Diagnostic value of bronchoalveolar lavage fluid galactomannan assay for invasive pulmonary aspergillosis in adults: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: To analyse the diagnostic accuracy of bronchoalveolar lavage fluid galactomannan (BALF-GM) assay for invasive pulmonary aspergillosis (IPA) in adults to determine the optimal diagnostic cut-off by meta-analysis. METHODS: PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI), and China Wanfang databases were searched to collect relevant studies on the diagnostic value of BALF-GM for IPA from inception to March 2022. The summary receiver operating characteristic (SROC) curve was drawn to determine the optimal diagnostic cut-off. RESULTS AND DISCUSSION: Nineteen articles (56 data sets) were included. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79 (95% CI: 0.72-0.84), 0.92 (95% CI: 0.88-0.94), 9.25 (95% CI: 6.84-12.52), 0.23 (95% CI: 0.18-0.30), 39.44 (95% CI: 29.55-52.65), and 0.92 (95% CI: 0.90-0.94), respectively. The area under the curves (AUCs) were 0.92, 0.86, 0.93, 0.89, 0.88, and 0.94 when the cut-off values were 0.5, 0.8, 1.0, 1.5, 2.0, and 3.0, respectively. Sixteen studies were included in the combined analysis when the cut-off value was 0.5. The results showed that the pooled sensitivity, specificity, PLR, NLR and DOR of BALF-GM (cut-off 0.5) for the diagnosis of IPA were 0.89 (95% CI: 0.83-0.93), 0.79 (95% CI: 0.71-0.86), 4.33 (95% CI: 3.04-6.16), 0.14 (95% CI: 0.09-0.22), and 31.51 (95% CI: 17.43-56.98). The AUC was 0.92 (95% CI: 0.89-0.94). WHAT IS NEW AND CONCLUSIONS: BALF-GM has excellent diagnostic accuracy for adult IPA, which can be diagnosed early and treated early to reduce the mortality rate. Considering the sensitivity, specificity, PLR and NLR, the recommended diagnostic cut-off of BALF-GM for adult IPA is 0.5.

Chemical profiling of Fritillariae thunbergii Miq prepared by different processing methods reveals two new quality markers: Zhebeininoside and imperialine-3-ß-D-glucoside.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae thunbergii Miq (FTM)exhibit versatile biological activities including the significant antitussive and expectorant activities. As a herbal medicine, the therapeutic effects of FTM may be expressed by multi-components which have complicated integration effects on multi-targets. With the time going, the different processing methods of FTM has been changed a lot. Thus，the study described the effect of processing methods to FTM and its quality. MATERIAL AND METHOD: Studies were undertaken by using UHPLC-LTQ Orbitrap MS and pharmacodynamic models. All reagents were involved of analytical grade. While a HPLC-ELSD's method has been developed and validated, a certified Quality System is conformed to ICH requirements. The experimental animals followed the animal welfare guidelines. AIM OF THE STUDY: We aimed to found the differences after the different processing methods of FTM, and to demonstrate the changes could be selected as quality control indicators, and established a method for simultaneous determination of these for quality control. RESULTS: we have previously found two new steroidal alkaloids: zhebeininoside and imperialine-3-ß-D-glucoside from the different processing methods of FTM, which is the difference between the different processing methods of FTM, mainly on the steroidal alkaloids. The activity analysis of zhebeininoside, imperialine-3-ß-D-glucoside, verticine and verticinone showed that the mouse model of cough expectorant has antitussive effect. The positive drug selected was dextromethorphan syrup. The positive group showed biological activity, but the blank group showed nothing. The model group showed illness which means that the model was effective. There are two ways of the mechanism of action of the expectorant action which can make sputum thin, reduce its viscosity, and be easy to cough up, or can accelerate the movement of mucous cilia in the respiratory tract and promote the discharge of sputum. In our study, the content of phenol red was significantly reduced in the administration group. CONCLUSIONS: To sum up, our results suggest that zhebeininoside and other three components cloud be selected as quality control indicators, and a method for simultaneous determination of zhebeininoside and other three components was established for quality control.

