Azo-Cyanamide Bridged Dinuclear Iron Complexes Exhibiting no Electronic Coupling but Moderate Magnetic Coupling between the two Iron Centers.

To investigate the effect of long-distance organic ligand on electronic coupling between metallic atoms, the mononuclear and dinuclear complexes [Cp(dppe)Fe(apc)] (1), [{Cp(dppe)Fe}2(µ-adpc)] (2), [{CpMe5(dppe)Fe}2(µ-adpc) (3) and their oxidized complexes [Cp(dppe)Fe(apc)][PF6] (1[PF6]), [{Cp(dppe)Fe}2(µ-adpc)][PF6] (2[PF6]2), [{CpMe5(dppe)Fe}2(µ-adpc)][PF6]2 (3[PF6]2) (Cp=1,3-cyclopentadiene, CpMe5=1,2,3,4,5-pentamethylcyclopentadiene, dppe=1,2-bis(diphenylphosphino)ethane), apc-=4-azo(phenylcyanamido)benzene and adpc2-=4,4'-azodi(phenylcyanamido)) were synthesized and characterized by cyclic voltammetry, UV-vis, single-crystal X-ray diffraction and Mössbauer spectra. Electrochemical measurements showed no electronic coupling between the two terminal Fe units, However, the investigation results of the magnetic properties of the two-electron oxidized complexes indicate the presence of moderate antiferromagnetic coupling across 18 Šdistance.

Characteristic activation pattern and network connectivity of prefrontal cortex in patients with type 2 diabetes mellitus and major depressive disorder during a verbal fluency task: A functional near-infrared spectroscopy study based on network-based statistic prediction.

INTRODUCTION: Type 2 diabetes (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction (NBS-predict) was adopted as data analysis method. RESULTS: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2MD and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: There was a distinctive activation pattern and network connectivity of the prefrontal cortex in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM.

Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from Cleistocalyx operculatus: A Synthetic Strategy Based on Biogenetic Building Blocks.

A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).

[Diagnosis and treatment of incomplete Kawasaki disease in children]. / å„¿ç«¥ä¸å®Œå ¨æ€§å·å´Žç— çš„è¯Šæ²».

Kawasaki disease (KD) is a febrile disease mainly observed in children aged <5 years, with medium- and small-vessel vasculitis as the main lesion. Although KD has been reported for more than 50 years and great progress has been made in the etiology and pathology of KD in recent years, there is still a lack of specific indicators for the early diagnosis of KD, especially with more difficulties in the diagnosis of incomplete Kawasaki disease (IKD). At present, there are no clear diagnostic criteria for IKD, which leads to the failure of the timely identification and standardized treatment of IKD in clinical practice and even induce the development of coronary artery lesion. This article reviews the concept, epidemiological features, diagnosis, treatment, and follow-up management of IKD, in order to deepen the understanding of IKD among clinical workers and help to improve the clinical diagnosis and treatment of KD in China.

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1.

AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.

Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

qSOFA predicted pneumonia mortality better than minor criteria and worse than CURB-65 with robust elements and higher convergence.

BACKGROUND: Limited data are available on the discriminatory capacity of quick sequential [sepsis-related] organ failure assessment (qSOFA) versus IDSA/ATS minor criteria for predicting mortality in patients with community-acquired pneumonia (CAP). METHODS: An observational prospective cohort study of 2116 patients with CAP was performed. Construct validity was determined using Cronbach α. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI). RESULTS: Overall in-hospital mortality was 6.43%. Mortality was 25.96% for patients with a qSOFA score of 2 or higher versus 3.05% for those with a qSOFA score less than 2 (odds ratio for mortality 6.57, P < 0.0001), and 13.85% for patients with at least 3 minor criteria versus 2.03% for those with 2 or fewer minor criteria (odds ratio for mortality 2.27, P < 0.0001). qSOFA had a higher correlation with mortality than minor criteria, as well as higher internal consistency (Cronbach alpha 0.43 versus 0.14) and diagnostic values of individual elements (larger AUROCs and higher Youden's indices). qSOFA ≥2 was less sensitive but more specific for predicting mortality than ≥3 minor criteria (qSOFA sensitivity 59.6%, specificity 88.3% and positive likelihood ratio 5.11 versus ≥3 minor criteria sensitivity 80.1%, specificity 65.8% and positive likelihood ratio 2.34). The predictive validity of qSOFA was good for mortality (AUROC = 0.868), was statistically greater than minor criteria, was equal to pneumonia severity index, and was inferior compared with CURB-65 (AUROC, 0.824, 0.902, 0.919; NRI, 0.088, -0.068, -0.103; respectively). CONCLUSIONS: The qSOFA predicted mortality in CAP better than IDSA/ATS minor criteria and worse than CURB-65 with robust elements and higher convergence. qSOFA as a bedside prompt might be positioned as a proxy for minor criteria and increase the recognition and thus merit more appropriate management of CAP patients likely to fare poorly, which might have implications for more accurate clinical triage decisions.

