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Background: Despite substantial efforts to investigate the inequalities in mental health among people with marginalized identities, most research has concentrated on single social identities rather than complete persons. The current study aimed to explore the mechanisms underlying the relationship between the intersectionality of multiple social identities with depression among US adults., Methods: Data for this study came from the National Health and Nutrition Examination Survey waves between 2015 and 2018, including a total of 11,268 US adults. A latent class analysis (LCA) was conducted to identify latent subpopulations based on sex, race/ethnicity, immigrant status, disability, household income, employment status, and education level. Interclass differences in lifestyle factors and depression were examined. Multiple mediation analysis was used to examine the mediating roles of lifestyle behaviors., Results: LCA identified four potential subpopulations: "least marginalized", "immigrant minorities", "disabled, less-educated non-workers", and "low-income minorities" groups. There was enormous heterogeneity in mental health among immigrant minority individuals. The "disabled, less-educated non-workers" group had the highest rates of depression; in contrast, the "immigrant minorities" group had the best mental health, even better than that of the "least marginalized" group. Distributions of lifestyle factors followed a similar pattern. In addition, lifestyle behaviors significantly mediated the relationship between intersectional social identities and depression., Limitations: The cross-sectional design prevented establishment of the causality of relationships., Conclusions: This study suggests that applying a person-centered approach is important when examining intersectional inequalities in mental health and highlights the effects of structural social hierarchies on individuals' health behaviors and mental health., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Parent‒child communication in migrant families is essential to family bonds and the mental health of left-behind children (LBC). Little is known about the different patterns of communication between migrant parents and LBC and associated communication quality and mental health outcomes., Methods: A sample of 2,183 Chinese children (mean age = 12.95 ± 1.29 years) from Anhui province, including LBC whose parents had both migrated (n = 1,025) and children whose parents had never migrated (never-LBC, n = 1,158), was analyzed. With the LBC sample, latent class analysis was applied to identify the patterns of parent‒child communication. Multinomial logistic regression analysis was conducted to assess the associations between the sociodemographic variables and class membership of LBC. Analysis of covariance and chi-square tests were used to compare communication quality and mental health outcome differences among the classes of LBC and between each of the classes and never-LBC., Results: Five latent classes of communication formed through different media or channels between migrant parents and their LBC were identified. Higher household economic status (OR = 2.81, p < 0.05) was associated with adequate communication. LBC in Class 1, defined by frequent technologically-mediated and face-to-face communication, had a significantly higher quality of communication with their migrant parents (F = 8.92, p < 0.001) and better mental health than those in other latent classes; these children did not have significantly worse mental health outcomes compared to never -LBC., Conclusions: Facilitating multichannel parent‒child communication is a practical way of reducing mental health inequities between LBC and their peers., (© 2024. The Author(s).)

Objective: To identify lifestyle patterns in emerging adults and examine the association of lifestyle patterns with overweight and depression. Methods: Data was from the National Health and Nutrition Examination Survey between 2011 and 2018. A latent class analysis (LCA) was conducted with 2,268 US emerging adults based on sedentary behavior, moderate-to-vigorous physical activity, diet, sleep, alcohol drinking, and cigarette smoking. The associations of lifestyle groups with overweight and depression were examined by logistic regression and were further stratified by employment status. Results: The LCA results favored a four-class solution: "unhealthy but non-substance use" (59%), "healthy but sleepless and drinking" (12%), "unhealthy lifestyle" (15%), and "healthy but sedentary" group (14%). Compared to the "unhealthy lifestyle" group, participants in the "unhealthy but non-substance use" (coef. = -1.44, SE = 0.27; OR = 0.40, 95% CI [0.26, 0.61]), "healthy but sleepless and drinking" (coef. = -1.49, SE = 0.35; OR = 0.38, 95% CI [0.20, 0.72]), and "healthy but sedentary" (coef. = -1.97, SE = 0.34; OR = 0.29, 95% CI [0.14, 0.57]) groups had lower depression severity and reported fewer depressive symptoms. Moreover, lifestyle groups and health outcomes showed different relationships among employed and unemployed participants. Conclusion: This study found that the combinations of lifestyle behaviors had synergistic effects on mental health, and such effects differed by employment status., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Xie, Fan, Luo and Chen.)

Nonpharmaceutical interventions are important for addressing the psychosocial needs of children living with atopic dermatitis (AD). The current study aimed to investigate the effects of an integrative body-mind-spirit (IBMS) intervention on the subjective experiences of affected children and explore the mechanisms underlying the effects. Using a drawing-based, qualitative approach, the current study conducted two rounds of interviews with 13 children (aged 8-12 years) diagnosed with moderate or severe AD before and after they attended the IBMS intervention. Data were analyzed by using the thematic analysis method. The IBMS intervention worked by changing participants' perceptions at the cognitive level, improving their coping strategies at the behavioral level, and constructing their social support network at the environmental level. Cognitive, behavioral, and environmental factors might mediate the relationships between the IBMS intervention and participants' psychological and physical outcomes. This study highlighted the wider inclusion of child-centered qualitative research in the evaluation of the effects of psychosocial interventions designed for children.

Background: Parents are significantly important in shaping the screen use of children within a family system. This study aimed to examine the associations of Chinese children's screen time (ST) over four years with parents' attitudes toward their own screen use and physical activities (PA) and health behaviors including their ST, PA, cigarette smoking, and alcohol drinking., Methods: The current study utilized data from two waves (2011 and 2015) of the China Health and Nutrition Survey (CHNS), including 1,941 mother-father-child triads in 2011 and 2,707 mother-father-child triads in 2015 (with children aged 0-17-years-old). The ST of children and the parental attitudes and health behaviors were measured via self-report or proxy-report (for children under 6 years old) questionnaires. Pool-OLS regression models were used to assess the associations of parental attitudes and health behaviors with the ST of children. Moderation models were built to assess whether these associations depended on the gender, age, and family income of children, as well as whether paternal and maternal influences were moderated by the other parent. A multilevel cross-lagged panel model (CLPM) was used to assess parental influences on children's ST over four years., Results: Paternal ST (β = 0.09, p < 0.001), maternal ST (β = 0.10, p < 0.001), and paternal alcohol drinking (β = 0.30, p < 0.05) were positively associated with children's ST. In addition, maternal smoking had a positive association with girls' ST (β = 0.53, p < 0.05). Moreover, the association between maternal ST and children's ST was observed to decline as family income increased (β = -0.03, p < 0.001). Paternal ST had a larger positive association with children's ST when the ST of mothers exceeded 14 h/week (β = 0.06, p < 0.05). Furthermore, lagged associations were found between paternal attitudes toward PA (β = -1.63, p < 0.05) or maternal cigarette smoking (β = 1.46, p < 0.05) and children's ST measured four years later., Conclusion: Children establish a healthy lifestyle within the family system. From the perspective of the healthy family climate, the current study suggests that future programs for reducing children's ST should be built through an integrative approach with special attention to parental attitudes and health behaviors., (© 2023. The Author(s).)

