The safety and efficacy of unicompartmental knee arthroplasty in outpatient surgical centers: A systematic review and meta-analysis.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an effective treatment method for knee osteoarthritis. With the development and implementation of enhanced recovery after surgery, UKA is now increasingly performed in outpatient surgical centers. However, there is ongoing debate regarding the safety and effectiveness of performing UKA in outpatient settings. METHODS: The search was performed to retrieve randomized controlled trials and cohort studies on outpatient UKA from PubMed, Cochrane Library, EMbase, CNKI, and WanFangData databases. The search was conducted from the inception of the databases until August 31, 2023. After independent screening, data extraction, and risk of bias evaluation by two researchers, meta-analysis was performed using RevMan 5.4 software. RESULTS: A total of eight studies involving 18,411 patients were included. The results showed that the postoperative transfusion rate in the outpatient group was lower than that in the inpatient group [OR = 0.36, 95%CI (0.24, 0.54), p < 0.00001], and the difference was statistically significant. However, there was no significant difference between the two groups in terms of readmission rate, reoperation rate, surgical site infection, and periprosthetic fracture. The differences were not statistically significant. CONCLUSION: Compared to the traditional inpatient route, the blood transfusion rate for single-condyle replacement in the outpatient operation center is lower, and there is no significant difference in readmission rate, reoperation rate, surgical site infection, and periprosthesis fracture. The outpatient approach to UKA is safe, feasible, and highly satisfactory for patients. However, the results have certain limitations, and a rigorous preoperative complication risk assessment can minimize the risk of UKA in outpatient surgery centers. TRIAL REGISTRATION: PROSPERO number CRD42023405373.

Rheumatoid arthritis is a protective factor against Alzheimer's disease: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Epidemiological evidence suggests that there is an association between rheumatoid arthritis (RA) and Alzheimer's disease (AD). However, the causal relationship between RA and AD remains unclear. Therefore, this study aimed to investigate the causal relationship between RA and AD. METHODS: Using publicly available genome-wide association study datasets, bidirectional two-sample Mendelian randomization (TSMR) was performed using the inverse-variance weighted (IVW), weighted median, MR‒Egger regression, simple mode, and weighted mode methods. RESULTS: The results of MR for the causal effect of RA on AD (IVW, odds ratio [OR] = 0.959, 95% confidence interval [CI]: 0.941-0.978, P = 2.752E-05; weighted median, OR = 0.960, 95% CI: 0.937-0.984, P = 0.001) revealed a causal association between genetic susceptibility to RA and an increased risk of AD. The results of MR for the causal effect of AD on RA (IVW, OR = 0.978, 95% CI: 0.906-1.056, P = 0.576; weighted median, OR = 0.966, 95% CI: 0.894-1.043, P = 0.382) indicated that there was no causal association between genetic susceptibility to AD and an increased risk of RA. CONCLUSIONS: The results of this two-way two-sample Mendelian randomization analysis revealed a causal association between genetic susceptibility to RA and a reduced risk of AD but did not reveal a causal association between genetic susceptibility to AD and an increased or reduced risk of RA.

Spatial and temporal plasticity of synaptic organization in anterior cingulate cortex following peripheral inflammatory pain: multi-electrode array recordings in rats.

To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array (MEA) technique and 2-dimensional current source density (2D-CSD) imaging were used in slice preparations of the anterior cingulate cortex (ACC) from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials (LFPs) and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation (LTP) and changes in LTP magnitude were also evaluated. We found that under naïve conditions, the current sink was initially generated in layer VI, then spread to layer V and finally confined to layers II-III. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers (V-VI) to superficial layers (II-III) where intra- and extracortical inputs terminate. In the ACC slices from rats in an inflamed state (for 2 h) caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed, showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naïve and saline controls. The change was more distinct in the superficial layers (II-III) than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers II-III by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.

Enhanced expression of proneurotrophins in elevated introcular pressure-induced rat retinal ischemia.

BACKGROUND: Proneurotrophins such as the precursor of nerve growth factor (proNGF) and the precursor of brain-derived neurotrophic factor (proBDNF) interacted with sortilin and p75(NTR) to form a complex capable of activating an apoptotic signaling. We found that the expression of p75(NTR) and sortilin was increased in ischemic retina induced by elevated intraocular pressure (IOP), but the protein expression changes of proNGF and proBDNF in the same situation were not clear. This study aimed to ascertain the protein expression changes of proNGF and proBDNF in ischemic retina induced by elevated IOP. METHODS: Expression of proBDNF and proNGF was examined by double-labeling immunochemistry in normal rat retina, examined using Western blotting and analyzed using statistical methods in ischemic retina induced by elevated IOP. RESULTS: Immunocytochemistry showed that the proBDNF expressed in the ganglion cell layer (GCL) while the proNGF primarily existed in both the nerve fiber layers (NFL) and large ganglion cell bodies of normal rat retina. Western blotting analysis demonstrated that the molecule weights of 28 kD (proBDNF)/25 kD (proNGF) band were increased significantly (P < 0.05) at days 3, 5 and 7 after retinal elevated-IOP-induced ischemia. CONCLUSION: ProBDNF expressed in the GCL and proNGF primarily presented in NFL and large ganglion cell bodies of normal rat retina, the protein expression forms of 28 kD proBDNF and 25 kD proNGF increased in ischemic retina induced by elevated IOP.

