Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children.

OBJECTIVE: To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. METHODS: 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. RESULTS: (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. CONCLUSION: Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children

Abstract Objective To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. Conclusion Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children?

Objective: By examining fractional exhaled nitric oxide (FeNO) levels and performing pulmonary function testing, this study explored whether the multicenter study on the normal range of FeNO in children in China can be used to evaluate standardized treatment efficacy in 6- to 12-year-old children with asthma. Methods: A total of 115 children aged 6-12 years old who were first diagnosed with asthma and received standardized asthma treatment from April 2018 to July 2022 were selected. According to the FeNO level at the first visit, the subjects were divided into different high- and low-FeNO groups according to the American Thoracic Society (ATS) guidelines and the Chinese multicenter study recommendations. The consistency of the two grouping methods and the differences between the high- and low-FeNO groups were compared after standardized treatment. The grouping method that was the most suitable for children in the cross group was discussed. Results: (i) There was fair consistency between the Chinese multicenter study recommendations and the ATS guidelines regarding the classification of high- and low-FeNO groups (Kappa = 0.338). (ii) Repeated-measures ANOVA showed that the level of improvement in FVC%, FEV1%, FEF25%, FEF50%, and FeNO in the American high- and low-FeNO groups differed with the duration of therapy (P < 0.05), however, there was no significant difference between the Chinese groups. (iii) FEV1% and FeNO improved more after treatment in the fixed high-FeNO group than in the cross group (P < 0.05). Conclusion: The Chinese multicenter study on the normal range of FeNO in children in China has a limited role in evaluating standardized asthma treatment efficacy in 6- to 12-year-old children. The ATS guidelines are currently recommended for clinical assessment of asthma treatment efficacy.

The machine learning model based on trajectory analysis of ribonucleic acid test results predicts the necessity of quarantine in recurrently positive patients with SARS-CoV-2 infection.

Background: SARS-CoV-2 patients re-experiencing positive nucleic acid test results after recovery is a concerning phenomenon. Current pandemic prevention strategy demands the quarantine of all recurrently positive patients. This study provided evidence on whether quarantine is required in those patients, and predictive algorithms to detect subjects with infectious possibility. Methods: This observational study recruited recurrently positive patients who were admitted to our shelter hospital between May 12 and June 10, 2022. The demographic and epidemiologic data was collected, and nucleic acid tests were performed daily. virus isolation was done in randomly selected cases. The group-based trajectory model was developed based on the cycle threshold (Ct) value variations. Machine learning models were validated for prediction accuracy. Results: Among the 494 subjects, 72.04% were asymptomatic, and 23.08% had a Ct value under 30 at recurrence. Two trajectories were identified with either rapid (92.24%) or delayed (7.76%) recovery of Ct values. The latter had significantly higher incidence of comorbidities; lower Ct value at recurrence; more persistent cough; and more frequently reported close contacts infection compared with those recovered rapidly. However, negative virus isolation was reported in all selected samples. Our predictive model can efficiently discriminate those with delayed Ct value recovery and infectious potentials. Conclusion: Quarantine seems to be unnecessary for the majority of re-positive patients who may have low transmission risks. Our predictive algorithm can screen out the suspiciously infectious individuals for quarantine. These findings may assist the enaction of SARS-CoV-2 pandemic prevention strategies regarding recurrently positive patients in the future.

A retrospective study of Pupingqinghua prescription versus Lianhuaqingwen in Chinese participants infected with SARS-CoV-2 Omicron variants.

