In vitro suppression of porcine epidemic diarrhea virus by Panax notoginseng saponins: assessing antiviral potential.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity below the concentration of 128 µg/mL in Vero cells. Using immunofluorescence assays (IFAs), an enzyme-linked immunosorbent assay (ELISA), and plaque formation assays, we observed a dose-dependent inhibition of PEDV infection by PNS within 24-48 hours postinfection. PNS exerts its anti-PEDV activity specifically at the genome replication stage, and mRNA-seq analysis demonstrated that treatment with PNS resulted in increased expression of various genes, including IFIT1 (interferon-induced protein with tetratricopeptide repeats 1), IFIT3 (interferon-induced protein with tetratricopeptide repeats 3), CFH (complement factor H), IGSF10 (immunoglobulin superfamily member 10), ID2 (inhibitor of DNA binding 2), SPP1 (secreted phosphoprotein 1), PLCB4 (phospholipase C beta 4), and FABP4 (fatty acid binding protein 4), but it resulted in decreased expression of IL1A (interleukin 1 alpha), TNFRSF19 (TNF receptor superfamily member 19), CDH8 (cadherin 8), DDIT3 (DNA damage inducible transcript 3), GADD45A (growth arrest and DNA damage inducible alpha), PTPRG (protein tyrosine phosphatase receptor type G), PCK2 (phosphoenolpyruvate carboxykinase 2), and ADGRA2 (adhesion G protein-coupled receptor A2). This study provides insights into the potential mechanisms underlying the antiviral effects of PNS. Taken together, the results suggest that the PNS might effectively regulate the defense response to the virus and have potential to be used in antiviral therapies.

A Novel Anti-CRISPR AcrIE9.2 Is Associated with Dissemination of blaKPC Plasmids in Klebsiella pneumoniae Sequence Type 15.

Sequence type (ST) 15 has become an emerging clone of carbapenem-resistant Klebsiella pneumoniae in which type I-E* CRISPR-Cas usually exists, indicating that the CRISPR-Cas system may not be able to block the transfer of blaKPC plasmids. The purpose of this study was to explore the mechanisms underlying dissemination of blaKPC plasmids in K. pneumoniae ST15. The type I-E* CRISPR-Cas system was present in 98.0% of 612 nonduplicate K. pneumoniae ST15 strains (88 clinical isolates and 524 from the NCBI database). Twelve ST15 clinical isolates were completely sequenced, and self-targeted protospacers were found on blaKPC plasmids flanked by a protospacer adjacent motif (PAM) of AAT in 11 isolates. The type I-E* CRISPR-Cas system was cloned from a clinical isolate and expressed in Escherichia coli BL21(DE3). In BL21(DE3) harboring the CRISPR system, the transformation efficiency of protospacer-bearing plasmids with a PAM of AAT was reduced by 96.2% compared to the empty vector, indicating that the type I-E* CRISPR-Cas system impeded blaKPC plasmid transfer. BLAST for known anti-CRISPR (Acr) amino acid sequences uncovered a novel AcrIE9-like protein with 40.5% to 44.6% sequence identity with AcrIE9 designated AcrIE9.2, which was present in 90.1% (146 of 162) of ST15 strains carrying both blaKPC and the CRISPR-Cas system. When AcrIE9.2 was cloned and expressed in a ST15 clinical isolate, the conjugation frequency of a CRISPR-targeted blaKPC plasmid was increased from 3.96 × 10-6 to 2.01 × 10-4 compared to the AcrIE9.2 absent strain. In conclusion, AcrIE9.2 may be associated with the dissemination of blaKPC in ST15 by repressing CRISPR-Cas activity.

Corticosteroids in patients undergoing cardiac surgery: A meta-analysis of 12,559 patients.

