Application of non-mydriatic fundus photography-assisted telemedicine in diabetic retinopathy screening.

BACKGROUND: Early screening and accurate staging of diabetic retinopathy (DR) can reduce blindness risk in type 2 diabetes patients. DR's complex pathogenesis involves many factors, making ophthalmologist screening alone insufficient for prevention and treatment. Often, endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early intervention. AIM: To explore the efficacy of non-mydriatic fundus photography (NMFP)-enhanced telemedicine in assessing DR and its various stages. METHODS: This retrospective study incorporated findings from an analysis of 93 diabetic patients, examining both NMFP-assisted telemedicine and fundus fluorescein angiography (FFA). It focused on assessing the concordance in DR detection between these two methodologies. Additionally, receiver operating characteristic (ROC) curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine, using FFA outcomes as the standard benchmark. RESULTS: In the context of DR diagnosis and staging, the kappa coefficients for NMFP-assisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively, indicating substantial intermethod agreement. Moreover, the NMFP-assisted telemedicine's predictive accuracy for positive FFA outcomes, as denoted by the area under the ROC curve, was remarkably high at 0.955, within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than 0.001. This predictive model exhibited a specificity of 100%, a sensitivity of 90.9%, and a Youden index of 0.909. CONCLUSION: NMFP-assisted telemedicine represents a pragmatic, objective, and precise modality for fundus examination, particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic patients. Its implementation in these scenarios is of paramount significance, enhancing the clinical accuracy in the diagnosis and therapeutic management of DR. This methodology not only streamlines patient evaluation but also contributes substantially to the optimization of clinical outcomes in DR management.

Nickel-Catalyzed Enantioselective Dearomative Heck-Reductive Allylic Defluorination Reaction of Indoles.

Herein, we describe a nickel-catalyzed asymmetric dearomative aryl-difluoroallylation reaction of indoles with α-trifluoromethyl alkenes as an electrophilic coupling partner. The reaction proceeds via a cascade sequence involving dearomative Heck cyclization and reductive allylic defluorination. A series of gem-difluoroallyl substituted indolines are obtained in moderate to good yields (36-77% yield) with excellent enantioselectivity (up to 99% ee). The reaction features broad functional group tolerance, scaled-up synthesis, and late-stage diversification.

Association between DRD2/ANKK1 rs1800497 C > T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis.

Background: Previous studies have suggested that the DRD2/ANKK1 rs1800497 C > T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C > T polymorphism and PTSD risk. Materials and methods: A total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. Result: Overall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14-2.62, P = 0.01, I2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis. Conclusion: Current evidence suggests that the DRD2/ANKK1 rs1800497 C > T polymorphism may contribute to PTSD susceptibility.

Benzenesulfonyl thiazoloimines as unique multitargeting antibacterial agents towards Enterococcus faecalis.

New efficient antimicrobial agents are urgently needed to combat invasive multidrug-resistant pathogens infections. Structurally unique benzenesulfonyl thiazoloimines (BSTIs) were exploited as novel potential antibacterial victors to confront terrific drug resistance. Some developed BSTIs exerted effectively antimicrobial efficacy against the tested strains. Notably, 2-pyridyl BSTI 14d exhibited good antibacterial activity against E. faecalis with MIC value of 1 µg/mL, which was superior to sulfathiazole and norfloxacin. The most active compound 14d not only showed rapid bactericidal properties and impeded E. faecalis biofilm formation to effectually relieve the development of drug resistance, but also performed low toxicity toward human red blood cells, human normal squamous epithelial cells and human non-neoplastic colon epithelial cells. Mechanistic investigation demonstrated that molecule 14d could exert efficient membrane destruction leading to the leakage of intracellular materials and metabolism inhibition, cause oxidative damage of E. faecalis through accumulation of excess reactive oxygen species and reduction of glutathione activity, and intercalate into DNA to hinder replication of DNA. Molecular docking indicated that the formation of 14d-dihydrofolate synthetase supramolecular complex could hinder the function of this enzyme. ADME analysis displayed that compound 14d possessed promising pharmacokinetic properties. These findings suggested that the newly developed benzenesulfonyl thiazoloimines with multitargeting antibacterial potential provided a new possibility for evading resistance.

Liver transplantation for giant hemangioma of the liver: A case report and review of the literature.

