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The (co)variance components and corresponding phenotypic and genetic parameters for growth traits and wool traits of economic importance were estimated in the Alpine Merino sheep population maintained at Gansu Provincial Sheep Breeding Technology Extension Station in northwestern China. Data from a maximum of 49,474 animals sired by 526 rams and born from 22,531 ewes over 20 years from 2000 to 2019 were used in this study. Birth type, age of dam, birth year, sex and/or management group, and age at measurement were initially fitted as fixed effects in an animal model with various random effects. Genetic groups were defined for all animals by the sire breed and breed genotype interacted with dam-strain flocks and were fitted as one of the random effects. Analyses were conducted using a residual maximum likelihood procedure (ASReml). Seven different animal models were fitted for all traits, and the most appropriate model with relevant random effects was selected through log-likelihood ratio testing. After identifying the appropriate model through single-trait analysis, bivariate analyses were used to obtain the phenotypic and genetic correlations among the traits. The estimates of additive direct heritability for birth weight (BWT), weaning weight (WWT), preweaning growth rate (prwADG), postweaning growth rate (powADG), yearling body weight (YWT), average fibre diameter (AFD), greasy fleece weight (GFW), clean fleece weight (CFW), yield (YLD), yearling wool staple length (YSL), coefficient of variation of average fibre diameter (FDcv) and wool visual fineness counts (VFC) were 0.30, 0.18, 0.18, 0.20, 0.29, 0.20, 0.19, 0.20, 0.35, 0.19, 0.16 and 0.13, respectively, with standard errors ranging from 0.02 to 0.05. The corresponding ratios of genetic group variance to additive genetic variance were significant and, respectively, 0.35, 0.80, 0.62, 0.26, 0.13, 1.06, 0.38, 0.64, 0.09, 0.12, 0.06 and 0.58. These results suggest for these traits that there is potential to exploit both the additive genetic variation and between genetic group variation although for most traits the between group variation was smaller than the variation within groups. Favourable genetic correlations were found among the growth traits, and between growth traits and fleece production traits, and among wool traits GFW, CFW, YSL and YLD. This study provides the required estimates of genetic parameters of both growth and wool traits of the new breed for the design of more effective breeding programmes.

BACKGROUND Acute kidney injury (AKI) is one of the most common acute pancreatitis (AP)-associated complications that has a significant effect on AP, but the factors affecting the AP patients’ survival rate remains unclear. AIM To assess the influences of AKI on the survival rate in AP patients. METHODS A total of 139 AP patients were included in this retrospective study. Patients were divided into AKI group (n = 72) and non-AKI group (n = 67) according to the occurrence of AKI. Data were collected from medical records of hospitalized patients. Then, these data were compared between the two groups and further analysis was performed. RESULTS AKI is more likely to occur in male AP patients (P = 0.009). AP patients in AKI group exhibited a significantly higher acute physiologic assessment and chronic health evaluation II score, higher Sequential Organ Failure Assessment score, lower Glasgow Coma Scale score, and higher demand for mechanical ventilation, infusion of vasopressors, and renal replacement therapy than AP patients in non-AKI group (P < 0.01, P < 0.01, P = 0.01, P = 0.001, P < 0.01, P < 0.01, respectively). Significant differences were noted in dose of norepinephrine and adrenaline, duration of mechanical ventilation, maximum and mean values of intra-peritoneal pressure (IPP), maximum and mean values of procalcitonin, maximum and mean serum levels of creatinine, minimum platelet count, and length of hospitalization. Among AP patients with AKI, the survival rate of surgical intensive care unit and in-hospital were only 23% and 21% of the corresponding rates in AP patients without AKI, respectively. The factors that influenced the AP patients’ survival rate included body mass index (BMI), mean values of IPP, minimum platelet count, and hospital day, of which mean values of IPP showed the greatest impact. CONCLUSION AP patients with AKI had a lower survival rate and worse relevant clinical outcomes than AP patients without AKI, which necessitates further attention to AP patients with AKI in surgical intensive care unit.

Background/objectives To identify visual trajectories and examine their relationships with physical and cognitive function in older Chinese adults. Design Population-based longitudinal study. Setting The Chinese Longitudinal Healthy Longevity Survey. Participants A total of 16,151 participants aged ≥65 years. Measurements Visual, physical (including activities of daily living [ADL] and instrumental ADL [IADL]), and cognitive function were assessed at baseline and subsequently every 3 years. ADI disability and IADL disability were defined as needing any help in any item of the Katz scale and a modified Lawton's scale, respectively. Cognitive impairment was defined as a Chinese version of the Mini-Mental State Examination score below 24. A group-based trajectory model was used to determine visual trajectories adjusted for age, sex, and education. Associations of visual trajectories with ADL disability, IADL disability, and cognitive impairment were evaluated using generalized estimating equation models adjusted for potential confounders. Results This study identified three distinct visual trajectories, including no decline (32.4%), moderate decline (48.3%), and progressive decline (19.3%) during the follow-up period. Compared with the no decline trajectory, both the moderate decline (ADL disability: OR = 2.75, 95% CI: 2.30-3.28; IADL disability: OR = 3.01, 95% CI: 2.74-3.31; cognitive impairment: OR = 3.37, 95% CI: 3.02-3.76) and the progressive decline (ADL disability: OR = 8.50, 95% CI: 6.55-11.02; IADL disability: OR = 12.96, 95% CI: 9.95-16.87; cognitive impairment: OR = 10.84, 95% CI: 8.89-13.23) trajectories were significantly associated with an increased risk of functional impairment. Compared with the moderate decline trajectory, the progressive decline trajectory was significantly associated with an increased risk of ADL disability (OR = 3.09, 95% CI: 2.46-3.89), IADL disability (OR = 4.30, 95% CI: 3.29-5.61), and cognitive impairment (OR = 3.22, 95% CI:2.63-3.93). Conclusion Older Chinese adults exhibit three distinct visual trajectories and those with decline trajectories in vision have an increased risk of functional impairment than those with a trajectory of no decline in vision.

Background Acute kidney injury (AKI) is widespread in the intensive care unit (ICU) and affects patient prognosis. According to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, the absolute and relative increases of serum creatinine (Scr) are classified into the same stage. Whether the prognosis of the two types of patients is similar in the ICU remains unclear. Methods According to the absolute and relative increase of Scr, AKI stage 1 and stage 3 patients were divided into stage 1a and 1b, stage 3a and 3b groups, respectively. Their demographics, laboratory results, clinical characteristics, and outcomes were analyzed retrospectively. Results Of the 345 eligible cases, we analyzed stage 1 because stage 3a group had only one patient. Using 53 or 61.88 µmol/L as the reference Scr (Scrref), no significant differences were observed in ICU mortality (P53=0.076, P61.88=0.070) or renal replacement therapy (RRT) ratio, (P53=0.356, P61.88=0.471) between stage 1a and 1b, but stage 1b had longer ICU length of stay (LOS) than stage 1a (P53

