Astrocyte PERK and IRE1 Signaling Contributes to Morphine Tolerance and Hyperalgesia through Upregulation of Lipocalin-2 and NLRP3 Inflammasome in the Rodent Spinal Cord.

BACKGROUND: Endoplasmic reticulum stress plays a crucial role in the pathogenesis of neuroinflammation and chronic pain. This study hypothesized that PRKR-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme type 1 (IRE1) regulate lipocalin-2 (LCN2) and Nod-like receptor family pyrin domain containing 3 (NLRP3) expression in astrocytes, thereby contributing to morphine tolerance and hyperalgesia. METHODS: The study was performed in Sprague-Dawley rats and C57/Bl6 mice of both sexes. The expression of LCN2 and NLRP3 was assessed by Western blotting. The tail-flick, von Frey, and Hargreaves tests were used to evaluate nociceptive behaviors. Chromatin immunoprecipitation was conducted to analyze the binding of activating transcription factor 4 (ATF4) to the promoters of LCN2 and TXNIP. Whole-cell patch-clamp recordings were used to evaluate neuronal excitability. RESULTS: Pharmacologic inhibition of PERK and IRE1 attenuated the development of morphine tolerance and hyperalgesia in male (tail latency on day 7, 8.0 ± 1.13 s in the morphine + GSK2656157 [10 µg] group vs. 5.8 ± 0.65 s in the morphine group; P = 0.04; n = 6 rats/group) and female (tail latency on day 7, 6.0 ± 0.84 s in the morphine + GSK2656157 [10 µg] group vs. 3.1 ± 1.09 s in the morphine group; P = 0.0005; n = 6 rats/group) rats. Activation of PERK and IRE1 upregulated expression of LCN2 and NLRP3 in vivo and in vitro. Chromatin immunoprecipitation analysis showed that ATF4 directly bound to the promoters of the LCN2 and TXNIP. Lipocalin-2 induced neuronal hyperexcitability in the spinal cord and dorsal root ganglia via melanocortin-4 receptor. CONCLUSIONS: Astrocyte endoplasmic reticulum stress sensors PERK and IRE1 facilitated morphine tolerance and hyperalgesia through upregulation of LCN2 and NLRP3 in the spinal cord.

Clinical observations in treatment of lower extremity varicose veins with trigger points acupuncture.

OBJECTIVES: To observe the effect of the acupuncture of myofascial trigger points (MTrPs) in the treatment of lower extremity varicose veins (LEVVs). METHODS: Overall, 260 patients with LEVVs participated in this study. LEVVs were selected based on diagnostic criteria of Clinical, Etiology, Anatomy, and Pathophysiology levels 2-5 and classified into six types on the basis of their anatomical positions. The MTrPs in the lower extremities were localized in accordance with the classification of LEVVs and treated by MTrPs acupuncture combined with self-massage and self-stretching. The interval between each treatment was 2 weeks to 1 month, depending on needling pain tolerance of each patient. An in-house evaluation was used to estimate the proportion of varicose veins in the lower limbs and their accompanying symptoms. The treatment effect was evaluated before each treatment and at 1-year follow-up. RESULTS: The mean evaluation score of LEVVs before the treatment course was 3.66 ± 1.19. After the course, this reduced to 1.18 ± 0.97, with the following response rates: 85% for excellent and good and 15% for medium. After 1-year follow-up, the mean evaluation score of all patients was 1.11 ± 0.92, with the following response rates: 87% for excellent and good, and 13% for medium. CONCLUSIONS: In some patients, MTrP acupuncture could cure LEVVs and its accompanying symptoms. These LEVVs are probably caused by fascia tension as a pre-pathology induced by the MTrPs.

Effect of Conventional and "Dental Truth or Dare" Board Game on Oral Hygiene Knowledge and Oral Hygiene Status of Preschool Children.

