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To investigate the protective effects of metformin on the diabetic mice with cognitive impairment induced by the combination of streptozotocin (STZ) and isoflurane anesthesia. The isoflurane-anesthetized cognitive impairment model mice were established and then observed via behavioral tests and histopathological examination. Then these model mice were randomly assigned to three groups, which received the PBS, low and high doses of metformin, respectively. The body weight, food and water consumption of model mice were measured every other day. The mechanisms of metformin on ameliorating the cognitive dysfunction were further investigated by histomorphological, biochemical and Western blot analysis. After 14-days treatment of metformin, the diabetic symptoms in STZ-induced diabetic mice were significantly alleviated. Metformin could restore the isoflurane- and STZ-induced hippocampal tissue damage, cognitive and memory impairment in exposed space via improving the oxidative stress, upregulating the contents of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the hippocampus tissues of diabetic mice. Furthermore, chronic treatment of metformin significantly down-regulated the expression of AGEs, RAGE, pNF-κB, iNOS, and COX-2. In conclusion, metformin can improve the isoflurane- and STZ-induced cognitive impairment in diabetic mice via improving oxidative stress and inhibiting the AGEs/RAGE/NF-κB signaling pathway.

AIM: To evaluate the effects, advantages, disadvantages, and indications of infrabrow skin excision to correct upper eyelid dermatochalasis in middle-aged and elderly Chinese women. METHODS: Sixty eyelids in 30 patients were subjected to this surgical procedure from January to June 2018. All patients had upper eyelid dermatochalasis, and the functions of their levator palpebrae were all normal. The primary indications of the procedure were upper lid dermatochalasis with lateral hooding. All 30 patients underwent infrabrow skin excision at Shanxi Eye Hospital. The degree of skin relaxation before and after surgery was evaluated in all patients, and surgical outcomes and postoperative complications were also assessed. RESULTS: All patients were female, ranging from 40 to 64 (mean: 53.20±7.10) years old. Skin relaxation of the upper eyelid was improved in all 30 patients. One month after the operation, 52 lids (86.7%) showed good results and 8 lids (13.33%) showed fair results. The objective Strasser system was applied to evaluate surgical results at 1 and 6 months. All patients had scores between 0 and 1 point, indicating good results. Preoperative unsatisfactory position and shape of the eyebrows were improved, and crow's feet and frontal lines were reduced. All patients were satisfied with the results. No complications related to wound dehiscence, lagophthalmos, or hypertrophic scars were observed. CONCLUSION: Infrabrow skin excision is a simple, useful operation to reconstruct the upper eyelids in selected patients of Chinese ancestry. This procedure not only retains the advantages of classic blepharoplasty, but also alleviates many eyebrow problems at the same time, and maintains the original shape of the eyelid, minimizes scarring, and produces a smoother, more youthful appearance.

Like the other spheres of economic activity, international trade is also a victim of the current Covid-19 pandemic. Therefore, taking this into consideration, this study examines the impact of the novel Covid-19 virus on international trade, by using monthly data from China and USA. For this purpose, we have referred to the novel Fourier causality test. The findings of the test show that there is a direct causal relationship between the Covid-19 related deaths and the exports and imports of China, while the Covid-19 cases do not have a causal relationship with the exports and imports of China in the pandemic. Moreover, the Covid-19 cases and deaths have a causal relationship with the exports and imports of USA. Thus, we found that there were heterogeneous effects experienced in both the countries. Based on these empirical findings, some policy implications have been suggested for the Chinese and USA economies.

Background This study aimed to explore the distribution of the erector spinal muscle plane block of the thoracic 12 vertebral body (T12) in the dorsal region guided by ultrasound. Methods A total of 28 patients, who underwent elective lumbar surgery, were enrolled in the present study. These patients were aged between 18 and 65 years, and the American Society of Anesthesiologists (ASA) grade was 1 or 2. The block of the T12 transverse process erector spinal muscle was performed under the guidance of ultrasound, and each side was injected with 25 ml of 0.4% ropivacaine hydrochloride + 2 mg of dexamethasone. The back areas were measured using the cold-warm method (the back area was divided into 11 areas [T7–S1] with the body surface marker). At 10, 20, 30, 40, 50, and 60 min after the drug injection, the effectiveness of the regional block was recorded. The presence of puncture hematoma, local anesthesia drug poisoning, nausea, vomiting, headache, and dizziness after the block was recorded. Results The range of the T12 transverse process block was basically fixed at 30 min after the single injection. No pneumothorax, hematoma, or local anesthetic poisoning occurred in any of the patients. Conclusion The effective longitudinal plane of the T12 transverse process erector spinal muscle block was mainly distributed in the T9–L5 dorsal cutaneous branches, and the distribution of the block area was safe and stable.

Interleukin (IL)-17A, a proinflammatory cytokine produced by T-helper (Th)17 cells, has been associated with autoimmune diseases. Type 1 diabetes (T1D) is caused either due to mutation of insulin gene or developed as an autoimmune disease. Studies have shown that IL-17A expression is upregulated in the pancreas in T1D patients and animal models. However, role or importance of IL-17A in T1D pathogenesis needs elucidation. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells through activating IL-17 receptor A (IL-17RA) is lacking. Ins2Akita (Akita) mouse, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis, was crossed with IL-17A-knockout mouse and male IL-17A-deficient Akita mice were used. Streptozotocin, a pancreatic β-cell-specific cytotoxin, was employed to induce a diabetic model in MIN6 cells, a mouse insulinoma cell line. IL-17A expression in the pancreas was upregulated in both Akita and streptozotocin-induced diabetic mice. IL-17A-knockout Akita mice manifested reduced blood glucose concentration and raised serum insulin level. IL-17A deficiency also decreased production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, IL-1β, and interferon (IFN)-γ in Akita mice. IL-17RA expression in MIN6 cells was upregulated by IL-17A. IL-17A enhanced expression of TNF-α, IL-1β, IFN-γ, and inducible nitric oxide synthase (iNOS) and further increased streptozotocin-induced expression of the inflammatory factors in MIN6 cells. IL-17A exacerbated streptozotocin-induced MIN6 cell apoptosis and insulin secretion impairment. Blocking IL-17RA with anti-IL-17RA-neutralizing antibody reduced all these deleterious effects of IL-17A on MIN6 cells. Collectively, IL-17A deficiency alleviated hyperglycemia, hypoinsulinemia, and inflammatory response in Akita mice that are characteristic for T1D. IL-17A exerted an alone and synergistic destruction with streptozotocin to pancreatic β cells through IL-17RA pathway. Thus, the data suggest that targeting IL-17A and/or IL-17RA is likely to preserve remaining β-cell function and treat T1D. Impact statement The participation of interleukin (IL)-17A in diabetic pathogenesis is suggested in animal models of autoimmune diabetes and in patients with type 1 diabetes (T1D), but with some contradictory results. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells is lacking. We showed that IL-17A deficiency alleviated diabetic signs including hyperglycemia, hypoinsulinemia, and inflammatory response in Ins2Akita (Akita) mice, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis. IL-17A enhanced inflammatory reaction, oxidative stress, and cell apoptosis but attenuated insulin level in mouse insulin-producing MIN6 cells. IL-17A had also a synergistic destruction to MIN6 cells with streptozotocin (STZ), a pancreatic β-cell-specific cytotoxin. Blocking IL-17 receptor A (IL-17RA) reduced all these deleterious effects of IL-17A on MIN6 cells. The results demonstrate the role and the importance of IL-17A in T1D pathogenesis and suggest a potential therapeutic strategy for T1D targeting IL-17A and/or IL-17RA.

