Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Partial cellular reprogramming stably restores the stemness of senescent epidermal stem cells.

OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones' generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs.

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome.

OBJECTIVE: Evidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study. DESIGN: A retrospective cohort study. SETTING: Five ICUs with their totally 130 beds in Taiwan. PATIENTS OR PARTICIPANTS: ARDS patients under invasive ventilation. INTERVENTIONS: No. MAIN VARIABLES OF INTEREST: 28-D mortality. RESULT: Totally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT=6.7ml/kg), intermediate (mean VT=8.9ml/kg) and high (mean VT=11.2ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P=0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92-1.97, P=0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n=66 for each group), their outcomes were also not significantly different. CONCLUSION: Intermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome / El volumen tidal intermedio es una opción aceptable para pacientes ventilados con síndrome de dificultad respiratoria aguda

Objective Evidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study. Design A retrospective cohort study. Setting Five ICUs with their totally 130 beds in Taiwan. Patients or participants ARDS patients under invasive ventilation. Interventions No. Main variables of interest 28-D mortality. Result Totally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT=6.7ml/kg), intermediate (mean VT=8.9ml/kg) and high (mean VT=11.2ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P=0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92–1.97, P=0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n=66 for each group), their outcomes were also not significantly different. Conclusio Intermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials (AU)

Objetivo La evidencia solo demuestra que el volumen tidal (VT) bajo supera al alto para el síndrome de dificultad respiratoria aguda (ARDS). La VT intermedia es un escenario común para los pacientes con ARDS y se ha demostrado que es tan eficaz como la VT baja en pacientes sin ARDS. No se ha estudiado la eficacia de la VT intermedia en el ARDS y es el objetivo de este estudio. Diseño Un estudio de cohorte retrospectivo. Ámbito Cinco UCI con un total de 130 camas en Taiwán. Pacientes o participantes Pacientes con ARDS bajo ventilación invasiva. Intervenciones No. Variables de interés principales Mortalidad 28-D. Resultado Un total de 382 pacientes, con 6958 configuraciones de ventilador elegibles para protección pulmonar, se clasificaron en bajo (VT medio=6,7ml/kg), intermedio (VT medio=8,9ml/kg) y alto (VT medio=11,2ml/kg). Grupos de VT. Con un ARDS inicial similar y una gravedad en la UCI, los grupos de VT intermedia y baja no difirieron en la mortalidad 28-D (47% vs. 63%, p=0,06) u otros resultados como mortalidad 90-D, días sin ventilador, dependencia del ventilador índice. El análisis multivariado reveló que la VT alta se asoció de forma independiente con la mortalidad 28-D y 90-D, pero la VT intermedia no se asoció significativamente con la mortalidad 28-D (HR 1,34, IC 0,92-1,97, p=0,13) o la mortalidad 90-D. Cuando los grupos de VT intermedia y baja se emparejaron en puntajes de propensión (n=66 para cada grupo), sus resultados tampoco fueron significativamente diferentes. Conclusión La VT intermedia, con resultados similares a la VT pequeña, es una opción aceptable para pacientes con ARDS ventilados. Esta conclusión necesita verificación a través de ensayos clínicos (AU)

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome.