Aim: To compare the benefits of didactic versus board game-based oral health instruction on oral health knowledge (OHK) and oral hygiene of preschool students. Materials and Methods: Participants were selected through computer-assisted randomization. (Eighty students were selected in both the 3- to 4-year-old and 5- to 6-year-old age groups, respectively, for a total of 160 participants). Forty participants of each age group were assigned randomly to Group A (PowerPoint® presentation) and 40 to Group B ("Dental Truth or Dare" board game-based instruction). OHK and debris index-simplified (DI-S) were assessed at preintervention, and at 1-week, 1-month, and 3-month postintervention timepoints. Results: OHK scores increased significantly in the 3- to 4-year-old subset of Group A at the 1-week postintervention timepoint but declined and approximated the baseline value at the 3-month timepoint. In contrast, compared to baseline, significantly improved OHK scores were observed at all 3 timepoints in both age groups in Group B, and were especially pronounced in the 5- to 6-year-old subset. Although the 3-month scores were slightly lower than the 1-week scores, they were well above baseline values. Pre- and postintervention DI-S scores did not change significantly in the 3- to 4-year-old subset of Group A. However, significant increases in good DI-S scores and decreases in fair and poor scores were observed between baseline and 3-month timepoints in the 5- to 6-year-old subset of Group A and in both age subsets of Group B (P ≤ 0.05). OHK and DI-S scores were significantly higher among 5-6-year-olds than among the 3-4-year olds in both Groups A and B (P ≤ 0.05). Age and board game intervention were the main determinants of higher OHK and lower DI-S scores. The impact of intervention mode (board game) was greater than that of age. Conclusion: Board game-based oral hygiene education conferred significant short-term retention, enhanced OHK, and reduced DI-S. We conclude that gaming is an easily implemented and cost-effective educational tool for the improvement of oral hygiene in preschool children.

Development and validation of a model for predicting the risk of suicide in patients with cancer.

OBJECTIVE: The objective of this study was to establish a nomogram model to predict SI in patients with cancer and further evaluate its performance. METHOD: This study was performed among 390 patients in oncology departments of Affiliated Hospital of Nantong University from April 2020 to January 2021. Of these, eligible patients who were diagnosed with cancer were split into training and validation cohorts according the ratio of 2:1 randomly. In the training cohort, multivariate regression was performed to determine the independent variables related to SI. A nomogram was built incorporating these variables. The model performance was evaluated by an independent validation cohort. RESULTS: The prevalence of SI in patients with cancer was 22.31% and 19.23% in training and validation cohorts, respectively. The nomogram model suggested independent variables for SI, including depression, emotional function, time after diagnosis, family function and educational status. The area under the curve (AUC) was 0.93 (95%CI, 0.90-0.97) and 0.82 (95%CI, 0.74-0.90) in training and validation cohorts respectively, which indicated good discrimination of the nomogram in predicting SI in cancer patients. The p-value of the goodness of fit (GOF) test was 0.197 and 0.974 in training and validation cohorts respectively, suggesting our nomogram model has acceptable calibration power, and the calibration curves further indicated good calibration power. CONCLUSION: In conclusion, the nomogram model for predicting individualized probability of SI could help clinical caregivers estimate the risk of SI in patients with cancer and provide appropriate management.

Suicide rates among people with serious mental illness: a systematic review and meta-analysis.

BACKGROUND: People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia). METHODS: PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex. RESULTS: Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3-406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5-417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4-1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60-2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7-50.4)]. CONCLUSIONS: The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

Application of improved Glasgow coma scale score as switching point for sequential invasive-noninvasive mechanical ventilation on chronic obstructive pulmonary disease (COPD) with respiratory failure.