Diabetic retinopathy (DR), the most common and serious ocular complication, recently has been perceived as a neurovascular inflammatory disease. However, role of adaptive immune inflammation driven by T lymphocytes in DR is not yet well elucidated. Therefore, this study aimed to clarify the role of interleukin (IL)-17A, a proinflammatory cytokine mainly produced by T lymphocytes, in retinal pathophysiology particularly in retinal neuronal death during DR process. Ins2Akita (Akita) diabetic mice 12 weeks after the onset of diabetes were used as a DR model. IL-17A-deficient diabetic mice were obtained by hybridization of IL-17A-knockout (IL-17A-KO) mouse with Akita mouse. Primarily cultured retinal Müller cells (RMCs) and retinal ganglion cells (RGCs) were treated with IL-17A in high-glucose (HG) condition. A transwell coculture of RGCs and RMCs whose IL-17 receptor A (IL-17RA) gene had been silenced with IL-17RA-shRNA was exposed to IL-17A in HG condition and the cocultured RGCs were assessed on their survival. Diabetic mice manifested increased retinal microvascular lesions, RMC activation and dysfunction, as well as RGC apoptosis. IL-17A-KO diabetic mice showed reduced retinal microvascular impairments, RMC abnormalities, and RGC apoptosis compared with diabetic mice. RMCs expressed IL-17RA. IL-17A exacerbated HG-induced RMC activation and dysfunction in vitro and silencing IL-17RA gene in RMCs abolished the IL-17A deleterious effects. In contrast, RGCs did not express IL-17RA and IL-17A did not further alter HG-induced RGC death. Notably, IL-17A aggravated HG-induced RGC death in the presence of intact RMCs but not in the presence of RMCs in which IL-17RA gene had been knocked down. These findings establish that IL-17A is actively involved in DR pathophysiology and particularly by RMC mediation it promotes RGC death. Collectively, we propose that antagonizing IL-17RA on RMCs may prevent retinal neuronal death and thereby slow down DR progression.

ObjectiveWe previously established a gross tissue response (GTR) system to evaluate the intraoperative response of perigastric tissue in patients with gastric cancers to neoadjuvant chemotherapy. This prospective cohort study aims to confirm the relationship between gross tissue response and clinicopathological characteristics and explore the possibility of using the GTR system to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.MethodsA total of 102 patients with gastric cancer from January 2019 to April 2020 were enrolled in this study. The degrees of fibrosis, edema, and effusion in the perigastric tissues were assessed intraoperatively according to the GTR system. We systematically analyzed the relations between GTR and clinicopathological characteristics, and then a prediction model that includes GTR was established to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.ResultsFinally, the study included 71 male patients and 31 female patients. The patients had an average age of 58.79 ± 1.03 years, BMI of 22.89 ± 0.29, and tumor diameter of 4.50 ± 0.27 cm. Among these patients, 17 underwent laparoscopic gastrectomy, 85 underwent open gastrectomy, the average operation time was 294.63 ± 4.84 minutes, and the mean volume of intraoperative blood loss was 94.65 ± 5.30 ml. The overall 30-day postoperative complication rate was 19.6% (20/102). The total GTR was significantly related to the primary tumor stage, operation time and 30-day postoperative complication rate (pConclusionAccording to the results of the present study, the gross tissue response (GTR) system is an effective tool that may be used to predict the risk of a difficult operation after neoadjuvant chemotherapy and postoperative complications. Although neoadjuvant chemotherapy improves the therapeutic effect, it also increases the risk of surgical trauma and postoperative complications.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03791268.

Rong-Hua Zheng,1,2 Xiao-Jie Bai,1 Wei-Wei Zhang,1 Jing Wang,1 Feng Bai,1 Cai-Ping Yan,1 Erskine A James,3 Himangshu S Bose,4 Ning-Ping Wang,1,4 Zhi-Qing Zhao1,41Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Medicine, Linfen Vocational and Technical College, Linfen, Shanxi, People’s Republic of China; 3Department of Internal Medicine, Navicent Health, Macon, GA, USA; 4Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USAObjective: Angiotensin II (Ang II) is known to contribute to the pathogenesis of heart failure by eliciting cardiac remodeling and dysfunction. The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study investigates whether GLP-1 receptor agonist liraglutide inhibits abdominal aortic constriction (AAC)-induced cardiac fibrosis and dysfunction through blocking Ang II type 1 receptor (AT1R) signaling.Methods: Sprague-Dawley rats were subjected to sham operation and abdominal aortic banding procedure for 16 weeks. In treated rats, liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or telmisartan (10 mg/kg/day), the AT1R blocker, was administered by gastric gavage.Results: Relative to the animals with AAC, liraglutide reduced protein level of the AT1R and upregulated the AT2R, as evidenced by reduced ratio of AT1R/AT2R (0.59±0.04 vs. 0.91±0.06, p

Rheumatic heart disease refers to the long-term damage of heart valves and results from an autoimmune response to group A Streptococcus infection. This study aimed to analyze the microbiota composition of patients with rheumatic heart disease and explore potential function of microbiota in this disease. First, we revealed significant alterations of microbiota in feces, subgingival plaques, and saliva of the patients compared to control subjects using 16S rRNA gene sequencing. Significantly different microbial diversity was observed in all three types of samples between the patients and control subjects. In the gut, the patients possessed higher levels of genera including Bifidobacterium and Eubacterium, and lower levels of genera including Lachnospira, Bacteroides, and Faecalibacterium. Coprococcus was identified as a super-generalist in fecal samples of the patients. Significant alterations were also observed in microbiota of subgingival plaques and saliva of the patients compared to control subjects. Second, we analyzed microbiota in mitral valves of the patients and identified microbes that could potentially transmit from the gut or oral cavity to heart valves, including Streptococcus. Third, we further analyzed the data using random forest model and demonstrated that microbiota in the gut, subgingival plaque or saliva could distinguish the patients from control subjects. Finally, we identified gut/oral microbes that significantly correlated with clinical indices of rheumatic heart disease. In conclusion, patients with rheumatic heart disease manifested important alterations in microbiota that might distinguish the patients from control subjects and correlated with severity of this disease.

