Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis.

The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman's bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits.

Assessment of ecotoxicity effects of aspirin on non-target organism (Daphnia magna) via analysis of the responses of oxidative stress, DNA methylation-related genes expressions and life traits changes.

Aspirin (acetylsalicylic acid, ASA), a widely used non-steroidal anti-inflammatory drug, was frequently detected in aquatic environments around the world. However, information on the potential toxic effects of aspirin on non-target aquatic invertebrates is limited. In the present study, we investigated the effects of ASA on the transcriptional expressions of antioxidant genes (Nrf2, Keap1, HO-1, GCLC, GPx, TRX, TrxR and Prx1) and DNA methylation genes (DNMT1, DNMT3 and TET2) in Daphnia magna (D. magna)for 24, 48 and 96 h and the changes of antioxidant enzymatic activity and GSH, MDA content for 48 h. The effects of ASA on the life traits of D. magna were also addressed via a 21-days chronic toxicity test. Results showed that the expressions of Nrf2 and its target genes (HO-1, GPx and TrxR, GCLC, TRX and Prx1) were induced to different degrees at 48 h and/or 96 h. The activity of antioxidant enzymes (SOD, CAT, GST and GPx) and MDA content increased but GSH content decreased, indicating that ASA caused oxidative stress in D. magna. ASA also changed the expression of DNA methylation genes, such as DNMT and TET2, in D. magna. We speculated that ASA may affect the antioxidant system responses through regulation of Nrf2/Keap1 signaling pathway, and/or through indirectly influencing DNA methylation levels by DNMT and TET gene expression, but the detailed mechanism needs further investigations. Chronic exposure to ASA for 21 days caused inhibitions on the growth, reproduction and behavior of D. magna (e.g., delaying days to the first brood and shortening the body length). In summary, ASA significantly affected the antioxidant responses of D. magna, and negatively disturbed its life traits in growth, development and reproduction.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY / 药物分析学报

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor / 药物分析学报

Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.

Analysis of refractive error factors in patients with high myopia combined with cataract after different operation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes in anterior chamber depth(ACD), axial length(AL), and corneal curvature(K)after operation in patients with high axial myopia combined with cataract, and the effect on postoperative mean refractive error(MFE)by different surgical approaches.METHODS: A total of 126 patients(126 eyes)performed cataract combined with intraocular lens(IOL)implantation were selected and divided into 3 groups according to different surgical approaches and axial length. Group A included 42 patients(42 eyes)who had cataract combined with high myopia and were performed cataract phacoemulsification combined with IOL implantation; Group B included 42 patients(42 eyes)who had cataract combined with high myopia and underwent small incision cataract extracapsular extraction combined with IOL implantation; Group C included 42 patients(42 eyes)who had cataract with normal axial length and underwent cataract phacoemulsification combined with IOL implantation. Then, the ACD, AL, K value and visual acuity of the three groups at 1d before operation and 3mo after operation were measured, and statistical analysis was performed.RESULTS: The differences in the mean values of preoperative and postoperative changes in ACD(△ACD)and AL(△AL)between groups A and B showed no statistical significance. The differences in the mean values of △ACD and △AL between groups A and C and groups B and C were both statistically significant(both P&#x0026;#x003C;0.01). △ACD and △AL in all three groups showed positive correlation(rA=0.855, rB=0.856, rC=0.639, all P&#x0026;#x003C;0.05). Furthermore, preoperative AL, △AL, △ACD and MFE in all three groups showed positive correlation(rA=0.874, 0.877, 0.858, rB=0.875, 0.879, 0.858, rC=0.428, 0.766, 0.862, all P&#x0026;#x003C;0.05). The standardized regression coefficients of groups A and B were △AL&#x0026;#x003E;△ACD(1.32 and 1.31 times), and the standardized regression coefficients of group C were △ACD&#x0026;#x003E;△AL(1.66 times).CONCLUSION: Different surgical procedures had no significant effect on the postoperative K value and MFE in patients with high axial myopia combined with cataract, of which main influencing factor is the change in the AL before and after surgery. The postoperative MFE in patients with normal AL was more due to the change of ACD.