Simultaneous multisite recordings of neural ensemble responses in the motor cortex of behaving rats to peripheral noxious heat and chemical stimuli.

Chronic motor cortex (MCx) stimulation (MCS) is an effective approach for patients with chronic, intractable neuropathic pain. However, the underlying neural mechanisms are less known. Combining an in vivo simultaneous multisite recording technique with a video-based behavioral tracker, simultaneous neuronal ensemble activities of the MCx and behavioral responses to noxious heat stimuli applied to bilateral hindpaw pads under naïve and inflammatory pain state were studied in freely behaving rats receiving prior implantation of microwire multielectrode array (2 × 4). Totally, 81 active units were sorted and separated from 40 microwire electrodes pre-implanted in the MCx of 5 rats. Under naïve state, 41% (33/81) units were responsive to contralateral, while 27% (22/81) were responsive to ipsilateral heat stimuli. However, the proportion of heat-responsive units under inflammatory pain state induced by subcutaneous bee venom (BV) injection was significantly increased when compared with saline control (BV vs. saline: 60% vs. 48% for contralateral and 51% vs. 37% for ipsilateral, P < 0.05, n = 81 units) as a consequence of recruitment of some previously heat non-responsive to heat sensitive units. Moreover, under the BV-inflamed condition, the discharge rate of the MCx neurons was significantly increased. The time course of increased spontaneous neuronal ensemble activities (n = 81) was in parallel with that of pain-related behaviors following BV injection. It is concluded that there are pain-related neurons in the MCx that can be functionally changed by peripheral inflammatory pain condition.

Differential roles of ERK, JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats: multi-electrode array recordings.

It is known that chronic pain affects various higher brain functions including perception, emotion, cognition, and memory. However, few studies have been performed to examine pain-induced synaptic plastic changes in the hippocampal formation (HF), an important region subserving affective-motivational component of pain. Our previous study has revealed a strong impact of peripheral persistent nociception on synaptic connection, transmission and function in the HF of rats, in both temporal and spatial domains, by using a newly developed MED64 multichannel recording system. However, the underlying signaling mechanisms for this pain-related spatial and temporal plasticity are still less understood. As an initial investigation, the present study attempted to examine potential different roles of the mitogen-activated protein kinase (MAPK) members in mediating this plastic phenomenon. By virtue of the three well-known MAPK inhibitors targeting extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK), respectively, in combination with the well-established MED64 multisite recording system, we found that pharmacological inhibition of the ERK- and JNK-mediated signaling pathway, at the plateau phase of the long-term potentiation (LTP), significantly decreased pain-enhanced LTP maintenance whereas similar blockade of p38 MAPK pathway dramatically further increased the potentiation. Regarding the spatial magnification of pain, ERK and p38 MAPK seemed to play opposing roles, with the former positively involved and the latter negatively involved, without any detectable effect of the JNK signaling pathway. Together, these results suggest differential roles of the specific members of the MAPK family in mediating pain-associated spatial and temporal plasticity in the HF, which are in good agreement with previous observations. In addition, a possible mechanistic separation between spatial and temporal magnification of pain is also indicated in this study.

Nociception-induced spatial and temporal plasticity of synaptic connection and function in the hippocampal formation of rats: a multi-electrode array recording.

BACKGROUND: Pain is known to be processed by a complex neural network (neuromatrix) in the brain. It is hypothesized that under pathological state, persistent or chronic pain can affect various higher brain functions through ascending pathways, leading to co-morbidities or mental disability of pain. However, so far the influences of pathological pain on the higher brain functions are less clear and this may hinder the advances in pain therapy. In the current study, we studied spatiotemporal plasticity of synaptic connection and function in the hippocampal formation (HF) in response to persistent nociception. RESULTS: On the hippocampal slices of rats which had suffered from persistent nociception for 2 h by receiving subcutaneous bee venom (BV) or formalin injection into one hand paw, multisite recordings were performed by an 8 x 8 multi-electrode array probe. The waveform of the field excitatory postsynaptic potential (fEPSP), induced by perforant path electrical stimulation and pharmacologically identified as being activity-dependent and mediated by ionotropic glutamate receptors, was consistently positive-going in the dentate gyrus (DG), while that in the CA1 was negative-going in shape in naïve and saline control groups. For the spatial characteristics of synaptic plasticity, BV- or formalin-induced persistent pain significantly increased the number of detectable fEPSP in both DG and CA1 area, implicating enlargement of the synaptic connection size by the injury or acute inflammation. Moreover, the input-output function of synaptic efficacy was shown to be distinctly enhanced by the injury with the stimulus-response curve being moved leftward compared to the control. For the temporal plasticity, long-term potentiation produced by theta burst stimulation (TBS) conditioning was also remarkably enhanced by pain. Moreover, it is strikingly noted that the shape of fEPSP waveform was drastically deformed or split by a TBS conditioning under the condition of persistent nociception, while that in naïve or saline control state was not affected. All these changes in synaptic connection and function, confirmed by the 2-dimentional current source density imaging, were found to be highly correlated with peripheral persistent nociception since pre-blockade of nociceptive impulses could eliminate all of them. Finally, the initial pharmacological investigation showed that AMPA/KA glutamate receptors might play more important roles in mediation of pain-associated spatiotemporal plasticity than NMDA receptors. CONCLUSION: Peripheral persistent nociception produces great impact upon the higher brain structures that lead to not only temporal plasticity, but also spatial plasticity of synaptic connection and function in the HF. The spatial plasticity of synaptic activities is more complex than the temporal plasticity, comprising of enlargement of synaptic connection size at network level, deformed fEPSP at local circuit level and, increased synaptic efficacy at cellular level. In addition, the multi-synaptic model established in the present investigation may open a new avenue for future studies of pain-related brain dysfunctions at the higher level of the neuromatrix.