Objective: To investigate the etiology, clinical characteristics, diagnosis, and treatment strategies and efficacy of pulsatile tinnitus (PT) caused by vascular anatomy abnormality., Methods: The clinical data of 45 patients with PT in our hospital from 2012 to 2019 were collected and retrospectively analyzed., Results: All 45 patients had vascular anatomical abnormalities. The patients were divided into 10 categories according to the different locations of vascular abnormalities: sigmoid sinus diverticulum (SSD), sigmoid sinus wall dehiscence (SSWD), SSWD with high jugular bulb, pure dilated mastoid emissary vein, aberrant internal carotid artery (ICA) in the middle ear, transverse-sigmoid sinus (TSS) transition stenosis, TSS transition stenosis with SSD, persistent occipital sinus stenosis, petrous segment stenosis of ICA, and dural arteriovenous fistula. All patients complained of PT synchronous with heartbeat rhythm. Endovascular interventional therapy and extravascular open surgery were used according to the location of the vascular lesions. Tinnitus disappeared in 41 patients, was significantly relieved in 3 patients, and was unchanged in 1 patient postoperatively. Except for one patient with transient headache postoperatively, no obvious complications occurred., Conclusion: PT caused by vascular anatomy abnormalities can be identified by detailed medical history and physical and imaging examination. PT can be relieved or even completely alleviated after appropriate surgical treatments., (© 2023. Huazhong University of Science and Technology.)

Objectives: Parents are often torn between their parenting roles in the family and working roles at the workplace. This study focused on the associations of parental employment with children's screen time (ST) on weekdays, weekends, and during the entire week. Methods: Unbalanced panel data including 2,977 children (aged 0-17 years) from five waves of the China Health and Nutrition Survey data from 2004 to 2015 were utilized. Two-way fixed effects models were fitted to examine the associations of parental employment status, working hours, and overwork with children's ST. Results: Compared to unemployment status, maternal formal employment positively predicted children's ST on both weekdays and weekends, while maternal informal employment was associated with increased children's ST on weekends. The more hours they worked, the more time their children spent using screens. Neither employment status nor the overwork of fathers was significant. Conclusion: Parental employment, especially maternal employment, was linked with the ST of children. More childcare-friendly labor policies are needed to promote healthy lifestyles among the next generation., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Xie, Luo, Chen and Zhou.)

Background: Stigma has been recently identified as a crucial factor associated with the psychosocial burden of those who have chronic skin diseases. The self-stigma experiences of children living with atopic dermatitis (AD) have yet to be fully investigated, and questions of how these children respond to public stigma and how AD symptoms further affect their self-stigma experiences remain unresolved. The current qualitative study aimed to (1) describe the main manifestations of self-stigma in children living with AD; (2) investigate factors that might influence their self-stigma experiences; and (3) explore the potential mechanisms underlying the impacts of AD on their psychosocial well-being from the self-stigma perspective., Methods: We performed a secondary analysis of the qualitative literal transcription data which were collected earlier by using the participatory, drawing-based qualitative interviews with 17 children aged 8-12 who were diagnosed with severe or moderate AD., Results: The qualitative findings indicated that the visible and invisible symptoms of AD and its management exerted unique influences on self-stigma in children living with AD, which manifested in cognitive, affective, and behavioral aspects and ultimately affected their psychosocial well-being., Conclusions: Findings of this study allowed us to advocate for eliminating public stigma of people with skin diseases and propose recommendations for helping children living with AD relieve their self-stigma., (© 2022. International Society of Behavioral Medicine.)

The strengths of drawing-based approaches for encouraging children's participation in health research and facilitating communication with them have been increasingly acknowledged in the medical literature. However, there is a lack of methodological discussion on drawing-based approaches suitable for researching children living with physical health problems. The present study systematically reviewed qualitative research using drawing-based approaches on the experiences of children living with physical health problems and summarised how the approaches were used as well. We identified 54 studies from five databases. The characteristics of qualitative methods and drawing-based approaches were analysed. To obtain an overall understanding of the illness-related experiences of these children, qualitative data generated from the included studies were synthesised using the thematic synthesis approach. This systematic review highlights the appropriateness and accuracy of the use of drawings-based approaches in health research with children on their illness-related experiences, fostering inclusive participation and engagement of young generations., (© 2022 John Wiley & Sons Ltd.)

Tax1 banding protein 1 (Tax1bp1) was originally identified as an NF-κB regulatory protein that participated in inflammatory, antiviral and innate immune processes. Tax1bp1 also functions as an autophagy receptor that plays a role in autophagy. Our previous study shows that Tax1bp1 protects against cardiomyopathy in STZ-induced diabetic mice. In this study we investigated the role of Tax1bp1 in heart failure. Pressure overload-induced heart failure model was established in mice by aortic banding (AB) surgery, and angiotensin II (Ang II)-induced heart failure model was established by infusion of Ang II through osmotic minipump for 4 weeks. We showed that the expression levels of Tax1bp1 in the heart were markedly increased 2 and 4 weeks after AB surgery. Knockdown of Tax1bp1 in mouse hearts significantly ameliorated both AB- and Ang II infusion-induced heart failure parameters. On the contrary, AB-induced heart failure was aggravated in cardiac-specific Tax1bp1 transgenic mice. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) under Ang II insult. We demonstrated that the pro-heart failure effect of Tax1bp1 resulted from its interaction with the E3 ligase ITCH to promote the transcription factor P73 ubiquitination and degradation, causing enhanced BCL2 interacting protein 3 (BNIP3)-mediated cardiomyocyte apoptosis. Knockdown ITCH or BNIP3 in NRCMs significantly reduced Ang II-induced apoptosis in vitro. Similarly, BNIP3 knockdown attenuated heart failure in cardiac-specific Tax1bp1 transgenic mice. In the left ventricles of heart failure patients, Tax1bp1 expression level was significantly increased; Tax1bp1 gene expression was negatively correlated with left ventricular ejection fraction in heart failure patients. Collectively, the Tax1bp1 increase in heart failure enhances ITCH-P73-BNIP3-mediated cardiomyocyte apoptosis and induced cardiac injury. Tax1bp1 may serve as a potent therapeutic target for the treatment of heart failure.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Knockout of Tax1bp1 in mouse hearts ameliorated heart failure induced by pressure overload.• Tax1bp1 interacts with the E3 ligase Itch to promote P73 ubiquitination and degradation, causing enhanced BNIP3-mediated apoptosis.• Tax1bp1 may become a target of new therapeutic methods for treating heart failure., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Ventilator-induced lung injury (VILI) is a complex pathophysiological process leading to acute respiratory distress syndrome (ARDS) and poor outcomes in affected patients. As a form of programmed cell death, pyroptosis is proposed to play an important role in the development of ARDS. Here we investigated whether treating mice with the specific RIPK1 inhibitor Necrostatin-1 (Nec-1) before mechanical ventilation could inhibit pyroptosis and alleviate lung injury in a mouse model., Methodologys: Anesthetized C57BL/6J mice received a transtracheal injection of Nec-1 (5 mg/kg) or vehicle (DMSO) 30 min before the experiment which was ventilated for up to 4 h. Lung damage was assessed macroscopically and histologically with oedema measured as the wet/dry ratio of lung tissues. The release of inflammatory mediators into bronchoalveolar lavage fluid (BALF) was assessed by ELISA measurements of TNF-α,interleukin-1β (IL-1β), and IL-6. The expression of RIPK1, ZBP1, caspase-1, and activated (cleaved) caspase-1 were analyzed using western blot and immunohistochemistry, and the levels of gasdermin-D (GSDMD) and IL-1β were analyzed by immunofluorescence staining., Results: High tidal ventilation produced time-dependent inflammation and lung injury in mice which could be significantly reduced by pretreatment with Nec-1. Notably, Nec-1 reduced the expression of key pyroptosis mediator proteins in lung tissues exposed to mechanical ventilation, including caspase-1, cleaved caspase-1, and GSDMD together with inhibiting the release of inflammatory cytokines., Conclusion: Nec-1 pretreatment alleviates pulmonary inflammatory responses and protects the lung from mechanical ventilation damage. The beneficial effects were mediated at least in part by inhibiting caspase-1-dependent pyroptosis through the RIPK1/ZBP1 pathway., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