Background Soil-transmitted helminths (STHs), such as hookworm, roundworm and whipworm, and food-borne trematodiases, including Clonorchis sinensis, remain a public health problem worldwide, especially in tropical and subtropical regions. Objective We aimed to determine the current prevalence of these parasites in Guangxi, China, which is located in a subtropical region. Methods A cross-sectional study and a 4-year longitudinal surveillance study were carried out. Stool samples were collected and examined microscopically for parasite eggs using the modified Kato-Katz thick smear method. Results The study subjects selected using stratified random cluster sampling for the cross-sectional study and longitudinal surveillance study numbered 15,683 and 24,429, respectively. In the cross-sectional study, hookworm, roundworm, whipworm, pinworm, C. sinensis, and tapeworm were found. The total prevalence of soil-transmitted helminths (STHs) was 6.4% (95% CI, 6.0-6.8). The prevalences of C. sinensis, hookworm, roundworm, whipworm, and pinworm were 10.6%, 4.2%, 0.3%, 0.3%, and 1.8%, respectively. The prevalence of C. sinensis in males (14.0%, 95% CI, 13.3-14.8) was significantly higher than in females (7.2%, 95% CI, 6.7-7.8) (P = 0.0001). The prevalence also was significantly higher in the medical worker group (20.8%, 95% CI, 12.9-28.7) than in all other occupational groups (10.5%, 95% CI, 10.0-11.0) (P = 0.0001). The prevalence of hookworm in females (5.3%, 95% CI, 4.8-5.8) was significantly higher than in males (3.0%, 95% CI, 2.6-3.3) (P = 0.0001). In the longitudinal surveillance study, the prevalence of C. sinensis and STHs in 2016, 2017, 2018, and 2019 were 12.0%, 6.0%, 11.0%, and 10.0% and 2.6%, 2.8%, 1.5%, and 1.5%, respectively. Conclusions Adult male and occupation of and medical workers are risk factors for infection with C. sinensis and hookworm. The prevalence rate of C. sinensis remains high while those of the other STHs are decreasing, suggesting that enhanced health education should be focused on C. sinensis in Guangxi.

Various studies have revealed an association between cigarette smoking and increased risk for multiple sclerosis (MS). However, its role in neuromyelitis optica spectrum disorder (NMOSD) remains elusive. Therefore, in the present case-control study, we aimed to assess the association of active and passive cigarette smoking with the risk of MS and NMOSD. Thirty-six patients with NMOSD, 46 patients with MS, and 122 healthy individuals were included in this study. Standardized questionnaires and telephone interviews were used to collect information regarding the active and passive cigarette smoking behaviors of the patients and normal controls. The risk of MS was significantly higher among smokers than among nonsmokers (odds ratio = 2.166, 95% confidence interval: 1.109–4.170; P = .027). Further analysis of the risk between active and passive smokers, male smokers and nonsmokers showed no statistical difference. However, neither smokers nor active smokers had a greater or lower risk of NMOSD than their nonsmoking counterparts. Our preliminary study showed no significant association between cigarette smoking and the risk of NMOSD, strongly suggesting that, unlike MS, cigarette smoking might not confer NMOSD susceptibility, at least in the Northern Han Chinese population.

Objective: This study aimed to investigate the effect of interleukin (IL)-21 and B cell lymphoma protein-6 on germinal center follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells and its relationship with the clinical features of inflammatory bowel disease (IBD).Methods: The expression of peripheral blood cytokines IL-21 and Bcl-6 mRNA was detected by reverse transcription–polymerase chain reaction. The distribution characteristics of Tfh and Tfr cells were detected using the triple immunofluorescence staining analysis.Results: The expression of IL-21 and Bcl-6 mRNA was upregulated in the ulcerative colitis (UC) and Crohn disease (CD) groups compared with that in the control group. Triple immunofluorescence staining showed that the number of Tfh cells in the intestinal germinal center obviously increased in the UC and CD groups compared with that in the control group, whereas the number of Tfr cells reduced.Conclusion: This study suggested that the Tfr and Tfh cells might be involved in the regulation of IBD. Bcl-6 and IL-21 can regulate the Tfh/Tfr ratio in the intestinal germinal center, promoting the occurrence and development of IBD.

Clinicians should expect controversial goals of care discussions in the surgical intensive care from time to time. Differing opinions about the likelihood of meaningful recovery in patients with chronic critical illness often exist between intensive care unit providers of different disciplines. Outcome predictions presented by health-care providers are often reflections of their own point of view that is influenced by provider experience, profession, and personal values, rather than the consequence of reliable scientific evaluation. In addition, family members of intensive care unit patients often develop acute cognitive, psychologic, and physical challenges. Providers in the surgical intensive care unit should approach goals-of-care discussions in a structured and interprofessional manner. This best practice paper highlights medical, legal and ethical implications of changing goals of care from prioritizing cure to prioritizing comfort and provides tools that help physicians become effective leaders in the multi-disciplinary management of patients with challenging prognostication.

