Pixel-by-pixel correction of beam hardening artifacts by bowtie filter in fan-beam CT.

Objective. Beam hardening (BH) artifacts in computed tomography (CT) images originate from the polychromatic nature of x-ray photons. In a CT system with a bowtie filter, residual BH artifacts remain when polynomial fits are used. These artifacts lead to worse visuals, reduced contrast, and inaccurate CT numbers. This work proposes a pixel-by-pixel correction (PPC) method to reduce the residual BH artifacts caused by a bowtie filter.Approach. The energy spectrum for each pixel at the detector after the photons pass through the bowtie filter was calculated. Then, the spectrum was filtered through a series of water slabs with different thicknesses. The polychromatic projection corresponding to the thickness of the water slab for each detector pixel could be obtained. Next, we carried out a water slab experiment with a mono energyE= 69 keV to get the monochromatic projection. The polychromatic and monochromatic projections were then fitted with a 2nd-order polynomial. The proposed method was evaluated on digital phantoms in a virtual CT system and phantoms in a real CT machine.Main results. In the case of a virtual CT system, the standard deviation of the line profile was reduced by 23.8%, 37.3%, and 14.3%, respectively, in the water phantom with different shapes. The difference of the linear attenuation coefficients (LAC) in the central and peripheral areas of an image was reduced from 0.010 to 0.003cm-1and 0.007cm-1to 0 in the biological tissue phantom and human phantom, respectively. The method was also validated using CT projection data obtained from Activion16 (Canon Medical Systems, Japan). The difference in the LAC in the central and peripheral areas can be reduced by a factor of two.Significance. The proposed PPC method can successfully remove the cupping artifacts in both virtual and authentic CT images. The scanned object's shapes and materials do not affect the technique.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Overall quality changes and deterioration mechanism of fragrant rapeseed oils during 6-Month storage.

The strong-fragrant rapeseed oil (SFRO) is a popular rapeseed oil in China with a low refining degree only degumming with hot water, which remarkably affects its storage stability. The present study compared the overall changes of physical/chemical/nutrient quality of FROs at various temperatures, light wavelengths and headspace volumes. Results showed that red light (680 nm) had a most significant adverse effect on the overall quality of SFRO with the higher correlation coefficients to PV and TOTOX of 0.71 and 0.70, and lower correlation coefficients to chlorophyll and tocopherol of -0.95 and -0.53, respectively. Further studies revealed that red light accelerated the oxidation of fragrant rapeseed oils by degrading chlorophyll to initiate the photo-oxidation process and synthesize high amount of secondary oxidation products including aliphatic and aromatic oxidized compounds from linolenic acid. These findings provided a reference to control the deterioration of FROs by preventing the transmittance of red light.

The Diagnostic Value of Serum TGF-ß1, p2PSA Combined with PSA in Prostate Cancer.

Objective: To investigate the diagnostic value of transforming growth factor-ß1 (TGF-ß1), prostate-specific antigen isomer 2 (p2PSA) combined with a prostate-specific antigen (PSA) in prostate cancer (PCa). Methods: From October 1, 2019 to September 1, 2022 we enrolled a total of 90 patients with PCa90 patients with PCa in the urology department of our hospital were selected as the PCa group, 90 patients with benign prostatic hyperplasia (BPH) were selected as the BPH group, and 90 healthy people were selected as a healthy control group. The levels of TGF-ß1, p2PSA and PSA in serum were detected, and the differences in TGF-ß1, p2PSA and PSA levels among the three groups and PCa patients with different pathological parameters were compared. Univariate and Logistic regression analyses were used to analyze the independent risk factors affecting the occurrence of PCa. With pathological results as the 'gold standard', the diagnostic efficacy of TGF-ß1, p2PSA and PSA alone and their combination for PCa was analyzed by the receiver operating characteristic (ROC) curve. Results: The levels of serum PSA, p2PSA, and TGF-ß1 in the PCa group were higher than those in the BPH group and control group (P < .001), and those in BPH group were higher than those in the control group (P < .001). The serum indexes of PCa group increased with the increase of Glerson grade and TNM stage (P < .001). The serum indexes of patients with lymph and bone metastasis were significantly higher than those without lymph and bone metastasis (P < .001). Logistic regression analysis showed that PSA, p2PSA and TGF-ß1 were independent risk factors for PCa (P < .001). The area under the ROC curve (AUC) of PSA, p2PSA, TGF-ß1 and combined detection were 0.738, 0.862, 0.821 and 0.932, respectively. The AUC of combined detection was greater than that of single detection (P < .001). Conclusion: The expression levels of serum TGF-ß1, p2PSA and PSA are related to PCa and are independent risk factors for PCa. The combined detection of the three groups can improve the diagnostic efficacy of PCa. Combined testing improves diagnostic accuracy for prostate cancer, allows for early intervention, and improves patient survival and confidence in treatment options. This will significantly improve the clinical management of prostate cancer. Future studies could explore other biomarkers or molecular indicators to further improve the accuracy of diagnosis and grading of prostate cancer. Additionally, differences between different populations and subtypes can be studied to better understand the heterogeneity of prostate cancer.