BACKGROUND: To compare the efficacy and feasibility of using a modified Glasgow coma scale (GCS) score of 13 or 15 as the criterion for switching chronic obstructive pulmonary disease (COPD) patients with respiratory failure to sequential invasive-noninvasive ventilation. METHODS: COPD patients with respiratory failure who had undergone endotracheal intubation and invasive mechanical ventilation (IMV) between June 2017 and June 2020 at 4 different hospitals in China were included. A total of 296 patients were randomly divided into 2 groups. In group A, the patients were extubated and immediately placed on noninvasive ventilation (NIV) when the modified GCS score reached 13. In group B, the same was done when the modified GCS score reached 15. RESULTS: No significant differences in the mean blood pressure, oxygenation index, arterial partial pressure of oxygen, and arterial partial pressure of carbon dioxide were seen between groups A and B before extubation and 3 hours after NIV. The re-intubation times were also similar in the 2 groups. Compared to group B, the length of hospital stay, incidence of ventilator associated pneumonia, and time of invasive ventilation were all significantly lower in group A (P = .041, .001, <.001). CONCLUSION: Using a modified GCS score of 13 as the criterion for switching from IMV to NIV can significantly reduce the duration of IMV, length of hospital stay, and incidence of ventilator associated pneumonia in COPD patients with respiratory failure.

The significance of cognitive-behavioral therapy on suicide: An umbrella review.

BACKGROUND: Suicide becomes a widespread public health concern. Cognitive-behavioral therapy (CBT) is used to correct negative thoughts and behaviors of patients at risk of suicide. The aim of this research is to summarize and evaluate the existing evidence to explore the impact of CBT on suicide. METHOD: We conducted a systematic searched in PubMed, Web of Science, Cochrane database from the first available year to March 2021. The methodological quality was evaluated by AMSTAR-2 tool, and the evidence quality was evaluated by GRADE classification. We summarized all the comparative effects of CBT on suicide, and used forest plots to describe the impact of CBT on suicide related outcomes included suicidal ideation, suicide attempts. The random effects model was used to summarize data. RESULTS: Nine systematic reviews and meta-analysis were included. Most of the systematic reviews and meta-analysis were of medium methodological and evidence quality. The impact of CBT on suicide outcomes could be divided into the following two categories: CBT reduced levels of suicidal ideation (SMD -0.28, 95 % CI -0.36 to -0.21), CBT relieved suicide attempts (RR 0.77, 95 % CI 0.69 to 0.87). CONCLUSION: Based on the current evidence, CBT could relieve suicide, including suicide ideation, suicide attempts. CBT is scalable and cost-effective. It is helpful for health professionals to formulate personalized CBT programs, promote clinical and community applications and integrate them into comprehensive suicide interventions and prevention strategies.

Relationship between depressive symptoms and internet usage time among adolescents: Results from a nationwide survey.

Adolescent depression is becoming a public health problem. In this study the association between depressive symptoms and internet usage time in adolescents was examined, with data collected from the China Education Tracking Survey (CEPS). The survey is publicly available and carried out nationwide. A logistic regression analysis was conducted with odds ratios (OR) and 95% confidence intervals (CI), the subgroup analysis examined the relationships between internet usage time and depressive symptoms. A total of 10,705 adolescents were involved, where 46.4% of them are caught by the internet for more than two hours per day. Adolescents keeping on the internet for 6-8 h per day were reported to have higher odds of depressive symptoms than adolescents who were free from it with the confounders of individual, family, and school adjusted, which were observed among groups with a medium family economic status without living with their father and with a sleep time less than nine hours. The results revealed that adolescents spending more time online had a higher risk of experiencing depression symptoms. This study suggested that it is helpful for mental health professionals to evaluate and develop prevention interventions for depressive symptoms in adolescents promptly through monitoring and managing online time.

COVID-19 in patients with systemic lupus erythematosus: A systematic review.

