there were 190 patients in each group after matching. In terms of efficacy， the effective rates of voriconazole generic drugs and original drugs were 62.63% and 59.47% （P＝0.528）； in terms of safety， the incidence of adverse reactions caused by generic drugs and original drugs of voriconazole was 13.68% and 7.89%， respectively（P＝0.069）. In terms of cost-effectiveness， the average total cost of generic drugs was 4 636.26 yuan， and that of original drugs was 8 613.20 yuan （P＜0.001）. After the implementation of National Centralized Drug Procurement， replacement rate of generic drugs increased to 87.30%， and DDDc decreased by 59.08%. CONCLUSIONS The efficacy and safety of voriconazole generic drugs are similar to those of original drugs in the treatment of fungal infection， and it is more cost-effective in terms of treatment cost.
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Purpose@#This study aimed to identify the risk factors and sonographic variables that could be integrated into a predictive model for endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) in women with abnormal uterine bleeding (AUB). @*Materials and Methods@#This retrospective study included 1837 patients who presented with AUB and underwent endometrial sampling. Multivariable logistic regression was developed based on clinical and sonographic covariates [endometrial thickness (ET), resistance index (RI) of the endometrial vasculature] assessed for their association with EC/AEH in the development group (n=1369), and a predictive nomogram was proposed. The model was validated in 468 patients. @*Results@#Histological examination revealed 167 patients (12.2%) with EC or AEH in the development group. Using multivariable logistic regression, the following variables were incorporated in the prediction of endometrial malignancy: metabolic diseases [odds ratio (OR)=7.764, 95% confidence intervals (CI) 5.042–11.955], family history (OR=3.555, 95% CI 1.055–11.971), age ≥40 years (OR=3.195, 95% CI 1.878–5.435), RI ≤0.5 (OR=8.733, 95% CI 4.311–17.692), and ET ≥10 mm (OR=8.479, 95% CI 5.440–13.216). :A nomogram was created using these five variables with an area under the curve of 0.837 (95% CI 0.800–0.874). The calibration curve showed good agreement between the observed and predicted occurrences. For the validation group, the model provided acceptable discrimination and calibration. @*Conclusion@#The proposed nomogram model showed moderate prediction accuracy in the differentiation between benign and malignant endometrial lesions among women with AUB.
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Objective:To investigate the anatomy of rectus femoris muscle flap and the anterolateral thigh muscle flap and their clinical application in reconstruction of large soft tissue defects after the removal of oral malignant tumour.Methods:From December 2006 to June 2009, 8 specimens of Chinese adult cadavers fixed in 10% formaldehyde were dissected to perform anatomy of anterolateral thigh region at the School of Basic Medical Sciences, Kunming Medical University. Anatomical images were analysed using Image-Pro Plus 6.0. Then, a retrospective study was performed on 19 patients who had postoperative defects after oral malignant tumour surgery and the defects were reconstructed with the rectus femoris muscle flap and the anterolateral thigh muscle flap from March 2020 to July 2022 at the Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital, Kunming Medical University. The postoperative defects of the 19 patients ranged from 3.0 cm×6.0 cm to 5.0 cm×10.0 cm. Ten rectus femoris muscle flaps, 8 anterolateral thigh muscle flaps and 1 combined rectus femoris muscle flap and anterolateral thigh muscle flap were used. The muscular flaps sized from 4.0 cm × 8.0 cm to 6.0 cm × 11.0 cm. Regular postoperative outpatient follow-ups were conducted.Results:The lengths of vessels of the harvested rectus femoris muscle flap and anterolateral thigh muscle flap were 63.4 mm± 12.9 mm and 112.5 mm± 19.6 mm, respectively. The starting outer diameters of the lateral circumflex thigh artery, the oblique branch of the lateral circumflex thigh artery and the descending branch of the lateral circumflex thigh artery were 2.92 mm±0.72 mm, 1.88 mm±0.23 mm and 2.29 mm±0.43 mm, respectively. Postoperative follow-up lasted for 7 to 32 months, with 17.5 months in average. Seventeen flaps were completely survived and the rectus femoris muscle flap was completely mucosalised 5 weeks after surgery. However, 2 rectus femoris muscle flaps had necrosis of which one was changed to a tongue flap reconstruction and the other encountered flap necrosis during postoperative radiotherapy and healed after debridement and dressing changes. There was no postoperative complication in the donor sites. Other than the 2 patients, all other 17 patients had satisfactory clinical outcomes.Conclusion:Both of the starting outer diameters and length of vessels of the femoris muscle flap and the anterolateral thigh muscle flap meet the requirements for reconstruction of maxillofacial defects, and both muscular flaps are simple to prepare, in good reconstructive results with few complication, as well as an excellent outcome. They are feasible approaches for reconstruction of large soft tissue defects left after the removal of an oral malignant tumour.
