Prevalence and plasma exosome-derive microRNA diagnostic biomarker screening of adolescent idiopathic scoliosis in Yunnan Province, China.

Background: Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study. Methods: From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs. Results: The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value. Conclusions: We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

Preoperative Heart Rate Variability During Sleep Predicts Vagus Nerve Stimulation Outcome Better in Patients With Drug-Resistant Epilepsy.

Objective: Vagus nerve stimulation (VNS) is an adjunctive and well-established treatment for patients with drug-resistant epilepsy (DRE). However, it is still difficult to identify patients who may benefit from VNS surgery. Our study aims to propose a VNS outcome prediction model based on machine learning with multidimensional preoperative heart rate variability (HRV) indices. Methods: The preoperative electrocardiography (ECG) of 59 patients with DRE and of 50 healthy controls were analyzed. Responders were defined as having at least 50% average monthly seizure frequency reduction at 1-year follow-up. Time domain, frequency domain, and non-linear indices of HRV were compared between 30 responders and 29 non-responders in awake and sleep states, respectively. For feature selection, univariate filter and recursive feature elimination (RFE) algorithms were performed to assess the importance of different HRV indices to VNS outcome prediction and improve the classification performance. Random forest (RF) was used to train the classifier, and leave-one-out (LOO) cross-validation was performed to evaluate the prediction model. Results: Among 52 HRV indices, 49 showed significant differences between DRE patients and healthy controls. In sleep state, 35 HRV indices of responders were significantly higher than those of non-responders, while 16 of them showed the same differences in awake state. Low-frequency power (LF) ranked first in the importance ranking results by univariate filter and RFE methods, respectively. With HRV indices in sleep state, our model achieved 74.6% accuracy, 80% precision, 70.6% recall, and 75% F1 for VNS outcome prediction, which was better than the optimal performance in awake state (65.3% accuracy, 66.4% precision, 70.5% recall, and 68.4% F1). Significance: With the ECG during sleep state and machine learning techniques, the statistical model based on preoperative HRV could achieve a better performance of VNS outcome prediction and, therefore, help patients who are not suitable for VNS to avoid the high cost of surgery and possible risks of long-term stimulation.

Experimental and molecular dynamics study into the surfactant effect upon coal wettability.

In order to improve the wettability and permeability of coal seams, the water injection efficiency of coal seams has to be boosted, the amount of dust generation has to be reduced, and coal and gas outburst must be prevented, and a surfactant is used to modulate the coal surface wettability. In this work, taking coal samples from Pingdingshan mine in Henan as the research object, their surface chemistry was initially scrutinized and then coal surface engineering via surfactants was inspected by a contact angle test. The coal wettability was ameliorated with surfactants, particularly using the 1 wt% non-ionic surfactant Triton X-100, which elicited a 47% lower contact angle than the raw coal. The surface free energy of the coal sample modified by 1.0 wt% Triton X-100 was increased from 44.51 mN m-1 to 49.52 mN m-1. The microstructural characteristics of coal samples allowed leveraging the Wiser model to construct three kinds of surfactant-coal adsorption models to dissect the adsorption configuration of the system. The results indicate that the addition of surfactants increases both the interaction of water with the coal and the diffusion coefficient of water molecules, resulting in the coal surface transformation from hydrophobicity to hydrophilicity. Our current work can provide salutary guidance and reference for coal water injection and dust suppression.

Preoperative Heart Rate Variability as Predictors of Vagus Nerve Stimulation Outcome in Patients with Drug-resistant Epilepsy.

Vagus nerve stimulation (VNS) is an adjunctive treatment for drug-resistant epilepsy (DRE). However, it is still difficult to predict which patients will respond to VNS treatment and to what extent. We aim to explore the relationship between preoperative heart rate variability (HRV) and VNS outcome. 50 healthy control subjects and 63 DRE patients who had received VNS implants and had at least one year of follow up were included. The preoperative HRV were analyzed by traditional linear methods and heart rhythm complexity analyses with multiscale entropy (MSE). DRE patients had significantly lower complexity indices (CI) as well as traditional linear HRV measurements than healthy controls. We also found that non-responders0 had significantly lower preoperative CI including Area 1-5, Area 6-15 and Area 6-20 than those in the responders0 while those of the non-responders50 had significantly lower RMSSD, pNN50, VLF, LF, HF, TP and LF/HF than the responders50. In receiver operating characteristic (ROC) curve analysis, Area 6-20 and RMSSD had the greatest discriminatory power for the responders0 and non-responders0, responders50 and non-responders50, respectively. Our results suggest that preoperative assessment of HRV by linear and MSE analysis can help in predicting VNS outcomes in patients with DRE.

