Cognitive dysfunction is recognized as one of the most concerning complications in aging as well as in disease states such as neurodegenerative disorders and stroke. Although previous studies mainly focused on local brain pathology, growing evidence highlights neuroimmune crosstalk as a key regulator of cognitive function. In particular, bidirectional communication between peripheral adaptive immunity and the central nervous system (CNS) has emerged as an important mechanism underlying cognitive dysfunction. T- and B-cell subsets exert distinct effects on cognitive regulation, ranging from maintaining homeostasis to driving neuroinflammation and dysfunction. Following blood-brain barrier disruption, peripheral lymphocytes infiltrate the CNS and reshape the neuroinflammatory microenvironment through interactions with distinct glial cells. In parallel, meningeal immunity and lymphatic drainage have been identified as critical interfaces linking peripheral and central immune responses in cognitive regulation. In this review, we summarize the multifaceted roles of adaptive immune T and B cells in cognitive dysfunction, with particular emphasis on their subset-specific features, their crosstalk with glial cells, and the contribution of meningeal immunity. We further discuss the potential underlying mechanisms, with the aim of providing insights that may inform therapeutic strategies for cognitive dysfunction.

OBJECTIVE:To evaluate the efficacy of Compound Muniziqi Granule (MNZQ) and explore its mechanisms in an imiquimod (IMQ)-induced psoriasiform mouse model. METHODS:IMQ cream was applied to dorsal skin to induce lesions. Treatment groups received MNZQ by oral gavage at 1.8, 3.6, and 5.4 g/kg/day, or methotrexate (MTX, 10 mg/kg/week). MNZQ was chemically characterized by UPLC-MS/MS to profile its metabolites. The curated metabolite set was then used for network analysis and molecular docking. Predicted targets and pathways were evaluated by in vivo outcomes (PASI scores and H&E histology) and bench validation, including RT-qPCR (Il17a/Il22), flow cytometry (Th17, γδ T17), and Western blotting for STAT3, AKT, mTOR, and their phosphorylated forms. RESULTS:MNZQ significantly improved clinical and histological indices. As a hypothesis-generating step, in silico network analysis and molecular docking prioritized Th17 differentiation and the IL-17, JAK-STAT, and PI3K-AKT pathways. Consistent with these predictions, MNZQ was associated with lower frequencies of Th17 and γδ T17 cells in skin, spleen, and draining lymph nodes, and with reduced Il17a/Il22 transcripts in lesions and draining nodes (no clear dose-response). At the protein level, lesional skin showed decreased phosphorylation of STAT3, AKT, and mTOR. CONCLUSION:The findings indicate that MNZQ exerts anti-psoriatic efficacy in vivo, concurrent with decreases in γδ T17/Th17 cells frequencies and attenuation of the pro-inflammatory JAK-STAT3 and PI3K-AKT-mTOR signaling pathways.

OBJECTIVE:Both clinical and animal studies indicate a high incidence of anxiety in psoriasis, though the underlying mechanisms remain poorly understood. Our previous review suggested that T cells, related cytokines, and blood-brain barrier (BBB) disruption might serve as potential links between the two conditions. This study aimed to investigate the mechanistic connection. METHODS:Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ). Anxiety-like behaviors were assessed through the open field test, elevated plus maze test, and light-dark box test. Microglial activation was evaluated by immunofluorescence and flow cytometry. Hippocampal inflammatory cytokine expression was measured by Western blot and qRT-PCR. Inflammatory factors in brain and periphery were flow cytometrically analyzed. BBB integrity was examined using Evans blue injection and tight junction protein expression. To elucidate the roles of microglia, IL-17A, and γδ T cells, each of them was separately depleted in psoriasis mouse models, with Tcrd-/- mice used for verification. RESULTS:IMQ-treated mice exhibited significant anxiety-like behaviors, increased pro-inflammatory (CD86+) microglial activation, elevated hippocampal IL-17A (mainly derived from γδ T cells), and impaired BBB integrity characterized by reduced ZO-1 and Occludin expression. Depletion of microglia, IL-17A, or γδ T cells significantly alleviated anxiety-like behaviors in psoriasis mouse models. Following microglial depletion, RORγt expression in brain γδ T cells decreased. Conversely, IL-17A neutralization or modeling on Tcrd-/- mice altered microglial activation patterns. CONCLUSION:Psoriasis mouse models exhibit anxiety-like behaviors accompanied by impaired BBB integrity. These effects are associated with γδ T cell-microglia interactions, in which IL-17A plays a crucial role.