Value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy in burn patients with sepsis / 中华烧伤杂志

Objective: To explore the value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy (SAE) in burn patients with sepsis. Methods: A retrospective case series study was conducted. From October 2018 to May 2021, 41 burn patients with sepsis who were admitted to Zhengzhou First People's Hospital met the inclusion criteria, including 23 males and 18 females, aged 18-65 (35±3) years. According to whether SAE occurred during hospitalization, the patients were divided into SAE group (21 cases) and non-SAE group (20 cases). The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores of patients were compared between the two groups. The serum levels of central nervous system specific protein S100β and neuron specific enolase (NSE) at 12, 24, and 48 h after sepsis diagnosis (hereinafter referred to as after diagnosis), the serum levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), Tau protein, adrenocorticotropic hormone (ACTH), and cortisol at 12, 24, 48, 72, 120, and 168 h after diagnosis, and the mean blood flow velocity of middle cerebral artery (VmMCA), pulsatility index, and cerebral blood flow index (CBFi) on 1, 3, and 7 d after diagnosis of patients in the two groups were counted. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. The independent variables to predict the occurrence of SAE was screened by multi-factor logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn for predicting the occurrence of SAE in burn patients with sepsis, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, and APACHE Ⅱ score of patients in the two groups were all similar (χ2=0.02, with t values of 0.71, 1.59, 0.91, and 1.07, respectively, P>0.05). At 12, 24, and 48 h after diagnosis, the serum levels of S100β and NSE of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 37.74, 77.84, 44.16, 22.51, 38.76, and 29.31, respectively, P<0.01). At 12, 24, 48, 72, 120, and 168 h after diagnosis, the serum levels of IL-10, Tau protein, and ACTH of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 10.68, 13.50, 10.59, 8.09, 7.17, 4.71, 5.51, 3.20, 3.61, 3.58, 3.28, 4.21, 5.91, 5.66, 4.98, 4.69, 4.78, and 2.97, respectively, P<0.01). At 12, 24, 48, 72, and 120 h after diagnosis, the serum levels of IL-6 and TNF-α of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 8.56, 7.32, 2.08, 2.53, 3.37, 4.44, 5.36, 5.35, 6.85, and 5.15, respectively, P<0.05 or P<0.01). At 12, 24, and 48 h after diagnosis, the serum level of cortisol of patients in SAE group was significantly higher than that in non-SAE group (with t values of 5.44, 5.46, and 3.55, respectively, P<0.01). On 1 d after diagnosis, the VmMCA and CBFi of patients in SAE group were significantly lower than those in non-SAE group (with t values of 2.94 and 2.67, respectively, P<0.05). On 1, 3, and 7 d after diagnosis, the pulsatile index of patients in SAE group was significantly higher than that in non-SAE group (with t values of 2.56, 3.20, and 3.12, respectively, P<0.05 or P<0.01). Serum IL-6 at 12 h after diagnosis, serum Tau protein at 24 h after diagnosis, serum ACTH at 24 h after diagnosis, and serum cortisol at 24 h after diagnosis were the independent risk factors for SAE complicated in burn patients with sepsis (with odds ratios of 2.42, 1.38, 4.29, and 4.19, 95% confidence interval of 1.76-3.82, 1.06-2.45, 1.37-6.68, and 3.32-8.79, respectively, P<0.01). For 41 burn patients with sepsis, the AUC of ROC of serum IL-6 at 12 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.84-1.00), the best threshold was 157 pg/mL, the sensitivity was 81%, and the specificity was 89%. The AUC of ROC of serum Tau protein at 24 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.82-1.00), the best threshold was 6.4 pg/mL, the sensitivity was 97%, and the specificity was 99%. The AUC of ROC of serum ACTH at 24 h after diagnosis for predicting SAE was 0.96 (95% confidence interval was 0.89-1.00), the best threshold was 14.7 pg/mL, the sensitivity was 90%, and the specificity was 94%. The AUC of ROC of serum cortisol at 24 h after diagnosis for predicting SAE was 0.93 (95% confidence interval was 0.86-1.00), the best threshold was 89 nmol/L, the sensitivity was 94%, and the specificity was 97%. Conclusions: Serum Tau protein, ACTH, and cortisol have high clinical diagnostic value for SAE complicated in burn patients with sepsis.