Response of Rat Tibia to Prolonged Unloading Under the Influence of Electrical Stimulation at the Dorsal Root Ganglion.

PURPOSE: Immobilization of weight bearing skeletons or microgravity results in disuse osteoporosis in both human and animals. Our previous study demonstrated that electrical stimulation at the dorsal root ganglion (DRG) with an implantable micro-electrical stimulation system (IMESS) could trigger secretion of bone anabolic calcitonin gene-related peptide (CGRP) and prevent bone loss in a short-term hindlimb unloading rat model. This study was designed to further investigate whether electrical stimulation to the DRG could prevent bone loss due to prolonged unloading. METHODS: Eighteen adult rats were randomly assigned into three groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with electrical stimulation (HUES). Electrical stimulation was applied via IMESS to the right DRGs at vertebral levels L4-L6 in HUES group for 6 weeks. RESULTS: Following unloading for 6 weeks, proximal tibia metaphysis was shown 64.0% decrease in bone mineral content (BMC) and 47.0% decrease in bone mineral density (BMD) in HU group while significant reduced bone lose with 2.7% increase in total BMC and only 9.2% decrease in total BMD in HUES group. Diaphyseal BMD decreased significantly in both HU and HUES group as compared with CC group. There was enhancement of CGRP expression in the DRGs in HUES group. CONCLUSION: This experimental study proved the proposed concept using electrical stimulation at the DRG for prevention of disuse-induced bone loss in a rat hindlimb suspension model.

The ability of anterior thalamic signals to predict seizures in temporal lobe epilepsy in kainate-treated rats.

OBJECTIVE: To analyze the local field potential (LFP) of the anterior nucleus of the thalamus (ANT) of epileptic rats using the Generic Osorio-Frei algorithm (GOFA), and to determine the ability of the ANT LFP to predict clinical seizures in temporal lobe epilepsy. METHODS: GOFA is an advanced real-time technique used to detect and predict seizures. In this article, GOFA was utilized to process the electrical signals of ANT and the motor cortex recorded in 12 rat models of temporal lobe epilepsy (TLE) induced via the injection of kainic acid into the unilateral hippocampus. The electroencephalography (EEG) data included (1) 161 clinical seizures (each contained a 10-min segment) involving the ANT and cortical regions and (2) one hundred three 10-min segments of randomly selected interictal (no seizure) data. RESULTS: Minimal false-positives (0.51 ± 0.36/h) and no false-negatives were detected based on the ANT LFP data processed using GOFA. In ANT LFP, the delay from electrographic onset (EO) to automated onset (AO) was 1.24 ± 0.47 s, and the delay from AO to clinical onset (CO) was 7.73 ± 3.23 s. The AO time occurred significantly earlier in the ANT than in the cortex (p = 0.001). In 75.2% of the clinical onsets predicted by ANT LFP, it was 1.37 ± 0.82 s ahead of the prediction of cortical potentials (CPs), and the remainder were 0.84 ± 0.31 s slower than the prediction of CPs. SIGNIFICANCE: ANT LFP appears to be an optimal option for the prediction of seizures in temporal lobe epilepsy. It was possible to upgrade the responsive neurostimulation system to emit electrical stimulation in response to the prediction of epileptic seizures based on the changes in the ANT LFP.

Potential Protective Effects of Chronic Anterior Thalamic Nucleus Stimulation on Hippocampal Neurons in Epileptic Monkeys.

BACKGROUND: Stimulation of the anterior nucleus of the thalamus (ANT) is effective in seizure reduction, but the mechanisms underlying the beneficial effects of ANT stimulation are unclear. OBJECTIVE: To assess the beneficial effects of ANT stimulation on hippocampal neurons of epileptic monkeys. METHODS: Chronic ANT stimulation was applied to kainic acid-induced epileptic monkeys. Behavioral seizures were continuously monitored. Immunohistochemical staining and western blot assays were performed to assess the hippocampal injury and the effects of ANT stimulation. RESULTS: The frequency of seizures was 42.8% lower in the stimulation group compared with the sham-stimulation group. Immunohistochemical staining and western blot analyses indicated that neuronal loss and apoptosis were less severe and that neurofilament synthesis was enhanced in the stimulation monkeys compared with the sham-stimulation group. These data showed that the hippocampal injury was less severe in monkeys in the stimulation group than in those in the sham-stimulation group. CONCLUSIONS: Our data suggest that chronic ANT stimulation may exert protective effects on hippocampal neurons and boost the regeneration of neuronal fibers. These effects may be closely related to the mechanisms of ANT stimulation in epilepsy treatment.