The objectives of the study were to review the articles to identify (a) the epidemiology of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19); (b) the clinical characteristics of SLE patients with COVID-19; (c) the treatment of COVID-19 in SLE patients; and (d) the impact of COVID-19 pandemic on SLE patients. PubMed was systematically reviewed for literature published from December 2019 to June 2021. Our search was limited to human studies, with language restriction of English. Studies were included if they reported COVID-19 in SLE patients. Our systematic review included 52 studies. The prevalence of COVID-19 infection ranged from 0.0% to 18.1% in SLE patients, and the hospitalisation rates ranged from 0.24% to 10.6%. COVID-19 infection is likely to mimic SLE flare. Hydroxychloroquine (HCQ) was ineffective in prevention of COVID-19, and SLE patients with COVID-19 faced difficulty in healthcare access, had financial constraints and suffered from psychological distress during the pandemic. The pandemic had a significant effect on mental and physical health. Adequate healthcare access, along with containment policies, social distancing measures and psychological nursing was required.

Tripartite intensive intervention for prevention of rebleeding in elderly patients with hypertensive cerebral hemorrhage.

BACKGROUND: Hypertensive cerebral hemorrhage (HICH) is the rupture and bleeding of vessels of the cerebral parenchyma caused by continuously elevated or violently fluctuating blood pressure. The condition is characterized by high disability and high mortality. Hematoma formation and resulting space-occupying effects following intracerebral hemorrhage are among the key causes of impaired neurological function and disability. Consequently, minimally invasive clearance of the hematoma is undertaken for the treatment of HICH because it can effectively relieve intracranial hypertension. Therefore, special attention should be given to the quality of medical and nursing interventions in the convalescent period after minimally invasive hematoma clearance. AIM: The study aim was to determine the value of intensive intervention, including doctors, nurses, and patient families, for the prevention of rebleeding in elderly patients with HICH during the first hospitalization for rehabilitation after the ictal event. METHODS: A total of 150 elderly HICH patients with minimally invasive hematoma evacuation in our hospital between May 2018 and May 2020 were selected and equally divided into two groups of 75 each by their planned intervention. The control group was given conventional nursing intervention and the observation group was given tripartite intensive intervention. The length of hospital stay, cost, complication rate, satisfaction rate, and rebleeding rate during hospitalization were recorded. Changes in cerebral blood flow indicators were recorded in both groups. Changes in the National Institutes of Health Stroke Scale (NIHSS) score, quality of life index (QLI) score, and health behavior score were evaluated at the National Institutes of Health. RESULTS: Duration of hospitalization was shorter in the in the observation group than in the control group, the hospitalization cost was less than in the control group, and the rate of rebleeding during hospitalization was lower than in the control group (all P < 0.05). There were no significant differences between the two groups before treatment (all P > 0.05). The mean flow rate (Qmean) and mean velocity (Vmean) of the two groups increased (P < 0.05), and the dynamic resistance and peripheral resistance decreased (P < 0.05). The Qmean and Vmean in the intervention group were higher than those in the control group (P < 0.05). Moreover, the dynamic resistance and peripheral resistance of the blood vessels were also lower in the intervention group than in the control group (P < 0.05). The difference in health behavior scores between the two groups before treatment was not significant (P > 0.05). In both groups, the scores for healthy behaviors such as emotion control, medication adherence, dietary management, exercise management, and self-monitoring were higher after than before treatment (P < 0.05), and the scores of healthy behaviors in the intervention group were higher than those in the control group (P < 0.05). There was no significant difference in the NIHSS and QLI scores between the two groups before treatment (P > 0.05). The QLI scores of the two groups increased (P < 0.05), and the NIHSS scores decreased (P < 0.05). The QLI scores of the intervention group were higher than those of the control group (P < 0.05), and the NIHSS score was correspondingly lower than that of the control group (P < 0.05). The incidence of respiratory infections, pressure sores, central hyperpyrexia, and deep venous thrombosis was lower in the intervention group than in the control group. Accordingly, the satisfaction rate was higher in the treatment group than that in the control group (P < 0.05). CONCLUSION: Intensive intervention by doctors, nurses, and families of elderly patients with HICH reduced the rate of rebleeding during hospitalization. It also reduced the incidence of complications, promoted rehabilitation, improved the quality of life, and enhanced nerve function. Additionally, it improved satisfaction and promoted healthy behaviors.

Incidence of suicide mortality among childhood cancer survivors: A population-based retrospective study.

The aim of our study was to investigate the suicide rates among childhood cancer survivors and assess factors associated with higher suicide risk. A review of data from Surveillance, Epidemiology, and End Results (SEER) program from 1975 to 2016 was performed for this study. This program is based on the US population and is supported by the US National Cancer Institute (NCI). Survivors diagnosed with childhood cancer were recorded. There were 40 suicides among 567,233 person-years, giving a suicide rate of 7.1 per 100,000 person-years. Compared with cancer diagnosed between 10 and 14 years old, survivors with cancer diagnosed between 0 and 4 years old had lower suicide risk. Females had a lower risk of suicide than males. Compared with survivors of thyroid cancer, the aHRs were 0.16 for acute lymphocytic leukemia, 0.15 for nodal Hodgkin's lymphoma, 0.14 for brain cancers and 0.09 for kidney cancers. Most suicides occurred after 15 years old. Suicide was a problem for survivors, especially those with thyroid cancer. Beside treating patients holistically, early psychological interventions such as communicating effectively, providing social support and follow-up care related to psychological health are needed.

Inhibiting BDNF/TrkB.T1 receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia.

BACKGROUND: Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. A truncated isoform of the tropomyosin receptor kinase B (TrkB) receptor TrkB.T1, as a high-affinity receptor of BDNF, is upregulated in multiple nervous system injuries, and such upregulation is associated with pain. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB.T1 in the peripheral nervous system (PNS) during PHN is unclear. This study aimed to investigate whether BDNF/TrkB.T1 contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs). METHODS: Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by detecting the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB.T1-ASIC3 signaling inhibition on the behavior, neuronal excitability, and inflammatory response during RTX-induced PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells. RESULTS: RTX injection induced mechanical allodynia and upregulated the protein expression of BDNF, TrkB.T1, ASIC3, TRAF6, nNOS, and c-Fos, as well as increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the abovementioned effects of RTX, except for BDNF and TrkB.T1 protein expression. In addition, inhibition of TrkB.T1 blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling, and hyperexcitability of neurons. RTX-induced BDNF upregulation was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level, and enhanced IL-6, IL-1ß, and TNF-α levels in PC-12 cells, which was blocked by shRNA-ASIC3 transfection. CONCLUSION: These findings demonstrate that inhibiting BDNF/TrkB.T1 reduced inflammation, decreased neuronal hyperexcitability, and improved mechanical allodynia through regulating the ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.

Peripheral immunological features of COVID-19 patients in Taizhou, China: A retrospective study.

BACKGROUND: Abnormal peripheral immunological features are associated with the progression of coronavirus disease 2019 (COVID-19). METHODS: Clinical and laboratory data were retrieved in a cohort of 146 laboratory-confirmed COVID-19 patients. Potential risk factors for the development of severe COVID-19 were evaluated. RESULTS: On admission, lymphocytes, CD3+, CD4+ and CD8+ T cells, eosinophils, and albumin and pre-albumin were dramatically lower, whereas neutrophils, and interleukin (IL)-10, C-reactive protein (CRP), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly higher in severe cases. By the second week after discharge, all variables improved to normal levels. Covariate logistic regression results showed that the CD8+ cell count and CRP level were independent risk factors for severe COVID-19. CONCLUSION: Lower peripheral immune cell subsets in patients with severe disease recovered to normal levels as early as the second week after discharge. CD8+ T cell counts and CRP levels on admission are independent predictive factors for severe COVID-19.

Association between social support and suicidal ideation in patients with cancer: A systematic review and meta-analysis.

