Background Although recent studies have focused on the use of metformin in treating ischemic stroke, there is little literature to support whether it can treat intracerebral hemorrhage (ICH). Therefore, this study is aimed at evaluating the possible effects of prestroke metformin (MET) on ICH patients with type 2 diabetes. Methods From January 2010 to December 2019, all first-ever ICH patients with type 2 diabetes from our hospitals were included. All discharged patients would receive a one-time follow-up at 1 year after admission. Death, disability, and recurrence events were recorded. Results We included 730 patients for analysis (the median age: 65 [IQR, 56-72] years and 57.7% was men). Of those patients, 281 (38.5%) had received MET before ICH (MET+), whereas 449 (61.5%) had not (MET−). MET (+) patients had a lower median baseline hematoma volume than did MET (-) patients (9.6 ml [IQR, 5.3-22.4 ml] vs. 14.7 ml [IQR, 7.9-28.6 ml]; P < 0.001). The inhospital mortality events were not significantly reduced in the MET (+) group compared with the MET (-) group (6.4% vs 8.9%, respectively; absolute difference, −2.5% [95% CI, −3.9% to −0.7%]; OR, 0.70 [95% CI, 0.39 to 1.27]; P = 0.22). The 1-year mortality events were not significantly reduced in the MET (+) group compared with the MET (-) group (14.1% vs 17.4%, respectively; absolute difference, −3.3% [95% CI, −5.1% to −1.8%]; OR, 0.73 [95% CI, 0.47 to 1.14]; P = 0.16). The 1-year disability events were not significantly reduced in the MET (+) group compared with the MET (-) group (28.4% vs 34.1%, respectively; absolute difference, −5.7% [95% CI, −8.2% to −3.3%]; OR, 0.77 [95% CI, 0.52 to 1.13]; P = 0.18). Finally, the recurrence rates in those two groups were not significantly different (MET [+] vs. MET [-]: 6.4% vs. 5.9%; absolute difference, 0.5% [95% CI, 0.2% to 1.3%]; OR, 1.08 [95% CI, 0.51 to 2.28]; P = 0.84). Conclusions Pre-ICH metformin use was not associated with inhospital mortality and 1-year prognosis in diabetic ICH patients.

Many factors may influence breastfeeding during the perinatal period. Among them, labor analgesia can affect breastfeeding by relieving pain, improving mood or labor analgesia drug itself. However, at present, there are little data on this kind of research. The existing research mainly considers that labor analgesia is a physiological labor mode to be promoted clinically. This article introduces the current status of clinical research on labor analgesia, analyzes the possible adverse or beneficial effects on breastfeeding for different methods such as intrathecal labor analgesia, intravenous labor analgesia, inhalation labor analgesia, non-drug labor analgesia, etc to guide the breastfeeding management of women with labor analgesia.

