Melatonin restores endoplasmic reticulum homeostasis to protect injured neurons in a rat model of chronic cervical cord compression.

Cervical spondylotic myelopathy (CSM) refers to a chronic injury of the cervical cord caused by cervical intervertebral disc degeneration. Endoplasmic reticulum (ER) homeostasis is essential to counteract neuronal apoptosis. ER stress, an integral part of ER homeostasis, was observed in a rat model of chronic cervical cord compression in our previous study. However, the correlation between ER homeostasis and CSM remains unknown. The antioxidant melatonin is known to exert therapeutic effects in acute spinal cord injury, but the specific effects and their potential mechanisms in the pathological processes of CSM require further exploration. The present study hypothesized that ER homeostasis is essential for neuronal apoptosis in the CSM and that melatonin maintains this homeostasis. The results showed that ER stress led to neuronal apoptosis in rats with chronic cervical cord compression. Conversely, melatonin attenuates protein kinase R-like ER kinase-eukaryotic initiation factor 2α-C/EBP-homologous protein, inositol-requiring enzyme 1, and transcription factor 6 signaling pathways to release ER stress and prevents Bax translocation to the mitochondrion, thereby promoting motor recovery and protecting neurons in vivo. It also rescued primary rat cortical neurons from ER stress-induced glutamate toxicity in vitro. Moreover, melatonin remodels the ER morphology and restores homeostasis via ER-phagy in injured neurons. FAM134B, CCPG1, RTN3, and Sec. 62 are four known ER-phagy receptors. In this study, Sec. 62 was identified as a key melatonin factor in promoting ER-phagy and restoring ER homeostasis in damaged neurons in vivo and in vitro. In conclusion, melatonin suppresses neuronal apoptosis by reducing ER stress and promoting ER-phagy to restore ER morphology and homeostasis. The current results suggested that melatonin is a promising treatment for CSM owing to its restorative effect on ER homeostasis; however, well-designed randomized controlled trials must be carried out to further investigate its clinical effects.

Assessment of rehabilitation following subarachnoid haemorrhage in China: findings from the Chinese Stroke Center Alliance.

BACKGROUND: Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. METHODS: To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. RESULTS: Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.04 to 1.05) and care such as dysphagia screening (OR, 1.88; 95% CI, 1.73 to 2.04), DVT prophylaxis (OR, 1.56; 95% CI, 1.41 to 1.72) and vessel evaluation (OR, 1.80; 95% CI, 1.63 to 1.98). For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay (OR, 1.96; 95% CI, 1.81 to 2.12), a higher modified Rankin Scale (mRS) score at discharge (OR, 1.49; 95% CI, 1.36 to 1.64), and higher rates of discharge to a rehabilitation center (OR, 3.23; 95% CI, 1.81-5.75). CONCLUSION: More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients.

Shikonin inhibits neuronal apoptosis via regulating endoplasmic reticulum stress in the rat model of double-level chronic cervical cord compression.

Cervical spondylotic myelopathy (CSM) is a clinically symptomatic entity arising from the spinal cord compression by degenerative diseases. Although endoplasmic reticulum (ER) stress has been commonly observed in several neurodegenerative diseases, the relationship between ER stress and CSM remains unknown. Shikonin is known to protect PC12 by inhibiting apoptosis in vitro. This study hypothesised that ER stress was vital in neuronal apoptosis in CSM. Shikonin might inhibit such responses by regulating ER stress through the protein kinase-like ER kinase-eukaryotic translation initiation factor 2 α-subunit-C/EBP homologous protein (PERK-eIF2α-CHOP) signalling pathway. Thus, the aim of this study was evaluating the neuroprotective effect of shikonin in rats with double-level chronic cervical cord compression, as well as primary rat cortical neurons with glutamate-induced neurotoxicity. The result showed that ER stress-related upregulation of PERK-eIF2α-CHOP resulted in rat neuronal apoptosis after chronic cervical cord compression; then, shikonin promoted motor recovery and inhibited neuronal apoptosis by attenuating PERK-eIF2α-CHOP and prevented Bax translocation from cytoplasm to mitochondrion induced by CHOP of neurons in rats with chronic compression. Also, it was found that shikonin could protect rat primary cortical neuron against glutamate toxicity by regulating ER stress through the PERK-eIF2α-CHOP pathway in vitro. In conclusion, shikonin might inhibit neuronal apoptosis by regulating ER stress through attenuating the activation of PERK-eIF2α-CHOP.