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Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.
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OBJECTIVE@#To investigate the effect of Akt2 inhibitor on macrophage polarization in the periapical tissue in a rat model of periapical inflammation.@*METHODS@#Rat models of periapical inflammation were established in 28 normal SD rats by opening the pulp cavity of the mandibular first molars, followed by injection of normal saline and Akt2 inhibitor into the left and right medullary cavities, respectively. Four rats without any treatment served as the healthy control group. At 7, 14, 21 and 28 days after modeling, 7 rat models and 1 control rat were randomly selected for observation of inflammatory infiltration in the periapical tissues by X-ray and HE staining. Immunohistochemistry was used to detect the expression and localization of Akt2, macrophages and the inflammatory mediators. RT-PCR was performed to detect the mRNA expressions of Akt2, CD86, CD163, inflammatory mediators, miR-155-5p and C/EBPβ to analyze the changes in macrophage polarization.@*RESULTS@#X-ray and HE staining showed that periapical inflammation was the most obvious at 21 days after modeling in the rats. Immunohistochemistry and RT-PCR showed that compared with those in the control rats, the expressions of Akt2, CD86, CD163, miR-155-5p, C/EBPβ, and IL-10 increased significantly in the rat models at 21 days (P < 0.05). Compared with saline treatment, treatment with the Akt2 inhibitor significantly decreased the expression levels of Akt2, CD86, miR-155-5p and IL-6 and the ratio of CD86+M1/CD163+M2 macrophages (P < 0.05) and increased the expression levels of CD163, C/EBPβ and IL-10 in the rat models (P < 0.05).@*CONCLUSION@#Inhibition of Akt2 can delay the progression of periapical inflammation in rats and promote M2 macrophage polarization in the periapical inflammatory microenvironment possibly by reducing miR-155-5p expression and activating the expression of C/EBPβ in the Akt signaling pathway.
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Rats , Animals , Proto-Oncogene Proteins c-akt/metabolism , MicroRNAs/genetics , Interleukin-10 , Rats, Sprague-Dawley , Macrophages/metabolism , Inflammation/metabolismABSTRACT
{L-End}Objective To analyze the correlation between occupational burnout and sleep quality among steelworkers. {L-End}Methods A total of 11 491 steelworkers from a large steel enterprise in Gansu Province were selected as the research subjects using convenient sampling method. The Burnout Questionnaire and the Pittsburgh Sleep Quality Index Scale were used to investigate their occupational burnout and sleep quality. Hierarchical regression analysis was used to analyze the effects of occupational burnout on the sleep quality. {L-End}Results The detection rate of occupational burnout and sleep disorder were 50.4% and 39.0%, respectively. There was a positive correlation between the level of occupational burnout and the total score of sleep quality (Spearman correlation coefficient=0.454, P<0.05). The results of hierarchical regression analysis, adjusting for confounding factors such as gender, age, marital status, education level, alcohol consumption, exercise, weekly working hours, seniority, work shift, noise exposure, dust exposure, and high-temperature work, showed that the score of occupational burnout was positively related to the score of sleep quality(P<0.01), explaining 16.0% of the variance in the score of sleep quality among these steelworkers. {L-End}Conclusion The detection rate of occupational burnout and sleep disorders are relatively high among the steelworkers in this enterprise. Higher levels of occupational burnout are associated with poorer sleep quality. Alleviating occupational burnout among steelworkers may contribute to improving their sleep quality.