PLK1 and Smad4 are two important factors in prostate cancer initiation and progression. They have been reported to play the opposite role in Pten-deleted mice, one is an oncogene, the other is a tumor suppressor. Moreover, they could reversely regulate the PI3K/AKT/mTOR pathway and the activation of MYC. However, the connections between PLK1 and Smad4 have never been studied. Here, we showed that PLK1 could interact with Smad4 and promote the ubiquitination and degradation of Smad4 in PCa cells. PLK1 and PELO could bind to different domains of Smad4 and formed a protein complex. PELO facilitated the degradation of Smad4 through cooperating with PLK1, thereby resulting in proliferation and metastasis of prostate cancer cell. Changes in protein levels of Smad4 led to the alteration of biological function that caused by PLK1 in prostate cancer cells. Further studies showed that PELO upregulation was positively associated with high grade PCa and knockdown of PELO expression significantly decreased PCa cell proliferation and metastasis in vitro and vivo. PELO knockdown in PCa cells could enhance the tumor suppressive role of PLK1 inhibitor. In addition, blocking the interaction between PELO and Smad4 by using specific peptide could effectively inhibit PCa cell metastasis ability in vitro and vivo. Overall, these findings identified a novel regulatory relationship among PLK1, Smad4 and PELO, and provided a potential therapeutic strategy for advanced PCa therapy by co-targeting PLK1 and PELO., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: A burgeoning literature has found relationships between telomere length, telomerase activity, and human health and longevity. Although some research links a history of childhood adversity with shortened telomere length, our review found no prior research on the relationship between child maltreatment history and telomerase activity in adulthood. We hypothesized a negative relationship between child maltreatment and telomerase activity and hypothesized that the association would be moderated by sex., Methods: These relationships were tested on a sample of 262 Hong Kong Chinese adults (200 females versus 62 males) with mild to moderate depression., Results: Counterintuitively, emotional abuse was positively associated with telomerase activity, while other maltreatment types were non-significant. The positive relationship between emotional abuse and telomerase activity was significantly moderated by the sex of the participant., Conclusions: We advance two possible explanations for this finding (1) a culturally informed resilience explanation and (2) a homeostatic complexity explanation. The two explanations are not mutually exclusive. This trial is registered under Hong Kong Clinical Trial Register number HKCTR-1929., Significance Statement: Emotional abuse was significantly positively associated with telomerase activity. There are at least two non-mutually exclusive explanations for the findings. Simply put, either (1) in the cultural context of Hong Kong emotional abuse was not a risk factor, and/or (2) the conceptualization of telomerase activity as a straightforward indicator of longevity is overly simplistic. The first story we might term a "resilience explanation" while the second we might call a "homeostatic complexity" story.

The novel coronavirus disease (COVID-19) has spread all over the world in a short time. Information about the differences between COVID-19 patients with and without hypertension is limited. To explore the characteristics and outcomes differences between COVID-19 patients with and without hypertension, the medical records and cardiac biomarkers of 414 patients were analyzed. A total of 149 patients had a history of hypertension, while 265 patients did not have hypertension, and the groups were compared based on their clinical characteristics and laboratory findings as well as the hazard risk for composite outcomes, including intensive care unit (ICU) admission, mechanical ventilation, or death. The results are as follows. On admission, 22.1% of patients in hypertension group had elevated high sensitivity troponin I (hs-TNI > 26 pg/mL), which was higher than the proportion in the nonhypertension group (6.4%). Median NT-proBNP levels in patients with hypertension (141.9 pg/mL) were higher than those in patients without hypertension (77.3 pg/mL). Patients in the hypertension group had a higher risk for in-hospital death [HR: 2.57, 95% CI (1.46~4.51)]. However, the impact of hypertension on the prognosis was not significant after adjusting for age and sex. Multivariate Cox hazard regression confirmed that NT-proBNP levels in the highest tertile (upper 75 % of patients with hypertension) was an independent risk factor for in-hospital death in all COVID-19 patients. Taken together, hypertension per se had a modest impact on the prognosis in COVID-19 patients. In COVID-19 patients with and without hypertension, NT-proBNP may be a better predictor of prognosis than hs-TNI., Competing Interests: The authors declare no conflicts of interest., (© 2020 Yao et al. Published by IMR Press.)

High-mobility group AT-hook2 (HMGA2), serving as an architectural transcription factor, participates in plenty of biological processes. Our study is aimed at illustrating the effect of HMGA2 on hypoxia-induced HUVEC injury and the underlying mechanism. To induce hypoxia-related cell injury, HUVECs were exposed to hypoxic condition for 12-24 h. Molecular expression was determined by Western blot analysis, real-time PCR and immunofluorescence staining. Cell migration was monitored by wound healing assay and Transwell chamber assay. Cell proliferation and apoptosis were measured by MTT assay kits and TUNEL staining. In this study, we discovered that HMGA2 was upregulated in hypoxia-induced HUVECs. Overexpression of HMGA2 promoted cell migration, decreased the apoptosis ratio in response to hypoxia stimulation, while HMGA2 knockdown inhibited cell migration and accelerated apoptosis in HUVECs under hypoxic condition. Mechanistically, we found that HMGA2 induced increased expression of HIF-1α,VEGF, eNOS and AKT. eNOS knockdown significantly reduced HMGA2-mediated pro-migration effects, and AKT knockdown strikingly counteracted HMGA2-mediated anti-apoptotic effect. Hence, our data indicated that HMGA2 promoted cell migration by regulating HIF-1α/VGEF/eNOS signaling and prevented cell apoptosis by activating HIF-1α/VGEF/AKT signaling in HUVECs.

