Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance.

Prolyl hydroxylase domain (PHD)-containing enzyme 3 (PHD3) belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases. PHD3 catalyzes proline hydroxylation of hypoxia-inducible factor α (HIF-α) and promotes HIF-α proteasomal degradation through coordination with the pVHL complex under normoxic conditions. However, the relationship between PHD3 and the hypoxic response is not well understood. In this study, we used quantitative real-time PCR assay and O-dianisidine staining to characterize the hypoxic response in zebrafish deficient in phd3. We found that the hypoxia-responsive genes are upregulated and the number of erythrocytes was increased in phd3-null zebrafish compared with their wild-type siblings. On the other hand, we show overexpression of phd3 suppresses HIF-transcriptional activation. In addition, we demonstrate phd3 promotes polyubiquitination of zebrafish hif-1/2α proteins, leading to their proteasomal degradation. Finally, we found that compared with wild-type zebrafish, phd3-null zebrafish are more resistant to hypoxia treatment. Therefore, we conclude phd3 has a role in hypoxia tolerance. These results highlight the importance of modulation of the hypoxia signaling pathway by phd3 in hypoxia adaptation.

Resolving Ultraviolet-Visible Spectra for Complex Dissolved Mixtures of Multitudinous Organic Matters in Aerosols.

Light-absorbing organic aerosols, referred to as brown carbon (BrC), play a vital role in the global climate and air quality. Due to the complexity of BrC chromophores, the identified absorbing substances in the ambient atmosphere are very limited. However, without comprehensive knowledge of the complex absorbing compounds in BrC, our understanding of its sources, formation, and evolution mechanisms remains superficial, leading to great uncertainty in climatic and atmospheric models. To address this gap, we developed a constrained non-negative matrix factorization (NMF) model to resolve the individual ultraviolet-visible spectrum for each substance in dissolved organic aerosols, with the power of ultrahigh-performance liquid chromatography-diode array detector-ultrahigh-resolution mass spectrometry (UHPLC-DAD-UHRMS). The resolved spectra were validated by selected standard substances and validation samples. Approximately 40,000 light-absorbing substances were recognized at the MS1 level. It turns out that BrC is composed of a vast number of substances rather than a few prominent chromophores in the urban atmosphere. Previous understanding of the absorbing feature of BrC based on a few identified compounds could be biased. Weak-absorbing substances missed previously play an important role in BrC absorption when they are integrated due to their overwhelming number. This model brings the property exploration of complex dissolved organic mixtures to a molecular level, laying a foundation for identifying potentially significant compositions and obtaining a comprehensive chemical picture.

An imported malaria case with repeated episodes of neurological syndromes resulting from different Plasmodium species.

BACKGROUND: Imported cerebral malaria (CM) cases in non-endemic areas are often misdiagnosed, which delays treatment. Post-malaria neurological syndrome (PMNS) after recovery from severe malaria can also complicate diagnosis. CASE: We report an imported malaria case from West Africa with two sequential episodes with neurological syndromes within about a month. The first episode was diagnosed as CM with microscopy-positive Plasmodium falciparum infection. The second episode, occurring a month after the recovery from the first CM episode, was consistent with PMNS, since malaria parasites were not detected by microscopy in peripheral blood smears. However, this diagnosis was complicated by the detection of Plasmodium vivax in peripheral blood by PCR, suggesting a potential cause of the second episode by P. vivax. CONCLUSION: This study suggests that PMNS often occurs after severe falciparum malaria. Concurrent P. vivax infection with pathogenic biomass being predominantly extravascular further complicates accurate diagnosis.

Mitochondrial transfer of α-synuclein mediates carbon disulfide-induced mitochondrial dysfunction and neurotoxicity.

Exposure to carbon disulfide (CS2) is a recognized risk factor in the pathogenesis of Parkinson's disease, yet the underlying mechanisms of deleterious effects on mitochondrial integrity have remained elusive. Here, through establishing CS2 exposure models in rat and SH-SY5Y cells, we demonstrated that highly expressed α-synuclein (α-Syn) is transferred to mitochondria via membrane proteins such as Tom20 and leads to mitochondrial dysfunction and mitochondrial oxidative stress, which ultimately causes neuronal injury. We first found significant mitochondrial damage and oxidative stress in CS2-exposed rat midbrain and SH-SY5Y cells and showed that mitochondrial oxidative stress was the main factor of mitochondrial damage by Mitoquinone intervention. Further experiments revealed that CS2 exposure led to the accumulation of α-Syn in mitochondria and that α-Syn co-immunoprecipitated with mitochondrial membrane proteins. Finally, the use of an α-Syn inhibitor (ELN484228) and small interfering RNA (siRNA) effectively mitigated the accumulation of α-Syn in neurons, as well as the inhibition of mitochondrial membrane potential, caused by CS2 exposure. In conclusion, our study identifies the translocation of α-Syn to mitochondria and the impairment of mitochondrial function, which has important implications for the broader understanding and treatment of neurodegenerative diseases associated with environmental toxins.

