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Background: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide., Objective: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status., Methods: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities., Results: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities., Conclusion: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes., Competing Interests: Conflict of interest: Wei-jie Guan has nothing to disclose. Conflict of interest: Wen-hua Liang has nothing to disclose. Conflict of interest: Yi Zhao has nothing to disclose. Conflict of interest: Heng-rui Liang has nothing to disclose. Conflict of interest: Zi-sheng Chen has nothing to disclose. Conflict of interest: Yi-min Li has nothing to disclose. Conflict of interest: Xiao-qing Liu has nothing to disclose. Conflict of interest: Ru-chong Chen has nothing to disclose. Conflict of interest: Chun-li Tang has nothing to disclose. Conflict of interest: Tao Wang has nothing to disclose. Conflict of interest: Chun-quan Ou has nothing to disclose. Conflict of interest: Li has nothing to disclose. Conflict of interest: Ping-yan Chen has nothing to disclose. Conflict of interest: Ling Sang has nothing to disclose. Conflict of interest: Wei Wang has nothing to disclose. Conflict of interest: Jian-fu Li has nothing to disclose. Conflict of interest: Cai-chen Li has nothing to disclose. Conflict of interest: Li-min Ou has nothing to disclose. Conflict of interest: Bo Cheng has nothing to disclose. Conflict of interest: Shan Xiong has nothing to disclose. Conflict of interest: Zheng-yi Ni has nothing to disclose. Conflict of interest: Jie Xiang has nothing to disclose. Conflict of interest: Yu Hu has nothing to disclose. Conflict of interest: Lei Liu has nothing to disclose. Conflict of interest: Hong Shan has nothing to disclose. Conflict of interest: Chun-liang Lei has nothing to disclose. Conflict of interest: Yi-xiang Peng has nothing to disclose. Conflict of interest: Li Wei has nothing to disclose. Conflict of interest: Yong Liu has nothing to disclose. Conflict of interest: Ya-hua Hu has nothing to disclose. Conflict of interest: Peng has nothing to disclose. Conflict of interest: Jian-ming Wang has nothing to disclose. Conflict of interest: Ji-yang Liu has nothing to disclose. Conflict of interest: Zhong Chen has nothing to disclose. Conflict of interest: Gang Li has nothing to disclose. Conflict of interest: Zhi-jian Zheng has nothing to disclose. Conflict of interest: Shao-qin Qiu has nothing to disclose. Conflict of interest: Jie Luo has nothing to disclose. Conflict of interest: Chang-jiang Ye has nothing to disclose. Conflict of interest: Shao-yong Zhu has nothing to disclose. Conflict of interest: Lin-ling Cheng has nothing to disclose. Conflict of interest: Feng Ye has nothing to disclose. Conflict of interest: Shi-yue Li has nothing to disclose. Conflict of interest: Jin-ping Zheng has nothing to disclose. Conflict of interest: Nuo-fu Zhang has nothing to disclose. Conflict of interest: Nan-shan Zhong reports grants from the National Health Commission and Dept of Science and Technology of Guangdong Province, during the conduct of the study. Conflict of interest: Jian-xing He has nothing to disclose., (Copyright ©ERS 2020.)

Objective: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD., Methods: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pS 21 GSK3α, and the number of hippocampal senile plaques (SP) was observed., Results: The proteins of P85α, P110α, GSK3α and pS 21 GSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group ( P <0.001), and the distribution level of pS 21 GSK3α, P85α and P110α was significantly decreased ( P <0.01, P <0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased ( P <0.001), and the distribution level of pS 21 GSK3α, P85α and P110α in hippocampus was significantly increased ( P <0.05, P <0.001). The Western blot results showed compared with the control group, the expression of pS 21 GSK3α, P85α and P110α as well as the ratio of pS 21 GSK3α/GSK3α in the hippocampus in the model group were significantly decreased ( P <0.001), and the expression of GSK3α was increased ( P <0.05); compared with the model group, the expression of pS 21 GSK3α, P85α, P110α and the ratio of pS 21 GSK3α/GSK3α in the hippocampus in the treatment group were significantly increased ( P <0.01, P <0.001), and the expression of GSK3α was decreased ( P <0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased ( P <0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased ( P <0.01)., Conclusion: EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.

The water of the Longzici Spring catchment is the source of industrial, agricultural, and urban domestic water in Linfen City, Shanxi Province. It is of great significance to identify the sources and influencing factors of karst water resources for their development and utilization, and the protection of the ecological environment. Taking the karst groundwater in the Longzici Spring Area as the research object, systematic sample collection and isotope analysis were carried out. Hydrochemistry methods (Durov diagram, ion ratio system, Gibbs diagram, hydrogen and oxygen isotopes, and sulfur isotopes) were used to analyze the hydrochemical characteristics of groundwater. The hydrogeochemical and environmental isotopic characteristics of Longzici Spring water are revealed. The hydrochemical field of karst groundwater in the Longzici Spring domain has obvious zonation, from the deep buried detention area to the supply area to the runoff and discharge area. The hydrochemical types of karst groundwater detention area are SO 4 -Ca and SO 4 -Ca·Mg, with total dissolved solids (TDS) of 960.5-2340 mg·L -1 ; the supply area is HCO 3 -Ca·Mg and HCO 3 ·SO 4 -Ca·Mg, with TDS of 340.5-562 mg·L -1 ; and the runoff and discharge areas are SO 4 ·HCO 3 -Ca·Mg·Na, SO 4 ·HCO 3 -Ca, and SO 4 ·HCO 3 -Ca·Mg, with TDS of 494.0-1168.5 mg·L -1 . The karst groundwater is mainly SO 4 ·HCO 3 -Ca and SO 4 ·HCO 3 -Ca·Mg type water. The content range of sulfate ions is 61.6-1503 mg·L -1 , with an average of 481.4 mg·L -1 . A total of 70.3% of the karst groundwater SO 4 2- samples exceed the standard. The sulfate ions in karst groundwater mainly come from the dissolution of gypsum in the Ordovician aquifer and the oxidation of pyrite in a coal aquifer. The ratio of sulfate ions in the Longzici Spring catchment that come from pyrite oxidation in water is 20.2%. According to the analysis of hydrogen, oxygen and sulfur isotopes, 70% of karst groundwater is polluted by the acid water of coal mines to different degrees. Using the software PHREEQC, it is concluded that the hydrochemical characteristics of the study area are mainly affected by dissolution and dedolomitization, rock salt, and gypsum.

Background: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients., Methods: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death., Results: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission., Conclusions: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)., (Copyright © 2020 Massachusetts Medical Society.)

Objective: To investigate the effect of electroacupuncture (EA) combined with Donepezil on learning-memory ability and gene expression of β-amyloid (Aβ) clearance-related factors in the hippocampus in senescence-accelerated mouse prone 8 (SAMP8) mice, so as to explore their synthetic effect in improving dementia of Alzheimer's disease (AD)．., Methods: Male SAMP8 mice (30-week-old) were randomly divided into model, medication and EA＋medication groups ( n ＝6 mice in each group), and other 6 senescence-resistant 1 (SAMR1) mice were used as the control group. Mice of the medication and EA＋medication group received gavage of Donepezil (1.3 mg•kg －1 •d －1 ) once daily for 4 weeks. EA (2 Hz, 1 mA) was applied to "Baihui"(GV20) and "Yintang" (EX-HN3) for 15 min, once daily, 6 days a week for 4 weeks for rats in the EA＋medication group. The Morris water maze (MWM) task (including place navigation tests and space exploration trials) was used to assess the mouse's learning-memory ability. Histopathological changes of hippocampus tissue were observed by H．E. staining. The expression levels of matrix metalloprotein 9 (MMP-9), low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (Pgp, an important drug transporter responsible for multidrug resistance), Claudin-5 (a component of tight junction strands that serves as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets of blood-brain barrier, BBB) and Aβ mRNAs of the hippocampus tissue were detected by quantitative real-time PCR., Results: Compared with the control group, the average escape latency of place navigation tests, and the expression levels of MMP-9 and Aβ mRNAs were significantly increased ( P <0.01), and the number of platform quadrant-crossing times of space exploration trials, and the expression levels of LRP-1, Pgp and Claudin-5 mRNAs considerably decreased in the model group ( P <0.01). After the intervention, the learning-memory ability was significantly improved in the medication and EA＋medication groups ( P <0.01， P <0.05), the expression levels of Aβ mRNAs in the medication and EA＋medication groups and MMP-9 mRNA in the EA＋medication group were obviously down-regulated ( P <0.01), and those of LRP-1 and Pgp mRNAs in the medication and EA＋medication groups and Claudin-5 mRNA in the EA＋medication group were remarkably up-regulated ( P <0.05, P <0.01). The therapeutic effect of EA＋medication was apparently superior to that of simple medication in shortening the escape latency ( P <0.05， P <0.01) and in down-regulating the expression of MMP-9 and Aβ mRNAs( P <0.01), and in increasing the number of platform quadrant-crossing times( P <0.01), and expression levels of LRP-1, Pgp and Claudin-5 mRNAs ( P <0.01). H．E. staining showed scatted and loose arrangement of neurons in the hippocampus, with reduction of number of cell layers and unclear nucleoli, which was relatively milder in the medication and EA＋medication groups., Conclusion: EA can enhance the effect of Donepezil in improving learning-memory ability in AD mice possibly by regulating expression of MMP-9, LRP-1, Pgp and Claudin-5 mRNAs and strengthening the effect of Donepezil in transporting Aβ via BBB.