Objective: Evidence only proves low surpasses high tidal volume (V T) for acute respiratory distress syndrome (ARDS). Intermediate V T is a common setting for ARDS patients and has been demonstrated as effective as low V T in non-ARDS patients. The effectiveness of intermediate V T in ARDS has not been studied and is the objective of this study. Design: A retrospective cohort study. Setting: Five ICUs with their totally 130 beds in Taiwan. Patients or participants: ARDS patients under invasive ventilation. Interventions: No. Main variables of interest: 28-D mortality. Result: Totally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean V T = 6.7 ml/kg), intermediate (mean V T = 8.9 ml/kg) and high (mean V T = 11.2 ml/kg) V T groups. With similar baseline ARDS and ICU severities, intermediate and low V T groups did not differ in 28-D mortality (47% vs. 63%, P = 0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high V T was independently associated with 28-D and 90-D mortality, but intermediate V T was not significantly associated with 28-D mortality (HR 1.34, CI 0.92-1.97, P = 0.13) or 90-D mortality. When the intermediate and low V T groups were matched in propensity scores (n = 66 for each group), their outcomes were also not significantly different. Conclusion: Intermediate V T, with its outcomes similar to small V T, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Objetivo: La evidencia solo demuestra que el volumen tidal (VT) bajo supera al alto para el síndrome de dificultad respiratoria aguda (ARDS). La VT intermedia es un escenario común para los pacientes con ARDS y se ha demostrado que es tan eficaz como la VT baja en pacientes sin ARDS. No se ha estudiado la eficacia de la VT intermedia en el ARDS y es el objetivo de este estudio. Diseño: Un estudio de cohorte retrospectivo. Ámbito: Cinco UCI con un total de 130 camas en Taiwán. Pacientes o participantes: Pacientes con ARDS bajo ventilación invasiva. Intervenciones: No. Variables de interés principales: Mortalidad 28-D. Resultado: Un total de 382 pacientes, con 6958 configuraciones de ventilador elegibles para protección pulmonar, se clasificaron en bajo (VT medio = 6,7 ml/kg), intermedio (VT medio = 8,9 ml/kg) y alto (VT medio = 11,2 ml/kg). Grupos de VT. Con un ARDS inicial similar y una gravedad en la UCI, los grupos de VT intermedia y baja no difirieron en la mortalidad 28-D (47% vs. 63%, p = 0,06) u otros resultados como mortalidad 90-D, días sin ventilador, dependencia del ventilador índice. El análisis multivariado reveló que la VT alta se asoció de forma independiente con la mortalidad 28-D y 90-D, pero la VT intermedia no se asoció significativamente con la mortalidad 28-D (HR 1,34, IC 0,92-1,97, p = 0,13) o la mortalidad 90-D. Cuando los grupos de VT intermedia y baja se emparejaron en puntajes de propensión (n = 66 para cada grupo), sus resultados tampoco fueron significativamente diferentes. Conclusión: La VT intermedia, con resultados similares a la VT pequeña, es una opción aceptable para pacientes con ARDS ventilados. Esta conclusión necesita verificación a través de ensayos clínicos.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Non-invasive evaluation of the common carotid artery in normal adults using ultrasound radiofrequency data technology.

AIM: To evaluate the changes in CCA-IMT and vascular elasticity in healthy subjects in relation to age using radiofrequency data technology, to produce reference values for potential clinical applications. MATERIALS AND METHODS: The following variables were measured in 160 subjects using radiofrequency data techniques: CCA-IMT, carotid distensibility (CD), local pulse-wave velocity (PWVß), and stiffness (ß). The subjects were divided into four age groups (30-39, 40-49, 50-59, and 60-69 years), with 20 men and 20 women in each group. The above parameters were compared among the different age groups. RESULTS: CCA-IMT increased significantly with age (p<0.05). CD decreased significantly in the 40-49-years compared with the 30-39-years age group (p<0.05). PWVß showed a significant increase in the 30-39-, 40-49-, and 50-59-years age groups (p<0.05). ß increased significantly in the 50-59- compared with the 40-49-years age group (p<0.05). Compared with the 50-59-years age group, CD, PWVß, and ß showed no significant changes in the 60-69-years age group (p>0.05), with mean values of 329.39 ± 102.06 µm, 7.22 ± 1.91 m/s, and 10.04 ± 4.91, respectively. CONCLUSION: Ultrasound radiofrequency data technology provides a non-invasive method for quantitatively and accurately assessing increased CCA-IMT and reduced vascular elasticity in healthy subjects in different age groups. The reference values produced in this study will be useful in clinical practice.

Use of convalescent plasma therapy in eight individuals with mild COVID-19.

Coronavirus disease 2019 (COVID-19) is still a global epidemic. Several studies of individuals with severe COVID-19 regard convalescent plasma (CP) transfusion as an effective therapy. However, no significant improvements are found in randomized clinical trials of CP treatment. Until now, data for individuals with mild COVID-19 transfused CP were lacking. This study recruited eight individuals with mild COVID-19 who received at least one dose of CP transfusion. After CP therapy, the clinical symptoms of all individuals improved. Lymphocyte counts tended to increase, and lactate dehydrogenase, creatine kinase and aspartate aminotransferase tended to decrease. However, C-reactive protein increased transiently in three individuals. The median time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test to become negative was 2.5 days after CP transfusion. The study shows the potential benefits of CP. Meanwhile, CP probably enhances the inflammatory response to SARS-CoV-2 temporarily in people with insufficient antiviral immunity. However, the effects of CP are not permanent.