Mammalian target of rapamycin (mTOR) and a ribosomal protein S6 kinase (p70S6K) mediate tissue fibrosis and negatively regulate autophagy. This study aims to investigate whether glucagon-like peptide-1 (GLP-1) analog liraglutide protects the heart against aortic banding-induced cardiac fibrosis and dysfunction through inhibiting mTOR/p70S6K signaling and promoting autophagy activity. Male SD rats were randomly divided into four groups (n = 6/each group): sham operated control; abdominal aortic constriction (AAC); liraglutide treatment during AAC (0.3 mg/kg, injected subcutaneously twice daily); rapamycin treatment during AAC (0.2 mg/kg/day, administered by gastric gavage). Relative to the animals with AAC on week 16, liraglutide treatment significantly reduced heart/body weight ratio, inhibited cardiomyocyte hypertrophy, and augmented plasma GLP-1 level and tissue GLP-1 receptor expression. Phosphorylation of mTOR/p70S6K, populations of myofibroblasts and synthesis of collagen I/III in the myocardium were simultaneously inhibited. Furthermore, autophagy regulating proteins: LC3-II/LC3-I ratio and Beclin-1 were upregulated, and p62 was downregulated by liraglutide. Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. In line with these modifications, treatment with liraglutide and rapamycin significantly reduced perivascular/interstitial fibrosis, and preserved systolic/diastolic function. These results suggest that the inhibitory effects of liraglutide on cardiac fibrosis and dysfunction are potentially mediated by inhibiting mTOR/p70S6K signaling and enhancing autophagy activity.

Objectives:In New York City, a multi-disciplinary Mass Casualty Consultation team is proposed to support prioritization of patients for coordinated inter-facility transfer after a large-scale mass casualty event. This study examines factors that influence consultation team prioritization decisions.Methods:As part of a multi-hospital functional exercise, 2 teams prioritized the same set of 69 patient profiles. Prioritization decisions were compared between teams. Agreement between teams was assessed based on patient profile demographics and injury severity. An investigator interviewed team leaders to determine reasons for discordant transfer decisions.Results:The 2 teams differed significantly in the total number of transfers recommended (49 vs 36; P = 0.003). However, there was substantial agreement when recommending transfer to burn centers, with 85.5% agreement and inter-rater reliability of 0.67 (confidence interval: 0.49–0.85). There was better agreement for patients with a higher acuity of injuries. Based on interviews, the most common reason for discordance was insider knowledge of the local community hospital and its capabilities.Conclusions:A multi-disciplinary Mass Casualty Consultation team was able to rapidly prioritize patients for coordinated secondary transfer using limited clinical information. Training for consultation teams should emphasize guidelines for transfer based on existing services at sending and receiving hospitals, as knowledge of local community hospital capabilities influence physician decision-making.

Nanostructured thermal barrier coatings (nano-TBCs) are being extensively studied because of their excellent thermal barrier properties. The occurrence of sintering in TBCs is inevitable in service; however, accelerated sintering of the nano-TBCs may cause premature failure. This study focuses on the changes of microstructure and thermal conductivity of bimodal nano-TBCs during thermal exposure. Results show that there are two stages in the sintering process. It was found that the thermal conductivity increased rapidly in the first stage (from 0 to 20 h), with the rate of increase in normalized thermal conductivity equal to 140% of bimodal coating. The continuous healing of the pores was the main structural change. During the following stage (20 to 100 h), the thermal conductivity decreased with the rate of increase in normalized thermal conductivity equal to − 8% of bimodal coating. The change of structure was the opening of pores. Furthermore, self-enhancing behavior of bimodal composite coatings was discovered. The phenomenon of inevitable sintering in thermodynamics can be used to introduce large-aspect-ratio pores in the in-depth direction, which can greatly slow down the increase in thermal conductivity in service and ultimately increase the lifetime of the thermal insulation. Based on a full study of the sintering mechanism of composite coatings, the present study sheds light on the structural adjustments that lead to a lower thermal conductivity and longer service life in the advanced TBC during high-temperature service.

The 21st century brought many changes to the world. From witnessing a technological boom and awareness about the environment to renewable energy and conscious use of natural resources, the current century had offered a lot in the previous two decades. However, the question of natural resources being a curse or a blessing to the natural resource-producing economies is still unanswered and gathers many scholars' attention. The current study investigates the volatility of natural resources, oil and gold, and studies the impact of volatility in natural resource prices for resource-producing economies. The global market for crude oil has experienced significant downturns during the last two decades, the financial crisis of 2008 and the Covid 19 crisis of 2020, for instance. Compared to that, the global gold market has experienced relatively less impactful downturns during the same period. We explore how the volatility in oil and gold prices impact the growth of the resource-producing economies. The study is conducted on the top oil-producing countries and the top gold-producing countries on data from 2000 to 2020. The study finds that in the long run, the volatility in both oil and gold markets could be detrimental to the economic growth as measured by the GDP for the resource-producing economies. Our research also shows that the impact of the volatility in prices on the growth of economies is not consistent for all resource-producing economies in the short-term using PMG/ARDL methodology.

To improve the energy efficiency of supercomputer center, a novel energy system aimed at enhancing cooling efficiency while reusing waste heat is proposed. The energy system integrates a plug-type spray cooling system with a two-stage absorption chiller driven by spray cooling waste heat. Overall modeling of integrated energy system is analyzed based on spray cooling model and absorption chiller model. Energy saving evaluation is conducted based on Dawning 5000A supercomputer in China. It is found that the novel energy system is much efficient than the original energy system in all seasons. The energy saving effect is highly affected by inlet temperature of spray cooling. With the increase of inlet temperature, the spray cooling capacity decreases while the absorption cooling capacity increases. Thus, an optimal inlet temperature of 55 °C is obtained at which the lowest cooling power consumption, lowest power utilization effectiveness (PUE) and highest energy saving efficiency (ESE) can be achieved. Taken Dawning 5000A supercomputer for example, the system can achieve ESE as high as 49% and PUE within best practice scenario of 1.44. At the optimal design, cooling power consumption only accounts for 16%. Power consumption devoted to running the IT equipment is improved from 60% to 67%.

The morphology and pattern (including orientation and aspect ratio) of pores in thermal barrier coatings (TBCs) significantly affect their thermal insulation performance. In this work, finite element analysis was used to comprehensively understand the thermal insulation effect of pores and correlate the effective thermal conductivity with the structure. The results indicated that intersplat pores, and in particular their aspect ratio, dominantly affect the heat transfer in the top coat. The effective thermal conductivity decreased as a function of aspect ratio, since a larger aspect ratio often corresponds to a greater proportion of effective length of the pores. However, in conventional plasma-sprayed TBCs, intersplat pores often fail to maximize thermal insulation due to their distinct lower aspect ratios. Therefore, considering this effect of aspect ratio, a new structure design with multiscale pores is proposed and a corresponding structural model developed to correlate the thermal properties with this pore-rich structure. The predictions of the model are well consistent with experimental data. This study provides comprehensive understanding of the effect of pores on the thermal insulation performance, shedding light on the possibility of structural tailoring to obtain advanced TBCs with lower thermal conductivity.