Background: Resilience is a psychological construct referring to one's positive adaptation in response to adversity. Evidence suggests that resilience may contribute to various function domains in adults with chronic physical disabilities., Purpose: To test hypothesized temporal associations between resilience and four function domains (anxiety, depression, social role satisfaction, and physical function) in individuals with chronic physical disabilities., Methods: Participants were 1,574 adults with one of four chronic physical disabilities (spinal cord injury, muscular dystrophy, multiple sclerosis, or postpolio myelitis syndrome) who were participating in a large, ongoing USA-based longitudinal survey study. Three surveys were mailed on an approximately yearly basis. Resilience was assessed using the Connor-Davidson Resilience Scale 10-item (CDRSC-10) and each function domain was assessed using the respective Patient Reported Outcome Measurement System (PROMIS) short-form., Results: Cross-lagged path models evidenced statistically significant reciprocal relationships between resilience and each function domain except physical function. The standardized lagged coefficients corresponding to resilience predicting social role satisfaction (T1-T2 = 0.09, T2-T3 = 0.09) had similar effect sizes as those corresponding to social role satisfaction predicting resilience (T1-T2 = 0.11, T2-T3 = 0.04), although resilience was a slightly stronger predictor in the second lag. In models assessing psychological function, resilience was a stronger predictor of later psychological function (resilience-to-anxiety, T1-T2 = -0.15, T2-T3 = -0.11; resilience-to-depression, T1-T2 = -0.21, T2-T3 = -0.13) than the inverse (anxiety-to-resilience, T1-T2 = -0.11, T2-T3 = -0.06; depression-to-resilience, T1-T2 = -0.12, T2-T3 = -0.05)., Conclusions: The study findings suggest that resilience is a significant prospective predictor of psychological and social function over time in individuals with chronic physical disabilities., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Programmed cell death protein 10 (PCDP10) is widely distributed in animal tissues and exerts extensive biological effects. This study aimed to investigate the effect of Schistosoma japonicum PCDP10 (SjPCDP10) on the fecundity of schistosomes. We performed real-time PCR to assess Sjpcdp10 expression levels at different developmental stages of S. japonicum. Immunoprotection against S. japonicum was assessed in vivo in mice, and Sjpcdp10 expression was inhibited via RNA interference (RNAi) to determine its role in fecundity. Real-time PCR analysis revealed that Sjpcdp10 mRNA was expressed during different developmental stages in S. japonicum, reaching maximum and minimum levels in female worms and lung-stage schistosomula, respectively. Recombinant SjPCDP10 had a molecular weight of approximately 28 kDa, displaying good immunogenicity but poor immunoprotection. SjPCDP10 was primarily localized in the egg, eggshell, epiphragm of adult worms, and especially the vitelline glands of female worms. RNAi-mediated knockdown of Sjpcdp10 by greater than 90%, and the protein expression decreased by 73%, reduced the number of eggs per female worm significantly more than RNAi-mediated knockdown of Egfp (negative control) (P < 0.05). The present results indicate that Sjpcdp10 knockdown affects the fecundity of schistosomes and may play a vital role in oogenesis.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a candidate subunit vaccine that induces protective immunity and elicits partial resistance to Schistosoma japonicum upon mouse and livestock vaccination. This study aimed to evaluate the effect of regulatory T cells (Tregs), which were defined as CD4 + CD25 + Foxp3 + cells, on the efficacy of a GAPDH vaccine against S. japonicum. BALB/c female mice were randomly divided into five groups as follows: normal, infected control, anti-CD25 monoclonal antibody (anti-CD25 mAb), GAPDH group, and co-treated with anti-CD25 mAb and GAPDH group. The worm reduction and liver egg reduction rates in the GAPDH group were 32.46% and 35.43%, respectively, which increased to 60.09% and 58.78%, respectively, after anti-CD25 mAb administration. Compared with those in the infected control group, the percentage of Tregs in the spleen decreased significantly when GAPDH and anti-CD25 mAb were used either alone or in combination. Furthermore, secretions associated with the Th1 response increased in splenocytes of the anti-CD25 mAb group, whereas the Th1 and Th2 responses increased in splenocytes of the GAPDH and co-treated groups. Compared to that in the infected control group, granuloma diameter in the GAPDH and co-treated groups increased slightly, but there were no significant differences among the groups. Our results indicate that the protective effect of the GAPDH vaccines can be improved by decreasing Tregs and enhancing the Th1- and Th2-type immune responses. Therefore, anti-CD25 mAb and GAPDH might exert synergistic effects to clear parasites by decreasing the frequency of Tregs and increasing the Th1- and Th2-type immune responses., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Insulin resistance (IR) is the impaired insulin response that causes decreased glucose tolerance. Electrical stimulation (ES) can improve insulin sensitivity in the skeletal muscle. However, the underlying molecular mechanisms remain to be elucidated. In the present study, the effect of ES and diet therapy on IR and the role of the mammalian target of rapamycin (mTOR) pathway in the improvement of IR by ES were investigated. A total of 70 Sprague‑Dawley male rats were divided into five groups: Normal (n=10), IR control (n=15), diet (n=15), ES (n=15) and ES + diet (n=15) groups. An IR rat model was established by high‑fat and high‑carbohydrate diet for 5 weeks and confirmed by measurement of fasting plasma glucose (FPG), insulin, insulin sensitivity index (ISI) and IR index. ES on the Zusanli (ST36), Sanyinjiao (SP 6) and Weiwanxiashu (EX‑B3) acupoints and the low‑fat and low‑carbohydrate diet demonstrated protective effects. The body weight, concentrations of FPG, insulin, triglycerides (TG), free fatty acids (FFA) and total cholesterol (TC) of the rats were detected. Pathologic changes in the liver and pancreatic tissues were assessed. Western blotting and immunohistochemistry were performed to determine the role of PI3K/Akt/mTOR signaling. Results demonstrated that ES and diet therapy significantly increased ISI and reduced FPG, IR index, FFA, TG, TC and weight. Inflammatory cell infiltration in the liver and pancreatic tissues was ameliorated and lipid droplets and cavitation in hepatocyte were decreased after ES and diet therapy. The administration of ES and diet therapy also enhanced glucose transport by the upregulation of glucose transporter 4 and accelerated glycogen synthesis through the suppression of glycogen synthase kinase 3α/β via PI3K/Akt/mTOR signaling. Hence, the present results demonstrated that ES combined with diet therapy improved IR through PI3K/Akt/mTOR signaling. The proposed therapy was superior to the method of diet alone.

Objective: To observe the effect of electroacupuncture (EA) on the expression of apolipoprotein E (ApoE) and related proteins of inflammation and anti-oxidative stress in spinal cord in mice with spinal cord injury (SCI), so as to explore its mechanisms underlying function repair., Methods: Thirty-six female C57BL/6 mice were equally randomized into 3 groups: sham operation, model and EA. The SCI model was established by clamping the spinal cord for 25 s with a serrefine after laminectomy of the 1 st lumbar vertebra (L1). EA (1.5 Hz/7.5 Hz, 1.0 mA) was applied to bila-teral "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 10 min, once a day for 7 days. The hindlimb locomotor function was assessed according to the state of the range of motion, coordination, claw gesture of the hind leg ankle-joint, trunk stabi-lity and the tail posture by using Basso Mouse Scale(BMS). The histopathological changes of the injured area of the spinal cord were determined by H.E. staining. The expression levels of ApoE, phosphorylated nuclear transcription factor-κB(p-NF-κB), interleukin 1 beta(IL-1β), phosphorylated extracellular regulatory protein kinase(p-ERK1/2), extracellular regulatory protein kinase(ERK1/2), nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxidase-1(HO-1) in the spinal cord were detected by Western blot, and the glial fibrillary acidic protein (GFAP)-positive astrocytes were displayed by immunofluorescence staining., Results: After modeling, the BMS scores were significantly decreased in the model group compared with the sham operation group ( P <0.05). Following EA, the BMS scores were markedly increased in the EA group relevant to the model group ( P <0.05), suggesting an improvement of the hindlimb locomotor function. H.E. stain showed structural disorder with lots of cavities, severe inflammatory infiltration with large quantity of inflammatory cells, and apparent reduction of normal neurons in the injured spinal cord tissue of model group, which was milder in the EA group. The expression levels of ApoE, p-NF-κB, IL-1β, p-ERK1/2 (not ERK1/2), Nrf2 and HO-1 were significantly increased in the model group than those in the sham operation group ( P <0.05). Compared with the model group, the expression levels of ApoE, p-ERK1/2, Nrf2 and HO-1 were further notably up-regulated ( P <0.05), and those of p-NF-κB and IL-1β proteins obviously down-regulated in the EA group ( P <0.05). Immunoflorescence staining showed that the number of GFAP-positive cells was apparently increased in the model group compared with the sham operation group and observably decreased in the EA group relevant to the model group ( P <0.05)., Conclusion: EA can significantly improve locomotor function in SCI mice, which is associated with its effects in reducing inflammation, oxi-dative stress reactions and reactive astrocyte proliferation via up-regulating expression of ApoE, p-ERK1/2, and Nrf2/HO-1 (antioxidant pathway) and inhibiting IL-1β and NF-κB expression.