A comprehensive and systematic review of the potential neuroprotective effect of quercetin in rat models of spinal cord injury.

CONTEXT: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. OBJECTIVE: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. DATA SOURCES: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. STUDY SELECTION: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. RESULTS: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. CONCLUSIONS: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

Epidemiological study of calcified aortic valve stenosis in a Chinese community population.

BACKGROUND AND AIMS: Due to the ageing global population, calcified aortic valve disease is currently the most common cardiac valve disorder. This study aimed to investigate the prevalence and the risk factors for calcified aortic valve stenosis (CAVS), and develop a prediction model for predicting CAVS risk. METHODS AND RESULTS: This study was derived from the cross-sectional baseline survey of the PRECISE study (NCT03178448). The demographic, clinical and laboratory information of each participant was obtained. Univariable and multivariable logistic regression models were used to determine CAVS risk factors. A prediction model for predicting CAVS risk based on risk factors was developed and the result was performed by nomogram. The discrimination of the prediction model was assessed by receiver operating characteristic curve analysis. The degree of fitting for the prediction model was assessed by calibration curve analysis. A total of 3067 participants (1427 men and 1640 women) were included. The prevalence of CAVS among those aged below 60 years old, 60-70 years old and over 70 years old was 4.1%, 10.3% and 21.9%, respectively. Multivariable regression analysis revealed that age (OR: 1.099; 95% CI: 1.076 to 1.123, p<0.001), pulse pressure (OR: 1.020; 95% CI: 1.009 to 1.031, p<0.001), uric acid (OR: 1.003; 95% CI: 1.001 to 1.004, p<0.001), glycosylated haemoglobin (HbA1c) (OR: 1.152; 95% CI: 1.028 to 1.292, p=0.015) and lipoprotein(a) (OR: 1.002; 95% CI: 1.001 to 1.002, p<0.001) were independent risk factors for CAVS. High-density lipoprotein cholesterol (HDL-C) was a protective factor for CAVS (OR: 0.539; 95% CI: 0.349 to 0.831, p=0.005). The prediction model including the above risk factors showed a risk prediction of CAVS with good discrimination. The area under the curve value was found to be 0.743 (95% CI: 0.711 to 0.775). CONCLUSION: CAVS is currently prevalent in the elderly Chinese population. Age, pulse pressure, HbA1c, lower-level HDL-C, lipoprotein(a) and uric acid are the independent risk factors for CAVS.

Cross-cultural adaptation of The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire: A methodological systematic review.

BACKGROUND: The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is a reliable and sensitive measure of disability to determine functional status and evaluate curative effects in low back pain, it has now been cross-cultural translated into many other languages and adapted for use in different countries. We aim to evaluate the translation procedures and measurement properties of cross-cultural adaptations of the JOABPEQ. METHODS: Studies related to cross-cultural adaptation of the JOABPEQ in a specific language/culture were searched in PubMed, Embase, CINAHL, SciELO, PsycINFO, SinoMed, and Web of Science from their inception to March 2022. The Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and the Consensus-based Standards for the Selection of Health Status Measurement Instruments guideline were used for evaluation. RESULTS: Nine different versions of cross-cultural JOABPEQ adaptations in 8 different languages/cultures were included. The adaptation process was not strictly performed, such as standard forward translation and expert committee review were rarely reported. Content validity (8/9), floor and ceiling effects (3/9), reliability (4/9), and interpretability (6/9) were assessed in most of the adaptations, while agreement (2/9), responsiveness (2/9), and the internal consistency (2/9) were not. JOABPEQ can replace functional and quality of life score to reduce the burden of scientific research. CONCLUSION: We recommend Persian-Iranian, simplified Chinese-Chinese Mandarin, Thai and Gunaydin G's Turkish adaptations for application. The numerical pain rating scale/visual analogue scale in low back pain and lower extremities, as well as numbness in lower extremities could not be neglected in JOABPEQ adaptations.