Clearance of amyloid-beta (Aβ) from the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Current studies mainly focus on the central approach of Aβ clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aβ, suggesting that the peripheral approach of removing Aβ from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aβ burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aβ concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from 6 months of age (prevention study) or 9 months of age (treatment study). The Aβ in the interstitial fluid (ISF) was collected using microdialysis. Behavioural performance, long-term potentiation (LTP), Aβ burden and other AD-type pathologies were measured after 1 month of peritoneal dialysis. Peritoneal dialysis significantly reduced plasma Aβ levels in both CKD patients and APP/PS1 mice. Aβ levels in the brain ISF of APP/PS1 mice immediately decreased after reduction of Aβ in the blood during peritoneal dialysis. In both prevention and treatment studies, peritoneal dialysis substantially reduced Aβ deposition, attenuated other AD-type pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, and synaptic dysfunction, and rescued the behavioural deficits of APPswe/PS1 mice. Importantly, the Aβ phagocytosis function of microglia was enhanced in APP/PS1 mice after peritoneal dialysis. Our study suggests that peritoneal dialysis is a promising therapeutic method for AD, and Aβ clearance using a peripheral approach could be a desirable therapeutic strategy for AD. Refereed/Peer-reviewed

Objective: We previously have established the gross tissue response (GTR) system to evaluate the intraoperative perigastric tissue response after neoadjuvant chemotherapy of gastric cancers. This prospective cohort study aims to confirm the relationship among gross tissue response, postoperative complications, and pathological tumor regression. Methods: A total of 156 gastric cancer cases from January 2018 to December 2019 were enrolled in the study. The fibrosis, edema, and effusion degree of perigastric tissues was intraoperative assessed according to the GTR system. We systematically analyzed relations among the GTR system, clinicopathological characteristics, and postoperative 30-day complications. Results: Finally, the study had included 107 males and 49 female patients. The overall incidence rate of postoperative 30-day complications was 26.28% (41/156). Fibrosis, edema and the total score of the GTR system were significantly related to operation time and postoperative 30-day complications (p

To investigate the influence of carotid artery stenting (CAS) with embolic protection device (EPD) on the cognitive function of patients with near-occlusion of the cervical internal carotid artery (ICA).From February 2014 to December 2017, a total of 79 symptomatic patients were recruited in this study. Of these patients, 31 patients refused to receive CAS therapy. They were divided into the CAS group (48 patients) and the medical treatment group (31 patients). Montreal cognitive assessment (MoCA) instrument was used for the evaluation of cognitive function. The analyzed endpoints included cumulative 12 month incidence of ipsilateral ischemic cerebrovascular events and MoCA scores at 1 month and 12 months after treatment.Cumulative 12 months incidence of ipsilateral ischemic cerebrovascular events was lower in patients who underwent CAS than in patients on medical treatment (P 0.05). In CAS group, the total MoCA score, scores of attention and delayed recall at months 1 and 12 increased when compared with those at baseline (P 0.05). In medical treatment group, the total MoCA score and attention score at month 12 decreased when compared with those at baseline (P 0.05). In CAS group, the total MoCA score, scores of line connection test, drawing clock, attention and delayed recall were improved at 1 and 12 months when compared with medical treatment at the same time points (P 0.05).CAS with EPD not only decreases the risk of ipsilateral TIA and stroke but also may improve the cognitive function of symptomatic patients with ICA near-occlusion.

Background Interstitial lung disease (ILD) is a common complication of connective tissue disease (CTD) and a leading cause of morbidity and mortality. There are various lung ultrasound (LUS) scoring systems with different lung intercostal spaces (LIS). The purpose of this meta-analysis was to find a simplified LUS method for the assessment of CTD-ILD. Methods We systematically retrieved lung ultrasound diagnostic studies on CTD-ILD in PubMed, Embase, and Web of Science databases. Summary diagnostic accuracy, including sensitivity, specificity, and area under the curve (AUC), was analyzed. Subgroup analysis was conducted according to different LIS and diseases. Results The 11 studies included in this meta-analysis comprised a total of 487 patients with CTD. The pooled sensitivity and specificity of the LUS were 0.859 (95% confidence interval (CI) 0.812–0.898) and 0.839 (95% CI 0.782–0.886), respectively, illustrating its great value for CTD-ILD diagnosis. In addition, there were six methods to evaluate LIS, including 72, 65, 50, 14, 10, and all LIS. The pooled sensitivity and specificity of 14 LIS were 0.982 (95% CI 0.904–1.000) and 0.875 (95% CI 0.710–0.965), respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odd ratio (DOR) of 14 LIS were 7.297 (95% CI 6.050–17.45), 0.029 (95% CI 0.006–0.147), and 292.30 (95% CI 35.53–2403.8), respectively. Moreover, the AUC for systemic sclerosis (SSc) and rheumatoid arthritis (RA) was 0.929 and 0.981, respectively; the DOR for SSc and RA was 42.93 (95% CI 17.75–103.79) and 80.24 (95% CI 8.107–796.09), respectively. Conclusions We found a modified and simplified method of LUS, by scanning 14 LIS in a short time, which had a very high sensitivity and specificity.

In this paper, a method has been proposed for high efficiency unidirectional optical transmission diode at 1550 nm. We use a new composite structure, holographic polymer dispersed liquid crystal (H-PDLC) grating-photonic crystal (PC), to realize it. There exists the directional band gap for the PC structure in 1550 nm. Therefore, it is possible to use the H-PDLC Bragg grating to shift the incident angle to a particular value to satisfy the condition so that the PC energy band can be moved from the pseudo-band gap to the passband to achieve the purpose of unidirectional transmission optical diode with high-efficiency. So that when the 1550 nm beam diffracted from the H-PDLC grating to incident the PC structure, it will transmit the composite structure almost totally, but it will be completely none reflected from PC surface. The simulation results show that the forward transmittance is 94.1% and the backward transmittance is near 0. At the same time, H-PDLC grating provide a method to adjust the transmittance of the composite structure diode with its electrically-controlled characteristics. This composite structure design provides another efficient method for the realization of all-optical diodes in the field of optical communication.

