[Analysis of curative effects of chemoembolization with drug-loaded microspheres of different particle sizes for the treatment of hepatocellular carcinoma].

Objective: To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma. Methods: Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 µm (small particle size) and 300~500 µm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P＜0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results: The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P1 month=0.012, P3 month=0.009, P6 month=0.008, P＜0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant (P＜0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant (P=0.182). Conclusions: In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.

Ensayos clínicos con medicamentos registrados en España sobre COVID-19: situación casi dos años después de la declaración de pandemia / Clinical trials with COVID-19 registered medicines in Spain: situation almost two years after pandemic declaration

JUSTIFICACIÓN: la COVID-19 es una enfermedad causada por el virus SARS-CoV-2, detectado en diciembre de 2019. Poco después, en marzo de 2020, fue considerada pandemia por la OMS. Dicha pandemia ha supuesto un aumento de la investigación a la vez que un entorno de incertidumbre que favorece la desinformación, evidenciado la necesidad de información detallada, confiable, accesible y regularmente actualizada. OBJETIVOS: Caracterizar los ensayos clínicos con medicamentos sobre la COVID-19 registrados en España hasta diciembre de 2021. MATERIAL Y MÉTODOS: se realizó un estudio observacional descriptivo de tipo transversal sobre los ensayos clínicos con medicamentos relacionados con la COVID-19 (diciembre de 2021). La fuente de datos fue el Registro Español de estudios clínicos (REec) en el que se aplicó como filtro la palabra clave “COVID-19”. Las variables de estudio fueron: promotor, población (participantes), ámbito de estudio, estado del estudio, centro-s, tipo de tratamiento, fase del ensayo e identificación de los medicamentos ensayados. Se creó un grupo interdisciplinar de trabajo constituido por profesionales de la salud y de otros ámbitos. El registro de los datos se realizó mediante una hoja Excel, clasificando la información para su posterior análisis. RESULTADOS Y DISCUSIÓN: se cuantificaron un total de 196 ensayos clínicos con medicamentos. 148 presentan un promotor nacional y los 48 restantes un promotor internacional. La fuente de financiación principal de los ensayos clínicos proviene de instituciones privadas (n=116). (AU)

Suplementación de la vitamina D: Análisis de las presentaciones y dosificaciones disponibles en España, China, Ecuador y Colombia / Vitamin D supplementation: Analysis of presentations and dosages available in Spain, China, Ecuador and Colombia

JUSTIFICACIÓN: en la actualidad, están aumentando las notificaciones de reacciones adversas graves asociadas a la vitamina D que parecen relacionarse con errores de prescripción y el uso de suplementos a dosis altas. OBJETIVOS: describir los medicamentos de vitamina D monocomponente (colecalciferol y calcifediol) comercializados en China, Colombia, Ecuador y España, y realizar un análisis comparativo entre los diferentes países. MATERIAL Y MÉTODOS: estudio transversal descriptivo (enero 2022) a nivel internacional. Se obtuvo la información a través de las bases de datos de las agencias reguladoras de cada país: NMPA (China), INVIMA (Colombia), ARCSA (Ecuador) y CIMA de la AEMPS (España), de acceso público a través de Internet. RESULTADOS Y DISCUSIÓN: se contabilizó un total de 51 medicamentos, de los cuales 31 (60,8 %) se comercializan en España, 10 (19,6 %) en Ecuador, 6 (11,8 %) en Colombia y 4 (7,8 %) en China. Se encontró un número mayor de presentaciones disponibles para la población adulta de los suplementos de colecalciferol que para la población pediátrica en España y Ecuador. Respecto a calcifediol, en los cuatro países existen menos presentaciones comercializadas para la población adulta y China es el único país que comercializa calcifediol para la población pediátrica. Respecto a las formas farmacéuticas disponibles (solución oral, ampollas y cápsulas/comprimidos), Colombia lidera el número de presentaciones en solución oral (33 %), seguido de España (30 %) y Ecuador (10 %), mientras que en China no se encuentra disponible esta forma farmacéutica y sí en ampollas (China un 50%, seguido de Colombia con un 33 %). (AU)