Objective: To compare the postoperative functional prognosis of transanal mesorectal excision (taTME) and conventional total mesorectal excision (TME) in rectal cancer. Methods: Totally 49 patients underwent taTME and 478 patients underwent conventional TME at Department of Gastroenterological Surgery, Peking University People's Hospital from January 2015 to December 2019 were retrospectively collected. Propensity score matching method was used to perform 1 versus 1 matching between the taTME and conventional TME groups, and 36 pairs of patients were successfully matched. After matching, the median age of patients in taTME group and conventional TME group was 60.5 (16.0) years and 60.5 (13.0) years ( M ( Q(R) )), respectively, and the proportion of male patients was 66.7% (24/36) and 55.6% (20/36) , respectively. EORTC QLQ-C30 scale was used to assess quality of life, low anterior resection syndrome (LARS) scale and Wexner constipation score were used to evaluate anal function, international prostate symptom score (IPSS) was used to evaluate urinary function,international index of erectile function (IIEF) -5 and female sexual function index (FSFI) score were used to evaluate male and female sexual function, respectively, and generalized anxiety disorder (GAD-7) and patient health questionnaire (PHQ-9) scale were used to evaluate psych function. The t test, Mann-Whitney U test, χ(2) test, and Fisher exact test were used for comparison between groups, and Wilcoxon rank sum test or McNemar test was used for comparison between paired data. Results: There were no significant differences in surgery time, postoperative hospital stays, conversion rate, morbidity rate, surgery cost, and numbers of lymph node yield between the two groups (all P> 0.05). Compared with the conventional TME group, the intraoperative blood loss in the taTME group was significantly higher (100 (100) ml vs . 80 (50) ml, U =424.5, P= 0.010), the prophylactic stoma rate was significantly higher (96.9%(31/36) vs . 63.6%(21/36), χ(2)=11.218, P< 0.01), the total hospitalization cost was significantly lower (74 297.7 (16 746.4) CNY vs . 91 781.3 (26 228.4) CNY, U =413.0, P= 0.008). There were no significant differences in anal and urinary function between the two groups (LARS scalescore: Z= -0.513, P= 0.608, Wexner constipation score: Z= -0.992, P= 0.321, IPSS: Z= -1.807, P= 0.071). In terms of psych function, significant difference in GAD-7 scale was seen between the two groups ( Z= -2.311, P= 0.021), patients with generalized anxiety disorder accounting for 26.7% (8/30) and 46.9% (15/32), respectively. Conclusions: Compared with conventional TME surgery, taTME has a significantly increased blood loss and prophylactic stoma rate. There are no significant difference in the incidence of postoperative anal, urinary, and sexual dysfunction between taTME and conventinal TME. taTME can alleviate the financial burden and general anxiety disorder to a certain extent.

Objective: To investigate the efficacy and prognosis of three surgical methods for presacral recurrent rectal cancer (PRRC). Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) primary rectal cancer without distant metastasis and undergoing radical surgery; (2) patients undergoing radical surgery after the diagnosis of PRRC; (3) complete inpatient, outpatient and follow-up data. Clinical data of 47 patients meeting the above criteria who underwent operation at the Department of Gastrointestinal Surgery, The Peking University People's Hospital from January 2008 to December 2017 were reviewed and analyzed retrospectively. Of the 47 patients, 31 were male and 16 were female; the mean age was 57 years old; 9 (19.1%) were low differentiation or signet ring cell carcinoma, 38 (80.9%) were medium differentiation; 19 (40.4%) received neoadjuvant therapy. According to operative procedure, 22 patients were in the abdominal/abdominoperineal resection group, 15 in the sacrectomy group and 10 in the abdominosacral resection group. The operative data, postoperative data and prognosis were compared among the three groups. Survival curve was conducted using the Kaplan-Meier method, and log-rank test was used to compare survival difference among three groups. Results: There were no significant differences in baseline data among three groups (all P >0.05). All the 47 patients completed the radical resection successfully. The mean operation time was (4.7±2.1) hours, the median intraoperative blood loss was 600 ml, and the median postoperative hospitalization time was 17 days. Fifteen cases (31.9%) had perioperative complications, of which 3 cases were grade III-IV. There was no perioperative death. The mean operative time was (7.4±1.6) hours in the abdominosacral resection group, (4.9±1.6) hours in the abdominal/abdominoperineal resection group, and (3.0±1.1) hours in the sacroectomy group, with a significant difference ( F =25.071, P <0.001). There were no significant differences in intraoperative blood loss, postoperative hospitalization days and perioperative complications among the three groups (all P >0.05). The median follow-up period of all the patients was 24 months, 12 cases (25.5%) developed postoperative dysfunction. The incidence of postoperative dysfunction in the abdominosacral resection group was 5/10, which was higher than 4/15 in the sacrectomy group and 3/22 (13.6%) in the abdominoperineal resection group with statistically significant difference (χ(2)=9.307, P =0.010). The 1-year and 3-year overall survival rates were 86.1% and 40.2% respectively. The 1-year overall survival rates were 86.0%, 86.7% and 83.3%, and the 3-year overall survival rates were 33.2%, 40.0% and 62.5% in the abdominal/abdominoperineal resection group, sacrectomy group and abdominosacral resection group, respectively, whose difference was not statistically significant (χ(2)=0.222, P =0.895). Conclusions: Abdominal/abdominoperineal resection, sacrectomy and abdominosacral resection are all effective for PRRC. Intraoperative function protection should be concerned for patients undergoing abdominosacral resection.

Objective: To investigate the clinicopathological features and prognostic factors in patients with presacral recurrent rectal cancer (PRRC). Methods: PRRC was defined as recurrence of rectal cancer after radical surgery involving posteriorly the presacral soft tissue, the sacrum/coccyx, and/or sacral nerve root. The diagnosis is confirmed with clinical symptoms (pain of pelvis/back/lower limb, bloody stools, increased frequency of defecation, and abnormal secretions), physical examination of perineal or pelvic masses, radiological findings, colonoscopy with histopathological biopsy, and the evaluation by multi-disciplinary team (MDT). Inclusion criteria: (1) primary rectal cancer undergoing radical surgery without distant metastasis; (2) PRRC was diagnosed; (3) complete inpatient, outpatient and follow-up data. According to the above criteria, clinical data of 72 patients with PRRC in Peking University People's Hospital from January 2008 to December 2017 were retrospectively analyzed. The clinicopathological features and follow-up data were summarized. Cox proportional hazard models was used to analyze the prognostic factors of PRRC. Results: Among 72 patients, 45 were male and 27 were female with a male-to-female ratio of 1.7:1.0. The median age at recurrence was 58 (34 to 83) years and the median interval from surgery to recurrence was 2.0 (0.2 to 17.0) years. The main symptom was pain in 48.6% (35/72) of patients. In addition, gastrointestinal symptoms were found in 25.0% (18/72) of patients. The presacral recurrent sites were presacral fascia in 36 (50.0%) patients, lower sacrum (S3~S5 or coccyx) in 25 (34.7%) patients, and higher sacrum (S1~S2) in 11 (15.3%) patients. Forty-seven (65.3%) patients underwent radical surgery (abdominal resection, abdominoperineal resection, sacrectomy, abdominosacral resection), 12 (16.7%) underwent non-radical surgery (colostomy, cytoreductive surgery), and 13 (18.1%) did not undergo any surgery but only receive palliative chemoradiotherapy and nutritional support treatment. Thirty-three (45.8%) patients received radiotherapy and/or chemotherapy (oxaliplatin, 5-fluorouracil, capecitabine, irinotecan, etc.). All the patients received follow-up, and the median follow-up time was 19 (2 to 72) months. The median overall survival time was 14 (1 to 65) months. The 1- and 3-year overall survival rates were 67.1% and 32.0%, respectively. Univariate analysis showed that age at recurrence ( P =0.031) and radical resection ( P <0.001) were associated with prognosis. Multivariate analysis demonstrated that radical resection was independent factor of good prognosis (RR=0.140, 95%CI: 0.061-0.322, P <0.001). Conclusions: Patients tend to develop presacral recurrent rectal cancer within 2 years after primary surgery. The main symptom is pain. Patients undergoing radical resection have a relatively good prognosis.