Realgar-Induced Neurotoxicity: Crosstalk Between the Autophagic Flux and the p62-NRF2 Feedback Loop Mediates p62 Accumulation to Promote Apoptosis.

Realgar is a traditional Chinese medicine that contains arsenic. It has been reported that the abuse of medicine-containing realgar has potential central nervous system (CNS) toxicity, but the toxicity mechanism has not been elucidated. In this study, we established an in vivo realgar exposure model and selected the end product of realgar metabolism, DMA, to treat SH-SY5Y cells in vitro. Many assays, including behavioral, analytical chemistry, and molecular biology, were used to elucidate the roles of the autophagic flux and the p62-NRF2 feedback loop in realgar-induced neurotoxicity. The results showed that arsenic could accumulate in the brain, causing cognitive impairment and anxiety-like behavior. Realgar impairs the ultrastructure of neurons, promotes apoptosis, perturbs autophagic flux homeostasis, amplifies the p62-NRF2 feedback loop, and leads to p62 accumulation. Further analysis showed that realgar promotes the formation of the Beclin1-Vps34 complex by activating JNK/c-Jun to induce autophagy and recruit p62. Meanwhile, realgar inhibits the activities of CTSB and CTSD and changes the acidity of lysosomes, leading to the inhibition of p62 degradation and p62 accumulation. Moreover, the amplified p62-NRF2 feedback loop is involved in the accumulation of p62. Its accumulation promotes neuronal apoptosis by upregulating the expression levels of Bax and cleaved caspase-9, resulting in neurotoxicity. Taken together, these data suggest that realgar can perturb the crosstalk between the autophagic flux and the p62-NRF2 feedback loop to mediate p62 accumulation, promote apoptosis, and induce neurotoxicity. Realgar promotes p62 accumulation to produce neurotoxicity by perturbing the autophagic flux and p62-NRF2 feedback loop crosstalk.

Multi-centre, prospective randomized comparison of three different substrate ablation strategies for persistent atrial fibrillation.

AIMS: The optimal strategy for persistent atrial fibrillation (PerAF) is poorly defined. We conducted a multicentre, randomized, prospective trial to compare the outcomes of different ablation strategies for PerAF. METHODS AND RESULTS: We enrolled 450 patients and randomly assigned them in a 1:1:1 ratio to undergo pulmonary vein isolation and subsequently undergo the following three different ablation strategies: anatomical guided ablation (ANAT group, n = 150), electrogram guided ablation (EGM group, n = 150), and extensive electro-anatomical guided ablation (EXT group, n = 150). The primary endpoint was freedom from atrial fibrillation (AF) lasting longer than 30 s at 12 months after a single ablation procedure. After 12 months of follow-up, 72% (108) of patients in the EXT group were free from AF recurrence, as compared with the 64% (96) in the EGM group (P = 0.116), and 54% (81) in the ANAT group (P = 0.002). The EXT group showed less AF/atrial tachycardia recurrence than the EGM group (60% vs. 50%, P = 0.064) and the ANAT group (60% vs. 37.3%, P < 0.001). The EXT group showed the highest rate of AF termination (66.7%), followed by 56.7% in the EGM group, and 20.7% in the ANAT group. The AF termination signified less AF recurrence at 12 months compared to patients without AF termination (30.1% vs. 42.7%, P = 0.008). Safety endpoints did not differ significantly between the three groups (P = 0.924). CONCLUSIONS: Electro-anatomical guided ablation achieved the most favourable outcomes among the three ablation strategies. The AF termination is a reliable ablation endpoint.