High-fat diet exacerbated motor dysfunction via necroptosis and neuroinflammation in acrylamide-induced neurotoxicity in mice.

Health risks associated with acrylamide (ACR) or high-fat diet (HFD) exposure alone have been widely concerned in recent years. In a realistic situation, ACR and HFD are generally co-existence, and both are risk factors for the development of neurological diseases. The purpose of the present study was to investigate the combined effects of ACR and HFD on the motor nerve function. As a result, neurobehavioral tests and Nissl staining disclosed that long-term HFD exacerbated motor dysfunction and the damage of spinal cord motor neurons in ACR-exposed mice. Co-exposure of ACR and HFD resulted in morphological changes in neuronal mitochondria of the spinal cord, a significantly reduced mitochondrial subunits NDUFS1, UQCRC2, and MTCO1, released the mitochondrial DNA (mtDNA) into the cytoplasm, and promoted the production of reactive oxygen species (ROS). Combined exposure of HFD and ACR activated the calpain/CDK5/Drp1 axis and caused the mitochondrial excessive division, ultimately increasing MLKL-mediated necroptosis in spinal cord motor neurons. Meanwhile, HFD significantly exacerbated ACR-induced activation of NFkB, NLRP3 inflammasome, and cGAS-STING pathway. Taken together, our findings demonstrated that combined exposure of ACR and HFD aggravated the damage of spinal cord motor neurons via neuroinflammation and necroptosis signaling pathway, pointing to additive effects in mice than the individual stress effects.

The short and long-term impact of nonpharmaceutical interventions on the prevalence of varicella in Xi'an during the COVID-19 pandemic.

Varicella is a highly prevalent infectious disease with a similar transmission pathway to coronavirus disease 2019 (COVID-19). In the context of the COVID-19 pandemic, anti-COVID-19 nonpharmaceutical interventions (NPIs) have been implemented to prevent the spread of the infection. This study aims to analyze varicella's epidemiological characteristics and further investigate the effect of anti-COVID-19 NPIs on varicella in Xi'an, northwestern China. Based on the varicella surveillance data, search engine indices, meteorological factors from 2011 to 2021 in Xi'an, and different levels of emergency response to COVID-19 during the pandemic, we applied Bayesian Structural Time Series models and interrupted time series analysis to predict the counterfactual incidence of varicella and quantify the impact of varying NPIs intensities on varicella. From 2011 to 2021, varicella incidence increased, especially in 2019, with a high incidence of 111.69/100 000. However, there was a sharp decrease of 43.18% in 2020 compared with 2019, and the peak of varicella incidence in 2020 was lower than in previous years from the 21st to the 25th week. In 2021, the seasonality of varicella incidence gradually returned to a seasonal pattern in 2011-2019. The results suggest that anti-COVID-19 NPIs effectively reduce the incidence of varicella, and the reduction has spatiotemporal heterogeneity.

Modelling the pulse population-wide nucleic acid screening in mitigating and stopping COVID-19 outbreaks in China.

BACKGROUND: During 2021-2022, mainland China experienced multiple times of local COVID-19 outbreaks in several cities, including Yangzhou, Xi'an etc., and the Chinese government persistently adopted the zero-COVID policy in combating with the local outbreaks. METHODS: We develop a mathematical model with pulse population-wide nucleic acid screening, part of the zero-COVID policy, to reveal its role in controlling the spread of COVID-19. We calibrate the model by fitting the COVID-19 epidemic data of the local outbreaks in Yangzhou and Xi'an, China. Sensitivity analysis is conducted to investigate the impact of population-wide nucleic acid screening on controlling the outbreak of COVID-19. RESULTS: Without the screening, the cumulative number of confirmed cases increases by [Formula: see text] and [Formula: see text] in Yangzhou and Xi'an, respectively. Meanwhile, the screening program helps to shorten the lockdown period for more than one month when we aim at controlling the cases into zero. Considering its role in mitigating the epidemics, we observe a paradox phenomenon of the screening rate in avoiding the runs on medical resource. That is, the screening will aggravate the runs on medical resource when the screening rate is small, while it helps to relieve the runs on medical resource if the screening rate is high enough. We also conclude that the screening has limited effects on mitigating the epidemics if the outbreak is in a high epidemic level or there has already been runs on medical resources. Alternatively, a smaller screening population per time with a higher screening frequency may be a better program to avoid the runs on medical resources. CONCLUSIONS: The population-wide nucleic acid screening strategy plays an important role in quickly controlling and stopping the local outbreaks under the zero-COVID policy. However, it has limited impacts and even increase the potential risk of the runs on medical resource for containing the large scale outbreaks.