Objective: To investigate the effect of electroacupuncture (EA) on muscular atrophy and expression of microRNAs (Mir-1, Mir-133a, Mir-133b) and some proliferation-related factors of muscle satellite cells as histone deacetylase4 (HDAC4) and the paired box transcription factor Pax7 (Pax7) in skeletal muscle atrophy rats., Methods: Twenty-four male SD rats were randomly and equally divided into sham operation, model and EA groups. The skeletal muscle atrophy model was established by transection of the right sciatic nerve. EA (2 Hz, 1 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, seven times a week for 2 weeks. The wet weight of bilateral gastrocnemius muscles was measured to calculate the ratio of weight between the affected gastrocnemius muscle and healthy gastrocnemius muscle. The cross-sectional area (CSA) of the gastrocnemius muscle on the affected side was measured after H.E. staining. The expression levels of Mir-1, Mir-133a, Mir-133b, HDAC4 mRNA and Pax7 mRNA in the gastrocnemius muscle tissue were detected using quantitative real time-PCR., Results: Compared with the sham operation group, the ratio of wet weight and CSA of the gastrocnemius muscle, and the expression levels of Mir-1 and Mir-133a were significantly decreased in the model group ( P <0.01, P <0.05), while the expression levels of HDAC4 mRNA and Mir-133b significantly up-regulated in the model group ( P <0.05). Following EA intervention, the decreased levels of the ratio of wet weight and CSA of the gastrocnemius muscle were significantly suppressed ( P <0.01), suggesting an inhibition of the skeletal muscle atrophy, and the expression levels of Pax7 and HDAC4 mRNAs were notably up-regulated ( P <0.05), and those of Mir-1, Mir-133a and Mir-133b were significantly or further significantly down-regulated relevant to the model group ( P <0.05)., Conclusion: EA intervention can delay muscular atrophy in rats with denervated gastrocnemius muscle, which may be related with its function in up-regulating the expression of Pax7 and HDAC4 mRNAs and down-regulating the expression of Mir-1, Mir-133a and Mir-133b.

Objective: To observe the effect of electroacupuncture (EA) on anti-oxidant function of Leydig cells in aged rats with low testosterone, so as to reveal its underlying mechanism of anti-aging of male reproduction., Methods: Eighteen 20 months old SD rats were divided into aged control, medication and EA groups( n =6 in each group), and other 6 young male SD rats (2 months of age) were used as the youth control group. The rats of the youth and the aged control groups received subcutaneous injection of 0.9% normal saline (7 mg·kg -1 ·3 d -1 ) for 8 weeks, and those of the medication group received abdominal subcutaneous injection of Testosterone Propionate (7 mg·kg -1 ·3 d -1 ) for 8 weeks. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral "Shenshu" (BL23) and "Guanyuan" (CV4) for 15 min, once daily for 8 weeks except the weekends. The levels of serum total testosterone (TT) and free testosterone (FT) were determined by enzyme linked immune sorbent assay (ELISA), the immunoactivity of phosphorylated extracellular signal-regulated protein kinase (p-ERK) was detected by immunohistochemistry, and the expression levels of ERK, p-ERK, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in the testis tissues were determined by Western blot., Results: Before and after the treatment, the levels of serum TT and FT in the aged control group were significantly lower than those of the youth control group ( P <0.01). After the treatment, the serum TT and FT contents in the EA and medication groups were obviously higher than those in the aged control group ( P <0.01). Compared with the youth control group, the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins were significantly down-regulated in the aged control group ( P <0.01), while in comparison with the aged control group, the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins were significantly up-regulated in the medication and EA groups ( P <0.01). The therapeutic effect of EA was notably superior to that of medication in up-regulating the immunoactivity of p-ERK, and the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins ( P <0.01). No significant differences were found between the EA and medication groups in the increased levels of serum TT and FT after the intervention ( P >0.05)., Conclusion: EA intervention may increase testosterone level of the aged rats, which may be related to its effects in triggering ERK /Nrf2 /HO-1 signaling (anti-oxidative stress signal pathway) in the testis.

Aims: The aim of this study was to evaluate the effect of anti-CTLA-4 monoclonal antibody (mAb) on 26-kDa glutathione-S-transferase (GST) vaccine-induced immunity against Schistosoma japonicum infection., Methods and Results: Mice immunized with GST before infection with S japonicum cercariae were injected with anti-CTLA-4 mAb. Worm reduction rate of GST was increased from 25.41% in mice with GST immunization to 52.48% in mice with GST plus anti-CTLA-4 mAb. The percentages of regulatory T cells (Tregs) were significantly higher following administration of both GST and anti-CTLA-4 mAb, or anti-CTLA-4 mAb alone. Elevated levels of IFN-γ, IL-2, IL-4 and IL-5 were observed., Conclusion: These results demonstrated that CTLA-4 may inhibit the protective effect of GST vaccine, and anti-CTLA-4 mAb may be used as an adjuvant to enhance the immune protection conferred by the GST vaccine by enhancing Th1- and Th2-type immune response., (© 2019 John Wiley & Sons Ltd.)

Schistosomiasis is a devastating disease caused by Schistosoma infection. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has emerged as a candidate vaccine component against Schistosoma japonicum, but only confers partial protection. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates T cell activation and shows negative effects on vaccine-induced immune protection; however, its potential influence on the protective effects of a GAPDH vaccine against S. japonicum and the underlying mechanism remain unclear. In this study, we established a mouse model of S. japonicum infection, and the mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), GAPDH, and GAPDH combined with anti-CTLA-4 mAb groups to compare the protective effects against infection and the consequent tissue damage. The worm reduction rate in the GAPDH-treated infected mice was 26.58%, which increased to 54.61% when combined with anti-CTLA-4 mAb. The frequency of regulatory T cells (Tregs) was significantly higher in the anti-CTLA-4 mAb group and was lower in the GAPDH group. However, both anti-CTLA-4 mAb and GAPDH elevated the levels of the cytokines IFN-γ, IL-2, IL-4, and IL-5 in the spleens of infected mice, and their combination further enhanced cytokine production. The diameter of egg granuloma in the anti-CTLA-4 mAb group and combined treatment group increased significantly compared to that of the other groups. These results suggest that anti-CTLA-4 mAb can be used as an adjuvant to enhance the immune protection of the GAPDH vaccine via inducing the Th1 immune response, although this comes at the cost of enhanced body injury.

The prevalence of T1D in developed societies is partly based on the hygiene hypothesis, that is, the loss of exposure to infectious agents accompanies the loss of immune stimuli shaping the immune system during development. Indeed, the components of parasites, such as Schistosoma, have been reported to ameliorate or prevent the development of T1D, which might be associated with immune cell activity especially that of regulatory T cells (Tregs). Schistosoma infection can lead to the expansion of Treg. Herein, we provide a comprehensive overview of the involvement of Tregs in the response against Schistosoma infection and the mechanism of Schistosoma-associated host protection against T1D., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The unique thermogenic capacity of brown adipocyte makes it an attractive target for antiobesity treatments. Several epigenetic regulators can control brown adipocyte development. In this study, we show that SIRT5, a member of the sirtuins, is required for brown adipocyte differentiation and essential for brown adipogenic gene activation in vitro. Furthermore, we find out that knockdown of SIRT5 reduces intracellular α-ketoglutarate concentration, which leads to elevated H3K9me2 and H3K9me3 levels at promoter regions of Pparγ and Prdm16 loci. Finally, we discover that SIRT5 knockout mice on the Sv129 background exhibit less browning capacity in subcutaneous white adipose tissue compared with controls and show apparent cold intolerance, suggesting that SIRT5 can modulate the browning process in vivo. Thus, our study uncovers a new biological function of SIRT5 in brown adipocyte differentiation and a mechanism by which SIRT5 regulates brown adipogenic gene activation at least partly through an indirect effect on histone modifications. Our study extends the linkage between epigenetics and cell differentiation., (© 2019 by the American Diabetes Association.)

Type 2 diabetes is a metabolic disorder characterized by persistently elevated glucose levels. There is no effective treatment strategy for this condition, and it poses a massive economic burden globally. Schistosoma soluble egg antigen (SEA)-induced immunomodulatory mechanisms have been reported in the treatment of autoimmune disease. This study aimed to determine the ability of Schistosoma japonicum SEA to protect against type 2 diabetes in Lep r db / db mice and understand the associated mechanisms. The mice were divided into four groups: C57BL/6 (the normal group), SEA (C57BL/6 mice treated with SEA), Lep r db / db , and SEA and Lep r db / db co-treatment groups. The mice in the SEA and co-treatment groups were injected with 50 μg of SEA (twice a week for 6 weeks), and the same volume of PBS was used as control. Blood glucose, insulin, and HOMA-IR levels were measured in all mice, which were sacrificed 6 weeks after the last SEA administration. Flow cytometry was used to detect the percentages of regulatory T cells in splenocytes. ELISA was used to detect the levels of IFN-γ, IL-2, IL-4, and IL-5 in cell culture supernatants. Compared with the mice in the Lep r db / db group, the mice in the SEA + Lep r db / db group exhibited significantly reduced insulin resistance, as evidenced by the enhancement of wound healing. The frequency of spleen regulatory T cells increased significantly after SEA administration; meanwhile, the secretion of IL-4 and IL-5 in spleen cells was elevated. These results indicate that SEA can reduce insulin resistance and provide new targets for the treatment of type 2 diabetes. The potential mechanisms might be associated with increases in regulatory T cells and Th2 cytokines in Lep r db / db mice, which warrants further investigation.

