Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

OBJECTIVE: To investigate the anti-adhesive effect and underlying mechanism of dynamic and static stress stimulation on the early healing process of rat Achilles tendon injury. METHODS: Achilles tendon tissues of 15 male Sprague Dawley (SD) rats aged 4-6 weeks were isolated and cultured by enzyme digestion method. Rat Achilles tendon cells were treated with tumor necrosis factor α to construct the Achilles tendon injury cell model, and dynamic stress stimulation (dynamic group) and static stress stimulation (static group) were applied respectively, while the control group was not treated. Live/dead cell double staining was used to detect cell activity, ELISA assay was used to detect the expression of α smooth muscle actin (α-SMA), and real-time fluorescence quantitative PCR was used to detect the mRNA expression of collagen type Ⅰ (COL1A1), collagen type Ⅲ (COL3A1), and Scleraxis (SCX). Thirty male SD rats aged 4-6 weeks underwent Achilles tendon suture and were randomly divided into dynamic group (treated by dynamic stress stimulation), static group (treated by static stress stimulation), and control group (untreated), with 10 rats in each group. HE staining and scoring were performed to evaluate the healing of Achilles tendon at 8 days after operation. COL1A1 and COL3A1 protein expressions were detected by immunohistochemical staining, α-SMA and SCX protein expressions were detected by Western blot, and maximum tendon breaking force and tendon stiffness were detected by biomechanical stretching test. RESULTS: In vitro cell experiment, when compared to the static group, the number of living cells in the dynamic group was higher, the expression of α-SMA protein was decreased, the relative expression of COL3A1 mRNA was decreased, and the relative expression of SCX mRNA was increased, and the differences were all significant ( P<0.05). In the in vivo animal experiment, when compared to the static group, the tendon healing in the dynamic group was better, the HE staining score was lower, the expression of COL1A1 protein was increased, the expression of COL3A1 protein was decreased, the relative expression of SCX protein was increased, the relative expression of α-SMA protein was decreased, and the tendon stiffness was increased, the differences were all significant ( P<0.05). CONCLUSION Compared with static stress stimulation, the dynamic stress stimulation improves the fibrosis of the scar tissue of the rat Achilles tendon, promote the recovery of the biomechanical property of the Achilles tendon, and has obvious anti-adhesion effect.
Animals ; Achilles Tendon/injuries* ; Male ; Rats ; Rats, Sprague-Dawley ; Collagen Type I/metabolism* ; Collagen Type III/metabolism* ; Tendon Injuries/therapy* ; Wound Healing ; Stress, Mechanical ; Actins/metabolism* ; Cells, Cultured ; Tissue Adhesions/prevention & control* ; Tumor Necrosis Factor-alpha/metabolism* ; RNA, Messenger/genetics* ; Disease Models, Animal ; Collagen Type I, alpha 1 Chain/metabolism* ; Biomechanical Phenomena ; Basic Helix-Loop-Helix Transcription Factors

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
Animals ; Disease Models, Animal ; Hydrocephalus/genetics* ; Mice ; Mice, Knockout ; Neurons ; beta Catenin/genetics*

Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.

Objective To investigate the diagnostic and clinical significance of computerized tomography (CT) attenuation values (hounsfield unit,HU) in hydronephrosis with infection.Methods One hundred and eighty-five cases of upper urinary tract calculi with hydronephrosis from June 2014 to June 2016 were retrospectively analyzed.There were 82 males and 103 females with a mean age of (52.3 ± 13.1)years old,ranging 18-80 years old.58 cases suffered hydronephrosis without infection,55 cases suffered acute pyelonephritis and 72 cases suffered pyonephrosis.The CT attenuation values of the renal pelvis urine in three groups were measured.Results The CT attenuation value of hydronephrosis without infection group was (5.61 ± 3.67) HU,95 ％ CI(4.64-6.57) H U.In acute pyelonephritis group,CT attenuation value was (8.35 ± 5.63) HU,95％ CI(6.83-9.87) HU.In pyonephrosis group,the CT attenuation value was (13.92 ± 6.21) HU,95％ CI (12.46-5.38) HU.The CT attenuation value of pyelonephritis compared with that of hydronephrosis without infection was significant different.(P ＜ 0.01).The CT attenuation value of the patients with pyonephrosis was significantly higher than that of patients without infection and with pyelonephritis (P ＜ 0.01).Conclusions The CT attenuation value of renal pelvis urine can predict intrarenal infection.Furthermore,The measurement of CT attenuation value has some clinical significance in preoperative evaluation of hydronephrosis with infection.

Objective To understand the epidemic status quo and influencing factors of Kashin-Beck disease among children in mountain areas of Jilin Province.Methods Two hundred eighty-two severe endemic areas in 18 counties were selected and stratified by random cluster sampling method,and the status quo of KashinBeck disease prevalence was investigated among 7-12 year-old children according to the Diagnostic Criteria of Kashin-Beck Disease (WS/T 207-2010).In the meantime,the annual household income and the proportion of economic crops replanted,grain out-sourced,and returning farmlands to forests and grass were surveyed in the disease affected areas.Results A total of 14 162 children were investigated who had no clinical symptoms.Among them,28 cases were detected positive using X-ray with a detection rate of 1.98‰,while most of the cases were metaphysis positive.The annual household income (≥5 000 Yuan vs.＜ 5 000 Yuan) in the year 2009-2011 had a significant impact on the incidence of Kashin-Beck disease (1.47‰ vs.3.67‰,x2 =6.179,P ＜ 0.05),while the areas of returning farmland to forests and grass which accounted ＞ 1％ had no significant influence on the incidence compared with that ≤ 1％ (3.30‰ vs.1.57‰,x2 =3.876,P ＞ 0.05);the areas of economic crops replanting which accounted ＞ 10％ had no significant influence on the incidence compared with that ≤ 10％ (3.07‰ vs.1.65‰,x2 =2.565,P ＞ 0.05);the proportion of grain out-sourcing which accounted ＞ 50％ had no significant influence on the incidence compared with that ≤50％ (3.07‰ vs.1.65‰,x2 =2.565,P ＞ 0.05).Conehision Up to 2012,the disease among 7-12 year-old children of the mountain areas of Jilin Province have basically met the standard of Kashin-Beck disease elimination and the situation remains stable;furthermore,the household income has a significant impact on the incidence of Kashin-Beck disease.