OBJECTIVE: Corticosteroids can attenuate the inflammatory response to cardiopulmonary bypass, but their benefits on clinical outcomes are unclear. We conducted a meta-analysis to evaluate whether corticosteroid therapy affects outcomes in patients undergoing cardiac surgery. METHODS: We searched PubMed, Embase, EBSCO and Cochrane databases from 1 January 2010 to 14 March 2022 for randomized controlled trials (RCTs) that assessed corticosteroid versus non- corticosteroid therapy in patients undergoing cardiac surgery. The primary outcome was in-hospital mortality. Secondary outcomes were renal failure, infection, delirium, intensive care unit (ICU) and hospital stay. RESULTS: Four RCTs including 12,559 patients (6265 randomized to corticosteroid therapy and 6294 to non-corticosteroid therapy) were included. One-hundred and 92 of 6265 patients (3.1%) randomized to the corticosteroid group versus 221 of 6294 patients (3.5%) randomized to the non-corticosteroid group experienced death during hospitalization. Compared the control group, corticosteroid therapy did not significantly reduce in-hospital mortality, with an RR of 0.87 (0.72-1.06), p = .16. There was no difference in the incidence of infection (RR 0.78 (0.56-1.10), p = .16), delirium during hospitalization (RR 1.01 (0.90-1.14), p = .85), or the length of hospital stay (MD -0.13 (-0.32 to 0.05), p = .17). However, corticosteroid therapy significantly reduced the risk of renal failure ( RR 0.82 (0.67-0.99), p = .04), and the length of ICU stay (MD -0.41 (-0.65 to -0.17), p < .01). CONCLUSIONS: Corticosteroids did not significantly reduce the rates of in-hospital mortality, infection, or delirium, but reduce the incidence of renal failure and the length of ICU stay.

Pseudomonas defluvii sp. nov., isolated from hospital sewage.

A novel Gram-negative, obligate aerobic, mobile, rod-shaped and non-spore-forming bacterial strain, WCHP16T, was isolated from the wastewater treatment plant at West China Hospital in Chengdu, PR China. It was characterized using a polyphasic approach. Analysis of its 16S rRNA gene sequence showed that strain WCHP16T belonged to the genus Pseudomonas with the highest similarity to Pseudomonas qingdaonensis JJ3T (99.34 %), Pseudomonas shirazica VM14T (99.0 %), Pseudomonas plecoglossicida NBRC 103162T (99.0 %) and Pseudomonas asiatica RYU5T (99.0 %). Phylogenomic analysis based on 107 core gene sequences demonstrated that WCHP16T was a member of the Pseudomonas putida group but was distant from all closely related species. Whole-genome comparisons, using average nucleotide identity based on blast (ANIb) and in silico DNA-DNA hybridization (isDDH), confirmed low genome relatedness to all the known Pseudomonas species (below the recommended thresholds of 95 % [ANIb] and 70 % [isDDH] for species delineation). Phenotypic characterization tests showed that the utilization of phenylacetic acid and capric acid, but not d-arabitol, and inability to produce fluorescent (King B medium) in combination could distinguish this strain from other related species of the genus Pseudomonas. Therefore, based on genetic and phenotypic evidence, it is clear that strain WCHP16T represents a novel species, for which the name Pseudomonas defluvii sp. nov. is proposed. The type strain is WCHP16T (GDMCC1.1215T=CCTCC AB 2017103T=KCTC 52991T).

Estimating the ploidy of Gracilariopsis lemaneiformis at both the cellular and genomic level1.

