Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

INTRODUCTIONThe proteins found in tears play an important role in maintaining the ocular surface and changes in tear protein components may reflect changes in the health of the ocular surface. Proteomics provides a comprehensive approach for cataloguing all the proteins of the tear proteome, which will help to elucidate disease pathogenesis, make clinical diagnoses and evaluate the influence of medications on the structure, composition and secretion of tear proteins. In this study, an alternative proteomic strategy was investigated to explore the human tear proteome.

MATERIALS AND METHODSTear samples were obtained from patients who had pterygium and were collected on the first day and third day after pterygium surgery. Tears pooled from 6 patients were used in the analysis. Reverse-phase high-pressure liquid chromatograph (RPHPLC) was used as the first step to separate intact proteins into 21 peaks. Each fraction was then tryptic-digested and analysed by nanoLC-nano-ESI-MS/MS to characterise the protein components in each fraction.

RESULTSIn total, 60 tear proteins were identified with high confidence, including well-known abundant tear proteins, and tear-specific proteins such as lacritin and proline-rich proteins. Among them, proline-rich protein 5 was found for the first time in tear fluid. A large number of plasma proteins were also observed in tear fluid.

CONCLUSIONSThe results showed that the proteomic strategy used in this study was successfully applied to analyse tear proteome.

Eye Proteins ; analysis ; Humans ; Mass Spectrometry ; methods ; Proteome ; Tears ; chemistry

The effect of the menstrual cycle on the diurnal cortisol rhythm was investigated in 15 normally cyclic healthy women during reproductive life. Salivary cortisol was measured by radioimmunoassay in samples collected every 2 h for 24 h during the four phases of the menstrual cycle: menstrual phase, late follicular/peri-ovulation phase, early to mid luteal phase and late luteal phase, respectively. Distinct diurnal rhythms of free cortisol were found throughout the menstrual cycle by using a nonlinear periodic regression model. The model was characterized by an asymmetrically peaked diurnal cycle and ultradian harmonics. There was a trend to higher troughs and significantly shorter peak-width in phase II and phase IV compared to phase I. The ultradian amplitude in phase IV was significantly lower compared with phase I and showed a trend of decrease compared with phase II. The results suggest that the daily cortisol secretion is modulated by the phase of the menstrual cycle.
Adult ; Circadian Rhythm ; Female ; Humans ; Hydrocortisone ; secretion ; Luteal Phase ; Menstrual Cycle ; Radioimmunoassay ; Salvia ; metabolism

Background: The aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid. Methods: Using a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light. Results: Median total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009). Conclusions The use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.

Background: The aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid. Methods: Using a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light. Results: Median total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009). Conclusions The use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.

OBJECTIVETo investigate the impact of novel P2Y(12) receptor inhibitors including prasugrel or ticagrelor on platelet reactivity in patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI), and provide clinical data for novel oral P2Y(12) receptor inhibitors use among Chinese patients.

METHODSBetween October 2011 to February 2014, 174 consecutive patients (135 males; (67.8±11.8) years old) with ACS undergoing PCI in Kiang Wu Hospital, Macau were prospectively enrolled in this study. Oral aspirin and one P2Y(12) receptor inhibitor were administered for 5 days or above after PCI, patients were divided into clopidogrel, prasugrel and ticagrelor groups in accordance with the agent administered. Platelet reactivity of the patients was detected by VerifyNow P2Y(12) reaction unit (PRU); and the high on-treatment platelet reactivity (HPR) and non-HPR were defined as PRU≥208 and PRU<208 respectively. Patients with HPR during clopidogrel therapy were switched either to prasugrel or ticagrelor, or continued the same treatment; and then the platelet reactivity was monitored again.

RESULTSThere were 113 clopidogrel cases (64.9%), 20 prasugrel cases (11.5%) and 41 ticagrelor cases (23.6%). Fifty-seven cases (32.8%) were defined as HPR post P2Y(12) receptor inhibitor use, in which 55 cases (55/113, 48.7%) were treated with clopidogrel. The degree of inhibition of platelet reactivity was significantly different in patients on clopidogrel, prasugrel and ticagrelor therapy, percent inhibition assayed by the VerifyNow P2Y(12) system was 28.2%±23.5%, 61.4%±26.7% and 81.3%±19.8% respectively (P<0.05). Different degree of platelet reactivity was achieved by the 3 P2Y(12) receptor inhibitors at multiple time points. The among-group differences in platelet reactivity became apparent at the early treatment stage (P<0.05). Platelet aggregation decreased significantly in patients switched from clopidogrel to prasugrel or ticagrelor (P<0.05).