Elevated Blood Selenium Level has a Non-Linear Association with Risk of Anemia in U.S.A. Adults: Data from the NHANES 2011-2016.

BACKGROUND: Only a few epidemiological studies have reported the association between blood selenium and the prevalence of anemia. To date, the evidence is limited and inconsistent. METHODS: We enrolled 9,335 participants (≥ 20 years) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016 to assess the link between blood selenium and the risk of anemia. Multivariate logistic regression analysis and a generalized additive model (GAM) was applied to assess the relationship between blood selenium and anemia risk. RESULTS: We found a significant adverse association between blood selenium and the prevalence of anemia after adjusting for all potential covariates (OR = 0.98, 95% CI: 0.97, 0.98, p < 0.001). After a sequence of sensitive analyses, the conclusion remains stable (p for trend < 0.001). However, a non-linear relationship was detected based on GAM. We calculated a turning point of 205.89 µg/L using a two-piecewise linear regression model. CONCLUSIONS: When blood selenium level is lower than 205.89 µg/L, blood selenium level is inversely associated with the risk of anemia. Our results provide a new strategy to reduce the risk of anemia.

Crosstalk between autophagy and the Keap1-Nrf2-ARE pathway regulates realgar-induced neurotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, the main component of which is As2S2 or As4S4 (≥90%), is a traditional Chinese natural medicine that has been used to treat carbuncles, furuncles, snake and insect bites, abdominal pain caused by parasitic worms, and epilepsy in China for many years. Because realgar contains arsenic, chronic or excessive use of single-flavor realgar and realgar-containing Chinese patent medicine can lead to drug-induced arsenic poisoning, but the exact mechanism underlying its toxicity to the central nervous system is unclear. AIM OF THE STUDY: The aim of this study was to clarify the mechanism of realgar-induced neurotoxicity and to investigate the effects of realgar on autophagy and the Keap1-Nrf2-ARE pathway. MATERIALS AND METHODS: We used rats treated with the autophagy inhibitor 3-methyladenine (3-MA) or adeno-associated virus (AAV2/9-r-shRNA-Sqstm1, sh-p62) to investigate realgar-induced neurotoxicity and explore the specific relationship between autophagy and the Keap1-Nrf2-ARE pathway (the Nrf2 pathway) in the cerebral cortex. Molecular docking analysis was used to assess the interactions among the Nrf2, p62 and Keap1 proteins. RESULTS: Our results showed that arsenic from realgar accumulated in the brain and blood to cause neuronal and synaptic damage, decrease exploratory behavior and spontaneous movement, and impair memory ability in rats. The mechanism may have involved realgar-mediated autophagy impairment and continuous activation of the Nrf2 pathway via the LC3-p62-Keap1-Nrf2 axis. However, because this activation of the Nrf2 pathway was not sufficient to counteract oxidative damage, apoptosis was aggravated in the cerebral cortex. CONCLUSIONS: This study revealed that autophagy, the Nrf2 pathway, and apoptosis are involved in realgar-induced central nervous system toxicity and identified p62 as the hub of the LC3-p62-Keap1-Nrf2 axis in the regulation of autophagy, the Nrf2 pathway, and apoptosis.

Integrating pharmacological evaluation and computational identification for deciphering the action mechanism of Yunpi-Huoxue-Sanjie formula alleviates diabetic cardiomyopathy.