Effects of the polyhalogenated carbazoles 3-bromocarbazole and 1,3,6,8-tetrabromocarbazole on soil microbial communities.

Soil ecosystems are being more contaminated with polyhalogenated carbazoles (PHCZs), which raising much attention about their impact on soil microorganisms. 3-Bromocarbazole (3-BCZ) and 1,3,6,8-tetrabromocarbazole (1,3,6,8-TBCZ) are two typical PHCZs with high detection rates in the soil environment. However, ecological risk research on these two PHCZs in soil is still lacking. In the present study, after 80 days of exposure, the ecological influence of 3-BCZ and 1,3,6,8-TBCZ was investigated based on 16S rDNA sequencing, ITS sequencing, gene (16S rDNA, ITS, amoA, nifH, narG and cbbL) abundance and soil enzyme activity. The results showed that the bacterial 16S rDNA gene abundance significantly decreased under 3-BCZ and 1,3,6,8-TBCZ exposure after 80 days of incubation. The fungal ITS gene abundance significantly decreased under 1,3,6,8-TBCZ (10 mg/kg) exposure. PHCZs contributed to the alteration of bacteria and fungi community abundance. Bacteria Sphingomonas, RB41 and fungus Mortierella, Cercophora were identified as the most dominant genera. The two PHCZs consistently decreased the relative abundance of Sphingomonas, Lysobacter, Dokdonella, Mortierella and Cercophora etc at 80th day. These keystone taxa are related to the degradation of organic compounds, carbon metabolism, and nitrogen metabolism and may thus have influence on soil ecological functions. Bacterial and fungal functions were estimated using functional annotation of prokaryotic taxa (FAPROTAX) and fungi functional guild (FUNGuild), respectively. The nitrogen and carbon metabolism pathway were affected by 3-BCZ and 1,3,6,8-TBCZ. The soil nitrogen-related functions of aerobic ammonia oxidation were decreased but the soil carbon-related functions of methanol oxidation, fermentation, and hydrocarbon degradation were increased at 80th day. The effects of 3-BCZ and 1,3,6,8-TBCZ on the abundances of the amoA, nifH, narG, and cbbL genes showed a negative trend. These results elucidate the ecological effects of PHCZs and extend our knowledge on the structure and function of soil microorganisms in PHCZ-contaminated ecosystems.

Novel SCCmec type XV (7A) and two pseudo-SCCmec variants in foodborne MRSA in China.

BACKGROUND: Staphylococcal cassette chromosome mec (SCCmec) elements are highly diverse and have been classified into 14 types. Novel SCCmec variants have been frequently detected from humans and animals but rarely from food. OBJECTIVES: To characterize a novel SCCmec type and two SCCmec variants identified from food-associated MRSA in China. METHODS: Three MRSA (NV_1, NT_611 and NT_8) collected from retail foods in China were subjected to WGS and the SCCmec elements were determined. RESULTS: The novel SCCmecXV identified in NV_1 carried the mec gene complex class A (mecI-mecR1-mecA-IS431) and the ccr gene complex 7 (ccrA1B6), and a Tn558-mediated phenicol exporter gene fexA was detected in this SCCmecXV cassette. The pseudo-SCCmec elements ΨSCCmecNT_611 and ΨSCCmecNT_8 showed a truncated SCCmec pattern, carrying the class C2 mec gene complex but missing the ccr genes. The ΨSCCmecNT_611 element shared more similarities with those of Staphylococcus haemolyticus (AB478934.1) and carried a heavy metal resistance gene cluster cadD-cadX-arsC-arsB-arsR-copA. The ΨSCCmecNT_8 MRSA exhibited a highly resistant phenotype, showing the absence of a 19.3 kb segment compared with the reference SCCmecXII element (CP019945.1). Notably, a 46 kb region containing multiple transposons encoding antimicrobial or metal resistance genes flanked by IS431 or IS256 was identified ∼30 kb downstream from the mec gene complex in ΨSCCmecNT_8, which might explain such high resistance in MRSA NT_8. CONCLUSIONS: Our finding of novel and pseudo-SCCmec elements reflected the ongoing intra/interspecies genetic rearrangements in staphylococci. Further study will be needed to investigate the biological significance and prevalence of those SCCmec variants along the food chain.