Research progress on the predictive role of serum Krebs von den Lungen-6 in pulmonary diseases / 中国职业医学

Early diagnosis of pulmonary diseases is of great significance for their prevention and treatment. Serum Krebs von den Lungen-6 (KL-6) assay can reflect the damage degree of alveolar epithelium and stromal tissue, and is simple, non-invasive and low-cost. Pervious study showed that the serum KL-6 level was higher in patients with various interstitial lung diseases (e.g. idiopathic pulmonary fibrosis and connective tissue disease, primary Sjögren's syndrome, rheumatoid arthritis, idiopathic inflammatory myopathy and systemic sclerosis combined with interstitial lung disease), non-small cell lung cancer, various pneumonias and chronic obstructive pulmonary disease compared to healthy controls. Therefore, serum KL-6 has good sensitivity and specificity for the early diagnosis of these diseases. Occupational pneumoconiosis is an interstitial lung disease with a well-established etiology. Pervious study has shown that serum KL-6 level was higher in patients with occupational silicosis, occupational asbestosis, and dust-exposed workers compared to healthy controls. However, due to the limited sample size and the inconsistent findings on different studies, further research is needed to study the role of serum KL-6 in the early diagnosis of pneumoconiosis. Future studies should increase the sample size, improve the detection methods for serum KL-6, explore its feasibility as an early diagnostic biomarker for occupational pulmonary diseases, and investigate the efficacy andvalue of its combined application with other biomarkers in the early diagnosis of various pulmonary diseases, including occupational lung diseases, to fully exploit its predictive role in pulmonary diseases.

The role of surfactant associated protein-A in silicosis / 中国职业医学

Objective: To investigate the role of surfactant associated protein-A (SP-A) in the development and progression of silicosis, and its mechanism. Methods: Homozygous and heterozygous mice of SP-A knockout of specific pathogen free (SPF) grade were selected for mating, and mice with SP-A-/- genotype were selected for subsequent experiments. SP-A wild-type (SP-A+/+) and SP-A-/- mice were divided into SP-A+/+ control group, SP-A-/- control group, SP-A+/+ silicosis group and SP-A-/- silicosis group with six mice in each group by random number table method. Mice in both silicosis groups were given 20.0 μL 250 g/L silica suspension by tracheal exposure, and mice in both control groups were injected with 0.9% sodium chloride solution at the same volume. On the 28th day after modeling, mice were sacrificed. Lung tissues were used for lung histopathology examination. The apoptosis of alveolar type Ⅱ epithelial cells of mice was detected by TUNEL method. The mRNA expression of B-lymphoblastoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 in lung tissues of mice was detected by quantitative real-time polymerase chain reaction. Results: The histopathological result of mice showed that thickened alveolar septum, scattered silicon nodule and collagen fiber formation were observed in the mice lungs of SP-A+/+ silicosis group, and a large number of inflammatory cells were observed in silicosis nodule, after exposure to silica dust. SP-A-/- silicosis group resulted in a more severe pulmonary inflammation and interstitial fibrosis compared to SP-A+/+ silicosis group. The apoptosis of alveolar type Ⅱ epithelial cells and the mRNA relative expression levels of Bax, Caspase-3 and Caspase-9 in lung tissues of mice in each silicosis groups were increased compared with their control groups (all P<0.05). The above four indexes of mice in SP-A-/- silicosis group were higher than those in SP-A+/+ silicosis group (all P<0.05). There was no significant difference in the expression of Bcl-2 mRNA in lung tissues of these four groups (P>0.05). Conclusion: Knockout of SP-A can aggravate inflammation and pulmonary fibrosis in silicosis model mice, and promote apoptosis of alveolar type Ⅱ epithelial cells. The mechanism may be related to the Bcl-2/Bax/Caspase-3 signaling pathway which affects the apoptosis of mitochondrial pathway.

Research progress of anti-fibrotic drugs that inhibit epithelial-mesenchymal transition in pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is the end-stage pathological change of lung diseases, which seriously affects the respiratory function of human body. A large number of studies at home and abroad have confirmed that epithelial-mesenchymal transition (EMT) is an important intermediate stage in the development of pulmonary fibrosis. Inhibition of multiple pathways upstream and downstream of EMT, such as the classical Smads pathway and non-Smads pathway of TGF-1 can effectively inhibit the process of EMT and alleviate pulmonary fibrosis. This article will review the main conclusions of the mechanism of action of EMT as a target to improve the pathology of pulmonary fibrosis so far, and provide a theoretical basis and research direction for further research and development of anti-pulmonary fibrosis drugs.