Ensayos clínicos con medicamentos registrados en España sobre la covid-19: Estudio comparativo de los años 2020 y 2021 / Clinical trials with covid-19 registered medicines in Spain: A comparative study of the years 2020 and 2021

JUSTIFICACIÓN: la situación sanitaria actual debido a la pandemia por la COVID-19 ha puesto en evidencia la importancia de la investigación, desarrollo e innovación (I+D+i) de los países, dada la repercusión en la mejora en salud y calidad de vida. OBJETIVOS: realizar un análisis comparativo de los ensayos clínicos con medicamentos relacionados con la COVID-19 registrados en España en 2020 y 2021. MATERIAL Y MÉTODOS: estudio observacional, descriptivo y transversal, con dos fechas de corte: 27 de octubre de 2020 y 21 de diciembre de 2021. La fuente de información fue la base de datos pública Registro Español de estudios clínicos (REec), utilizando el término “COVID-19” en el apartado de búsqueda avanzada. Las variables de estudio fueron: promotor, número de centros participantes, ámbito, estado del estudio, fase, número, género y edad de los voluntarios. El análisis de los datos se realizó mediante una hoja Excel, clasificando toda la información para su posterior análisis. RESULTADOS/DISCUSIÓN: en octubre de 2020 había 127 ensayos clínicos con medicamentos relacionados con la COVID-19 (75 en estado de reclutamiento, 11 finalizado el reclutamiento, 8 iniciados, 25 no iniciados y 8 finalizados) y en diciembre de 2021 había 196 (64, 36, 0, 35 y 61, respectivamente), por tanto, se observó un incremento del 54,3 % en el número de estudios un año después. El promotor mayoritario continuó siendo nacional (80,3 % en 2020 y 75,5 % en 2021), aumentando el patrocinio privado (49,6 % en 2020 frente al 59,2 % en 2021) frente al público. El ámbito de estudio principal siguió siendo la eficacia y seguridad de los medicamentos ensayados para la COVID-19, dado que alrededor del 80 % incluyeron estas características entre sus objetivos primarios en los dos años analizados. (AU)

[Prediction of perioperative hyperkalemia in dialysis patients with secondary hyperparathyroidism].

Objective: To explore the influencing factors for serum potassium >4.4 mmol/L in the morning of parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism (SHPT). Methods: The clinical data of 72 patients with SHPT who received regular hemodialysis and underwent parathyroidectomy in Guangdong Provincial People's Hospital from January 2012 to December 2018 were analyzed retrospectively. There were 37 males and 35 females, aged from 25 to 69 years, and the dialysis timespan was from 0.5 to 11 years. The levels of parathyroid hormone, serum potassium and serum calcium before hemodialysis were examined one day before operation, and hemodialysis time and dewatering volume after hemodialysis without heparin were recorded, and also the level of serum potassium in the morning of parathyroidectomy was detected. The occurrences of hyperkalemia during and after operation were studied. The factors related to hyperkalemia in the morning of parathyroidectomy were evaluated by Pearson or Spearman correlation analysis, and the cut-off values of risk factors were calculated by receiver operating characteristic (ROC) curve. Results: Serum potassium >4.4 mmol/L in the morning of parathyroidectomy existed in 23 of 72 patients. Correlation analysis showed that serum potassium one day before operation ((4.93±0.56)mmol/L, r=0.656, P<0.001) and dehydration volume ((2.37±0.75)L, r=0.261, P=0.027) were positively correlated with serum potassium in the morning of parathyroidectomy((4.16±0.54)mmol/L). Serum potassium before hemodialysis one day before operation was a main predictor for serum potassium in the morning of parathyroidectomy (AUC=0.791, P<0.001). The cut-off value of serum potassium before hemodialysis one day before operation was 5.0 mmol/L. Conclusion: Serum potassium before hemodialysis one day before operation in patients with SHPT can predict serum potassium in the morning of parathyroidectomy, offering imformation for the safety of operation.

WAPL maintains a cohesin loading cycle to preserve cell-type-specific distal gene regulation.

