Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients' quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.
Humans ; Chronic Pain/physiopathology* ; Animals ; Neuroglia/metabolism* ; Chemokine CCL2/metabolism* ; Receptors, CCR2/metabolism*

Objective To explore the quantitative evaluation of integrity risk prevention and control in public hospitals,provide reference for improving the quality and efficiency of integrity risk prevention and control.Methods Self-designed"Inspection Standards for Integrity Risk Prevention and Control of Power Matters in Public Hospitals"was used to score and rate the power matters provided by each functional department/clinical department of West China Hospital of Sichuan University from three aspects:the clarity of power operation process,the accuracy of finding integrity risk points,the effectiveness of prevention and control measures.Results A total of 236 power matters of the hospital were inspected for integrity risk prevention and control,and according to the inspection criteria,57 items were rated as first grade,103 items were rated as second grade,and 76 items were rated as third grade,accounting for 24.15％,43.64％and 32.20％,respectively.The score for the special work of integrity risk prevention and control was 5.82±1.92 points,of which the process dimension score was 2.11±0.75 points,the risk points dimension score was 1.89±0.92 points,the prevention and control dimension score is 1.89± 0.79 points,which reflects the problems of unclear workflow,inaccurate finding of individual risk points,and unspecified prevention and control measures in some units.Conclusion Hospitals should focus on the concreteness,accuracy,salience and quantification in the long-term construction of integrity risk prevention and control from the aspects of thought,behavior,effectiveness and evaluation.

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

To ensure the safety of the commercially available chenpi, a convenient and fast analytical method was developed for the determination of 133 pesticide residues in chenpi using gas chromatography-tandem mass spectrometry (GC-MS/MS). In this study, different extraction solvents, redissolution solvents and adsorbents were tested according to the recovery and purification effect to obtain a modified QuEChERS method. The samples were extracted with acetonitrile. During the clean-up step, octadecyl-modified silica (C18) and graphitized carbon black (GCB) were selected, and aminopropyl (NH2) was used instead of primary secondary amine (PSA) because of its weaker ion exchange capacity which had little effect on the recovery of ditalimfos. Samples were quantified by matrix-matched calibration with internal stan-dards. All pesticides showed good linearity in the respective range, both with values of r2 >0.99. The average recoveries of the pesticides spiked samples ranged from 70.0％ to 112.2％ with the RSDs of 0.2％–14.4％. The modified QuEChERS method was validated and applied to twenty real samples. Five pesticides were found in eight batches, but no pesticide exceeded the maximum residue limits (MRL, MRL reference to European commission).

Objective     To analyze the use of modified pericardial oblique sinus approach in surgical repair for total anomalous pulmonary venous connection in neonates. Methods     Between May 2005 and December 2015, 67 consecutive neonates with supracardiac or infracardiac type total anomalous pulmonary venous connection who underwent surgical repair in our institute were included in this study. The patients are divided into three groups according to the different approaches including a sulcus approach group (6 patients), a superior approach group (14 patients), and a modified pericardial oblique sinus approach group (47 patients). There were 53 males and 14 females at median age of 12.5 (7.0, 20.5) d.  Results     The time of cardiopulmonary bypass [88 (80.0, 107.0) min vs. 135 (121.0, 157.0) min, P<0.05] and aortic cross clamping of the modified pericardial oblique sinus approach group was significantly shorter than that of the sulcus approach group [45 (39.0, 53.0) min vs. 80 (73.0, 85.0) min, P<0.05]. Perioperative mortality (2.1% vs. 28.6%, P<0.05) was significantly lower in the modified pericardial oblique sinus approach group than that in the superior approach group. The long-term mortality (4.3% vs. 60.0%, P<0.05) was significantly lower in the modified pericardial oblique sinus approach group than that in the sulcus approach group or the superior approach group . The rate of pulmonary venous stenosis was significantly lower in the modified pericardial oblique sinus approach group than that in the sulcus approach group (2.1% vs. 50.0%, P<0.05) or superior approach group (2.1% vs. 35.7%, P<0.05).  Conclusions     In surgical correction of neonatal supracardiac and infracardiac total anomalous pulmonary venous, compared with the traditional surgical approach, the modified pericardial oblique sinus pathway can provide excellent surgical space and has a good surgical prognosis.

Decompression, Surgical ; Gout ; Humans ; Lumbar Vertebrae ; Spinal Stenosis

Objective To observe the clinical efficacy of warm needling plus Chinese medication for external application in treating post-stroke shoulder pain. Method Two hundred patients with post-stroke shoulder pain were randomized into a treatment group and a control group, 100 cases each. The two groups both received rehabilitation training for shoulder joint. In addition, the treatment group was given warm needling plus Chinese medication for external application, while the control group was given warm needling. Visual Analogue Scale (VAS) for pain, upper-limb Fugl-Mayer Assessment (FMA) and Modified Barthel Index (MBI) were adopted to evaluate the two groups before and after the treatment. The clinical efficacies of the two groups were also compared. Result The total effective rate was 100.0％ in the treatment group versus 87.0％ in the control group, and the between-group difference was statistically significant (P<0.01). The VAS, FMA and MBI scores were significantly changed after the treatment in both groups (P<0.01). After the treatment, the VAS, FMA and MBI scores of the treatment group were significantly different from those of the control group (P<0.05, P<0.01). Conclusion Warm needling plus Chinese medication for external application and rehabilitation training can obviously reduce post-stroke shoulder pain, and enhance the upper-limb motor function and activities of daily living.