Background: Coronavirus disease (COVID-19) seriously endangers global public health. Pupingqinghua prescription (PPQH) is an herbal formula from traditional Chinese medicine used for treatment of SARS-CoV-2 infection. This study aims to evaluate the clinical efficacy and safety of PPQH in Chinese participants infected with the SARS-CoV-2 Omicron variant. Methods: A total of 873 SARS-CoV-2 (Omicron)-infected patients were included. Among them, the patients were divided into the PPQH group (653 cases) and LHQW group (220 cases) according to different medications. The effectiveness indicators (hematological indicators, Ct values of novel Coronavirus nucleic acid tests, and viral load-shedding time) and safety indicators (liver and kidney function and adverse events) were analyzed. Results: There was no significant difference in baseline characteristics between the PPQH group and the LHQW group, except the gender; After the treatment, the levels of IL-5, IL-6, IL-10, NK cells, and INF-α of the patients in the PPQH group showed a downward trend (p < 0.05); The viral load shedding time was 5.0 (5.0, 7.0) in the PPQH group and 5.0 (4.0, 7.0) in the LHQW group; both PPQH and LHQW can shorten the duration of symptoms of fever, cough, and sore throat. The re-positive rate of COVID-19 test was 1.5 % in the PPQH group and 2.3 % in the LHQW group. In terms of safety, the levels of γ-GTT decreased significantly (p < 0.01); gastrointestinal reaction was the primary adverse reaction, and the reaction rate was 4.7 % in the PPQH group and 9.5 % in the LHQW group. Conclusion: PPQH can shorten the length of hospital stay and improve clinical symptoms of patients with SARS-COV-2 (Omicron), and it also has a good safety profile.

Electreted Sandwich Membranes with Persistent Electrical Stimulation for Enhanced Bone Regeneration.

Physiologically relevant electrical microenvironments play an indispensable role in manipulating bone metabolism. Although implanted biomaterials that simulate the electrical properties of natural tissues using conductive or piezoelectric materials have been introduced in the field of bone regeneration, the application of electret materials to provide stable and persistent electrical stimulation has rarely been studied in biomaterial design. In this study, a silicon dioxide electret-incorporated poly(dimethylsiloxane) (SiO2/PDMS) composite electroactive membrane was designed and fabricated to explore its bone regeneration efficacy. SiO2 electrets were homogeneously dispersed in the PDMS matrix, and sandwich-like composite membranes were fabricated using a facile layer-by-layer blade-coating method. Following the encapsulation, electret polarization was conducted to obtain the electreted composite membranes. The surface potential of the composite membrane could be adjusted to a bone-promotive biopotential by tuning the electret concentration, and the prepared membranes exhibited favorable electrical stability during an observation period of up to 42 days. In vitro biological experiments indicated that the electreted SiO2/PDMS membrane promoted cellular activity and osteogenic differentiation of mesenchymal stem cells. In vivo, the electreted composite membrane remarkably facilitated bone regeneration through persistent endogenous electrical stimulation. These findings suggest that the electreted sandwich-like membranes, which maintain a stable and physiological electrical microenvironment, are promising candidates for enhancing bone regeneration.

microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82.

OBJECTIVE: Exosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82). METHODS: miR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model. RESULTS: miR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis. CONCLUSION: The study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.

Can the nucleic acid Ct value of discharged patients infected with SARS-CoV-2 Omicron variant be 35?--A retrospective study on fluctuation of nucleic acid Ct values in SNIEC mobile cabin hospital.

Objective: To explore the meaning of cycle threshold (Ct) value fluctuation and the appropriateness of setting the discharge Ct value to 35, which is the current standard in Chinese guidelines. Method: A retrospective study was conducted on 95 patients with Ct value fluctuation (Ct value below 35 on day 3; group A) and 97 patients with a normal discharge process (control; group B). Their clinical characteristics and follow-up data were collected. Results: (1) There was no significant difference between the groups in age, gender distribution, number of vaccinations, initial ORF-Ct value, and initial N-Ct value. The proportion of patients complicated with chronic internal disorders, respiratory symptoms, and abnormal chest radiology in group A was significantly higher than that in group B. (2) Between the two groups, there was no significant difference in the ORF-Ct or N-Ct value on day 1, but the ORF-Ct and N-Ct values of group B on days 2 to 4 were significantly higher than those of group A. (3) There was no significant difference between the groups in the ORF-Ct value at discharge, but there was a significant difference in the N-Ct value at discharge. Seven days after discharge, almost 100% of the patients had been cured. The mean negative conversion interval of nucleic acid of the patients in group A was 14.5 ± 4.6 days, which was longer than that of the patients in group B (11.8 ± 4 days). (4) Logistic regression analysis showed that the ORF-Ct value on day 2 was the key factor influencing the Ct value fluctuation. Conclusion: The fluctuation of Ct value is only a normal phenomenon in the recovery period of the disease, and there is no need for excessive intervention. It is reasonable to set the Ct value of the discharge standard to 35 and retest the nucleic acid on the 10th day after discharge for patients with underlying diseases or symptoms.

