Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

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 To compare the effectiveness of loop-mediated isothermal amplification (LAMP) assay and microscopic examinations for detection of Schistosoma japonicum infections in Oncomelania hupensis in transmission-interrupted regions, so as to provide insights into the optimization of snail surveillance tools in these regions. Methods Four hilly schistosomiasis-endemic villages where transmission interruption was achieved were selected in Heqing County of Yunnan Province as the study villages, including Xinzhuang and Gule villages in hilly regions and Lianyi and Yitou villages in dam regions. Snail survey was performed by means of systematic sampling combined with environmental sampling in July 2018. All captured snails were identified for S. japonicum infections using microscopy. In addition, 10 to 20 snails were randomly sampled from each snail habitat following microscopy, numbered according to environments and subjected to LAMP assay. The positive rate of settings with S. japonicum-infected snails was compared among villages. Results A total of 7 949 living snails were captured from 83 snail habitats in 4 villages, and no S. japonicum infection was detected in snails. There were 226 mixed samples containing 1 786 snails subjected to LAMP assay, and positive LAMP assay was found in 3 mixed samples from 3 snail habitats in 2 dam villages. The positive rates of settings with S. japonicum-infected snails were comparable between Lianyi Village (one setting) and Yitou Village (2 set tings) (5.89% vs. 14.29%, P = 0.344). However, the overall positive rate of settings with S. japonicum-infected snails was significantly higher in dam villages (9.67%, 3/31) than in hilly villages (0) (P = 0.048). Conclusions LAMP assay is more sensitive to detect S. japonicum infections in O. hupensis than conventional microcopy method, which may serve as a supplementary method for detection of S. japonicum infections in O. hupensis in high-risk snail habitats in hilly transmission-interrupted regions.

Introduction: To collate the pharmacological literature of safflower and lay a foundation for its later development. Methods: Collect and sort out the literature of modern periodicals, and the study the pharmacology of Safflower in academic websites. Conclusion The pharmacological study and clinical medication of Mongolian medicine Safflower were studied in this paper. Safflower is one of the clinical medicines of Mongolian medicine, which is often used to treat liver diseases and is known as "the best of the liver". It has the functions of blocking blood vessels, irregular menstruation, clearing liver heat, nourishing, relieving pain and detumescence. Through collecting and sorting out the pharmacological studies of Safflower in modern periodicals and academic websites, we conclude that safflower can protect liver, expand blood vessels, anticoagulation, ischemic injury, lowering blood lipids, stimulating uterus, analgesic and sedative effects on nervous system, nourishing, anti-inflammatory, anti-oxidation, anti-cancer and anti-aging.

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

OBJECTIVETo determine whether patterns of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) were classified based on symptoms and signs, and explore whether individual characteristics were correlated with membership in particular pattern.

METHODSSymptom-based latent class analysis (LCA) was used to determine whether patterns of EV71-HFMD existed in a sample of 433 cases from a clinical data warehouse system. Logistic regression was then performed to explore whether demographic, and laboratory data were associated with pattern membership.

RESULTSLCA demonstrated a two-subgroup solution with an optimal fit, deduced according to the Bayesian Information Criterion minima. Hot pattern (59.1% of all patients) was characterized by a very high fever and high endorsement rates for classical HFMD symptoms (i.e., rash on the extremities, blisters, and oral mucosa lesions). Non-hot pattern (40.9% of all patients) was characterized by classical HFMD symptoms. The multiple logistic regression results suggest that white blood cell counts and aspartate transaminase were positively correlated with the hot pattern (adjust odds ratio=1.07, 95% confidence interval: 1.006-1.115; adjust odds ratio=1.051, 95% confidence interval: 1.019-1.084; respectively).

CONCLUSIONSLCA on reported symptoms and signs in a retrospective study allowed different subgroups with meaningful clinical correlates to be defined. These findings provide evidence for targeted prevention and treatment interventions.

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RTG was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RT(G) were investigated. The risk factors for high RT(G) were analyzed using non-conditional logistic regression analysis. Our results found that RT(G) of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RT(G). Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RT(G) (P < 0.05). Further stratified analysis revealed that RT(G) in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RT(G) is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors.

Objective To evaluate the efficacy of Lianhua Dingchuan Tablets in bronchial asthma.Methods Fifty BALB/C mice were randomly and equally divided into control (Con) group,ovalbumin (OVA) group,dexamethasone (DEX) group,high-dose Lianhua group,low-dose Lianhua group.The mice were sensitized and challenged with OVA plus aluminium hydroxide to establish asthmatic model and were pre-treated 30 minutes before challenge.Specific airway resistance (sRaw) was used to evaluate airway hyperresponsiveness,and airway inflammatory changes were measured.ELISA and Magnetic Luminex(R) were used to quantified the levels of IL-4,IL-13 and INF-γ.Results Airway resistance significantly decreased in DEX group and High-dose Lianhua group (P＜0.05).Levels of inflammatory cells and IL-13 in BALF evidently reduced in DEX group,high-dose Lianhua group and low-dose Lianhua group (P ＜ 0.05),while IL-13 level in serum only decreased in DEX group.There was no significant changes in the levels of IL 4 and INF γ among those groups.Conclusions Lianhua Dingchuan Tablets might relieve the symptoms of asthma by reducing IL-13 level and inhibiting the airway inflammation.

Objective:To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms.Methods:Ihe mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages.The PGE2,prostaglandin E receptor (EP) 4 agonist,EP4 RNAi,and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage.The levels of HMGB 1 was determined by Western blot.Results:Compared with LPS alone treatment,the expression of HMGB 1 in peritoneal macrophages was increased obviously after 24 h by treatment with PGE2 and LPS,and it was also increased after the combined treatment of EP4 receptor agonist with LPS for 24 h (both P<0.05);compared with the PGE2+LPS treatment,the level of HMGB1 was decreased after knockdown of EP4 receptor expression (P<0.05);compared with EP4 receptor agonist +LPS treatment,there was no difference in HMGB1 levels in mice after the treatment with DN.CREB plasmid to suppress CREB function (P>0.05);compared with LPS alone treatment,the combined treatment of EP4 receptor agonist with LPS for 24 h could up-regulate the phosphorylation of epidermal growth factor receptor (EGFR) and protein kinase B (Akt) thr308 (P<0.05),which were blocked by EGFR inhibitor.Once Akt specific inhibitor was used before EP4 and LPS treatment,the expression of HMGB1 was declined (P<0.05).Conclusion:PGE2 can up-regulate the expression of HMGB1 in sepsis of peritoneal macrophages through EP4 receptor,which may be related to the activation of EGFR/PI3K/Akt signaling pathway.