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Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
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Animals , Humans , Sarcopenia/metabolism , Forkhead Box Protein O3/metabolism , Muscle, Skeletal/metabolism , Aging/metabolism , Primates/metabolismABSTRACT
Objective:To explore the application value of case-based learning (CBL) combined with role-playing mode in clinical practice teaching for international students in department of dermatology.Methods:International students from Batch 2013 and Batch 2014 of MBBS (Bachelor of Medicine and Bachelor of Surgery, MBBS) Program of Sichuan University were recruited and divided into study and control group respectively. CBL combined with role-playing mode and traditional lecture-based learning (LBL) was adopted in the study group. The control group adopted the traditional LBL only. The points of knowledge gain, degree of interest inspiration, analytical ability and communication skill were assessed within the study group by questionnaire, meanwhile the final-test scores were compared between the study and control groups. SPSS 17.0 was used for t test, and signed rank-sum test of paired design was used for comparison. Results:Within the study group, the points of knowledge gain, degree of interest inspiration, analytical ability and communication skill for CBL combined with role-playing mode[95 (91,100)] were significantly higher than those of LBL [84 (78, 100)], and the final-test scores were significantly higher in study group [(90.23±4.78) points] than those in control group [(82.51±7.57) points] ( P<0.05). Conclusion:Clinical practice teaching for international medical students can be improved with the CBL combined with role-playing mode based on traditional LBL, which is worthy of widely application in future clinical education.
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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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At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%-50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).
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Female , Humans , Endometriosis/pathology , Endometrium/pathology , Ki-67 Antigen/metabolism , Quality of Life , Recurrence , Telomerase/metabolism , Up-RegulationABSTRACT
Objective:Through retrospective analysis of perioperative management data of ambulatory thyroid surgery under the concept of enhanced recovery after surgery (ERAS), we provide foundation for the safe implementation of ambulatory thyroid surgery.Methods:From January 2019 to December 2019, patients undergoing thyroid surgery were enrolled in the study under the concept of ERAS at the ambulatory surgery center of Xiangya Hospital, Central South University. Data of patients during perioperative period were collected, including adverse events, anesthesia recovery, postoperative and post-discharge recovery were recorded.Results:This study was included 703 cases of patients, thyroid nodules in 374 cases, thyroid malignant tumor in 329 cases. There were no significance difference in the operation time, anesthesia time, wake up of time, and postanesthesia care unit (PACU) time between the two groups (all P>0.05). No hypertension, hypotension, tachycardia, bradycardia or other arrhythmias occurred during perioperative period. No adverse events such as intraoperative awareness and delay of wake up occurred. No severe pain, nausea, vomiting, dizziness and other discomfort occurred after surgery. All 703 patients were discharged from hospital within 24 hours. Conclusions:Anesthesiologists participate in patient management according to the perioperative medicine requirements, and ambulatory thyroid surgery may be performed safely under the concept of ERAS.