Effects of continuous goal-directed analgesia on fluid resuscitation of massive burn patients during shock / 中华烧伤杂志

Objective: To investigate the effects of continuous goal-directed analgesia on fluid resuscitation during shock stage in patients with massive burns, providing a basis for rational optimization of analgesia protocols in patients with burn shock. Methods: A retrospective case series study was conducted. One hundred and thirty-six patients with massive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital from January 2015 to December 2020, and the patients were divided into continuous analgesia (CA) group (68 cases,with average age of 44 years old) and intermittent analgesia (IA) group (68 cases,with average age of 45 years old) according to whether sufentanil injection was continuously used for intravenous analgesia during the shock stage. The patients in the 2 groups were predominantly male. Before and at 72 h of treatment, the severity of disease and trauma pain of patients in the 2 groups were scored by the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and the visual analogue scale (VAS). Hematocrit, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation in central venous blood (ScvO2), rehydration coefficient, blood lactate value, hourly urine output, and the adverse reactions such as hypotension, nausea, vomiting, dizziness, skeletal muscle tonicity, respiratory depression, bradycardia, pruritus, and drug addiction of patients in the 2 groups during the treatment were recorded at the 1st, 2nd, and 3rd 24 h post-injury. Data were statistically analyzed with analysis of variance for repeated measurement, paired or independent sample t test, Bonferroni correction,chi-square test and Mann-Whitney U test. Results: Before treatment, APACHE Ⅱ and VAS scores of patients in the 2 groups were close (with t values of -0.67 and 0.32, respectively, P>0.05); At 72 h of treatment, APACHE Ⅱ and VAS scores of patients in CA group were 8.5±2.2 and 2.5±1.6, both of which were significantly lower than (15.2±3.0) and (7.9±2.0) of patients in IA group, respectively (with t values of -14.94 and -17.46, respectively, P<0.01). Compared with the pre-treatment period, the APACHE Ⅱ and VAS scores of patients in IA group decreased significantly at 72 h of treatment (with t values of 11.35 and 30.59, respectively, P<0.01); the changes in APACHE Ⅱ and VAS scores of patients at 72 h of treatment in comparison with those of patients before treatment in CA group were all similar to those of patients in IA group (with t values of 4.00 and 4.82, respectively, P<0.01). Compared with those of patients in IA group, there were no significant changes in CVP, hematocrit, heart rate, ScvO2, and MAP of patients in CA group at all three 24 h post-injury (with t values of <0.01, 0.12, 2.10, 1.55, 0.03; 0.13, 0.22, <0.01, 0.17, 0.49; 0.63, 0.06, 0.04, 2.79, and 2.33, respectively, P>0.05). Compared with those of patients in IA group at the 1st 24 h post-injury, CVP, ScvO2 and MAP of patients were significantly higher at the 2nd and 3rd 24 h post-injury (with t values of -10.10, -9.31, -8.89; -10.81, -4.65, and -9.43, respectively, P<0.01), and the heart rate of patients was significantly lower at the 2nd and 3rd 24 h post-injury (with t values of 7.53 and 7.78, respectively, P<0.01), and the hematocrit of patients decreased significantly only at the 3rd 24 h post-injury (t=15.55, P<0.01); the changes of CVP, ScvO2, MAP and heart rate of patients at the 2nd and the 3rd 24 h post-injury, and HCT of patients at the 3rd 24 h post-injury, in comparison with those of patients at the 1st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of -12.25, -10.24, -8.99, 9.42, -8.83, -7.53, -11.57, 10.44, and 12.91, respectively, P<0.01). Compared with those of patients in IA group, the rehydration coefficient of patients in CA group was significantly higher only at the 3rd 24 h post-injury (t=5.60, P<0.05), blood lactate value of patients in CA group was significantly lower at the 1st and 2nd 24 h post-injury (with t values of 4.32 and 14.52, respectively, P<0.05 or P<0.01), the hourly urine output of patients in CA group increased significantly at the 1st, 2nd, and 3rd 24 h post-injury (with t values of 24.65, 13.12, and 5.63, respectively, P<0.05 or P<0.01). Compared with the those of patients at the 1st 24 h post-injury, the rehydration coefficient of patients in IA group decreased significantly at the 2nd and the 3rd 24 h post-injury (with t values of 33.98 and 36.91, respectively, P<0.01), the blood lactate values of patients in IA group decreased significantly at the 2nd and the 3rd 24 h post-injury (with t values of 8.20 and 11.68, respectively, P<0.01), and the hourly urine output of patients in IA group was significantly increased at the 2nd and the 3rd 24 h post-injury (with t values of -3.52 and -5.92, respectively, P<0.01); the changes of rehydration coefficients and blood lactate values of patients at the 2nd and the 3rd 24 h post-injury in comparison with those of patients at the 1st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of 35.64, 33.64, 9.86, and 12.56, respectively, P<0.01), but hourly urine output of patients in CA group increased significantly only at the 3rd 24 h compared with that of patients at the 1st 24 h post-injury (t=-3.07, P<0.01). Adverse reactions such as hypotension, nausea, vomiting, dizziness, bradycardia, and pruritus occurred rarely in patients of the 2 groups, and none of the patients had skeletal muscle tonicity, respiratory depression, or drug addiction. The incidence of adverse reactions of patients in CA group was similar to that in IA group (χ2=0.08, P>0.05). Conclusions: Continuous goal-directed analgesia can effectively relieve pain and improve vital signs of patients with large burns. Meanwhile it has little impact on volume load, which can assist in correcting ischemia and hypoxia during the shock period and help patients get through the shock period smoothly.