Sepsis is a life-threatening disease characterized by a dysregulated immune response to infection, often leading to neuroinflammation. As a known immunomodulator, Maresin-1 (MaR1) may have potential applications in the treatment of sepsis-induced neuroinflammation, but its effects in this context are unknown. We used a mouse cecum ligation and puncture (CLP)-induced sepsis model and an in vitro lipopolysaccharide (LPS)-induced neuroinflammatory model of BV2 microglia. Expression of microglial cell markers (IBA1, CD11B, CD68, CD86 and CD206) and pro-inflammatory markers (iNOS and COX2) was assessed. The role of MaR1 in regulating the P38 MAPK pathway was explored using the P38 MAPK inhibitor SB203580. In the CLP model, an increased proportion of M1-type microglia was observed, and MaR1 was able to reverse it. However, the combination of SB203580 and MaR1 did not enhance the therapeutic effect compared to SB20580 alone. In vitro experiments, MaR1 inhibited LPS-induced P38 MAPK nuclear translocation and decreased the expression of pro-inflammatory markers such as iNOS and COX2. As with the animal results, no stacking effect could be obtained with the co-administration of SB203580 and MaR1. Our findings suggest that MaR1 attenuates sepsis-induced neuroinflammation mainly by inhibiting phosphorylation of P38 MAPK in microglial cells. This suggests that MaR1 may have a potential therapeutic role in the treatment of sepsis neuroinflammation. Maresin-1 reduces the proportion of M1-type microglia in sepsis mice. Maresin-1 reduces the expression levels of iNOS and COX2 in microglia in vitro. Maresin-1 affects nuclear translocation of p38 MAPK in microglia.

Research on exercise and brain disorders has traditionally focused on its direct regulatory effects on neurons and synapses, neglecting peripheral organ-mediated pathways. To address this gap, this review proposes the novel concept of the ''multi-organ-brain axis.'' This concept posits that during brain disorders, functional alterations in peripheral organs such as skeletal muscle, heart, liver, adipose tissue, and spleen can disrupt metabolic and immune homeostasis, thereby bidirectionally modulating brain function via signaling molecules and metabolites. Under this framework, we further clarify that exercise not only exerts neuroprotective effects directly in the central nervous system, but also triggers a series of peripheral adaptive responses via the “multi-organ-brain axis,” including myokine secretion, adipokine spectrum reshaping, cardiac metabolic peptide release, and hepatic detoxification enhancement. These organ-level changes can cross the blood-brain barrier to improve synaptic plasticity, regulate microglia phenotypes, and optimize cerebral energy metabolism, ultimately creating an overall environment conducive to brain homeostasis.

BACKGROUND:Post-stroke cognitive impairment (PSCI) is a major source of morbidity and mortality after stroke, but the pathological mechanisms remain unclear. Previous studies have demonstrated that the CX3CR1 receptor plays a crucial role in maintaining an early protective microenvironment after stroke, but whether it persistently influences cognitive dysfunction in the chronic phase requires further investigation. METHODS:Mouse was used to establish a middle cerebral artery occlusion (MCAO)/reperfusion model to study PSCI. Cognitive function was assessed by the Morris water maze (MWM) and the novel object recognition test. Neurogenesis was assessed by immunofluorescence staining with Nestin+ /Ki67+ and DCX+ /BrdU+ double-positive cells. The cerebral damage was monitored by [18 F]-DPA-714 positron emission tomography, Nissel, and TTC staining. The pyroptosis was histologically, biochemically, and electron microscopically examined. RESULTS:Upon MCAO, at 28 to 35 days, CX3CR1 knockout (CX3CR1-/- ) mice had better cognitive behavioral performance both in MWM and novel object recognition test than their CX3CR1+/- counterparts. Upon MCAO, at 7 days, CX3CR1-/- mice increased the numbers of Nestin+ /Ki67+ and DCX+ /BrdU+ cells, and meanwhile it decreased the protein expression of GSDMD, NLRP3 inflammasome subunit, caspase-1, mature IL-1β/IL-18, and p-P65 in the hippocampus as compared with CX3CR1+/- mice. In addition, CX3CR1-/- mice could reverse infarct volume in the hippocampus region post-stroke. CONCLUSION:Our study demonstrated that CX3CR1 gene deletion was beneficial to PSCI recovery. The mechanism might lie in inhibited pyroptosis and enhanced neurogenesis. CX3CR1 receptor may serve as a therapeutic target for improving the PSCI.