MicroRNA-338 in MSCs-derived exosomes inhibits cardiomyocyte apoptosis in myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) is caused by myocardial ischemia and hypoxia, which causes irreversible damage to the myocardium and seriously endangers human health. Exosomes are small, monolayer-structured extracellular vesicles that transport proteins, lipids, mRNAs, and miRNAs between cells. Mesenchymal stem cells (MSCs) can secrete a large number of exosomes and play a role in many pathophysiological processes. The purpose of this paper was to investigate the role of exosomal microRNA-338 (miR-338) in MI and its underlying mechanism of action. MATERIALS AND METHODS: We transfected rat bone marrow-derived MSCs with miR-338 mimic or negative control and extracted exosomes secreted by MSCs. Expression of miR-338 in MSCs, exosomes, and H9c2 cells co-cultured with exosomes was detected by PCR. Then, we treated H9c2 cells with H2O2. We transfected miR-338 inhibitor into H9c2 cells co-cultured with exosomes to further study the function of miR-338. Apoptosis of H9c2 cells were observed by Western blot, flow cytometry, and cell staining. We also established a MI rat model to study the function in vivo and injected exosomes in the myocardium. Seven days later, we used echocardiography to detect the heart function of rats. RESULTS: MiR-338 was upregulated in MSCs transfected with miR-338 mimic, exosomes, and H9c2 cells co-cultured with exosomes. When H9c2 cells were co-cultured with exosomes overexpressing miR-338, the expression of Bax was decreased while the expression of Bcl-2 was increased, and the apoptosis rate was also decreased as shown in flow cytometry, and the amount of caspase3 fluorescence was also decreased. Cardiac function was markedly improved after intramyocardial injection of exosomes overexpressing miR-338 in rats. It was demonstrated using computational tools, Western blot, and Luciferase reporter gene experiments that miR-338 could regulate JNK pathway via targeting MAP3K2. CONCLUSIONS: Exosomal miR-338 can inhibit cardiomyocyte apoptosis and improve cardiac function in rats with myocardial infarction by regulating MAP3K2/JNK signaling pathway.

MiR-29 inhibits neuronal apoptosis in rats with cerebral infarction through regulating Akt signaling pathway.

OBJECTIVE: The aim of this study was to explore the influence of micro ribonucleic acid (miR)-29 on neuronal apoptosis in rats with cerebral infarction by regulating the protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: Sham group (n=12), Model group (n=12), and Inhibitor group (n=12). Common carotid artery, external carotid artery, and internal carotid artery were only exposed in the Sham group. However, the ischemia-reperfusion model was established by the suture method in the other two groups. After modeling, artificial cerebrospinal fluid was injected into the lateral ventricle in the rats of the Sham and Model groups. Similarly, miR-29 inhibitor was injected into the lateral ventricle in the rats of the Inhibitor group. At 24 h postoperatively, the sampling was performed. Zea-Longa score was used to evaluate the neurological deficit of rats. Meanwhile, the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in cerebral tissues were detected via immunohistochemistry. The protein expression levels of Akt and phosphorylated Akt (p-Akt) were determined using Western blotting. Furthermore, the expression of miR-29 and cell apoptosis were detected via quantitative Polymerase Chain Reaction (qPCR) and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. RESULTS: Compared with Sham group, Model, and Inhibitor groups had substantially raised the Zea-Longa scores (p<0.05). The Zea-Longa score in the Model group was markedly lower than that of the Inhibitor group (p<0.05). The positive expression level of Bax was remarkably upregulated (p<0.05). However, the positive expression level of Bcl-2 declined dramatically in both Model group and Inhibitor group when compared with the Sham group (p<0.05). Besides, the Model group exhibited significantly lower positive expression level of Bax and higher positive expression level of Bcl-2 than the Inhibitor group (p<0.05). The relative protein expression level of p-Akt markedly increased in the Model and Inhibitor groups when compared with the Sham group (p<0.05). However, it was considerably higher in the Model group than that of the Inhibitor group (p<0.05). In comparison with the Sham group, both Model group and Inhibitor group exerted substantially elevated expression level of miR-29 (p<0.05). The relative expression level of miR-29 in the Model group was significantly upregulated when compared with the Inhibitor group (p<0.05). The apoptosis rate of cells in both Model group and Inhibitor group was markedly higher than that of the Sham group (p<0.05). Furthermore, the Model group showed remarkably lower apoptosis rate than the Inhibitor group (p<0.05). CONCLUSIONS: MiR-29 inhibits neuronal apoptosis in cerebral infarction rats by upregulating the Akt signaling pathway, thereby serving as a protector.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway.

OBJECTIVE: To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway. MATERIALS AND METHODS: A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting. RESULTS: The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p<0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p<0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p<0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p<0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p<0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p<0.05), while they were higher in model group than those in control group (p<0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p<0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p<0.05). CONCLUSIONS: MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal.

Galanin receptor 1 plays an antinociceptive effect via inhibiting PKA activation in the nucleus accumbens of rats with neuropathic pain.

Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14(th) and 28(th) day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.