Imbalance between excitatory and inhibitory amino acids at spinal level is associated with maintenance of persistent pain-related behaviors.

Although the postsynaptic events responsible for development of pathological pain have been intensively studied, the relative contribution of presynaptic neurotransmitters to the whole process remains less elucidated. In the present investigation, we sought to measure temporal changes in spinal release of both excitatory amino acids (EAAs, glutamate and aspartate) and inhibitory amino acids (IAAs, glycine, ?-aminobutyric acid and taurine) in response to peripheral inflammatory pain state. The results showed that following peripheral chemical insult induced by subcutaneous bee venom (BV) injection, there was an initial, parallel increase in spinal release of both EAAs and IAAs, however, the balance between them was gradually disrupted when pain persisted longer, with EAAs remaining at higher level but IAAs at a level below the baseline. Moreover, the EAAs-IAAs imbalance at the spinal level was dependent upon the ongoing activity from the peripheral injury site. Intrathecal blockade of ionotropic (NMDA and non-NMDA) and metabotropic (mGluRI, II, III) glutamate receptors, respectively, resulted in a differential inhibition of BV-induced different types of pain (persistent nociception vs. hyperalgesia, or thermal vs. mechanical hyperalgesia), implicating that spinal antagonism of any specific glutamate receptor subtype fails to block all types of pain-related behaviors. This result provides a new line of evidence emphasizing an importance of restoration of EAAs-IAAs balance at the spinal level to prevent persistence or chronicity of pain.

Spatiotemporal characteristics of pain-associated neuronal activities in primary somatosensory cortex induced by peripheral persistent nociception.

The primary somatosensory cortex (S1 area) is one of the key brain structures for central processing of somatic noxious information to produce pain perception. However, so far, the spatiotemporal characteristics of neuronal activities associated with peripheral persistent nociception have rarely been studied. In the present report, we used c-Fos as a neuronal marker to analyze spatial and temporal patterns of pain-related neuronal activities within the S1 area of rats subjecting to subcutaneous (s.c.) injection of bee venom (BV) solution, a well-established animal model of persistent pain. In naïve and saline-treated rats, c-Fos-labeled neurons were diffusely and sparsely distributed in the hindlimb region of S1 area. Following s.c. BV injection, c-Fos-labeled neurons became densely increased in superficial layers (II-III) and less increased in deep layers (IV-VI). The mean number of c-Fos positive neurons in the layers II-III began to increase at 1h and reached a peak at 2h after BV treatment that was followed by a gradual decrease afterward. The time course of c-Fos expression in the layers IV-VI was in parallel with that of the superficial layers, but with a much lower density and magnitude. The present results demonstrated that BV-induced peripheral persistent nociception could evoke increased neuronal activities in the S1 area with predominant localization in layers II-III.

Phosphorylation of c-Jun N-terminal kinase isoforms and their different roles in spinal cord dorsal horn and primary somatosensory cortex.

The present study was undertaken to investigate whether isoforms of c-Jun N-terminal kinase (JNK 46 kDa and 54 kDa), one component of the mitogen-activated protein kinase (MAPK) family, might show region-related differential activation patterns in both naïve and pain-experiencing rats. In naïve rats, no significant difference was observed in total expression level of the two JNK isoforms between spinal cord and primary somatosensory cortex (S1 area). However, phosphorylated JNK 46 kDa was normally expressed in the S1 area, but not in the spinal cord, while neither of the two structures contained phosphorylated JNK 54 kDa. Subcutaneous bee venom (BV)-induced persistent pain stimulation resulted in a significant increase in the phosphorylation of both JNK isoforms in each area for a long period (lasting at least 48 h). Nevertheless, JNK 46 kDa exhibited a much higher activation than JNK 54 kDa in the spinal cord, whereas the same noxious stimulation elicited evident activation of JNK 54 kDa in the S1 area, leaving JNK 46 kDa less affected. Intraplantar injection of sterile saline solution, causing acute and transient pain, produced almost the same changes in activation profile of the two JNK isoforms as found in the BV-treated rats. These results implicate that individual members of the JNK family may be associated with specific regions of nociceptive processing. Also, the two JNK isoforms are supposed to function differently according to their locations within the rat central nervous system.