The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sites. Paradoxically, stabilization of cohesin binding, following WAPL ablation, results in depletion of cohesin from these cell-type-specific regions, loss of gene expression and differentiation. Chromosome conformation capture experiments show that cohesin turnover is important for maintaining promoter-enhancer loops. Binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 (POU5F1) and SOX2, but not NANOG. We show the importance of cohesin turnover in controlling transcription and propose that a cycle of cohesin loading and off-loading, instead of static cohesin binding, mediates promoter and enhancer interactions critical for gene regulation.

Higher frequency electrical stimulation enhanced myloglossus satellite cell differentiation by upregulating expression of Pax7 mRNA, MyoD, myogenin and MyHC protein.

OBJECTIVE: We investigated the effect of electrical stimulation (ES) of varying pulse frequency on differentiation and proliferation of canine myloglossus satellite cells in vitro. MATERIALS AND METHODS: Cellular viability and proliferation were assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and flow cytometry fluorescence-activated cell sorting analysis. Cellular differentiation and expression of mark molecule were assayed by Real Time-PCR and Western blot. RESULTS: With increasing frequency ES, we found a significant increase in Myod (r=0.988, p<0.0001), myogenin (r=0.988, p<0.0001), MyHC-slow (r=0.988, p<0.0001), MyHC-fast (r=0.875, p<0.0001) protein expression, and Pax7 mRNA expression (r=0.712, p=0.001). CONCLUSIONS: Pax7 mRNA expression and MyoD, myogenin, and MyHC protein expression were increased with increment of electrical stimulation frequency in myloglossus muscle satellite. Higher frequency ES enhanced myloglossus satellite cell differentiation, not proliferation and viability.

[The surgical effectiveness of montgomery thyroplasty implant on patients with unilateral vocal fold paralysis].

Objective: To investigate the efficacy of type I thyroplasty with Montgomery prosthesis implantation for the treatment of unilateral vocal fold paralysis. Methods: From May 2015 to March 2019, 46 patients (24 males, 22 females, with age range of 23-77) with unilateral vocal fold paralysis underwent thyroplasty with Montgomery prosthesis implantation in the Department of Otorhinolaryngology Head and Neck Surgery in both the First Affiliated Hospital of Navy Medical University and Guangdong Provincial People's Hospital. The assessment methods included GRBAS auditory perception assessment, acoustic analysis such as Jitter, Shimmer, NHR and maximum phonation time (MPT). Results: Postoperative videostroboscopy observed the displacement of paralyzed vocal fold to the midline in 44 cases as well as significantly reduced glottic fissures during phonation. In the other 2 cases, glottic fissure did not reduce significantly. Compared with preoperative data, the scores of all parameters in GRBAS auditory perception assessment were lower except the parameter S, and the acoustic analysis parameters (jitter, shimmer, NHR) were smaller, and MPT was longer. All the difference was statistically significant (P<0.001). Revision surgery was performed in 2 patients with poor results. No serious complications occurred in all the cases. Conclusions: For the patients with unilateral vocal fold paralysis who are not suitable for the laryngeal reinnervation surgery due to old age or long course of denervation, thyroplasty with Montgomery prosthesis implantation can effectively improve the voice of patients with high safety,which is worthy of promotion.

Hemorrhagic patterns and their risk factors in patients with moyamoya disease.