Background: Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as Diabetic cardiomyopathy (DCM). However, potential targets and molecular mechanisms remain unclear. Therefore, our research was designed to evaluate rat myocardial morphology, fat metabolism and oxidative stress to verify myocardial protective effect of YP-SJ formula in vivo. And then to explore and validate its probable mechanism through network pharmacology and experiments in vitro and in vivo. Methods: In this study, DCM rats were randomly divided into five groups: control group, model group, and three YP-SJ formula groups (low-dose, middle-dose, and high-dose groups). Experimental rats were treated with 6 g/kg/d, 12 g/kg/d and 24 g/kg/d YP-SJ formula by gavage for 10 weeks, respectively. Cardiac function of rats was measured by high-resolution small-animal imaging system. The cells were divided into control group, high glucose group, high glucose + control serum group, high glucose + dosed serum group, high glucose + NC-siRNA group, high glucose + siRNA-FoxO1 group. The extent of autophagy was measured by flow cytometry, immunofluorescence, and western blotting. Results: It was found that YP-SJ formula could effectively improve cardiac systolic function in DCM rats. We identified 46 major candidate YP-SJ formula targets that are closely related to the progression of DCM. Enrichment analysis revealed key targets of YP-SJ formula related to environmental information processing, organic systems, and the metabolic occurrence of reactive oxygen species. Meanwhile, we verified that YP-SJ formula can increase the expression of forkhead box protein O1 (FoxO1), autophagy-related protein 7 (Atg7), Beclin 1, and light chain 3 (LC3), and decrease the expression of phosphorylated FoxO1 in vitro and in vivo. The results showed that YP-SJ formula could activate the FoxO1 signaling pathway associated with DCM rats. Further experiments showed that YP-SJ formula could improve cardiac function by regulating autophagy. Conclusion: YP-SJ formula treats DCM by modulating targets that play a key role in autophagy, improving myocardial function through a multi-component, multi-level, multi-target, multi-pathway, and multi-mechanism approach.

Computational identification of Shenshao Ningxin Yin as an effective treatment for novel coronavirus infection (COVID-19) with myocarditis.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the 2019 coronavirus disease (COVID-19), which has killed more than 4.5 million people. SARS-CoV-2 causes severe respiratory distress syndrome by targeting the lungs and also induces myocardial damage. Shenshao Ningxin Yin (SNY) has been used for more than 700 years to treat influenza. Previous randomized controlled trials (RCTs) have demonstrated that SNY can improve the clinical symptoms of viral myocarditis, reverse arrhythmia, and reduce the level of myocardial damage markers. METHODS: This work uses a rational computational strategy to identify existing drug molecules that target host pathways for the treatment of COVID-19 with myocarditis. Disease and drug targets were input into the STRING database to construct proteinɃprotein interaction networks. The Metascape database was used for GO and KEGG enrichment analysis. RESULTS: SNY signaling modulated the pathways of coronavirus disease, including COVID-19, Ras signaling, viral myocarditis, and TNF signaling pathways. Tumor necrosis factor (TNF), cellular tumor antigen p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), and the signal transducer and activator of transcription 3 (STAT3) were the pivotal targets of SNY. The components of SNY bound well with the pivotal targets, indicating there were potential biological activities. CONCLUSION: Our findings reveal the pharmacological role and molecular mechanism of SNY for the treatment of COVID-19 with myocarditis. We also, for the first time, demonstrate that SNY displays multi-component, multi-target, and multi-pathway characteristics with a complex mechanism of action.

Exploration of the anti-insomnia mechanism of Ganoderma by central-peripheral multi-level interaction network analysis.

BACKGROUND: Ganoderma (Lingzhi in Chinese) has shown good clinical outcomes in the treatment of insomnia, restlessness, and palpitation. However, the mechanism by which Ganoderma ameliorates insomnia is unclear. We explored the mechanism of the anti-insomnia effect of Ganoderma using systems pharmacology from the perspective of central-peripheral multi-level interaction network analysis. METHODS: The active components and central active components of Ganoderma were obtained from the TCMIP and TCMSP databases, then screened to determine their pharmacokinetic properties. The potential target genes of these components were identified using the Swiss Target Prediction and TCMSP databases. The results were matched with the insomnia target genes obtained from the GeneCards, OMIM, DisGeNET, and TCMIP databases. Overlapping targets were subjected to multi-level interaction network analysis and enrichment analysis using the STRING, Metascape, and BioGPS databases. The networks analysed were protein-protein interaction (PPI), drug-component-target gene, component-target gene-organ, and target gene-extended disease; we also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: In total, 34 sedative-hypnotic components (including 5 central active components) were identified, corresponding to 51 target genes. Multi-level interaction network analysis and enrichment analysis demonstrated that Ganoderma exerted an anti-insomnia effect via multiple central-peripheral mechanisms simultaneously, mainly by regulating cell apoptosis/survival and cytokine expression through core target genes such as TNF, CASP3, JUN, and HSP90αA1; it also affected immune regulation and apoptosis. Therefore, Ganoderma has potential as an adjuvant therapy for insomnia-related complications. CONCLUSION: Ganoderma exerts an anti-insomnia effect via complex central-peripheral multi-level interaction networks.