Major depression disorder is a severe and recurrent neuropsychological disorder characterized by lowered mood and social activity and cognitive impairment. Owing to unclear molecular mechanisms of depression, limited interventions are available in clinic. In this study we investigated the role of dynorphin/κ opioid receptor system in the development of depression. Mice were subjected to chronic social defeat stress for 14 days. Chronic social defeat stress induced significant social avoidance in mice characterized by decreased time duration in the interaction zone and increased time duration in the corner zone. Pre-administration of a κ opioid receptor antagonist norBNI (10 mg/kg, i.p.) could prevent the development of social avoidance induced by chronic social defeat stress. Social avoidance was not observed in κ opioid receptor knockout mice subjected to chronic social defeat stress. We further revealed that social defeat stress activated c-fos and ERK signaling in the amygdala without affecting the NAc, hippocampus and hypothalamus, and ERK activation was blocked by systemic injection of norBNI. Finally, the expression of dynorphin A, the endogenous ligand of κ opioid receptor, was significantly increased in the amygdala following social defeat stress; microinjection of norBNI into the amygdala prevented the development of depressive-like behaviors caused by social defeat stress. The present study demonstrates that upregulated dynorphin/κ opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on κ opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(Plt;0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(Plt;0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Temporomandibular disorder (TMD) is a complicated and multi‑factorial disease related to inflammation and cartilage destruction. Intra‑articular injection of xanthan gum (XG) has been demonstrated to protect the joint cartilage and reduce osteoarthritis progression. However, the role and mechanism of XG in TMD is still unclear. In the present study, chondrocytes were isolated from rats and identified by immunofluorescence. Cells were stimulated by XG or interleukin (IL)‑1β. Cell viability was analyzed by MTT assay. Tumor necrosis factor α (TNF‑α) and IL‑6 levels were determined by ELISA. The expression of monocyte chemoattractive protein‑1 (MCP‑1), inducible nitric oxide synthase (iNOS), collagens, matrix metalloproteinases (MMPs), peptidyl‑prolyl isomerase 1 (Pin1) and phosphorylated nuclear factor κB (NF‑κB) p65 (p‑p65) was analyzed by quantitative PCR or western blotting. MMP activity was assessed by gelatin zymography. Compared with the control, XG treatment partially reversed the IL‑1β‑reduced cell viability. In addition, IL‑1β stimulation increased inflammatory cytokine expression, including TNF‑α, IL‑6 secretion, MCP‑1 and iNOS expression, whereas XG treatment reduced the expression of these inflammatory cytokines compared with that of the IL‑1β‑stimulated cells. Additionally, XG increased the expression of collagen, but reduced MMP expression and activity as compared with that in the IL‑1β group. In addition, XG treatment prevented the IL‑1β‑increased Pin1 and p‑p65 expression. These data suggested that XG reduced the expression of inflammatory cytokines and may maintain the balance between collagens and MMPs partially through the Pin1/NF‑κB signaling pathway in IL‑1β‑stimulated temporomandibular chondrocytes. Therefore, XG may be useful in the treatment of TMD.

Background Multimorbidity has become a prominent problem worldwide; however, few population-based studies have been conducted among older Chinese with multimorbidity. This study aimed to examine the prevalence of multimorbidity and explore its common patterns among a nationally representative sample of older Chinese. Methods This study used data from the China Health and Retirement Longitudinal Study and included 19,841 participants aged at least 50 years. The prevalence of individual chronic diseases and multimorbidity during 2011–2015 were evaluated among the entire cohort and according to residential regions and gender. The relationships between participants’ demographic characteristics and multimorbidity were examined using logistic regression model. Patterns of multimorbidity were explored using hierarchical cluster analysis and association rule mining. Results Multimorbidity occurred in 42.4% of the participants. The prevalence of multimorbidity was higher among women (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.13–1.51) and urban residents (OR = 1.14, 95% CI: 1.02–1.27) than their respective counterparts after accounting for potential confounders of age, education, smoking, and alcohol consumption. Hierarchical cluster analysis revealed four common multimorbidity patterns: the vascular-metabolic cluster, the stomach-arthritis cluster, the cognitive-emotional cluster, and the hepatorenal cluster. Regional differences were found in the distributions of stroke and memory-related disease. Most combinations of conditions and urban–rural difference in multimorbidity patterns from hierarchical cluster analysis were also observed in association rule mining. Conclusion The prevalence and patterns of multimorbidity vary by gender and residential regions among older Chinese. Women and urban residents are more vulnerable to multimorbidity. Future studies are needed to understand the mechanisms underlying the identified multimorbidity patterns and their policy and interventional implications.

Background:. An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. Methods:. Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. Results:. Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. Conclusion:. Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. Trial Registration:. www.chictr.org.cn (No. ChiCTR-DDD-17013842)

Background and Objectives. Tourniquet-induced ischemia/reperfusion (I/R) injury is a common clinical problem for patients receiving surgery. The objective of this study is to determine if oxycodone (Oxy) reduces skeletal muscle I/R damage induced by tourniquet placement and explores the underlying mechanisms. Method. Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. Results. Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. Conclusion. Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function.

Background The long non‐coding RNA HAND2 antisense RNA 1 (HAND2‐AS1) acts as a tumor suppressor in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we aimed to investigate the function of HAND2‐AS1 in HCC. Methods The expression levels of HAND2‐AS1 and runt‐related transcription factor 2 (RUNX2) were determined in patients with HCC and HCC cell lines using quantitative real‐time polymerase chain reaction and western blot analyses. Cell proliferation was determined using Cell Counting Kit‐8 assay, and the correlation between HAND2‐AS1 and RUNX2 expression was also investigated. Results The plasma level of HAND2‐AS1 was downregulated and that of RUNX2 was upregulated in patients with early‐stage HCC compared with those in healthy controls. No significant differences in the plasma levels of HAND2‐AS1 and RUNX2 were found among hepatitis B virus (HBV)‐positive, hepatitis C virus (HCV)‐positive, and HBV‐ and HCV‐negative patients with HCC. The plasma levels of HAND2‐AS1 and RUNX2 were inversely correlated in the patient groups but not in the control group. HAND2‐AS1 overexpression led to the downregulation of RUNX2 expression in human HCC cells, whereas RUNX2 failed to significantly affect HAND2‐AS1 expression. HAND2‐AS1 overexpression inhibited and RUNX2 overexpression promoted the proliferation of HCC cells. RUNX2 overexpression attenuated the inhibitory effects of HAND2‐AS1 overexpression on cancer cell proliferation. Conclusion HAND2‐AS1 overexpression inhibits cancer cell proliferation in HCC by downregulating RUNX2 expression., HAND2‐AS1 overexpression significantly inhibited whereas RUNX2 overexpression significantly promoted the proliferation of SNU‐398 (A) and SNU‐182 (B) cells. RUNX2 overexpression partially compensated the adverse effects of HAND2‐AS1 overexpression on cancer cell proliferation. Consistent with the cell proliferation data, co‐transfection of HAND2‐AS1 and RUNX2 led to upregulation of HAND2‐AS1 and downregulation of HAND2‐AS1 mRNA expression (*p < 0.05).