The impact of anti-COVID-19 nonpharmaceutical interventions on hand, foot, and mouth disease-A spatiotemporal perspective in Xi'an, northwestern China.

Growing evidence has shown that anti-COVID-19 nonpharmaceutical interventions (NPIs) can support prevention and control of various infectious diseases, including intestinal diseases. However, most studies focused on the short-term mitigating impact and neglected the dynamic impact over time. This study is aimed to investigate the dynamic impact of anti-COVID-19 NPIs on hand, foot, and mouth disease (HFMD) over time in Xi'an City, northwestern China. Based on the surveillance data of HFMD, meteorological and web search data, Bayesian Structural Time Series model and interrupted time series analysis were performed to quantitatively measure the impact of NPIs in sequent phases with different intensities and to predict the counterfactual number of HFMD cases. From 2013 to 2021, a total number of 172,898 HFMD cases were reported in Xi'an. In 2020, there appeared a significant decrease in HFMD incidence (-94.52%, 95% CI: -97.54% to -81.95%) in the first half of the year and the peak period shifted from June to October by a small margin of 6.74% compared to the previous years of 2013 to 2019. In 2021, the seasonality of HFMD incidence gradually returned to the bimodal temporal variation pattern with a significant average decline of 61.09%. In particular, the impact of NPIs on HFMD was more evident among young children (0-3 years), and the HFMD incidence reported in industrial areas had an unexpected increase of 51.71% in 2020 autumn and winter. Results suggested that both direct and indirect NPIs should be implemented as effective public health measures to reduce infectious disease and improve surveillance strategies, and HFMD incidence in Xi'an experienced a significant rebound to the previous seasonality after a prominent decline influenced by the anti-COVID-19 NPIs.

The effectiveness of various control strategies: An insight from a comparison modelling study.

Several local outbreaks have occurred and been suppressed with the dynamic zero-COVID policy and widely promoted vaccination program implemented in China. The epidemic duration and final size vary significantly in different cities, which may be attributed to different implementation patterns and intensities of non-pharmaceutical interventions (NPIs). It's important to capture the underlying mechanism to explore more efficient implementation patterns of NPIs in order to prevent the future resurgence. In this study, outbreaks caused by Delta variant in Xi'an, Yangzhou and Guangzhou in 2021 are chosen as the examples. A novel model dividing the population into three groups is proposed to describe the heterogeneity of control interventions. The model is calibrated and key parameters related to NPIs are estimated by using multi-source epidemic data. The estimation results show a lower transmission probability but a higher initial reproduction number in Xi'an. Sensitivity analysis are conducted to investigate the impact of various control measures in different epidemic phases. The results identify the vital role of enhancing closed-off management, strengthening tracing and testing intensities, on shortening the epidemic durations and reducing the final size. Further, we find that sufficiently implemented closed-off management would prevent the city from lockdown. Strengthening the tracing other than the testing strategy in the initial stage is more effective on containing the epidemic in a shorter duration with less infections.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Stanniocalcin1 knockdown induces ferroptosis and suppresses glycolysis in prostate cancer via the Nrf2 pathway.

Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not clear. The viability of PC-3 and DU145 cells was detected by CCK-8 assay. The relative Fe2+ level was detected by an Iron Assay Kit. MDA level was detected by Lipid Peroxidation MDA Assay Kit. Glucose uptake and lactate product were measured by Glycolysis Assay Kit and Lactate Assay Kit. In this study, STC1 was highly expressed in prostate cancer tissue specimens and cells. STC1 knockdown suppressed prostate cancer cell proliferation, and upregulated Fe2+ level, reduced glutathione (GSH) level, downregulated GPX4 and SLC7A11 protein expressions in PC-3 cells and DU145 cells. Besides, STC1 knockdown decreased glucose uptake, lactate product, and ATP level, as well as downregulated glycolysis-related protein HK2 and LDHA protein expressions. In addition, STC1 knockdown repressed the Nrf2/HO-1/NQO1 pathway. Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells. Moreover, Nrf2 pathway activator Oltipraz reversed the effect of STC1 knockdown on Fe2+ level and GPX4, SLC7A11, HK2, LDHA protein expressions in PC-3 cells and DU145 cells. Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.