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed., Competing Interests: The authors have declared that no competing interests exist.

Atopic dermatitis (AD) imposes significant physical and psychosocial burdens on affected children. However, little has been done to learn from the subjective experiences, perspectives and emotions of children living with AD. Their voices are not heard in healthcare settings. This study aims to share these children's voices and provide a deep understanding of the subjective experiences of children living with AD. We conducted qualitative research by conducting semi-structured interviews and analysing the drawings of 17 children in Hong Kong aged between 8 and 12 years who were diagnosed with AD. Using a phenomenological approach, we transcribed, coded and described the interviews. We found that for the children in this study, living with AD meant contending with an accumulation of challenges and crises. At the individual level, the essential experience of living with AD manifested a vicious cycle of skin and mental issues. At the family level, conflicts between children and parents concerning AD management coexisted with parental support. The children commonly experienced bullying and isolation in school and discrimination and stigmatisation in their neighbourhood, thereby making living with AD a traumatic experience. The synergy between individual and environmental factors contributed to shaping an incapable and wounded "self" living with AD. Based on our findings, we propose a child-centred biopsychosocial framework for understanding the living experiences of children with AD. This study suggests different practice strategies for healthcare professionals working with the individual challenges experienced by children living with AD and the challenges these children experience in their family, school, and neighbourhood. The needs of these children should be addressed through an integrated, holistic approach for improving their long-term health outcomes., (© 2019 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Aims : The High Mobility Group A1 (HMGA1) proteins, serving as a dynamic regulator of gene transcription and chromatin remodeling, play an influential part in the pathological process of a large number of cardiovascular diseases. However, the precise role of HMGA1 in sepsis induced cardiomyopathy (SIC) remains unintelligible. This research was designed to illustrate the effect of HMGA1 involved in SIC. Methods and Results : Cardiomyocyte-specific HMGA1 overexpression was obtained using an adeno-associated virus system with intramyocardial injection in mice heart. The model of SIC in mice was constructed via intraperitoneal injection of lipopolysaccharide (LPS) for 6h. H9c2 rat cardiomyocytes was stimulated with LPS for 12h. HMGA1 expression was upregulated in murine inflammatory hearts as well as LPS stimulated H9c2 cardiomyocytes. HMGA1-overexpressing exhibited aggravated cardiac dysfunction, cardiac inflammation as well as cells apoptosis following LPS treatment both in vivo and in vitro experiment. Interestingly, HMGA1 knockdown in H9c2 cardiomyocytes attenuated LPS-induced cardiomyocyte inflammation, but aggravated cell apoptosis. Mechanistically, we found that overexpression of HMGA1 induced increased expression of cyclooxygenase-2 (COX-2). COX-2 inhibitor alleviated the aggravation of inflammation and apoptosis in HMGA1 overexpressed H9c2 cardiomyocytes whereas HMGA1 knockdown induced a reduction in signal transducer and activators of transcription 3 (STAT3) expression. STAT3 agonist reversed HMGA1 silence induced anti-inflammatory effects, while ameliorated cell apoptosis induced by LPS. Conclusion : In conclusion, our results suggest that overexpression of HMGA1 aggravated cardiomyocytes inflammation and apoptosis by up-regulating COX-2 expression, while silence of HMGA1 expression attenuated inflammation but aggregated cell apoptosis via down-regulation of STAT3., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cardiac remodelling refers to a series of changes in the size, shape, wall thickness and tissue structure of the ventricle because of myocardial injury or increased pressure load. Studies have shown that cardiac remodelling plays a significant role in the development of heart failure. Zingerone, a monomer component extracted from ginger, has been proven to possess various properties including antioxidant, anti-inflammatory, anticancer and antidiabetic properties. As oxidative stress and inflammation contribute to acute and chronic myocardial injury, we explored the role of zingerone in cardiac remodelling. Mice were subjected to aortic banding (AB) or sham surgery and then received intragastric administration of zingerone or saline for 25 days. In vitro, neonatal rat cardiomyocytes (NRCMs) were treated with zingerone (50 and 250 μmol/L) when challenged with phenylephrine (PE). We observed that zingerone effectively suppressed cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Mechanistically, Zingerone enhanced the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) activation via increasing the phosphorylation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Additionally, we used Nrf2-knockout (KO) and eNOS-KO mice and found that Nrf2 or eNOS deficiency counteracts these cardioprotective effects of zingerone in vivo. Together, we concluded that zingerone may be a potent treatment for cardiac remodelling that suppresses oxidative stress via the eNOS/Nrf2 pathway., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Assessing the psychological effects on children and adolescents of suffering atopic dermatitis (AD) is essential, when planning successful management. This study aimed to systematically review the literature regarding risk of mental disorders in children and adolescents with, or without, AD; and to explore confounders. We identified potentially relevant studies from EMBASE, MEDLINE, PsycINFO, ERIC, the British Nursing Index, the Family and Society Studies Worldwide, the Social Work Abstracts, and the Sociological Abstracts from inception to Sep 30, 2018. Investigators independently screened titles and abstracts, and then full-texts. Investigators independently extracted data from included studies. Meta-analyses using random-effects models were performed, reporting odds ratios (ORs; 95% CIs). Thirty-seven studies ( n = 2,068,911 children/ adolescents) were included. Meta-analysis of 35 studies found that children and adolescents with AD had significantly higher risk of total mental disorders than those without AD (OR = 1.652; 95% CI, 1.463-1.864). There was no significant difference in risks for ADHD (OR = 1.563; 95% CI, 1.382-1.769); sleep disorders (OR = 2.100; 95% CI, 1.322-3.336); anxiety (OR = 1.339; 95% CI, 1.062-1.687); depression (OR = 1.402 95% CI, 1.256-1.565); conduct disorder (OR = 1.494 95% CI, 1.230-1.815); or ASD (OR = 2.574; 95% CI, 1.469-4.510; Q b = 8.344, p = 0.138). Race/ethnicity of child, target of comparison, type of studies, representativeness of the sample, measures of AD and mental disorders were significant moderators for total mental disorders. Integrated, holistic, multidisciplinary management of pediatric AD is significantly important, which emphasizes the well-being of the whole person.

Context: Parent-child book reading (PCBR) is effective at improving young children's language, literacy, brain, and cognitive development. The psychosocial effects of PCBR interventions are unclear., Objective: To systematically review and synthesize the effects of PCBR interventions on psychosocial functioning of children and parents., Data Sources: We searched ERIC, PsycINFO, Medline, Embase, PubMed, Applied Social Sciences Index and Abstracts, Social Services Abstracts, Sociological Abstracts, Family and Society Studies Worldwide, and Social Work Abstracts. We hand searched references of previous literature reviews., Study Selection: Randomized controlled trials., Data Extraction: By using a standardized coding scheme, data were extracted regarding sample, intervention, and study characteristics., Results: We included 19 interventions (3264 families). PCBR interventions improved the psychosocial functioning of children and parents compared with controls (standardized mean difference: 0.185; 95% confidence interval: 0.077 to 0.293). The assumption of homogeneity was rejected ( Q = 40.010; P < .01). Two moderator variables contributed to between-group variance: method of data collection (observation less than interview; Q b = 7.497; P < .01) and rater (reported by others less than self-reported; Q b = 21.368; P < .01). There was no significant difference between effects of PCBR interventions on psychosocial outcomes of parents or children ( Q b = 0.376; P = .540)., Limitations: The ratio of moderating variables to the included studies limited interpretation of the findings., Conclusions: PCBR interventions are positively and significantly beneficial to the psychosocial functioning of both children and parents., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