To validate that treadmill exercise promotes neurofunctional recovery post ischemic stroke and to specifically explore the role of the CX3CL1/CX3CR1 signaling pathway in this treadmill-mediated recovery process. C57BL/6 J mice were used to establish a middle cerebral artery occlusion (MCAO) model. From days 5 to 28 post-stroke, the experimental group did 10-min treadmill sessions twice daily at 12 r/min; the control group remained inactive. On day 6 post-stroke, mice received three intraperitoneal injections of Bromodeoxyuridine (BrdU) or PBS. On days 1, 3, and 5 post-stroke, mice received intracerebroventricular injections of exogenous recombinant CX3CL1, CX3CL1 antagonist, or PBS. The modified neurological severity score (mNSS) and the corner test were used to assess sensorimotor function, and the morris water maze (MWM) test was employed to evaluate cognitive function. Western blot detected CX3CL1 and CX3CR1 protein expression, while immunofluorescence observed these proteins, neurogenesis in the subventricular zone (SVZ), rostral migratory stream (RMS), and dentate gyrus (DG), along with Iba1 and CD68 co-expression. ELISA quantified IL-1β, IL-4, and IL-10 levels. Treadmill exercise significantly improved neurofunctional recovery in MCAO mice, enhanced neurogenesis in the RMS and SVZ, and increased the expression of CX3CL1 and CX3CR1. The CX3CL1/CX3CR1 axis enhanced the impact of treadmill exercise on neurofunctional recovery, promoting neurogenesis in the RMS and SVZ, and reducing inflammation. Additionally, this axis also enhanced neurogenesis and suppressed microglial activation in the DG induced by treadmill exercise. This study demonstrates the CX3CL1/CX3CR1 pathway as critical for treadmill-induced post-stroke recovery, indicating its potential target for exercise mimetics in rehabilitation.

We analyzed adverse events (AEs) related to adalimumab and etanercept using the Food and Drug Administration Adverse Event Reporting System (FAERS) to detect unexpected AEs. Subsequently, we compared the discrepancy in serious outcomes involving the same injection site reactions (ISRs) between two different medications. Four algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were used to identify AE signals. These signals were standardized to preferred terms (PTs), and categorized at the system organ classification (SOC) level using the MedDRA system for further analysis. Serious outcomes were defined as death, disability, hospitalization, or life-threatening. The term “multiple serious outcomes” refers to instances that involve two or more of these serious consequences. Adalimumab had 186,697 AE reports (736 PTs and 28 SOCs), while etanercept had 289,989 AE reports (294 PTs and 21 SOCs). At the PT level, we identified new unexpected AEs in adalimumab that related to multiple serious outcomes like intestinal obstruction, osteoarthritis, hernia, paternal drugs affecting the fetus, intestinal fistula, anal fistula, and postoperative adhesion. At the PT level of etanercept, we discerned unanticipated AEs related to multiple serious outcomes such as knee arthroplasty, joint destruction, finger deformity, and Felty’s syndrome. At the SOC level, we paid special attention to the gastrointestinal disorders in adalimumab, with many unexpected PTs, as well as the vascular disorders and cardiac disorders in etanercept. For both drugs, the most common SOC is general disorders and administration site conditions, with ISRs being the most prevalent AEs within this category. The results indicate that etanercept has a greater variety of serious outcomes involving shared ISRs than adalimumab (p < 0.01) and also exhibits higher reported rates for these serious consequences (p < 0.01). Upon individual analysis, we identified unanticipated AEs in adalimumab and etanercept, respectively. Comparative analysis suggests that, despite similar ISRs, etanercept necessitates heightened vigilance due to its potential for more serious outcomes.