Objective: To observe the effect of electroacupuncture (EA) combined with transplantation of Schwann cells (SCs) on limb locomotor, myelin sheath repair and expression of CD4 and CD8 in compressed spinal cord injury (CSCI) rats, so as to explore its mechanisms underlying improvement of CSCI., Methods: A total of 45 female SD rats were randomly divided into normal control, model, EA, Schwann cell (SC) transplantation, and EA＋SC transplantation groups ( n ＝9 rats in each group). The CSCI model was established by laminectomy at T12-L2 and clip compression. Rats of the SC transplantation group accepted injection of the cultured SC suspension (2×10 6 /6 µL) into the central, upper and lower sites of the injured spinal cord (5 mm in depth) 7-8 days after CSCI modeling. EA (2 Hz) was applied to bilateral "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 10 min, once daily and 6 days a week for 3 weeks. The Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) was used to evaluate the function state of CSCI. Morphological changes of the regional injured tissue were observed under light microscope after H．E. staining. The myelin sheath repair state and survival of SCs were detected by Luxol fast blue (LFB) staining and immunofluorescence histochemistry, and the expression of CD4, CD8 and P0 of the injured spinal cord was detected by Western blot., Results: Compared with the normal control group, the BBB scores at the time-points of 0 d, and 1, 2, and 3 weeks were significantly decreased in the model group ( P <0.001), and those of the EA＋SC transplantation group at the 2 nd and 3 rd week were significantly higher than those of the model group ( P <0.05). No significant changes of BBB scores were found after EA and SC transplantation relevant to the model group ( P >0.05). LFB staining showed a disordered arrangement of the nerve fibers in the white matter, myelinociasis and obvious decrease of the medullated fibers in the model group, and these situations were relatively milder in both EA and SC transplantation groups and obviously milder in the EA＋SC transplantation group. H．E. staining displayed that the structure of the injured region of the spinal cord was incomplete, accompanied with a large number of defect cavities and neuronal karyopyknosis in the model group, while the structure was relatively clear, with an increase of the normal neurons and fewer neuronal karyopyknosis in the EA＋SC transplantation group. Compared with the normal control group, MBP in the model group was significantly decreased ( P <0.001)，and P0 was significantly increased ( P <0.001). Compared with the model group, the expressions of MBP and P0 were significantly increased in the EA, SC transplantation, and EA＋SC transplantation groups ( P <0.01, P <0.001), and was significantly higher in the EA＋SC transplantation group than in both EA and SC transplantation groups ( P <0.001). The average immunofluorescence intensity of Hoechst33342-labeled SCs was significantly higher in the EA＋SC transplantation group than in the SC transplantation group ( P <0.05). After CSCI, the expression levels of spinal CD4, CD8 and P0 proteins had no significant changes in comparison with the normal control group ( P >0.05), while after the intervention and in comparison with the model group, the expression levels of P0 protein were significantly increased in the EA, SC transplantation and EA＋SC transplantation groups ( P <0.05), and was significantly higher in the EA＋SC transplantation group than in both EA and SC transplantation groups ( P <0.05). The expression levels of CD4 and CD8 proteins were significantly lower in the EA＋SC transplantation group than in the SC transplantation group ( P <0.05)．., Conclusion: EA＋SCs transplantation can improve the locomotor function in CSCI rats, which may be related to its effects in increasing the survival of transplanted SCs to promote the remyelination and in reducing the immune rejecting reaction.

Objective: To investigate the therapeutic effects of massage on denervated skeletal muscle atrophy in rats and its mechanism., Methods: Forty-eight male SD rats were randomly divided into model group (n=24) and massage group (n=24). Gastrocnemius muscle atrophy model was established by transecting the right tibial nerve of rat. On the second day after operation, the gastrocnemius muscle of the rats in the massage group was given manual intervention and the model group was not intervened. Six rats were sacrificed at the four time points of 0 d, 7 d, 14 d and 21 d. The gastrocnemius of the rats were obtained and measured the wet mass ratio after weighing. Cross-sectional area and diameter of the muscle fiber were measured after HE staining. The relative expressions of miR-23a, Akt, MuRF1 and MAFbx mRNA were tested with qPCR., Results: Compared with 0 d, the wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle showed a progressive decline in the model group and massage group. The wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle in the massage group were higher than those in the model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expressions of MuRF1, MAFbx and Akt mRNA were increased first and then were decreased in the model group and massage group. The expression of MuRF1 mRNA in massage group was lower than that in model group on 7 d and 21 d (P＜0.05, P＜0.01). The expression of MAFbx mRNA in massage group was lower than that in model group on 7 d, 14 d and 21 d (P＜0.01, P＜0.05, P＜0.01). The expression of Akt mRNA in massage group was higher than that in model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expression of miR-23a mRNA was increased in the model group and massage group on 21 d, and the expression of miR-23a mRNA in massage group was higher than that in model group (P＜ 0.05)., Conclusion: Massage can delay the atrophy of denervated skeletal muscle. The mechanism may be related to up-regulation of the expression of miR-23a and Akt mRNA, down-regulation of the expressions of MuRF1 and MAFbx mRNA, inhibition of protein degradation rate, and reduction of skeletal muscle protein degradation.

Background: With advanced age and chronic illness, the life expectancy of a patient with colorectal cancer (CRC) becomes less dependent on the malignant disease and more on their pre-morbid condition. Justifying major surgery for these elderly patients can be challenging. An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients., Aim: To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system., Methods: In this retrospective cohort study, patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database. Patients with evidence of metastatic disease, and those who underwent emergency surgery or had surgery for benign colorectal conditions were excluded from the analysis. The primary outcome was overall 3-year overall survival (OS) following surgery. A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital, South Korea. Statistical analyses were performed using Stata/MP Version 15.1., Results: A total of 1267 patients were identified for analysis. The median post-operative length of stay was 8 [interquartile range (IQR) 6-12] d and median follow-up duration was 47 (IQR 19-75) mo. Median OS was 78 (IQR 65-85) mo. Following multivariate analysis, the factors significant for predicting overall mortality were serum albumin < 35 g/dL, serum carcinoembryonic antigen ≥ 20 µg/L, T stage 3 or 4, moderate tumor cell differentiation or worse, mucinous histology, rectal tumors, and pre-existing chronic obstructive lung disease. Advanced age alone was not found to be significant. The Korean cohort consisted of 910 patients. The Singapore cohort exhibited a poorer OS, likely due to a higher proportion of advanced cancers. Despite the clinicopathologic differences, there was successful validation of the model following recalibration. An interactive online calculator was designed to facilitate post-operative survival prediction, available at http://bit.ly/sgh&#95;crc. The main limitation of the study was selection bias, as patients who had undergone surgery would have tended to be physiologically fitter., Conclusion: This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process. Validation with an external population strengthens the generalizability of this model., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Objective: To observe the therapeutic effect of electroacupuncture (EA) of "Zusanli" (ST36) and " Ashi "-point on the healthy side (opposing needling) on muscular injury and expression of myogenin (myoG) and fast myosin skeletal heavy chain (Fast MyHC) proteins in the gastrocnemius muscle (GM) tissues in skeletal muscle contusion rats，so as to explore its mechanism underlying improvement of skeletal muscle injury., Methods: A total of 54 male SD rats were divided into normal control (n ＝ 6)，model ( n ＝24) and opposing needling (EA, n ＝24) groups. The latter two groups were further randomized into 3, 5, 7 and 14 d subgroups ( n ＝6 per subgroup). The skeletal muscle contusion model of the hind-limb was established by using a self-made striking device. EA (1 Hz/3 Hz，1－2 mA) was applied to ST36 and " Ashi "-point on the uninjured side of the hind-limb for 15 min every time, once a day for 3, 5, 7 and 14 days, respectively. The injured GM was harvested on the 3 rd, 5 th, 7 th and 14 th day after muscular contusion. The morphological changes of the injured GM and the mean cross-sectional areas (CSAs) of the neonatal muscle cells were observed by microscope after H．E. staining. The immunoactivity of desmin protein (myogenic marker protein of myoblast cell) of GM was detected by immunofluorescence stain on the 7 th day after injury, and the expression levels of myoG (on the 3 rd and 5 th day after injury) and fast MyHC protein of GM tissues (on the 7 th and 14 th day after injury) were detected by Western blot., Results: H．E. staining of GS tissue showed fewer neuronal myocytes with disordered arrangement at different sizes, and appearance of some collagenous fibers among the mesenchyme on day 7 and 14 after muscular contusion, which was relatively milder in the EA group. In the EA group, the CSA values of the neonatal muscle cells were significantly larger than those in the model group on the day 7 th ( P <0.05), 14 th ( P <0.001) after injury. On day 7 after muscular contusion, the desmin was found to express on the cellular membrane of GM in the normal control group, while in the model group, the desmin expressed mainly in the cellular plasma in the model group, and on the cellular membrane of neonatal myocytes in the EA group, respectively. The desmin positive myocytes showed disordered arrangement and different sizes after muscular contusion, whereas the situations of the EA group were close to those of the normal control group. Desmin expression was up-regulated in the EA group compared with the model group which was not significant difference ( P >0.05). On the 3 rd and 5 th day after muscular contusion, the expression level of myoG protein was significantly up-regulated in the model group compared with the normal control group ( P <0.001), and significantly up-regulated in the EA group than that in the model group ( P <0.001). On the 7 th and14 th day after contusion, the expression level of fast MyHC protein was significantly down-regulated in the model group relevant to the normal control group ( P <0.001), and markedly up-regulated in the EA group relevant to the model group ( P <0.01)．., Conclusion: EA of ST36 and " Ashi "-point on the contralateral limb can up-regulate the expression of myoG and fast MyHC proteins of GM in acute skeletal muscle contusion rats, which may contribute to its effect in promoting the repair of skeletal muscle injury.