Structures, plasmon-enhanced luminescence, and applications of heterostructure phosphors.

Heterostructure phosphor composites have been used widely in the fields of targeted bio-probes and bio-imaging, hyperthermia treatment, photocatalysis, solar cells, and fingerprint identification. The structures, plasmon-enhanced luminescence and mechanism of metal/fluorophore heterostructure composites, such as core-shell nanocrystals, multilayers, adhesion, islands, arrays, and composite optical glass, are reviewed in detail. Their extended applications were explored widely since the surface plasmon resonance effect increased the up-conversion efficiency of fluorophores significantly. We summarize their synthesis methods, size and shape control, absorption and excitation spectra, plasmon-enhanced up-conversion luminescence, and specific applications. The most important results acquired in each case are summarized, and the main challenges that need to be overcome are discussed.

Diagnostic value of microRNA-25 in patients with non-small cell lung cancer in Chinese population: A systematic review and meta-analysis.

OBJECTIVE: Previous studies have shown that microRNA-25 (miR-25) plays a key role in the occurrence and development of non-small cell lung cancer (NSCLC). Many studies have shown that there is a significant increment of miR-25 in circulating blood of patients with NSCLC. The meta-analysis aims to explore diagnostic value of miR-25 in NSCLC in Chinese population. METHODS: PubMed, Web of science, Excerpta Medica Database, China national knowledge infrastructure and China Wanfang database were searched to collect studies upon correlation between miR-25 and diagnosis of the patients with NSCLC until April 2020. Combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristic curve were calculated by Stata 15.0 software. Literature assessment was conducted according to quality assessment of diagnostic accuracy studies, and documents with scores above or equal to 11 were included in this meta-analysis. RESULTS: Six studies were included, including 480 cases with NSCLC and 451 healthy controls. The combined sensitivity (0.75, 95% confidence interval [CI]: 0.69∼0.80), specificity (0.81, 95% CI: 0.76∼0.86), positive likelihood ratio (4.04, 95% CI: 3.14∼5.20), negative likelihood ratio (0.31, 95% CI: 0.25∼0.37), diagnostic odds ratio (13.09, 95% CI: 9.37∼18.29) and area under curve (0.85, 95% CI: 0.82∼0.88) indicated that miR-25 had desirable diagnostic accuracy for NSCLC. CONCLUSION: MiR-25 can be applied in diagnosis of NSCLC and has potential of becoming a biomarker for detection of patients with early NSCLC in Chinese population.

Discovery of potent small molecule PROTACs targeting mutant EGFR.