BACKGROUND AND PURPOSE: The aim was to describe the profiles of hemorrhagic patterns of moyamoya disease (MMD) and analyze the risk factors in a large population. METHODS: A total of 335 conservatively managed MMD patients with hemorrhage in our hospital were included in this cross-sectional study. The correlation between clinical and angiographic characteristics and hemorrhagic patterns (anterior or posterior hemorrhage) was assessed in the hemorrhagic hemisphere by univariate and multivariate logistic regression models. In addition, stratified analysis was performed. RESULTS: The 335 hemorrhagic hemispheres (patients) comprised 179 (53.4%) anterior and 156 (46.6%) posterior hemorrhages. For all cases, age at onset [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.96-1.00; P = 0.048] and choroidal anastomosis (OR 1.87; 95% CI 1.19-2.94; P = 0.007) were found by multivariate regression analysis to be negatively and positively associated with a significantly increased risk of posterior hemorrhage, respectively. After stratified analysis, hypertension (OR 0.37; 95% CI 0.14-0.97; P = 0.043) was identified by multivariate regression analysis as a risk factor for anterior hemorrhage in patients without dilation of choroidal anastomosis. On the other hand, choroidal anastomosis (OR 2.62; 95% CI 1.02-6.72; P = 0.045) and involvement of the posterior cerebral artery (OR 3.39; 95% CI 1.20-9.63; P = 0.022) were associated with significantly increased risk of posterior hemorrhage in children and young adults (<30 years of age). CONCLUSIONS: A dynamic change in hemorrhagic patterns in MMD patients with increasing age at onset was observed. Choroidal anastomosis is a predictor of posterior hemorrhage. Hypertension is a risk factor for anterior hemorrhage in patients without extreme dilation of choroidal anastomosis.

[The application of amodified scalp retractor in the craniotomy for intracranial aneurysms].

Objective: To investigate the application of a modified scalp retractor in the craniotomy for intracranial aneurysms withlateral supraorbital approach. Methods: From January 2019 to April 2020, a total of 32 patients with anterior circulation aneurysms clipping by superior lateral orbital approach were selected from Beijing Tiantan Hospital and Peking University International Hospital. The subjects were randomly divided into the traditional scalp retractor group and the modified scalp retractor group utilizing a random number table, with 16 patients in each group. The number of intraoperative retractor adjustment, incision length, postoperative scalp necrosis rate, postoperative wound healing grade, postoperative neurosurgical satisfaction score and patients' satisfaction score for incision were compared between the two groups. Results: The number of retractor adjustment in the modified scalp retractors group was significantly less than that in the traditional scalp retractor group (10.1±2.2 vs 14.2±3.6, P<0.05) . Incision length was also significantly shorter than that of the conventional scalp retractor group ( (10.1±1.0) cm vs (13.9±0.9) cm, P<0.05) .Neurosurgeons were significantly more satisfied with modified scalp retractors than the traditional scalp retractors (8.1±0.9 vs 6.0±0.9, P<0.05). There was no significant difference in postoperative scalp necrosis rate between two groups (P>0.05). Conclusion: The modified scalp retractor group is superior to the traditional scalp retractor group in the craniotomy for intracranial aneurysms with later supraorbital approach, with shorter in cision, less retractor adjustment and shorter surgical time.

Angiographic characteristics in Moyamoya disease with the p.R4810K variant: a propensity score-matched analysis.

BACKGROUND AND PURPOSE: The p.R4810K variant was identified as a strong susceptibility in patients with Moyamoya disease (MMD). The aim of this study was to investigate the angiographic characteristics in MMD with the p.R4810K variant. METHODS: Angiographic characteristics were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching, including Suzuki stage, collateral circulation and external carotid artery (ECA) collateral. Collateral circulation was graded with scores ranging from 0 to 12: posterior collateral circulation from the posterior cerebral artery to the middle cerebral artery and anterior cerebral artery was scored from 0 to 6; anterior collateral circulation was scored as 6 to 0 corresponding to Suzuki stages 0 to 6. RESULTS: A total of 489 patients were screened; 133 pairs were obtained after 1:1 propensity score matching. Compared with the patients in the GA group, unilateral MMD was more frequent in the GG group (P = 0.026). Hemispheres in the GA group (86/266) had more posterior cerebral artery involvement than hemispheres in the GG group (48/266) (P < 0.001). Hemispheres in the GA group had a lower grade in collateral circulation than hemispheres in the GG group (P = 0.011), but ECA collateral was more frequently observed in the GA group than in the GG group (53.4% vs. 39.8%, P = 0.002). Superficial temporal artery and occipital artery collateral was more frequently observed in the GA group than in the GG group (P < 0.05). CONCLUSIONS: Patients in the GA group had lower grades in collateral circulation than patients in the GG group, but ECA collateral was more frequently observed in the GA group than in the GG group.

Therapeutic effect of interleukin-10 in keloid fibroblasts by suppression of TGF-ß/Smad pathway.