In-hospital mortality and SpO2 incritical care patients with cerebral injury: data from the MIMIC­IV Database.

BACKGROUND: Evidence regarding the relationship between in-hospital mortality and SpO2 was low oxygen saturations are often thought to be harmful, new research in patients with brain damage has found that high oxygen saturation actually enhances mortality. However, there is currently no clear study to point out the appropriate range for oxygen saturation in patients with craniocerebral diseases.  METHODS: By screening all patients in the MIMIC IV database, 3823 patients with craniocerebral diseases (according to ICD-9 codes and ICD-10) were selected, and non-linear regression was used to analyze the relationship between in-hospital mortality and oxygen saturation. Covariates for all patients included age, weight, diagnosis, duration of ICU stay, duration of oxygen therapy, etc. RESULTS: In-hospital mortality in patients with TBI and SAH was kept to a minimum when oxygen saturation was in the 94-96 range. And in all patients, the relationship between oxygen saturation and in-hospital mortality was U-shaped. Subgroup analysis of the relationship between oxygen saturation and mortality in patients with metabolic encephalopathy and other encephalopathy also draws similar conclusions In-hospital mortality and oxygen saturation were all U-shaped in patients with subarachnoid hemorrhage, metabolic and toxic encephalopathy, cerebral infarction, and other encephalopathy, but the nonlinear regression was statistically significant only in patients with cerebral infarction (p for nonlinearity = 0.002). CONCLUSION: Focusing too much on the lower limit of oxygen saturation and ignoring too high oxygen saturation can also lead to increase in-hospital mortality. For patients with TBI and SAH, maintaining oxygen saturation at 94-96% will minimize the in-hospital mortality of patients.

[Anti-tumor effect of Huaier extract supernatant on human gastric cancer HGC-27 and MGC-803 cells].

The purpose of this study was to investigate the effect of Huaier extract supernatant(HES) on the proliferation, apoptosis, autophagy, and migration of human gastric cancer HGC-27 and MGC-803 cells and its molecular mechanisms. The main components in HES were preliminarily analyzed by high-performance liquid chromatography-mass spectrometry(HPLC-MS). Methyl thiazolyl tetrazolium(MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine(EdU) staining assay were used to explore the effect of HES on the proliferation of human gastric cancer HGC-27 and MGC-803 cells. Hoechst staining and flow cytometry assay were used to determine the effect of HES on apoptosis of human gastric cancer HGC-27 and MGC-803 cells. Acridine orange staining and cell scratch assay were used to determine the effect of HES on autophagy and migration of human gastric cancer HGC-27 and MGC-803 cells, respectively. Western blot was used to investigate the regulatory effect of HES on the expression levels of proteins related to apoptosis, epithelial-mesenchymal transition(EMT), and signaling pathways in human gastric cancer HGC-27 and MGC-803 cells. The results showed that HES mainly contained some components with high polarities. HES significantly reduced the cell viability of human gastric cancer cells in a dose-and time-dependent manner. The IC_(50 )values after 48 h of HES treatment in human gastric cancer HGC-27 and MGC-803 cells were 7.56 and 10.77 g·L~(-1), respectively. Meanwhile, HES inhibited the colony-forming ability and short-term proliferation of human gastric cancer cells. The apoptosis rates of HGC-27 and MGC-803 cells treated with 8 g·L~(-1) HES for 72 h were 62.13%±8.92% and 54.50%±3.26%, respectively. HES also promoted autophagy in human gastric cancer cells and impaired their migration ability in vitro. Moreover, HES up-regulated the cleavage of the apoptosis marker poly ADP-ribose polymerase(PARP) and the protein expression level of the epithelial cell marker E-cadherin, and down-regulated the protein levels of phosphorylated-mammalian target of rapamycin(p-mTOR), phosphorylated-S6(p-S6), and phosphorylated-extracellular signal-regulated kinase(p-ERK) in human gastric cancer cells. Therefore, HES is one of the effective anti-tumor components of Huaier, which inhibits the proliferation and migration of human gastric cancer cells, and induces apoptosis and autophagy. Moreover, the mTOR signal and ERK signal may be involved in the anti-gastric cancer effect of HES. This study provides novel references for the in-depth research and clinical application of Huaier. It is also of great significance to promote the scientific development and utilization of Huaier.

[Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease]. / å·å´Žç— æ€¥æ€§æœŸè‚æŸå®³ä¸Žå† çŠ¶åŠ¨è„‰æŸä¼¤å’Œå ç–«çƒè›‹ç™½æ— ååº”çš„å ³ç³».

OBJECTIVES: To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. METHODS: The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. RESULTS: Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). CONCLUSIONS: Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.

The study of 9,10-dihydroacridine derivatives as a new and effective molecular scaffold for antibacterial agent development.

The emergence of worldwide spreading drug-resistant bacteria has been a serious threat to public health during the past decades. The development of new and effective antibacterial agents to address this critical issue is an urgent action. In the present study, we investigated the antibacterial activity of two 9,10-dihydroacridine derivatives and their mechanism. Both compounds were found possessing strong antibacterial activity against some selected Gram-positive bacteria including MRSA, VISA and VRE. The biological study suggests that the compounds promoted FtsZ polymerization and also disrupted Z-ring formation at the dividing site and consequently, the bacterial cell division is interrupted and causing cell death.

A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers with high mortality and poor prognosis, and the investigation on new approaches and effective drugs for HCC therapy is of great significance. In our study, we demonstrate that treatment with cinobufagin, a natural compound isolated from traditional chinese medicine Chansu, reduces proliferation and the colony formation capacity of the human hepatoma cells in vitro, in addition, cinobufagin induces mitotic arrest in human hepatoma cells. The results of a network pharmacology-based analysis show that EGFR, MAPK1, PTK2, CDK2, MAPK3, ESR1, CDK1, PRKCA, AR, and CSNK2A1 are the key targets involved in the anti-tumor activities of cinobufagin, additionally, several signaling pathways such as proteoglycans in cancer, pathways in cancer, HIF-1 signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and PI3K-AKT signaling pathway are identified as the potential pathways involved in the inhibitory effects of cinobufagin against HCC. Furthermore, at the molecular level, we find that cinobufagin decreases EGFR expression and CDK2 activity in human hepatoma cells. Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells. We also demonstrate that EGFR positively regulates CDK2 expression. Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells. Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC.

Pestalotiopsis trachicarpicola, a novel pathogen causes twig blight of Pinus bungeana (Pinaceae: Pinoideae) in China.

Pinus bungeana is one of indigenous trees in China and widely distributed in poor and arid regions for vegetation and industrial woody use. However, since a high-incidence disease threatens the growth of mature P. bungeana tree in the garden and in the plantation every year, the overwintering shoots were infected and died in the next spring with a ratio over 70%, but the cause was beyond understood. A total of 120 fungal isolates were separated from symptomatic twigs by histological isolation methods, including Pestalotiopsis spp., Fusarium spp., Trichothecium spp., Penicillium and some unknown fungal species. Pestalotiopsis spp. was dominant, accounting for 85%. Morphological observation under microcopy showed all Pestalotiopsis species are identical, and six isolations among them were randomly selected for pathogenicity tests. Fulfilling Koch's postulates showed that all six isolates of Pestalotiopsis spp. were pathogens of twig blight, causing the same symptoms as observed in the field, while other non-Pestalotiopsis isolates were avirulent to P. bungeana twigs. Multi-gene (ITS, tub2 and TEF1) analysis and morphological observation revealed that all the six Pestalotiopsis isolates belonged to P. trachicarpicola. To our knowledge, this is the first study reporting P. trachicarpicola as the pathogens responsible for P. bungeana twig blight in China.

[Research progress on anti-tumor effect of Chinese dragon's blood].

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.

Weighted Epworth sleepiness scale predicted the apnea-hypopnea index better.

