Application of online to offline teaching mode in the training of non-anesthesiology residents in the department of anesthesiology: a randomized, controlled trial.

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology. Trial design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University. Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups. Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p < 0.01). Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness.

SpatialcoGCN: deconvolution and spatial information-aware simulation of spatial transcriptomics data via deep graph co-embedding.

Spatial transcriptomics (ST) data have emerged as a pivotal approach to comprehending the function and interplay of cells within intricate tissues. Nonetheless, analyses of ST data are restricted by the low spatial resolution and limited number of ribonucleic acid transcripts that can be detected with several popular ST techniques. In this study, we propose that both of the above issues can be significantly improved by introducing a deep graph co-embedding framework. First, we establish a self-supervised, co-graph convolution network-based deep learning model termed SpatialcoGCN, which leverages single-cell data to deconvolve the cell mixtures in spatial data. Evaluations of SpatialcoGCN on a series of simulated ST data and real ST datasets from human ductal carcinoma in situ, developing human heart and mouse brain suggest that SpatialcoGCN could outperform other state-of-the-art cell type deconvolution methods in estimating per-spot cell composition. Moreover, with competitive accuracy, SpatialcoGCN could also recover the spatial distribution of transcripts that are not detected by raw ST data. With a similar co-embedding framework, we further established a spatial information-aware ST data simulation method, SpatialcoGCN-Sim. SpatialcoGCN-Sim could generate simulated ST data with high similarity to real datasets. Together, our approaches provide efficient tools for studying the spatial organization of heterogeneous cells within complex tissues.

Impaired neuronal macroautophagy in the prelimbic cortex contributes to comorbid anxiety-like behaviors in rats with chronic neuropathic pain.

A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL. Chemogenetic inactivation of this comorbid anxiety-related neuronal ensemble relieved pain-induced anxiety-like behaviors. Rescuing macroautophagy impairment in this neuronal ensemble relieved chronic pain-associated anxiety and mechanical allodynia and restored synaptic homeostasis at the molecular level. By contrast, artificial disruption of macroautophagy induced early-onset co-morbid anxiety in neuropathic rats, but not general anxiety in normal rats. Taken together, our work identifies causal linkage between PrL neuronal macroautophagy dysfunction and comorbid anxiety in neuropathic pain and provides novel insights into the role of PrL by differentiating its contribution in pain-induced comorbid anxiety from its modulation over general anxiety-like behaviors.Abbreviation: AAV: adeno-associated viruses; ACC: anterior cingulate cortex; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; CAMK2/CaMKII: calcium/calmodulin-dependent protein kinase II; CNO: clozapine-N-oxide; CQ: chloroquine; DIA: data independent acquisition; DIO: double floxed inverse orf; DLG4/PSD-95: discs large MAGUK scaffold protein 4; Dox: doxycycline; GABA: γ-aminobutyric acid; GFP: green fluorescent protein; GO: gene ontology; Gi: inhibitory guanine nucleotide-binding proteins; HsCHRM4/M4D: human cholinergic receptor muscarinic 4; HsSYN: human synapsin; KEGG: Kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; LC3-II: PE conjugated microtubule-associated protein 1 light chain3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mPFC: medial prefrontal cortex; P2A: 2A self-cleaving peptide; PPI: protein-protein interaction networks; PrL: prelimbic cortex; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; rtTA: reverse tetracycline-transactivator; SDS-PAGE: sodium dodecylsulfate-polyacrylamide gel electrophoresis; SHANK3: SH3 and multiple ankyrin repeat domains 3; SLC1A1/EAAC1: solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, systemXag), member 1; SNAP23: synaptosomal-associated protein 23; SNI:spared nerve injury; SQSTM1/p62: sequestosome 1; SYT3: synaptotagmin 3; TRE: tetracycline-responsive element; TRE3G: third-generation tetracycline-responsive element.

Pain Comorbidities with Attention Deficit: A Narrative Review of Clinical and Preclinical Research.

A negative correlation exists between attention and pain. The cognitive impairments linked to pain can significantly impede a patient's healing process and everyday tasks, particularly for individuals experiencing persistent pain. Furthermore, it has been demonstrated that diversion can effectively decrease pain levels in individuals. The focus of this review is to analyze clinical trials and fundamental investigations regarding alterations in focus and persistent discomfort. Moreover, we investigated the common neuroanatomy associated with attention and pain. Furthermore, we examined the impact of various neuromodulators on the transmission of pain and processes related to attention, while also considering the potential neural mechanisms that contribute to the co-occurrence of pain and attention deficits. Further investigation in this field will enhance our comprehension of patient symptoms and the underlying pathophysiology, ultimately resulting in more objective approaches to treatment.