Clinical observation on recombinant human endostatin combined with chemotherapy for advanced gastrointestinal cancer.

OBJECTIVE: To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rh- endostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer. MATERIALS AND METHODS: A total of 70 patients with advanced gastrointestinal adenocarcioma confirmed by histopathology and/or cytological examination were divided into group A (37 patients) and group B (33 patients). Patients in group A were given intravenous drip of 15 mg endostar added into 500 mL normal saline, once every other day until the cessation of chemotherapy or patients' maximal tolerance to chemotherapy. Patients in group B received chemotherapy alone. Two groups selected the same chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of 180 mg/m2 irinotecan, intravenous drip of 200 mg/m2 calcium folinate (CF) and 400 mg/m2 5-fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 400 mg/m2 5-Fu for 46 h. FOLFOX4 scheme: intravenous injection of 85 mg/m2 oxaliplatin (L-OHP), 200 mg/m2 calcium folinate (CF) and 400 mg/m2 5-FU on d1 for 2 h, and then continuous intravenous pumping of 2 400 mg/m2 5-Fu for 46 h. XELOX scheme: oral administration of 1 500 mg/m2 xeloda (or tegafur 50~60 mg) in twice during d1~14 and intravenous drip of 135 mg/m2 L-OHP on d1 for 2 h. The modified FOLFOX scheme: intravenous injection of 135 mg/m2 L-OHP on d1 for 2 h, 200 mg/m2 CF and 1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy regimens which were same as Group A, but no addition of endostar. Before chemotherapy, patients were given intravenous injection of 8 mg ondansetron, intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for prevention of vomiting, protection of liver and stomach as well as symptomatic supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was evaluated every 2 cycles. RESULTS: 32 patients in Group A could be evaluated, and the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%, respectively. 31 patients in Groups could be evaluated, and the RR and DCR were 32.26% and 54.84%, respectively. The differences between 2 groups were significant. The toxic effects include myelosuppression, gastrointestinal reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. CONCLUSIONS: Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study.

Dorsal root ganglion electrical stimulation promoted intertransverse process spinal fusion without decortications and bone grafting: a proof-of-concept study.

BACKGROUND CONTEXT: Periosteum, endosteum, and bone are innervated by sensory nerves expressing calcitonin gene-related peptide (CGRP), which is a known osteoanabolic peptide and plays an important role in fracture healing and spinal fusion. Synthesis and release of CGRP are found in sensory neurons located in the dorsal root ganglions (DRGs) and can be upregulated by electrical stimulation (ES) at DRG. PURPOSE: To prove our study hypothesis on the potential of precise ES at DRG through implantable microelectrical stimulation system (IMESS) for its effect on promoting spinal fusion in a rat model without decortications and bone grafting. STUDY DESIGN: An experimental animal study. METHODS: A novel IMESS was developed for stimulating L4-L6 DRG in rats. Sixteen rats were used and divided equally into the control group without ES and the ES group, with a daily 20 minutes ES to DRG for 6 weeks. At the end of 6 weeks, radiography and microcomputed tomography were conducted to evaluate new bone formation and spinal fusion. Bilateral L4-L6 DRGs were harvested for immunohistochemistry and quantification of neurons with upregulated CGRP expression. RESULTS: In the ES group, rate of radiographic fusion with complete and uninterrupted bony bridging was 100% (8/8) at the right L4/L5 transverse processes and 75% (6/8) at the right L5/L6 transverse processes. Bony callus formation was absent at the left L4-L6 transverse processes in the ES group and in bilateral L4-L6 transverse processes in the control group. CONCLUSIONS: We proved for the first time that precise ES at DRG through IMESS effectively promoted intertransverse process fusion in rat model without decortications and bone grafting. Electrical stimulation at DRG might be an attractive minimal invasive bioengineering approach and an alternative therapy for intertransverse process fusion that is increasingly being used for the treatment of degenerative spine disorders.