[Effect of preoperative carbohydrates intake on the gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures].

OBJECTIVE: To investigate the effect of 300 mL carbohydrates intake two hours before sur-gery on the gastric volume (GV) in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures by using gastric antrum sonography, and further assess the risk of reflux aspiration. METHODS: From June 2020 to February 2021, a total of 80 patients, aged 18-65 years, body mass index (BMI) 18-35 kg/m2, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for gynecological laparoscopic procedures positioning in trendelenburg were recruited and divided into two groups: the observation group (n =40) and the control group (n=40). In the observation group, solid food was restricted after 24:00, the patients were required to take 300 mL carbohydrates two hours before surgery. In the control group, solid food and liquid intake were restricted after 24:00 the night before surgery. The cross-sectional area (CSA) of gastric antrum was measured in supine position and right lateral decubitus position before anesthesia. Primary outcome was gastric volume (GV) in each group. Secondary outcome included Perlas A semi-quantitative grading and gastric volume/weight (GV/W). All the patients received assessment of preoperative feeling of thirsty and hunger with visual analogue scale (VAS). RESULTS: Complete data were available in eighty patients. GV was (58.8±23.6) mL in the intervention group vs. (56.3±22.1) mL in the control group, GV/W was (0.97±0.39) mL/kg vs. (0.95±0.35) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 24 patients (60%), 1 in 15 patients (37.5%), 2 in 1 patient (2.5%) in the intervention group and 0 in 25 (62.5%), 1 in 13 (32.5%), 2 in 2 (5%) in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). A total of 3 patients (1 in the intervention group and 2 in the control group) with Perlas A semi-quantitative grading 2 were treated with special intervention, no aspiration case was observed in this study. The observation group endured less thirst and hunger (P＜0.05). CONCLUSION: Three hundred mL carbohydrates intake two hours before surgery along with ultrasound guided gastric content monitoring does not increase gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic surgery, and is helpful in minimizing disturbance to the patient's physiological needs, therefore leading to better clinical outcome.

[Research Progress in Physiological Evaluation and Treatment of Visually Induced Motion Sickness in Virtual Reality].

Visually induced motion sickness(VIMS)is the major barrier to be broken in the development of virtual reality(VR)technology,which seriously affects the progress in the VR industry.Therefore,the detection and evaluation of VIMS has become a hot research topic nowadays.We review the progress in physiological assessment of VIMS in VR based on several physiological indicators,including electroencephalogram(EEG),postural sway,eye movements,heart rate variability,and skin electrical signals,and summarize the available therapies,aiming to provide an outlook on the future research directions of VIMS.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

BACKGROUND: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. METHODS: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. RESULTS: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment. CONCLUSIONS: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Machine learning is an effective method to predict the 90-day prognosis of patients with transient ischemic attack and minor stroke.