Epidermal growth factor receptor (EGFR) is an important therapeutic target for the treatment of non-small cell lung cancer. A number of efficacious EGFR tyrosine kinase inhibitors have been developed. However, acquired drug resistance largely encumbered their clinical practicability. Therefore, there is an urgent need to develop new therapeutic regime. Herein, we designed and synthesized a set of EGFR-targeting small molecule PROTACs which showed promising efficacy. In particular, VHL-recruiting compound P3 showed potent anti-proliferative activity against HCC827 and H1975 cell lines with IC50 values of 0.83 and 203.01 nM, respectively. Furthermore, both EGFRdel19 and EGFRL858R/T790M could be significantly induced to be degraded under treatment of P3 with DC50 values of 0.51 and 126.2 nM, respectively. Compound P3 was able to dramatically suppress EGFR pathway signal transduction. Moreover, compound P3 could significantly induce cell apoptosis, arrest cell cycle and suppress cell colony formation. In addition, we identified that ubiquitination was indispensable in the degradation process, and found that the degradation was related to autophagy. Our work would provide an alternative approach for development of potentially effective EGFR degraders and give a new clue for investigation of PROTAC-induced protein degradation.

Meta-analysis of diagnostic and prognostic value of miR-126 in non-small cell lung cancer.

In recent years, many studies on the relationship between the expression of microRNA-126 (miR-126) and the diagnostic and prognostic value of non-small cell lung cancer (NSCLC) have been made, but the results were still controversial. The aim is to explore the expression of miR-126 and the diagnosis and prognosis value of NSCLC, and to provide relevant evidence for clinical diagnosis and treatment. Literature related to miR-126 and NSCLC were searched in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang from the inception to February 2020. Stata 15.0 was used for meta-analysis. The diagnostic value data were used to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the prognostic value data were used to calculate the pooled risk ratio (hazard ratio, HR) of overall survival (OS) and its 95% confidence interval (95% CI). Thirteen studies were included, among which five were related to diagnosis containing 439 patients and 463 healthy controls, and eight related to prognosis containing 1102 patients. The results of miR-126 expression and diagnostic value of NSCLC showed that the pooled sensitivity was 0.83 (95% CI: 0.59-0.94), specificity = 0.83 (95% CI: 0.71-0.90), PLR = 4.78 (95% CI: 2.97-7.69), NLR = 0.20 (95% CI: 0.08-0.54), DOR = 23.48 (95% CI: 7.87-70.10), and the area under the summ ary receiver operating characteristic curve (SROC) was 0.89 (95% CI: 0.86-0.91). The results of prognostic value indicated that the expression of miR-126 was related to the OS of NSCLC (HR = 0.79, 95% CI: 0.63-0.98). In conclusion, the expression of miR-126 has medium diagnostic value, and it is related to the prognosis of patients with NSCLC, with poor prognosis of miR-126 low expression.

W941, a new PI3K inhibitor, exhibits preferable anti-proliferative activities against nonsmall cell lung cancer with autophagy inhibitors.

The PI3K pathway is aberrantly activated in many cancers and plays a critical role in tumour cell proliferation and survival, making it a rational therapeutic target. In the present study, the effects and the underlying mechanism of a new PI3K inhibitor, W941, were investigated in non-small-cell lung cancer (NSCLC). The results of this study showed that W941 inhibited the growth of A549 and Hcc827 cells with IC50 values of 0.12 and 0.23 µM, respectively, and that W941 markedly inhibited the growth of A549 xenograft tumours in a nude mouse model without decreasing body weight. Western blotting assays showed that W941 inhibited the phosphorylation of downstream proteins in the PI3K pathway (AKT, mTOR, p70S6K and 4EBP1) in both A549 and Hcc827 cells. In addition, after W941 treatment, a dose-dependent increase in the ratio of the LC3-II/I ratio was observed. When cells were pre-treated with chloroquine or bafilomycin A1, W941 increased the LC3-II/I ratio, suggesting that W941 acted as an autophagy inducer. Moreover, autophagy blockers enhanced apoptosis after W941 treatment, indicating that W941-induced autophagy actually protected the cells against its cytotoxicity. Our findings suggest that the combination of a PI3K inhibitor with an autophagy inhibitor might be a novel option for NSCLC treatment.

The dual luciferase reporter system and RT-qPCR strategies for screening of MicroRNA-21 small-molecule inhibitors.