Objective: Few studies have investigated the effects of dexmedetomidine (DEX) on breastfeeding after cesarean delivery. A randomized double-blind controlled trial was conducted to investigate whether the administration of DEX, immediately after delivery and for patient-controlled intravenous analgesia (PCIA), can be beneficial for breastfeeding. Patients and Methods: One hundred sixty parturients scheduled for elective cesarean section under spinal anesthesia were randomly allocated to the DEX group (a loading dose of DEX was pumped at 0.5 mu g/kg within 10 min, followed by a further infusion of DEX at 0.5 mu g/kg/h until the end of the surgery and PCIA for 2 days with DEX plus sufentanil) or the standard care group (infusion saline intraoperatively, and PCIA for 2 days with sufentanil). The number of days required to switch to exclusive breastfeeding within six weeks of delivery, the time to first lactation and breast milk volume on day 1 and day 2 after delivery were recorded. Recovery quality, comfort, anxiety, depression, postoperative analgesia, and adverse reactions of parturients were also assessed. Results: Compared with the standard care group, parturients in the DEX group could be converted to exclusive breastfeeding earlier (11 [14] vs 8 [10] days, log-rank P=0.025), the first lactation time was sooner (28.38 [13.82] vs 33.79 [14.85] hrs, P=0.024), and the amount of breast milk on the second day after delivery increased (P=0.012). There was no difference between the two groups in postpartum uterine contraction pain, but postpartum rest and movement VAS scores and recovery quality score in the DEX group were better than those in the standard care group (all P<0.05). Moreover, the hospital anxiety and depression scale and anxiety subscale score on the second day after delivery and the comfort score on the third day after delivery in the DEX group were significantly better than those in the standard care group (5 [5] vs 6 [8], 2 [2] vs 3 [3], 83.58 [6.75] vs 80.48 [6.58]; P=0.013, P=0.005, P=0.006, respectively). The incidence of adverse events, such as bradycardia, vomiting, hypersomnia, hypertension and hypotension, was not significantly different between the DEX and standard care groups (6.9% vs 2.7%, 5.6% vs 13.7%, 4.2% vs 0%, 5.6% vs 2.7%, 11.1% vs 8.2%; P=0.275, P=0.158, P=0.366, P=0.681, P=0.556, respectively), except more parturients experienced nausea in the standard care group than in the DEX group (28.8% vs 11.1%, P=0.012). Furthermore, there was no difference in Neonatal Behavioral Neurological Assessment scores on the first and second days after delivery between the DEX and standard care groups (38 [3] vs 37 [2], 38.5 [2] vs 38 [2]; P=0.173, P=0.312, respectively). Conclusion: The application of DEX in the perioperative period of cesarean section was not only conducive to the early conversion of infant feeding to exclusive breastfeeding but could also improve the recovery quality and comfort of the parturient, optimize analgesia, shorten the time to first lactation, and increase lactation.

Objectives: Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by motor dysfunctions. Dopaminergic neuron loss, inflammation and oxidative stress responses play key roles in the pathogenisis of PD. Osthole (Ost), a natural coumarin derivative, isolated from various herbs such as Cnidium monnieri (L.), has anti-inflammatory, anti-apoptotic and anti-oxidative stress properties. However, whether it has effects on PD is unknown. Methods: In this study, mice were subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection to induce PD symptoms, and treated with osthole. Stepping and cylinder tests were performed to determine their motor function. Immunohistochemical and immunofluorescence staining were performed to detect tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba-1). The expression levels of inflammatory cytokines and oxidative stress factors were detected by qPCR and ELISA. Notch signaling pathway was investigated by western blot. Results: We found that injection of MPTP induced motor deficits in mice, enhanced the loss dopaminergic neurons and the activation of microglia, increased inflammatory and oxidative stress responses, and inhibited Notch signaling pathway. Osthole treatment suppressed theses MPTP-induced alterations. Conclusion: In conclusion, osthole attenuates PD symptoms by suppressing Notch signaling pathway.

Toll-like receptor 4 (TLR4) is a key component in innate immunity and has been linked to central nervous system (CNS) inflammation diseases, such as multiple sclerosis (MS), an inflammatory disorder induced by autoreactive Th17 cells. In our study, we found that TLR4 deficient (TLR4−/−) mice were inadequate to induce experimental autoimmune encephalomyelitis (EAE), characterized by low clinic score and weight loss, alleviative demyelinating, as well as decreased inflammatory cell infiltration in the spinal cord. In the lesion area of EAE mice, loss of TLR4 down-regulated the secretion of inflammatory cytokines and chemokine CCL25. Furthermore, the expression of CCR9 was decreased and chemotactic migration was attenuated in TLR4−/− Th17 cells. Our results demonstrate that TLR4 may mediate Th17 infiltration through CCL25/CCR9 signal during pathogenesis of EAE.

According to the previous research, metformin, a medication utilized for type 2 diabetes management, inhibits neural aging and reduces infarct size by enhancing angiogenesis in a mouse stroke model. What is more, metformin administration also promotes neural precursor cells proliferation, migration, as well as differentiation for newborn mice with hypoxia-ischemia brain injury. However, whether metformin regulates neurogenesis in an adult rat ischemia/reperfusion (I/R) model remains unclear. The current research found that metformin administration reduced neuronal damage in the CA1 area of hippocampus in a rat model of I/R. The number of neuronal nuclei positive neuron was significantly increased and glial fibrillary acidic protein positive astrocyte became obviously declined in the CA1 region in I/R rats treated with metformin. It was further demonstrated that metformin promoted neuroblasts proliferation and neuronal differentiation in the subgranular zone of the dentate gyrus and inhibited the formation of astrocyte. Our study indicates that activation of endogenous neuroblasts using metformin will become a favorable target in therapeutic intervention of cerebral ischemia injury models.

