Impact of multimodal analgesia on postoperative anxiety and depression following total knee arthroplasty.

BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) can cause negative emotions, such as anxiety and depression, which can severely affect a patient's long-term quality of life. OBJECTIVE: This study aimed to investigate the impact of multimodal analgesia (MMA) on postoperative anxiety and depression following total knee arthroplasty. METHODS: This study included 161 patients who underwent TKA from October 2020 to October 2022 in the First Affiliated Hospital of Wannan Medical College, including 79 cases in the control group and 82 cases in the multimodal analgesia group (MMA). The MMA group were administered acetaminophen 0.5 g/d orally 3 days before the surgery, and an ultrasound-guided fascia iliac compartment block (FICB) with 0.25% ropivacaine 30 ml in the inguinal region ipsilateral to the surgery was performed 1 h before surgery. After the surgery, 100 ml solution includes 100 mg ropivacaine, 2.5 mg morphine, and 0.25 mg epinephrine for intra-articular and periarticular injection. Postoperative conventional intravenous analgesia was used in the control group, including 100 mg ropivacaine, 2.5 mg morphine, and 0.25 mg epinephrine for intra-articular and periarticular injection. Patients were scored for pain, anxiety, and depression in the ward at 3 and 7 days postoperatively, and postoperative patients were scored using telephone callbacks at 3 months postoperatively. RESULTS: It was found that the visual analog scale (VAS) scores for pain at rest at 3 days, 7 days, and 3 months postoperatively were significantly lower in the MMA group than in the control group (P < 0.05). The scores for pain with movement were significantly lower in the MMA group than in the control group at 3 days and 7 days postoperatively (P < 0.01), but they were similar at 3 months postoperatively. Compared to the control group, the MMA group had significantly higher American Knee Society scores (AKS) at 3 days, 7 days, and 3 months postoperatively (P < 0.05). Compared to the control group, the MMA group had significantly higher Lower Extremity Functional Scale and Hospital Anxiety and Depression Scale scores (HADS) (P < 0.05) at 3 days and 7 days postoperatively; compared to the control group, the MMA group had a significantly shorter hospital stay (P < 0.01). CONCLUSION: Multimodal analgesia can alleviate postoperative anxiety and depression in the short term, reduce perioperative pain, improve postoperative recovery, and shorten the length of hospital stay.

The complete chloroplast genome sequence of Salvia miltiorrhiza, a medicinal plant for preventing and treating vascular dementia.

S. miltiorrhiza is a perennial herb of the genus Salvia (Lamiaceae), which is an important medicinal plant for preventing and treating vascular dementia. The complete chloroplast genome sequence of Salvia miltiorrhiza was characterized from Illumina pair-end sequencing. The chloroplast genome of S. miltiorrhiza was 152,680 bp in length, containing a large single-copy region (LSC) of 84,104 bp, a small single-copy region (SSC) of 17,638 bp, and two inverted repeat (IR) regions of 25,469 bp. The overall GC content is 38.70%, while the correponding values of the LSC, SSC, and IR regions are 36.2%, 31.9%, and 43.2%, respectively. The genome contains 131 complete genes, including 86 protein-coding genes (62 protein-coding gene species), 37 tRNA genes (29 tRNA species) and 8 rRNA genes (4 rRNA species). The Neighbour-joining phylogenetic analysis showed that S. miltiorrhiza and Salvia przewalskii clustered together as sisters to other Salvia species.

Protective effects of Tongxinluo on cerebral ischemia/reperfusion injury related to Connexin 43/Calpain II/Bax/Caspase-3 pathway in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL) is a multifunctional traditional Chinese medicine and has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Numerous studies demonstrate that TXL is a novel neuroprotective drug, however, the mechanisms are largely unknown. AIM OF THE STUDY: we aimed to demonstrate the protective effect of TXL on cerebral ischemia/reperfusion (I/R) injury and provide the evidence for the involvement of Connexin 43/Calpain II/ Bax/Caspase-3 pathway in TXL-mediated neuroprotection. METHODS: Focal cerebral I/R injury were induced by transient middle cerebral artery occlusion (MCAO, for 90min) in adult male Sprague-Dawley rats. We estimated the effects of TXL on I/R injury including neurological deficit assessment and cerebral infarct volume measurement via TTC staining, and detected the protein expression of Connexin 43 (Cx43) by western blot. Furthermore, after the intracerebroventricular injection of carbenoxolone (CBX, the inhibitor of Cx43) at 30min before MCAO surgery, Calpain II, Bax and cleaved Caspased-3 immunoreactivity in ischemic penumbra region was detected by immunofluorescent staining, and cell apoptosis was detected by TUNEL staining. RESULTS: TXL treatment greatly improved neurological deficit and reduced the infarction volume compared to MCAO with buffer treatment (P<0.05), and TXL pre-post treatment showed better results than TXL pre-treatment. TXL pre-post treatment significantly up-regulated Cx43 protein expression at 3d, 7d and 14d post-injury compared to MCAO with buffer treatment (P<0.05). Meanwhile, the immunoreactivity of Calpain II, Bax and cleaved Caspase-3 in ischemic penumbra region was obviously decreased by TXL pre-post treatment compared to MCAO group (P<0.05). However, with the treatment of the Cx43 inhibitor, CBX, the down-regulated effect of TXL on Calpain II, Bax and cleaved Caspase-3 immunoreactivity was abolished (P<0.05). Moreover, the protective effect of TXL against neuron apoptosis in penumbra region was conteracted by CBX (P<0.05). CONCLUSIONS: TXL could effectively protect against I/R injury and reduced cell death via Cx43/Calpain II/Bax/Caspase-3 pathway, which contribute to I/R injury prevention and therapy.

