Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.

Abstract To analyzes the characteristics, problems and enlightenment of physical activity observation tools, so as to provide reference for researchers to quickly and accurately choose appropriate observation tools to evaluate children s and adolescents physical activity. Literature search is conducted in eight databases of Chinese and English, including CNKI, Wanfang, VIP, Web of Science, PubMed, Medline, ERIC, and SPORTDiscus. Ultimately, eight observation tools for assessing physical activity in children and adolescents are included. Through summarization and comparison, it is found that the applications of those tools cover multiple age groups, the observation indicators cover multiple dimensions for each with varying emphases, and the applicable contexts vary in their specific background information, and recording methods tend to be quantitative. However, several issues remain to be addressed in practical applications. First, the observation indicators need to be supplemented and improved; second, physical activity in community environments and academic classrooms requires further attention; third, physical activity intensity needs to be scientifically evaluated; fourth, observation and recording methods need to be integrated and innovated; fifth, the number of observation subjects needs to be expanded. Future research could focus on developing observation tools tailored to the characteristics of Chinese children and adolescents, while drawing on foreign observation tools to comprehensively assess physical activity among children and adolescents.

Objective To explore the effects of fecal microbiota transplantation on blood uric acid(UA)metabolism,adverse reactions,and gout control in patients with refractory gout.Methods A total of 102 patients with refractory gout in the First Affiliated Hospital of Medical College of Shantou University from June 2020 to June 2023 were randomly divided into two groups,with 51 cases in each group.Control group received benzbromarone and febuxostat treatment,while the observation group re-ceived fecal microbiota transplantation.The gout control status and occurrence of adverse reactions were observed in both groups;intestinal flora,UA,levels of C-reactive protein(CRP),interleukin-18(IL-18),interleukin-6(IL-6),and scores of joint pain,swelling and limited mobility were compared between the two groups before and after treatment.Results Five patients in each group were lost to follow-up.The total gout control rate in the observation group was 89.13％,which was significantly higher than 69.57％ in the control group(P＜0.05).At 4 and 12 weeks after treatment,the levels of Escherichia coli,UA,CRP,IL-18 and IL-6 as well as the scores of joint swelling,pain and limited mobility in the observation group were significantly lower than those in the control group,while the lev-els of Bifidobacterium,Lactobacillus and Bifidobacterium to Escherichia coli(B/E)ratio were signifi-cantly higher than those in the control group(P＜0.01).The total incidence of adverse reactions was 10.87％ in the observation group and 6.52％ in the control group,with no significant between-group difference(P＞0.05).Conclusion Fecal microbiota transplantation has a definite therapeutic effect for patients with refractory gout,which can significantly reduce UA level and control clinical symptoms,and its mechanism may be related to the correction of intestinal flora imbalance.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.

Background: The impact of para-aortic lymphadenectomy (PALD) on prognosis and quality of life (QoL) for IB2-IIA2 cervical cancer patients remain controversial. And whether intraoperative frozen pathology exam on common iliac lymph nodes could help predict para-aortic lymph node (PALN) metastasis was unanswered with high-level evidence. Methods A multi-center, randomized controlled study is intended to investigate the effect of PALD on the prognosis and QoL in cervical cancer patients and to assess the value of intraoperative frozen pathological evaluation of common iliac nodes metastasis for the prediction of PALN metastasis. After choosing whether to receive intraoperative frozen pathological examination of bilateral common iliac lymph nodes, eligible patients will be randomly assigned (1:1) to receive PALD or not. The primary end point is 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events (AEs) caused by PALD, AEs caused by radiotherapy and QoL. A total of 728 patients will be enrolled from 8 hospitals in China within 3-year period and followed up for 5 years.

In order to explore the treatment of Her-2 positive breast cancer patients who failed in multi-line treatments, we retrospectively analyzed the clinical data of a patient with refractory Her-2 positive breast cancer.The patient was initially diagnosed as Her-2 positive advanced breast cancer.After six line treatment in the outer hospital, the patient′s condition was basically in a progressive state.The breast tumor was broken and purulent, the lung metastasis increased, and the patient′s quality of life was poor.The patient was admitted to Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical University, after MDT discussion, we gave pyrrolotinib combined with capecitabine treatment, the chest wound healed gradually, the lung metastasis gradually reduced, and the quality of life was better.A retrospective analysis of this case showed that pyrrolidine combined with capecitabine may bring hope to Her-2 positive breast cancer patients who failed to receive multi-line therapies, especially those who failed to target therapy.