The present study evaluated the impact of blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4) activity on the protective effect elicited by the fatty acid binding protein (FABP) vaccine against Schistosoma japonicum infection. Mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), FABP, and combination (anti-CTLA-4 mAb and FABP) groups. An assessment of the S. japonicum worm and egg burden in the infected mice revealed that the worm reduction-rate induced by FABP administration was increased from 26.58 to 54.61% by co-administration of the monoclonal anti-CTLA antibody (anti-CTLA-4 mAb). Furthermore, the regulatory T cell (Treg) percentage was significantly increased in mice after administration of the anti-CTLA-4 mAb, but not the FABP vaccine, and elevated levels of the cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-5 were observed in infected mice that were administered the anti-CTLA-4 mAb. Notably, the diameter of egg granulomas in the anti-CTLA-4 mAb and combination groups was significantly increased compared to that observed in the infected control group. Together, these results suggest that co-administering the FABP vaccine and anti-CTLA-4 treatment may have synergistically increased the immunoprotective effect of the FABP vaccine by promoting T-helper 1-type immune responses, while incurring increased tissue damage.

Objective: To observe the effect of electroacupuncture (EA) on morphological changes of denervated gastrocnemius(GS) and the expression of fork-head protein(FOXO3A), muscle atrophy F-box(MAFbx)and myogenic differentiation antigen (Myod1) in sciatic nerve injury rats, so as to reveal its mechanism underlying improvement of myoatrophy., Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups ( n ＝6 per group). The model of gastrocnemius atrophy was established by crushing the right sciatic nerve. Then, EA (2 Hz) was applied to the right "Zusanli" (ST36) and "Huantiao" (GB30) for 10 min, once a day for 14 successive days. The wet weight of the GS on both sides was weighted to calculate the wet weight ratio (the injured side /the healthy side), and the cross-sectional area (CSA) and diameter of GS fibers were measured after H．E. staining. The expressions of FOXO3A, MAFbx and Myod1 protein and mRNA in the GS tissue were tested using Western blot and fluorescence quantitative PCR, separately., Results: Following modeling, the GS wet weight ratio, CSA and fiber diameter were smaller in the model group than those in the sham group ( P <0.01), and were significantly higher in the EA group than in the model group ( P <0.01). H．E. staining showed that the GS fibers became smaller and the myocyte got round in the model group, while the GS fibers were bigger and the myocyte was relatively regular in morphology in the EA group. After modeling, the expression levels of FOXO3A, MAFbx and Myod1 mRNA and protein were evidently higher in the model group ( P <0.01); Moreover, after EA treatment, modeling-induced increasing of expression levels of FOXO3A and MAFbx mRNA and protein were revised ( P <0.01), while the increased expression level of Myod1 was further up-regulated relavant to that in the model group ( P <0.01)．., Conclusion: EA of ST36 and GB30 can suppress the up-regulated expression of FOXO3A and MAFbx mRNA and protein and further promote the expression of Myod1 mRNA and protein in the GS tissue in rats with denervated GS atrophy, which may contribute to its function in relieving the myoatrophy, promoting the skeletal muscle protein hydrolysis and differentiation of satellite cells.

Type 1 diabetes (T1D) is an autoimmune disease in which cells of the immune system destroy pancreatic β cells, which secrete insulin. The high prevalence of T1D in developed societies may be explained by environmental changes, including lower exposure to helminths. Indeed, infection by helminths such as Schistosoma, Filaria, and Heligmosomoides polygyrus and their by-products has been reported to ameliorate or prevent the development of T1D in human and animal models. Helminths can trigger distinct immune regulatory pathways, often involving adaptive immune cells that include T helper 2 (Th2) cells and regulatory T cells (Tregs) and innate immune cells that include dendritic cells, macrophages, and invariant natural killer T cells, which may act synergistically to induce Tregs in a Toll-like receptor-dependent manner. Cytokines such as interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-β also play an important role in protection from T1D. Herein, we provide a comprehensive review of the effects and mechanisms underlying protection against T1D by helminths.

The aim of this study was to investigate the effect of Schistosoma japonicum glutathione S-transferase (SjGST) on the developmental stages of the parasite. We found that the mRNA levels of GST were higher in schistosomula obtained from the host and the eggs than that in other developmental stages. SjGST was mainly distributed in the egg shells, teguments of the worms, and part of the parenchyma of the worms. GST knockdown with RNA interference in S. japonicum worms resulted in a silencing rate higher than 80%. The egg reduction rate (18%) and abnormal egg ratio (28%) were significantly higher (P < 0.05) in the GST-silenced group than in the negative control group. These results indicate that SjGST plays an important role in the fecundity of S. japonicum, specifically in egg formation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: There is a dearth of studies on long term hearing status and behavioural patterns among cleft lip and/or palate children after their primary lip and palate closure in Malaysia. This study describes the audiology status and behavioural patterns in a group of school aged children with cleft lip and/or palate., Method: A cross sectional study was carried out where caretakers of cleft lip and/or palate were asked to complete the translated Malay language version of Strength Difficulties Questionnaire. The hearing status of the children was analyzed based on recent pure tone audiometric and tympanogram results. The patients' age, gender, type of cleft pathology, age of palatal surgery and behavioural patterns were examined for their potential relationship with hearing status., Results: A total of 74 children (148 ears) aged between 7 and 17 years with cleft lip and/or palate were recruited. The result showed 37 ears (25.0%) had hearing loss with majority suffered from mild conductive hearing loss. There were 16 ears (10.8%) that had persistent middle ear effusion. Hearing improvement occurred when palatal repair was performed at the age of less than 1 year old. (p = 0.015) There was no significant relationship between patients' gender, age, type of cleft and history of myringotomy with their hearing status. In terms of behavioural patterns, 16.3% were abnormal for total behavioural score, 39.2% for peer problem and 17.6% for conduct problem. For prosocial behaviour, 16.3% were rated low and very low. There was fair correlation between age and hyperactivity problems (r = 0.44). Patients' gender, type of cleft pathology, had been teased apart and hearing status was found not related to behavioural problems., Conclusion: Cleft lip and/or palate patients have a good longterm hearing outcome. Majority had normal hearing and if there is hearing impairment, it is only a mild loss. Early palatal repair surgery before the age of 1 year can significantly reduce the risk of hearing loss. Cleft lip and/or palate patients experienced peer problems. There was no significant correlation between behavioural difficulty and hearing status among school-aged children with cleft lip and palate., (Copyright © 2018. Published by Elsevier B.V.)

Schistosomiasis is one of the most devastating parasitic diseases, making it imperative to develop efficient vaccines to control the causative flatworms called schistosomes. Regulatory T cells (Tregs) and the Th1 immune response have been implicated in the effectiveness of vaccines to control schistosomiasis, but the mechanisms underlying their effects are unclear. In this study, we evaluated the role of Tregs on the efficacy of the 14 kDa FABP (fatty acid-binding protein) vaccine against Schistosoma japonicum. BALB/c female mice were randomly divided into five groups: an uninfected group, infected control group, anti-CD25 monoclonal antibody (anti-CD25 mAb) group, FABP group, and combined anti-CD25 mAb and FABP group. Compared with FABP alone, a combined treatment with FABP and anti-CD25 mAb increased the rate of S. japonicum inhibition in mice from 30.3 to 56.08% and decreased the number of eggs per gram of liver. Compared with that of the infected control group, the percentage of Tregs in the spleen decreased significantly after single or combined treatment with FABP and anti-CD25 mAb, while it increased gradually in the anti-CD25 mAb group. Further, the secretion of Th1 cytokines, IFN-γ, and IL-2 increased in splenocytes in the anti-CD25 mAb group. Our results indicate that anti-CD25 mAb partially blocks Tregs and concomitantly enhances the Th1 type immune response, thereby enhancing the protective effect of the FABP vaccine.

