Case report: Hypnic headache responds to agomelatine-a potential prophylactic treatment option.

Introduction: Hypnic headache (HH) is a rare primary headache that is characterized by strict sleep-related attacks. However, the pathophysiology of HH remains unclear. The nocturnal nature of this activity suggests a hypothalamic involvement. The pathogenesis of HH may involve the brain structure that regulates circadian rhythms and is related to an imbalance between hormones, such as melatonin and serotonin. Currently, evidence-based medicine for HH pharmacotherapy is lacking. Acute and prophylactic treatment of HH is based on only a few case reports. Here, we report a case study in which agomelatine showed desirable responsiveness for the prophylactic treatment of HH for the first time. Case description: We present the case of a 58-year-old woman with a 3-year history of nocturnal left temporal pain that awakened her during the wee hours. Brain magnetic resonance imaging did not reveal any midline structural abnormalities associated with circadian rhythms. Polysomnography revealed headache-related awakening at approximately 5:40 am, after the last rapid eye movement phase. No sleep apnea-hypopnea events were observed, without oxygen saturation or blood pressure abnormalities. The patient was prescribed agomelatine 25 mg at bedtime as a prophylactic treatment. In the following month, the frequency and severity of the headaches decreased by 80%. After 3 months, the patient's headache completely resolved, and the medication was discontinued. Conclusion: HH only occurs during sleep in the real world, leading to substantial sleep disturbances in older populations. Headache center neurologists need to focus on the prophylactic treatment of patients before bedtime to avoid nocturnal awakening. Agomelatine is a potential prophylactic treatment option for patients with HH.

Application of CRISPR in Filamentous Fungi and Macrofungi: From Component Function to Development Potentiality.

Fungi, particularly filamentous fungi and macrofungi, have a very powerful ability to produce secondary metabolites and can serve as excellent chassis cells for the production of enzymes or natural products of great value in synthetic biology. Thus, it is imperative to establish simple, reliable, and efficient techniques for their genetic modification. However, the heterokaryosis of some fungi and the dominance of nonhomologous end-joining (NHEJ) repair mechanisms in vivo have been greatly affecting the efficiency of fungal gene editing. In recent years, the CRISPR/Cas9 system has been applied as a widely used gene editing technology in life science research and has also played an important role in the genetic modification of filamentous and macrofungi. The various functional components (cas9, sgRNA, promoter, and screening marker) of the CRISPR/Cas9 system and its development, as well as the difficulties and potential of the CRISPR/Cas9 system in filamentous fungus and macrofungi, are the main topics of this paper.

Effects of Traditional Chinese Acupuncture Compared with Sham Acupuncture on the Explosive Force Production by the Forearm Muscles in Female: A Randomized Controlled Trial.

BACKGROUND: Acupuncture can effectively enhance musculoskeletal rehabilitation, with effects such as reduced pain intensity and muscle tension and decreased disability. OBJECTIVE: The purpose of this study was to determine the efficacy of traditional Chinese acupuncture (TCA) compared with sham acupuncture (SA) in explosive force production by the forearm muscles in females. METHODS: A total of 32 subjects were included and randomly assigned to two groups: TCA group (n = 16): stimulated specific acupoints including Quchi (LI11), Shousanli (LI10), Hegu (LI4), Xiaohai (SI8), Tianjing (SJ10), and Waiguan (SJ5) for 15 minutes; SA group (n = 16): using superficial needle insertion at nonacupoints without stimulation. The subjects warmed up for the 3-time isokinetic test with an angular velocity of 30°/s and then performed a set of 15 full flexion (Flex) and extension (Ext) with an angular velocity of 180°/s using the CON-TREX isokinetic test training system recorded as the pretest. After acupuncture for 15 min, perform a set of the same isokinetic movement isokinetic records as the posttest. The average max torque, average work, average power, average peak power, average max speed, and total work were collected to evaluate the forearm explosive force changes. Use two-way repeated measures ANOVA to compare the difference before and after acupuncture between two groups. RESULTS: The results showed that acupuncture conditions (sham acupuncture as well as true acupuncture) and the intervention times (not acupuncture or acupuncture for 15 min) have a significant interaction effect on forearm explosive force and joint stiffness (P < 0.05). The simple main effect showed that the selected parameters of the TCA group increased significantly after acupuncture (P < 0.05), while the SA group did not (P > 0.05). We speculate that the activation of muscle may be related to the selected acupuncture points. CONCLUSION: Acupuncture can produce excitation in motor nerves and muscles, and nerve stimulation increases the recruitment of motor units, thus improving the muscle explosive force.