The determination of the ploidy level of an organism is a prerequisite for studies of evolution, cellular function, and genomic construction. Identification of the ploidy of the economically important red alga Gracilariopsis lemaneiformis has been hindered by its small genome and large number of chromosomes. Therefore, in the current study, PloidyNGS, a tool that calculates the number of reads supporting different alleles at each position along the genome sequence, and fluorescence in situ hybridization coupled with tyramide signal amplification (TSA-FISH) were used to clarify the ploidy of G. lemaneiformis. In addition, flow cytometry (FCM) was used to estimate the ploidy of different somatic cells. The PloidyNGS results showed that most of the alleles in the gametophyte were monomorphic, whereas the TSA-FISH results showed that one hybridization signal was observed in gametophytic nuclei and two in tetrasporophytic nuclei when the nuclei were hybridized by single copy gene probes. These results confirmed that G. lemaneiformis is a haploid in the gametophytic generation and diploid in the sporophytic generation. Moreover, the FCM result suggested that G. lemaneiformis was not an endopolyploid. Based on previous studies, we hypothesize that the nuclear number is important for the cellular differentiation and function of this species. We also suggest that G. lemaneiformis evolved from a paleopolyploid, the genome of which has been diploidized, and that traces of genomic doubling are no longer apparent. Thus, this study provides important evidence for further studies on the evolution and genomes of red algae.

Therapeutic effects of saponin components on porcine reproductive and respiratory syndrome virus-infected piglets.

The present study aimed to evaluate the potential therapeutic effects of Anemoside B4 (AB4), Panax notoginseng saponins (PNS), Notoginsenoside R1 (SR1), Saikosaponin A (SSA) and Saikosaponin D (SSD) on piglets infected with porcine reproductive and respiratory syndrome virus (PRRSV). A total of 132 completely healthy piglets were randomly divided into 22 groups consisting of six animals each. Control piglets were intramuscularly injected with 2 ml of PRRSV (NJGC strain) solution containing 106  TCID50  virus/ml. For low-, middle- and high-dose saponin treatment groups, the piglets were initially administrated with the same volume of PRRSV solution, followed by intraperitoneal injection with AB4, PNS, SR1, SSA or SSD at 1, 5 or 10 mg/kg b.w. on day 3. The piglets in drug control group were intraperitoneally injected with 10 mg/kg b.w. of each saponin without prior PRRS challenge, while those in blank control group were injected with the same amount of normal saline. The results indicated that all the five saponin components could decrease the incidence and severity of PRRSV-induced immunopathological damages, including the elevated body temperature, weight loss, anaemia and internal inflammation. Moreover, the saponin components could enhance protein absorption and immune responses. Taken together, this study reveals that the saponin components are effective against PRRSV infection and strengthen the immune system and thus may serve as potential antiviral therapeutic agents.

Klebsiella huaxiensis sp. nov., recovered from human urine.

A strain of a member of the genus Klebsiella, WCHKl090001, was recovered from a human urine sample in PR China in 2017. Phylogenetic analysis based on gyrA and rpoB housekeeping genes revealed that the strain was distinct from any previously described species of the genus Klebsiella though it was clustered with the Klebsiella oxytoca phylogroup, including Klebsiella grimontii, Klebsiella michiganensis and Klebsiella oxytoca. The whole-genome sequence of strain WCHKl090001 has an up to 87.18 % average nucleotide identity with those of type strains of all known species of the genus Klebsiella. In silico DNA-DNA hybridization (isDDH) values between strain WCHKl090001 and type strains of all known species of the genus Klebsiella ranged from 22.3 to 35.2 %. Strain WCHKl090001 could be distinguished from species of the Klebsiella oxytocaphylogroup by its negative Voges-Proskauer reaction. Genotypic and phenotypic characteristics from this study indicate that strain WCHKl090001 should be considered to represent a novel species of the genus Klebsiella, for which the name Klebsiellahuaxiensis sp. nov. is proposed. The type strain is WCHKl090001T (=GDMCC 1.1379T=CNCTC 7650T).

Pseudomonas sichuanensis sp. nov., isolated from hospital sewage.