The reporting of suspected CSA cases to authorities in a timely manner is important in preventing continued abuse and protecting abused children at early ages. The current study seeks to explore parents' intentions of reporting their own children's CSA experiences to authorities as well as their reporting willingness when they become aware of possible CSA cases happening to children in other families. Two rounds of semi-structured interviews were conducted among a sample of 26 parents in Beijing; these parents were purposefully selected so as to be diverse in terms of gender, age, and socioeconomic status. The data were analyzed thematically. The findings showed that the reporting of suspected CSA to authorities was a choice made by only a few Chinese parents; it was often even a last resort. By using a holistic-interactionistic approach, the interaction between Chinese parents' intentions of reporting CSA and the Chinese socio-cultural context was analyzed as a dynamic and continuously ongoing process. The impacts of the definition and perceptions of CSA on reporting, the balance of children's rights and parents' power, and the double effect of informal social control are discussed. The implications, both locally and globally, are also discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) has been widely applied during thyroid surgery. However, the safe range of stimulation intensity for IONM remains undetermined., Methods: Total thyroidectomies were performed on twenty dogs, and their RLNs were stimulated with a current of 5-20 mA (step-wise in 5 mA increments) for 1 min. The evoked electromyography (EMG) of vocal muscles before and after supramaximal stimulation were recorded and compared. Acute microstructural morphological changes in the RLNs were observed immediately postoperatively under an electron microscope., Results: The average stimulating threshold for RLNs stimulated with 15 mA and 20 mA showed no significant changes compared to the unstimulated RLNs (15 mA group: 0.320 ± 0.123 mA vs. 0.315 ± 0.097 mA, P = 0.847; 20 mA group: 0.305 ± 0.101 mA vs. 0.300 ± 0.103 mA, P = 0.758). Similar outcomes were shown in average evoked EMG amplitude (15 mA group: 1,026 ± 268 μV vs. 1,021 ± 273 μV, P = 0.834; 20 mA group: 1,162 ± 275 μV vs. 1,200 ± 258 μV, P = 0.148). However, obvious acute microstructural morphological changes were observed in the nerves that were stimulated with 20 mA., Conclusions: A stimulation intensity less than 15 mA might be safe for IONM of the RLN.

Purpose: To compare the clinicopathological data and long-term survival of gastric cancer patients in China and Korea., Materials and Methods: Patients who had undergone gastrectomy for gastric cancer between 1998 and 2009 in 2 high-volume institutions in both China (n=1,637) and Korea (n=2,231) were retrospectively evaluated. Clinicopathological variables, overall survival (OS), progression-free survival (PFS), and surgery-related complications were assessed for all patients and compared between the 2 institutions., Results: Chinese patients included in the study were significantly older and had a significantly lower body mass index (BMI) than the Korean patients. Esophagogastric junction tumors were more frequent in Chinese patients. However, the number of patients with stage I gastric cancer, the number of harvested lymph nodes, and the number of total gastrectomies were significantly higher in the Korean population. Korean patients also presented with fewer undifferentiated tumors than Chinese patients. Furthermore, Korean patients had prolonged OS and PFS for stage III cancers only. BMI, tumor-node-metastasis (TNM) stage, tumor invasion, number of positive lymph nodes, and distant metastases were all independent factors affecting OS and PFS., Conclusions: Although China and Korea are neighboring Asian countries, the clinicopathological characteristics of Chinese patients are significantly different from those of Korean patients. Korean gastric cancer patients had longer OS and PFS than Chinese patients. Influencing factors included TNM stage, tumor invasion, and lymph node metastasis.

The synthesis and characterization of four dinuclear 3d-4f complexes [M(II)Ln(III)(L)(DBM)3] (ZnDy = 1, CoY = 2, CoDy = 3·3.5CH3CN, CoGd = 4·3.5CH3CN) are reported (H2L = N,N'-dimethyl-N,N'-(2-hydroxy-3-methoxy-5-methyl-benzyl)ethylenediamine, DBM(-) = anion of 1,3-diphenyl-propane-1,3-dione). In each of the four complexes, the M(II) ion occupies the internal N2O2 site whereas the Ln(III) ion occupies the external O4 site. There are diphenoxo bridges between the M(II) and Ln(III) ions in these complexes. The remaining coordination sites are occupied by three DBM(-) anions. Direct current (dc) magnetic susceptibility measurements indicate the presence of intramolecular ferromagnetic interactions in complexes 3 and 4. The magnetic coupling constant, JCoGd, of complex 4 is estimated to be 0.26 cm(-1) (H = -2JCoGdSCoSGd). Alternating current (ac) magnetic susceptibility studies reveal that complexes 1 and 2 show field-induced single molecule magnet behavior, with ΔE values of 36.5 K and 8.56 K, respectively. Complex 3 shows frequency dependent out-of-phase signals, indicating the presence of a slow relaxation of the magnetization, whereas complex 4 does not display slow magnetization relaxation.

The synthesis and characterization of three isomorphous complexes [NiII(L)LnIII(DBM)₃] (Ln = Gd (1·2.5CH₃CN·0.5H₂O), Tb (2·2CH₃CN·0.5MeOH), and Dy (3·2CH₃CN·0.5MeOH·0.5H₂O)) are reported (H₂L = N,N'-dimethyl-N,N'-(2-hydroxy-3-methoxy-5-methylbenzyl)ethylenediamine, DBM⁻ = anion of 1,3-diphenylpropane-1,3-dione). The flexible ligand L²⁻ contains an N₂O₂-inner and an O₄-outer coordination site. There are diphenoxo bridges between NiII and LnIII ions in these complexes. The remaining coordination sites are occupied by DBM⁻ anions. Direct current (dc) magnetic susceptibility measurements indicate the presence of intramolecular ferromagnetic interactions in desolvated complexes 1-3. The magnetic coupling constant JNiGd in complex 1 is estimated to be 1.11 cm⁻¹ (H = -2JNiGdSNiSGd). Alternating current (ac) magnetic susceptibility studies reveal that complexes 2 and 3 show frequency-dependent out-of-phase signals, which indicate that they exhibit SMM behavior. The energy barriers for complexes 2 and 3 under a 2 kOe applied direct current (dc) magnetic field are estimated from Arrhenius plots to be 14.4 and 11.3 K, respectively.

A supramolecular strategy has been applied to construct two tetranuclear lanthanide complexes for investigating the magnetic properties of individual lanthanide ions. The Ln(III) complexes (Ln = Dy, Tb) display field-induced slow magnetization relaxation, typical of single-molecule magnet behavior. The four lanthanide ions in the molecules are well separated by distances of ca. 9 Å, and thus the slow magnetization relaxation should be assigned to single-ion magnet (SIM) behavior. Therefore, the present complexes are novel supramolecular aggregates of four isolated SIMs.