The therapeutic potential of microRNA-21 (miR-21) small-molecule inhibitors has been of particular interest to medicinal chemists. Moreover, the development of more facile screening methods is lacking. In the present study, two potential screening strategies for miR-21 small-molecule inhibitor including the stem-loop reverse transcription-quantitative PCR and dual luciferase reporter assay system were demonstrated and discussed in detail. A pmirGLO-miR21cswt plasmid and its two different mutants were constructed for dual luciferase reporter assay system. In addition, the sensitivity and specificity of these two methods were validated. Our results demonstrated that both strategies are decent choices for the screening of small-molecule inhibitors for miR-21 and possibly other miRNAs. Eventually, we applied our optimized strategy to discover and characterize several promising compounds such as azobenzene derivate A, enoxacin, and norfloxacin for their potential impact on intracellular miR-21 concentration.

Discovery of 2-(aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6- substituted triazine as PI3K and BRAF dual inhibitor.

AIM: The discovery and development of novel agents simultaneously targeting PI3K/AKT/mammalian target of rapamycin and Ras/RAF/MEK, two signaling pathways, are urgent to improve the curative effect of kinase inhibitors and overcome acquired resistance. METHODS/RESULTS: In the present study, 2-(2-aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6-(N-cyclopropyl-N- (1-benzoylpiperidin-4-yl))triazines/pyrimidines were designed as PI3K and BRAF dual inhibitors. The synthesized 20 compounds exhibited potent antiproliferative effects in vitro against HCT116, A375, MCF-7, Colo205, A549 and LOVO cancer cell lines. The tested compounds A6, A7, A9 and A11 remarkably displayed inhibitory activities toward both PI3Kα and BRAFV600E. CONCLUSION: These results indicated that our design compounds can serve as potent PI3Kα and BRAFV600E dual inhibitors and effective antiproliferative agents, which can be further optimized to discover more potent PI3Kα and BRAFV600E dual inhibitors.

Sodium selenite induces apoptosis and inhibits autophagy in human synovial sarcoma cell line SW982 in vitro.

The present study aimed to examine the effects of sodium selenite on the SW982 human synovial sarcoma cell line in relation to cell viability, apoptosis and autophagy. The results indicated that sodium selenite reduced cell viability and induced apoptosis by activating caspase­3 and members of the poly (ADP­ribose) polymerase and Bcl­2 protein families in SW982 cells. Furthermore, autophagy was also suppressed by sodium selenite treatment in SW982 cells, and apoptosis was upregulated in cells co­treated with sodium selenite and the autophagy inhibitor 3­methyladenine. By contrast, apoptosis was downregulated when sodium selenite was combined with rapamycin, an inducer of autophagy. The results indicated that autophagy may protect cells from the cytotoxicity of sodium selenite. The present study results demonstrated that sodium selenite induced apoptosis and inhibited autophagy and autophagy­protected cells from death by antagonizing sodium selenite­induced apoptosis in SW982 cells in vitro.

Topically administered rhGM-CSF affects PPARß expression in the stasis zone.

Using a rat comb thermal damage model, we investigated the effects of topically administered recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on peroxisome proliferator-activated receptor PPARß expression. We created bilateral comb scald models on the backs of fifty Sprague-Dawley rats. The left sides of the backs served as the experimental group and the right sides served as the control group. The experimental group received topically applied rhGM-CSF hydrogel and the control group did not. The survival situations of the stasis zones were compared between the experimental and control groups on the 1st, 3rd, 7th, 14th and 21st post-burn days. Tissues from the surviving stasis zones of both groups were collected at different time-points. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used to detect the PPARß mRNA and protein expression levels. Immunohistochemical methods were applied to detect the localization of PPARß protein expression. The results showed that, first, the tissue viability numbers for the stasis zones of the experimental group were significantly increased compared with those of the control group. Second, RT-PCR revealed that the PPARß mRNA expression first increased and then gradually declined in both groups. At all time-points, the expression level in the experimental group was increased compared with that in the control group and the highest expression levels were observed in both groups on the 3rd post-burn day. Third, western blot analysis revealed that the PPARß protein expression in both groups increased after thermal damage and then gradually decreased. PPARß protein expression in the experimental group was greater than that in the control group, and the highest expression quantities in both groups were observed on the 3rd post-burn day. In conclusion, rhGM-CSF hydrogel effectively promotes the expression of PPARß, and the hydrogel had a specific protective effect for the stasis zone.