The combination of astragalus membranaceus and ligustrazine ameliorates micro-haemorrhage by maintaining blood-brain barrier integrity in cerebrally ischaemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Haemorrhagic transformation is an asymptomatic event that frequently occurs after following ischaemic stroke, particularly when pharmaceutical thrombolysis is used. However, the mechanism responsible for haemorrhagic transformation remains unknown, and therapeutics have not been identified. In this study, we administered a combination of astragalus membranaceus and ligustrazine to rats with cerebral ischaemia that had undergone thrombolysis. We analysed the effect of this combination on the attenuation of haemorrhagic transformation and the maintenance of blood-brain barrier integrity. METHODS: A rat model of focal cerebral ischaemia was induced with autologous blood clot injections. Thrombolysis was performed via the intravenous injection of rt-PA. Astragalus membranaceus, ligustrazine or a combination of Astragalus membranaceus and ligustrazine was administered immediately after the clot injection. The cerebral infarct area, neurological deficits, blood-brain barrier integrity, and cerebral haemorrhage status were determined after 3, 6 and 24h of ischaemia. The ultrastructure of the blood-brain barrier was examined with a transmission electron microscope. The expression of tight junction proteins, including claudin-1, claudin-5, occludin, and zonula occludens-1, and matrix metallopeptidase-9 activation was further evaluated in terms of their roles in the protective effects of the combination drug on the integrity of the blood-brain barrier. RESULTS: Ischaemia-induced Evans blue leakage and cerebral haemorrhage were markedly reduced in the combination drug-treated rats compared to the rats treated with either astragalus membranaceus or ligustrazine alone (p<0.05). The disruption of the ultrastructure of the blood-brain barrier and the neurological deficits were ameliorated by the combination treatment (p<0.05). The reductions in the expression of laudin-1, claudin-5, occludin, and ZO-1 were smaller in the rats that received the combination treatment. In addition, MMP-9 activity was suppressed in the combination-treated rats compared to the controls (p<0.05). CONCLUSIONS: Treatment with a combination of astragalus membranaceus and ligustrazine alleviated ischaemia-induced micro-haemorrhage transformation by maintaining the integrity of the blood-brain barrier.

Neuronal nitric oxide synthase, as a downstream signaling molecule of c­jun, regulates the survival of differentiated PC12 cells.

The high expression of c-jun and neuronal nitric oxide synthase (nNOS) generally occurs in neurons following the generation of various animal models of central neuronal diseases. However, the mechanism between them in neuronal disease remains to be elucidated. Our previous studies demonstrated that the expression of c­jun always occurs prior to expression of nNOS in motoneuron injuries and suppression of c­jun expression by c­jun siRNA decreased nNOS expression in differentiated PC12 cells. The present study aimed to examine whether there was an association of up and downstream regulation or crosstalk between c­jun and nNOS in neurons. Using a culture of differentiated PC12 cells in vitro, the expression of nNOS and c-jun in cells was investigated by immunofluorescence. The nNOS inhibitor 7­nitroindazole (7­NI) was used in differentiated PC12 cells to downregulate the expression of nNOS. The optimal concentration of 7­NI on the viability and survival of cultured differentiated PC12 cells was selected using a 3­(4,5-dimethylthiazol-2-yl)­2,5-diphenyltetrazolium assay and the effects of 7­NI on the activity of constitutive nitric oxide synthase (cNOS) in differentiated PC12 cells were determined using a NOS Activity Detection kit. The effects of 7­NI on the gene expression of nNOS and c­jun were detected by western blot analysis. The results from the immunofluorescence demonstrated that the c­jun and nNOS protein were constantly expressed in PC12 cells. The cell viability of differentiated PC12 cells were significantly inhibited by treatment with 200 and 400 µmol/l 7­NI, and the expression levels of the nNOS protein were significantly inhibited by treatment with 200 µmol/l 7­NI. However, 7­NI had no significant effect on the protein expression level of c­jun and the total activities of cNOS. Based on our previous studies, which revealed that the nNOS gene was a downstream signaling molecule of the JNK/c­jun signaling pathway in cultured neurons, the expression of nNOS downstream was able to be regulated by c­jun which was the upstream molecule. Therefore, these results indicated that the association between them involved up and downregulation instead of crosstalk.