Comparative study of the bacterial distribution and antimicrobial susceptibility of uropathogens in older and younger patients with urinary stones.

BACKGROUND: This study compared the bacterial spectrum and antibiotic susceptibility of uropathogens in older and younger patients with urinary stones to provide appropriate antibiotic management. METHODS: We retrospectively reviewed urinary tract infection patients with urolithiasis, presented to Xiangya Hospital from March 2014 to April 2021. Patients were divided into older and younger groups according to 60 years of age. The bacterial spectrum and drug sensitivity of uropathogens were compared. RESULTS: A total of 542 strains of uropathogens (177 in older and 365 in younger groups) were isolated from 507 patients. E. coli (41.8% vs 43.6%) remains the most common pathogen, followed by E. faecalis (6.2% vs 9.6%) in older and younger groups, respectively. Particularly, K. pneumoniae was significantly more frequent in older (9.6%) than in younger group (4.7%, P < .05). E. faecium was substantially more prevalent in older group (6.2%) than in younger group (2.7%, P < .05). The proportion of males increased in older patients (47.3%) than in younger patients (34.9%, P = 0.007). In both groups, major Gram-negative bacteria (E. coli and K. pneumoniae) revealed a high sensitivity over 70% to piperacillin/tazobactam, imipenem and amikacin, whereas the resistance level was high to penicillin, tetracycline and vancomycin. Major Gram-positive (E. faecalis and E. faecium) isolates demonstrated high sensitivity of over 50% to gentamicin and vancomycin in both groups. Furthermore, uropathogens isolated from younger urolithiasis patients were more susceptible to antimicrobials than those isolated from older patients. CONCLUSIONS: The male increased in the older urolithiasis patients with UTI and uropathogens microbial spectrum in older urolithiasis patients are different from younger. High susceptibility and age should be utilized in empirical antibiotic selection to avoid increased multidrug-resistant bacteria.

Gender differences in the microbial spectrum and antibiotic sensitivity of uropathogens isolated from patients with urinary stones.

PURPOSE: The characteristics and resistance patterns of urine bacteriology urolithiasis patients between male and female have not been extensively studied. This study aims to investigate the gender differences in microbial spectrum and antibiotic susceptibility of uropathogens isolated from urolithiasis patients and provide insights for appropriate antimicrobial therapies. MATERIALS AND METHODS: We retrospectively collected clinical microbiology data from urine culture in urolithiasis patients between March 2014 and December 2018 in Xiangya Hospital. Then the patients were divided into male and female groups. The microbial spectrum and frequency of susceptibility to antibiotics were compared. RESULTS: A total of 359 uropathogen isolates were collected from 335 patients, including 144 males (43.0%) and 191 females (57.0%). E. coli dominated in both groups, indicating higher frequency in females (53.2%) than in males (26.6%, p < 0.001), followed by E. faecalis, with higher frequency in males (15.6%) than in females (2.9%, p < 0.001). Major Gram-negative (E. coli and K. pneumoniae) bacteria showed high sensitivity to cefoperazone/sulbactam, cefotetan, piperacillin/ tazobactam, and amikacin. In contrast, the resistance level was high to penicillin, tetracycline, and vancomycin in both groups. Gram-positive (E. faecalis and E. faecium) isolates demonstrated high sensitivity to gentamicin and vancomycin in both groups. Furthermore, uropathogens isolated from female urolithiasis patients were more susceptible to antimicrobials than males. CONCLUSIONS: Uropathogen microbial spectrum in female urolithiasis patients is different from males. High susceptibility antibiotics should be used empirically according to gender to avoid multidrug-resistant bacteria increase.

Dexmedetomidine attenuates one-lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta-analysis.

One-lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti-inflammatory effects in lung tissues in pre-clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine's anti-inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta-analysis investigated the anti-inflammatory property of dexmedetomidine perioperatively [T1 (30-min OLV), T2 (90-min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine's intraoperative administration resulted in a significant reduction in serum concentration of interleukin-6, tumor necrosis factor-α and other inflammatory cytokines perioperatively. By calculating specific I2 index, significant heterogeneity was observed on all occasions, with I2 index ranging from 95% to 99%. For IL-6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%-0%; p < 0.00001). Besides, pulmonary oxygenation was ameliorated in the dexmedetomidine group comparing with the control group. In conclusion, perioperative administration of dexmedetomidine can attenuate OLV induced inflammation, ameliorate pulmonary oxygenation, and may be conducive to a decreased occurrence of postoperative complications and better prognosis. However, the results should be prudently interpreted due to the evidence of heterogeneity and the limited number of studies.