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Objective:To compare the laboratory diagnostic methods of Mycoplasma pneumonia(MP) and evaluate its clinical value.Methods:A prospective study.Throat swabs and double sera of children with MP infection were collected from December 2016 to January 2017 in Shengjing Hospital Affiliated to China Medical University; throat swab samples of healthy children aged 3 to 5 in Chaoyang District, Beijing were collected from March to May 2017.Passive agglutination (PA) was used to detect the double serum.Taking the 4-fold increase or decrease of the specific antibody titer of the double serum as the gold standard, the receiver operating characteristic curve (ROC) was drawn, and the laboratory methods for detecting MP infection were compared and evaluated.Results:(1)A total of 93 children with MP infection were clinically diagnosed, including 42 males (45.2%) and 51 females (54.8%), with an average age of 5.5 years.Sixty cases (64.5%) of MP infection were diagnosed.There were 349 healthy children, 198 males and 151 females, with an average age of 4.3 years.The positive rate of throat swab culture was 0.6% (2 cases), and the positive rate of fluorescent quantitative PCR(qPCR) was 18.9% (66 cases). (2) The culture specificity was the highest (100.0%) and the sensitivity was the lowest (65.0%). PA and enzyme linked immunosorbent assay (ELISA) were used to detect a single serum in the acute phase, the sensitivity was 71.7% and 86.5% respectively.ROC curve suggested that the current clinical diagnostic threshold MP specific antibody IgM ≥ 1∶160 was not the best diagnostic threshold.Molecular biological diagnostic methods were the most sensitive, RNA simultaneous and testing (SAT) was 85.0% and qPCR was 93.0%; while the specificity was low, 75.7% (SAT) and 63.6% (qPCR), respectively.(3) At the same time, MP nucleic acid (SAT, PCR) of throat swabs and a single serum (ELISA, PA) of children in acute phase were detected, the sensitivity was increased to 95.0%-100.0%, and the specificity was 63.6%-75.7%.Conclusions:Molecular biology is highly sensitive in diagnosing MP infection.It has asymptomatic infection or is carried after infection.Whether it needs treatment needs to be combined with clinical practice, when MP detection is positive.The detection of a single serum in the acute phase with a course of about 1 week has high sensitivity and is of reference value for the diagnosis of MP infection, but the diagnosis needs to be combined with clinical practice.The sensitivity and accuracy of detecting MP infection by single serological test combined with SAT in acute phase are higher than that by single application.
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Objective:To evaluate short-term clinical efficacy and safety of a cooling gel containing calcium-based antimicrobial peptide compounds (CAPCS cooling gel) combined with desonide cream in the treatment of atopic dermatitis (AD) in children.Methods:From November 2019 to September 2020, a randomized, double-blind controlled clinical trial was conducted in 60 children with AD enrolled from Department of Dermatology and Venereology, West China Hospital, Sichuan University. The 60 patients were randomly and equally divided into 2 groups: test group treated with topical desonide cream in the morning and evening as well as topical CAPCS cooling gel at noon during the first 3 days of treatment, followed by topical CAPCS cooling gel in the morning, at midday and in the evening for 11 days; control group treated with topical desonide cream in the morning and evening as well as topical CAPCS-free placebo gel at noon during the first 3 days of treatment, followed by topical CAPCS-free placebo gel in the morning, at midday and in the evening for 11 days. The treatment lasted 2 weeks. Finally, 56 AD patients completed the follow-up, and 28 in each group were included into the following analysis. Clinical indices, such as eczema area and severity index (EASI) , visual analogue scale (VAS) , investigator′s global assessment (IGA) and dermatology life quality index (DLQI) , were recorded before, 7 ± 3 days and 14 ± 3 days after the treatment, so were adverse reactions.Results:After 1-week treatment, 1 patient in the test group and 1 in the control group showed response to the treatment, with the response rate being 3.57% in both groups; after 2-week treatment, 12 patients in the test group and 2 in the control group showed response to the treatment, with response rates being 42.86% and 7.14% respectively; there were significant differences in the treatment outcomes between the two groups after 1- and 2-week treatment ( Z = -4.318, -5.474, respectively, both P < 0.05) . There was no significant difference in the EASI, VAS, IGA or DLQI score between the two groups before treatment (all P > 0.05) ; nonparametric Friedman test showed a significant difference in the changing trend of the EASI score over time between the two groups ( χ2 = 45.720, P < 0.05) . Two-way repeated measurement analysis of variance showed a significant difference in the VAS score ( F = 10.738, P = 0.002) , but no significant difference in IGA or DLQI score between the test group and control group after 1-week treatment ( F = 0.066, 0.804, P = 0.135, 0.374, respectively) ; after 2-week treatment, there were significant differences in the VAS, IGA and DLQI score between the 2 groups ( F = 67.313, 38.949, 51.503, respectively, all P < 0.001) . During the clinical study period, 1 adverse event occurred in the test group and control group each, which manifested as tingling or irritating sensation at the topically treated sites, and there was no significant difference in the incidence rate of adverse events between the two groups ( P > 0.05) . Conclusion:Short-term topical application of CAPCS cooling gel combined with desonide cream is effective for the treatment of AD in children, and does not increase the incidence of adverse reactions compared with the placebo.