OBJECTIVE: We aimed to investigate factors related to the 90-day poor prognosis (mRS≥3) in patients with transient ischemic attack (TIA) or minor stroke, construct 90-day poor prognosis prediction models for patients with TIA or minor stroke, and compare the predictive performance of machine learning models and Logistic model. METHOD: We selected TIA and minor stroke patients from a prospective registry study (CNSR-III). Demographic characteristics,smoking history, drinking history(≥20g/day), physiological data, medical history,secondary prevention treatment, in-hospital evaluation and education,laboratory data, neurological severity, mRS score and TOAST classification of patients were assessed. Univariate and multivariate logistic regression analyses were performed in the training set to identify predictors associated with poor outcome (mRS≥3). The predictors were used to establish machine learning models and the traditional Logistic model, which were randomly divided into the training set and test set according to the ratio of 70:30. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. The evaluation indicators of the model included the area under the curve (AUC) of the discrimination index and the Brier score (or calibration plot) of the calibration index. RESULT: A total of 10967 patients with TIA and minor stroke were enrolled in this study, with an average age of 61.77 ± 11.18 years, and women accounted for 30.68%. Factors associated with the poor prognosis in TIA and minor stroke patients included sex, age, stroke history, heart rate, D-dimer, creatinine, TOAST classification, admission mRS, discharge mRS, and discharge NIHSS score. All models, both those constructed by Logistic regression and those by machine learning, performed well in predicting the 90-day poor prognosis (AUC >0.800). The best performing AUC in the test set was the Catboost model (AUC=0.839), followed by the XGBoost, GBDT, random forest and Adaboost model (AUCs equal to 0.838, 0, 835, 0.832, 0.823, respectively). The performance of Catboost and XGBoost in predicting poor prognosis at 90-day was better than the Logistic model, and the difference was statistically significant(P<0.05). All models, both those constructed by Logistic regression and those by machine learning had good calibration. CONCLUSION: Machine learning algorithms were not inferior to the Logistic regression model in predicting the poor prognosis of patients with TIA and minor stroke at 90-day. Among them, the Catboost model had the best predictive performance. All models provided good discrimination.

Dose-response relationship between dietary inflammatory index and diabetic kidney disease in US adults.

OBJECTIVE: The impact of the dietary potential inflammatory effect on diabetic kidney disease (DKD) has not been adequately investigated. The present study aimed to explore the association between dietary inflammatory index (DII) and DKD in US adults. DESIGN: This is a cross-sectional study. SETTING: Data from the National Health and Nutrition Examination Survey (2007-2016) were used. DII was calculated from 24-h dietary recall interviews. DKD was defined as diabetes with albuminuria, impaired glomerular filtration rate or both. Logistic regression and restricted cubic spline models were adopted to evaluate the associations. PARTICIPANTS: Data from the National Health and Nutrition Examination Survey (2007-2016) were used, which can provide the information of participants. RESULTS: Four thousand two-hundred and sixty-four participants were included in this study. The adjusted OR of DKD was 1·04 (95 % CI 0·81, 1·36) for quartile 2, 1·24 (95 % CI 0·97, 1·59) for quartile 3 and 1·64 (95 % CI 1·24, 2·17) for quartile 4, respectively, compared with the quartile 1 of DII. A linear dose-response pattern was observed between DII and DKD (Pnonlinearity = 0·73). In the stratified analyses, the OR for quartile 4 of DII were significant among adults with higher educational level (OR 1·83, 95 % CI 1·26, 2·66) and overweight or obese participants (OR 1·67, 95 % CI 1·23, 2·28), but not among the corresponding another subgroup. The interaction effects between DII and stratified factors on DKD were not statistically significant (all P values for interactions were >0·05). CONCLUSIONS: Our findings suggest that a pro-inflammatory diet, shown by a higher DII score, is associated with increased odd of DKD.

P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack.

BACKGROUND AND PURPOSE: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. METHODS: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I2 test. RESULTS: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68-0.83], I2=0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90-1.89], I2=0%), cardiovascular death (RR, 1.34 [95% CI, 0.56-3.17], I2=0%), mild bleeding (RR, 1.25 [95% CI, 0.37-4.29], I2=94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62-3.39], I2=0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16-4.08], I2=41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75-4.67], I2=0%) or ticagrelor (RR, 2.17 [95% CI, 1.16-4.08], I2=37%) but not within 21 days or clopidogrel. CONCLUSIONS: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

Differential responses of bone to angiotensin II and angiotensin(1-7): beneficial effects of ANG(1-7) on bone with exposure to high glucose.

