Adipose tissue-derived mesenchymal stem cells attenuate lung inflammation and fibrosis in the bleomycin-induced pulmonary fibrosis rat model via caveolin-1/NF-kB signaling axis.

Stem cells have emerged as promising therapeutic options for several human diseases, including pulmonary fibrosis (PF). In this study, we investigated the therapeutic effects of adipose tissue-derived mesenchymal stem cells (ADMSCs) in the bleomycin-induced PF model rats and the underlying mechanisms. The PF model rats were generated by intratracheal injections of 5 mg/kg bleomycin sulfate. The ADMSC group rats were generated by injecting 2×10(6) ADMSCs via the tail vein at 0, 12, and 24 h after bleomycin injection. The control, PF, and ADMSC group rats were sacrificed on day 21 after bleomycin injections and the changes in lung histology and the levels of pro-inflammatory cytokines, collagen I, and caveolin-1 (Cav-1), and the activity of the NF-kappaB signaling pathway in the lung tissues was assessed by hematoxylin-eosin staining, ELISA, and western blotting assays. The lung tissues of the PF model rats showed significant infiltration of neutrophils, tissue destruction, and collagen deposition, but these effects were abrogated by the ADMSCs. The levels of pro-inflammatory cytokines such as IL-6, IL-1beta, and TGF-beta1 were elevated in the lung tissues and the bronchoalveolar lavage fluid (BALF) of the bleomycin-induced PF model rats, but these effects were reversed by the ADMSCs. The lung tissues of the PF model rats showed significant downregulation of Cav-1 and significantly higher activation of the pro-inflammatory NF-kappaB pathway. However, administration of the ADMSCs restored the expression levels of Cav-1 and suppressed the NF-kappaB signaling pathway in the lungs of the bleomycin-induced PF model rats. In conclusion, this study demonstrated that the ADMSCs protected against bleomycin-induced PF in the rat model by modulating the Cav-1/NF-kappaB axis.

[Identification and genetic analysis of new mutations in EYA1 gene of BOS syndrome].

Objective: To analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis. Methods: Clinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing. Results: There were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) in EYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family. Conclusions: A novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.

[Analysis of genetic characteristics in two Chinese children of type â ¡ Waardenburg syndrome].

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.

[A comparative study on diagnosis of silicosis by digital and high kV film-screen chest radiography].

Objective: To explore the feasibility of soft copy image of chest digital radiography (DR(SC)) in pneumoconiosis diagnosis by observing the reading effect of DR(SC) and comparing it with high kV film-screen chest radiography (FSR(HkV)) . To provide a basis for the establishment of a regional information network platform for pneumoconiosis diagnosis. Methods: A total of 119 miners who were exposed to silica dust and engaged in copper or lead-zinc mining were collected by the Third People's Hospital of Yunnan from October 2017 to August 2019. The pulmonary X-ray findings of DRSC and FSR(HkV) in each case were independently judged and diagnosed by three experienced diagnostic physicians, and the final decision was made according to the consensus of most doctors. The consistency of the two imaging methods was analyzed by observing the main small opacity shape, the overall density, the range of distribution, the aggregation of the small opacity and the big opacity, and the diagnosis stage. Results: there were 118 males and 1 female with an average age of 46.21 years. Average exposure time 7.38 years. The pulmonary X-ray findings of 113 cases with two imaging methods were mainly the round small opacity of p,q and r,but the reticular irregular opacity were not prominent, Only one case of FSR(HkV) judgment p shape and DR(SC) judgment q shape were observed, The coincidence rate was 99.12% (112/113) . huger opacity were observed in the other 6 cases. The coincidence rate was 95.51% (4/89) between pneumoconiosis-free and stageⅠ, and there was no significant difference between stageⅡand stage Ⅲ (30/30, P>0.05) . Conclusion: The x-ray findings of Silicosis with small round shadow in lung can be used by DR(SC) in diagnosis and staging.

Measurement of electron temperature fluctuations on J-TEXT via correlation ECE.