ObjectiveTo investigate the correlation between the pain rating index (PRi), which is an index derived from processed electroencephalography signals, and the end-tidal sevoflurane concentration (ETsevo).MethodsThis study involved 50 adults with a body mass index of 18 to 25 kg/m2who were undergoing elective surgery under general anesthesia. Thyrocricocentesis was performed with 2.5 mL of 2% tetracaine for endotracheal surface anesthesia, and intravenous injections of midazolam, etomidate, and rocuronium were then administered. The patients’ tracheas were intubated and their ventilatory rate was adjusted to maintain the partial pressure of end-tidal carbon dioxide at 30 to 35 mmHg. Anesthesia was maintained with sevoflurane. The ETsevo was adjusted to maintain anesthesia at 0.6, 0.8, 1.0, and 1.2 minimum alveolar concentration for 15 minutes each, and the PRi, mean arterial pressure (MAP), and heart rate were recorded at each concentration.ResultsA negative correlation was found between the PRi and ETsevo (−0.882) and between the MAP and ETsevo (−0.571). A low positive correlation was found between the PRi and MAP (0.484).ConclusionsThe PRi showed a high negative correlation with the ETsevo. Therefore, the PRi can be used to guide the depth regulation of sevoflurane anesthesia. Clinical trial registration number: ChiCTR-IPR-17012092

BACKGROUND Female gender has been associated with worse outcomes after cardiovascular surgery and critical illness. We investigated the effect of gender on perioperative outcomes following robotic-assisted pulmonary lobectomy. METHODS We retrospectively analyzed 282 consecutive patients who underwent robotic-assisted pulmonary lobectomy by one surgeon over 53 months. Perioperative outcomes and clinically significant intraoperative and postoperative complications, including respiratory and cardiovascular events, were noted. Chi-Square (χ2), Fisher's exact test, Analysis of Variance (ANOVA), Student's t-test, and Kruskal-Wallis or Mood's median test were used to compare variables, with significance at P≤0.05. RESULTS There were 128 men (mean age, 68.8 yr) and 154 women (mean age, 65.9 yr; P=0.02). Women had higher preoperative forced expiratory volume in 1 second as percent of predicted (FEV1%; P=0.001). There were more former smokers in the male cohort (P=0.03) and more nonsmokers in the female cohort (P

Practical and integrated spray cooling system is urgently needed for the cooling of high-performance electronic chips due to the growth requirements of thermal management in workstation. The integration of multi heat sources and the management of integral system are particularly lacking. In order to fill the vacancies in the study of plug-chip spray cooling, an integrated cooling enclosure was designed in this paper. Multi heat sources were placed in sealed space and the heat was removed by spray. The printed circuit board plug-ins and radio frequency resistors were used as analog motherboards and chips, respectively. The enhanced surfaces with four different geometries and the plain surface were studied under the conditions of different inclination angles. The results were compared and the maximum critical heat flux (CHF) was obtained. Moreover, with the intention of the overall management of multi-heat source in integrated enclosure, the effect of the flow rate and the temperature disequilibrium, and the pulse heating in the process of transient cooling were also analyzed. In addition, a comprehensive assessment system, used to evaluate the practicality of spray cooling experimental devices, was proposed and the performance of enclosure was evaluated.

Background— There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. Methods and Results— The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p =0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10–2.24; P =0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. Conclusions— OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01306526.

Background: To explore whether the multiparametric radiomics nomogram on computed tomography (CT) images based on radiomics and relevant indices of esophageal varices(EV) can be used for predicting the EV severity in patients with cirrhotic livers. Methods: 136 consecutive patients with clinicopathologically confirmed liver cirrhosis from January 2016 to August 2018 were included for the predictive model development, patients were divided into non-conspicuous EV group(mild-to-moderate EV,n=30) and conspicuous EV group (severe EV,n=106) according to standard endoscopy validation. The radiomic scores(Rad-scores) were constructed from radiomics features of regions of interest(ROIs) in left liver(LL) and right liver(RL) respectively. The multiparametric nomogram was combined the better performance Rad-score and EV-relevant indices, the calibration, discrimination and clinical usefulness of developed nomogram were evaluated using calibration curves, decision curve analysis(DCA) and net reclassification index(NRI) analysis respectively. Findings: The LL Rad-score calculated from radiomics features was selected with relatively higher area under the curve(AUC; 0.88,training cohort; 0.865,validation cohort). In addition, cross-sectional surface area(CSA) was identified as the important predictor(P

With the rapid change of the times, the advent of the “Internet+” era, consumer demand continues to be personalized, and gradually promote the transformation of the production mode of motor manufacturing enterprises. Under the premise of satisfying customer needs and increasing participation, based on the characteristics of the production of motor companies, and combined with the status quo of motor manufacturing, through the company’s on-site inspection and enterprise needs analysis, in order to build a personalized manufacturing management system for motor manufacturing manufacturers. At the same time, the physical data model of the system and the structure and module of the personalized customization platform system were respectively developed and designed using Power Designer modeling software and J2EE technology. Through the practical application of the company, the customer’s experience with personalized design and the real-time interaction between the company and the customer are realized. The distance between the enterprise and the customer is shortened and take the customer as the center of the production mode is implemented.

Importance Despite a high disease burden, there is no effective treatment for respiratory syncytial virus (RSV) infection. Objectives To determine whether administration of azithromycin (AZM) to children with RSV-induced respiratory failure is safe and to define the effect of AZM therapy on nasal matrix metalloproteinase 9 (MMP-9) levels. Design, Setting, and Participants This randomized, double-blind, placebo-controlled phase 2 trial was conducted at a single tertiary pediatric intensive care unit from February 2016 to February 2019. The study included children with RSV infection who were admitted to the pediatric intensive care unit and required respiratory support via positive pressure ventilation (invasive and noninvasive). A total of 147 children were screened; 90 were excluded for not meeting inclusion criteria, having an absent legal guardian, lacking pharmacy support, or having a language barrier and 9 declined participation, resulting in 48 patients enrolled in the study. Intervention Receipt of standard dose AZM (10 mg/kg/d), high-dose AZM (20 mg/kg/d), or a matching placebo of normal saline intravenously for 3 days. Main Outcomes and Measures Nasal and endotracheal samples were collected at baseline as well as at 24 hours and 48 hours after start of treatment. The secondary outcome was to determine treatment effect on clinical outcome measures, including days of positive pressure ventilation and length of hospital stay. Results A total of 48 patients were enrolled in the trial, with a median (range) age at randomization of 12 (1 to 125) months; 36 participants (75.0%) were younger than 2 years. Overall, 26 participants (54.2%) were boys, and 29 (60.4%) had a comorbidity. A total of 16 patients were randomized into each trial group (ie, placebo, standard-dose AZM, and high-dose AZM). Baseline demographic characteristics were comparable among the 3 groups. Both doses of AZM were safe, with no adverse events observed. No difference in nasal MMP-9 levels were observed between treatment groups. Among those who required mechanical ventilation and received high-dose AZM, endotracheal active and total MMP-9 levels were lower on day 3. Compared with baseline, active and total MMP-9 levels in endotracheal aspirates were 1.0 log lower in the high-dose AZM group (active MMP-9: 99.8% CI, −1.28 to −0.64;P Conclusions and Relevance In this phase 2 randomized clinical trial, both doses of AZM were safe. While nasal MMP-9 levels were unchanged among treatment groups, endotracheal MMP-9 levels were lower among those who received high-dose AZM. The positive secondary clinical outcome, while exploratory, provides insight for end points in a multicenter randomized trial. Trial Registration ClinicalTrials.gov Identifier:NCT02707523