T cells are the main force of anti-infection and antitumor and are also involved in autoimmune diseases. During the development of these diseases, T cells need to rapidly produce large amounts of energy to satisfy their activation, proliferation, and differentiation. In this review, we introduced lactate dehydrogenase A(LDHA), predominantly involved in glycolysis, which provides energy for T cells and plays a dual role in disease by mediating lactate production, non-classical enzyme activity, and oxidative stress. Mechanistically, the signaling molecule can interact with the LDHA promoter or regulate LDHA activity through post-translational modifications. These latest findings suggest that modulation of LDHA may have considerable therapeutic effects in diseases where T-cell activation is an important pathogenesis.

Purpose This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors. Methods Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery. Results The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) (P <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C (P <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (P<0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (P <0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C (P <0.05). Conclusion Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.

Sepsis acute kidney injury (SAKI) is a common complication of sepsis, accounting for 26-50 % of all acute kidney injury (AKI). AKI is an independent risk factor for increased mortality risk in patients with sepsis. The excessive inflammatory cascade reaction in SAKI is one of the main causes of kidney damage. Both the innate immune system and the adaptive immune system are involved in the inflammation process of SAKI. Under the action of endotoxin, neutrophils, monocytes, macrophages, T cells and other complex immune network reactions occur, and a large number of endogenous inflammatory mediators are released, resulting in the amplification and loss of control of the inflammatory response. The study of immune cells in SAKI will help improve the understanding of the immune mechanisms of SAKI, and will lay a foundation for the development of new diagnostic and therapeutic targets. This article reviews the role of known immune mechanisms in the occurrence and development of SAKI, with a view to finding new targets for SAKI treatment.

Neuropathic pain is a common type of chronic pain, primarily caused by peripheral nerve injury. Different T-cell subtypes play various roles in neuropathic pain caused by peripheral nerve damage. Peripheral nerve damage can lead to co-infiltration of neurons and other inflammatory cells, thereby altering the cellular microenvironment and affecting cellular metabolism. By elaborating on the above, we first relate chronic pain to T-cell energy metabolism. Then we summarize the molecules that have affected T-cell energy metabolism in the past five years and divide them into two categories. The first category could play a role in neuropathic pain, and we explain their roles in T-cell function and chronic pain, respectively. The second category has not yet been involved in neuropathic pain, and we focus on how they affect T-cell function by influencing T-cell metabolism. By discussing the above content, this review provides a reference for studying the direct relationship between chronic pain and T-cell metabolism and searching for potential therapeutic targets for the treatment of chronic pain on the level of T-cell energy metabolism.

Opioids are mainly used as adjuncts to the induction and maintenance of general anesthesia, postoperative analgesia, and treating moderate to severe cancer pain and chronic pain. However, the hazards of these drugs to various organ organs still need to be further explored. This study used the US FDA Adverse Event Reporting System (FAERS) database to determine whether commonly receiving opioids was higher than the baseline risk for all other medications. FAERS was asked about adverse events (AEs) for the opioids "morphine," "fentanyl," "oxycodone," "hydromorphone," "sufentanil," and "remifentanil" from the first quarter of 2004 (2004Q1) through the second quarter of 2023 (2023Q2). Disproportionality signaling analysis was performed by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). AEs with system organ classes (SOCs) of "cardiac disease," "neurologic disease," and "respiratory, thoracic, and mediastinal disease" were then screened. The statistical analysis included 12,819,518 reports in the FAERS database from 2004Q1 to 2023Q2, of which 236,619 AEs were reported as "primary suspect" for the six drugs mentioned above, which were selected as "cardiac disorders," "nervous system disorders," and "respiratory, thoracic and mediastinal disorders." Some AEs identified in this study are consistent with the drug labeling, such as bradycardia, respiratory depression, and somnolence. In addition, some unexpected and significant acute adverse drug reactions (ADRs), such as toxic leukoencephalopathy and coma, may occur. This study identified potential new and unexpected ADRs for opioids, providing valuable evidence for safety studies of opioids.