Objective: To explore the short-term outcomes and safety of complete mesocolic excision (CME) in elderly patients with colon cancer., Methods: The clinical pathological factors of 71 patients with colon cancer undergoing CME procedure by the same group of surgeons were analyzed retrospectively from November 2009 to February 2012. The elderly group(≥70 years) and the non-elderly group(<70 years) were compared regarding short-term outcomes and safety., Results: Similar extent of resection could be achieved in the elderly and non-elderly groups in terms of area of mesentery[(13 049±4332) vs. (13 163±4725) mm2, P=0.916], distance between the tumor and the high ligation site[(95±22) vs. (98±20) mm, P=0.516], distance between normal bowel and high ligation site [(130±25) vs. (128±25) mm, P=0.731], the length of colon [(262±60) vs. (245±49) mm, P=0.212], and lymph nodes retrieved(22.0±6.4 vs. 24.8±9.9, P=0.168). The mean operative time, intraoperative blood loss, postoperative complications, time to first flatus, time to first bowel movement, drainage removal time, diet resumption, drainage volume in three days after surgery, and hospital deaths showed no statistical significances(all P>0.05), while hospital stay and expenses of the elderly group were significantly increased(both P<0.01)., Conclusion: Elderly patients undergoing elective CME operation can achieve similar operative extent and lymph nodes harvest, and the surgical risk is not increased.

The synthesis and characterizations of a family of isomorphous [Mn(III)(2)M(III)(4)L(2)(μ(4)-O)(2)(N(3))(2)(CH(3)O)(2)(CH(3)OH)(4)(NO(3))(2)]·2H(2)O (M = Y(1), Gd(2), Tb(3), Dy(4)) are reported, where H(4)L = N,N'-dihydroxyethyl-N,N'-(2-hydroxy-4,5-dimethylbenzyl)ethylenediamine. They were obtained from the reactions of H(4)L with M(NO(3))(3)·6H(2)O, Mn(ClO(4))(2)·6H(2)O, NaN(3) and NEt(3) in a 1:1:1:2:2 molar ratio. The core structure consists of a Mn(2)M(4) unit. The four M(III) ions that are held together by two μ(4)-bridging oxygen atoms form a butterfly M(4) moiety. The M(4) core is further connected to the two five-coordinate trigonal-bipyramidal Mn(III) ions via one μ(4)-O(2-), two alkyloxo and one methoxo triple bridges. Magnetic susceptibility measurements indicate the presence of intramolecular antiferromagnetic interactions in complex 2, and overall intramolecular ferromagnetic interactions in complexes 3 and 4. The alternating current (AC) magnetic susceptibility studies revealed that complexes 3 and 4 showed frequency-dependent out-of-phase signals, which indicates that they exhibit slow relaxation of the magnetization.

An FTIR spectrum fitting algorithm based on continuous wavelet transform is proposed. In calculating the factor of difference spectrum, the algorithm takes into account both the original spectrum and its continuous wavelet transformed spectra, which effectively overcomes the problem of reference peak selection and manual factor selection in most commercial software. The detailed discussions on wavelet scale, order and basis are included. The spectral fitting is performed on six wavelet basis functions and the obtained scale factor is used to quantify the content of liquor, and the corresponding mean absolute error ranges from 0.047 to 0.072, and the standard deviation ranges from 0.056 to 0.091. Experimental results show that the CWT combined with least squares fitting provides an accurate and reliable new method for FTIR spectral subtraction.

Objective: To compare the short-term efficacy and safety between complete mesocolic excision (CME) and traditional radical resection in colon cancer., Methods: Between January 2008 and August 2011, 92 patients undergoing elective open surgery for colon were included in the study. CME was performed in 54 patients in the period from November 2009 to August 2011. The other 38 patients underwent traditional radical resection from January 2008 to October 2009. Short-term outcomes were compared between the patients of two different time periods., Results: Lymph nodes retrieved in the CME group (22.2 ± 8.0) were significant more than that in the control group (18.6 ± 4.7)(P<0.05). In patients with stage III cancer, CME group was associated with higher lymph node counts (23.8 ± 7.6 vs. 16.7 ± 3.6, P<0.01), however, there were no significant differences for those with stage I and stage II cancer (P>0.05). The number of positive lymph nodes and metastatic lymph node ratio (LNR) for stage III patients in two groups were not significantly different (P>0.05). There were no differences in operation time, time to first bowel movement, hospital stay, and postoperative complications between the two groups (P>0.05). However, intraoperative blood loss in the CME group was significantly reduced (median, 100 vs. 115 ml, P<0.05)., Conclusions: CME can achieve en-bloc resection of the tumor and mesocolon, and have optimal lymph nodes harvest. Despite wider resection extent with CME technique, the surgical risk and postoperative complications are not increased and the short-term efficacy is good.

Objective: To evaluate the learning curve of complete mesocolic excision(CME) for colon cancer., Methods: Clinical data of 75 cases in whom CME was performed by a group of surgeons in the Department of Gastrointestinal Surgery, Peking University People's Hospital from November 2009 to June 2011 were reviewed. The patients were divided into three groups(groups A, B, C, 25 cases in each group) by operative chronologic sequence., Results: There were no significant differences in age, sex, preoperative staging, cancer location, operation history of abdomen, ASA among the three groups(P>0.05). The operative time in group A was (205.4 ± 53.2) min and decreased to (180.4 ± 29.7) min in group B and (169.8 ± 41.3) min in group C (P<0.05). The postoperative hospital stay decreased from (17.8 ± 10.9) d in group A to(12.9 ± 4.1) d in group B and(11.0 ± 3.5) d in group C(P<0.05). The postoperative complication rate decreased from 32%(8/25) in group A and 36%(9/25) to 8%(2/25) in group C. The specimen quality was superior in group C compared to group A (WEST grade C above were 20 and 11 respectively, P<0.05). There were no significant differences in intraoperative bleeding, time to first flatus, postoperative fasting time, number of retrieved lymph nodes among the three groups(P>0.05)., Conclusion: From the learning curve of CME, surgeons can learn CME skill after performing 25 cases.

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.

Aim: To investigate the effect of omega-3 fatty acid parenteral supplementation postoperatively on clinical outcomes and immunomodulation in colorectal cancer patients., Methods: Forty-two patients undergoing radical colorectal cancer resection with an indication for total parenteral nutrition postoperatively were enrolled in this prospective, double-blind, randomized, controlled study. Patients received total parenteral nutrition supplemented with either soybean oil (LCT; Intralipid, Fresenius-Kabi, SO group, n = 21) or a combination of omega-3 fish oil and soybean oil (LCT:fish oil = 5:1, fish oil; Omegaven, Fresenius-Kabi, FO group, n = 21), up to a total of 1.2 g lipid/kg per day for 7 d postoperatively. A same volume calorie and nitrogen was administrated. Routine blood test, biochemistry, systemic levels of IL-6 and TNF-alpha, percentage of CD3+, CD4+, and CD8+ lymphocytes were evaluated preoperatively and on postoperative d 1 and 8. Patient outcome was evaluated considering mortality during the hospital stay, length of postoperative hospital stay, and occurrence of infectious complications., Results: Both lipid regimens were well tolerated. No differences between the two groups were noticed in demographics, baseline blood test, biochemistry, serum levels of IL-6 and TNF-alpha, percentage of CD4+, CD8+ lymphocytes, and ratios of CD4+/CD8+. Compared with those on postoperative d 1, serum IL-6 levels on postoperative d 8 were significantly depressed in the FO group than in the reference group (-44.43 +/- 30.53 vs -8.39 +/- 69.08, P = 0.039). Simultaneously, the ratios of CD4+/CD8+ were significantly increased in the FO group (0.92 +/- 0.62 vs 0.25 +/- 1.22, P = 0.035). In addition, depression of serum TNF-alpha levels (-0.82 +/- 2.71 vs 0.27 +/- 1.67, P = 0.125) and elevation of CD3+ and CD4+ lymphocyte percentage (12.85 +/- 11.61 vs 3.84 +/- 19.62, P = 0.081, 17.80 +/- 10.86 vs 9.66 +/- 17.55, P = 0.084, respectively) were higher in the FO group than in the reference group. Patients in the FO group tended to need a shorter postoperative hospital stay (17.45 +/- 4.80 d vs 19.62 +/- 5.59 d, P = 0.19). No statistically significant difference was found when stratified to mortality and occurrence of infectious complications., Conclusion: Postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcomes in colorectal cancer patients undergoing radical resection by lowering the magnitude of inflammatory responses and modulating the immune response.