In the current health care field, benefit from the provision of medical big data, machine learning can be used to obtain knowledge from the data. Machine learning methods can describe cases from an objective perspective, and predictions of diagnostic results can be generated from a combination of related pathological factors. The introduction of machine learning for the way of medical diagnosis and the accuracy of diagnosis is a major change and inevitable direction of the future medical model. In this paper, the random forest algorithm is used to analyze the medical case diagnosis of breast cancer. The random forest algorithm can combine the characteristics of multiple eigenvalues, and the combined results of multiple decision trees can be used to improve the prediction accuracy. Based on the ensemble learning method of random forests, the results of multiple weak classifiers can be combined to produce accurate classification results. In this paper, a random forest algorithm is used to discuss the case of breast cancer case diagnosis and obtain high prediction accuracy. It has practical significance for auxiliary medical diagnosis.

Natural frequency and modes of rocket sled system were gained by modal analysis. In order to decrease the influence of the resonance on the structure destruction, vibration characteristics of rocket sled was analyzed as dynamic testing after designing of sled structure. The rocket sled geometry is established in Solid Works and the geometry is imported into ANSYS Workbench to conduct a modal analysis in order to obtain the natural frequency and vibration model of track and single track sled. Frequency dimension and deformation position were obtained. The results shows that natural frequency of track and single track sled differed greatly and resonance of sled system hadn't happen as dynamic test.

To obtain more reliable localization performance, we propose a new image forgery localization scheme, which fuses the output of two diverse tools, based on PRNU and PatchMatch algorithm, respectively. First, tampering possibility maps are obtained from each of the two approaches, and then Dempster-Shafer theory of evidence is used as decision fusion strategy to obtain the final localization map. Comparison with single approach shows an improvement in tampering localization accuracy.

Background: As the infant's best interests are determined through the perinatal decisions of family members and physicians, it is important to understand the factors that affect such decisions. This paper investigated the separate and combined effects of various factors related to perinatal decision making and sought to determine the best way to convey information in an unbiased manner to family members. Methods: In total, 613 participants were consecutively recruited. Each participant completed a series of surveys. All responses to four items were examined via a latent class analysis (LCA) to identify subgroups of participants with similar preferences for intensive care (IC) and comfort care (CC) regarding their potentially premature infant. Multiple logistic regression analyses were applied to identify the sociodemographic predictors for the classification of participants into different subgroups. Results: χ2-tests indicated that perinatal decision making for Item 2 was influenced by framing information, whereas decision making wasn't affected by presentation modes. Furthermore, the endorsement rates of IC significantly decreased with the information increased from brief to detailed, regardless of framing or presentation mode. The LCA indicated that a 3-subgroup model, which included the IC, CC, and variation subgroups, was optimal. Logistic regression analyses demonstrated that, compared with the IC subgroup, negative framing, higher education, parenthood, and poor numeracy predicted participants' preferences for CC. Meanwhile, worrying about physical or mental disabilities predicted preferences for CC and sensitivity to the amount of information provided regarding treatment options (variation subgroup). Conclusions: Perinatal decision making is affected by many factors, suggesting that more detailed information, improved understandability of numerical data, and a neutral tone of voice regarding therapeutic outcomes would be helpful for the families of premature infants to make unbiased decisions. Our findings should be replicated in future research.

Background Preoperative serum inflammatory markers have been correlated with survival outcomes after resection of hepatocellular carcinoma (HCC). Whether they can predict microvascular invasion (MVI) in HCC is still unknown. This study aimed to evaluate the association of inflammatory markers with MVI, and develop a simple and inexpensive preoperative prediction model for MVI. Methods We developed a novel index using routine laboratory tests to predict MVI. The index was developed based on a study on patients with HCC, and validated in an internal cohort and another external cohort. The infiltration of CD8+ T cells in tumors was measured using immunohistochemistry. The prediction accuracy was evaluated with the area under the receiver operating characteristic curve (AUC). Results There were 165 patients in the training cohort, 107 patients in the internal validation cohort and 80 patients in the external validation cohort. On multivariable analysis in the training cohort, alkaline phosphatase (ALP) and lymphocyte count were independent predictors of MVI. Thus, the ALP-to-lymphocyte ratio (ALR) was developed. The AUCs of the ALR for MVI were higher than the other conventional clinical indices. An optimal cutoff point for the ALR of 69.9 stratified HCC patients into the high (≥69.9) and low ( Conclusion ALR was a simple, accurate and inexpensive alternative to predict MVI and an independent risk factor of prognosis for HCC patients. The dismal survival outcomes in patients with high ALR scores were related to decreased infiltrations of CD8+ T cells in tumors.

The study of practical and integrated spray cooling system with high cooling capacity is necessary for workstation or supercomputer since the increasing heat flux seriously affects the longevity and stability of electronic chips. In this paper, a novel plug-chip spray cooling enclosure was designed to study thermal control in the host. The electronic mainboard array was replaced by the printed circuit board array and the heat flow of electronic chips was simulated by the electric power of radio frequency resistances. HFE7100 and PF5060 were used as working fluids. The linear nozzle array was designed and the characteristics were estimated. The study focused on the effects of spray inclination angle on heat transfer performance under different working fluids, flow rates and fins directions in the transient and steady-state conditions. The results indicate that the surface temperature could reach steady rapidly when the spraying began. The inclination angle had a significant effect on heat transfer under different working conditions while the maximum critical heat flux was obtained at 75° inclination angle. The highest dissipated heat flux reached 81.6 W/cm2 at 51.1 °C surface temperature. In addition, volume flow rate and fins directions also had an extremely important influence on plug-chip spray cooling.