Influence of hypothyroidism on testicular mitochondrial oxidative stress by activating the p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase signaling pathways in rats.

Thyroid hormone deficiency can impair testicular function. However, knowledge of the effects of mitogen-activated protein kinase (MAPK) pathways on testicular mitochondrial oxidative damage induced by hypothyroidism is still rudimentary. This study aims to explore the possible mechanisms of testicular mitochondrial oxidative damage in hypothyroidism rats. Wistar male rats were randomly divided into control (C), low- (L), and high-hypothyroidism (H) groups (1 ml/100 g body weights (BWs)/day 0, 0.001% and 0.1% propylthiouracil, respectively) by intragastric gavage for 60 days. Blood samples were collected to measure the levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH). Testicular mitochondrial homogenates were used to measure the activities of superoxide dismutase (SOD), catalase (CAT), and Ca2+-ATPase as well as protein and mRNA expression of androgen receptor (AR), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Results showed that the BWs, testes weights, and levels of T3 and T4 were all significantly decreased and the testes coefficient and level of TSH were significantly increased in the H group. There were significant decreases in SOD activity in the H group as well as decreases in CAT and Ca2+-ATPase activities in the L and H groups. Additionally, protein expression of AR decreased significantly and protein expression of phosphorylated p38MAPK and JNK increased significantly in the H group. Therefore, the study suggests that hypothyroidism could affect male reproductive function by disturbing expression of AR, changing the activity of Ca2+-ATPase, inducing oxidative stress and then leading to activation of p38MAPK and JNK signaling in the testicular mitochondria.

Jagged2 promotes cancer stem cell properties of triple negative breast cancer cells and paclitaxel resistance via regulating microRNA-200.

OBJECTIVE: To investigate the role of Jagged2 in triple negative breast cancer (TNBC) and its underlying mechanism. PATIENTS AND METHODS: Breast cancer tissues of patients diagnosed with TNBC in Fujian Medical University Affiliated MinDong Hospital from January 2015 to September 2017 were selected. TNBC patients were divided into the paclitaxel-resistant group (n=34) and non-resistance group (n=11). Jagged2 expression in paclitaxel-resistant group and non-resistance group before and after treatment was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR), respectively. After Jagged2 knockdown in paclitaxel-resistant MDA-MB-231 cells (MDA-MB-231/TXR), expression of CD44+CD24-ESA+ subset was detected by flow cytometry. MicroRNA-200 expression was detected after Jagged2 knockdown in MDA-MB-231/TXR cells. RESULTS: Jagged2 was highly expressed in paclitaxel-resistant TNBC tissues and cells. Jagged2 expression was found to be associated with cancer stem cell (CSC) properties of TNBC cells. Knockdown of Jagged2 inhibited CSC properties and paclitaxel resistance, whereas upregulated microRNA-200 expression. The inhibited CSC properties and paclitaxel resistance induced by Jagged2 knockdown were reversed by microRNA-200 knockdown. CONCLUSIONS: Jagged2 maintains CSC properties of TNBC cells and paclitaxel resistance via regulating microRNA-200.

Incidence and risk factors for hip fracture in elderly patients undergoing lumbar spine surgery: a nationwide database study with 11-year follow-up.

Impaired functional movement may occur after spinal surgery, which increases risk of fall episode and hip fracture. Patients with long-segment thoracolumbar spine fusions had a significantly higher risk of hip fracture than those with only discectomies. Fall prevention is necessary due to the highly increased hip fracture risk. INTRODUCTION: Spinal surgeries are performed to treat spondylolisthesis, fractures, scoliosis, or other deformities. Impaired balance mechanisms and functional movement may occur after spinal surgery. Fall episodes may cause hip fractures, which have negative impacts on quality of life and increase mortality. The incidence of hip fracture after spinal surgery is still unknown. The aim of this study was to examine the association between various types of spinal surgeries and hip fractures in the elderly by using a nationwide database. We hypothesized that the spinal surgeries may increase hip fracture risk in the elderly. METHODS: We used the National Health Insurance Research Database (NHIRD) to identify 3345 patients undergoing spinal surgery and a random dataset to identify 6690 age-, sex- and Charlson comorbidity index (CCI)-matched controls to compare the incidence of hip fractures in an 11-year follow-up period. We also enrolled 82,730 patients with spinal surgeries from the inpatient dataset to investigate the impact of different types of spinal surgeries. RESULTS: Patients who received spinal surgeries had higher risks of hip fractures, especially patients aged 60 to 79 years and female patients. The patients with long-segment thoracolumbar spinal fusions had a significantly higher risk of hip fracture than those with only discectomies. Short segmental lumbar spine fusions also slightly increased the risk of hip fracture compared with discectomies. CONCLUSION: Fall prevention for the elderly undergoing lumbar spinal surgery is necessary due to the highly increased hip fracture risk.