A bacterial strain, designated WCHPs060039T, was isolated from hospital sewage in China. The strain was Gram-stain-negative, obligate aerobic, flagellum-motile and positive for oxidase and catalase. A preliminary analysis of the 16S rRNA gene sequences indicated that strain WCHPs060039T belonged to the genus Pseudomonasand was closely related to members of the Pseudomonas putida group, with the highest similarities to Pseudomonas entomophila L48T (99.5 %), Pseudomonas mosselii CIP 105259T (99.52 %), Pseudomonas taiwanensis BCRC 17751T (99.45 %) and Pseudomonas plecoglossicida NBRC 103162T (99.31 %). Whole genome sequencing of the strain was performed. Phylogenetic analysis based on a set of core gene sequences revealed that the strain was distinct from its closest Pseudomonas species. Average nucleotide identity based on blast and in silico DNA-DNA hybridizationrevealed low genome relatedness to its closest Pseudomonas species (below the recommended thresholds of 95 and 70 %, respectively, for species delineation). The major fatty acids of the strain were 16:0, 17:0 cyclo, summed feature 3 (16:1ω7c/16:1ω6c and 16:1ω6c/16:1ω7c) and summed feature 8 (18:1ω7c). The ability to utilize inositol, sorbitol and d-glucuronic acid could differentiate strain WCHPs060039T from the closely related Pseudomonas species. It is therefore evident that strain WCHPs060039T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas sichuanensis sp. nov. is proposed. The type strain is WCHPs060039T (GDMCC 1.1424T=CNCTC 7662T).

Providencia huaxiensis sp. nov., recovered from a human rectal swab.

Strain WCHPr000369T was recovered from a human rectal swab in China in 2015. Phylogenetic analysis based on its 16S rRNA gene suggested that the strain belonged to the genus Providencia. The genome sequence of the strain had a 77.30-90.43% average nucleotide identity (ANI) and 20.9-41.5 % in silico DNA-DNA hybridization (isDDH) score with those of type strains of known Providencia species. The ANI and isDDH values indicated that the strain was likely to belong to a new species. Multi-locus sequence analysis on the fusA, lepA, leuS, gyrB and ileS housekeeping genes also revealed that the strain was distinct from any previously described species of the genus Providencia. Strain WCHPr000369T could be distinguished from all known Providencia species by the combination of positive urease reaction and the ability to utilize citrate. Genotypic and phenotypic characteristics from this study indicated that strain WCHPr000369T should be considered to represent a novel species of the genus Providencia, for which the name Providencia huaxiensis sp. nov. is proposed. The type strain is WCHPr000369T (=GDMCC1.1382T=KCTC 62577T).

Effects of sinomenine in LPS-associated diseases are related to inhibition of LBP, Mac-1, and L-selectin levels.

The aim of the research was to investigate the anti-endotoxin and anti-inflammatory effects of Sinomenine, an agent commonly found in Chinese herbal medicines. Endotoxin (i.e., 1 mg lipopolysaccharide (LPS)/kg)) was administered via intraperitoneal (IP) injection to piglets in high-, middle-, and low-dose sinomenine groups. Piglets were then treated with 1, 5 or 10 mg/kg sinomenine, intramuscularly (i.m.), 3 hr after LPS. Vehicle was administered, as above, to drug control group piglets followed 3 hr later by 10 mg/kg sinomenine i.m.. LPS control group piglets were challenged with 1 mg/kg LPS IP, followed by vehicle i.m., and naïve control piglets were treated with normal saline IP, followed by normal saline i.m., as above. Temperatures were measured, and blood samples were collected from the precaval veins of piglets at 12, 24, and 48 hr post-LPS or vehicle injection. Clinical signs were recorded, and index levels were analyzed via ELISA. Sinomenine was found to reduce the incidence and severity of LPS-induced toxicities, including body temperature elevation, cell adhesion, and systemic inflammation. These data suggest that sinomenine may be effective for regulating inflammatory responses and has the potential for use as an anti-endotoxin therapy.

Acinetobacter sichuanensis sp. nov., recovered from hospital sewage in China.