Congenital bile duct cysts, which is a kind of malformation of bile duct, will lead to the inflammation in the bile duct system for a long time. Therefore, patients with cholelithiasis and cyst canceration have a risk. Surgical operation is the only treatment option for the congenital bile duct cysts patients. Resection of the cysts and complete " biliary-pancreatic duct shunt" are the key points of the standardized treatment of congenital bile duct cysts. The non-standard surgical treatment will bring the postoperative complications such as the stricture of choledochojejunostomy, the remnant cysts and even the canceration of cysts, which will seriously affect the quality of life and threaten the health of patients. Based on the retrospective study of congenital bile duct cysts patients in Eastern Hepatobiliary Hospital, the author proposed a new classification system according to the pathological and anatomical characteristics of congenital bile duct cysts. The congenital bile duct cysts can be divided into three regions and five types, i. e. localized type and diffuse type of extrahepatic bile duct cysts of hilar, trunk and terminal type; central type; and intrahepatic bile duct cysts of limited and diffuse type. It is our hope that this typing system will accurately guide the design and implementation of surgical treatment plans for congenital bile duct cysts and reduce the risk of long-term postoperative complications for patients.

This article reported 2 cases primary renal Ewing sarcoma (PRES)/primitive neuroectodermal tumor (PNET). By reviewing literature, renal PRES/PNET has a high degree of malignancy, and early symptoms are not typical. It needs to be combined with clinical manifestations, imaging examinations and pathological examination results. At present, surgical treatment is the main treatment, combined with radiotherapy and chemotherapy or targeted treatment might help.

Objective:To assess the bacterial profiles and antimicrobial susceptibility patterns in uropathogens, and help to inform the empiric treatment decisions for urinary tract infection in outpatient settings.Methods:A single institutional retrospective analysis was performed on positive urine cultures from outpatient settings between January 1998 and December 2018. To analyze changes over time, trends analysis were undertaken on bacterial profiles, antimicrobial susceptibility and resistance.Results:A total of 1.172 pathogenic bacteria were isolated after exclusion of duplicate strains originated from the same patient, including 991(84.6%) Gram-negative bacterial strains and 181(15.4%) Gram-positive strains. The most common Gram-negative uropathogens were Escherichia coli (60.8%) and Klebsiella pneumonia (8.1%). Enterococcus faecalis (4.6%) was the predominant Gram-positive strain. The detection rate of Escherichia coli increased significantly, from 50.8% to 63.2% ( χ2=7.978, P=0.046), and no significant difference was observed in the distribution of major uropathogenic bacteria over the 20 years (all P>0.05). The proportion of extended-spectrum β-lactamase (ESBLs) producing strains increased significantly across the 20 years ( P<0.05). The resistance rates of Escherichia coli to amoxicillin and clavulanate potassium, aztreonam, ceftazidime, ciprofloxacin and sulbactam + cefoperazone increased significantly (all P<0.05). All the isolates sustained high susceptibility to tazobactam + piperacillin, amikacin, imipenem and nitrofurantoin (95.0%, 95.7%, 97.9% and 91.1%). Similar to those of Escherichia coli, Klebsiella pneumoniae remained a high and stable sensitivity to tazobactam+piperacillin, amikacin and imipenem during the 20 years (79.1%, 88.0% and 80.3%). However, the proportion of ESBLs producing strains increased significantly ( P<0.05). Among Gram-positive bacteria isolates, the sensitivity rates of Enterococcus faecalis to ampicillin, nitrofurantoin and penicillin G were 100.0%. No vancomycin resistant strain was detected in Gram-positive bacteria. Conclusions:From 1998 to 2018, Escherichia coli and Klebsiella pneumoniae are the most common Gram-negative bacteria uropathogens obtained in outpatient settings. Significant increases of resistance to some antimicrobial agents such as second- and third-generation cephalosporins and fluoroquinolones are observed during the 20 years and high susceptibilities to tazobactam+piperacillin, amikacin, imipenem and nitrofurantoin sustain over time. Local treatment strategies of urinary tract infections on outpatient basis should be made according to epidemiology of drug resistance and individual characteristics to control the spread and curb the prevalence of drug resistant.