The cytokine erythropoietin (Epo) is tissue-protective in preclinical models of ischemic, traumatic, toxic, and inflammatory injuries. We have recently characterized Epo derivatives that do not bind to the Epo receptor (EpoR) yet are tissue-protective. For example, carbamylated Epo (CEpo) does not stimulate erythropoiesis, yet it prevents tissue injury in a wide variety of in vivo and in vitro models. These observations suggest that another receptor is responsible for the tissue-protective actions of Epo. Notably, prior investigation suggests that EpoR physically interacts with the common beta receptor (betacR), the signal-transducing subunit shared by the granulocyte-macrophage colony stimulating factor, and the IL-3 and IL-5 receptors. However, because betacR knockout mice exhibit normal erythrocyte maturation, betacR is not required for erythropoiesis. We hypothesized that betacR in combination with the EpoR expressed by nonhematopoietic cells constitutes a tissue-protective receptor. In support of this hypothesis, membrane proteins prepared from rat brain, heart, liver, or kidney were greatly enriched in EpoR after passage over either Epo or CEpo columns but covalently bound in a complex with betacR. Further, antibodies against EpoR coimmunoprecipitated betacR from membranes prepared from neuronal-like P-19 cells that respond to Epo-induced tissue protection. Immunocytochemical studies of spinal cord neurons and cardiomyocytes protected by Epo demonstrated cellular colocalization of Epo betacR and EpoR. Finally, as predicted by the hypothesis, neither Epo nor CEpo was active in cardiomyocyte or spinal cord injury models performed in the betacR knockout mouse. These data support the concept that EpoR and betacR comprise a tissue-protective heteroreceptor.

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did not increase the hematocrit of mice or rats. AsialoEPO appeared promptly within the cerebrospinal fluid after i.v. administration; intravenously administered radioiodine-labeled asialoEPO bound to neurons within the hippocampus and cortex in a pattern corresponding to the distribution of the EPO receptor. Most importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection.

This unit contains three protocols that can be used to determine iNOS expression in mouse macrophage-like cells, RAW 264.7, by measuring end product, protein, and mRNA. A bacterial product, lipopolysaccharide (LPS), stimulates iNOS expression in RAW 264.7 cells.

Treatment of human colorectal cancer cells HT29 with interleukin 1beta (IL-1beta) induces expression of the multidrug resistance protein (MRP1) gene encoding the ATP-dependent glutathione S-conjugate export (GS-X) pump and the gamma-glutamylcysteine synthetase (gamma-GCSh) gene encoding heavy (catalytic) subunit of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the biosynthesis of glutathione (GSH). The induction can be suppressed by N(G)-methyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS). These results suggest that IL-1beta-mediated MRP1 and gamma-GCSh induction involve nitric oxide (NO) -related signaling. Further supports to the involvement of NO in the induction of MRP1 and gamma-GCSh expression are made by the following observations. (i) Expression of MRP1 and gamma-GCSh genes were induced by treating the cells with NO donors, i.e., S-nitro-N-acetyl-D,L-penicillamide (SNAP) and S-nitroso-L-glutathione, in a concentration-dependent manner. (ii) Ectopic expression of inducible NOS (iNOS) activity by transfecting expressible recombinant iNOS cDNA encoding functional iNOS but not the nonfunctional version resulted in elevated expression of MRP1 and gamma-GCSh. We also demonstrated that HT-29 cells treated with either 1L-1beta or SNAP induced ceramide production, and addition of C2 or C6 ceramides into cultured HT-29 cells resulted in induction of gamma-GCSh but not MRP1 expression. Collectively, our results demonstrate that induction of MRP1 and gamma-GCSh by IL-1beta is regulated, at least in part, by an NO-related signaling, and induction of gamma-GCSh is by NO-related ceramide signaling., (Copyright 2000 Wiley-Liss, Inc.)

In Salmonella typhimurium, ahpC encodes subunit C of alkyl hydroperoxide reductase, an enzyme that reduces organic peroxides. Here, we asked if ahpC could protect cells from reactive nitrogen intermediates (RNI). Salmonella disrupted in ahpC became hypersusceptible to RNI. ahpC from either Mycobacterium tuberculosis or S. typhimurium fully complemented the defect. Unlike protection against cumene hydroperoxide, protection afforded by ahpC against RNI was independent of the reducing flavoprotein, AhpF. Mycobacterial ahpC protected human cells from necrosis and apoptosis caused by RNI delivered exogenously or produced endogenously by transfected nitric oxide synthase. Resistance to RNI appears to be a physiologic function of ahpC. ahpC is the most widely distributed gene known that protects cells directly from RNI, and provides an enzymatic defense against an element of antitubercular immunity.

We have synthesized more than 80 novel triterpenoids, all derivatives of oleanolic and ursolic acid, as potential anti-inflammatory and chemopreventive agents. These triterpenoids have been tested for their ability to suppress the de novo formation of two enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2), using IFN-gamma-stimulated primary mouse macrophages or lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as assay systems. Two synthetic oleananes, 3,12-dioxoolean-1-en-28-oic acid (TP-69) and 3,11-dioxoolean-1,12-dien-28-oic acid (TP-72), were highly active inhibitors of de novo formation of both iNOS and COX-2. Both TP-69 and TP-72 blocked the increase in iNOS or COX-2 mRNA induced by IFN-gamma or LPS. In addition, TP-72 suppressed NF-KB activation in primary macrophages treated with the combination of IFN-gamma and LPS or IFN-gamma and tumor necrosis factor. The 3-alpha(axial)-epimer of ursolic acid suppressed de novo formation of COX-2, in contrast to naturally occurring 3-beta(equatorial)-ursolic acid. Inhibitory effects of TP-69 or TP-72 on iNOS formation were not blocked by the glucocorticoid receptor antagonist RU-486, indicating that these triterpenoids do not act through the glucocorticoid receptor, nor does TP-72 act as an iNOS or COX-2 enzyme inhibitor when added to RAW cells in which synthesis of these two enzymes in response to LPS has already been induced. It may be possible to develop triterpenoids as useful agents for chemoprevention of cancer or other chronic diseases with an inflammatory component.