Experimental characterization of enhanced SNCR process with carbonaceous gas additives.

Carbonaceous gases such as CO and alkanes are commonly used as additives to enhance the selective non-catalytic reduction (SNCR) performance due to their high reducibility. This study compared the effect of CO and CH4 on NO reduction in a tubular reactor with simulated flue gas. The enhancement of C3H8 on SNCR process was tested at extremely low temperature, i.e. 650 °C. Experimental results suggested that reactions between NH3 and SO2 were favored at low temperatures and the competition for NH3 between SO2 and NO was influenced by gas additives. A maximum downward shift of 25 °C and 100 °C in temperature window for 50% NO reduction efficiency was obtained with the addition of CO and CH4, respectively. Considerable CO emission was observed with addition of CH4. The addition of CH4 contributed to the formation of a self-accelerating reaction route within NO/O2/NH3 SNCR reaction system. NO2 produced from NO accelerates the oxidation of CH4 to CO, while the oxidation of CH4 returns to enhance the NO reduction globally. Optimal NO reduction of 44% was achieved with addition of C3H8 at 650 °C. Substantial portion of C3H8 was partially oxidized to CO and the remaining was converted into C2H4 and C3H6 during the SNCR process. Oxidative dehydrogenation of C3H8 was involved. High reactivity of C3H6 and C2H4 favored the further oxidation and cracking to produce CO. These differences in oxidation behavior significantly influence the promotion capacities of CO, CH4 and C3H8 for NO reduction.

[Treatment of PTA Wastewater by Modified Anode Microbial Fuel Cell].

The purpose of this study was to investigate the effect of different modified anodes on the microbial fuel cell(MFC) and the effect of MFC on the treatment of refractory wastewater. Based on a single room air cathode, the anode of MFC was modified by 0.10 g of tourmaline, 75% manganese bioxide/halloysite nanotube(MnO2/HNT) and multi-walled carbon nanotube-carboxyl(MWCNT-COOH), respectively. The results showed that, the removal rate of purified terephthalic acid(PTA) was higher than 70%, and the chemical oxygen demand(COD) removal rate was more than 79% in MFC with different modified anodes. Compared with others, MFC with MWCNT-COOH modified anode obtained the maximum output voltage and maximum power density, which were 529 mV and 252.73 mW·m-2, respectively.

[Bidirectional regulation of Pam3CSK4?induced inflammatory response by ATP?binding cassette transporter A1 knockdown in mouse mononuclear macrophages in vitro].

OBJECTIVE: To investigate the regulatory effect of ATP?binding cassette transporter A1 (ABCA1) knockdown on inflammatory response induced by Pam3CSK4 in mouse mononuclear macrophage RAW264.7 cell line. METHODS: A mouse mononuclear macrophage RAW264.7 cell line with stable ABCA1 knockdown was constructed and stimulated with Toll?like receptor 2 (TLR2) ligand Pam3CSK4, and the changes in the transcriptional levels of the proinflammatory and anti-inflammatory cytokines were analyzed in this cell model. RESULTS: In RAW264.7 cells, ABCA1 knockdown significantly up-regulated Pam3CSK4 stimulation?induced expressions of IL?1ß, TNF?α and IL?6 and also enhanced the expression of transcription factor cAMP?dependent transcription factor 3 (ATF3) without obviously affecting the expressions of the transcription factors ATF1, ATF2, ATF4 or ATF5. CONCLUSION: ABCA1 knockdown in macrophages may have both proinflammatory and anti?inflammatory effects. ABCA1 knockdown up?regulates the transcription of ATF3 possibly through a mechanism that is different from that for the other members of the ATF protein family.