The capabilities of the joint-Texas experimental tokamak correlation electron cyclotron emission (CECE) diagnostic have recently been extended with an upgrade. Four new yttrium iron garnet (YIG) filters from 4 GHz to 18 GHz with a bandwidth of 90 ∼ 230 MHz are added to the previous 4 channels. Optical optimization of the transmission line has improved the poloidal resolution, which allows k θ < 3.08 cm-1. The improvement of video amplifiers allows the frequency and amplitude gain to be adjusted discretely from 200 kHz to 1 MHz and from 200 to 1000, respectively, for different situations. A controller is designed to remotely adjust the center frequency of the YIG filters. Based on the CECE, the distribution and the effect of magnetohydrodynamic instabilities on electron temperature fluctuations have been observed. The experiment results show good performance of the upgraded CECE diagnostic.

[The technique of retaining part of the external auditory canal posterior wall with epitympanoplasty in soft wall reconstruction treating middle ear cholesteatoma].

Objective:To investigate the surgical treatment of cholesteatoma of the middle ear. Method:A retrospective analysis of patients from June 2013 to July 2016 diagnosed as cholesteatoma. 137 ears were divided into A group (retaining part of the external auditory canal posterior wall with epitympanoplasty in soft wall reconstruction for 75 ears) and B group (canal wall down mastoidotympanoplasty for 62 ears). the extent and damage of cholesteatoma were observed, comparing the time of dry ear and epithelial postoperative, the incidence of complications such as dizziness and hearing changes. Result:compared with B group, the postoperative dry ear time, epithelial time and hearing improvement in the A group were obviously improved, and the incidence of vertigo after operation was decreased, and the anatomical and physiological functions of the external auditory canal were protected. Conclusiont:The technique of retaining part of the external auditory canal posterior wall with epitympanoplasty in soft wall reconstruction is conductive to the removal of lesions and normal anatomical and physiological protection to external auditory canal, can prevent the forming of the abstraction pocket effectively and the recurrence of cholesteatoma, has clinical and practical value.

Antidepressant use during pregnancy and the risk of attention-deficit/hyperactivity disorder in the children: a meta-analysis of cohort studies.

BACKGROUND: Evidence for the relationship between antidepressant use during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in the children is conflicting. OBJECTIVE: To assess the association between fetal exposure to antidepressant drugs and the subsequent development of ADHD. SEARCH STRATEGY: A systematic literature search was conducted in PubMed, EMBASE, PsycINFO, and CINAHL databases to identify relevant cohort studies published from inception until October 2017. SELECTION CRITERIA: Cohort studies, identifying children with ADHD diagnosis and linking antidepressant use during pregnancy in their mothers. DATA COLLECTION: Two reviewers independently abstracted data and assessed study quality. MAIN RESULTS: The literature search identified six relevant cohort studies with association between antidepressant exposure during pregnancy and the risk of ADHD in children [hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.14-1.57]. However, the association was not statistically significant when the reference group was mothers with psychiatric disorders not treated during pregnancy (HR 0.96; 95% CI 0.76-1.2; n = 2 studies). Moreover, preconception exposure to antidepressants was significantly associated with increased risk of ADHD (HR 1.82; 95% CI 1.54-2.15; n = 3 studies). CONCLUSIONS: The significant association between antidepressant exposure during pregnancy and ADHD in the children can be partially explained by confounding by indication. Given the low number of included studies, further studies with prospective designs that use validated measurements and controls for important confounders are needed to verify our findings. TWEETABLE ABSTRACT: Antidepressant use during pregnancy may be not associated with ADHD in the offspring.

[Analysis of blood lead level of children living around lead-zinc mines].

Objective: To investigate the blood lead level of children living around lead-zinc mining areas, in order to analyze its distribution features of the population. Methods: In August 2016, three natural villiages around lead-zinc mines were selected randomly as survey sites, which were grouped A, B and C according to each distances from the center field, totally 1 379 children from the three villages were selected by cluster random sampling method as the investigation subjects, and their elbow peripheral vein blood samples were collected to determine the blood lead level by graphite furnace atomic absorption spectrometry. The distribution features of blood lead in different district, gender and age groups were compared and analyzed. Results: The median and quartile range of blood lead were 0.066 and 0.058 mg/L respectively. The blood lead levels of 341 children were esceeding 100 µg/L and that account for 24.73%. The median blood lead showed statistical significant differrnce among three groups (P<0.01) , and the medians from high to low were: 0.075 mg/L (A) , 0.065 mg/L (B) and 0.059 mg/L (C) respectively. The average blood lead of male was higher than that of female (P<0.01) . There was significant difference in blood lead levels among different aged groups (P<0.01) , and the high blood lead rate dicreased with the increase of age (P<0.01) . Results of multivariate logistic regression analysis showed that there was a high risk of excessive lead in the blood lead of boys aged 1-6 years from the center of the area. Conclusion: The blood lead level of children living around lead-zinc mining areas is relatively high. There are difference in district distribution, gender and age.