Osteoporosis, diabetes, and hypertension are common concurrent chronic disorders. This study aimed to explore the respective effects of angiotensin II (ANG II) and angiotensin(1-7) [ANG(1-7)], active peptides in the renin-angiotensin system, on osteoblasts and osteoclasts under high-glucose level, as well as to investigate the osteo-preservative effects of ANG II type 1 receptor (AT1R) blocker and ANG(1-7) in diabetic spontaneously hypertensive rats (SHR). ANG II and ANG(1-7), respectively, decreased and increased the formation of calcified nodules and alkaline phosphatase activity in MC3T3-E1 cells under high-glucose level, and respectively stimulated and inhibited the number of matured osteoclasts and pit resorptive area in RANKL-induced bone marrow macrophages. Olmesartan and Mas receptor antagonist A779 could abolish those effects. ANG II and ANG(1-7), respectively, downregulated and upregulated the expressions of osteogenesis factors in MC3T3-E1 cells. ANG II promoted the expressions of cathepsin K and MMP9 in RAW 264.7 cells, whereas ANG(1-7) repressed these osteoclastogenesis factors. ANG II rapidly increased the phosphorylation of Akt and p38 in RAW 264.7 cells, whereas ANG(1-7) markedly reduced the phosphorylation of p38 and ERK under high-glucose condition. After treatments of diabetic SHR with valsartan and ANG(1-7), a significant increase in trabecular bone area, bone mineral density, and mechanical strength was only found in the ANG(1-7)-treated group. Treatment with ANG(1-7) significantly suppressed the increase in renin expression and ANG II content in the bone of SHR. Taken together, ANG II/AT1R and ANG(1-7)/Mas distinctly regulated the differentiation and functions of osteoblasts and osteoclasts upon exposure to high-glucose condition. ANG(1-7) could protect SHR from diabetes-induced osteoporosis.

Muscone suppresses inflammatory responses and neuronal damage in a rat model of cervical spondylotic myelopathy by regulating Drp1-dependent mitochondrial fission.

Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti-inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the effects of muscone on a rat model of chronic cervical cord compression, as well as activated BV2 cells and injured neurons, were assessed. The results showed that muscone intervention improved motor function compared with vehicle-treated rats. Indeed, muscone attenuated pro-inflammatory cytokine expression, neuronal-apoptosis indicators in the lesion area, and activation of the nod-like receptor family pyrin domain-containing 3 inflammasome, nuclear transcription factor-κB, and dynamin-related protein 1 in Iba1- and ßIII-tubulin-labeled cells. Compared with vehicle-treated rats, compression sites of muscone-treated animals exhibited elongated mitochondrial morphologies in individual cell types and reduced reactive oxygen species. In vitro results indicated that muscone suppressed microglial activation and neuronal damage by regulating related-inflammatory or apoptotic molecules. Moreover, muscone inhibited dynamin-related protein 1 activation in activated BV2 cells and injured neurons, whereby it rescued mitochondrial fragmentation and reactive oxygen species production, which regulate a wide range of inflammatory and apoptotic molecules. Our findings reveal that muscone attenuates neuroinflammation and neuronal damage in rats with chronic cervical cord compression by regulating mitochondrial fission events, suggesting its promise for CSM therapy.

A comparison between the low back pain scales for patients with lumbar disc herniation: validity, reliability, and responsiveness.

BACKGROUND: Although the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Numerical Pain Rating Scale (NPRS), Oswestry Disability Index (ODI), Roland Morris Disability Questionnaire (RMDQ), and Short Form 36 Health Survey (SF-36) has shown a preferable psychometric properties in patients with low back pain (LBP), but no study has yet determined these in conservative treatment of patients with lumbar disc herniation (LDH). Thus the current study aimed to compare those scales in LDH patients receiving conservative treatment to select the better option to assess the severity of disease. METHODS: LDH patients were invited to complete the JOABPEQ, NPRS, ODI, RMDQ, and SF-36 twice. The internal consistency was evaluated by the Cronbach's α. Test-retest reliability was tested by the intraclass correlation coefficient (ICC). The relationships of these scales were evaluated by the Pearson correlation coefficients (r). The responsiveness was operationalised using the receiver operating characteristic (ROC) curve, as well as the comparison of smallest detectable change (SDC), minimum important change (MIC). RESULTS: A total of 353 LDH patients were enrolled. Four subscales of the Chinese JOABPEQ were over 0.70, then the ICCs for the test-retest reliability were over 0.75. For functional status, remarked negative correlations could be seen between JOABPEQ Q2-Q4 and ODI, as well as RMDQ (r = - 0.634 to - 0.752). For general health status, remarkable positive correlations could also be seen between Q5 Mental health and SF-36 PCS (r = 0.724) as well as SF-36 MCS (r = 0.736). Besides, the area under of the curves (AUC) of the JOABPEQ ranged from 0.743 to 0.827, indicating acceptale responsiveness, as well as the NPRS, ODI, and RMDQ. CONCLUSION: NPRS, and ODI or RMDQ is recommended in studies related to LDH patients, while if the quality of life also is needed to observe, the NPRS, and JOABPEQ would be more appropriate rather than SF-36.