OBJECTIVE: To quantitatively examine the relationship between social support and suicidal ideation (SI) among patients with cancer and identify the moderators that influence the magnitude of this association. METHODS: Publications were searched in PubMed, PsycINFO, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from database inception to May, 2020. Correlation coefficients (r) were chosen as the effect size with a random model to evaluate the overall effect size between social support and SI in patients with cancer. To assess statistical heterogeneity, we examined potential moderator variables on the social support and SI. RESULTS: A total of 881 studies were identified in initial search, and twelve studies were eligible. A negative, small but significant correlation (r = -0.22, 95% CIs: -0.30,-0.14, p < 0.001) was observed between social support and SI in patients with cancer, with a significant heterogeneity (I2  = 95.24%, Q = 231.27, p < 0.001). Moderator analyses indicated that race/ethnicity (Q(1) = 8.4, p < 0.05) and measurements of social support (Q(3) = 9.78, p < 0.05) and SI (Q(3) = 9.69, p < 0.05) significantly moderate the effect size between social support and SI. CONCLUSION: Taken together, we found a negative yet significant association between social support and SI in patients with cancer, which supported the importance of social support for the prevention of SI in patients with cancer.

Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes.

BACKGROUND: Astrocytes are highly glycolytic cells that play a crucial role in chronic pain. Recently it has been found that inflammation and metabolism are related to the inflammatory stimuli closely that cause cellular metabolic changes. Pyruvate kinase M2 (PKM2) is a critical metabolic kinase in aerobic glycolysis or the Warburg effect. Besides, it also plays a crucial role in cell proliferation and signal transduction, but its role in astrocytes is still unclear. METHODS: The chronic inflammatory pain model was set up by intraplantar injection of complete Freund's adjuvant (CFA) in Sprague Dawley (SD) rats as well as the cell model was constructed by lipopolysaccharide-treated primary astrocytes. Von Frey filament stimulation was used to continuously observe the changes of pain behavior in rats after modeling. Then, immunofluorescence staining and Western blot tests were used to observe the expression levels of glial fibrillary acidic protein (GFAP), pyruvate kinase (PKM2), signal transducers and activators of transcription 3 (STAT3) and high mobility group box-1 protein (HMGB1). After that, specific kits measured lactate contents. Finally, we observed the platelet-rich plasma's (PRP) effect on mechanical hyperalgesia in rats with inflammatory pain induced by CFA and its effect on related signal molecules. RESULTS: We found that in the CFA-induced inflammatory pain model, astrocytes were significantly activated, GFAP was increased, PKM2 was significantly up-regulated, and the glycolytic product lactate was increased. Also, intrathecal injection of PRP increased the pain threshold, inhibited the activation of astrocytes, and decreased the expression of PKM2 and aerobic glycolysis; in LPS-activated primary astrocytes as an in vitro model, we found PKM2 translocation activationSTAT3 signaling resulted in sustained activation of astrocyte marker GFAP, and the expression level and localization of p-STAT3 were correlated with PKM2. PRP could inhibit the activation of astrocytes, reduce the expression of PKM2 and the expression levels of glycolysis and GFAP, GLUT1, and p-STAT3 in astrocytes. CONCLUSIONS: Our findings suggest PKM2 not only plays a glycolytic role in astrocytes, but also plays a crucial role in astrocyte-activated signaling pathways, and PRP attenuates CFA induced inflammatory pain by inhibiting aerobic glycolysis in astrocytes, providing a new therapeutic target for the treatment of inflammatory pain.

Incidence of suicide death in patients with cancer: A systematic review and meta-analysis.