[The Screening for Long Non-coding RNAs Related to Vein Graft Failure in Rat External Jugular Vein-Carotid Bypass Models].

OBJECTIVE: This study was designed to show the time-dependent changes in the expression profiles of long non-coding RNAs (lncRNAs) in rat vein grafts by using the high-throughput sequencing technique, and subsequently figure out lncRNAs related to vein graft failure. METHODS: The whole SD rats were randomly classified into four groups according to different sampling time points (0, 7, 14 and 28 days after surgery, respectively; n=3 per group). The day 0 group was set as a control, and the other three groups were set as experimental groups (the model of external jugular vein-carotid artery bypass was prepared in the experimental group). We identified the differentially expressed lncRNAs of the vein graft sample at different sampling time points with high-throughput sequencing, and verified these results using the technique of real-time quantitative PCR (RT-qPCR). Meanwhile, we used Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to screen lncRNAs which may play roles in the restenosis process of vein grafts. The function of lncRNA-mRNA pairs was predicted. We subsequently used RT-qPCR to verify these lncRNAs. RESULTS: A total of 2 572 sustained differentially expressed lncRNAs were identified in our study. We showed the top ten differentially expressed lncRNAs at each post-operative time point. Through GO analysis and KEGG pathway analysis, we revealed the sustained differentially expressed genes which may be involved in VGF-related biological process, cellular component, molecular function and biological pathways. Finally, we screened 15 pairs of lncRNA-mRNA, including MRAK083052- Nrp1, which may play roles in mediating the restenosis of vein graft. And the results of RT-qPCR were consistent with the results of the high-throughput sequencing. CONCLUSION: The present study investigated the time-dependent changes in the expression profiles of lncRNAs in vein grafts. We also screened 15 pairs of lncRNA-mRNA which may paly roles in vein graft failure.

[Correlation of Krebs Von Den Lungen-6（KL-6） Expression and Perioperative Pulmonary Function in Adults Receiving Continuing Low-volume Ventilation during Valve Surgery].

OBJECTIVE: To investigate the influence of continuous low-volume ventilation in cardiopulmonary bypass (CPB) on the expression of krebs von den lungen-6 (KL-6) and perioperative pulmonary function in adults undergoing valve surgery. METHODS: From 2017 Sept. to 2018 Jan., 60 patients who received valve replacement surgery were prospectively comprised in this study. We randomly allocated these patients into control group ( n=30, non-ventilation) and experimental group ( n=30, continuous low-volume ventilation during CPB). At different perioperative time points, we identified the dynamic changes of pulmonary function and biomarkers which expressed in serum and bronchoalveolar lavage fluid (BALF). Meanwhile, we also compared perioperative clinical outcomes of the two groups. RESULTS: The expression of serum KL-6 and BALF KL-6 in the two groups were both statistically significant（ P＜0.05）. The oxygenation index increased with time and reached to the top point at T 1, then subsequently decreased with time ( P＜0.05). The alveolar-arterial oxygen tension difference (P A-aO 2) in the two groups fluctuate with time, the differences have no statistical significance. According to linear correlation, the serum KL-6 level was negatively correlated with oxygenation indexes ( r=－0.525, P=0.003), while it was positively correlated with P A-aO 2 ( r=0.489, P=0.006). There were no significant differences between the two groups in clinical outcomes. CONCLUSION: Continuing low-volume ventilation during CPB could decrease the expression level of KL-6, while it has no significant influence on perioperative outcomes.