This study aims to explore effect of initiation of renal replacement therapy (RRT) on mortality in acute pancreatitis (AP) patients. In this study, a total of 92 patients from the surgical intensive care unit (SICU) of the Second Affiliated Hospital of Harbin Medical University who were diagnosed with AP and underwent RRT or not between January 2014 and December 2018 were included in this retrospective study. Demographic and clinical data were obtained on admission to SICU. Patients were divided into early initiation of RRT group (n = 44) and delayed initiation of RRT group (n = 48). Duration of mechanical ventilation (MV), intra-peritoneal pressure, vasopressors infusion, body temperature, procalcitonin, creatinine, platelet counts, length of hospital stay and prognosis were recorded during hospitalization, and then compared between groups. Patients with delayed initiation of RRT exhibited significantly higher APACHE II score, SOFA score and lower GCS score than those with early initiation of RRT (P

To investigate the role and mechanism of fenofibrate in renal fibrosis induced by unilateral ureteral obstruction in mice, and to provide a potential therapeutic target for renal fibrosis.31 adult male C57BL/6J mice were randomly divided into Sham operation group (Sham,Compared with the Sham group, the serum creatinine and blood urea nitrogen levels of UUO group increased (Fenofibrate reduced mice renal fibrosis caused by unilateral ureteral obstruction and its mechanism may be relate to its regulation effect on the expressions of renal tissue fibrosis related genes.

BACKGROUND Stoma reversal is associated with a high risk of wound infection. The gunsight and purse-string closure techniques are both effective alternatives for stoma reversal, but comparative studies are lacking. OBJECTIVE The purpose of this study was to compare the gunsight procedure with the purse-string closure technique when closing wounds after loop stoma reversal. DESIGN This was a nonblinded, multicenter prospective randomized study (clinicaltrials.gov No. NCT02053948). SETTINGS The study was conducted at a general surgery unit of 7 tertiary academic medical centers. PATIENTS A total of 143 patients undergoing loop stoma reversal were included in the study (72 in the gunsight group and 71 in the purse-string group) between November 2013 and December 2017. INTERVENTION Patients were randomly assigned to undergo either gunsight or purse-string closure procedure. MAIN OUTCOME MEASURES Primary outcome was wound healing time. Secondary outcomes were the incidence of surgical site infection, morbidity, and patient satisfaction. RESULTS No differences were found between the 2 groups in terms of surgical site infection, intraoperative blood loss, and postoperative hospital stay. The gunsight procedure had a shorter wound healing time compared with the purse-string procedure (17 vs 25 d; p < 0.001). A patient satisfaction questionnaire showed that the gunsight group had a higher score level of patient satisfaction with respect to wound healing time (p < 0.001) and total patient satisfaction score (p = 0.01) than the purse-string group. LIMITATIONS Treatment teams were not blinded, and there was operator dependence of techniques. CONCLUSIONS The gunsight and purse-string techniques are effective procedures for stoma reversal and both have a low incidence of surgical site infection. The gunsight technique is associated with shorter wound healing time, higher levels of patient satisfaction with regard to healing time, and overall final score and is recommended as the closure technique of choice. See Video Abstract at http://links.lww.com/DCR/B319. EL PROCEDIMIENTO DE GUNSIGHT VERSUS EL PROCEDIMIENTO DE JARETA, PARA EL CIERRE DE HERIDAS, DESPUeS DE REVERSIoN DE ESTOMA: UN ENSAYO, MULTICeNTRICO, PROSPECTIVO Y RANDOMIZADO: La reversion de estoma esta asociada con un alto riesgo de infeccion de la herida. Las tecnicas de gunsight y de jareta, son eficaces alternativas en la reversion de estoma, pero faltan estudios comparativos.Comparar el procedimiento de gunsight con la tecnica de jareta, despues de la reversion de estoma en asa.Estudio multicentrico, prospectivo y randomizado ciego (NCT02053948).Realizado en la unidad de cirugia general, de siete centros medicos academicos terciarios.Se incluyeron en el estudio, un total de 143 pacientes sometidos a reversion de estoma de asa (72 en el grupo de gunsight y 71 en el grupo de jareta) entre noviembre de 2013 y diciembre de 2017.Los pacientes fueron asignados aleatoriamente, para someterse a un procedimiento de cierre de gunsight o de jareta.El resultado primario fue el tiempo de cicatrizacion de la herida. Los resultados secundarios fueron la incidencia de infeccion del sitio quirurgico, morbilidad y satisfaccion del paciente.No se encontraron diferencias entre los dos grupos en terminos de infeccion del sitio quirurgico, perdida de sangre intraoperatoria o estadia hospitalaria postoperatoria. El procedimiento de gunsight tuvo un tiempo mas corto en la cicatrizacion de la herida, en comparacion con el procedimiento de jareta (17 dias frente a 25 dias, p

The mechanisms underlying the two-way relationship between diabetes mellitus (DM) and periodontitis are unclear. We examined a possible effect of galectin-3 (Gal-3), a factor in DM and bone metabolism, on periodontitis with or without DM. Using enzyme-linked immunosorbent assay, we detected saliva Gal-3 in patients with periodontitis, with or without type 2 diabetes mellitus (T2DM). In animal models, we measured periodontal bone microarchitecture via micro computed tomography, and detected Gal-3, Runt-related transcription factor 2 (Runx2), and interleukin-6 (IL-6) expression in alveolar bone. Applying dual luciferase reporter assay, we explored the target binding of miR-124-3p and Gal-3. We examined osteocyte-derived exosomes with transmission electron microscopy and detected miR-124-3p, Gal-3, and IL-6 expression in exosomes. Saliva Gal-3 was increased in DM compared with controls but decreased in patients with moderate periodontitis and DM compared with those who had moderate periodontitis only. Alveolar bone mass was increased in DM and exacerbated in DM with periodontitis. Gal-3 and Runx2 were both increased in periodontitis and DM compared with controls, but decreased in DM with periodontitis compared with DM alone. MiR-124-3p targeted and inhibited Gal-3 expression in vitro. Osteocytes secreted exosomes carrying miR-124-3p, Gal-3, and IL-6, which were influenced by high glucose. These findings indicate that osteocyte-derived exosomes carrying miR-124-3p may regulate Gal-3 expression of osteoblasts, especially under high-glucose conditions, suggesting a possible mechanism for DM-related alveolar bone pathologies.

To explore the multimorbidity prevalence and patterns among middle-aged and older adults from China. Data on thirteen chronic diseases were collected from 2,097,150 participants aged over 45 years between January 1st 2011 and December 31st 2015 from Beijing Medical Claim Data for Employees. Association rule mining and hierarchical cluster analysis were applied to assess multimorbidity patterns. Multimorbidity prevalence was 51.6% and 81.3% in the middle-aged and older groups, respectively. The most prevalent disease pair was that of osteoarthritis and rheumatoid arthritis (OARA) with hypertension (HT) (middle-aged: 22.5%, older: 41.8%). Ischaemic heart disease (IHD), HT, and OARA constituted the most common triad combination (middle-aged: 11.0%, older: 31.2%). Among the middle-aged group, the strongest associations were found in a combination of cerebrovascular disease (CBD), OARA, and HT with IHD in males (lift = 3.49), and CBD, OARA, and COPD with IHD in females (lift = 3.24). Among older patients, glaucoma and cataracts in females (lift = 2.95), and IHD, OARA, and glaucoma combined with cataracts in males (lift = 2.45) were observed. Visual impairment clusters, a mixed cluster of OARA, IHD, COPD, and cardiometabolic clusters were detected. Multimorbidity is prevalent among middle-aged and older Chinese individuals. The observations of multimorbidity patterns have implications for improving preventive care and developing appropriate guidelines for morbidity treatment.

Summary: Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence.