Runjing Decoction alleviated cyclophosphamide-induced oligoasthenospermia rats by inhibiting cell apoptosis via RXFP1/AKT/FOXO1 pathway.

Runjing Decoction (RJD) is a prescription of traditional Chinese medicine for the treatment of oligoasthenospermia. However, the molecular mechanism of RJD on oligoasthenospermia still remains unknown. A model of oligoasthenospermia was induced in 30 Sprague Dawley rats by intraperitoneal injection of cyclophosphamide at 35 mg/kg per day for 5 days and treated by intragastric RJD (13.5 g/kg) or L-carnitine (100 mg/kg) for 14 days. The body weight, testis and epididymis weight, grade A spermatozoa, grade B spermatozoa, the percentage of sperm forward motility (PR%), the sperm activity rate and the sperm density of rats were evaluated before and after RJD treatment. The testis apoptosis was determined by TUNEL staining. The expressions of RXFP1, FoxO1, PI3K, Akt, Bax and Bcl-2 were determined by qRT-PCR and Western blot, respectively. After RJD treatment, the grade A spermatozoa, sperm PR%, sperm activity and sperm density were significantly increased relative to those in model rats. Cell apoptosis of testis tissue was reversed by RJD. RJD suppressed cell apoptosis, inhibited the expression of RXFP1, FOXO1, PI3K, AKT and Bax, and promoted the expression levels of Bcl-2 in testicular tissue of oligoasthenospermia rats. RJD could alleviate sperm quality and testis damage in oligoasthenospermia rats by inhibiting RXFP1/AKT/FOXO1 pathway.

Sparrows use a medicinal herb to defend against parasites and increase offspring condition.

The incorporation of aromatic plants into nests by birds is suspected to constitute an example of preventative medicine use, whereby the phytochemical compounds within plants reduce infestation by parasites and increase offspring condition [1,2]. In China, russet sparrows (Passer cinnamomeus) incorporate wormwood (Artemisia verlotorum) leaves into their nests around the same time that local people hang wormwood from their doors as a traditional custom during the Dragon Boat Festival. The belief that this behaviour confers protection against ill health [3] is supported by the description of anti-parasite compounds in wormwood [4]. It has been suggested that the incorporation of fresh wormwood leaves into nests may serve a similar function for sparrows. Here we show that sparrows choose nest location and resupply established nests with fresh wormwood leaves using olfactory cues, that nests containing wormwood leaves have lower ectoparasite loads, and that nests with more wormwood leaves produce heavier chicks. Our results indicate that sparrows use wormwood as a preventative medicine to control ectoparasites and improve the body mass of their offspring.

[Multi-index optimization of extraction process of Fengyin Decoction based on BAS-GA-BP neural network combined with entropy weight method].

To optimize the ethanol extraction technology parameters of Fengyin Decoction by orthogonal experiment combined with beetle antennae search(BAS)-genetic algorithm(GA)-back propagation neural network(BPNN). Based on single factor investigation, the extraction temperature, ethanol volume, extraction time, and ethanol concentration were used as orthogonal experiment factors, and entropy weight method was used to calculate the comprehensive scores of aloe-emodin, glycyrrhizic acid ammonium salt, rhein, emodin, chrysophanol, physcion, cinnamaldehyde, 6-gingerol, extraction ratio and fingerprint similarity. BAS-BPNN model was established, and then, GA was used to predict the optimal extraction process. The results showed that BAS-BPNN was optimized to obtain the optimal ethanol extraction process of Fengyin Decoction as follows: extraction temperature of 87 ℃, adding 9 times of 75 % ethanol, and extracting for 47 minutes, with a comprehensive score of 1.052 9. Meanwhile, the optimal process parameters obtained by orthogonal design were as follows: the extraction temperature of 80 ℃, adding 10 times of 75% ethanol, extracting for 30 minutes, with a comprehensive score of 1.003 7. The comprehensive score of the process obtained from the BAS-BPNN model was slightly better than that from the orthogonal test, indicating that the optimized process from BAS-BPNN model was more ideal, so it was finally determined as the best extraction process for Fengyin Decoction. The process of Fengyin Decoction obtained from BAS-GA-BPNN has high extraction efficiency and good stability, which provides reference for the subsequent development and quality control.