S100A8/A9, a heterodimer complex composed of calcium-binding proteins S100A8 and S100A9, is significantly increased in the serum of multiple sclerosis (MS) patients. Relevant reports have revealed that MS pathology is commonly associated with the activation of microglial cells and the damage of oligodendrocyte precursor cells (OPCs). Moreover, microglia activation following stimulation increases the expression of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which further exacerbate the damage to OPCs. In this study, we were the first to confirm that S100A8/A9 treatment induced the activation, proliferation and migration of the murine microglia cell line BV-2; moreover, this treatment caused the cells to switch from an anti-inflammatory activated (M2) phenotype to a pro-inflammatory activated (M1) phenotype. Meanwhile, the level of the phosphorylated nuclear factor-κB (p-NF-κB) P65 protein was remarkably elevated, and the production of pro-inflammatory factors (IL-1β, TNF-α, MMP-9) and chemokines (CCL2, CCL3, CXCL10) was also increased in the S100A8/A9-treated BV-2 microglial cells. Inhibition of NF-κB P65 phosphorylation reversed the effects of S100A8/A9 on the production of pro-inflammatory factors and chemokines. We also explored the effects of S100A8/A9 and S100A8/A9-activated BV-2 microglial cells on the viability of OPCs. The results showed that both the S100A8/A9 complex and the conditioned medium (CM) of the S100A8/A9-activated BV-2 microglial cells resulted in OPC apoptosis, which was more pronounced in the case of the CM treatment. However, OPC apoptosis in the CM group was obviously decreased through the inhibition of NF-κB p65 phosphorylation. This study indicates that S100A8/A9 induces the activation of BV-2 microglial cells and promotes the production of pro-inflammatory factors by activating the NF-κB signaling pathway, which further exacerbates OPC damage.

The inhibition of demyelination and the promotion of remyelination are both considerable challenges in the therapeutic process for many central nervous system (CNS) diseases. Increasing evidence has demonstrated that neuroglial activation and neuroinflammation are responsible for myelin sheath damage during demyelinating disorders. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in demyelination have remained unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the corpus callosum in a demyelinated mouse model induced by cuprizone (CPZ). RN-1734, a TRPV4-antagonist, clearly alleviated demyelination and inhibited glial activation and the production of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) without altering the number of olig2-positive cells. In vitro, RN-1734 treatment clearly inhibited the influx of calcium and decreased the levels of IL-1 beta and TNF-alpha in lipopolysaccharide (LPS)activated microglial cells by suppressing NF-kappa B P65 phosphorylation. Apoptosis of oligodendrocyte induced by LPS-activated microglia was also alleviated by RN-1734. The results suggest that activation of TRPV4 in microglia is involved in oligodendrocyte apoptosis through the activation of the NF-kappa B signaling pathway, thus revealing a new mechanism of CNS demyelination.

Urotensin II (U-II), a cyclic peptide originally isolated from the caudal neurosecretory system of fishes, can produce proinflammatory effects through its specific G protein-coupled receptor, GPR14. Neuropathic pain, a devastating disease, is related to excessive inflammation in the spinal dorsal horn. However, the relationship between U-II and neuropathic pain has not been reported. This study was designed to investigate the effect of U-II antagonist on neuropathic pain and to understand the associated mechanisms. We reported that U-II and its receptor GPR14 were persistently upregulated and activated in the dorsal horn of L4-6 spinal cord segments after chronic constriction injury (CCI) in rats. Intrathecal injection of SB657510, a specific antagonist against U-II, reversed CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found that SB657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor-κB (NF-κB) p65 as well as subsequent secretion of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). It was also showed that both the JNK inhibitor SP600125 and the NF-κB inhibitor PDTC significantly attenuated thermal hyperalgesia and mechanical allodynia in CCI rats. Our present research showed that U-II receptor antagonist alleviated neuropathic pain possibly through the suppression of the JNK/NF-κB pathway in CCI rats, which will contribute to the better understanding of function of U-II and pathogenesis of neuropathic pain.