CONCLUSIONNovel oral P2Y(12) receptor inhibitors are more effective in inhibiting platelet reactivity in ACS patients, and our results show that novel oral P2Y(12) receptor inhibitors provide a new option for ACS patients with HPR post clopidogrel or high-risk features of ischemic complications, including stent thrombosis and post-PCI ischemic events.

Acute Coronary Syndrome ; Adenosine ; analogs & derivatives ; Aged ; Aspirin ; Blood Platelets ; Female ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; Platelet Function Tests ; Prasugrel Hydrochloride ; Prospective Studies ; Ticlopidine ; analogs & derivatives

Objective: To understand the prevalence of major human parasitic diseases and related factors in Henan province. Methods: This stratified sampling survey was carried out according to the requirement of national survey protocol of major human parasitic diseases, 2014-2015. The prevalence of soil-transmitted helminths infection, taeniasis and intestinal protozoiasis were surveyed in 104 sites selected from 35 counties (districts) and the prevalence of clonorchiasis was surveyed in 62 sites selected from 37 townships. In each survey spot, 250 persons were surveyed. A total of 26 866 persons and 15 893 persons were surveyed. Modified Kato-Katz thick smear was used to detect the eggs of intestinal helminthes. Tube fecal culture was used to identify the species of hookworm. The Enterobius eggs were detected in children aged 3 to 6 years by using adhesive tape. The cyst and trophozoite of intestinal protozoa were examined with physiological saline direct smear method and iodine stain method. Results: The overall infestation rate of intestinal parasites was2.02% in Henan, and the worm infection rate was higher than protozoa infection rate. Fourteen kinds of intestinal parasites were found, including nematode (5 species), trematode (2 species), and protozoan (7 species). The infection rate of Enterobius vermicularis was highest, and Qinba Mountain ecological area had the highest infestation rate of intestinal parasites in 4 ecological areas of Henan. There was no significant difference in intestinal parasite infection rate between males and females (χ(2)=3.630, P=0.057), and the differences in intestinal parasite infection rate among different age groups had significance (χ(2)=124.783, P=0.000 1). The infection rate reached the peak in age group ≤9 years and the major parasite was Enterobius vermicularis. Furthermore the overall human infection rate of parasite showed a downward trend with the increase of educational level of the people (χ(2)=70.969, P=0.000 1), the differences had significance (χ(2)=120.118, P=0.000 1). For different populations, the infection rate of intestinal parasites was highest among preschool children. The infection of intestinal helminth was mainly mild, only 2 severe cases were detected. The infection rate of Clonorchis sinensis in urban residents was only 0.006%. Logistic regression analysis showed that being preschool children (χ(2)=15.765, P=0.000 1) and drinking well water (χ(2)=45.589, P=0.000 1) were the risk factors for intestinal parasite infection, and annual income per capita of farmers was the protective factor against intestinal parasite infection. The infection rates of protozoa and intestinal parasites decreased sharply compared with the results of previous two surveys, and the rate of intestinal helminth infection also dropped sharply compared with the second survey. The numbers of protozoa, helminth and intestinal parasites detected in this survey were all less than the numbers found in the previous two surveys. Conclusions: Compared the results of three surveys in Henan, the infection rate of protozoa and intestinal parasites showed a downward trend. The prevention and treatment of Enterobius vermicularis infection in children should be the key point of parasitic disease control in the future.
Animals ; Child ; Child, Preschool ; Clonorchiasis/epidemiology* ; Farmers ; Feces/parasitology* ; Female ; Helminthiasis/epidemiology* ; Helminths ; Humans ; Intestinal Diseases, Parasitic/parasitology* ; Male ; Prevalence ; Protective Factors ; Risk Factors ; Rural Population ; Soil Microbiology ; Surveys and Questionnaires ; Taeniasis/epidemiology* ; Trematode Infections/parasitology* ; Urban Population ; Water Wells