[Clinical value of health-related quality of life evaluation in community patients with hepatitis B].

Chronic hepatitis B (CHB) is a major infectious disease which threatens people's health around the world. Health-related quality of life (HRQoL) has become an important index for evaluating the treatment and prognosis of patients with CHB. Many studies abroad have shown that the HRQoL of patients with CHB is influenced by various factors. Disease severity, clinical symptoms, and low self-efficacy are important influencing factors for patients' quality of life. Anti-viral therapy, proper physical therapy, or psychological intervention can significantly improve the HRQoL of community CHB patients, and HRQoL is even significantly improved in patients undergoing liver transplantation one year ago. These studies provide valid evidence for antiviral therapy for hepatitis B patients and liver transplantation techniques from the psychological level. At present, there still lacks studies on HRQoL of CHB patients in China. This article summarizes the measurement tools for HRQoL widely used in recent years in China and foreign countries, reviews the research advances in HRQoL in community patients with CHB, and discusses the perspectives for future studies.

Electron cyclotron emission radiometer upgrade on the J-TEXT tokamak.

To meet experimental requirements, the J-TEXT electron cyclotron emission (ECE) diagnostic is being upgraded. The front end antenna and transmission line have been modified and a new 8-channel W-band detecting unit has been developed. The improved ECE system will extend the frequency range from 94.5-124.5 GHz to 80.5-124.5 GHz. This will enable the system to cover the most plasma in the radius direction for BT = 1.8-2.2 T, and it even can cover almost the whole plasma range ρ = - 0.8-0.9 (minus means the high field side) at BT = 1.8 T. A new auxiliary channel bank with 8 narrow band, tunable yttrium iron garnet filters is planned to add to the ECE system. Due to observations along a major radius, perpendicular to BT, and relatively low electron temperature, Doppler and relativistic broadening are minimal and thus high spatial resolution measurements can be made at variable locations with these tunable channels.

Design of the 2D electron cyclotron emission imaging instrument for the J-TEXT tokamak.

A new 2D Electron Cyclotron Emission Imaging (ECEI) diagnostic is being developed for the J-TEXT tokamak. It will provide the 2D electron temperature information with high spatial, temporal, and temperature resolution. The new ECEI instrument is being designed to support fundamental physics investigations on J-TEXT including MHD, disruption prediction, and energy transport. The diagnostic contains two dual dipole antenna arrays corresponding to F band (90-140 GHz) and W band (75-110 GHz), respectively, and comprises a total of 256 channels. The system can observe the same magnetic surface at both the high field side and low field side simultaneously. An advanced optical system has been designed which permits the two arrays to focus on a wide continuous region or two radially separate regions with high imaging spatial resolution. It also incorporates excellent field curvature correction with field curvature adjustment lenses. An overview of the diagnostic and the technical progress including the new remote control technique are presented.

[Minimally invasive surgical techniques of cochlear implantation withround window pathways in young children].

Objective:To discuss the minimally invasive surgical techniques and the effect of cochlear implantation with round window pathways in young children(≤3 years).Method:One hundred and sixty patients with bilateral profound sensorineural hearin loss received MED-EL cochlear implantation,including 144 cases of normal middle and inner ear,4 cases of Mondini deformity,12 cases of large vestibular aqueduct syndrome.Result:Of 160 patients underwent CIs,148 patients were performed with round window pathways,the rate was 92.5%. Iit's difficult to exposure round window in 12 patients,performing from promontory.All electrodes of 158 cases with unilateral CI and 2 cases with bilateral CI were implanted successfully,in which the CI went normally and electrode array were protected well.All implant devices had worked normally and all patients had performed well during an average follow-up period of 8 month-3 years.Post-operatively complications of cerebrospinal fluid leakage,facial nerve injury haven't been found.Conclusion:Cochlear implantation could be performed in patients wit with round window pathways,and it is a safe and effective way in young children.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation.

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

The chemistry and biology of the bryostatins: potential PKC inhibitors in clinical development.