[on oligozoospermia and asthenospermia].

OBJECTIVE: To observe the clinical effect of Yihechun Capsules (YHC) on oligozoospermia and asthenospermia. METHODS: A total of 181 male patients with infertility were randomly divided into a YHC+Levocarnitine (LC) group (n = 93, including 42 cases of oligozoospermia, 20 cases of asthenospermia and 31 cases of oligoasthenospermia) and an LC control group (n = 88, including 39 cases of oligozoospermia, 22 cases of asthenospermia and 27 cases of oligoasthenospermia), the former treated with YHC (ï¼»0.3 g per capsuleï¼½, once 4 capsules, bid, 30 minutes after meal) combined with LC oral liquid (2－3 g/d, tid, at mealtime) and the latter with LC oral liquid only (2－3 g/d, tid, at mealtime). After 3 months of treatment, comparisons were made between the two groups of patients in sperm concentration, the percentages of grade a and grade a+b sperm, and the rate of pregnancy. RESULTS: Of the 181 patients, 5 in the YHC+LC group and 2 in the LC control group failed to complete the course of treatment. There were no statistically significant differences between the two groups of patients in the baseline sperm concentration and the percentages of grade a and grade a+b sperm (P > 0.05), wich were all markedly increased in both the YHC+LC and the LC control groups (P < 0.05) after 3 months of treatment. And the patients of the YHC+LC group, compared with the controls, showed even more significant increases, as the oligozoospermia patients in sperm concentration (ï¼»21.07 ± 6.98ï¼½ vs ï¼»16.56 ± 1.82ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»27.53 ± 3.34ï¼½% vs ï¼»26.88 ± 1.35ï¼½%, P < 0.05) and grade a+b sperm (ï¼»53.32 ± 3.16ï¼½% vs ï¼»52.63 ± 2.48ï¼½%, P < 0.05), the asthenospermia patients in sperm concentration (ï¼»26.36 ± 3.37ï¼½ vs ï¼»24.42 ± 2.21ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»25.28 ± 4.64ï¼½% vs ï¼»21.32 ± 3.28ï¼½%, P < 0.05) and grade a+b sperm (ï¼»49.19 ± 2.87ï¼½% vs ï¼»45.64 ± 1.78ï¼½%, P < 0.05), and the oligoasthenospermia patients in sperm concentration (ï¼»19.38 ± 3.39ï¼½ vs ï¼»18.75 ± 1.35ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»22.65 ± 4.81ï¼½% vs ï¼»21.31 ± 2.42ï¼½%, P < 0.05) and grade a+b sperm (ï¼»48.74 ± 5.61ï¼½% vs ï¼»44.36 ± 1.32ï¼½%, P < 0.05). The pregnancy rate was dramatically higher in the YHC+LC than in the LC control group (36.4% ï¼»32/88ï¼½ vs 15.1% ï¼»13/86ï¼½, P < 0.01). CONCLUSIONS: Yihechun Capsules combined with Levocarnitine oral liquid is evidently effective for the treatment of oligozoospermia and asthenospermia.

Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke.