A novel Acinetobacter strain, WCHAc060041T, was recovered from hospital sewage at West China Hospital in Chengdu, Sichuan Province, China. The strain was Gram-negative coccobacillus, non-spore-forming, non-motile and strictly aerobic. The genomic DNA G+C content was 37.02 mol%. The 16S rRNA and rpoB gene sequences of the strain were ≤98.2 and≤89.5 % identical to the type strains of all known Acinetobacter species, respectively. The strain formed a distinct branch based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry. Strain WCHAc060041T was subjected to whole genome sequencing. The average nucleotide identity based on blast (ANIb) and in silico DNA-DNA hybridization (isDDH) values between strain WCHAc060041T and type strains of other Acinetobacter species were ≤82.7 and ≤26.9 %, respectively. Strain WCHAc060041T could be distinguished from all known Acinetobacter species by its ability to assimilate gentisate and levulinate, but not to citrate (Simmons'). Genotypic and phenotypic characteristics from this study indicate that strain WCHAc060041T represents a novel species of the genus Acinetobacter, for which the name Acinetobacter sichuanensis sp. nov. is proposed. The type strain is WCHAc060041T (=CCTCC AB 2018118T=GDMCC 1.1383T=KCTC 62575T).

Acinetobacter wuhouensis sp. nov., isolated from hospital sewage.

We recovered eight strains of the genus Acinetobacter from hospital sewage at West China Hospital in Chengdu, China. Based on the comparative analysis of the rpoB sequence, these strains formed a strongly supported and internally coherent cluster (intra-cluster identity of ≥98.0 %), which was clearly separated from all known Acinetobacter species (≤91.1 %). The eight strains also formed a tight and distinct cluster based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In addition, the combination of their ability to assimilate 2,3-butanediol and phenylacetate, but not 4-hydroxybenzoate, and the inability to grow at 37 °C could distinguish these eight strains from all known Acinetobacter species. Whole-genomic sequencing has been performed for two selected strains, WCHA60T and WCHA62. There were 96.65 % average nucleotide identity (ANI) and 72 % in silico DNA-DNA hybridization (isDDH) values between WCHA60T and WCHA62, suggesting that the two strains indeed belonged to the same species. In contrast, the ANI and isDDH values between the two strains and the known Acinetobacter species were <83 and <30 %, respectively; both of which were far below the cut-off to define a bacterial species. Therefore, the eight strains should be considered to represent a novel species of the genus Acinetobacter, for which the name Acinetobacterwuhouensis sp. nov. is proposed. The type strain is WCHA60T (=CCTCC AB 2016204T=GDMCC 1.1100T=KCTC 52505T).

Protective effects of sinomenine against LPS-induced inflammation in piglets.

The aim of this study was to investigate in piglets, the anti-endotoxin and anti-inflammatory effects of sinomenine, an agent commonly found in Chinese herbal medicines. In high-, middle- and low-dose sinomenine groups, piglets were initially challenged with endotoxin (i.e., 1 mg lipopolysaccharide (LPS)/kg) by intraperitoneal (IP) injection and, 3 h later, intramuscularly (IM) with sinomenine at 1, 5, or 10 mg/kg. In a drug control group, piglets were dosed IP with vehicle and 3 h late IM with 10 mg/kg sinomenine while those in an LPS control group were challenged with 1 mg LPS/kg (IP) and then vehicle 3 h later; naïve control piglets were administered normal saline IP and then IM only. At 12, 24, and 48 h post-LPS/vehicle injection, blood samples were collected from the precaval vein of piglets. Clinical signs were recorded during the trial and index levels were analyzed by ELISA kits. The results revealed sinomenine could reduce the incidence/severity of certain LPS-induced toxicities, e.g., cell adhesion, systemic inflammation, and multiple organ dysfunction. Taken together, the data suggested to us that sinomenine might effectively be useful to regulate inflammatory responses as part of future anti-endotoxin therapies.

Acinetobacter defluvii sp. nov., recovered from hospital sewage.