Objective: To explore the effect of electroacupuncture(EA) on amyotrophia and expression of paired box7(Pax7), myogenic differentiation antigen-1 (Myod1), myogenin (Myog), myosin heavy chain- Ⅱa (Myh2), myosin heavy chain-Ⅱx (Myh1) and myosin heavy chain-Ⅰ (Myh7) of denervated gastrocnemius in rats with chronic constriction injury (CCI) of the right sciatic nerve, so as to explore its mechanisms underlying postponing development of amyotrophia., Methods: Sixty-six SD adult male rats were randomly divided into sham operation (sham) group ( n ＝24), model group ( n ＝24) and EA group ( n ＝18). The denervated muscle (gastrocnemius) atrophy model was established by CCI of the right sciatic nerve. EA (2 Hz，1.0 mA) was applied to the right "Zusanli"(ST36) and "Huantiao"(GB30) for 10 min, once a day, six times a week and for 1, 2 and 4 weeks, respectively. After complete dissection of bilateral gastrocnemius muscles, their wet weight levels were measured and the ratio of wet weight (＝that of the operation side/that of the non-operation side) was calculated, and the cross-sectional area (CSA) and diameter of the gastronemius were detected after fixation in 4% paraformaldehyde, sectioning, and H．E. staining. The expression levels of Pax7, Myod1, Myog, Myh2, Myh1 and Myh7 mRNAs in the gastrocnemius tissue after 3 weeks of modeling were detected with quantitative real time-PCR (qPCR)., Results: After 1 week of modeling, the ratios of wet weight of gastrocnemius and the CSA and fiber diameter at the 2 nd , 3 rd and 5 th week were significantly smaller in the model group than in the sham group ( P <0.05). The expression levels of Myod1 and Myog mRNAs were significantly up-regulated ( P <0.01), and those of Myh2, Myh1 and Myh7 considerably down-regulated in the model group compared with the sham group ( P <0.05, P <0.01). No significant changes were found in the expression levels of Pax7 mRNA after modeling and EA intervention ( P >0.05)．Following EA intervention, the CSA and diameterof the gastronemius were obviously increased ( P <0.05), and the expression levels of Myod1, Myog and Myh7 further markedly or remarkably up-regulated in comparison with the model group ( P <0.05, P <0.01). No significant changes were found in the ratio of wet weight of gastrocnemius at the 3 time-points, and the expression levels of Myh2 mRNA and Myh1 mRNA in the EA group relevant to the model group after 3 weeks of modeling ( P >0.05)., Conclusion: EA treatment may delay gastrocnemius atrophy in CCI rats, which is possibly associated with its effects in up-regulating the expression of Myod1, Myog and Myh7 mRNAs to control the differentiation of the satellite cells and the muscle fiber type transformation.

Background: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in patients with acute severe tracheal stenosis, yet data supporting the clinical use of H2-O2 are insufficient., Objectives: To evaluate the efficacy and safety of breathing H2-O2 in acute severe tracheal stenosis., Methods: Thirty-five consecutive patients with severe acute tracheal stenosis were recruited in this prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4 consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1) for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary endpoint was inspiratory effort as assessed by diaphragm electromyography (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in the ambient environment was obtained with 12 monitors. Adverse reactions during the inhalation were recorded., Results: The mean reduction in the EMGdi under H2-O2 was 10.53 ± 6.83%. The EMGdi significantly decreased during 2 H2-O2 inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3) (52.95 ± 15.00 vs. 42.46 ± 13.90 vs. 53.20 ± 14.74 vs. 42.50 ± 14.12% for Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77 ± 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and resistance parameters of IOS but not vital signs. No adverse reactions occurred. H2 was undetectable in the environment throughout the procedure., Conclusions: Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe tracheal stenosis and can be used for this purpose safely., (© 2018 S. Karger AG, Basel.)

Objective: To measure blood and follicular antimüllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technologies (ART) and to examine the direct action of insulin on AMH expression in human granulosa cells., Design: Prospective clinical and experimental study., Setting: University Hospital-based laboratory., Patient(s): Women with (n = 86) and without (n = 172) PCOS in ART., Intervention(s): Blood, follicular fluid, and luteinized granulosa cells were collected from PCOS and non-PCOS women in ART., Main Outcome Measure(s): Hormone levels in blood and fluid, and gene expression in granulosa cells., Result(s): Serum levels of AMH were elevated and inversely correlated with embryo cleavage rate in PCOS women in ART. Significant higher levels of AMH were also found in small and large follicles collected from PCOS women compared with non-PCOS women. Luteinized granulosa cells from PCOS women showed higher expression of AMH and its receptor AMHR2. Direct effect of insulin in increasing the expression of AMH in the isolated luteinized granulosa cells was observed, with the PCOS granulosa cells responding to a high dose of insulin. Cotreatment with AMH attenuated insulin-induced aromatase expression in the luteinized granulosa cells., Conclusion(s): These results suggest that insulin may contribute to AMH elevation in PCOS and that AMH counteracts insulin-promoted aromatase expression in granulosa cells., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the effect of electroacupuncture (EA) on the expression of synovial AMP-activated protein kinase (AMPK) protein α， arginase-1 mRNA, nitric oxide synthase 2 (NOS 2) mRNA, NOD-like receptor protein 3 (NLRP 3) mRNA, and interleukin-1 β (IL-1 β) mRNA in acute gouty arthritis (AGA) rats, so as to explore its mechanisms underlying improvement of AGA via M 1/M 2 macrophage polarization., Methods: Male Wistar rats were randomly divided into normal control, model, medication (colchicine) and EA groups ( n ＝15 rats in each group). The AGA model was established by injection of sodium urate crystal (MSU) suspension (0.2 mL) into the articular cavity of the left knee. The rats of the normal control group received articular injection of normal saline (0.2 mL) of the left knee, and those of the medication group were treated by gavage of the colchicine (0.3 mg•kg －1 •d －1 ) once daily for 7 days. EA (2 Hz/10 Hz, 1.0 mA) was applied to "Zusanli"(ST 36) and "Sanyinjiao" (SP 6) of the left hind limb for 10 min, once daily for 7 days. The inflammatory conditions of the synovial membrane tissue of the left knee joint were observed by H．E. staining. The expression levels of phosphorylated AMPKα (p-AMPKα) protein, and arginase-1 (a maker of M 2 macrophages) mRNA, NOS 2 (a maker of M 1 macrophages) mRNA, NLRP 3 mRNA, and IL-1 β mRNA in the knee joint synovial tissue were detected by Western blot and quantitative real-time PCR, respectively., Results: Compared with the normal group, the inflammatory cell infiltration of the synovial tissue was more severe, the expression of p-AMPKα protein was significantly decreased ( P <0.01), and the expression levels of arginase-1, NOS 2, IL-1 β and NLRP 3 mRNAs were considerably increased in the model group ( P <0.01). The expression levels of p-AMPKα protein and arginase-1 mRNA were significantly up-regulated, and those of NOS 2, IL-1 β and NLRP 3 mRNAs obviously down-regulated in both EA and medication groups relevant to the model group ( P <0.01, P <0.05), suggesting an increase of M 2 macrophage and a decrease of M 1 macrophage activity after EA. No significant differences were found between the EA and medication groups in up-regulating p-AMPKα expression and in down-regulating NOS 2, IL-1 β and NLRP 3 mRNA expression ( P >0.05), except higher up-regulation of arginase-1 mRNA in the medication group ( P <0.05)．., Conclusion: EA intervention can up-regulate the expression of arginase-1 mRNA and p-AMPKα protein, and down-regulate the expression of NOS 2, IL-1 β and NLRP 3 mRNAs in synovial tissues in AGA rats, which may contribute to its anti-inflammatory effect by promoting conversion of macrophages from M 1 pro-inflammatory phenotype to M 2 anti-inflammatory phenotype.

Aim: The intensity and duration of surveillance for rectal cancer after surgical resection remain contentious. We evaluated the pattern of recurrences in a rectal cancer cohort followed up beyond 10 years., Methods: An analysis was performed on a retrospective database of 326 patients with rectal cancer who underwent curative surgical resection from 1999 to 2007. The above study duration was chosen to ensure at least 10 years of follow-up. Data on patient demographics, peri-operative details, and follow-up outcomes were extracted from the database. The pattern of recurrences and investigative modality that detected recurrences was identified. Patients were followed up until either year 2016 or the day of their demise., Results: Two hundred seventeen patients (66.6%) were male and 109 patients (33.3%) female. Median age was 64 years old. Close to a third of the patients received adjuvant therapy (34%). Among the 326 patients studied, 29.8% of (97/326) patients developed recurrence. 7.7% (25/326) had loco-regional recurrence while 22.1% (72/326) had distant metastasis. Median time to recurrence was 16 months (4-83) and 18 months (3-81), respectively. Computed tomography scan was the best modality to detect both loco-regional and distant recurrences (48% in loco-regional and 41.7% in distant metastasis). The most common site of distant metastasis is the lung (34.7%). The salvage rate for loco-regional and distant recurrences was 52 and 12.5%, respectively., Conclusion: The predominant pattern of recurrence in rectal cancer is distant disease. Surveillance regimes may need to be altered to increase early detection of distant metastases.