Objectives Depressive symptoms are commonly seen among patients with multiple chronic somatic conditions, or somatic multimorbidity (SMM); however, little is known about the relationships between depressive symptoms and different SMM combinations. Our study aimed to delineate the patterns of SMM and their longitudinal associations with depressive symptoms among a nationally representative sample of middle-aged and older Chinese adults. Design We employed a longitudinal design. Setting and Participants Older adults (N = 10,084) aged ≥45 years from the China Health and Retirement Longitudinal Study 2011-2015 participated (mean age = 57.7 years at baseline; 53.3% men). Methods Sixteen chronic somatic conditions were ascertained at baseline via questionnaires. Depression was assessed with the Center for Epidemiological Studies Depression Scale at baseline and during follow-up. Patterns of SMM were identified via exploratory factor analyses. Generalized estimating equations were used to evaluate the longitudinal associations between patterns of SMM and the presence of depressive symptoms at follow-up. Results Compared with participants with no somatic condition, those with 1, 2, and 3 or more somatic conditions had a 21%, 66%, and 111% greater risk, respectively, for the presence of depressive symptoms. Increased factor scores for 4 patterns identified, cardio-metabolic pattern [adjusted odds ratio (AOR) 1.12, 95% confidence interval (CI) 1.06, 1.20], respiratory pattern (AOR 1.25, 95% CI 1.17, 1.33), arthritic-digestive-visual pattern (AOR 1.29, 95% CI 1.22, 1.37), and hepatic-renal-skeletal pattern (AOR 1.09, 95% CI 1.02, 1.16), were all associated with a higher risk of having depressive symptoms. Conclusions and Implications All SMM patterns were independently associated with depression among middle-aged and older Chinese adults, with greater odds for people with comorbid arthritic-digestive-visual conditions and respiratory conditions. Clinical practitioners should treat the middle-aged and older population under a multiple-condition framework combining SMM and mental disorders.

Background This prospective study compared pharmacokinetics (PK) and pharmacodynamics (PD) of linezolid in patients with sepsis receiving continuous venovenous hemofiltration (CVVH) with patients receiving extended daily hemofiltration (EDH). Methods Patients with sepsis treated with linezolid and CVVH or EDH were included. Serial blood samples were collected and linezolid concentrations measured. PKs were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement. Results From 20 patients, 320 blood samples were collected for PK and PD analysis. PK profiles of linezolid were best described by a 2-compartment model. PK parameters were not significantly different between EDH and CVVH groups and were associated with body weight, renal replacement therapy (RRT) duration, and sequential organ failure assessment score. Monte Carlo simulations showed poor fractional target attainment for a minimum inhibitory concentration (MIC) of 2 mg/L with standard 600 mg intravenous administration every 12 hours. Conclusions Patients with sepsis receiving RRT exhibited variability in PK/PD parameters for linezolid. PK parameters were not significantly different between CVVH- and EDH-treated patients. Higher probability of target attainment would be achievable at a MIC of 2 mg/L in EDH patients. Higher linezolid doses should be considered for patients on RRT to achieve adequate blood levels.

Context: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (FK506) may be an option for organ transplantation patients.Objective: In this study, w...

κ Opioid receptor system is widely implicated in the regulation of emotion. However, the findings about the role on anxiety in rodents are highly controversial, since both anxiogenic- and anxiolytic-like effects have been reported with κ opioid receptor activation. The mechanism and the underlying neuroanatomical substrates are unexplored. In the present study, we first investigated the effects of κ agonist U50,488H on anxiety-related behaviors over a wide range of doses, and we found that U50,488H produced dual effects in anxiety, with low dose being anxiogenic and high dose being anxiolytic. To assess the potential neuroanatomical substrates, we used phosphorylation of extracellular signal-related kinase1/2 (pERK1/2) to map the underlying neural circuits. We found that the anxiogenic effect of U50,488H was paralleled by an increase of pERK1/2 in the nucleus accumbens, whereas the anxiolytic effect was paralleled by an increase of pERK1/2 in the lateral septal nucleus. We then examined the behavioral consequences with locally microinjection of U50,488H, and we found that microinjection of U50,488H into the nucleus accumbens exerted anxiogenic-like effects, whereas microinjection of U50,488H into the lateral septal nucleus. Both effects can be abolished by κ antagonist nor-BNI pretreatment. To the best of our knowledge, the present work firstly provides the neuroanatomical sites that mediating the dual anxiogenic- and anxiolytic-like effects of U50,488H in mice. This study may help to explain current controversial role of κ receptor activation in anxiety-related behaviors in rodents, and may open new perspectives in the areas of anxiety disorders and κ receptor function.

It has been suggested that the up-regulation of uncoupling proteins (UCPs) decreases reactive oxygen species (ROS) production, in which case there should be a negative relationship between UCPs expression and ROS levels. In this study, the effects of temperature and food restriction on ROS levels and metabolic rate, UCP1 mRNA expression and antioxidant levels were examined in the brown adipose tissue (BAT) of the striped hamsters (Cricetulus barabensis). The metabolic rate and food intake of hamsters which had been restricted to 80% of ad libitum food intake, and acclimated to a warm temperature (30°C), decreased significantly compared to a control group. Hydrogen peroxide (H2O2) levels were 42.9% lower in food restricted hamsters than in the control. Malonadialdehyde (MDA) levels of hamsters acclimated to 30°C that were fed ad libitum were significantly higher than those of the control group, but 60.1% lower than hamsters that had been acclimated to the same temperature but subject to food restriction. There were significantly positive correlations between H2O2 and, MDA levels, catalase activity, and total antioxidant capacity. Cytochrome c oxidase activity and UCP1 mRNA expression significantly decreased in food restricted hamsters compared to the control. These results suggest that warmer temperatures increase oxidative stress in BAT by causing the down-regulation of UCP1 expression and decreased antioxidant activity, but food restriction may attenuate the effects.

Rewarding memories induced by addictive drugs may contribute to persistent drug-seeking behaviors, which is an important contributing factor to drug addiction. However, the biological mechanisms underlying drug-associated rewarding memories have not yet been fully understood, especially the new synthetic drugs, such as amphetamine-type stimulants (ATS). In this study, using the rat-conditioned place preference (CPP) model, a classic animal model for the reward-associated effects of addictive drugs, we found that the expression level of GABAA α1 subunits was significantly decreased in the dorsal striatum (Dstr) after conditioned methamphetamine (METH) pairing, and no significant differences were observed in the other four rewarding memory-associated areas (medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala (Amy), and dorsal hippocampus (DH)). Intra-Dstr injection of either the GABAA receptor agonist muscimol or the specific α1GABAA receptor-preferring benzodiazepine (BDZ) agonist zolpidem significantly abolished METH CPP formation. Thus, this study extends previous findings by showing that GABAA receptors, particularly the α1-containing GABAA receptors, may be strongly implicated in METH-associated rewarding memories. This work provides us with a new perspective on the goal of treating ATS addiction.