MicroRNA-520a-3p inhibits cell growth and metastasis of non-small cell lung cancer through PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis. MATERIALS AND METHODS: The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively. Transwell assay was used to evaluate the cell migration and invasion. The protein expression levels related PI3K/AKT/mTOR signaling pathways were measured by Western blot. RESULTS: The results showed that miR-520a-3p overexpression could significantly inhibit cell proliferation and induce apoptosis, suppress cell migration and invasion. MiR-520a-3p overexpression could markedly reduce the ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) compared with control. However, miR-520a-3p overexpression could increase caspase-3 expression compared with control group. After inhibited the expression of miR-520a-3p, the capacity of cell proliferation, migration and invasion were increased, cell apoptosis was inhibited compared with control group. The ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, MMP-2 and MMP-9 were increased compared with control group. CONCLUSIONS: Our study suggested that miR-520a-3p could suppress the NSCLC proliferation, migration and invasion through PI3K/AKT/mTOR signaling pathway.

Generating Rasch-based activity of daily living measures from the Spinal Cord Injury Longitudinal Aging Study.

STUDY DESIGN: Retrospective Longitudinal Study. OBJECTIVES: (1) To determine whether the Spinal Cord Injury Activities of Daily Living (SCI_ADL) measure shows adequate item-level and precision psychometrics; (2) to investigate whether the SCI_ADL measure effectively detects ADL changes across time; (3) to describe self-care task(s) participants can and cannot do across time. SETTING: Two Midwestern hospitals and 1 Southeastern specialty hospital in 1993. METHODS: All participants were adults with traumatic SCI of at least 1-year duration at enrollment. We used 20-year (1993-2013) retrospective longitudinal data and categorized participants into three injury levels: C1-C4 (cervical; n=50), C5-C8 (n=126) and T1-S5 (thoracic, lumbar and sacral; n=168). We first examined psychometrics of the SCI_ADL with factor and Rasch analyses; then we investigated longitudinal change of SCI_ADL scores at three time points over 20 years (1993, 2003 and 2013) using generalized linear mixed modeling and post hoc analyses. RESULTS: The SCI_ADL measure demonstrated unidimensionality, person strata of 2.9, high Cronbach's α (0.93) and fair person reliability (0.76). T1-S5 had the highest measures, following C5-C8 and C1-C4 at three time points (P<0.05). The C1-C4 and T1-S5 groups showed significant decreases from 2003 to 2013; however, none of the three groups showed significant differences from 1993 to 2003 (P<0.05). CONCLUSIONS: The SCI_ADL measure could detect longitudinal ADL changes of the population with SCI across time. The C1-C4 group decreased the most in ADLs, indicating higher need of long-term services and rehabilitation.

Microbial sensor for drug susceptibility testing of Mycobacterium tuberculosis.

AIMS: Drug susceptibility testing (DST) of clinical isolates of Mycobacterium tuberculosis is critical in treating tuberculosis. We demonstrate the possibility of using a microbial sensor to perform DST of M. tuberculosis and shorten the time required for DST. METHODS AND RESULTS: The sensor is made of an oxygen electrode with M. tuberculosis cells attached to its surface. This sensor monitors the residual oxygen consumption of M. tuberculosis cells after treatment with anti-TB drugs with glycerine as a carbon source. In principle, after drug pretreatment for 4-5 days, the response differences between the sensors made of drug-sensitive isolates are distinguishable from the sensors made of drug-resistant isolates. The susceptibility of the M. tuberculosis H37Ra strain, its mutants and 35 clinical isolates to six common anti-TB drugs: rifampicin, isoniazid, streptomycin, ethambutol, levofloxacin and para-aminosalicylic acid were tested using the proposed method. The results agreed well with the gold standard method (LJ) and were determined in significantly less time. The whole procedure takes approximately 11 days and therefore has the potential to inform clinical decisions. CONCLUSIONS: To our knowledge, this is the first study that demonstrates the possible application of a dissolved oxygen electrode-based microbial sensor in M. tuberculosis drug resistance testing. This study used the microbial sensor to perform DST of M. tuberculosis and shorten the time required for DST. SIGNIFICANCE AND IMPACT OF THE STUDY: The overall detection result of the microbial sensor agreed well with that of the conventional LJ proportion method and takes less time than the existing phenotypic methods. In future studies, we will build an O2 electrode array microbial sensor reactor to enable a high-throughput drug resistance analysis.