Acupuncture for delayed sleep-wake phase disorder: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD).@*METHODS@#A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups.@*RESULTS@#Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05).@*CONCLUSION@#Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.

Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection / 生物医学工程学杂志

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.

Evaluation of Extrathyroidal Extension of Papillary Thyroid Microcarcinoma With Three-Dimensional Tomographic Ultrasound Imaging / 中国医学科学院学报

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ2=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ2=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ2=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ2=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ2=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.

Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency.@*METHODS@#A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups.@*RESULTS@#After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01).@*CONCLUSION@#Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

Analyzing the association between polymorphism of CES1 and MUC5B genes and methyl acetate poisoning by whole exome sequencing / 中国职业医学

Objective To detect and analyze the susceptibility genes of methyl acetate poisoning in patients by whole exome sequencing. Methods Two patients with occupational acute severe methyl acetate poisoning and their first-degree relatives who work in the same occupation and position with similar working hours were selected as the research subjects by judgment sampling method. Peripheral blood was collected for whole exome sequencing. The sequencing data was compared with the public genome database to screen the mutation sites and find out the gene sites related to methyl acetate poisoning. The suspected pathogenic mutation genes were annotated and interpreted. Results The results of whole exome sequencing showed that there were 40 differential genes between the patients with methyl acetate poisoning and their first-degree relatives, including 80 single nucleotide polymorphisms and eight Indel with specific marker sequence index. Among these, the genes with strong correlation were carboxyesterase 1 (CES1) and mucin (MUC) 5B. The CES1 gene loci c.248C>T (p.Ser83Leu) heterozygous mutations, MUC5B gene loci c.6635C>T (p.Thr2212Met) and c.7685C>T (p.Thr2562Met) heterozygous mutations in patients with methyl acetate poisoning were detected. They were missense mutations. By constructing a protein-protein interaction network, a total of 11 pairs of interactions with high levels of evidence were identified, involving genes such as lysine methyltransferase 2C, HECT and RLD domains containing E3 ubiquitin protein ligase 2, neutrophil cytoplasmic factor 1, nicotinamide adenine dinucleotide phosphate oxidase 3, C-terminal binding protein 2, zinc finger protein 717, FSHD region gene 2 family member C, FSHD region gene 1, MUC4, MUC6, MUC5B, and MUC12. Conclusion The polymorphism of CES1 and MUC5B genes may be related to the occurrence and development of methyl acetate poisoning in patients.

Exploring the mechanism of action of curcumin in the treatment of silicosis based on network pharmacology and molecular docking / 中国职业医学

Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.

Inhibition of lead-induced hepatic inflammation by inhibiting neutrophil granule protein in mice / 中国职业医学

Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups： control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.

A novel three-dimensional flow-through graphite felt-matrix cathode for in-situ hydrogen peroxide generation in multi-environment systems-Multiphysics modeling for in-situ hydrogen peroxide generation.

In order to achieve in-situ H2O2 generation in multi-environment systems, polyvinylpyrrolidone (PVP) and modified carbon nitride (t-g-C3N4) are co-doped onto graphite felt-matrix (GF-matrix) by electrodeposition to develop a novel cathode electrode. By means of 3D-X-ray CT, High-Resolution Transmission Electron Microscope (HRTEM), X-ray Photoelectron Spectrometer (XPS), Raman and Electrochemical Workstation, microscopic physical-chemical properties of materials are researched to optimize the electrode structure. Results show that the optimal electrode presents over H2O2 production rate of 2000 mgL-1·h-1, and as high as current efficiency of 93% to 98% in simulated freshwater (50 mM Na2SO4, pH = 1-12) at 20 mAcm-2. Furthermore, we built an original three-dimensional (3D) flow-through GF-matrix cathode model on H2O2 generation in simulated freshwater, explaining solution pH change reasons from solution inlet to outlet.

Application of laparoscopic internal iliac artery temporary occlusion and uterine repair combined with hysteroscopic aspiration in type III cesarean scar pregnancy.