Large benign hepatic masses as a rare indication for liver transplantation have been reported less frequently. These liver transplantations are complex, with high intraoperative bleeding, high perioperative complication rates, and high mortality rates due to difficulties in visualization, especially when they have undergone various percutaneous operations or open surgery, resulting in severe perihepatic adhesions. Here is a case report of a patient admitted to our hospital who underwent liver transplantation after suffering from a giant hemangioma in liver transplantation for 10 years and who had received multiple interventional treatments ineffective in the past.

Prognostic value of CD247 in patients with head and neck squamous cell carcinoma: bioinformatic analysis of TCGA database.

Background: Head and neck squamous cell carcinoma (HNSC) is the 7th most common type of cancer in the world. Through the advantages of The Cancer Genome Atlas (TCGA) large-scale sequencing-based genome analysis technology, we can explore the potential molecular mechanisms that can improve the prognosis of HNSC patients. Methods: The HNSC transcriptome and clinical data were downloaded from TCGA database. A univariate survival analysis and differential expression analysis were conducted to obtain the intersection gene set. A protein-protein interaction (PPI) analysis, modular analysis, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were then conducted to identify the hub genes. Clinical correlation analysis, univariate and multivariate Cox regression analyses were performed on the identified hub genes to determine the prognostic impact of hub genes on HNSC patients. Results: In total, 601 intersecting gene sets were obtained. A modular analysis was conducted, and the highest scoring module was 19.304. Based on the GO/KEGG enrichment analysis results, CD247 molecule (CD247) was ultimately selected as the gene for this study. The CD247 were divided into a high-expression group and a low-expression group. The Kaplan-Meier survival curve analysis showed that there was a significant difference between the 2 groups (P<0.0001). The median survival time of the low-expression CD247 group was 30.9 months, and the 5-year survival rate was 36.4%. While the median survival time of the high-expression CD247 group was 68.8 months, and the 5-year survival rate was 52.3%. The clinical correlation analysis showed that CD247 was significantly negatively correlated with pathological tumor stage (pT) and pathological nodal extracapsular spread. Gene Set Enrichment Analysis (GSEA) showed that CD247 activating KEGG pathway hsa04650 and hsa04660. Conclusions: CD247 is an independent protective factor in the prognosis of HNSC patients. By activating the hsa04650 and hsa04660 pathways, the expression of interferon gamma, interleukin (IL)-2, and IL-10 is promoted, which in turn improves the tumor immune monitoring ability of the body, induces tumor cell apoptosis, and inhibits tumor cell growth. CD247 is a potential target for improving the clinical treatment effect of HNSC and the prognosis of patients.

Naringenin regulates gut microbiota and SIRT1/ PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome.

PURPOSE: To evaluate the effect of naringenin on improving PCOS and explore the mechanism. METHODS: Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1ɑ, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested. RESULTS: By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1ɑ, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated. CONCLUSION: Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1ɑ signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.

[Clinical Observation of Recombinant Bovine Basic Fibroblast Growth Factor as an Adjuvant Therapy for Patients with Atrophic Acne Scar].

Objective To study the influence of recombinant bovine basic fibroblast growth factor as an adjuvant therapy on scar alleviation and inflammatory cytokines in patients with atrophic acne scar. Methods The random number table was employed to randomly assign 120 patients with atrophic acne scar into a test group and a control group.Both groups of patients were treated with CO2 lattice laser.After the operation,the control group was routinely smeared with erythromycin ointment and the test group was coated with recombinant bovine basic fibroblast growth factor gel.The clinical efficacy,clinical indicators,scar alleviation,and inflammatory cytokine levels before and after treatment were compared,and adverse reactions were counted. Results The test group had higher total effective rate(P=0.040) and lower total incidence of adverse reactions(P=0.028) than the control group.Compared with the control group,the test group showcased short erythema duration after treatment(P=0.025),early scab forming(P=0.002),and early edema regression(P<0.001).After treatment,the proportion of grade 1 scars graded by Goodman and Baron's acne scar grading system in the test group and control group increased(P=0.001,P=0.027),and the proportion of grade 4 scars decreased(P<0.001,P=0.034).Moreover,the proportion of grade 1 scars in the test group was higher than that in the control group(P=0.031) after treatment,and the proportion of grade 4 scars presented an opposite trend(P=0.031).After treatment,the levels of tumor necrosis factor-α(TNF-α) and interleukin-1ß(IL-1ß) in both groups declined(all P<0.001),and the test group had lower TNF-α and IL-1ß levels than the control group(all P<0.001). Conclusion The recombinant bovine basic fibroblast growth factor gel as an adjuvant therapy of CO2 lattice laser can effectively alleviate the atrophic acne scar,relieve local inflammatory reaction,and has good curative effect and less adverse reactions.

Effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants: a Meta analysis. / é¢„é˜²æ€§ä½¿ç”¨æ°´è§£è›‹ç™½é æ–¹å¥¶å¯¹æ—©äº§å„¿èƒƒè‚ é“ç–¾ç— åŠä½“æ ¼ç”Ÿé•¿å½±å“çš„Meta分析.

OBJECTIVES: To systematically evaluate the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical development in preterm infants. METHODS: A computerized search was performed in the databases including China National Knowledge Infrastructure, Wanfang Data, Weipu, PubMed, Embase, and the Cochrane Library to identify randomized controlled trials of the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants. RevMan 5.3 software was used to perform a Meta analysis for the included studies. RESULTS: A total of 7 randomized controlled studies were included. The results of Meta analysis showed that compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula could reduce the risk of neonatal necrotizing enterocolitis (RR=0.40, P=0.04) and feeding intolerance (RR=0.40, P=0.005), and had no significant effect on the growth of weight, length and head circumference (P>0.05). CONCLUSIONS: Compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula in preterm infants may reduce the occurrence of necrotizing enterocolitis and feeding intolerance, and can meet the nutrient requirement of physical development. However, the evidence is limited, and the results of this study cannot support the routine prophylactic use of hydrolyzed protein formula in preterm infants.

Near work, screen time, outdoor time and myopia in schoolchildren in the Sunflower Myopia AEEC Consortium.

PURPOSE: To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC). METHODS: We analysed AEEC cross-sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population-based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL. RESULTS: Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was -0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11-1.24), more total near work (OR = 1.05; 95% CI, 1.02-1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75-0.88) were associated with myopia (p's < 0.05). These factors were similarly associated with SE and AL (p's < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83). CONCLUSION: In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.

Characterization of a novel cysteine protease in Trichinella spiralis and its role in larval intrusion, development and fecundity.

The aim of this study was to investigate the biological properties of a novel gut-specific cysteine protease in Trichinella spiralis (TsGSCP) and its role in larval intrusion, development and fecundity. TsGSCP has a functional C1 peptidase domain; C1 peptidase belongs to cathepsin B family. The TsGSCP gene cloned and expressed in Escherichia coli BL21 showed intensive immunogenicity. qPCR and Western blotting revealed that TsGSCP mRNA and protein were expressed at various T. spiralis stages, but their expression levels in intestinal infectious larvae (IIL) were clearly higher than those in muscle larvae (ML), adult worms (AWs) and new-born larvae (NBL). Indirect immunofluorescence (IIF) analysis showed that TsGSCP was primarily located at the outer cuticle and the intrauterine embryos of this parasite. rTsGSCP showed the ability to specifically bind with IECs, and the binding site is within the IEC cytoplasm. rTsGSCP accelerated larval intrusion into host intestinal epithelial cells (IECs), whereas anti-rTsGSCP antibodies suppressed larval intrusion; the acceleration and suppression was induced by rTsGSCP and anti-rTsGSCP antibodies, respectively, in a dose-dependent manner. When ML were transfected with TsGSCP-specific dsRNA, TsGSCP expression and enzymatic activity were reduced by 46.82 and 37.39%, respectively, and the capacity of the larvae to intrude into IECs was also obviously impeded. Intestinal AW burden and adult female length and fecundity were significantly decreased in the group of mice infected with dsRNA-transfected ML compared to the control dsRNA and PBS groups. The results showed that TsGSCP plays a principal role in gut intrusion, worm development and fecundity in the T. spiralis lifecycle and might be a candidate target for vaccine development against Trichinella intrusion and infection.

Simultaneous quantification of 24 aldehydes and ketones in oysters (Crassostrea gigas) with different thermal processing procedures by HPLC-electrospray tandem mass spectrometry.