Medical implementation practice and its medical performance evaluation of a giant makeshift hospital during the COVID-19 pandemic: An innovative model response to a public health emergency in Shanghai, China.

Introduction: In confronting the sudden COVID-19 epidemic, China and other countries have been under great pressure to block virus transmission and reduce fatalities. Converting large-scale public venues into makeshift hospitals is a popular response. This addresses the outbreak and can maintain smooth operation of a country or region's healthcare system during a pandemic. However, large makeshift hospitals, such as the Shanghai New International Expo Center (SNIEC) makeshift hospital, which was one of the largest makeshift hospitals in the world, face two major problems: Effective and precise transfer of patients and heterogeneity of the medical care teams. Methods: To solve these problems, this study presents the medical practices of the SNIEC makeshift hospital in Shanghai, China. The experiences include constructing two groups, developing a medical management protocol, implementing a multi-dimensional management mode to screen patients, transferring them effectively, and achieving homogeneous quality of medical care. To evaluate the medical practice performance of the SNIEC makeshift hospital, 41,941 infected patients were retrospectively reviewed from March 31 to May 23, 2022. Multivariate logistic regression method and a tree-augmented naive (TAN) Bayesian network mode were used. Results: We identified that the three most important variables were chronic disease, age, and type of cabin, with importance values of 0.63, 0.15, and 0.11, respectively. The constructed TAN Bayesian network model had good predictive values; the overall correct rates of the model-training dataset partition and test dataset partition were 99.19 and 99.05%, respectively, and the respective values for the area under the receiver operating characteristic curve were 0.939 and 0.957. Conclusion: The medical practice in the SNIEC makeshift hospital was implemented well, had good medical care performance, and could be copied worldwide as a practical intervention to fight the epidemic in China and other developing countries.

P38 mitogen-activated protein kinase promotes Wnt/ß-catenin signaling by impeding Dickkofp-1 expression during Haemophilus parasuis infection.

Haemophilus parasuis induces severe acute systemic infection in pigs, characterized by fibrinous polyserositis, polyarthritis and meningitis. Our previous study demonstrated that H. parasuis induced the activation of p38 mitogen-activated protein kinase (MAPK) pathway, increasing the expression of proinflammatory genes and mediating H. parasuis-induced inflammation. Moreover, Wnt/ß-catenin signaling activation induced by H. parasuis disrupts the adherens junction between epithelial cells and initiates the epithelial-mesenchymal transition (EMT). In the present study, p38 MAPK was found to be involved in the accumulation of nuclear location of ß-catenin during H. parasuis infection in PK-15 and NPTr cells, via modulating the expression of dickkofp-1 (DKK-1), a negative regulator of Wnt/ß-catenin signaling. We generated DKK-1 knockout cell lines by CRISPR/Cas9-mediated genome editing in PK-15 and NPTr cells, and found that knockout of DKK-1 led to the dysfunction of p38 MAPK in regulating Wnt/ß-catenin signaling activity in H. parasuis-infected cells. Furthermore, p38 MAPK activity was independent of the activation of Wnt/ß-catenin signaling during H. parasuis infection. This is the first study to explore the crosstalk between p38 MAPK and Wnt/ß-catenin signaling during H. parasuis infection. It provides a more comprehensive view of intracellular signaling pathways during pathogenic bacteria-induced acute inflammation.

A systematic review of the clinical and genetic characteristics of Chinese patients with cystic fibrosis.