Characterization of integrons among Escherichia coli in a region at high incidence of ESBL-EC.

Objective : The aim of study was to investigate the distribution of the integrons in Escherichia coli (E. coli) isolates, and analyze the possible relationship between the antimicrobial resistance profiles and the integrons. Methods : The antimicrobial profiles of 376 E. coli strains were analysed by disk diffusion test. The integron genes and variable regions were detected by PCR. Some amplicons were sequenced to determine the gene cassettes style. Results : Of 376 isolates, 223 isolates (59.3%) were confirmed as ESBL-EC. Comparison to ESBL-negative E. coli, the high rates of resistance to the third and fourth generation of cephalosporins, penicillins and amikacin were found in ESBL-EC. Only class 1 was integron detected in the isolates, and the prevalence of it was 66.5%. It was commonly found in ESBL-EC (77.6%, 173/223), which was higher than that of ESBL-negative E. coli (50.3%, 77/153) (p<0.001). Six different genes cassettes were detected in this study and were classified into three groups: dfr17-aadA5, dfrA12-aadA2 and aacA4-CmlA1. Additionally, more than one gene array harboured in 13.9% isolates of ESBL-EC, while in 9.1% isolates of ESBL-negative E.coli. Conclusion : The high incidence of ESBL-EC with resistance to multiple antibiotics were detected in the isolates from Blood stream infection (BSI). More resistant gene cassettes in ESBL-EC may partially underlie the high resistance to amikacin, while no relation exists between the high incidence of ESBL-EC and classes 1~ 3 integrons in this region.

Membrane stretch and cytoplasmic Ca2+ independently modulate stretch-activated BK channel activity.

Large conductance Ca(2+)-activated K(+) (BK) channels are responsible for changes in chemical and physical signals such as Ca(2+), Mg(2+) and membrane potentials. Previously, we reported that a BK channel cloned from chick heart (SAKCaC) is activated by membrane stretch. Molecular cloning and subsequent functional characterization of SAKCaC have shown that both the membrane stretch and intracellular Ca(2+) signal allosterically regulate the channel activity via the linker of the gating ring complex. Here we investigate how these two gating principles interact with each other. We found that stretch force activated SAKCaC in the absence of cytoplasmic Ca(2+). Lack of Ca(2+) bowl (a calcium binding motif) in SAKCaC diminished the Ca(2+)-dependent activation, but the mechanosensitivity of channel was intact. We also found that the abrogation of STREX (a proposed mechanosensing apparatus) in SAKCaC abolished the mechanosensitivity without altering the Ca(2+) sensitivity of channels. These observations indicate that membrane stretch and intracellular Ca(2+) could independently modulate SAKCaC activity.

[Effects of electroacupuncture of unilateral and bilateral "zusanli" (ST 36) on serum TNF-alpha, IL-1 and IL-4 levels in rats with chronic inflammatory pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on serum tumor necrosis factor-alpha (TNF-alpha), IL-1 and IL-4 levels in rats with chronic inflammatory pain, so as to investigate its underlying mechanism in relieving pain. Methods Forty-eight SD rats were randomized into control, model, EA-unilateral ST 36, and EA-bilateral ST 36 groups, with 12 rats in each. Chronic inflammatory pain model was established by intradermal injection of Freund's complete adjuvant (0.1 mL) into the right paw. EA (2 Hz/100 Hz, 1-2-3 mA) was applied to the unilateral "Zusanli" (ST 36) and bilateral "Zusanli" (ST 36) for 30 min, once every 3 days and continuously for 4 weeks. Serum TNF-alpha, IL-1 and IL-4 contents were detected by enzyme linked immunosorbent assay. Results Compared with the control group, serum TNF-alpha, IL-1 and IL-4 contents of the model group increased significantly (P < 0.01), while in comparison with the model group, the levels of the 3 indexes were decreased considerably in both unilateral and bilateral ST 36 groups (P < 0.01). No significant differences were found between the unilateral ST 36 and bilateral ST 36 groups in serum TNF-alpha, IL-1 and IL-4 contents (P > 0.05). CONCLUSION: EA can effectively lower serum TNF-alpha, IL-1 and IL-4 levels in inflammatory pain rats, which may contribute to its effect in relieving inflammatory pain.

[Current research and development trend of implantable neuro-stimulator].

This paper introduces the current application of various kinds of implantable neuro-stimulator at home and abroad, and also analyzes its development trend.