Multi-index optimization of extraction process of Fengyin Decoction based on BAS-GA-BP neural network combined with entropy weight method / 中国中药杂志

To optimize the ethanol extraction technology parameters of Fengyin Decoction by orthogonal experiment combined with beetle antennae search(BAS)-genetic algorithm(GA)-back propagation neural network(BPNN). Based on single factor investigation, the extraction temperature, ethanol volume, extraction time, and ethanol concentration were used as orthogonal experiment factors, and entropy weight method was used to calculate the comprehensive scores of aloe-emodin, glycyrrhizic acid ammonium salt, rhein, emodin, chrysophanol, physcion, cinnamaldehyde, 6-gingerol, extraction ratio and fingerprint similarity. BAS-BPNN model was established, and then, GA was used to predict the optimal extraction process. The results showed that BAS-BPNN was optimized to obtain the optimal ethanol extraction process of Fengyin Decoction as follows: extraction temperature of 87 ℃, adding 9 times of 75 % ethanol, and extracting for 47 minutes, with a comprehensive score of 1.052 9. Meanwhile, the optimal process parameters obtained by orthogonal design were as follows: the extraction temperature of 80 ℃, adding 10 times of 75% ethanol, extracting for 30 minutes, with a comprehensive score of 1.003 7. The comprehensive score of the process obtained from the BAS-BPNN model was slightly better than that from the orthogonal test, indicating that the optimized process from BAS-BPNN model was more ideal, so it was finally determined as the best extraction process for Fengyin Decoction. The process of Fengyin Decoction obtained from BAS-GA-BPNN has high extraction efficiency and good stability, which provides reference for the subsequent development and quality control.

The novel methyltransferase SETD4 regulates TLR agonist-induced expression of cytokines through methylation of lysine 4 at histone 3 in macrophages.

The production of inflammatory cytokines is closely related to pathogen-associated molecular pattern (PAMP)-triggered activation of the Toll-like receptor (TLR), intracellular signal transduction pathways such as MAPK and NF-κB, and histone modifications. Histone methylation, a type of histone modifications, is mainly accomplished by a class of SET family proteins containing highly conserved SET domains. In the present study, we found that SET domain-containing protein 4 (SETD4) regulated inflammatory cytokines in response to TLR agonists. LPS stimulation led to the enhanced SETD4 expression, while the increased IL-6 and TNF-α release from LPS-stimulated RAW264.7 cells was attenuated by depletion of SETD4 using RNA interference. The results were further confirmed in BMDMs and pMφ isolated from SETD4-deficient mice where SETD4-/- macrophages treated with LPS, BLP or Poly(I:C) showed down-regulated IL-6 and TNF-α mRNA and protein levels when compared with SETD4+/+ macrophages. Moreover, the mRNA levels of all NF-κB-dependent genes including IL-1ß, IL-10, NFKBA, DUSP1, CCL2, CCL5, and CXCL10 in SETD4-/- macrophages were substantially reduced. To further clarify the regulatory mechanism(s) by which SETD4 modulates inflammatory cytokines, we examined the effect of SETD4 on the activation of MAPK and NF-κB signalling pathways, and found that knockout of SETD4 had no effect on phosphorylation of p38, ERK, JNK, p65, and IκBα. Notably, SETD4 translocated quickly from the cytosol to the nucleus upon LPS stimulation, suggesting that SETD4 may exert its regulatory function downstream of the MAPK and NF-κB pathways. To characterize this, we performed an in vitro HMTase assay to measure histone methyltransferase (HMTase) activity of SETD4. H3K4me1 and H3K4me2 levels were enhanced dramatically with the supplementation of SETD4, whereas both H3K4me1 and H3K4me2 were strongly attenuated in SETD4-/- BMDMs. Moreover, the LPS-stimulated recruitment of H3K4me1 and H3K4me2 at both TNF-α and IL-6 promoters was severely impaired in SETD4-/- BMDMs. Collectively, these results demonstrate that SETD4 positively regulates IL-6 and TNF-α expression in TLR agonist-stimulated macrophages by directly activating H3K4 methylation.