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Objective:To investigate the effect of ionizing radiation on the ferroptosis of skin cells and the potential therapeutic strategy of ferroptosis inhibitor Ferrostatin-1 (Fer-1) on irradiated skin cells.Methods:HaCaT cells were pre-treated with Fer-1 before X-ray irradiation. After irradiation, CCK-8 assay and LDH release assay were used to detect cell viability and cell death, flow cytometry was used to detect the lipid peroxidation levels, crystal violet staining assay was used to detect colony forming ability, and the expressions of ferroptosis related proteins ACSL4 and GPX4 were detected by Western blot.Results:The cell viability of HaCaT cells was significantly decreased ( t=5.63, 8.74, P<0.05) and the release of LDH was significantly increased ( t=3.98, 5.08, 9.27, P<0.05) after different doses of X-ray irradiation. The cell viability was improved ( t=5.79, P<0.05) and the release of LDH was reduced ( t=12.36, 11.96, 18.13, 9.96, P<0.05) after the pre-treatment with Fer-1. The lipid peroxidation levels of HaCaT cells were significantly increased ( t=9.59, P<0.05) and the clonogenic survival ability were reduced ( t=4.26, P<0.05) after 10 Gy X-ray irradiation, while Fer-1 pre-treatment reduced ( t=6.48, 17.04, P<0.05) the increase of lipid peroxidation level induced by X-ray irradiation and also effectively restore ( t=3.96, P<0.05) the clonogenic survival ability. The expressions of ACSL4 and GPX4 were decreased after 10 Gy X-ray irradiation, while they recovered to normal level ( t=5.23, 7.16, 4.78, 8.29, 6.43, P<0.05) after the pre-treatment with Fer-1. Conclusions:Ferroptosis inhibitor Fer-1 alleviates the progress of radiation-induced skin injury by inhibiting ferroptosis after ionizing radiation at the cellular level, which provides a potential strategy for the protection of radiation injury.
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Objective:To evaluate the clinicopathological characteristics and prognosis of IgA nephropathy (IgAN) patients with microangiopathy lesions and with no hypertension.Methods:Adult IgAN patients without hypertension were selected from Peking University First Hospital. All kidney biopsies were independently reviewed by 2 investigators. Patients were divided into three groups (microangiopathy group, simple arterio/arteriolosclerosis group and normal vascular group) by renal arteriolar lesions. Composite kidney end point event defined as a ≥30% reduction in estimated glomerular filtration rate (eGFR) and end-stage kidney disease. Cox regression analysis was used to test the association between microangiopathy lesions and the outcomes.Results:A total of 420 patients were included in this study, of which 37(8.8%) patients had renal arteriolar microangiopathy lesions, 134 (31.9%) patients had simple arterio/ arteriolosclerosis, and the others had no vascular lesion. Compared with simple arterio/arteriolosclerosis group or non-vascular lesion group, patients with renal arteriolar microangiopathy lesions had more severe urine protein ( P=0.002), worse renal function ( P<0.001), higher proportion of segmental glomerulosclerosis and/or balloon adhesion (S1), tubular atrophy/interstitial fibrosis (T1/2), cellular/fibrocellular crescents (C1/2) (all P<0.05). During the follow-up, 20(54.1%) patients with microangiopathy lesions, 45(33.6%) patients with simple arterio/arteriolosclerosis and 82(32.9%) patients without vascular lesion reached the composite kidney end points ( χ2=6.491, P=0.039). In a multivariable Cox regression model, the presence of microangiopathy lesions was an independent risk factor for kidney disease progression in IgAN patients ( HR=1.872, 95% CI 1.044-3.357, P=0.035), and simple arterio/arteriolosclerosis was not a risk factor for kidney disease progression. Conclusion:It is not uncommon for non-hypertensive patients with IgAN having microangiopathy lesions, which suggests that hypertension is not the sole risk factor for microangiopathy lesions.