Bidirectional regulation of Pam3CSK4?induced inflammatory response by ATP?binding cassette transporter A1 knockdown in mouse mononuclear macrophages in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the regulatory effect of ATP?binding cassette transporter A1 (ABCA1) knockdown on inflammatory response induced by Pam3CSK4 in mouse mononuclear macrophage RAW264.7 cell line.</p><p><b>METHODS</b>A mouse mononuclear macrophage RAW264.7 cell line with stable ABCA1 knockdown was constructed and stimulated with Toll?like receptor 2 (TLR2) ligand Pam3CSK4, and the changes in the transcriptional levels of the proinflammatory and anti-inflammatory cytokines were analyzed in this cell model.</p><p><b>RESULTS</b>In RAW264.7 cells, ABCA1 knockdown significantly up-regulated Pam3CSK4 stimulation?induced expressions of IL?1β, TNF?α and IL?6 and also enhanced the expression of transcription factor cAMP?dependent transcription factor 3 (ATF3) without obviously affecting the expressions of the transcription factors ATF1, ATF2, ATF4 or ATF5.</p><p><b>CONCLUSION</b>ABCA1 knockdown in macrophages may have both proinflammatory and anti?inflammatory effects. ABCA1 knockdown up?regulates the transcription of ATF3 possibly through a mechanism that is different from that for the other members of the ATF protein family.</p>

Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of HMGB1 prevents rheumatoid arthritis progression.

High-mobility group box 1 (HMGB1) is associated with the development of rheumatoid arthritis (RA). Recent studies have shown that methotrexate (MTX) may inhibit the expression of HMGB1. This study examined whether HMGB1 might be involved in the treatment of RA using MTX. Synovial tissues were collected from RA patients who were treated with MTX for at least 6 months (RA-MTX group, 7 cases) and from those without MTX treatment (RA-noMTX group, 7 cases). Additionally, patients with osteoarthritis (OA group, 7 cases) were used as controls. The expression and locations of HMGB1 in the tissues were detected using real-time PCR, western blot, and immunohistochemistry. Additionally, OA-fibroblast-like synoviocytes (FLSs) and RA-FLSs were isolated and cultured, and the expression of HMGB1 was reduced in these cells by transfection with HMGB1 siRNA. Cell proliferation, migration, and invasion abilities were detected. Furthermore, the effects of HMGB1 on matrix metalloproteinase (MMP)-2 and MMP-13 were measured using western blot analysis. At the tissue level, HMGB1 expression in synovial membrane did not differ significantly between the OA and RA-MTX groups, but was significantly lower in these groups than in the RA-noMTX group. In cell experiments, the cell doubling time in the RA-FLS HMGB1 siRNA group was significantly extended compared with that in the RA-FLS negative control (NC)-siRNA group. The amount of cell migration and invasion in the RA-FLS HMGB1 siRNA group was significantly lower compared with that in the NC-siRNA group; the MMP-2 and MMP-13 expression levels were also lower. These results showed that MTX reduced HMGB1 expression in RA synovial tissues, and through the downregulation of HMGB1 expression in tissues, MTX may slow disease progression of RA.

Activation of α1 adrenoceptors in ventrolateral orbital cortex attenuates allodynia induced by spared nerve injury in rats.

Recent studies have demonstrated that noradrenaline acting in the ventrolateral orbital cortex (VLO) can potentially reduce allodynia induced by spared nerve injury (SNI), and this effect is mediated by α2 adrenoceptor. The present study examined the effect of the α1 adrenoceptors in the VLO on allodynia induced by SNI in the rats. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of selective α1 adrenoceptor agonist methoxamine (20, 50, 100 µg in 0.5 µl) into the VLO, contralateral to the site of nerve injury, increased PWT in a dose-dependent manner. This effect was antagonized by pre-microinjection of the selective α1 adrenoceptor antagonist benoxathian into the same VLO site, and blocked by electrolytic lesion of the ventrolateral periaqueductal gray (PAG). Furthermore, pre-administration of non-selective glutamate receptor antagonist kynurenic acid, phospholipase C (PLC) inhibitor U73122, and protein kinase C (PKC) inhibitor chelerythrine to the VLO also blocked methoxamine-induced inhibition of allodynia. These results suggest that activation of α1 adrenoceptors in the VLO can potentially reduce allodynia induced by SNI. This effect may be direct excitation of the VLO neurons, via PLC-PKC signaling pathway, projecting to the PAG or facilitating glutamate release and then indirectly exciting the VLO output neurons projecting to the PAG, leading to activation of the PAG-brainstem descending inhibitory system which depresses the nociceptive transmission at the spinal cord level.