Effect of low-level laser therapy on tooth-related pain and somatosensory function evoked by orthodontic treatment.

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm-2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.

Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal function in patients with chronic renal failure: A meta-analysis of randomized controlled trials
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OBJECTIVE: Rheum officinale is a traditional medicinal herb used widely in China to treat chronic renal failure, but the proof of evidence-based medicine is poor. This meta-analysis aims to assess the benefits of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) supplemented with Rheum officinale for delaying the progression of chronic renal failure. MATERIALS AND METHODS: The MEDLINE, EMBASE, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases were searched to identify studies published before September 2016 that investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and blood urea nitrogen (BUN) levels in chronic renal failure patients. Review Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects models were used to analyze the data. RESULTS: The meta-analysis included nine clinical trials. Comparisons of patients before and after treatment with ACEI/ARB plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted in significantly greater reductions in SCr (short-term: weighted mean difference (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71, 95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long-term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. CONCLUSION: In patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB significantly lowered both SCr and BUN, particularly after long-term administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the treatment of patients with impaired renal function.
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Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients.

BACKGROUND AND PURPOSE: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. METHODS: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). CONCLUSIONS: Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Atorvastatin improves pathological changes in the aged kidney by upregulating peroxisome proliferator-activated receptor expression and reducing matrix metalloproteinase-9 and transforming growth factor-ß1 levels.

OBJECTIVE: To investigate the effects of atorvastatin (AVT) on renal function and renal pathological changes in the aged rat and explore their possible mechanisms. METHODS: Twenty-month-old, normal female Wistar rats were divided into three groups: group A (n=8) was fed high-dose AVT (10mg/kg/d); group B (n=8) was fed low-dose AVT (1mg/kg/d); and group C (controls, n=8) received the same volume of normal saline; 3-month-old, normal female Wistar rats served as young normal controls (n=8). All rats were sacrificed following a 4-month treatment period. Serum creatinine and blood lipid levels were measured. The glomerular sclerosis index and tubulointerstitial lesions were determined using renal periodic acid-Schiff-stained paraffin sections. The mRNA and protein expressions of matrix metalloproteinases (MMP)-9 and -2, tissue inhibitors of metalloproteinase (TIMP)-1 and -2, transforming growth factor-ß1 (TGF-ß1), and peroxisome proliferator-activated receptors (PPARs) were examined using reverse transcription polymerase chain reactions and Western blots, respectively. RESULTS: Serum lipid (including serum cholesterol and serum triglycerides) levels in aged rats were significantly higher than those in young rats (p<0.05). Compared to the aged control group, high-dose AVT was associated with significantly lower serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in aged rats (p<0.05); low-dose AVT was associated only with lower serum LDL-C levels (p<0.05). Renal morphological changes in aged rats included focal glomerulosclerosis, infiltration of inflammatory cells, and arteriole sclerosis. Improved renal pathology was observed in aged, AVT-treated rats, and included a decreased glomerular sclerosis index and tubulointerstitial lesion score, especially in those receiving high-dose AVT. Additionally, renal artery wall thickening, luminal narrowing, and arteriolosclerosis were significantly less severe in aged rats receiving high-dose AVT. Upregulated expression of MMP-9 and TGF-ß1 was observed in the renal tissue of aged rats. AVT treatment was associated with a reversal of these phenomena and upregulated expression of TIMP-1, PPARα, PPARß, and PPARγ in aged rats. CONCLUSION: AVT improved the renal pathology of aged rats. These effects may have been induced by the lowering of blood lipids, maintaining the MMP/TIMP balance, and downregulating the expression of TGF-ß1. AVT may reduce the levels of MMP-9 and TGF-ß in aged rats by upregulating the expression of PPARs.