Dynamic Changes of the Infralimbic Cortex and Its Regulation of the Prelimbic Cortex in Rats with Chronic Inflammatory Pain.

The prelimbic cortex (PL) is actively engaged in pain modulation. The infralimbic cortex (IL) has been reported to regulate the PL. However, how this regulation affects pain remains unclear. In the present study, we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli, but a temporary hypo-function of the IL by in vivo electrophysiological recording in rats with peripheral inflammation. Manipulation of the PL or IL had opposite effects on thermal hyperalgesia. Furthermore, the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL. Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia, whereas its inhibition exacerbated chronic pain. Overall, our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain: hypo-function of the IL leads to hyperactivity of the PL, which regulates thermal hyperalgesia, and thus contributes to the chronicity of pain.

Ventral Hippocampal CA1 Pyramidal Neurons Encode Nociceptive Information.

As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats. Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions: the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli, whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties. Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors. Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats, whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain. These results provide direct evidence for the representations of nociceptive information in vCA1.

HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice.

Chronic pain is a significant health problem worldwide. Recent evidence has suggested that the ventral hippocampus is dysfunctional in humans and rodents, with decreased neuronal excitability and connectivity with other brain regions, parallel pain chronicity, and persistent nociceptive hypersensitivity. But the molecular mechanisms underlying hippocampal modulation of pain remain poorly elucidated. In this study, we used ex vivo whole-cell patch-clamp recording, immunofluorescence staining, and behavioral tests to examine whether hyperpolarization-activated cyclic nucleotide-gated channels 2 (HCN2) in the ventral hippocampal CA1 (vCA1) were involved in regulating nociceptive perception and CFA-induced inflammatory pain in mice. Reduced sag potential and firing rate of action potentials were observed in vCA1 pyramidal neurons from CFA-injected mice. Moreover, the expression of HCN2, but not HCN1, in vCA1 decreased in mice injected with CFA. HCN2 knockdown in vCA1 pyramidal neurons induced thermal hypersensitivity, whereas overexpression of HCN2 alleviated thermal hyperalgesia induced by intraplantar injection of CFA in mice. Our findings suggest that HCN2 in the vCA1 plays an active role in pain modulation and could be a promising target for the treatment of chronic pain.

Simulation and evaluation of increased imaging service capacity at the MRI department using reduced coil-setting times.

The wait times for patients from their appointments to receiving magnetic resonance imaging (MRI) are usually long. To reduce this wait time, the present study proposed that service time wastage could be reduced by adjusting MRI examination scheduling by prioritizing patients who require examinations involving the same type of coil. This approach can reduce patient wait times and thereby maximize MRI departments' service times. To simulate an MRI department's action workflow, 2,447 MRI examination logs containing the deidentified information of patients and radiation technologists from the MRI department of a medical center were used, and a hybrid simulation model that combined discrete-event and agent-based simulations was developed. The experiment was conducted in two stages. In the first stage, the service time was increased by adjusting the examination schedule and thereby reducing the number of coil changes. In the second stage, the maximum number of additional patients that could be examined daily was determined. The average number of coil changes per day for the four MRI scanners of the aforementioned medical center was reduced by approximately 27. Thus, the MRI department gained 97.17 min/d, which enabled them to examine three additional patients per month. Consequently, the net monthly income of the hospital increased from US$17,067 to US$30,196, and the patient wait times for MRI examinations requiring the use of flexible torso and head, shoulder, 8-inch head, and torso MRI coils were shortened by 6 d and 23 h, 2 d and 15 h, 2 d and 9 h, and 16 h, respectively. Adjusting MRI examination scheduling by prioritizing patients that require the use of the same coil could reduce the coil-setting time, increase the daily number of patients who are examined, increase the net income of the MRI department, and shorten patient wait times for MRI examinations. Minimizing the operating times of specific examinations to maximize the number of services provided per day does not require additional personnel or resources. The results of the experimental simulations can be used as a reference by radiology department managers designing scheduling rules for examination appointments.

Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats.

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents. In vivo electrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.

Ventral hippocampal CA1 modulates pain behaviors in mice with peripheral inflammation.