The bryostatins, powerful protein kinase C (PKC) agonists, are a family of complex macrolactone natural products. They are originally isolated from the marine bryozoan Bugula neritina. So far tweenty bryostatins have been obtained naturally and exhibit a remarkable range of biological activities, including antineoplastic activity, synergistic chemotheoreputic activity, cognition and memory enhancement, etc. Of the 20 known members, the most extensively studied is bryostatin 1. The effects of bryostatin 1 are mainly linked to its ability of selectively modulating the function of various individual protein kinase C (PKC) isozymes. Moreover, bryostatin 1, or in combination with other agents, has been proposed for phase I and phase II clinical trials. The bryostatins have excellent biological properties, but are scarce in nature. Therefore, it has attracted considerable interests in structural modification over the past two decades. In this review, we will attempt to summarize the main developments that have occurred in the structure-activity relationship and biology of bryostatins over the period 1982-2011.

Intestinal microbiota and innate immunity-related gene alteration in cirrhotic rats with liver transplantation.

BACKGROUND: The present study investigated the alteration of intestinal microbiota, innate immunity-related genes, and bacterial translocation in rats with cirrhosis and liver transplantation. METHODS: Specific pathogen-free Sprague-Dawley rats were randomized into 4 groups: (1) normal controls (N); (2) liver cirrhosis (LC); (3) normal control groups with liver transplantation (LTN); and (4) liver cirrhosis with liver transplantation (LTC). We examined plasma endotoxin, bacterial tacslocation, denaturing gradient gel electrophoresis (DGGE) profile of intestinal mucosa-associated bacteria, abundance of key bacterial populations, and expression of innate immunity-related gene. RESULTS: The LTC and LC group, showed higher endotoxin levels (1.08±0.73 EU/mL and 0.74±0.70 EU/mL, respectively) than the N group (0.27±0.13 EU/mL; P<.05). the incidence of bacterial translocation (BT) to liver and mesenteric lymph nodes (MLN), and the number of total bacteria were increased significantly in the LTC and LC groups compared with the N group (P<.05). The counts of Lactobacilli and Bacteroides were lower, whereas Enterobacteria were higher in the LC than the N group (P<.05). Mucins (MUC2, MUC3) and Toll-like receptors (TLR2, TLR4) messenger RNA (mRNA) expression were significantly higher in the LC and LTC groups than the N group (P<.05). The marked difference between the groups in the overall structure of the bacterial community was also generated by DGGE profiles. CONCLUSION: Liver cirrhosis disturbs intestinal microbiota and innate immunity-related genes, which contributes to endotoxemia and bacterial translocation. These had not completely recovered in cirrhotic rats until 1 month after orthotopic liver transplantation.

Synthesis and biological activity of chiral dihydropyrazole: potential lead for drug design.

Dihydropyrazole, a small bioactive molecule, is a prominent structural motif found in numerous pharmaceutically active compounds. The chiral dihydropyrazole structure has been demonstrated to bear important biological activities such as anticancer, antimicrobial, antimalarial, antinociceptive, antiviral, antitubercular, antiinflammatory, anticonvulsant and steroidal, and can also act as MAO inhibitors, CB1 receptor antagonists and nitric oxide synthase inhibitors. The review describes the latest advances in the synthesis of dihydropyrazole derivatives incorporating physiologically active substances. It is the first attempt at a general and systematic account of the extensive literature data on this subject.

Studies on the chemical constituents of Psoralea corylifolia L.

A new isoflavone, corylinin (1), along with six known compounds, isopsoralen (2), psoralen (3), sophoracoumestan A (4), neobavaisoflavone (5), daidzin (6) and uracil (7), have been isolated from the dried fruits of Psoralea corylifolia L. The structure of 1 was established as 7,4'-dihydroxy-3'-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone on the basis of the spectroscopic methods. Structures of the known compounds were identified by comparison of the literature.

Two new 18-carbon norditerpenoid alkaloids from Aconitum sinomontanum.

Two new 18-carbon norditerpenoid alkaloids, sinaconitines A (1) and B (2), together with two known alkaloids, ranaconitine (3) and lappaconitine (4), were isolated from the roots of Aconitum sinomontanum. Their structures were elucidated on the basis of spectral evidences and X-ray crystallographic analysis for 1. Furthermore, the reversed 13C NMR assignments for C-10 and C-13 of 3, 4, puberanine, puberanidine and demethyllappaconitine were revised. Compounds 1-4 were evaluated for cyclooxygenase-2 (COX-2) enzyme inhibitory activity. However, they did not show any inhibition at 10 microM.