To investigate the efficacy and safety of laparoscopic internal iliac artery temporary occlusion and uterine repair combined with hysteroscopic aspiration in type III cesarean scar pregnancy. 135 cases of cesarean scar pregnancy in Guangzhou Women and Children's Hospital from November 2017 to November 2020 were collected and 32 cases of type III patients were retrospectively analyzed. They were divided into internal iliac artery temporary occlusion (IIATO) group (21 cases), and bilateral uterine artery embolization (UAE) group (11 cases). The general condition, intraoperative bleeding, postoperative complications, and prognosis of the two groups were analyzed. In the IIATO group, the bilateral internal iliac arteries were temporarily blocked with No. 10 silk thread under laparoscopy. The scar pregnancy clearance and repair of the scar were performed after incision. Subsequently, we performed hysteroscopic aspiration. After the operation, the internal iliac artery ligation thread was removed. In the UAE group, the patients were treated with bilateral uterine artery embolization. Laparoscopic uterine scar repair and hysteroscopy aspiration were performed within 24 hours after embolization. There was no significant difference in age, times of pregnancy, times of cesarean section and gestational weeks between the two groups (P>0.05). No significant differences were observed in the diameter of gestational sac or gestational mass and serum human chorionic gonadotropin (ß-hCG) level between the two groups before operation (P>0.05). The operations were successfully completed in 32 patients, and intraoperative blood loss was 67.14±32.78 ml and 71.35±31.56 ml, respectively (P<0.05). The length of hospital stay was 5.14±0.32 day and 4.97±0.21 day, respectively. No peri-procedural bleeding occurred and no secondary surgeries were required. Laparoscopic internal iliac artery temporary occlusion and uterine repair combined with hysteroscopic aspiration is an effective and safe treatment for type III cesarean scar pregnancy, with less postoperative complications and better protection of fertility function for patients.

The lncRNA PVT1/miR-423-5p axis is positively correlated with the severity of bronchial asthma

Bronchial asthma (BA) is a serious problem affecting the quality of life of patients. Long noncoding RNAs (lncRNAs) are involved in BA. This study set out to investigate expressions of PVT1/miR-423-5p in the serum of BA patients and its clinical value on BA diagnosis and evaluation. This study included the same number (N = 100) of patients with BA at remission (BA-R), BA at exacerbation (BA-E), and healthy controls. PVT1 level was increased in BA-R and BA-E patients, and PVT1 level was higher in BA-E patients than BA-R patients. miR-141-3p targeted PVT1. miR-423-5p was downregulated in the serum of BA patients and was negatively correlated with PVT1. Area under ROC curve of PVT1/miR-423-5p axis on BA-R patients was 0.837 with sensitivity 0.74, specificity 0.84, while that of BA-E was 0.974 with sensitivity 0.87 and specificity 0.95. PVT1/miR-423-5p axis was negatively correlated with FEV1/FVC, FEV1% pred, and IL-10, and positively correlated with IgE, TNF-α, and IL-6. PVT1 and PVT1/miR-423-5p axis were associated with increased severity while miR-423-5p axis was negatively associated with BA severity. In conclusion, increased levels of PVT1/miR-423-5p had higher diagnostic efficiency on BA patients, especially patients with acute exacerbation (AU)

Effects of aerobic exercise on hippocampal SUMOylation in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease. SUMOylation, a post-translational modification, has been found to be dysregulated in the AD brain and to exacerbate learning and memory disabilities and increase amyloid beta (Aß) expression further. To investigate whether exercise-induced alleviation of AD was associated with SUMOylation, which still remains unknown, 3-month-old C57BL/6 mice and APP/PS1 transgenic mice were randomly divided into the wild-type control (WC), wild-type exercise (WE), APP/PS1 control (AC), and APP/PS1 exercise (AE) groups. Mice in the exercise groups underwent a 3-month treadmill exercise regimen. We observed impaired learning and memory abilities in APP/PS1 mice, but the 3-month treadmill exercise regimen improved spatial learning and memory abilities in wild-type and APP/PS1 mice. In addition, senile plaques, SUMO1 mRNA, and SENP1 mRNA levels increased in the hippocampi of APP/PS1 mice. However, 3-month treadmill exercise decreased the levels of senile plaques, SUMO1 mRNA and SENP1 mRNA as well as may reduce SUMO1 modification in 6-month-old APP/PS1 mice, but SUMO2 mRNA expression, SUMO2/3 modification, and overall SUMOylation levels did not significantly change. Our results suggest that the impaired learning and memory abilities and aggregations of Aß may relate to increased hippocampal SUMO1 transcription levels; the beneficial effects of treadmill exercise on learning and memory performances and AD pathogenesis may associated with the abatement of SUMO1 modification, but may not with SUMO2/3 modification.