Background and Purpose- Emergency medical services (EMSs) are critical for early treatment of patients with ischemic stroke, yet data on EMS utilization and its association with timely treatment in China are still limited. Methods- We examined data from the Chinese Stroke Center Alliance for patients with ischemic stroke from June 2015 to June 2018. Absolute standardized difference was used for covariates' balance assessments. We used multivariable logistic models with the generalized estimating equations to account for intrahospital clustering in identifying demographic and clinical factors associated with EMS use as well as in evaluating the association of EMS use with timely treatment. Results- Of the 560 447 patients with ischemic stroke analyzed, only 69 841 (12.5%) were transported by EMS. Multivariable-adjusted results indicated that those with younger age, lower levels of education, less insurance coverage, lower income, lower stroke severity, hypertension, diabetes mellitus, and peripheral vascular disease were less likely to use EMS. However, a history of cardiovascular diseases was associated with increased EMS usage. Compared with self-transport, EMS transport was associated with significantly shorter onset-to-door time, door-to-needle time (if prenotification was sent), earlier arrival (adjusted odds ratio [95% CIs] were 2.07 [1.95-2.20] for onset-to-door time ≤2 hours, 2.32 [2.18-2.47] for onset-to-door time ≤3.5 hours), and more rapid treatment (2.96 [2.88-3.05] for IV-tPA [intravenous recombinant tissue-type plasminogen activator] in eligible patients, 1.70 [1.62-1.77] for treatment with IV-tPA by 3 hours if onset-to-door time ≤2 hours, and 1.76 [1.70-1.83] for treatment with IV-tPA by 4.5 hours if onset-to-door time ≤3.5 hours). Conclusions- Although EMS transportation is associated with substantial reductions in prehospital delay and improved likelihood of early arrival and timely treatment, rate of utilization is currently low among Chinese patients with ischemic stroke. Developing an efficient EMS system and promoting culture-adapted education efforts are necessary for improving EMS activation.

Atrial Fibrillation Known Before or Detected After Stroke Share Similar Risk of Ischemic Stroke Recurrence and Death.

Background and Purpose- We aim to compare the risk of 1-year ischemic stroke recurrence and death for atrial fibrillation diagnosed after stroke (AFDAS), atrial fibrillation known before stroke (KAF), and sinus rhythm (SR). Methods- From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals in the China National Stroke Registry II. Based on heart rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We explored the relationship between heart rhythm groups and 1-year ischemic stroke recurrence or death by using Cox regression adjusted for multiple covariates. Considering that death is a competing risk for stroke recurrence, we used the competing risks analysis of Fine and Gray and subdistribution Cox proportional hazards to test the association between heart rhythm and 1-year outcomes. Results- Among 19 604 ischemic stroke patients, 17 727 had SR, 495 AFDAS, and 1382 KAF. At 1 year, 54 (10.9%) patients with AFDAS, 182 (13.2%) with KAF, and 1008 (5.7%) with SR had recurrent ischemic strokes ( P<0.0001). Mortality was 22.0% in patients with AFDAS, 22.1% in patients with KAF, and 7.0% in patients with SR ( P<0.0001). AFDAS-related ischemic stroke recurrence adjusted risk was higher than that of SR (adjusted subdistribution hazard ratios, 1.61; 95% CI, 1.29-2.01) but not different from that of KAF (adjusted subdistribution hazard ratio, 1.12; 95% CI, 0.87-1.45]). The adjusted risk of 1-year death for AFDAS was also higher than that of SR (hazard ratio, 1.70; 95% CI, 1.37-2.12) and not different from that of KAF (hazard ratio, 1.10; 95% CI, 0.86-1.41). Conclusions- This study showed that AFDAS had similar risk of 1-year ischemic stroke recurrence and mortality when compared with KAF and higher risk when compared with SR. The potential risk of AFDAS should be given more emphasis, and appropriate treatment is needed to achieve reduction in the incidence of stroke recurrence and mortality.

Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review.

Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta-analysis, subgroup analysis, and network meta-analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole-treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p < 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta-analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality.