Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate. METHODS: The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated. RESULTS: There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively. CONCLUSION The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.
Humans ; Colistin/adverse effects* ; Anti-Bacterial Agents/therapeutic use* ; Meropenem/adverse effects* ; Treatment Outcome ; Gram-Negative Bacteria ; Hematologic Diseases

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ² test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and β-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.
Endoscopes ; Esophageal and Gastric Varices/complications* ; Gastrointestinal Hemorrhage/surgery* ; Humans ; Hypertension, Portal/complications* ; Ligation ; Liver Cirrhosis/complications* ; Prothrombin ; Sclerotherapy ; Tissue Adhesives ; Varicose Veins ; Venous Thrombosis/complications*

Abstract: Objective　To analyze the distribution and drug resistance evolution characteristics of pathogenic bacteria of bloodstream infection in nine tertiary hospitals in Yunnan Province from 2017 to 2021, so as to provide reliable basis for rational selection of antibiotics in clinic. Methods Using the drug sensitive paper method or instrument method, the bacteria identification and drug sensitivity test were carried out in nine tertiary hospitals in different regions according to the unified technical scheme. The results were judged according to the Clinical and Laboratory Standards Institute (CLSI) breakpoint standard in 2021, and use WHONET5.6 for data statistical analysis. Results A total of 12 003 strains of pathogenic bacteria were isolated from bloodstream infection samples in the past five years, including 7 442 strains of Gram-negative bacteria (62.0%) and 4562 strains of Gram-positive bacteria (38.0%), with an increasing trend in the number of isolated strains; of these, 163 strains (1.4%) were isolated from outpatients and 11 840 strains (98.6%) were isolated from inpatients. The top three gram-negative bacteria were Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, of which 309 strains (4.2%) were carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 29 strains (0.4%) carbapenem-resistant Escherichia coli and 19 strains (0.3%) carbapenem-resistant Enterobacter cloacae, and the number of CR-KPN was on the rise year by year. The top three Gram-positive bacteria were coagulase-negative staphylococci, Staphylococcus aureus and Enterococcus faecium, of which methicillin-resistant Staphylococcus aureus (MRSA) was detected for 213 strains, accounting for 27.7%, and decreased from 40.0% in 2017 to 23.4% in 2021, showing a downward trend year by year. No vancomycin-resistant staphylococci and enterococci were found. Conclusions The detection and composition of bloodstream infection pathogenic bacteria in multicenter have not changed much in the past five years, but each hospital has its own characteristics. The number of carbapenem resistant Enterobacteriaceae increased year by year, which should be paid more attention.

ObjectiveTo explore the predictive value of CT based radiomics model in differentiating Borrmann type Ⅳ gastric cancer （GC） from primary gastric lymphoma （PGL）. MethodsA total of 186 cases （Borrmann type Ⅳ GC： 132； PGL： 86） pathologically diagnosed by surgical resection and/or endoscopic biopsy were enrolled from June 2008 to April 2018 retrospectively. Radiomics features were extracted from CT arterial phase and venous phase images by computed algorithm， and selected by least absolute shrinkage and selection operator （Lasso） logistic regression， and then the CT-based radiomics models were established. CT subjective signs were reviewed to build CT subjective signs model， while CT subjective signs and radiomics signature were assembled to build combined model. The receiver operating characteristic （ROC） curve was used to evaluate the performance of CT subjective sign model， radiomics model and the combined model. ResultsTwo signs（the bright line sign of serosa and the irregular nodular protrusion on the serosa side）were selected into the CT subjective sign model. Among the radiomics features， 9 venous phase features， 8 arterial phase features and 14 arteriovenous combination features related to tumor classification were selected， and the corresponding radiomics models were constructed respectively. When the cut-off value of CT subjective sign model was 0.188， the area under curve （AUC） was 0.846， the sensitivity was 61.9%， the specificity was 81.7%， and the accuracy was 76.5%. The cut-off values of arterial phase， venous phase and arteriovenous phase radiomics model were -0.315， -0.669 and -0.858， respectively， and the AUCs were 0.864， 0.955 and 0.890， the sensitivity were 71.4%， 95.2% and 81.0%， the specificity were 85.0%， 88.3% and 80.0%， the accuracy were 81.5%， 90.1% and 80.3%， respectively. The cut-off values of arterial phase， venous phase and arteriovenous phase in the combined model were 0.257， 0.556 and 0.497， respectively， and the AUCs were 0.883， 0.956 and 0.918， the sensitivity was 71.4%， 90.5% and 71.4%， the specificity was 85.0%， 93.3% and 90.0% and the accuracy were 81.5%， 92.6% and 85.2%， respectively. The diagnostic performance of the models from high to low were the combined model， radiomics model and CT subjective finding model （ P< 0.001）， and CT venous phase images were more effective in the differential diagnosis of the two tumors. ConclusionsThe radiomics model based on the arterial and venous phases CT images could differentiate Borrmann type Ⅳ gastric carcinoma from primary gastric lymphoma effectively.