OBJECTIVES: To investigate and summarize the clinical and genetic characteristics of Chinese cystic fibrosis (CF) patients to improve clinicians' understanding and decrease the rates of misdiagnosis and missed diagnoses in China. METHODS: The EMBASE, Cochrane Library, PubMed and SinoMed databases were searched for studies involving Chinese CF patients from January 1975 to August 2019. RESULTS: In total, 113 Chinese patients, including 53 males and 60 females, were reported. Nineteen patients had a family history of CF. The median age at diagnosis was 8.7 years. Among Chinese CF patients, 70.8% had bronchiectasis, 9.7% had a hemoptysis history, 33.6% had clubbed fingers, 17.7% had allergic bronchopulmonary aspergillosis, and 29.2% had chronic diarrhea; the incidence of malnutrition was 52.2%. Five patients had jaundice, 26 patients had hepatomegaly, and 9 patients had meconium ileus in the neonatal period, and the incidence of liver cirrhosis was 5.3%. The predominant organism in airways was Pseudomonas aeruginosa, followed by Staphylococcus aureus. Seventy-nine patients underwent the sweat test, and all of them were positive, with an average chloride ion level of 122.2 mmol/L. Eighty-eight Chinese CF patients underwent genetic testing, and 74 CF transmembrane conductance regulator (CFTR) gene mutations were reported. The most common gene mutation was c.2909G→A. One Phe508del gene mutation was observed. CONCLUSION: The common clinical manifestations and CFTR gene mutations in Chinese CF patients are different from those in Caucasian patients. The age at CF diagnosis in China is relatively old, suggesting that the CF incidence in China may be seriously underestimated.

Pathogenicity and Molecular Typing of Fowl Adenovirus-Associated With Hepatitis/Hydropericardium Syndrome in Central China (2015-2018).

In central China, a large number of broiler and layer flocks have suffered from outbreaks of severe hepatitis/hydropericardium syndrome (HHS). This resulted in huge economic losses to the poultry industry, from 2015 to 2018. To identify the specific pathogen and study its pathogenicity, 195 samples from Hubei, Jiangxi, Anhui, Hunan, and Henan provinces in central China were collected. The samples were screened for the adenovirus hexon gene, and neighbor joining was used for the phylogenetic reconstruction of the sequences. Among the collected samples, 122 were found to be positive for fowl adenovirus (FAdV) by PCR, and 73 isolates were obtained. The predominant viral serotype was serotype 4 (FAdV-4), which was found in 48 isolates, while 24 were serotype 10 (FAdV-10), and one was serotype 2 (FAdV-2). The CH/HBTF /1710 isolate was selected for further experiment and inoculated into 33-day-old specific pathogen-free chickens via intramuscular injection or oral administration to evaluate pathogenicity. It was found that the mortality for chickens infected by intramuscular injection or oral administration was 70 and 60%, respectively. Necropsy revealed mild to severe hepatitis and hydropericardium at 5 and 7 days after infection. Ancestor analyses indicated that all of the FAdV-4 strains obtained in this study shared a common Indian precursor and had a close genetic relationship with the JSJ13, SDSX, HN/151025, and SDDM-15 strains common in China.

Isolation and Identification of Porcine Deltacoronavirus and Alteration of Immunoglobulin Transport Receptors in the Intestinal Mucosa of PDCoV-Infected Piglets.

Porcine deltacoronavirus (PDCoV) is a porcine enteropathogenic coronavirus that causes watery diarrhea, vomiting, and frequently death in piglets, causing serious economic losses to the pig industry. The strain CHN-JS-2017 was isolated and identified by cytopathology, immunofluorescence assays, transmission electron microscopy, and sequence analysis. A nucleotide sequence alignment showed that the whole genome of CHN-JS-2017 is 97.4%-99.6% identical to other PDCoV strains. The pathogenicity of the CHN-JS-2017 strain was investigated in orally inoculated five-day-old piglets; the piglets developed acute, watery diarrhea, but all recovered and survived. CHN-JS-2017 infection-induced microscopic lesions were observed, and viral antigens were detected mainly by immunohistochemical staining in the small intestine. The neonatal Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) are crucial immunoglobulin (Ig) receptors for the transcytosis ofimmunoglobulin G (IgG), IgA, or IgM. Importantly, CHN-JS-2017 infected five-day-old piglets could significantly down-regulate the expression of FcRn, pIgR, and nuclear factor-kappa B (NF-κB)in the intestinal mucosa. Note that the level of FcRn mRNA in the intestinal mucosa of normal piglets is positively correlated with pIgR and NF-κB. At the same time, the expressions of FcRn, pIgR, and NF-κB mRNA are also positively correlated in infected piglets. These results may help explain the immunological and pathological changes associated with porcine deltacorononirus infection.