Aldehydes and ketones are secondary oxidation products resulting from lipid oxidation that occurs during food processing. These small molecule compounds not only have an impact on the quality, odor and flavor of food, but also play a role in the pathogenesis of many human diseases. In this study, a HPLC-MS/MS analytical method was developed and validated for the simultaneous determination of 24 aldehydes and ketones. The coefficients of determination (R2) for all aldehydes and ketones were higher than 0.9975 at the range of 0.2-2000 ng/mL. The recoveries were in the range 71.20-108.13% with RSD < 10%. The method was tested by analyzing lipids from oysters with different thermal processing (boiling, frying, roasting and air frying) procedures; the highest concentration for saturated aldehydes and ketones while the highest content of unsaturated aldehydes in boiling treatment. Meanwhile, fatty acid oxidative decomposition was in agreement with aldehydes and ketones formation. Moreover, principal component analysis, orthogonal partial least-squares discriminant analysis and variable importance in projection value showed that lipid oxidation is positively related to the formation of a variety of aldehydes and ketones.

A facile reaction to access novel structural sulfonyl-hybridized imidazolyl ethanols as potential DNA-targeting antibacterial agents.

A novel type of sulfonyl-hybridized imidazolyl ethanols as potential DNA-targeting antibacterial agents was constructed via the unique ring-opened reaction of oxiranes by imidazoles for the first time. Some developed target hybrids showed potential antimicrobial potency against the tested microbes. Especially, imidazole derivative 5f could strongly suppressed the growth of MRSA (MIC = 4 µg/mL), which was 2-fold and 16-fold more potent than the positive control sulfathiazole and norfloxacin. This compound exhibited quite low propensity to induce bacterial resistance. Antibacterial mechanism exploration indicated that compound 5f could embed in MRSA DNA to form steady 5f-DNA complex, which possibly hinder DNA replication to exert antimicrobial behavior. Molecular docking showed that molecule 5f could bind with dihydrofolate synthetase through hydrogen bonds. These results implied that imidazole derivative 5f could be served as a promising molecule for the exploration of novel antibacterial candidates.

Nomogram Model for Predicting the Risk of Multidrug-Resistant Bacteria Infection in Diabetic Foot Patients.

OBJECTIVE: This study established an individualized nomogram for predicting the risk of multidrug-resistant bacterial (MDRB) infection in patients with the diabetic foot (DF), and providing a reference for clinical prevention and treatment. METHODS: A total of 199 DF patients admitted to the hospital from July 2015 to December 2018 were included in this study. The pathogenic bacteria at the site of infection were detected and the factors affecting the occurrence of MDRB infection in DF patients summarized. The R software was used to draw the nomogram, and the Bootstrap Method used to internally verify the model. The calibration curve and the Harrell's Concordance Index (C-index) were used to evaluate the predictive effect of the nomogram model. RESULTS: Logistic regression analysis showed that age, course of diabetes, previous use of antibacterial drugs, types of antibacterial drugs, and osteoporosis were risk factors for multidrug-resistant infections in DF (P<0.05). The area under the receiver operating characteristic curve (AUC, Area Under Curve) of the nomogram model after internal verification was 0.773 (95% CI: 0.704-0.830). The mean absolute error between the predicted probability of infection in the nomogram and the actual occurrence of MDRB was 0.032, indicating that the nomogram model had good forecasting efficiency and stability. CONCLUSION: The risk factors for multidrug-resistant infections in DF are age, course of diabetes, previous use of antibacterial drugs, types of antibacterial drugs used, and osteoporosis. The nomogram model drawn on these risk factors has good predictive accuracy and can assist medical staff in formulating targeted infection prevention strategies for patients.

The Impact of Weather and Air Pollution on Viral Infection and Disease Outcome Among Pediatric Pneumonia Patients in Chongqing, China, from 2009 to 2018: A Prospective Observational Study.

BACKGROUND: For pediatric pneumonia, the meteorological and air pollution indicators have been frequently investigated for their association with viral circulation but not for their impact on disease severity. METHODS: We performed a 10-year prospective, observational study in 1 hospital in Chongqing, China, to recruit children with pneumonia. Eight commonly seen respiratory viruses were tested. Autoregressive distributed lag (ADL) and random forest (RF) models were used to fit monthly detection rates of each virus at the population level and to predict the possibility of severe pneumonia at the individual level, respectively. RESULTS: Between 2009 and 2018, 6611 pediatric pneumonia patients were included, and 4846 (73.3%) tested positive for at least 1 respiratory virus. The patient median age was 9 months (interquartile range, 4‒20). ADL models demonstrated a decent fitting of detection rates of R2 > 0.7 for respiratory syncytial virus, human rhinovirus, parainfluenza virus, and human metapneumovirus. Based on the RF models, the area under the curve for host-related factors alone was 0.88 (95% confidence interval [CI], .87‒.89) and 0.86 (95% CI, .85‒.88) for meteorological and air pollution indicators alone and 0.62 (95% CI, .60‒.63) for viral infections alone. The final model indicated that 9 weather and air pollution indicators were important determinants of severe pneumonia, with a relative contribution of 62.53%, which is significantly higher than respiratory viral infections (7.36%). CONCLUSIONS: Meteorological and air pollution predictors contributed more to severe pneumonia in children than did respiratory viruses. These meteorological data could help predict times when children would be at increased risk for severe pneumonia and when interventions, such as reducing outdoor activities, may be warranted.