Background: Laparoscopic low anterior resection for rectal cancer has superior short-term benefits compared to open surgery. When operative conditions do not favour a totally-laparoscopic (TL) approach, a hybrid operation can be performed. In this laparoscopic-assisted (LA) approach, mobilization and vessel ligation are performed laparoscopically, with total mesorectal excision and distal transection performed either partially or totally in an extra-corporeal fashion. We compared short-term post-operative and oncological outcomes of both approaches., Methods: A prospectively collected database of patients who underwent laparoscopic low anterior resection for rectal cancer between January 2009 and December 2014 was retrospectively analysed. Demographics, post-operative and oncological outcomes were compared., Results: Of 174 patients, 97 were completed by TL, 62 by LA and the remaining 15 were converted to open. Baseline demographics were similar. LA group compared to TL group had bulkier rectal cancers (6.75 cm 3 versus 4.50 cm 3 , P = 0.04) which were lower (6 cm versus 7 cm from anal verge, P = 0.02). They were of a more advanced tumour grade and had greater incidence of lymphovascular invasion. Yet, post-operative outcomes such as time to diet, pain scores, hospitalization duration, wound-related and anastomotic complications, 30-day morbidity and mortality were similar. There was no difference in oncological adequacy, including circumferential resection margins, distal margins, lymph node harvest and 2-year local recurrence rates., Conclusion: Laparoscopic-assisted low anterior resection enables minimally invasive rectal surgery to be performed despite unfavourable tumour factors and technical challenges; and compares favourably with TL approach in terms of short-term outcomes and oncological safety., (© 2018 Royal Australasian College of Surgeons.)

Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Furthermore, prolonged unresolved liver fibrosis may gradually progress to cirrhosis, and eventually evolve into hepatocellular carcinoma (HCC). Corydalis saxicola Bunting (CS), a type of traditional Chinese folk medicine, has been reported to have hepatoprotective effects on the liver. However, the exact mechanism of how it cures liver fibrosis requires further elucidation. In this work, an integrated approach combining proton nuclear magnetic resonance ( 1 H-NMR)-based metabonomics and network pharmacology was adopted to elucidate the anti-fibrosis mechanism of CS. Metabonomic study of serum biochemical changes by carbon tetrachloride (CCl 4 )-induced liver fibrosis in rats after CS treatment were performed using 1 H-NMR analysis. Metabolic profiling by means of partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl 4 was reduced after CS treatment. As a result, lipids, leucine, alanine, acetate, O-acetyl-glycoprotein and creatine were significantly restored after CS treatment, which regulated valine, leucine and isoleucine metabolism; arginine and proline metabolism; lipid metabolism and pyruvate metabolism. Additionally, 157 potential targets of CS and 265 targets of liver fibrosis were identified by means of network pharmacology. Subsequently, 5 target proteins, which are the intersection of potential CS targets and liver fibrosis targets, indicated that CS has potential anti-fibrosis effects through regulating alanine aminotransferase (ALT) activity, the farnesoid X receptor (FXR), cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1) and angiotensinogen. Chelerythrine and sanguinarine were the potential active compounds in CS for treating liver fibrosis through regulating ALT activity. This study is the first report to study the anti-fibrosis effects of CS on the basis of combining a metabonomics and network pharmacology approaches, and it may be a potentially powerful tool to study the efficacy and mechanisms of traditional Chinese folk medicines., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Microsatellite instability in colorectal cancer (CRC) and its long-term outcomes remains poorly studied in Asians. We investigate the prognostic significance of microsatellite instability in an Asian population and assess its clinical impact in patients who undergo adjuvant chemotherapy., Methods: Six hundred fifty-four consecutive CRC patients who underwent surgical resection between January 2010 and December 2012 were recruited. Survival was estimated using the Kaplan-Meier approach. Univariate Cox proportional hazard models were used to estimate the hazard ratios for variables associated with survival. A subgroup analyses was performed for stage III patients who underwent chemotherapy to evaluate the prognostic significance of microsatellite instability in this group., Results: Five hundred ninety-one (90.4%) patients were microsatellite stable (MSS) while 63 (9.6%) were microsatellite instable (MSI). Three years recurrence-free survival (RFS) and disease-specific survival (DSS) were 83.7 versus 73.7% (p = 0.295) and 87.1 versus 91.2% (p = 0.307) in MSS and MSI tumors, respectively. Among stage III patients who received adjuvant therapy, MSI status was found to be an adverse prognostic factor for RFS (HR 2.74 (95% CI 1.43-5.26), p = 0.002). This remained significant on multivariate analysis (HR 2.38 (95% CI 1.15-4.93), p = 0.018). Adjuvant chemotherapy was associated with survival benefit for patients with MSS tumors (HR 0.35, 95% CI 0.17-0.69, p = 0.002) but not MSI tumors (HR 0.67, 95% CI 0.08-8.15, p = 0.750)., Conclusions: MSI status is not a prognostic indicator in the general CRC population but appears to be an adverse prognostic indicator for RFS in stage III CRC patients who received adjuvant chemotherapy.

The role of stem cells in the development of solid tumors remains controversial. In colorectal cancers (CRC), this is complicated by the conflicting "top-down" or "bottom-up" hypotheses of cancer initiation. We profiled the expressions of genes from the top (T) and bottom (B) crypt fractions of normal-appearing human colonic mucosa (M) at least 20 cm away from the tumor as a baseline and compared this to the genes of matched mucosa adjacent to tumors (M T ) in twenty-three sporadic CRC patients. In thirteen patients, the genetic distance (M-M T ) between the B fractions is smaller than the distance between the T fractions, indicating that the expressions diverge further in the top fractions (B < T). In the remaining patients, the reverse effect is observed (B > T). Assuming that a greater genetic divergence in the top or bottom fractions indicates that position as the initiation site, it is thus equally likely that human CRC initiates from 'top-down' via de-differentiated colonocytes or 'bottom-up' via dysregulated intestinal stem cells. Dysregulated genes that persist until tumor stage are not limited to tumor suppressors or oncogenes but include metabolic and transporter genes such as CA7, PHLPP2, and AQP8., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Synchronous polypectomy in colonic malignancies is contentious due to the perceived risks of tumour implantation at polypectomy sites (PS). We assess the risks of tumour implantation after synchronous polypectomy., Methods: An analysis of all endoscopies for cancer that were accompanied by synchronous polypectomies from 2005 to 2009 was performed. The incidence of metachronous colorectal cancers located at the same segment of a previous PS was the surrogate for tumour implantation. Data on patient demographics, tumour and polyp location(s) and follow-up outcomes were extracted. The rate of metachronous lesions at the same segment of a previous PS between patients who had all synchronous PS resected (Group A) and patients with PS left in-situ (Group B) were compared., Results: Two hundred and eighty-four patients had synchronous polypectomy performed during their initial endoscopy for cancer. Three patients were lost to follow-up and, in the remaining 281 patients, 87 (31.0%) were in Group A while 194 (69%) were in Group B. Median age, gender, tumour location, tumour stage, and pathological characteristics were similar between both groups. 2 (0.7%) patients developed local recurrences. Six (2.1%) patients developed metachronous lesions, four of which were located at the same segment where synchronous polypectomy was previously performed. The rates of metachronous lesions at the PS in groups A and B were similar at 1.1% (1/87) and 1.5% (3/194), respectively (p = 0.795)., Conclusion: Malignant implantation after synchronous polypectomy in the setting of a newly diagnosed cancer remains unproven. Even if tumor implantation did occur, the incidence is likely low.

Purpose: Cervical disc arthroplasty has been a popular alternative to traditional arthrodesis treatment for maintaining postoperative cervical spine mobility. However, certain adverse reactions to cervical disc arthroplasty have emerged during the last few decades., Methods: Metallosis or metalloma is a rarely reported complication after spinal fusion or spinal arthroplasty surgery. We report on the first metallosis case occurring in a patient who received Bryan Disc implantation approximately 8 years earlier. She was involved in a traffic accident and sustained a whiplash injury to the cervical spine one and a half years ago. The traumatic Bryan Disc loosening developed after the traffic accident, causing metallosis., Results: To the best of our knowledge, this is the first reported case of spinal metallosis caused by the Bryan Disc. A series of metallosis cases reported in the literature are also reviewed., Conclusions: Although uncommon, intraspinal metallosis or metalloma should be considered as an infrequent cause of delayed neurological symptoms after spinal surgery involving metallic instrumentation, especially after disc arthroplasty. Once metallosis is suspected, immediate metallic implant removal is mandatory for definite diagnosis and treatment.