Chronic pain is one of the most significant medical problems throughout the world. Recent evidence has confirmed the hippocampus as an active modulator of pain chronicity, but the underlying mechanisms remain unclear. Using in vivo electrophysiology, we identify a neural ensemble in the ventral hippocampal CA1 (vCA1) that shows inhibitory responses to noxious but not innocuous stimuli. Following peripheral inflammation, this ensemble becomes responsive to innocuous stimuli, representing hypersensitivity. Mimicking the inhibition of vCA1 neurons using chemogenetics induces chronic pain-like behaviors in naive mice, whereas activating vCA1 neurons in mice with peripheral inflammation results in a reduction of pain-related behaviors. Pathway-specific manipulation of vCA1 projections to basolateral amygdala (BLA) and infralimbic cortex (IL) shows that these pathways are differentially involved in pain modulation at different temporal stages of chronic inflammatory pain. These results confirm a crucial role of the vCA1 and its circuits in modulating the development of chronic pain.

A nociceptive neuronal ensemble in the dorsomedial prefrontal cortex underlies pain chronicity.

Pain chronicity involves unpleasant experience in both somatosensory and affective aspects, accompanied with the prefrontal cortex (PFC) neuroplastic alterations. However, whether specific PFC neuronal ensembles underlie pain chronicity remains elusive. Here we identify a nociceptive neuronal ensemble in the dorsomedial prefrontal cortex (dmPFC), which shows prominent reactivity to nociceptive stimuli. We observed that this ensemble shows distinct molecular characteristics and is densely connected to pain-related regions including basolateral amygdala (BLA) and lateral parabrachial nuclei (LPB). Prolonged chemogenetic activation of this nociceptive neuronal ensemble, but not a randomly transfected subset of dmPFC neurons, induces chronic pain-like behaviors in normal mice. By contrast, silencing the nociceptive dmPFC neurons relieves both pain hypersensitivity and anxiety in mice with chronic inflammatory pain. These results suggest the presence of specific dmPFC neuronal ensembles in processing nociceptive information and regulating pain chronicity.

Cognitive Impairments and blood-brain Barrier Damage in a Mouse Model of Chronic Cerebral Hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is commonly involved in various brain diseases. Tight junction proteins (TJs) are key components constituting the anatomical substrate of the blood-brain barrier (BBB). Changes in cognitive function and BBB after CCH and their relationship need further exploration. To investigate the effect of CCH on cognition and BBB, we developed a bilateral common carotid artery stenosis (BCAS) model in Tie2-GFP mice. Mice manifested cognitive impairments accompanied with increased microglia after the BCAS operation. BCAS mice also exhibited increased BBB permeability at all time points set from D1 to D42. Furthermore, BCAS mice showed reduced expression of TJs 42 d after the operation. In addition, correct entrances of mice in radial arm maze test had a moderate negative correlation with EB extravasation. Our data suggested that BCAS could lead to cognitive deficits, microglia increase and BBB dysfunction characterized by increased BBB permeability and reduced TJs expression level. BBB permeability may be involved in the cognitive impairments induced by CCH.

Retracted: Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitis.

This publication has been retracted by the Editor due to the identification of non-original figure images that raise concerns regarding the credibility and originality of the study. Reference: You-Dong Wan, Rui-Xue Zhu, Zhong-Zheng Bian, Xin-Ting Pan. Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitisy. Med Sci Monit, 2019; 25: 4609-4616. DOI: 10.12659/MSM.914538.

CircUBE2Q2 promotes differentiation of cattle muscle stem cells and is a potential regulatory molecule of skeletal muscle development.

BACKGROUND: The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. RESULTS: Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. CONCLUSIONS: CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.

Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice.

Background: Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Methods: Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. Results: The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1ß, TNF-α, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1ß, TNF-α, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Conclusions: Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.

A Hybrid Titanium-Softmaterial, High-Strength, Transparent Cranial Window for Transcranial Injection and Neuroimaging.

A transparent and penetrable cranial window is essential for neuroimaging, transcranial injection and comprehensive understanding of cortical functions. For these applications, cranial windows made from glass coverslip, polydimethylsiloxane (PDMS), polymethylmethacrylate, crystal and silicone hydrogel have offered remarkable convenience. However, there is a lack of high-strength, high-transparency, penetrable cranial window with clinical application potential. We engineer high-strength hybrid Titanium-PDMS (Ti-PDMS) cranial windows, which allow large transparent area for in vivo two-photon imaging, and provide a soft window for transcranial injection. Laser scanning and 3D printing techniques are used to match the hybrid cranial window to different skull morphology. A multi-cycle degassing pouring process ensures a good combination of PDMS and Ti frame. Ti-PDMS cranial windows have a high fracture strength matching human skull bone, excellent light transmittance up to 94.4%, and refractive index close to biological tissue. Ti-PDMS cranial windows show excellent bio-compatibility during 21-week implantation in mice. Dye injection shows that the PDMS window has a "self-sealing" to keep liquid from leaking out. Two-photon imaging for brain tissues could be achieved up to 450 µm in z-depth. As a novel brain-computer-interface, this Ti-PDMS device offers an alternative choice for in vivo drug delivery, optical experiments, ultrasonic treatment and electrophysiology recording.