Itch is an unpleasant feeling that triggers scratching behavior. Much progress has been made in identifying the mechanism of itch at the peripheral and spinal levels, however, itch circuits in the brain remain largely unexplored. We previously found that anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) inputs modulated histamine-induced itch sensation, but how itch information was transmitted to ACC remained unclear. Here, we demonstrated that the anteromedial thalamic nucleus (AM) was activated during histaminergic itch, and there existed reciprocal neuronal projections between AM and ACC. Disconnection between AM and ACC resulted in a significant reduction of histaminergic, but not nonhistaminergic, itch-related scratching behavior. Optogenetic activation of AM-ACC, but not ACC-AM, projections evoked histaminergic itch sensation. Thus, our studies firstly reveal that AM is critical for histaminergic itch sensation and AM-ACC projections modulate histaminergic itch-induced scratching behavior.

Dezocine is becoming dominated in China market for relieving moderate to severe pain. It is believed that Dezocine’s clinical efficacy and little chance to provoke adverse events during the therapeutic process are mainly attributed to its partial agonist activity at the μ opioid receptor. In the present work, we comprehensively studied the pharmacological characterization of Dezocine and identified that the analgesic effect of Dezocine was a result of action at both the κ and μ opioid receptors. We firstly found that Dezocine displayed preferential binding to μ opioid receptor over κ and δ opioid receptors. Dezocine, on its own, weakly stimulated G protein activation in cells expressing κ and μ receptors, but in the presence of full κ agonist U50,488 H and μ agonist DAMGO, Dezocine inhibited U50,488H- and DAMGO-mediated G protein activation, indicating that Dezocine was a κ partial agonist and μ partial agonist. Then the in intro results were verified by in vivo studies in mice. We observed that Dezocine-produced antinociception was significantly inhibited by κ antagonist nor-BNI and μ antagonist β-FNA pretreatment, indicating that Dezocine-mediated antinociception was via both the κ and μ opioid receptors. When co-administrating of Dezocine with U50,488 H or morphine, Dezocine was capable of inhibiting U50,488H- or morphine-induced antinociception. Finally, κ receptor activation-associated side effect sedation was investigated. We found that Dezocine displayed limited sedative effect with a ceiling effecting at a moderate dose. Thus, our work led to a better understanding of the analgesic mechanism of action of Dezocine in vivo.

The association between morphine withdrawal and depressive-like symptoms is well documented, however, the role of dynorphin/κ opioid receptor system and the underlying neural substrates have not been fully understood. In the present study, we found that four weeks morphine abstinence after a chronic escalating morphine regimen significantly induced depressive-like behaviors in mice. Prodynorphin mRNA and protein levels were increased in the nucleus accumbens (NAc) after four weeks of morphine withdrawal. Local injection of κ opioid receptor antagonist nor-Binaltorphimine (norBNI) in the NAc significantly blocked the expression of depressive-like behaviors without influencing general locomotor activity. Thus, the present study extends previous findings by showing that prolonged morphine withdrawal-induced depressive-like behaviors are regulated by dynorphin/κ opioid receptor system, and shed light on the κ opioid receptor antagonists as potential therapeutic agents for the treatment of depressive-like behaviors induced by opiate withdrawal.

AIM: To determine the expression and significance of filamin A (FLNa) in colorectal adenocarcinoma tissue. METHODS: The expression of FLNa in 46 colorectal cancer tissues and normal tissues was detected by immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, and its relationship with clinical parameters and prognosis was analyzed. RESULTS: The positive expression of FLNa in cancer tissues was lower than that in normal mucosa, and the difference was statistically significant. The expression of FLNa correlated with liver metastasis, lymph node metastasis and rectal invasion depth, regardless of sex, age, tumor location, tumor size, gross shape and histological type of colorectal carcinoma. Multivariate analysis showed that FLNa was an independent risk factor for postoperative survival of patients with colorectal adenocarcinoma. Moreover, survival analysis showed that the expression level of FLNa was closely related with survival of patients with colorectal adenocarcinoma. The results of RT-PCR and Western blotting were consistent with those of immunohistochemistry. CONCLUSION: FLNa showed low expression in colorectal adenocarcinoma, high correlation with the incidence and development of colorectal cancer, and was considered an indicator of prognosis.

The abuse of amphetamine-type stimulants (ATS) has become a global public health issue in recent years, these new-type drugs can cause addiction and serious cognitive impairment . However, there are no effective methods for the prevention and treatment of ATS addiction at present. Repetitive transcranial magnetic stimulation (rTMS) is a painless and non-invasive new therapeutic approach that has been used for the treatment of depression and other neuropsychiatric disorders , but whether it can be used to treat drug addiction is unclear. In the present study, we investigated the possible effects of rTMS on methamphetamine(METH)-induced conditioned place preference (CPP). High-frequency (10 Hz) and low-frequency stimulation patterns (1 Hz) were applied to test the effect of rTMS on METH-induced CPP. The results showed that low-frequency but not high-frequency rTMS could block METH-CPP, accompanied with a downregulation of gamma-aminobutyric acid type B receptor subunit 1 (GABA BR1) expression in rat dorsolateral striatum. These results suggested that low-frequency rTMS could effectively inhibit the development of METH addiction and shed light on the rTMS as a potential approach for the prevention of drug addiction.

Objective To explore whether baseline body composition and other clinical factors are associated with incomplete immune response after highly active antiretroviral therapy(HAART)in Chinese men with human immunodeficiency virus(HIV)or acquired immunodeficiency syndrome(AIDS).Methods A retrospective study was conducted among HIV/AIDS male patients who achieved viral suppression(maintained HIV-1 RNA levels400 copies/ml)after a year of HAART between 2007 and 2015.Clinical,immunological,and virological data were collected from patients' files,including weight,height,and whole body composition measured within one month prior to staring HAART.Body mass index(BMI),lean mass index(LMI),fat mass index(FMI),and body bone mineral content/height were adjusted by height.According to whether the patients experienced incomplete immune responses(CD4 cell count350 cells/μl)after a year of HAART,the patients were divided into two groups:the complete immune response(CD4 cell count≥350 cells/μl)and the incomplete immune response(CD4 cell count350 cells/μl),respectively.Student's t test,chi-square test,and Wilcoxon rank test were used to assess differences between these two groups.Multiple Logistic regression analysis was used to assess factors associated with an incomplete immune response in patients with sustained viral suppression.Results Totally 84 HIV/AIDS male patients with viral suppression were included in this study.There were statistical differences between these two groups in terms of age(Z=-2.479,P=0.013),baseline BMI(t=2.030,P=0.045),LMI(t=2.200,P=0.029),and CD4 cell count(Z=6.416,P=0.000).However,there was no statistical differences in viral load,FMI,body bone mineral content/height,HAART duration,and HAART regimen(all P0.05).BMI[OR=0.742,95% confidence interval(CI)=0.554-0.993,P=0.044],LMI(OR=0.459,95% CI=0.249-0.844,P=0.012),HAART duration(OR=10.161,95% CI=1.110-93.052,P=0.040),baseline CD4 cell count(OR=80.051,95% CI=8.396-762.563,P=0.000)were significantly associated with incomplete immune response.Age(OR=1.497,95% CI=0.213-10.505,P=0.685),viral load(OR=0.333,95% CI=0.071-1.572,P=0.164),FMI(OR=0.797,95% CI=0.546-1.164,P=0.240),body bone mineral content/height(OR=1.145,95% CI=0.037-35.676,P=0.938)and HAART regimen(OR=0.430,95% CI=0.159-1.159,P=0.095)were not associated with incomplete immune response.Conclusions Baseline CD4 cell count and HAART duration may affect immune response.Patients with higher baseline BMI or higher LMI may be less likely to develop incomplete immune response.Baseline FMI and body bone mineral content/height ratio are not associated with incomplete immune response.目的 分析不同体成分及其他因素与中国男性人类免疫缺陷病毒(HIV)或获得性免疫缺陷综合征(AIDS)患者接受高效抗逆转录病毒治疗(HAART)后免疫重建不全的相关性。方法 回顾性分析2007年至2015年接受HAART 1年以上并获得病毒抑制(HIV-1 RNA400拷贝/ml)的男性HIV/AIDS患者资料,包括患者临床、免疫学及病毒学资料,其中包括HAART开始前1个月内测量的患者体质量、身高、全身体成分。经身高校正后得到体质量指数(BMI)、肌肉指数(LMI)、脂肪指数(FMI)、骨矿含量/身高。根据患者接受HAART 1年后是否出现免疫重建不全(CD4细胞计数350细胞/μl),将患者分为免疫学未完全应答组(CD4细胞计数350细胞/μl)、免疫学完全应答组(CD4细胞计数≥350细胞/μl)。应用

Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma–associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma–associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma–associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma–associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma–associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma–associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma–associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma–associated 1 in renal cell carcinoma, and urothelial carcinoma–associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma–associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma–associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.

Repeated exposure to methamphetamine (METH) can cause severe neurotoxicity to the cortical neurons. In the present study, we investigated the effect of METH on cognitive function deficits, and determined the neuroprotective effects of memantine (MEM) on memory impairment induced by METH. The protein levels of Bcl-2 and cleaved caspase-3 in prefrontal cortex (PFC) were further examined to exploring the underlying mechanism. We found that repeated METH administration impaired long term (24h) memory retention without affecting short term (5min) memory retention. Co-administration of MEM with METH before training session significantly improved METH-induced cognitive function. METH significantly decreased expression level of Bcl-2 and increased expression level of cleaved caspase-3 in the PFC. The changes can be prevented by MEM pretreatment. Thus, these results demonstrated that MEM pretreatment reversed METH-induced changes of protein levels of apoptotic-related gene, and produced protective effects against METH-induced cognitive deficits, suggesting the effectiveness of MEM may be due to its anti-apoptotic activity.

By using immunostaining and three-dimensional reconstruction, the anatomical organization of the antennal lobe glomeruli of the female cotton bollworm Helicoverpa armigera was investigated. Eighty-one glomeruli were identified, 15 of which were not previously discovered. The general anatomical organization of the AL of female is similar to that of male and all glomeruli were classified into four sub-groups, including the female-specific glomerular complex, posterior complex, labial-palp pit organ glomerulus, and ordinary glomeruli. A global-wide comparison on the complete glomerular map of female and male was performed and for the first time the quantitative difference in volume for each individual homologous glomerulus was analyzed. We found that the sexual dimorphism includes not only the sex-specific glomeruli but also some of the other glomeruli. The findings in the present study may provide a reference to examine the antennal-lobe organization more in detail and to identify new glomeruli in other moth species. In addition, the complete identification and global-wide comparison of the sexes provide an important basis for mapping the function of distinct glomeruli and for understanding neural mechanisms underlying sexually dimorphic olfactory behaviors. © The Author(s) 2016. Published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Self-care is critical for postdischarge heart failure (HF) patients. Short message service (SMS) is a promising way to promote HF self-care. The aim of this study is to investigate knowledge status in Chinese HF patients, as well as the acceptance of SMS as a way to improve self-care. A survey using a self-developed questionnaire was conducted in patients with decompensated HF 2 days before discharge. A total of 540 patients completed the survey. Among them, only 69.8% and 63.3% of patients were aware of their HF status and medication regimen, respectively. A total of 95.6% patients were willing to receive SMS. Patient himself/herself, caregiver, or both patient and caregiver were almost equally selected as the preferred receiver of SMS. Educational and/or reminder SMS was considered “very helpful” by 50.2% of the patients as a way of promoting self-care, similar to that of telephone education and brochure education. “Take your medicine”, “avoid getting flu,” and “keep follow-up” were regarded as the most important self-care contents, whereas “weigh yourself every day” and “restrict fluid intake” were considered the least important. As a way of promoting HF self-care, SMS intervention combining educational and reminder function might be well accepted by HF patients in China. The status of HF, medication, weight control, and fluid restriction should be emphasized during the practice. Caution should be drawn as the survey was not tested elsewhere. Further clinical trials would be conducted to examine the effect of SMS intervention on self-care behaviors and outcomes of HF patients.

To study the impacts of exposure to electromagnetic radiation (EMR) on liver function in rats.Twenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/ d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and those of malondialdehyde (MDA) and glutathione (GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl- 2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling (TUNEL) method was used for analysis of apoptosis in liver.Compared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes (P0.05), while the contents of MDA increased (P0.01) and those of GSH decreased (P0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group (all P0.01).The exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.

This study investigates anatomical organization of the antennal lobe (AL) glomeruli of the male cotton bollworm Helicoverpa armigera by synaptic antibody staining combined with three-dimensional reconstruction. To identify all glomeruli, their boundaries were accurately determined by means of several additional staining techniques visualizing the neuron categories forming the characteristic spherical neuropils. In total, 78-80 glomeruli were identified in the male H. armigera. The number of glomeruli was considerably larger than that previously reported in this species. Thus, compared with previous studies, we identified 15 new glomeruli, G63-G77. Most of them are located in the posterior part of the AL, which was previously considered to be a part of the protocerebrum. From the general anatomical organization of the AL glomeruli of H. armigera, we classified these neuropil structures into four groups, the macroglomerular complex, posterior complex, labial-palp pit organ glomerulus, and ordinary glomeruli. The complete identification of glomeruli is important for future studies seeking to explore further the coding mechanisms residing within the primary olfactory center of the moth brain. J. Comp. Neurol. 524:2993-3013, 2016. © 2016 Wiley Periodicals, Inc.

The mirid bug Apolygus lucorum (Meyer-Dür), a polyphagous pest, is dependent on olfactory cues to locate various host plant species and mates. In this study, we traced the projection pathway of the antennal sensory neurons and visualized their projection patterns in the central nervous system of A. lucorum through confocal microscopy and digital reconstructions. We also examined the glomerular organization of the primary olfactory center of the brain, the antennal lobe, and created a three-dimensional model of the glomeruli. We found that the axons of the sensory neurons project into the brain via the ipsilateral antennal nerve, and descend further into the gnathal ganglion, prothoracic ganglion, mesothoracic ganglion, and metathoracic ganglion, and reach as far as to the abdominal ganglion. Such a projection pattern indicates that antennal sensory neurons of A. lucorum may be potentially directly connected to motor neurons. The antennal lobe, however, is the major target area of antennal sensory neurons. The antennal lobe is composed of a large number of glomeruli, i.e. 70-80 glomeruli in one AL of A. lucorum. The results of this study which provide information about the basic anatomical arrangement of the brain olfactory center of A. lucorum, are important for further investigations of chemosensory encoding mechanisms of the mirid bug.