A Gram-stain-negative, non-motile Acinetobacter strain, WCHA30T, was isolated from hospital sewage in West China Hospital of Sichuan University in Chengdu, south-western China. Strain WCHA30T was a non-spore-forming, catalase-positive, oxidase-negative, strictly aerobic coccobacillus. The DNA G+C content was 38 mol%. Phylogenetic analysis based on 16S rRNA, rpoB and gyrB gene sequences revealed that the strain was distinct from any previously described species of the genus Acinetobacter. Strain WCHA30T could be distinguished from all known Acinetobacter species by its ability to assimilate ß-alanine but not l-glutamate. Genotypic and phenotypic characteristics from this study indicate that strain WCHA30T should be considered to represent a novel species of the genus Acinetobacter, for which the name Acinetobacter defluvii sp. nov. is proposed. The type strain is WCHA30T (=CCTCC AB 2016203T=GDMCC 1.1101T=KCTC 52503T).

Expression and Purification of a Functional Porcine Soluble Triggering Receptor Expressed on Myeloid Cells 1.

Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a vital role in the pathogen-triggered amplification loop required for proinflammatory responses. Blockade of TREM-1 signaling may inhibit expansion of sepsis and prolong survival of animals. In the present study, the gene of porcine soluble TREM-1 was cloned and expressed in E. coli. After purification, the bioactivity of recombinant porcine soluble TREM-1 was tested in vitro on porcine alveolar macrophages. The results showed that supplementation with the recombinant porcine sTREM-1 protein rapidly and dose-dependently attenuated the upregulation of cytokines (IL-1ß, IL-2, IL-4, IL-8, IL-10, IL-12, IL-16, IL-18, and TNF-α) caused by LPS stimulation in the cultured porcine alveolar macrophages. These results indicate that the recombinant porcine sTREM-1 protein can prevent TREM-1-mediated hyperinflammatory responses after exposure to LPS.

Effects of sodium bicarbonate concentration on growth, photosynthesis, and carbonic anhydrase activity of macroalgae Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae (Gracilariales, Rhodophyta).

There is potential for bicarbonate to improve crop yields and economic efficiency of marine algae. However, few studies have focused on the effect of bicarbonate on the growth, photosynthesis, and enzyme activity associated with carbon utilization, especially in commercial macroalgae. Here, the addition of bicarbonate (up to 420 mg L(-1)) to macroalgal cultures has been evaluated for Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae with respect to growth rate, photosynthetic activity, carbonic anhydrase activity, and biochemical composition. The results showed that the effects of NaHCO3 on growth, chlorophyll a, phycoerythrin, photosynthetic oxygen evolution, photochemical parameters of PSI and PSII, carbonic anhydrase activity, and nitrogen content were significant (P < 0.05) and followed the same pattern in the three species. The parameter values were promoted in lower NaHCO3 concentrations (up to 252 or 336 mg L(-1)) and inhibited in higher NaHCO3 concentrations (>336 mg L(-1) for Gp. lemaneiformis and >420 mg L(-1) for the other two species). Moreover, species-specific differences induced by supplementation with bicarbonate were discovered during culture. Optimal concentrations of NaHCO3 used in this study were 252 mg L(-1) for Gp. lemaneiformis and 336 mg L(-1) for G. vermiculophylla and G. chouae. These results suggest that an adequate supplementation of sodium bicarbonate is a viable strategy for promoting growth and photosynthetic activity in some macroalgae as well as for improving biochemical composition. The study will help to accelerate the growth rate of algae and improve the quality of thalli, and will also be useful for enhancing the understanding of carbon utilization in macroalgae.

Anti-endotoxin and anti-inflammatory effects of Chinese herbal medicinal alkaloid ingredients in vivo.