In this study, the data of pediatric diarrhea clinic of Gansu Provincial Maternal and Child Health Hospital from January 1, 2014 to December 31, 2018 and Tianshui First Hospital from January 1, 2015 to December 31, 2018 were collected. Standardized precipitation index (SPI) and meteorological drought composite index (MCI) were used as drought indicators. Quasi-Poisson generalized additive model was used to analyze the correlation between drought and pediatric diarrhea outpatient visits. During the study period, the dry days in Lanzhou city and Tianshui city were 298 and 379 days according to SPI-1, 303 and 398 days according to MCI, respectively. There were 57 147 and 18 703 cases of diarrhea in children aged 0-6 years in Gansu Provincial Maternal and Child Health Hospital and Tianshui First Hospital, respectively. MCI and SPI (SPI-1) based on monthly precipitation were negatively correlated with the number of pediatric diarrhea outpatients. Compared with the non-drought period, SPI-1 showed the strongest correlation between middle drought and pediatric diarrhea outpatients, with an increase of 13.4% (95%CI: 7.9%-19.3%) and 20.0% (95%CI: 12.7%-27.8%) in Lanzhou city and Tianshui city, respectively. According to MCI, the outpatients with diarrhea in Tianshui children increased by 60.5% (95%CI: 3.4%-149.0%) due to extreme drought.
Child ; Humans ; Outpatients ; Diarrhea/epidemiology* ; Cities ; China/epidemiology*

As a common soft tissue disease, the mechanism of tendinopathy has not been clarified and is lack of effective treatment method. Change of tissue fibrosis is the one of the main pathological features. Transforming growth factor beta 1 (TGF-β1), which is one of the important factor, participated in fibrosis. Inconsonant expressions of TGF-β1 could be found in tendinopathy. The studies are still controversial, but the vast majority of studies had showed that TGF-β1 was abnormal, and it is given priority to increase, which means that TGF-β1 plays an important role in the process of tendinopathy. In the process of tendon injuries and repairs, the time of TGF-β1 increasing is inconsistent. The time for TGF-β1 plays a significant role has not been determined. TGF-β1 has abnormal expressions in both tendinopathy and tendon repairs, which are two opposite processes. Thus, it may not be a one-way adjustment factor, but has a pleiotropic. Recent studies showed that TGF-β1 was considered as binding to receptor and transferring signal into the cell. Now there are three different receptors are found. The classical pathway of TGF-β1 in intracellular signal transduction is mainly through activation of Smad pathway. In the same time, there are also some non-classical pathways. TGF-β1 could break balance of extracellular matrix, which may be a reason to cause tendinopathy. But the regulations of TGF-β1 on the extracellular matrix are complex and diverse, further studies are required. Existing researches showed that the performance of treatments on tendinopathy is unsatisfied by blocking TGF-β1 downstream pathway. Therefore, it is a good way to study the upstream mechanism of produce TGF-β1. It may be an effective method to find new targets to inhibit the development of tendinopathy better by finding the original source of TGF-β1.
Fibrosis ; Humans ; Signal Transduction ; Tendinopathy ; Transforming Growth Factor beta1

OBJECTIVE: To investigate the correlation of E-cadherin expression level with the clinical characterastics in children with acute leukemia (AL), and to explore the possible regulatory mechanism. METHODS: Real-time quantitative RT-PCR was applied to detect the expression level of E-cadherin in bone marrow samples from 135 child patients diagnosed as AL, and its relevance with clinical indicators was statistically analyzed. The expression levels of E-cadherin, β-catenin, and Akt/p-Akt were detected by using Western blot. The bone marrow samples from 22 children with non-malignant hematological diseases were used as controls. RESULTS: The expression level of E-cadherin significantly decreased in newly diagnosed patients with all 3 types of AL as compared with bone marrow samples from control group (P<0.01). In B-ALL group, compared with standard risk group, E-cadherin expression level significantly decreased in intermediate risk group (P<0.05). Moreover,the expression level of E-cadherin mRNA was also reduced in splenomegaly group (P<0.01). However, the correlation of E-cadherin level with clinical characteristics was not found in T-ALL and AML (P>0.05). The expression level of E-cadherin in the patients from Common-B-ALL group was higher than B-ALL patients with other immunophenotypes (P<0.01), while no significant difference was found among patients grouped by FAB classification. By the correlation analysis of measured data, lower E-cadherin expression level was found to be related with high WBC count and serum lactic dehydrogenase level (LDH) (r=-0.419, r=-0.269), but with low blood platelet count in B-ALL (r=0.335). In T-ALL, expression of E-cadherin was found to be negatively correlated with LDH and percentage of immature cells in the bone marrow (r=-0.567, r=-0.557). In addition, the lower expression of E-cadherin was also found to be related with WBC count and percentage of immature cells in the bone marrow in newly diagnosed AML patients (r=-0.368, r=-0.391). Compared with control group, the expression of E-cadherin was down-regulated significantly (P<0.01), while β-catenin, Akt significantly was up-regulated in 3 types of AL patients (P<0.01). The expression of p-Akt and p-Akt/Akt was up-regulated significantly in T-ALL (P<0.01). CONCLUSION Lower expression of E-cadherin is related factor of unfavourable prognosis in children with acute leukemia. The expression deficiency or down-regulation of E-cadherin may activate Wnt/β-catenin and PI3K/ Akt signaling pathways to promote the genesis and progress of haematological malignancies, thus resulting in a series of malignant biological behaviors in cells. E-cadherin may be a new prognostic indicator for pediatric acute leukemia, thus to guide individualized hemotherapy.
Acute Disease ; Bone Marrow ; Cadherins ; Child ; Humans ; Leukemia, Myeloid, Acute ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho-logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel-lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha-ride peptide (GLPP) has therapeutic effect on NAFLD. METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic path-ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato-cytes induced by oleic acid and palmitic acid. CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.