OBJECTIVE: Keloids are a skin disorder where the skin goes beyond the original border of the wound or trauma, resulting in functional and cosmetic deformities, displeasure, itching, pain, psychological stress, and patient dissatisfaction. This study aimed to explore the therapeutic effect of interleukin-10 (IL-10) on the proliferation of keloid fibroblasts. PATIENTS AND METHODS: Keloid fibroblasts were isolated, primarily cultured, and treated with IL-10 at different concentrations. Normal skin fibroblasts were used as normal control. Immunofluorescent staining was performed to identify the establishment of keloid, as well as normal skin fibroblast. Cell Counting Kit-8 (CCK-8) was carried out to monitor the proliferative variation, while Western blot was conducted to detect the expression variation of key members involved in the TGF-ß/Smad signaling pathway. RESULTS: Identified by the IF staining of Vimentin, a classical biomarker of fibroblast, both primary culture of keloid and normal skin fibroblasts have been established. Compared with control, the proliferation of Keloid fibroblasts was shown to be significantly suppressed on treatment with IL-10 in a time and dose-dependent manner. Expression of P-Smad2/3 and Smad4 were increasingly down-regulated, whereas Smad-7 was up-regulated with the increasing concentration of IL-10. By contrast, the variation of Smad 2/3 expressions was hardly influenced. Furthermore, the Collagen Type I and Collagen Type II were found to be markedly decreased after treatment with IL-10. CONCLUSIONS: IL-10 was shown to be able to significantly inhibit the proliferation of keloid fibroblasts, which was explicitly and strongly suggestive of its potential therapeutic effect in the management of keloid.

[Clinical observation of the low back pain and posterior thigh pain in the early stage after percutaneous endoscopic lumbar discectomy].

Objective: To evaluate the incidence, causes and prognosis of the low back pain and posterior thigh pain in the early stage after percutaneous endoscopic lumbar discectomy (PELD). Methods: A total of 88 patients who underwent PELD from December 2017 to June 2018 in the First Affiliated Hospital of Anhui Medical University were enrolled in this study. PELD was performed by posterior-lateral approach and the interlaminar approach in 44 cases, respectively. During the 3-month of follow-up post PELD, the number of cases who suffered low back pain and posterior thigh pain, complications and postoperative treatments were all followed and evaluated. Results: All the 88 cases underwent PELD successfully. Twelve cases (27.3%) suffered low back pain after PELD by posterior-lateral approach totally, 4 patients (9.1%) were new cases and the low back pain aggravated after PELD in the other 8 cases (18.2%). The posterior thigh pain occurred in 9 cases (20.4%) after PELD in posterior-lateral approach group, of them, 5 patients (11.4%) were new cases and it was aggravated in 4(9.1%) cases after the surgery. As for the low back pain after PELD performed by the interlaminar approach, 7(15.9%) cases suffered low back pain and 1 case (2.3%) occurred after surgery. The posterior thigh pain happened in 5 cases (11.4%) after PELD in the interlaminar approach group, 2 cases (4.6%) were new cases and the pain was aggravated in 3 cases (6.8%) after surgery. According the classification of MacNab, 42 of 88 cases were classified excellent, 25 cases good, 17 cases fair and 4 cases poor after PELD. Totally 18 cases were classified into fair and poor because of the low back pain or the posterior thigh pain during the follow-up. Furthermore, none of 88 cases had infection or nerve root injury after surgery. All cases suffering the low back pain or the posterior thigh pain treated conservatively and no one needed surgery again. Conclusions: The pain in low back or posterior thigh may be one of the complications after PELD, and it can be treated conservatively. Incidence of the low back pain or the posterior thigh pain after PELD with posterior-lateral approach is higher than that in patients with interlaminar approach, and it may affect the efficacy of PELD.

Four weeks of hypoxia training improves cutaneous microcirculation in trained rowers.