The aim of the present study was to determine the most meaningful preoperative prognostic factor of cancer-related death in ovarian cancer patients by comparing potentially prognostic systemic inflammatory response (SIR) markers. The levels of fibrinogen, albumin, C-reactive protein (CRP), and serum cancer antigen-125 (CA-125) and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were evaluated in 190 ovarian cancer patients to identify predictors of overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analyses. Patients with a PLR203 had a shorter PFS and OS than the patients in PLR ≤203 group (11 vs. 24 months and 28 vs. 64 months). Univariate analyses revealed that tumor stage, postoperative residual tumor mass, ascites, and the levels of all SIR markers were associated with PFS and OS. Multivariate analysis revealed that PLR was independently associated with PFS (hazard ratio [HR] 1.852, 95% confidence interval [CI] 1.271-2.697, P = 0.001) and OS (HR 2.158, 95%CI 1.468-3.171, P 0.001), as well as tumor stage and postoperative residual tumor mass. In contrast, fibrinogen remained significant only for PFS (HR 1.724, 95%CI 1.197-2.482, P = 0.003). Patients with a PLR203 were more prone to have advanced tumor stage (P = 0.002), postoperative residual tumor mass2 cm (P = 0.032), malignant ascites (P 0.001), and all the other elevated SIR markers (P 0.001). Preoperative PLR is superior to other SIR markers (CA-125, NLR, fibrinogen, CRP, and albumin) as a predictor of survival in ovarian cancer patients.

The impact dynamics of spatial multi-link flexible multibody system is studied based on the continuous contact force method (CCFM). According to the rigid-flexible coupling dynamic theory of flexible multibody system, the rigid-flexible coupling continuous dynamic equations of the system are established by using the recursive Lagrange method. The impact dynamic equations of the system are stylized derived on the use of CCFM basing on the nonlinear spring-damper model. The contact separation criterion is given to achieve the conversion and calculation of the dynamic model for the system at different stages. An impact dynamic simulation example for a two-link planar flexible multibody system is given, as well as the global dynamic response. The results show that the impact dynamic solving method based on CCFM can be used for the global impact dynamics of multi-link flexible multibody systems. The dynamic behavior of the system changes dramatically during the impact process. The large overall motion, the small deformation motion and the impact effect are coupled.

Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration (CFDA) as a first-in-class gene therapy product to treat head and neck cancer, and entered the commercial market in 2004. Gendicine is a biological therapy that is delivered via minimally invasive intratumoral injection, as well as by intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed by Gendicine-transduced cells is a tumor suppressor that is activated by cellular stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis, senescence, and/or autophagy, depending upon cellular stress conditions. Based on 12 years of commercial use in30,000 patients, and30 published clinical studies, Gendicine has exhibited an exemplary safety record, and when combined with chemotherapy and radiotherapy has demonstrated significantly higher response rates than for standard therapies alone. In addition to head and neck cancer, Gendicine has been successfully applied to treat various other cancer types and different stages of disease. Thirteen published studies that include long-term survival data showed that Gendicine combination regimens yield progression-free survival times that are significantly longer than standard therapies alone. Although the p53 gene is mutated in50% of all human cancers, p53 mutation status did not significantly influence efficacy outcomes and long-term survival rate for Ad-p53-treated patients. To date, Shenzhen SiBiono GeneTech has manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements, and 169,571 vials (1.0 × 10

Background/Aims: Anion channels such as chloride channel are known to participate in the regulation of a wide variety of cellular processes including development, differentiation, proliferation, apoptosis and regeneration. This study was designed to examine the effect of the non-selective anion channel blocker 4,4'-Diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) on cardiac function and apoptosis using a rat model of ischemia/reperfusion (I/R). Methods: Fifty male SD rats were randomly divided into the following groups including sham, I/R and I/R+DIDS (7, 14 or 28 mg/kg). In DIDS group, rats received DIDS treatment (4 ml/kg/hr) at the beginning of reperfusion for 2 hrs using a programmed micro-pump. Cardiac function was evaluated including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) as well as positive and negative maximal derivatives of left ventricular pressure (± dP/dtmax). Myocardial infarct size was detected using the double staining with 2, 3, 5-triphenyl-2H-tetra-zolium chloride (TTC) and Evan's blue dye. DNA ladder, TUNEL assay, Bax and Bcl-2 protein levels were evaluated. Levels of ROS and Akt phosphorylation were detected. Results: I/R injury compromised cardiac function as manifested by reduced LVSP and ± dP/dtmax as well as pronounced apoptosis. I/R-induced cardiac anomalies were markedly ameliorated by DIDS. DIDS retarded I/R-induced myocardial infarct and apoptosis. In addition, DIDS ameliorated I/R-induced ROS production and Akt dephosphorylation in the heart. Conclusion: Taken together, our data revealed that DIDS may protect cardiomyocytes against I/R injury as evidenced by improved cardiac function, Bcl-2, Akt phosphorylation, and reduced myocardial apoptosis, Bax expression, ROS production and myocardial infarct size.

The purpose of this study was to elucidate whether treatment with cyclosporine induces myocardial fibrosis and hypertension that may potentially be mediated by activation of angiotensin II Ang II and induction of inflammation In C BL mice cyclosporine at the doses of mg kg day or mg kg day was administrated by gastric gavage In different groups angiotensin II Ang II AT receptor blocker telmisartan mg kg day or anti inflammatory compound curcumin mg kg day was co administered with cyclosporine Treatment with cyclosporine for weeks did not alter the protein expression including AT and AT receptors monocyte chemotactic protein transforming growth factor beta collagen I and collagen III but increased expression of angiotensin converting enzyme relative to the sham control Interstitial macrophage infiltration and myofibroblast proliferation were not changed by cyclosporine consistent with lack of collagen deposition in the interstitial perivascular regions Co administration of telmisartan or curcumin with cyclosporine also had no effect on any of the parameters measured There was a trend in increase of blood pressure with high dose of cyclosporine alone and decrease of blood pressure when cyclosporine was co administered with telmisartan or curcumin but these changes did not achieve the statistical differences among the groups These data suggest that cyclosporine has no direct effect on myocardial fibrosis and blood pressure in healthy individuals and it may be considered as an adjunctive therapy with commonly used drugs to treat cardiovascular diseases nbsp