Sodium aescinate ameliorates chronic neuropathic pain in male mice via suppressing JNK/p38-mediated microglia activation.

OBJECTIVE: A study confirmed that sodium aescinate (SA) can effectively relieve bone cancer pain, but its role in neuropathic pain (NP) remains confused. METHODS: Eighty male mice were randomly divided into four groups: sham+vehicle, sham+SA (40 µg/L, intrathecal injection), chronic contraction injury (CCI)+vehicle, CCI+SA. Behavioral assessments were used to evaluate the locomotor activity and paw withdrawal threshold (PWT) of mice. At the end of the study, spinal cord tissues were collected for histopathological analysis. The JNK/p38 signaling activation, Iba-1 expression, pro-inflammatory cytokines levels, and microglia subtype were assessed by western blotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and flow cytometry with CD86/CD206, respectively. RESULTS: Early treatment with SA delayed the development of mechanical allodynia in CCI mice. Repeated SA treatment could prominently increase the reduction of PWT induced by CCI, and improve the locomotor activity of CCI mice. Mechanically, CCI surgery induced significant up-regulation of p-JNK and p-p38 protein levels, increased number and M1/M2 ratio of microglia, as well as pro-inflammatory factors in the spinal cords of mice, which could be blocked after SA administration. CONCLUSIONS: SA might suppress the activation of microglia and neuroinflammation by selectively inhibiting the JNK/p38 signaling pathway, thereby alleviating CCI-induced NP in male mice.

Shenling Baizhu San supresses colitis associated colorectal cancer through inhibition of epithelial-mesenchymal transition and myeloid-derived suppressor infiltration.

BACKGROUND: Shenling Baizhu San (SBS) is a well-known and classical Chinese medicine formula. It has been used for treatment of gastrointestinal disorders for about nine hundred years. Recent reports showed that it was effective in curing colitis and ameliorating the major manifestations of postoperational colorectal cancer (CRC). This study was to evaluate the effects of SBS on azoxymethane (AOM) and dextran sodium sulfate (DSS) induced colitis associated CRC (caCRC) and to analyze the underlying mechanism of SBS in preventing CRC. METHODS: The colon tissue of mice in different group was determined by immunohistochemistry and western blot. TGF-ß1 in serum was measured by ELISA. Myeloid-derived suppressor cells (MDSCs) were identified by flow cytometry and immunohistochemistry. RESULTS: The formed neoplasms phenotypically resembled human caCRC with upregulated ß-catenin, p53 and proliferating cell nuclear antigen (PCNA). SBS treatment reduced the death rate of mice and decreased the incidence and multiplicity of colonic neoplasms. SBS decreased the number of MDSCs and the level of transforming growth factor ß1 (TGF-ß1). SBS alleviated epithelial mesenchymal transition (EMT) through downregulating N-cadherin (N-cad), Vimentin, Fibronectin, Snail, and upregulating E-cadherin (E-cad). It reduced the activation of Wnt5a and EMT induced by TGF-ß1. CONCLUSIONS: SBS reduced the death rate through decreasing the incidence and multiplicity of colonic tumors. SBS lowered MDSCs infiltration and inhibited TGF-ß1 induced EMT to exert its anti-caCRC effects.

Clinical Study of Stellate Ganglion Block Combined with General Anesthesia on Hemodynamics, Cognitive Function, and Gastrointestinal Function in Elderly Patients Undergoing Partial Hepatectomy.

Partial hepatectomy under general anesthesia is prone to hemodynamic alterations, and stress reactions are the main contributing factors to postoperative cognitive function in elderly partial hepatectomy patients. Postoperative cognitive dysfunction increases the incidence of postoperative complications and long-term morbidity and mortality in elderly patients. With the increasing trend of aging population and the gradual increase of elderly people undergoing surgical treatment, it is especially important to study the corresponding prevention and treatment measures. In this study, a total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. The changes in hemorheology, stress-related indexes, cognitive function, postoperative pain, and gastrointestinal function were compared between the two groups The results showed that SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.