Ischemic stroke (IS) is a major cause of morbidity and mortality worldwide, accounting for 75-80% of all strokes. Under conditions of ischemia and hypoxia, neurons suffer damage or death, leading to a series of secondary immune reactions. Microglia, the earliest activated immune cells, can exert neurotoxic or neuroprotective effects on neurons through secretion of factors. There exists a complex interaction between neurons and microglia during this process. Moreover, the interaction between them becomes even more complex due to differences in the infarct area and reperfusion time. This review first elaborates on the differences in neuronal death modes between the ischemic core and penumbra, and then introduces the differences in microglial markers across different infarct areas with varying reperfusion time, indicating distinct functions. Finally, we focus on exploring the interaction modes between neurons and microglia in order to precisely target beneficial interactions and inhibit harmful ones, thus providing new therapeutic strategies for the treatment of IS.

Objective. Neuromuscular blocking agents (NMBAs) are part of the three elements of general anaesthesia (sedation, analgesia, and muscle relaxation), which can relax muscles and facilitate intubation and surgery. It has been reported that cancer cells are prone to invasion or metastasis during surgery, but various anaesthetics are currently used in cancer resection, particularly NMBA, and the effects on cancer cell behavior are poorly understood. Guidelines for the correct application of NMBA in cancer surgery have not been reported; therefore, the aim of this paper is to explore the relationship between NMBA and cancer. Methods. Two investigators independently searched PubMed, Embase, the Cochrane Library, Web of Science, and CBM for articles of NMBA and cancer. Results. The available evidence suggests that cisatracurium may be more appropriate for use in anaesthesia for cancer surgery, while rocuronium deserves further attention, particularly for breast and gastric cancer surgery, and vecuronium is suitable for breast cancer and non-small-cell lung cancer, while it is used with caution in gastric cancer. Also, the relationship between NMBA (mivacurium, succinylcholine, gantacurium, and decamethonium bromide) and cancer is unclear and deserves further study. Conclusion. The effect of different NMBAs on cancer cells varies, and the effect of some NMBAs on cancer cells is unclear, and most of the current findings are only from in vitro studies, which need to be validated by further clinical studies in the future to better guide the clinical application of NMBAs.

Dexmedetomidine has been identified as a useful adjunct to improve the effect of nerve blocks in adults; however, its effect for children has not yet been fully investigated. This meta‐analysis aimed to evaluate the reliability and efficacy of dexmedetomidine as a local anesthetic adjunct for pediatric surgeries. Eligible studies were searched in Cochrane, Embase, PubMed, and CBM. RevMan 5.4 was used to assess the risk of bias of each study and perform statistical analysis. Stata 15.0 was used to evaluate the publication bias of primary outcomes. Thirteen randomized controlled trial (RCTs) involving 722 patients aged 6 months to 12 years were harvested. Statistical analysis showed that dexmedetomidine resulted in: a significantly longer duration of analgesia (standardized mean difference [SMD], 7.16; 95% confidence interval [95%CI], 4.88 to 9.43; P < .001; I 2 = 98%); a reduction in the 1‐hour pain score (mean difference [MD], –0.27; 95%CI, –0.47 to –0.06; P = .01; I 2 = 28%); cumulative doses of rescue analgesic required of 2 doses (risk ratio [RR], 0.26; 95%CI, 0.14 to 0.49; P < .001; I 2 = 0) or 3 doses (RR, 0.04; 95%CI, 0.01 to 0.16; P < .001; I 2 = 4%); the frequency of emergence agitation (RR, 0.44; 95%CI, 0.22 to 0.91; P = .03; I 2 = 0); and a reduction in the onset time of blocks (mean difference –3.56; 95%CI, –6.39 to –0.74; P = .01; I 2 = 90%). However, the incidence of some side effects, including hypotension, bradycardia, nausea and vomiting, pruritis, urinary retention, and respiratory depression, did not significantly differ between the dexmedetomidine group and the placebo group. Therefore, dexmedetomidine is a reliable and efficient adjunct to local anesthetics in children.

As we all know, dexmedetomidine (DEX), as a highly selective α2 adrenergic receptor agonist, exerts sedative, anti-anxiety and hypnotic effects by inhibiting the discharge of norepinephrine neurons in locus coeruleus and GABA-related hypnotic pathways. However, the role of DEX in anti-inflammatory and immune regulation has gradually attracted the attention of researchers in recent years. The α2 adrenergic receptor is one of the members of the adrenergic receptor family, which is widely present in a variety of immune cells and mediates the biological behavior of the inflammatory immune system. At present, there have been more and more studies on the effects of DEX on immune cells and inflammatory responses, but few studies have systematically explored the anti-inflammatory and immunomodulatory effects of DEX. Here, we comprehensively review the published human and animal studies related to DEX, summarize the effects of DEX on immune cells and its role in related diseases, and propose potential research direction.