Overexpression of Pitx1 attenuates the senescence of chondrocytes from osteoarthritis degeneration cartilage-A self-controlled model for studying the etiology and treatment of osteoarthritis.

To explore the role of low expression of Pitx1 in degenerative cartilage tissue. A cartilage injury model was established by using the cartilage scratch method. The newly generated tissue by BrdU labeled in injured cartilage region expressed SOX-9 and Col2A1 in 5-week-old rats. Compared with that, the number of BrdU-positive cells was lower in 4-month-old cartilage injury model rats. Compared with that in lateral cartilage, the expression of Pitx1 was lower in medial cartilage. Compared with chondrocytes derived from the lateral cartilage, chondrocytes derived from the medial cartilage exhibited significantly increased cell aging, as determined by SA-ß-GAL staining; downregulated Pitx1 expression; reduced autophagy levels; and decreased Col2A1 expression in a chondrogenic differentiation assay. Inhibition of Pitx1 expression in chondrocytes from the lateral cartilage significantly increased the ratio of cell senescence. Overexpression of Pitx1 in chondrocytes derived from the medial cartilage decreased the cell senescence ratio. In a luciferase assay, Pitx1 was found to promote Sirt1 gene transcription. Decreased Pitx1 expression is an essential cause of cartilage degeneration in the medial tibial plateau. The described self-controlled model is an excellent way to study OA etiology and screen therapeutic drugs for OA.

Activation of the leptin pathway by high expression of the long form of the leptin receptor (Ob-Rb) accelerates chondrocyte senescence in osteoarthritis.

OBJECTIVES: Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb. METHODS: The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin. RESULTS: In total, 12 cases were found to have severe medial cartilage wear compared with the lateral cartilage. Immunofluorescence showed that the expression of Ob-Rb in the medial cartilage of the tibial plateau was high. High levels of leptin led to cell cycle arrest and inhibited autophagy. After overexpression of Ob-Rb, the physiological dose of leptin induced cell senescence in the chondrocytes. High doses of leptin inhibited autophagy by activating the mTOR signalling pathway. Blockade of the mTOR signalling pathway could restore autophagy and partially reverse senescence induced by leptin in chondrocytes. CONCLUSION: In summary, the present study demonstrated that high doses of leptin induce cell senescence by activating the mTOR pathway in chondrocytes from OA cartilage. Highly expressed Ob-Rb accelerates chondrocyte senescence by activating the leptin pathway in OA.Cite this article: X. Zhao, P. Huang, G. Li, L. Zhendong, G. Hu, Q. Xu. Activation of the leptin pathway by high expression of the long form of the leptin receptor (Ob-Rb) accelerates chondrocyte senescence in osteoarthritis. Bone Joint Res 2019;8:425-436. DOI: 10.1302/2046-3758.89.BJR-2018-0325.R2.

Sevoflurane downregulates insulin-like growth factor-1 to inhibit cell proliferation, invasion and trigger apoptosis in glioma through the PI3K/AKT signaling pathway.