BACKGROUND Tumor markers are widely used in clinical practice and have become important indicators in assessing cancer progress. There is increasing concern that chemotherapy combined with traditional Chinese medicine has effects in decreasing the level of tumor markers. OBJECTIVE To investigate the effects of chemotherapy combined with Kangliu Zengxiao Decoction (KLZX), a compound Chinese herbal drug, on tumor markers carbohydrate antigen 50 (CA 50), cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in patients with advanced non-small-cell lung cancer (NSCLC) and to explore the relationships between clinical efficacy and tumor markers. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS Patients were included from Punan Hospital of Shanghai Pudong New District and Longhua Hospital between October 2008 and December 2009. Seventy-four subjects with advanced NSCLC were randomly assigned into treatment group (n=37) and control group (n=37). Patients in the control group were treated with chemotherapy alone while patients in the treatment group were treated with chemotherapy combined with KLZX. Chemotherapy of NP (vinorelbine + cisplatin) was given for two cycles and patients in the treatment group were administered with KLZX during chemotherapy. MAIN OUTCOME MEASURES Levels of CA50, CYFRA21-1 and CEA before and after treatment were evaluated and the relationship between changes in levels of tumor makers and tumor size, clinical symptoms and living condition score (Karnofsky score) was analyzed. RESULTS No patients achieved a complete remission. The disease control rates (complete remission (CR)+partial remission (PR)+no change (NC)) were 89.20% (33/37) and 70.30% (26/37) in the treatment and control group respectively (P

Background GRB-associated binding protein 2 (GAB2) may function as a risk factor in the pathogenesis of Alzheimer disease (AD). A recent large genome-wide association study (GWAS) has identified a significant association of rs10793294 polymorphism within the GAB2 gene with AD in Caucasians. While there are no studies on the association of rs10793294 polymorphism with AD risk in the Chinese population. Methods The study investigated 358 sporadic late-onset AD (LOAD) and 366 healthy controls matched for sex and age in a Han Chinese population. The rs10793294 polymorphism within the GAB2 gene was genotyped using MALDI-TOF mass spectrometry. Results The C allele of the rs10793294 polymorphism within GAB2 was significantly associated with an increased risk of LOAD (OR = 1.33, 95% CI = 1.04–1.72, P = 0.029). Significance was observed in APOEe4 carriers (genotype P = 0.039, allele P = 0.016). While in APOE e4 non-carriers, significant differences were observed in alleles (P = 0.039) but not in genotypes (P = 0.304). Logistic regression revealed that rs10793294 polymorphism was still strongly associated with LOAD in dominant model (OR = 2.58, 95% CI = 1.22–5.45, P = 0.013) and additive model (OR = 1.38, 95% CI = 1.05–1.80, P = 0.020) after adjusting for age, gender, and the APOE e4 status. Conclusions Our findings implicate GAB2 as a susceptibility gene for LOAD in Han Chinese.

Summary Objective To investigate the efficacy and safety of Antiwei, a traditional Chinese prescription, in the treatment of influenza. Methods In a multi-center, randomized, double-blind, placebo-controlled trial, we recruited 480 adults aged 18 to 65 years within 36 h of onset of influenza-like symptoms. There were 225 patients with confirmed influenza. Eligible patients were randomly assigned 6 g of Antiwei (n = 360) or placebo (n = 120) twice daily for three days. All patients recorded their temperature and symptoms on diary cards during treatment. Analyses were performed in both the influenza-like population and the influenza-confirmed population. Results Antiwei increased patients’ recovery by 17% (P

Monoamine oxidase (MAO) A is a critical enzyme in the catabolism of dopamine. Dysfunction of dopaminergic systems has been implicated in the pathophysiology of schizophrenia, suggesting that MAOA gene variation might be associated with the disorder. MAOA gene variation was compared between 234 Chinese schizophrenic patients and 121 healthy controls. Three polymorphic markers of the MAOA gene were analyzed using PCR techniques: two MAOA restriction fragment length polymorphisms (RFLP), − 941G/T and − 1460C/T, and the variable number tandem repeats (VNTR) in the promoter region. Linkage disequilibrium and haplotype analyses were performed with Bonferroni correction for multiple testing. In single marker analyses the 941T allele was significantly associated with schizophrenia in men (p = 0.01). Haplotype analyses revealed a significant overall difference (p = 0.03) between schizophrenia and control men, with higher frequencies of haplotypes containing the major allele (T) of − 941T/G and the short allele (3 repeats) of the VNTR polymorphisms. No significant associations were detected for females using single markers or haplotypes. These findings suggest that genetic variants in MAOA may play a role in susceptibility to schizophrenia in Chinese men.

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome.

Summary Hypermethylation of CpG islands is well known as a major inactivation mechanism of tumor suppressor genes. E-cadherin (E-cad) as a tumor invasion suppressor has been reported in several invasive and metastatic carcinomas. However, its significance in carcinogenesis of primary non-small cell lung cancer (NSCLC) is not well documented. This study was designed to assess the significance with 95 pairs of carefully collected NSCLC tumors and corresponding nonmalignant tissue samples. We carried out PCR-SSCP (single-strand conformation polymorphism) and PCR-RFLP (restriction fragment length polymorphism) screening for DNA variants, bisulfite conversion-specific MSP for methylation analysis, reverse transcription (RT)-PCR for mRNA and immunohistochemistry (IHC) for protein expression assays. To investigate effect of promoter-hypermethylation on E-cad expression, we also did demethylation experiment in six cell lines. First, we found that the −160A carriers (a single nucleotide polymorphism (SNP) in the promoter region of E-cad ) had an increased risk for lung cancer development when compared to DNA from healthy volunteers (OR (odds ratio)=2.81; 95% CI (confidence interval), 1.36–5.86). Methylation of E-cad occurred with a significantly higher frequency in tumors than corresponding normal peritumoral tissues ( P −5 ). Reduced expression of E-cad was detected as a distinct molecular feature of tumors in comparison to corresponding counterparts. Moreover, the methylation alteration was detected more frequently in low-differentiated tumors than in well-differentiated ones. Defective expression of E-cad in methylated cell lines was markedly recovered after treated with 5-Aza-dC (5-aza-2′-deoxycytidine). Thus, promoter-hypermethylation of E-cad is significantly associated with its defective expression and tumor differentiation, and the demethylating observation proposes a therapeutic strategy to reverse the tumor's malignancy by restoring normal expression of E-cad.

Schizophrenia is associated with various abnormalities in the immune system. Suppression of inflammatory cytokines by cigarette smoke is well-established. The purpose of this study was to determine any differences in cytokine profiles in smokers and nonsmokers with schizophrenia and whether there were any relationships among altered cytokine profiles and psychopathological symptoms.Serum interleukin (IL)-2, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha levels were measured in 96 male inpatients with DSM-IV schizophrenia: 66 smokers and 30 nonsmokers. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).The positive PANSS symptoms were lower in smokers than nonsmokers, while the negative symptoms were lower in those who smoked more cigarettes. Cytokine levels were positively correlated: IL-2 level with IL-6 and IL-6 with both IL-8 and TNF-alpha. Both IL-2 and IL-6, but not IL-8 or TNF-alpha, were significantly lower in smokers than nonsmokers (p0.002; p0.01). Lower IL-2 levels correlated with fewer negative symptoms and with smoking more cigarettes.The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced suppression of some inflammatory cytokines.