[Risk Factors for Adverse Aortic Remodeling in Post-TEVAR Patients with Acute Stanford B Aortic Dissection].

OBJECTIVES: To assess morphological changes of distal aorta and the risk factors for adverse aortic remodeling inpost-TEVAR（thoracic endovascular aortic repair） patients with acute Stanford B aortic dissection. METHODS: We retrospectively investigated the patients who underwent TEVAR for a type B dissection between October 2005 and December 2015. CT angiogram (CTA) was obtained for each patients preoperatively, postoperatively and during the post-operational follow-up. Based on Criadol partition principle, we divided the aorta into descending thoracic aorta area, suprarenal abdominal aorta area, infrarenal abdominal aorta area and iliac artery area, and evaluated the distribution of aortic tears and the form of true and false lumen in different aortic partition. Univariate and multivariate logistic regression analyses were used to analyze the risk factors affecting distal aortic remodeling. RESULTS: Of 216 patients (mean follow-up (3.9±2.1) years) who were regularly followed up in our center, 47 patients (21.8%) occurred adverse remodeling in distal aorta. Univariate logistic regression indicated that abnormal aortic wall structure (Marfan's syndrome) and patent false lumen (existence of distal tears, decreased complete false lumen thrombosis) were associated with distal aortic adverse remodeling. Multivariate logistic regression showed that more tears in descending thoracic aorta area ( OR=1.36, 95% CI=1.12-1.58, P=0.005) and less tears in infrarenal abdominal aorta area ( OR=0.49, 95% CI=0.22-0.71, P<0.001) were independent risk factors affecting remodeling in distal aorta after TEVAR. CONCLUSIONS: Aortic wall structure abnormalities, a patent false lumen, more tears in descending thoracic aorta area, less tears in infrarenal abdominal aorta area are independent risk factors for adverse aortic remodeling in post-TEVAR patients with acute Stanford B aortic dissection.

[Effect of cultivation substrate on growth and active component contents of Anoectochilus roburghii from three different origins].

Three different origins of Anoectochilus roburghii were used as experimental materials to study the effect of three different substrate( peat soil-river sand-peanut shell) radio on survival rate,plant height,stem diameter,plant fresh weight,root number,the longest root length,root diameter,and the contents of polysaccharide,flavonoids,and polyphenol. The results showed that when the substrate ratio was 4 ∶2 ∶2,the survival rate of A. roburghii from different origins was the highest,and the plant height,stem diameter,plant fresh weight,the longest root length and root diameter were also the largest. The cultivation substrate had no significant effect on the polysaccharide content of A. roxburghii and A. formosanus. When the substrate ratio was 4 ∶ 2 ∶ 2,the polysaccharide content of A.chapaensis was significantly lower than that of the other two combinations. When the substrate ratio was 4 ∶2 ∶1,the flavonoid content of A. formosanus was higher than that of the other two combinations. When the substrate ratio was 4 ∶2 ∶2,A. formosanus and A. chapaensis had higher polyphenol content.

[Impacts of Land Use and Landscape Patterns on Heavy Metal Accumulation in Soil].