BACKGROUND: The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS items to develop a weighted ESS scoring system improve the accuracy of the AHI prediction? It is warranted to explore the intriguing hypotheses. METHODS: Seven hundred fifty-six adult patients with suspicion of obstructive sleep apnoea syndrome (OSAS) were prospectively recruited to a derivation cohort. This was tested against a prospective validation cohort of 810 adult patients with suspected OSAS. Each ESS item's increased odds ratio for the corresponding AHI was calculated using univariate logistic regression. The receiver operating characteristic curves were created and the areas under the curves (AUCs) were calculated to illustrate and compare the accuracy of the indices. RESULTS: The higher the ESS item-score, the closer the relationship with the corresponding AHI. The odds ratios decreased as a result of the increased AHI. The ESS items were of unequal weight in predicting the corresponding AHI and a weighted ESS was developed. The coincidence rates with the corresponding AHI, body mass indices, and neck circumferences rose as the scores increased, whereas nocturnal nadir oxygen saturations decreased, and the weighted ESS was more strongly associated with these indices, compared with the ESS. The capability in predicting the patients without OSAS or with severe OSAS was strong, especially the latter, and the weighted ESS orchestrated manifest improvement in screening the patients with simple snoring. The patterns of sensitivities, specificities, and Youden's indices of the four ranks of weighted ESS for predicting the corresponding AHI were better than those of the ESS, and the AUCs of weighted ESS were greater than the corresponding areas of ESS in the two cohorts. CONCLUSIONS: The weighted ESS orchestrated significant improvement in predicting the AHI, indicating that the capability in predicting the patients without OSAS or with severe OSAS was strong, which might have implications for clinical triage decisions to prioritize patients for polysomnography.

Cold-inducible RNA-binding protein might determine the severity and the presences of major/minor criteria for severe community-acquired pneumonia and best predicted mortality.

BACKGROUND: Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis. METHODS: A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices. RESULTS: Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices. CONCLUSIONS: CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.

Sensory nerves protect from the progression of early stage osteoarthritis in mice.

PURPOSE: Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice. MATERIALS AND METHODS: OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression. RESULTS: Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group. CONCLUSIONS: Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

Association of ABCB1 polymorphisms with lipid homeostasis and liver injury response to atorvastatin in the Chinese population.

The present research was to assess the relationship between ABCB1 (G2677T/A, C3435T) polymorphisms and lipid homeostasis as well as risk of liver injury induced by atorvastatin in in-patients from China. The lipid levels (total cholesterol, high-density lipoprotein, triglycerides) as well as metabolic enzymes of hepar (glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, alkaline phosphatase, γ-glutamyl transpeptidase) in plasma for 162 patients were measured at baseline and after approximately 6 months of atorvastatin treatment. Polymorphisms of the ABCB1 gene were determined using the Snapshot technique. The associations between genetic polymorphisms and lipid levels as well as hepar indexes were evaluated at the end of medical treatment. Based on one-way ANOVA analysis, patients with the 2677GG or 3435TT genotypes showed a remarkable decrease in percentage when the level of TC was above 4.00 mmol·L-1, separately (P < 0.05). There was a significant decrease in percentage in the frequency of patients with the 2677GG genotype (low-density lipoprotein > 2.00 mmol·L-1) (P < 0.05). The level of glutamic-pyruvic transaminase in patients with the 2677GG or 3435CC genotype displayed a significantly increase in percentage, respectively (P < 0.05). The ABCB1 G-C haplotype carriers were associated with an increased risk of AILI. The results provide evidence for clinically individualised utilisation of atorvastatin for lipid homeostasis as well as risk of induced liver injury in the Chinese population.

Development of a Rapid Approach for Detecting Sharp Eyespot Resistance in Seedling-Stage Wheat and Its Application in Chinese Wheat Cultivars.

Sharp eyespot, caused by Rhizoctonia cerealis, has become one of the most severe diseases affecting global wheat production in recent decades. Quick and efficient screening methods are required to accelerate the development of cultivars for sharp eyespot resistance in wheat breeding. Here, a two-step colonized wheat kernels (TSCWK) method for the inoculation and classification of sharp eyespot resistance in seedlings was established in a greenhouse. After preliminary verification of the reliability of the method in two replicates, 196 wheat cultivars were assessed for sharp eyespot resistance, and significant correlations were identified among the four replicates (r = 0.78 to 0.84; P < 0.01). Furthermore, the 196 cultivars were scored for sharp eyespot resistance at the milk-ripe stage using traditional toothpick inoculation in the field. Correlation and linear regression analysis showed that the application of this approach at the seedling stage showed good consistency with the traditional field method. Moreover, the scoring of 442 cultivars using the TSCWK method indicated that most cultivars from the Huanghuai valley were susceptible to R. cerealis, suggesting an urgent need to improve sharp eyespot resistance in this region. Additionally, the relative resistance index of sharp eyespot decreased in the surveyed cultivars of the region with time. This study offers a rapid and effective approach for the identification of wheat sharp eyespot resistance and provides valuable germplasm for improving sharp eyespot resistance in wheat breeding.

[Effect of Huaier aqueous extract on growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms].

This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.