Objective: To understand the epidemiological and etiological characteristics of mumps in Fujian province, 2005-2017. Methods: All the reported mumps cases were collected through the National Notifiable Disease Information Management System, 2005-2017. Active search and interviews were conducted to collect the information on vaccination of mumps. Throat swab specimens were collected for cells culture, genotyping and gene sequence analysis on mumps virus (MuV). Results: A total of 83 959 cases of mumps were reported in Fujian province from 2005 to 2017, with an average annual incidence of 17.6 per 100 000. Since 2007, the incidence appeared increasing but then decreasing, reaching the lowest level (7.5 per 100 000), after the setup of a monitoring program. Annually, the onset time of mumps showed an obvious two seasonal peaks, one from April to July, with a weakening trend, and the other from October to January with a rising trend. Most of the mumps cases occurred among students, kindergarten and scattered children (89.2%, 5 814/6 517), children aged 5-9 years (38.8%, 2 527/6 517), with cases reported from every region. Program from the pathogen surveillance showed that the transmission chain of G genotype mumps virus did exist in Fujian. Data from the sequence analysis revealed that mutations in the nucleotide of G genotype strain in 2015 had led to mutation of 6 amino acid sites in the SH gene coding region, resulting in the differences appearing in both nucleotide and amino acid homology with type A vaccine strain. Conclusions: The incidence of mumps decreased annually, in Fujian. Prevention programs should focus on primary and secondary school students. In Fujian province, we also noticed the transmission chain of mumps G genotype with some amino acid mutations in the SH gene coding region. Monitor programs on both epidemiologic and etiology, should be strengthened.
Child ; Child, Preschool ; China/epidemiology* ; Genotype ; Humans ; Incidence ; Mumps/epidemiology* ; Mumps virus/pathogenicity* ; Phylogeny ; Sequence Analysis

Meropenem is one of the most widely used special-grade antimicrobial agents in the treatment of neonatal sepsis.However,its irrational use has led to an increasingly severe problem of bacterial multidrug resistance.The guideline was developed following standardized methods and procedures,and provides 12 recommendations specifically addressing 9 clinical issues.The recommendations cover various aspects of meropenem use in neonates,including timing of administration,recommended dosage,extended infusion,monitoring and assessment,antimicrobial adjustment strategies,treatment duration,and treatment strategies for carbapenem-resistant Enterobacteriaceae infections.The aim of the guideline is to provide evidence-based recommendations and guidance for the rational use of meropenem in neonates with sepsis.[Chinese Journal of Contemporary Pediatrics,2024,26(2):107-117]

BACKGROUNDThe difference in clinical outcome between paclitaxal-eluting stents (PES) and sirolimus-eluting stents with bio-degradable polymer (SES-BDP) for bifurcation lesions remains unclear. The present study aimed to investigate the one-year clinical outcome after DK crush stenting using PES (Taxus(TM)) vs. SES-BDP (Excel(TM)) from our database.

METHODSA total of 275 patients (90 from the DKCRUSH-I and 185 from the DKCRUSH-II study) were studied. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at 12 months; including cardiac death, myocardial infarction (MI), or target vessel revascularization (TVR). The rate of binary restenosis and stent thrombosis served as secondary endpoints.

RESULTSAt follow-up, minimal luminal diameter (MLD) in the Taxus group was (2.11 ± 0.66) mm, with resultant increased target lesion revascularization (TLR) 12.2% and TVR 14.4%, significantly different from the Excel group; (2.47 ± 0.56) mm, P < 0.001, 3.2%, P = 0.006, 4.9%, P = 0.019, respectively. As a result there was a significant difference in MACE between the Taxus (20.0%) and Excel (10.3%, P = 0.038) groups. Overall stent thrombosis was monitored in 11 patients (4.0%), with five in the Excel group (2.7%) and six in the Taxus group (6.7%). All stent thrombosis in the Excel group was classified as early, and all were defined as late in the Taxus group.

CONCLUSIONThe Excel stent had lower rate of stent thrombosis, TLR, TVR, and composite MACE at 12-month after an indexed stenting procedure, compared to the Taxus stent.

Absorbable Implants ; Aged ; Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Paclitaxel ; therapeutic use ; Polymers ; Sirolimus ; therapeutic use