Abstract Background: Postoperative cognitive dysfunction (POCD) is a common complication after general anesthesia surgery, and the mechanism of POCD has not been completely studied yet. We aim to use bioinformatics to identify the potential key genes and pathways involved in the mechanism of POCD and explore the potential targeted drugs to treat POCD.Methods: Genes related to POCD were detected using pubmed2ensemble, then the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of these genes were annotated and visualized using GENECODIS. A protein‑protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape, and the Molecular Complex Detection (MCODE) was used to classify the candidate gene modules. Candidate genes were further validated again via Metascape and Cluego for a GO enrichment and KEGG pathway analysis. Finally, Drug-Gene Interaction Database (DGIDB) was used to identify the related drugs.Results: We identified 70 genes related to POCD and as follows 48 candidate genes were obtained following GO and KEGG enrichment analysis. 39 genes were obtained from a PPI network and one gene module including 12 crucial genes were obtained using the MCODE. Lastly, 5 genes including ACE, IL6, TNF, CCL2, CXCL8 related to 3 main signaling pathways---- hypertrophic cardiomyopathy, viral protein interaction with cytokine and cytokine receptor, and IL17 signaling pathway. Furthmore,26 targeted drugs were explored as potential therapeutic agents. Conclusion: In this study, we ultimately identified 5 target genes targetable by 26 drugs for POCD, related to 3 main signaling pathways.

Objective: To investigate the efficacy and safety of dexmedetomidine (DEX) for postoperative patient controlled intravenous analgesia (PCIA). Measurements: Two investigators independently searched Pubmed, Embase, Scopus, Cochrane Library and CBM for randomized controlled trials of DEX for PCIA. Main results: Thirty-seven studies with a total of 5,409 patients were included in this meta-analysis. Compared with analgesics alone, DEX for PCIA reduced pain score at 24 h [mean difference (MD) = −0.70; 95% confidence interval (CI): −0.85, −0.54; p < 0.00001, I 2 = 90%] and 48 h postoperatively (MD = −0.43; 95% CI: −0.52, −0.34; p < 0.00001, I 2 = 96%). Moreover, DEX reduced analgesics consumption during the first 24 h [standardized mean difference (SMD) = −0.25; 95% CI: −0.34, −0.16; p < 0.00001, I 2 = 91%] and the number of resuscitation analgesics administered [odds ratio (OR) = 0.54; 95% CI: 0.44, 0.66; p < 0.00001, I 2 = 72%]. Furthermore, DEX improved patient satisfaction (OR = 3.55; 95% CI: 2.36, 5.35; p < 0.00001, I 2 = 60%), and reduced incidence of side effects, such as postoperative nausea and vomiting (PONV) (OR = 0.47; 95% CI: 0.39, 0.57; p < 0.00001, I 2 = 59%) and pruritus after surgery (OR = 0.45; 95% CI: 0.30, 0.68; p = 0.0001, I 2 = 0%). Besides, DEX attenuates inflammatory cytokine levels, such as IL-6 (MD = −5.73; 95% CI: −8.34, −3.12; p < 0.00001, I 2 = 91%) and TNF-α (MD = −0.63; 95% CI: −0.76, −0.50; p < 0.00001, I 2 = 89%). Finally, DEX increased the risk of bradycardia (OR = 1.66; 95% CI: 1.12, 2.45; p = 0.01, I 2 = 15%), but the complication of hypotension did not differ between the two groups (OR = 1.30; 95% CI: 0.84, 2.04; p = 0.25, I 2 = 0%). Conclusion: DEX is used for postoperative PCIA analgesia, which can significantly improve the analgesic effect, effectively control postoperative inflammatory response, reduce the dosage and adverse reactions of analgesics, and improve postoperative patient satisfaction. Of course, the impact of the immunosuppressive effect of DEX on the prognosis of patients needs further study. Systematic review registration: CRD42022340933, https://www.crd.york.ac.uk/prospero/.