The aim of the research was to investigate the anti-endotoxin and anti-inflammatory effects of sinomenine, fangchinoline, stachydrine, chuanxionggzine, oxymartrine, and evodiamine alkaloids commonly found in Chinese herbal medicines. In an endotoxin (LPS) control group, each mouse was challenged with 1 mg LPS/kg by intraperitoneal (IP) injection. In high-, middle- and low-dose alkaloid groups, mice were initially challenged with 1 mg LPS/kg by IP injection and, 3 h later, dosed intramuscularly (IM) with one of the six alkaloids at one of three levels (1, 5, or 10 mg/kg body weight). In the drug control group, mice were dosed IM with 10 mg/kg body weight of a given alkaloid; mice in a naïve control group were administered the same volume of normal saline. The results revealed the six alkaloids could reduce the incidence/severity of LPS- induced toxicities, e.g., body temperature elevation, weight loss, systemic inflammation, multiple organ dysfunction. Taken together, the data suggested to us that these alkaloids might effectively regulate inflammatory responses and have a potential to be used in anti-endotoxin therapies.

Chinese herbal medicinal ingredients affect secretion of NO, IL-10, ICAM-1 and IL-2 by endothelial cells.

The aim of this study was to investigate the anti-endotoxin effects of sinomenine, fangchinoline, stachydrine, chuanxionggzine, oxymartrine and evodiamine alkaloids commonly found in Chinese herbal medicines. Porcine endothelial cells were challenged with 1 µg LPS/ml for 3 h and then treated with one of the six alkaloids at three concentrations (1, 5 or 10 µg/ml) for a further 21 h. The supernatants of the cultures were then collected and analyzed for levels of nitric oxide (NO), interleukin (IL)-10, intercellular cell adhesion molecule-1 (ICAM-1) and IL-2 using ELISA kits. The results revealed that sinomenine, stachydrine and chuanxionggzine inhibited production of NO; stachydrine and evodiamine inhibited secretion of IL-10; sinomenine and chuanxionggzine down-regulated ICAM-1 expression; oxymartrine and evodiamine decreased production of IL-2 by the LPS-stimulated endothelial cells. Overall, the data from these studies suggested to us that these six alkaloids might effectively reduce inflammatory responses in situ via changes in the formation of these key regulatory molecules/proteins.

Predictive value of 18F-FDG PET/CT radiomics for EGFR mutation status in non-small cell lung cancer: a systematic review and meta-analysis.

Objective: This study aimed to evaluate the value of 18F-FDG PET/CT radiomics in predicting EGFR gene mutations in non-small cell lung cancer by meta-analysis. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and CNKI databases were searched from the earliest available date to June 30, 2023. The meta-analysis was performed using the Stata 15.0 software. The methodological quality and risk of bias of included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score criteria. The possible causes of heterogeneity were analyzed by meta-regression. Results: A total of 17 studies involving 3763 non-small cell lung cancer patients were finally included. We analyzed 17 training cohorts and 10 validation cohorts independently. Within the training cohort, the application of 18F-FDG PET/CT radiomics in predicting EGFR mutations in NSCLC demonstrated a sensitivity of 0.76 (95% CI: 0.70-0.81) and a specificity of 0.78 (95% CI: 0.74-0.82), accompanied by a positive likelihood ratio of 3.5 (95% CI:3.0-4.2), a negative likelihood ratio of 0.31 (95% CI: 0.24-0.39), a diagnostic odds ratio of 11.0 (95% CI: 8.0-16.0), and an area under the curve (AUC) of 0.84 (95% CI: 0.80-0.87). In the validation cohort, the values included a sensitivity of 0.76 (95% CI: 0.67-0.83), a specificity of 0.75 (95% CI: 0.68-0.80), a positive likelihood ratio of 3.0 (95% CI:2.4-3.8), a negative likelihood ratio of 0.32 (95% CI: 0.24-0.44), a diagnostic odds ratio of 9 (95% CI: 6-15), and an AUC of 0.82 (95% CI: 0.78-0.85). The average Radiomics Quality Score (RQS) across studies was 10.47 ± 4.72. Meta-regression analysis identifies the application of deep learning and regions as sources of heterogeneity. Conclusion: 18F-FDG PET/CT radiomics may be useful in predicting mutation status of the EGFR gene in non-small cell lung cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022385364.