Land use cover change (LUCC) is one of the most important human activities that drive the evolution of the environment. It has great effect on the accumulation, distribution, and migration of heavy metals in the environment. Vegetation can absorb heavy metals directly, and it can also change the physical, chemical, and biological properties of soil and then control the mobility and activity of heavy metals in soil, which will eventually cause pollution of heavy metals in soil. In addition, the migration of heavy metals in soil is also affected by changes of landscape element composition and landscape pattern at sample points, plots, watersheds, and regional scales. Based on the soil sampling data and land use data of Ningbo city in 2003 and 2013, the decision tree classification method based on classification and regression tree algorithm was used to classify the land use and cover type. Single-factor pollution index and Nemero composite pollution index were used to evaluate the soil heavy metal pollution status. The landscape pattern indexes were used to explore the change of landscape patterns under different degrees of heavy metal accumulation. Finally, redundancy analysis and partial redundancy analysis were used to identify those landscape pattern factors that had the most significant impacts on the soil heavy metal accumulation in the study area. The results showed that:①The eight soil heavy metal elements including As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn presented different degree of accumulation from 2003 to 2013 in the study area, of which Hg, Ni, and Cr had the highest degree of accumulation. Most of the study area has been polluted by heavy metals, and the pollution degree in the heavily polluted areas is still increasing. ②Higher accumulation degrees of heavy metals was not distributed entirely in areas where land use types have always been construction land, or in areas where other types of land use had been converted to construction land. A considerable proportion of heavy metals accumulated in areas where land use types have always been cultivated land or converted from other types to cultivated land. ③Heavy metal polluted areas have fragmented, complex, and aggregated landscape pattern, and the correlation between this kind of landscape pattern characteristics and soil heavy metal accumulation in arable land, residential land, and industrial land was the highest. ④The higher the aggregation degree of construction land patch, the higher the accumulation degree of most heavy metals. The accumulation degree of Cu, Hg, Pb, and Cd increased significantly with the increase of landscape diversity and shape complexity of agricultural land. The closer the distance to the mining site, the more obvious the effect on the increase of Cd content.

[The Clinical Evaluation of Prosthetic Valve in Patients with Dysfunction Valve Endocarditis].

OBJECTIVE: To evaluate the outcomes of valve replacement of endocarditis using bioprothetic and mechanical valves. METHODS: This study comprised 52 patients [mean age (47±18) yr.,mean follow-up time (6.2±3.8) years] underwent valve endocarditis with bioprotheses,The control group were matched (3∶1) with 156 patients of endocarditis underwent mechanical valves replacement using the following variables: age±5 yr.,body mass index (BMI)±20%,time of operation±1 year,replacement position and sex ratio. And evaluate the effects of using bioprothetic and mechanical valves on perioperative and long-term outcomes of valve replacement of endocarditis. RESULTS: The perioperative mortality of the patients receiving bioprothetic and mechanical valves were 17.3%±2.2% and 19.9%±1.8%,respectively,which was independent of valve type (P=0.27). Long-term survival were 56.1%±5.2% and 61.2%±8.1%,respectively (P=0.58). Meanwhile,long-term complication-free survival were 75.0%±3.2% and 82.3%±4.4%,respectively (P=0.29). For the patients younger than or equal to 60 yr.,long-term reoperation rates for bioprothetic and mechanical valves were 41.4%±7.2% and 30.5%±5.4% (P=0.02). For the patients older than 60 yr.,however,reoperation rates were 24.1%±8.5% and 14.7%±5.7% (P=0.36). CONCLUSION: Perioperative mortality and long-term survival are independent to valve types in patients with endocarditis. Mechanical valve shows potential advantage compared with bioprothetic valve in the patients younger than 60-year-old.

Aortoesophageal fistula and arch pseudoaneurysm after removing of a swallowed chicken bone: a case report of one-stage hybrid treatment.

BACKGROUND: Aortoesophageal fistula (AEF) and arch pseudoaneurysm are rare complications induced by a foreign body, and considerable controversy remains regarding the appropriate management strategies. We herein report a successful one-stage hybrid treatment in a patient with AEF and arch pseudoaneurysm. CASE PRESENTATION: The patient, a 40-year-old man, presented to the emergency room because of intense retrosternal discomfort for 3 days and hematemesis for 3 h. The esophagoscopy and thoracic enhanced computed tomography (CT) showed two irregular mural ulcers in the esophagus and a large saccular pseudoaneurysm at the aortic isthmus, respectively. The laboratory examinations confirmed no widespread inflammation and infection. We have successfully performed a successful one-stage hybrid treatment for this patient. Six-month follow-up shows the patient is in good condition and the esophagoscopy reveals the two mural ulcers had completely healed. CONCLUSION: The treatment decision-making process should depend upon the patients' specific situations. Our case suggest the one-stage hybrid treatment could be an valuable alternative in some selected patients.