BACKGROUND: Growing evidence indicated the higher risk of suicide in cancer survivors compared with general population. Our aim is to systematically quantify the extent of suicide death and identify risk factors associated with the incidence of suicide in cancer patients. METHODS: We conducted a meta-analysis of relevant studies published in English or Chinese before May 20, 2020. Suicide rate and the number of suicide death were extracted. Our main outcome was suicide rate per 100,000 person-years with 95% CIs using random-effects model. RESULTS: The pooled incidence of suicide death was 39.72 per 100,000 person-years (95%CI, 33.91-46.52, I 2= 99.6%, P <0 .001). The suicide rate for cancer patients was higher in men (57.78, 95%CI, 47.31-70.56) than in women (14.47, 95%CI, 11.27-18.57). For both sexes combined, esophagus cancer had the highest rate of suicide (87.71, 95%CI, 27.42-280.54). By sex, suicide rates ranked first in males and females were pancreas cancer (195.70, 95%CI, 129.55-295.61) and esophagus cancer (18.34, 95%CI, 5.92-56.84), respectively. The highest suicide rate was 61.02(95%CI, 53.66-69.40) in Asia, and Oceania (24.07, 95%CI, 20.78-27.88) had lowest suicide rate. Suicide rate had a downward trend by years after diagnosis, with the first six months after cancer diagnosis clearly standing out (89.33, 95%CI, 50.64-157.58). LIMITATIONS: Included studies came from high-income countries and our results might not represent the suicide rate among cancer patients in low- and middle-income countries. CONCLUSIONS: The incidence of suicide among cancer patients was high despite the declined trend recent years, which emphasized psychological health aspects of interventions and perfecting suicide prevention programs.

Use of the modified Glasgow Coma Scale score to guide sequential invasive-noninvasive mechanical ventilation weaning in patients with AECOPD and respiratory failure.

Sequential invasive-noninvasive ventilation (NIV) improves the outcomes of patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no clear consensus on the optimal timing of the switch to sequential invasive-NIV in these patients. In the present study, a potential role for the modified Glasgow Coma Scale (GCS) score to guide sequential weaning was investigated. Patients with AECOPD and respiratory failure were prospectively recruited from three study centers (Wenling Hospital Affiliated to Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University and Changsha Central Hospital) between January 1st 2016 and December 31st 2018. Patients were randomly assigned to group A and B, with the switching point for sequential weaning strategy in the two groups being a modified GCS score ≥13 and 10 points, respectively. Each group included 240 patients. Baseline demographic characteristics were comparable in the two groups. The duration of invasive mechanical ventilation (IMV) in group A was significantly shorter than that in group B. However, there were no significant between-group differences with respect to the incidence of re-intubation, ventilator-associated pneumonia, in-hospital mortality or the length of hospital stay. Use of a modified GCS score ≥13 as the switching point for sequential invasive-NIV may help decrease the duration of IMV in patients with AECOPD and respiratory failure.

Up-regulation of miR-146b-3p protects septic mice with acute respiratory distress syndrome by inhibiting PI3K/AKT signaling pathway.

This study aimed to explore the role of miR-146b-3p in acute respiratory distress syndrome in septic mice. Ten mice were randomly selected as normal group (n = 10, without any treatment) and 60 septic mice with acute respiratory distress syndrome were divided into model group (n = 10, without any treatment), negative control (NC) mimic group (n = 10, injected with NC mimic), miR-146b-3p mimic group (n = 10, injected with miR-146b-3p mimic), si-NC group (n = 10, injected with PI3Kγ siRNA NC), si-PI3Kγ group (n = 10, injected with PI3Kγ silencing plasmid), and miR-146b-3p mimic + oe-PI3Kγ group (n = 10, injected with miR-146b-3p mimic + PI3Kγ overexpression plasmid). We found that miR-146b-3p negatively regulated PI3Kγ. Compared with normal group, model mice had decreased expression of miR-146b-3p, increased expressions of PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins, higher W/D ratio, and more serum IL-1ß and IL-18 content (all P < 0.05). All indicators in miR-146b-3p mimic group and si-PI3Kγ group were significantly improved as compared to model group (all P < 0.05). Over-expression of PI3Kγ could weaken the treatment effect of miR-146b-3p mimic in model mice. Therefore, up-regulation of miR-146b-3p can inhibit PI3K/AKT signaling pathway to improve acute respiratory distress syndrome in septic mice.

Erratum: Low-affinity neurotrophin receptor p75 of brain-derived neurotrophic factor contributes to cancer-induced bone pain by upregulating mTOR signaling.

[This corrects the article DOI: 10.3892/etm.2019.8097.].