Sevoflurane is a new type of inhalation anesthetic used widely in the clinic. It has the characteristics of rapid induction, rapid recovery, and less irritative to the airway. Studies have shown that sevoflurane can affect the invasion and migration of a variety of malignant tumors. However, its effects on human glioma cells and related mechanisms are not clear. Cultured U251 and U87 cells were pretreated with sevoflurane. The effect of sevoflurane on proliferation was evaluated by MTT, and cell migration assay, cell apoptosis, and invasion ability were evaluated by wound-healing assay, cell apoptosis, and Transwell assays. Insulin-like growth factor-1 (IGF-1) and PI3K/AKT signaling pathway gene expression in sevoflurane-treated cell lines was measured by western blotting analysis, respectively. 5% sevoflurane significantly inhibited proliferation ability in both U251 and U87 cells. Sevoflurane inhibited glioma cells invasion and migration, and promoted apoptosis. Sevoflurane inhibited IGF-1 and promoted the expression of apoptosis-related proteins in glioma cells. In addition, sevoflurane inhibited the PI3K/AKT signaling pathway in glioma cells. This study clarifies that sevoflurane inhibits proliferation, invasion, and migration, and promotes apoptosis in glioma cells. These effects are regulated by IGF-1, an upstream gene of the PI3K/AKT signaling pathway. These findings may be significant for the selection of anesthetic agents in glioma surgery to improve the prognosis of patients.

Increasing UCP2 expression and decreasing NOX1/4 expression maintain chondrocyte phenotype by reducing reactive oxygen species production.

The aim of this study is to demonstrate that improving the mitochondrial function can inhibite the loss of chondrocyte phenotype by regulating the expression of uncoupling protein 2(UCP2) and NADPH oxidase1/4(NOX1/4) to reduce the production of reactive oxygen species(ROS). The effects of mitochondrial biogenesis "master regular" peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcriptional factor A (TFAM), UCP2, and NOX1/4 on chondrocyte phenotype was examined. It was found that when the chondrocyte phenotype was lost, PGC-1α, UCP2, and TFAM expression decreased, while NOX1/4 expression increased. Inhibiting UCP2 expression promoted the loss of chondrocyte phenotype, and inhibiting NOX1/4 relieved the loss of the chondrocyte phenotype. After activating the PGC-1α-TFAM pathway, UCP2 increased and NOX1/4 decreased, which suppressed loss of the chondrocyte phenotype. After inhibiting NOX1/4, UCP2 expression increased. Increasing and decreasing UCP2 and NOX1/4 expression, respectively, helps maintain the chondrocyte phenotype and improve mitochondrial functioning by reducing reactive oxygen species production.

Hydrogen sulfide protects against myocardial ischemia and reperfusion injury by activating AMP-activated protein kinase to restore autophagic flux.

How hydrogen sulfide (H2S) protects against myocardial ischemia-reperfusion (I/R) injury is poorly understood. By using a slow-releasing H2S donor, we investigated if H2S protected against myocardial I/R injury by activating AMPK and restoring I/R-impaired autophagic flux. Male rats received anterior descending coronary artery occlusion followed by reperfusion. The H2S donor ADT and/or the AMPK inhibitor, compound C (CC), were administered after occlusion. Infarction was analyzed histologically. AMPK activation was assessed in the ischemic heart by analyzing phosphorylation of AMPK and S6 ribosomal protein. Autophagy was assessed by analyzing the following markers: microtubule-associated protein 1 light chain 3 (LC3) I and II, lysosome associated membrane protein-2 (LAMP-2), P62 and beclin-1. We further investigated if blocking autophagic flux with chloroquine abolished ADT cardioprotection in vivo. Myocardial I/R reduced serum H2S levels, which was elevated by ADT. ADT enhanced AMPK activation and reduced infarction following I/R, and both effects were abolished by AMPK inhibition. Myocardial I/R induced autophagosome accumulation, as evidenced by the increased ratios of LC3-II/LC3-I, upregulation of beclin-1 and P62 and reduction in LAMP-2. ADT blunted these autophagic changes induced by I/R, indicating that ADT restored I/R-impaired autophagic flux. The AMPK inhibitor CC blocked ADT effects on restoring I/R-impaired autophagy flux. Moreover, chloroquine pretreatment abolished cardioprotection of ADT and increased autophagosome accumulation in the ADT-treated heart following I/R. In conclusion, AMPK activation and subsequent restoration of I/R-impaired autophagic flux are unrecognized mechanisms underlying cardioprotective effects conferred by H2S donors.