[The Role of Bone Morphogenic Protein-4 in the Progression of Vein Graft Hyperplastic Remodeling under Hyperglycemic Condition].

OBJECTIVE: This study was designed to assess the vessel wall characteristics and the expression levels of bone morphogenic protein4(BMP4) and proliferating cell antigen Ki67 in vein grafts harvested from diabetic rats,and to investigate the role of BMP4 in progression of vein graft hyperplastic remodeling under hyperglycemic condition. METHODS: 48 male SpragueDawky rats [body mass (194±16) g] aged 8 weeks were randomly divided into diabetes mellitus (DM) group ( n=24) and nondiabetes mellitus (NDM) group ( n=24). The DM rats were induced by streptozotocin in combination with highsugar and highfat diet. The unilateral external jugular vein was interposition grafted into the common carotid arteries in the two groups. The vein grafts were harvested at preoperatively and 1,2 and 4 weeks postoperatively ( n=6) in each group. The morphological characteristics of the venous graft wall were evaluated by hematoxylineosin staining,and the expression levels and the distribution of Ki67 and BMP4 were assessed by immunohistochemistry analysis,then the expression of BMP4 gene and protein was measured by realtime polymerase chain reaction (RTPCR) and Western blot assay respectively. RESULTS: In the progression of rats vein grafts hyperplastic remodeling,the venous wall thickness of rats thickened with time increasing,and the intimal and medial thickness of the vein grafts harvested from DM rats were significantly higher than those from NDM rats at the same time postoperatively ( P<0.05). Ki-67 was highly xpressed in smooth muscle cells nucleus located in the rats vein grafts,and its expression level was up-regulated gradually in the progression of vein graft failure,and the Ki 67 positive cells of vein grafts from DM rats were significantly higher than those from NDM controls at the same period ( P<0.05). Immunohistochemistry analysis showed that BMP4 was expressed in smooth muscle cells cytoplasmof the rats vein grafts,combined with the results of RT-PCR and Western blot assay,there was a little BMP4 expression could be seen in venous wall of NDM rats,while BMP4 positive cells and the expression level of BMP4 gene and protein from DM rats vein grafts was increasing with obvious time dependence and significantly higher than the NDM rats ( P<0.05). CONCLUSION: The morphological and pathological changes within the venous wall were significantly correlated with the high expression levels of BMP4 in vein grafts harvested from diabetic rats,implying a potential role of BMP4 in the progression of accelerated vein graft failure under hyperglycemic condition.

Mitochondrial DNA­induced inflammatory damage contributes to myocardial ischemia reperfusion injury in rats: Cardioprotective role of epigallocatechin.

Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged­associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro­inflammatory mediator. Epigallocatechin­3­gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG­regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG­mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)­6 and ­8 were observed in the myocardial tissue following an I/R injury (P<0.05). However, EGCG administered prior to reperfusion was able to effectively downregulate the expression levels of plasma mtDNA, TNF and IL­6 and ­8 in the myocardial tissue following an I/R injury (P<0.05). Limited infarct size, reduced severity of myocardial injury and decreased incidence of ventricular arrhythmia were observed in the EGCG­treated group. However, the beneficial effects of EGCG in preventing myocardial I/R injury may be eliminated by a specific phosphoinositide­3­kinase (PI3K) inhibitor. These results suggested that EGCG­mediated cardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC­α serine/threonine­protein kinase associated signaling pathway.