Identification of prognostic and therapeutic value of CC chemokines in Urothelial bladder cancer: evidence from comprehensive bioinformatic analysis.

BACKGROUND: Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC. METHODS: ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein-protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics. RESULTS: The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). CONCLUSIONS: This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.

[Effect of Gaseous Pollutant Concentration on the Number of Daily Outpatient Visits for Acne in Lanzhou].

Objective To determine the relationship between air pollutants [SO2,NO2,8 hours average concentration of ozone(O38h)] and outpatient visits for acne in Lanzhou,China. Methods Data of daily outpatient visits for acne and concentrations of air pollutants(SO2,NO2,and O38h)from January 2013 to December 2017 were collected.With the control of long-term trend and day-of-week effect,a distributed lag nonlinear model was used to analyze the lag and cumulative effects of air pollutants on the outpatient visits.The model was established based on the different groups of gender and age. Results During the study period,the average daily outpatient visits were 34.94±15.27,and the average concentrations of SO2,NO2,and O38h were 24.09,43.77,and 82.94 µg/m3,respectively.The Spearman's correlation analysis showed that the daily outpatient visits for acne were positively correlated with NO2 concentration while negatively correlated with O38h concentration;SO2 concentration was negatively correlated with O38h concentration;NO2 concentration was positively correlated with SO2 and O38h concentrations.A 10 µg/m3 increase in daily concentrations of NO2 and SO2 was respectively associated with 2.61%(95% CI=0.98%-4.27%)and 1.71%(95% CI=0.54%-2.89%)increase in the outpatient visits for acne.A 10 µg/m3 increase in O38h concentration was associated with -0.62%(95% CI=-1.12%--0.11%)increase in the outpatient visits.Multipollutant models indicated that air pollutant concentrations were significantly associated with the daily outpatient visits for acne. Conclusions SO2 and NO2 are positively associated with daily dermatological department visits for acne in Lanzhou,while O38h concentration has a negative correlation with the visits.The sensitivity of acne daily outpatient visits to changes in SO2,NO2,and O38h varies among patients of different genders and at different ages.

Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function.

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague-Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1ß, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.

[Antimicrobial resistance, virulence factors, and molecular characterization of methicillin-resistant Staphylococcus aureus isolates cultured from ready-to-eat foods].

OBJECTIVE: To understand the antimicrobial resistance, virulence factors, and molecular characterization of MRSA isolates cultured from ready-to-eat(RTE) foods from several provinces in China. METHODS: Totally, 397 S. aureus isolates were collected from RTE foods from several provinces in China, in 2017. The mecA gene was amplified to detect the MRSA strains among all 397 isolates by a polymerase chain reaction(PCR) method. Furthermore, the antimicrobial susceptibility and virulence factors of the MRSA isolates were detected by broth microdilution method and PCR, respectively, while the molecular characterization of all MRSA isolates were analyzed by pulsed-field gel electrophoresis(PFGE). RESULTS: In total, 32 MRSA isolates were identified from 397 isolates. All 32 MRSA isolates were resistant to penicillin, oxacillin and cefoxitin. Meanwhile, 78. 1%, 65. 6%, 53. 1, 28. 1% and 12. 5% of the 32 MRSA isolates showed resistant to erythromycin, clindamycin, tetracycline, chloramphenicol, and ciprofloxacin, respectively. Resistance rates to gentamicin and trimethoprim-sulfamethoxazole of all MRSA isolates were less than 10%. Eleven drug resistant spectrums were identified and 29 out of 32 MRSA isolates were identified as multi-drug resistant(MDR) isolates and two isolates were found to resistant to 9 antimicrobial agents tested in this study. Of all, 27 MRSA isolates were detected to harboring 13 virulence genes with sel-q(56. 3%), sel-k(43. 8%), seb(28. 1%) and sec(18. 8%) genes being the top four frequently detected. Besides, the result also showed that two or more virulence genes could be detected in one MRSA isolate. Finally, all 32 MRSA were identified to have 26 PFGE patterns and no dominant PFGE patterns were found in this study. CONCLUSION: An overall high level antimicrobial resistance was found among RTE associated MRSA in China in 2017, so was the MDR condition. Virulence genes could be frequently detected in RTE associated MRSA isolates. The PFGE patterns of RTE associated MRSA showed wide distribution characteristics.