The amphibious snail, Oncomelania hupensis, primarily distributed in the Far East, is the only intermediate host of Schistosoma japonicum, which causes the most virulent form of schistosomiasis. Obligatory parasitism of snails is the main vehicle for human and livestock infection and depends primarily on parasite infectivity, snail defense capacity and specificity, and parasite-snail compatibility. Therefore, the schistosome-snail interaction is biomedically significant, particularly the molecular mechanisms involved in the innate immune response against S. japonicum. Several immune effectors and signaling pathways have been successfully identified in mollusks, especially in Biomphalaria glabrata, the intermediate snail host of S. mansoni; however, limited information is available for O. hupensis. Here, we identified 16 Toll-like receptors (TLRs) in O. hupensis. These O. hupensis TLRs (OhTLRs) are highly expressed in haemocytes, the primary immune cell of mollusks. Most of the OhTLRs were more highly expressed in female gonads than in other tissues, which may suggest maternal immune transfer in O. hupensis. After S. japonicum challenge, the expression levels of all of the OhTLRs were significantly up-regulated at 6 h post-challenge; many of the OhTLR expression levels were inhibited at later time points in haemocytes, while they were inhibited and fluctuated to varying degrees in other tissues. Additionally, we further determined the tissue-specific expression and dynamic response against S. japonicum of one of the TLR signaling adaptors, myeloid differentiation factor 88 (MyD88), from O. hupensis. Three OhMyD88 genes were highly expressed in haemocytes, and were up-regulated in haemocytes and inhibited in the head-foot muscle at the early time-point after S. japonicum challenge; however, these had slower changes and longer durations compared to OhTLRs. These results provide evidence suggesting that immune effectors are involved in innate immune responses of O. hupensis against S. japonicum and may play a role in the activation of different haemocytes, and not limited for the early response to S. japonicum invasion. Further investigation into the varied expression of OhTLRs in other tissues after S. japonicum challenge will improve our understanding of TLR function in innate immunity of O. hupensis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To observe the effect of electroacupuncture (EA) intervention on learning-memory ability and the expression of senile plaques (SP), amyloid precursor protein (APP), β-secretase 1(BACE 1) and insulin degrading enzyme (IDE) in the hippocampus in APP/presenilin 1 (PS 1) double transgenic Alzheimer's disease (AD) mice, so as to reveal its mechanisms underlying improvement of AD., Methods: A total of 18 male APP/PS 1 double transgenic AD mice were randomly divided into model, EA-2-week and EA-3-week groups ( n =6 in each). The control group was consisted of 6 male wild mice. EA (2 Hz, 2 mA) was applied to "Baihui" (GV 20) and bilateral "Shenshu" (BL 23) for 15 min, once a day, with 7 days being a therapeutic course, 2 or 3 courses altogether and with an one day's interval between every two courses. The spatial learning-memory ability was assessed using Morris water maze test during 5 days' training. The immunoactivity of SP in the hippocampus tissue was detected by immunohistochemistry, and the expression levels of APP, BACE 1 and IDE in the hippocampus were analyzed by Western blot., Results: Following modeling, the escape latency and path length of hidden platform tests were significantly increased ( P <0.01, P <0.05), and the platform crossing time of spatial probing test significantly decreased ( P <0.01) in the model group compared with the control group. After EA intervention, the escape latency on the 5 th day of training, and the path length on the 4 th and 5 th day of training in both EA-2-week and EA-3-week groups were significantly shorter relevant to the model group ( P <0.01), and those of the EA-3-week group were considerably shorter than those of the EA-2-week group in the escape latency and path length ( P <0.05, P <0.01). The platform crossing times of spatial probing test were significanthy increased in both EA-2-week and EA-3-week groups in comparison with the model group ( P <0.01), and that of the EA-3-week group was considerably increased compared with the EA-2-week group ( P <0.05). Immunohistochemical staining showed that the number of SP in the hippocampus was markedly increased in the model group compared with the control group ( P <0.01), and was markedly reduced in both EA-2-week and EA-3-week groups ( P <0.01), and that of the EA-3-week group was significantly decreased compared with the EA-2-week group ( P <0.01). The expression levels of hippocampal APP and BACE 1 proteins were significantly higher in the model group than in the control group ( P <0.01), and that of hippocampal IDE was markedly lower in the model group than in the control group ( P <0.01). After EA, the increased expression levels of APP and BACE 1 proteins and the decreased expression level of IDE in the EA-2-week and EA-3-week groups were significantly inhibited ( P <0.01). The effects of EA-3-week were significantly stronger than those of EA-2-week in down-regulating the expression of APP and BACE 1 proteins and up-regulating the expression of IDE ( P <0.01, P <0.05)., Conclusion: EA stimulation of GV 20 and BL 23 can improve the learning-memory ability in APP/PS 1 double transgenic AD mice, which may be related to its effects in down-regulating the expression of SP, APP and BACE 1 proteins and up-regulating the expression of IDE protein in the hippocampus.

Objectives: To explore the possible biological mechanism of skeletal muscle contusion repair through researching the changes in expression of autophagy-related genes and proteins in SD rats with acute skeletal muscle contusion., Methods: Six rats were randomly selected as the control group from 30 male SD rats, acute skeletal muscle contusion model were established in the remaining 24 rats with self-made hitter, then the model rats were randomly divided into 4 groups (3 d, 5 d, 7 d, 14 d groups, n =6). On the 3 rd , 5 th , 7 th and 14 th day after injury, injured gastrocnemius of each group was harvested. The morphological and the ultra-microstructure changes of gastrocnemius after injury were observed by HE staining and transmission electron microscope (TEM) respectively. The relative protein levels of (LC3-Ⅱ) and P62 of each group were observed by Western blot. The relative mRNA levels of atg7, atg10, atg12, atg16L1 of each group were observed by RTPCR., Results: The results of HE staining showed that compared with the control group, the inflammation reached its peak on the 5 th day after injury, new muscle fibers were clearly observed in 7 d group. The results of TEM showed that, compared with the control group, oncotic mitochondria could be clearly seen in the 3 d, 5 d, 7 d groups. Also, the Z line changed from disappearing to drift thickening, sarcoplasmic reticulum dilatation gradually improved, there was no evident difference between the 14 d group and the control group, suggesting that the damage has preliminarily healed. The results of Western blot showed that the expressions of LC3-Ⅱand P62 were increased at first and then decreased. The expression of LC3-Ⅱwas markedly up-regulated in the 3 d, 5 d, 7 d groups compared with the control group and the 14 d group ( P <0.01). Similarly, compared with the control group, the expression of P62 reached its peak on the 3 rd day after injury ( P <0. 01), and returned to normal level on the 14 th day. The results of RT-PCR showed that the expression of atg10 mRNA in the natural recovery group of 3 d, 5 d, 7 d, 14 d was firstly decreased and then increased, the atg10 mRNA was markedly down-regulated in the 3 d, 5 d, 7 d groups compared with the control group and the 14 d group ( P <0. 01). The expression of atg7, atg12, atg16L1 mRNA was generally increased at first and then decreased, it was markedly up-regulated in the 3 d, 5 d, 7 d groups compared with the control group and the 14 d group ( P <0.01, P <0.05, P <0.01)., Conclusions: The above results indicate that the autophagy is involved in repair of skeletal muscle injury by its autophagyrelated factors,regularly changes after contusion, and the rate of damage repair may be related to the level of autophagy.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.

Background: Multiple single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) risk. The role of structural or copy number variants (CNV) in CRC, however, remained unclear. We investigated the role of CNVs in patients with sporadic CRC., Methods: A genome-wide association study (GWAS) was performed on 1000 Singapore Chinese patients aged 50 years or more with no family history of CRC and 1000 ethnicity-matched, age-matched and gender-matched healthy controls using the Affymetrix SNP 6 platform. After 16 principal component corrections, univariate and multivariate segmentations followed by association testing were performed on 1830 samples that passed quality assurance tests., Results: A rare CNV region (CNVR) at chromosome 14q11 (OR=1.92 (95% CI 1.59 to 2.32), p=2.7e-12) encompassing CHD8 , and common CNVR at chromosomes 3q13.12 (OR=1.54 (95% CI 1.33 to 1.77), p=2.9e-9) and 12p12.3 (OR=1.69 (95% CI 1.41 to 2.01), p=2.8e-9) encompassing CD47 and RERG / ARHGDIB , respectively, were significantly associated with CRC risk. CNV loci were validated in an independent replication panel using an optimised copy number assay. Whole-genome expression data in matched tumours of a subset of cases demonstrated that copy number loss at CHD8 was significantly associated with dysregulation of several genes that perturb the Wnt , TP53 and inflammatory pathways., Conclusions: A rare CNVR at 14q11 encompassing the chromatin modifier CHD8 was significantly associated with sporadic CRC risk. Copy number loss at CHD8 altered expressions of genes implicated in colorectal tumourigenesis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: There has been much recent interest in the use of procalcitonin (PCT) as a marker of intra-abdominal infection (IAI) following colorectal surgery. However, the literature remains divided on the value of PCT in this setting. This meta-analysis aims to evaluate the value of PCT in predicting IAI after colorectal surgery., Methods: Systemic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews to identify studies evaluating the diagnostic accuracy of PCT as a predictor for detecting IAI on postoperative days (POD) 3 to 5 following colorectal surgery. A meta-analysis was performed using random effect model and pooled predictive parameters as well as cut-off values for POD 3 to 5 were derived., Results: Eight studies consisting 1629 patients were included. The pooled prevalence of IAI was 5.7% on POD 3, 9.7% on POD 4, and 6.3% on POD 5. The pooled AUC for POD 3 to 5 were 0.83 (95% CI 0.78-0.88), 0.79 (95% CI 0.64-0.93), and 0.94 (95% CI 0.91-0.97), respectively. The derived PCT cut-off values were 1.45 ng/ml on POD 3, 1.28 ng/ml on POD 4, and 1.26 ng/ml on POD 5. PCT had the highest diagnostic capability on POD 5 with diagnostic odds ratio of 32.9 (95% CI 15.01-69.88), sensitivity of 0.78 (95% CI 0.65-0.89), and specificity of 0.88 (95% CI 0.85-0.90)., Conclusions: PCT is a useful diagnostic predictor of IAI after colorectal surgery. It has the greatest diagnostic accuracy on POD 5 and can help guide safe discharge of patients after colorectal surgery.

Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 μg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 μg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spontaneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100β and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) (registration number: ChiCTR-IPR-16008113)., Competing Interests: None declared