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Objective To understand the impact of the clinic-pharmacy separation reform on a tertiary hospital in Beijing.Methods In a comparative analysis,data in the HIS of the hospital were analyzed in descriptive statistics,covering such data as the number of visits,expense per visit,medical income and income structure change in the period between June and December in 2016 and 2017,and were analyzed by the methods of t test and descriptive statistics as well.Results Compared with the same period between June and December in 2016,the number of visits at its outpatient department reduced by 12.06％,expense per visit increased by 31.42 yuan (P ＜ 0.05),while the expense per visit of patients with medical insurance increased by 28.51 yuan (P ＜ 0.05) between June and December in 2017.The number of hospitalizations at the inpatient department increased by 2.94％,expense per hospitalization increased by 877.71 yuan,and that of patients with medical insurance decreased by 42.87 yuan (P ＞ 0.05)between the abovementioned periods.The case mixed index of inpatients rose by 0.01,and patient satisfaction rose by 4.22 percentage points.Conclusions This reform has reduced outpatient visits at hospitals,increased the coefficient of difficulty of hospital inpatients,and improved patients' experiences for medical services.Hospitals are recommended to further their internal management in a fine manner,and curb unreasonable growth of medical expenses.
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0bjective To study the impact of aging on pancreatic atrophy,fibrosis and exocrine hy-pofunction in patients with post.ERCP pancreatitis(PEP)and its severity.Methods A retrospective study was conducted on 786 patients who underwent ERCP at the Affiliated Zhongshan Hospital of Dalian Universi-ty from June 201 1 to April 2018.Patients who were aged over 75 years were grouped into the elderly group while those aged less than 75 years were grouped into the younger group.The incidences and severity of post-ERCP pancreatitis in the two groups were analyzed.Results In the elderly group,there were 308 patients.The average age was(8 1.8±4.8)years.In the younger group,there were 478 patients.The average age was(57.7±12.0)years.The average operation time for the elderly group was(52.5±14.1)minutes,and that for the younger group was(50.7±14.9)minutes.There were no significant differences in opera-tion time and in the related factors between the two groups(P＞0.05).There was no significant difference in the rates of hyperamylasemia between the two groups(29.9％vs 30.1％,P＞0.05).The overall rate of PEP was 11.3％(89/786).In the elderly group,the rate of PEP was6.5％(20/308),which was signifi-cantly lower than that in the younger group(x2=11.765,P＜0.05).The rates of mild,moderate and severe PEP in the elderly group was significantly lower than those in the younger group(all P＜0.05).Hyperamylasemia and pancreatitis in the 2 groups were alleviated after conservative treatment.Conclusions Aging(≥75 years)resulted in pancreatic atrophy,fibrosis,exocrine hypofunction which had a protective effect on PEP.
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Objective@#To study the impact of aging on pancreatic atrophy, fibrosis and exocrine hypofunction in patients with post-ERCP pancreatitis (PEP) and its severity.@*Methods@#A retrospective study was conducted on 786 patients who underwent ERCP at the Affiliated Zhongshan Hospital of Dalian University from June 2011 to April 2018. Patients who were aged over 75 years were grouped into the elderly group while those aged less than 75 years were grouped into the younger group. The incidences and severity of post-ERCP pancreatitis in the two groups were analyzed.@*Results@#In the elderly group, there were 308 patients. The average age was (81.8±4.8) years. In the younger group, there were 478 patients. The average age was (57.7±12.0) years. The average operation time for the elderly group was (52.5±14.1) minutes, and that for the younger group was (50.7±14.9) minutes. There were no significant differences in operation time and in the related factors between the two groups (P>0.05). There was no significant difference in the rates of hyperamylasemia between the two groups (29.9% vs 30.1%, P>0.05). The overall rate of PEP was 11.3% (89/786). In the elderly group, the rate of PEP was 6.5% (20/308), which was significantly lower than that in the younger group (χ2=11.765, P<0.05). The rates of mild, moderate and severe PEP in the elderly group was significantly lower than those in the younger group (all P<0.05). Hyperamylasemia and pancreatitis in the 2 groups were alleviated after conservative treatment.@*Conclusions@#Aging (≥75 years) resulted in pancreatic atrophy, fibrosis, exocrine hypofunction which had a protective effect on PEP.