Hypoxia training can improve endurance performance. However, the specific benefits mechanism of hypoxia training is controversial, and there are just a few studies on the peripheral adaptation to hypoxia training. The main objective of this study was to observe the effects of hypoxia training on cutaneous blood flow (CBF), hypoxia-inducible factor (HIF), nitric oxide (NO), and vascular endothelial growth factor (VEGF). Twenty rowers were divided into two groups for four weeks of training, either hypoxia training (Living High, Exercise High and Training Low, HHL) or normoxia training (NOM). We tested cutaneous microcirculation by laser Doppler flowmeter and blood serum parameters by ELISA. HHL group improved the VO(2peak) and power at blood lactic acid of 4 mmol/l (P(4)) significantly. The CBF and the concentration of moving blood cells (CMBC) in the forearm of individuals in the HHL group increased significantly at the first week. The HIF level of the individuals in the HHL group increased at the fourth week. The NO of HHL group increased significantly at the fourth week. In collusion, four weeks of HHL training resulted in increased forearm cutaneous blood flow and transcutaneous oxygen pressure. HHL increases rowers' NO and VEGF, which may be the mechanism of increased blood flow. The increased of CBF seems to be related with improving performance.

HSP20-mediated cardiomyocyte exosomes improve cardiac function in mice with myocardial infarction by activating Akt signaling pathway.

OBJECTIVE: To explore the role of heat shock protein 20 (HSP20)-mediated cardiomyocyte exosomes in the cardiac function in mice with myocardial infarction via the activation of the protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 30 mice were enrolled to establish the model of myocardial infarction. Next, these mice were divided into three groups, namely Blank group (healthy mice), Model group (mouse models of myocardial infarction), and HSP20 group (mouse models of myocardial infarction transfected with lentivirus to overexpress HSP20). After that, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining assay was performed to detect myocardial apoptosis. Reactive oxygen species (ROS) accumulation in myocardial tissues was determined via dihydroethidium (DHE) staining assay. Western blotting was employed to analyze the expression level of Akt. The expression levels of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1ß) in HSP20-mediated cardiomyocyte exosomes were measured through quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: Compared with that in Blank group, the number of cardiomyocyte exosomes was increased in Model group and HSP20 group under anoxic conditions (p<0.05). The results of quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) proved that the HSP20 messenger ribonucleic acid (mRNA) expression in mediated cardiomyocyte exosomes was significantly lower in Model group than that in Blank group (p<0.05), while in HSP20 group, it was overtly higher than that in Model group but clearly lowered compared with that in Blank group (p<0.05). The protein expression of Akt in cardiomyocyte exosomes was evidently decreased in Model group compared with that in Blank group (p<0.05), while it was notably increased in HSP20 group compared with that in Model group (p<0.05). In comparison with Blank group, Model group had significantly elevated mRNA expression levels of TNF-α and IL-1ß. The mRNA expression levels of TNF-α and IL-1ß in HSP20 group were remarkably lower than those in Model group (p<0.05). The results of TUNEL assay revealed that the overexpression of HSP20 affected myocardial apoptosis. The myocardial apoptosis index in Model group [(38.42±2.52) %] was higher than that in Blank group [(9.74±1.21) %], HSP20 group had a significantly decreased myocardial apoptosis index [(22.36±2.13) %] in comparison with Model group (p<0.05). In accordance with DHE staining comparison, the accumulation of ROS in myocardial tissues in Model group was significantly higher than that in Blank group (p<0.05) and HSP20 group (p<0.05). CONCLUSIONS: We demonstrated that HSP20-mediated cardiomyocyte exosomes activate the AKT signaling pathway, repress TNF-α and IL-1ß factors, and alleviate myocardial infarction.

Linaclotide inhibits colonic and urinary bladder hypersensitivity in adult female rats following unpredictable neonatal stress.