Study on Analgesic Effects of Combined Thoracic Paravertebral Block Anesthesia or Erector Spinae Plane Block with Ultrasound Guided Transversus Abdominis Plane Block in Endoscopic Esophagectomy: A Clinical Anatomical Approach

SUMMARY: The application effect of transversus abdominis plane block (TAPB) combined with thoracic paravertebral block (TPVB) or erector spinae plane block (ESP) under ultrasound guidance in endoscopic radical resection of esophageal cancer under general anesthesia was studied. From March 2021 to February 2022, patients who underwent endoscopic radical resection of esophageal cancer in our hospital were selected as the research object, and 90 patients were selected as the samples. Patients were divided into groupA and group B according to the difference of blocking schemes. Group A received ESP and Group B received TPVB. The dosage of sufentanil, nerve block time, awakening time and extubation time of the two groups were counted. The postoperative pain, sedation effect, sleep satisfaction and analgesia satisfaction of the two groups were compared, and the complications of the two groups were observed. The nerve block time and extubation time in group A were shorter than those in group B (P0.05). At T2, T3 and T4, the visual analogue scale (VAS) scores of group A at rest and cough were significantly lower than those of group B (P0.05). The satisfaction of sleep and analgesia in group A was higher than that in group B (P0.05). The analgesic effect of ultrasound-guided TAPB combined with ESP is better than that of ultrasound-guided TAPB combined with TPVB, and it can shorten the time of nerve block and extubation, which is worth popularizing.

Se estudió el efecto de la aplicación del bloqueo del plano transverso del abdomen (TAPB) combinado con el bloqueo paravertebral torácico (TPVB) o el bloqueo del plano del erector de la columna (ESP) bajo guía ecográfica en la resección radical endoscópica del cáncer de esófago bajo anestesia general. Desde marzo de 2021 hasta febrero de 2022, en nuestro hospital, se seleccionaron como objeto de investigación pacientes sometidos a resección radical endoscópica de cáncer de esófago, y como muestra se seleccionaron 90 pacientes. Los pacientes se dividieron en el grupo A y el grupo B según la diferencia de esquemas de bloqueo. El grupo A recibió ESP y el grupo B recibió TPVB. Se contaron la dosis de sufentanilo, el tiempo de bloqueo nervioso, el tiempo de despertar y el tiempo de extubación de los dos grupos. Se compararon el dolor posoperatorio, el efecto de la sedación, la satisfacción del sueño y la satisfacción de la analgesia de los dos grupos y se observaron las complicaciones de los dos grupos. El tiempo de bloqueo nervioso y el tiempo de extubación en el grupo A fueron más cortos que los del grupo B (P0,05). En T2, T3 y T4, las puntuaciones de la escala visual analógica (EVA) del grupo A en repo- so y tos fueron significativamente más bajas que las del grupo B (P 0,05). La satisfacción del sueño y la analgesia en el grupo A fue mayor que en el grupo B (P0,05). El efecto analgésico de la TAPB guiada por ecografía combinada con ESP es mejor que el de la TAPB guiada por ecografía combinada con TPVB, y puede acortar el tiempo de bloqueo nervioso y extubación, lo que vale la pena popularizar.

A New Neural Pathway from the Ventral Striatum to the Nucleus Basalis of Meynert with Functional Implication to Learning and Memory.

The cholinergic neurons in the nucleus basalis of Meynert (NBM) are among the first group of neurons known to become degenerated in Alzheimer's disease, and thus the NBM is proposed to be involved in learning and memory. The marginal division (MrD) of the striatum is a newly discovered subdivision at the ventromedial border of the mammalian striatum and is considered to be one part of the ventral striatum involved in learning and memory. The present study provided evidence to support the hypothesis that the MrD and the NBM were structurally connected at cellular and subcellular levels with functional implications in learning and memory. First, when wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was stereotaxically injected into the NBM, fusiform neurons in the MrD were retrogradely labeled with WGA-HRP gray-blue particles and some of them were double stained in brown color by AchE staining method. Thus, cholinergic neurons of the MrD were shown to project to the neurons in the NBM. Second, in anterograde tract-tracing experiments where WGA-HRP was injected to the MrD, the labeled WGA-HRP was found to be anterogradely transported in axons from the MrD to the synaptic terminals with dendrites, axons, and perikaryons of the cholinergic neurons in the NBM when observed under an electronic microscope, indicating reciprocal structural connections between the MrD and the NBM. Third, when bilateral lesions of the MrD were injured with kainic acid in rats, degenerative terminals were observed in synapses of the NBM by an electronic microscope and severe learning and memory deficiency was found in these rats by the Y-maze behavioral test. Our results suggest reciprocal cholinergic connections between the MrD of the ventral striatum and the NBM, and implicate a role of the MrD-NBM pathway in learning and memory. The efferent fibers of cholinergic neurons in the NBM mainly project to the cortex, and severe reduction of the cholinergic innervation in the cortex is the common feature of Alzheimer's patients. The newly discovered cholinergic neural pathway between the MrD of the ventral striatum and the NBM is supposed involved in the memory circuitries of the brain and probably might play a role in the pathogenesis of the Alzheimer's disease.

Sources and elimination of interference in patch clamp electrophysiological experiment.

OBJECTIVE: The sources of the interference in the patch clamp electrophysiological experiments were investigated, and the methods for eliminating the interference, along with the authors experience, are introduced.