A Single-Center, Randomized, Double-Blind Study of 94 Patients Undergoing Surgery for Cerebral Glioma to Compare Postoperative Thromboprophylaxis with and without Rivaroxaban.

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Spontaneous pain as a challenge of research and management in chronic pain.

Spontaneous pain occurring without apparent external stimuli, is a significant complaint of individuals with chronic pain whose mechanisms, somewhat surprisingly, remain poorly understood. Over the past decades, neuroimaging studies start to reveal brain activities accompanying spontaneous pain. Meanwhile, a variety of animal models and behavioral tests have been established, including non-reflexive tests and free-choice tests, which have been shown to be effective in assessing spontaneous pain. For the spontaneous pain mechanisms, multiple lines of research mainly focus on three aspects: (1) sensitization of peripheral nociceptor receptors and ion channels, (2) spontaneous neuronal firing and abnormal activity patterns at the dorsal root ganglion and spinal cord level, (3) functional and structural alterations in the brain, particularly the limbic system and the medial pain pathway. Despite accumulating evidence revealing distinct neuronal mechanisms from evoked pain, we are still far from full understanding of spontaneous pain, leaving a big gap between bench and bedside for chronic pain treatment. A better understanding of the neural processes in chronic pain, with specific linkage as to which anatomical structures and molecules related to spontaneous pain perception and comorbidities, will greatly improve our ability to develop novel therapeutics.

Failed Primary Surgery in Congenital Scoliosis Caused by a Single Hemivertebra: Reasons and Revision Strategies.

OBJECTIVE: To analyze the factors causing failure of primary surgery in congenital scoliosis (CS) patients with single hemivertebra (SHV) undergoing posterior spinal fusion, and to elucidate the revision strategies. METHODS: In this retrospective study, a total of 32 CS patients secondary to SHV undergoing revision surgery from April 2010 to December 2017 due to failed primary surgery with more than 2 years follow-up were reviewed. The reasons for failure of primary surgery and revision strategies were analyzed for each patient. The radiographic parameters including coronal Cobb angle, segmental kyphosis (SK), coronal balance (CB), and sagittal vertical axis (SVA) were compared between pre- and post-revision. The complications during revision and follow-up were recorded. RESULTS: The mean age at revision surgery of the 32 CS patients was 15.8 ± 9.7 years and the average duration between primary and revision surgery was 31.0 ± 35.4 months. The reasons for failed primary surgery were severe post-operative curve progression of focal scoliosis in 14 cases (43.8%), implant failure in 17 (53.1%) and trunk imbalance in 12 (37.5%). The candidate revision strategies included thorough resection of residual hemivertebra and adjacent discs, extending fusion levels, complete pseudarthrosis resection, massive bone graft, replacement of broken rods, satellite rod fixation, horizontalization of upper/lower instrumented vertebrae and rigid fusion of structural compensatory curves were performed individually. After revision surgery, the coronal Cobb angle, SK, CB and SVA showed significant improvement (P < 0.05) with no significant correction loss during follow-up (P > 0.05). The intra-operative complications included alarming changes of neurologic monitoring in three (9.4%) patients and dual tear in two, while rod fracture re-occurred was detected in one patient at 18 months after revision. CONCLUSIONS: The common reasons for failed primary surgery in CS patients with SHV undergoing posterior spinal fusion were severe post-operative curve progression of focal scoliosis, implant failure and trunk imbalance. The revision strategies including thorough resection of residual hemivertebra and adjacent discs, extended fusion levels to structural curvature, complete pseudarthrosis resection, massive bone graft, replacement of broken internal fixation and horizontalization of upper/lower instrumented vertebrae should be individualized based on the causes of failed primary surgery.

Suppression of ventral hippocampal CA1 pyramidal neuronal activities enhances water intake.

Thirst is an important interoceptive response and drives water consumption. The hippocampus actively modulates food intake and energy metabolism, but direct evidence for the exact role of the hippocampus in modulating drinking behaviors is lacking. We observed decreased number of c-Fos-positive neurons in the ventral hippocampal CA1 (vCA1) after water restriction or hypertonic saline injection in rats. Suppressed vCA1 neuronal activities under the hypertonic state were further confirmed with in vivo electrophysiological recording, and the level of suppression paralleled both the duration and the total amount of water consumption. Chemogenetic inhibition of vCA1 pyramidal neurons increased water consumption in rats injected with both normal and hypertonic saline. These findings suggest that suppression of vCA1 pyramidal neuronal activities enhances water intake.