BACKGROUND: Irritable bowel syndrome (IBS) and bladder pain syndrome (BPS) are female-predominant, chronic functional pain disorders that are associated with early life stress (ELS) and therapeutic options for such patients remain limited. Linaclotide, a guanylate cyclase-C (GC-C) agonist, relieves abdominal pain and bowel symptoms in adult patients suffering from IBS with constipation. Here, we test the hypothesis that linaclotide will reverse colon and bladder hyperalgesia in a female-specific rodent model of adverse early life experience. METHODS: Neonatal rats were exposed to an odor-attachment learning paradigm of early life stress (ELS). In adulthood, the effect of linaclotide (3 µg kg-1  d-1 , p.o.) on colonic and bladder sensitivity was assessed via quantification of the visceromotor response to colorectal distension and the frequency of withdrawal responses to the application of von Frey hairs to the suprapubic region. In another cohort of rats, the effect of linaclotide on ELS-induced colonic and bladder permeability was investigated via measurements of transepithelial electrical resistance (TEER). KEY RESULTS: Rats exposed to unpredictable ELS exhibited colonic and bladder hypersensitivity that was significantly reduced by linaclotide compared to vehicle-treated controls. Colonic and bladder tissue isolated from adult rats exposed to unpredictable ELS exhibited a decrease in colonic and bladder TEER that was reversed by linaclotide. CONCLUSIONS AND INFERENCES: Our results demonstrate that neonatal rats exposed to unpredictable ELS develop increased sensitivity and permeability of the colon and bladder in adulthood through a mechanism involving activation of peripheral GC-C signaling.

A study of predictors for hyponatraemia in patients with cervical spinal cord injury.

STUDY DESIGN: A retrospective study. OBJECTIVES: The objectives of the study were to investigate the predictors for hyponatraemia in patients with cervical spinal cord injuries (CSCIs) and to define the relationship between magnetic resonance imaging (MRI) scans and hyponatraemia. SETTING: The study was carried out at The First Affiliated Hospital of Anhui Medical University. METHODS: A total of 292 patients with CSCIs were retrospectively reviewed to determine the predictors of hyponatraemia. Fourteen variables were extracted from the medical records: age, sex, blood pressure (BP), tracheostomy, serum potassium, serum chloride, serum bicarbonate, serum albumin, intravenous fluid intake and urine volume for 24 h, haematocrit, haemoglobin, neurological assessment and four MRI signal patterns. Univariate and multivariate analyses were used to determine the effect of each variable on hyponatraemia. RESULTS: Eighty-two of the 270 patients (30%) developed hyponatraemia. Univariate analyses indicated that the following variables were significant predictors of hyponatraemia: tracheostomy; the initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) A assessment; and haemorrhage changes on T2-weighted MRI scans, and low BP. Multivariate regression analyses revealed two variables were significant predictors of hyponatraemia: haemorrhage changes on T2-weighted MRI scans and low BP. CONCLUSIONS: Haemorrhage changes on MRI scans were closely associated with the onset of hyponatremia and could provide objective data for forecasting hyponatraemia in CSCI patients. Low BP was also a reasonable predictor of hyponatremia.

Clinical features and surgical outcomes of cervical spondylotic myelopathy in patients of different ages: a retrospective study.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: This study aims to compare the clinical features and surgical outcomes in patients with cervical spondylotic myelopathy (CSM) among different age groups. SETTING: The first Affiliated Hospital of Anhui Medical University, China. METHODS: A total of 460 patients with CSM who were surgically treated over the period of 1995-2009 were investigated. Considering the peak age (40-60 years old) for the onset of symptoms, we divided the patients into three groups by age: young (<40), middle-aged (40-60), and old (>60). The differences in symptoms, symptom durations, involved levels, surgical approaches and outcomes were evaluated. RESULTS: The number of symptoms and involved levels, symptom duration and posterior approach significantly increased with increasing age, whereas preoperative Japanese Orthopedic Association score decreased among the three groups. Spinal cord function improved after surgery in all groups. The highest degree of recovery occurred during the first 6 months after surgery, especially within the first week, and then reached a plateau. After 6 months, however, recovery continuously improved, stabilized and declined in the young, middle-aged, old groups, respectively. The recovery rate was not significantly different at an immediate period (1 week) after operation among the three groups, but was significantly different at later periods (3 or more months postoperatively). Three groups showed no difference in postoperative complication rates. CONCLUSION: The severity of CSM increased with increasing age. Age was inversely correlated with recovery, and recovery decreased as age increased. Six months post operation was the prime time for the recovery of spinal cord function.