The intrinsic or acquired resistance to multiple drugs (MDR) of cancer cells remains one of the main obstacles for chemotherapy. Development of small molecule targeting to hypoxia inducible factor-1 (HIF-1) has been recently proposed as strategy for treatments of drug-resistant solid tumors. In the present study, emodin, proven as a reactive oxygen species (ROS) generator by our previous work, was applied in combination with cisplatin and other chemotherapeutic drugs in the multidrug resistant prostate carcinoma cell line DU-145 and normal human dermal fibroblasts. Results showed that emodin/cisplatin co-treatment remarkably elevated ROS level and enhanced chemosensitivity in DU-145 cells, compared with cisplatin-only treatment, but exerted little effect on non-tumor cells. The effect of co-treatment on MDR1 gene and its upstream regulator HIF-1 was then investigated in DU-145. Co-treatment downregulated MDR1 expression and promoted drug retention, and meanwhile suppressed transactivation of HIF-1 in response to hypoxia without changing expression of HIF-1 alpha. The experiments on tumor-bearing mice showed that co-treatment inhibited the tumor growth in vivo, owing to oxidative stress and MDR1 down-regulation within tumors. HIF-1 transactivation and clonegenesis were suppressed in cells isolated from the tumors. Finally, examinations for the body weight, the organ histology and the antioxidant capacity of serum suggested that no systemic toxicity related to co-treatment was discernable. In conclusions, emodin, as a novel small inhibitor of HIF-1, may be recognized an effective adjunctive to improve efficacy of cytotoxic drugs in prostate cancer cells with over-activated HIF-1 and potent MDR.

κ opioid receptor agonists produce aversive effects in rodents, however the underlying mechanisms remain unclear. Activation of p38 mitogen-activated protein kinase (MAPK) has been discovered to play a critical role in the modulation of affective behaviors. The present study was undertaken to detect the possible involvement of p38 MAPK in the aversive effects induced by κ opioid receptor activation. We found that the κ opioid receptor agonist trans-(±)-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate salt (U50,488H) produced significant place aversion in mice as measured by the conditioned place preference procedure, accompanied with significant p38 MAPK activation in the amygdala, but not in the nucleus accumbens and hippocampus. Stereotaxic microinjection of the p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridy-l)-1H-imidazole (SB203580) into amygdala significantly inhibited p38 MAPK activation and completely blocked the conditioned place aversion in mice. Thus, these results suggested that activation of p38 MAPK in the amygdala was required to mediate κ opioid receptor-induced aversive behavior.

Aims The purpose of this study was to clarify the effect of mini-tyrosyl-tRNA synthetase/mini-tryptophanyl-tRNA synthetase (mini-TyrRS/mini-TrpRS) in ischemic angiogenesis in rhesus monkeys with acute myocardial infarction (AMI). Methods A 27-gauge needle was incorporated percutaneously into the left ventricular myocardium of rhesus monkeys with AMI. All monkeys were randomized to receive adenoviral vector mini-TyrRS/mini-TrpRS, which was administered as five injections into the infarcted myocardium, or saline or ad-null (control groups). The injections were guided by EnSite NavX left ventricular electroanatomical mapping. Mini-TyrRS/mini-TrpRS proteins were detected by Western blot and immunoprecipitation analyses. Microvessel density (MVD) per section was measured using immunostaining with a CD34 monoclonal antibody. Proliferating cardiomyocytes were identified through histological and immunohistochemical analyses. Myocardial perfusion and cardiac function were estimated by G-SPECT. Infarction size was also measured. Results Western blot analyses showed that compared to the normal zone, the expression level of mini-TyrRS/mini-TrpRS was significantly different in the infarction zone. G-SPECT analysis indicated that the mini-TyrRS group had better cardiac function and myocardial perfusion after the injection of ad-mini-TyrRS than before, while mini-TrpRS injection had a totally opposite effect. After mini-TyrRS was administered, there was less of an infarction zone and more proliferating cardiomyocytes and capillaries in the mini-TyrRS group compared to both of the control groups, and the ad-mini-TrpRS group had a totally opposite effect. Conclusion These results indicated that angiogenesis could be either stimulated by mini-TyrRS or inhibited by mini-TrpRS.

β-Arrestins function as signal transducers linking GPCRs to ERK1/2 signalling either by scaffolding members of ERK1/2s cascades or by transactivating receptor tyrosine kinases through Src-mediated release of transactivating factor. Recruitment of β-arrestins to the activated GPCRs is required for ERK1/2 activation. Our previous studies showed that δ receptors activate ERK1/2 through a β-arrestin-dependent mechanism without inducing β-arrestin binding to the δ receptors. However, the precise mechanisms involved remain to be established.ERK1/2 activation by δ receptor ligands was assessed using HEK293 cells in vitro and male Sprague Dawley rats in vivo. Immunoprecipitation, immunoblotting, siRNA transfection, intracerebroventricular injection and immunohistochemistry were used to elucidate the underlying mechanism.We identified a new signalling pathway in which recruitment of β-arrestin2 to the EGFR rather than δ receptor was required for its role in δ receptor-mediated ERK1/2 activation in response to H-Tyr-Tic-Phe-Phe-OH (TIPP) or morphine stimulation. Stimulation of the δ receptor with ligands leads to the phosphorylation of PKCδ, which acts upstream of EGFR transactivation and is needed for the release of the EGFR-activating factor, whereas β-arrestin2 was found to act downstream of the EGFR transactivation. Moreover, we demonstrated that coupling of the PKCδ/EGFR/β-arrestin2 transactivation pathway to δ receptor-mediated ERK1/2 activation was ligand-specific and the Ser(363) of δ receptors was crucial for ligand-specific implementation of this ERK1/2 activation pathway.The δ receptor-mediated activation of ERK1/2 is via ligand-specific transactivation of EGFR. This study adds new insights into the mechanism by which δ receptors activate ERK1/2.

To investigate the effects of Ginkgo biloba extract (EGb) administration on T lymphocyte subsets and superoxide dismutase (SOD) levels in schizophrenia.One hundred and nine schizophrenic inpatients were randomly assigned to 12 weeks of treatment with 360 mg/day of EGb plus a stable dose of 0.25 mg kg(-1) day(-1) of haloperidol and placebo plus the same dose of haloperidol using a double-blind design. Clinical efficacy was determined using the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms. T lymphocytes (CD3+), T helper cells (CD4+), T suppressor cells (CD8+), and IL-2-secreting cells were measured using the alkaline phosphatase/antialkaline phosphatase technique; and SOD levels were measured by radioimmunometric assay at baseline and at posttreatment, as compared to 30 sex- and age-matched normal subjects.Patients demonstrated significantly lower CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8 ratio, and significantly higher blood SOD levels than did healthy controls at baseline. There was a significantly negative relationship between SOD and CD4+ cells in the schizophrenic group at baseline. After a 12-week treatment, CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8 ratio, showed a significant increase, but a significant decrease in SOD levels in the EGb group. There was only a significant increase in CD4+ cells but no change in SOD levels in the placebo group. There was a significant correlation between the change in CD4+ cells at posttreatment vs pretreatment and a reduction of BPRS total score in the whole patient group.EGb may improve the decreased peripheral immune functions in schizophrenia. The beneficial effects of EGb on the immune systems and the improvement of schizophrenic symptoms may be medicated through its antioxidant activity.