Characterization of a Trichinella spiralis cathepsin X and its promotion for the larval invasion of mouse intestinal epithelial cells.

The aim of this study was to ascertain the characteristics of a Trichinella spiralis cathepsin X (TsCX) and its role on larval invasion of intestinal epithelial cells (IECs). The full-length of TsCX cDNA sequence was cloned and expressed in Escherichia coli BL21. The results of RT-PCR, IFA and Western blot revealed that TsCX was expressed at T. spiralis muscle larvae (ML), intestinal infective larvae, adult worm and newborn larvae, and it was located in whole worm section. The results of Far western and confocal microscopy demonstrated that there was a specific binding of rTsCX and IEC, and the binding site was located within the IEC cytoplasm. rTsCX promoted T. spiralis larval invasion of mouse IECs while anti-rTsCX antibody inhibited larval invasion into the IECs. Silencing TsCX by specific siRNA reduced the TsCX expression and larval invasive capacity. These results indicated that TsCX specifically binds to IECs and promotes larval invasion of intestinal epithelia, and it might be a potential target of vaccines against enteral stages of T. spiralis.

Association Between the Aldehyde Dehydrogenase-2 rs671 G>A Polymorphism and Head and Neck Cancer Susceptibility: A Meta-Analysis in East Asians.

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk. METHODS: A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power. RESULTS: Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I2  = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I2  = 81.9%). CONCLUSIONS: In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians.

Correlation between thrombocytopenia and host response in severe fever with thrombocytopenia syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.

An unexpected discovery toward novel membrane active sulfonyl thiazoles as potential MRSA DNA intercalators.

Aim: With the increasing emergence of drug-resistant bacteria, the need for new antimicrobial agents has become extremely urgent. This work was to develop sulfonyl thiazoles as potential antibacterial agents. Results & methodology: Novel hybrids of sulfonyl thiazoles were developed from commercial acetanilide and acetylthiazole. Hybrids 6e and 6f displayed excellent inhibitory efficacy against clinical methicillin-resistant Staphylococcus aureus (MRSA) (minimum inhibitory concentration = 1 µg/ml) without obvious toxicity toward normal mammalian cells (RAW 264.7). The combination uses were found to improve the antimicrobial ability. Further preliminary antibacterial mechanism experiments showed that the active molecule 6f could effectively interfere with MRSA membrane and insert into MRSA DNA. Conclusion: Compounds 6e and 6f could serve as potential DNA-targeting templates toward the development of promising antimicrobial agents.

Association between the pri-miR-26a-1 rs7372209 C>T polymorphism and cancer susceptibility: multivariate analysis and trial sequential analysis.

MiR-26 has been suggested to play a tumor-suppressive role in cancer development, which could be influenced by the mutate pri-miR-26ª-1. Molecular epidemiological studies have demonstrated some inconsistent associations between pri-miR-26ª-1 rs7372209 C>T polymorphism and cancer risk. We therefore performed this meta-analysis with multivariate statistic method to comprehensively evaluate the associations between rs7372209 C>T polymorphism and cancer risk. Eleven publications involving 6,709 patients and 6,514 controls were identified. Multivariate analysis indicated that the over-dominant genetic model was most likely. Pooled results indicated no significant association in the overall population (CC+TT vs. CT: OR=1.08, 95%CI=0.96-1.22, P=0.20, I2=54.4%), as well as the subgroup analysis according to ethnicity, control source, tumor locations, and HWE status of controls. In addition, heterogeneity, accumulative, sensitivity analysis, publication bias and trial sequential analysis (TSA) were conducted to test the statistical power. Overall, our results indicated that the pri-miR-26a-1 rs7372209 C>T polymorphism may not be a potential risk for cancer development.