OBJECTIVETo review the research methods of mass casualty incident (MCI) systematically and introduce the concept and characteristics of complexity science and artificial system, computational experiments and parallel execution (ACP) method.

DATA SOURCESWe searched PubMed, Web of Knowledge, China Wanfang and China Biology Medicine (CBM) databases for relevant studies. Searches were performed without year or language restrictions and used the combinations of the following key words: "mass casualty incident", "MCI", "research method", "complexity science", "ACP", "approach", "science", "model", "system" and "response".

STUDY SELECTIONArticles were searched using the above keywords and only those involving the research methods of mass casualty incident (MCI) were enrolled.

RESULTSResearch methods of MCI have increased markedly over the past few decades. For now, dominating research methods of MCI are theory-based approach, empirical approach, evidence-based science, mathematical modeling and computer simulation, simulation experiment, experimental methods, scenario approach and complexity science.

CONCLUSIONSThis article provides an overview of the development of research methodology for MCI. The progresses of routine research approaches and complexity science are briefly presented in this paper. Furthermore, the authors conclude that the reductionism underlying the exact science is not suitable for MCI complex systems. And the only feasible alternative is complexity science. Finally, this summary is followed by a review that ACP method combining artificial systems, computational experiments and parallel execution provides a new idea to address researches for complex MCI.

BACKGROUND: Whether the differences exist between adipose-derived stem cells isolated from different parts of rats when cultured in vitro has been poorly understood. OBJECTIVE: To compare the growth characteristics and adipogenic ability of adipose-derived stem cells isolated from different parts of rats. METHODS: Freshly isolated adipose-derived stem cells were obtained from 5 mL inguinal groove and greater omentum adipose tissue of F344 rats using type Ⅰ col agenase digestion method. Then, adipose-derived stem cells were counted and cultured in vitro. Morphological and growth characteristics of adipose-derived stem cells derived from the two sites were observed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was utilized to examine the doubling time of adipose-derived stem cells from different parts. The passage 2 adipose-derived stem cells were induced adipogenical y. Fourteen days after being induced, the differentiated cells were stained with oil red O and the positive cells were counted. The adipogenic differentiation ability of adipose-derived stem cells from the different parts was assessed. RESULTS AND CONCLUSION: (1) The number of adipose-derived stem cells from the greater omentum fat tissue in the same group was (281±10)×107/L, which was significantly higher than that from the inguinal groove fat tissue [(85±10)×107/L] (P < 0.01). Adipose-derived stem cells from the greater omentum and inguinal groove fat tissue achieved the exponential growth period on days 5 and 6, respectively, and achieved the platform period on days 9 and 10, respectively. The corresponding doubling time was 50 hours and 60 hours, respectively. After being passaged, adipose-derived stem cells grew in fibroblast-like shape actively. The adipogenic differentiation rate of adipose-derived stem cells from the greater omentum fat tissue was higher than that from the inguinal groove fat tissue [(38.90±2.86)% vs. (35.30±3.29)%, P < 0.01]. This shows that the number and the adipogenic differentiation ability of adipose-derived stem cells from different parts of the same F344 rat are different.

Developing countries are facing a big challenge of how to promote sexual and reproductive healthe Poverty erasion.reproductive health service promotion,schools and communities intervention,discussion between children and their parents encouragment are helpful to solve the sexual and reproductive problems with the adolescents

Objective To evalhate the protective effect of oral raloxifene on lung function after acute lung injury (ALI) in rats. Methods Thirty male adult Sprague-Dawley rats were used and divided into three groups: LPS raloxifene hydrochloric acid. group before secondary impact ( Group A, n = 10 ), LPS raloxifene hydrochloric acid group after secondary impact ( Group B, n = 10) and control group ( n = 10). All the rats were injected intraperitoneally with 5 mg/kg LPS. Raloxifene (30 mg/kg) was orally administered one hour before LPS injection and 14 hours after LPS injection in Groups A and B. The con-trol group remained free. All the animals were anesthetized by intraperitoneal injection of pentobarbital so-dium at 40 mg/kg and the femoral artery was cannulated 16 hours after LPS injection to measure the mean arterial pressure (MAP). All the rats received a direct intratracheal injection of hydrochloric acid ( pH = 1.2, 0.5 ml/kg). Before injection of hydrochloric acid and at 0. 5,1.5 and 4 hours after injection of hy-drochloric acid, the blood gas was measured. Fifteen rats ( five from each group) underwent a micro posi-tron emission tomography ( [18F] FDG microPET) scan of the thorax four hours after hydrochloric acid in-stillation. Then, the lung tissue was collected for histopathological examination. Results The Group B showed better pulmonary gas exchange and more stable MAP compared to the control group. The [18F] fluorodeoxyglueose uptake and histological lung injury score were 9. 01 ± 1.58 and 12.6 ± 0.97 respec-tively in Group B, which were higher than 4. 67 ± 1.33 and 9. 01 ± 1.58 respectively in control group (P < 0. 01 ). Conclusions Raloxifene exerts significant protective effect on lung function after ALI. [18F] FDG microPET is a useful method to evaluate the inflammatory reaction during ALI.