Background: The long-term outcomes of patients with chronic pain treated in a multidisciplinary pain management center remain variable. Objective: This study aims to evaluate the changes in outcomes of patient’s self...Background: The long-term outcomes of patients with chronic pain treated in a multidisciplinary pain management center remain variable. Objective: This study aims to evaluate the changes in outcomes of patient’s self-reported pain, psychosocial status, health related quality of life and gender differences following treatment in amultidisciplinary pain management centre. Design: A prospective longitudinal cross-sectional study uses questionnaires. Treatment Setting: A pragmatic and individualized patient centered approach in a tertiary level multidisciplinary pain management center. Subjects: Patients with chronic pain referred to the centre from 2004-2010. Outcome Measures: Pain Numerical Rating Scale (NRS), Pain Temporal Description (1 - 6), Pain Self- Efficacy Questionnaire (PSEQ), Depression Anxiety Stress Scales (DASS-21) and Short Form-36 (SF- 36). Follow-up questionnaires were sent at 6 and 12 months after initial assessment. Results: Mean duration of baseline chronic pain was 8.1 years and 61% of chronic pains were involving the musculoskeletal system. At 6 and 12 month follow-ups, 273 and 180 participants had been surveyed respectively. At 6-month follow-up, there were significant improvements on pain intensity (Cohen’s d = 0.8), pain self-efficacy (Cohen’s d = 0.47), depression and stress scores (Cohen’s d = 0.16) and six out of eight domains of SF-36 (Cohen’s d = 0.2 - 0.4). At 12-month follow-up, improvements were maintained on pain intensity, self-efficacy and three out of eight domains of SF-36. There were distinctive pre- and post-treatment gender differences in these outcomes and overall females showed better short- and long-term outcomes than males. Conclusion: Multidisciplinary pain management using an individualized patient centered approach remains an effective treatment for chronic pain in both the short- (6 month) and long-term (12 month). The distinctive pre- and post-treatment gender differences particularly in the psychological outcomes, suggest that it may be beneficial to further delineate and better manage vulnerable patient subgroups.展开更多
Neuropathic pain,a debilitating condition caused by dysfunction of the somatosensory nervous system,remains difficult to treat due to limited understanding of its molecular mechanisms.Bioinformatics analysis identifie...Neuropathic pain,a debilitating condition caused by dysfunction of the somatosensory nervous system,remains difficult to treat due to limited understanding of its molecular mechanisms.Bioinformatics analysis identified cerebellin 2(CBLN2)as highly enriched in human and murine proprioceptive and nociceptive neurons.We found that CBLN2 expression is persistently upregulated in dorsal root ganglia(DRG)following spinal nerve ligation(SNL)in mice.In addition,transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription.SNL also induced SOX11 upregulation,with SOX11 and CBLN2 co-localized in nociceptive neurons.The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia.High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes,including upregulation of numerous NF-κB downstream targets.Consistently,CBLN2 activated NF-κB signaling,and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity,proinflammatory cytokines and chemokines production,and neuronal hyperexcitability.Together,these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.展开更多
The cytochrome P450 proteins(CYP450s)have been implicated in catalyzing numerous important biological reactions and contribute to a variety of diseases.CYP26A1,a member of the CYP450 family,carries out the oxidative m...The cytochrome P450 proteins(CYP450s)have been implicated in catalyzing numerous important biological reactions and contribute to a variety of diseases.CYP26A1,a member of the CYP450 family,carries out the oxidative metabolism of retinoic acid(RA),the active metabolite of vitamin A.Here we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation(SNL).CYP26A1 was mainly expressed in spinal neurons and astrocytes.HPLC analysis displayed that the content of all-trans-RA(at-RA),the substrate of CYP26A1,was reduced in the spinal cord on day 7 after SNL.Inhibition of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic pain.Talarozole also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine(IL-10)production.The RA receptors RARα,RXRβ,and RXRγwere expressed in spinal neurons and glial cells.The promoter of Il-10 has several binding sites for RA receptors,and at-RA directly increased Il-10 mRNA expression in vitro.Finally,intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and microglia.Collectively,the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial activation.CYP26A1 may be a potential therapeutic target for the treatment of neuropathic pain.展开更多
Lumbar synovial cysts are benign fluid collections thought to form in a background of facet joint degeneration, allowing for fluid to leak from the joint capsule and form cysts in the synovium. Although often asymptom...Lumbar synovial cysts are benign fluid collections thought to form in a background of facet joint degeneration, allowing for fluid to leak from the joint capsule and form cysts in the synovium. Although often asymptomatic, patients with symptomatic synovial cysts will present with low back pain and possibly an associated radiculopathy. Clinicians can consider conservative management, epidural steroid injection, surgical intervention, or facet joint block with aspiration and rupture. This case describes a 59-year-old male facilities manager with intermittent low back pain for one year with worsening right-sided radicular symptoms secondary to a lumbar facet joint synovial cyst in the context of severe facet arthropathy and microinstability. The patient’s low back pain and radicular symptoms were refractory to conservative treatment. Imaging demonstrated a lumbar synovial cyst and subsequent management included transforaminal epidural steroid injection and facet joint block with cyst aspiration and rupture. The patient’s radicular pain resolved but axial lumbar pain returned after 3 weeks of relief. Follow-up imaging demonstrated decreased cyst size with fluid accumulation and joint space widening. Although the cyst was successfully decompressed with resolution of radicular pain, the underlying facet arthropathy remains contributing to persistent axial low back pain and potential for continued degenerative changes including cyst recurrence.展开更多
BACKGROUND Intracranial hypotension(IH)is a disorder involving cerebrospinal fluid(CSF)hypovolemia due to spontaneous or traumatic spinal CSF leakage and is easily being misdiagnosed or missed,especially in these pati...BACKGROUND Intracranial hypotension(IH)is a disorder involving cerebrospinal fluid(CSF)hypovolemia due to spontaneous or traumatic spinal CSF leakage and is easily being misdiagnosed or missed,especially in these patients without the prototypical manifestation of an orthostatic headache.At present,the management of IH with both cranial nerve VI palsy and bilateral subdural hematomas(SDHs)is still unclear.CASE SUMMARY A 67-year-old male Chinese patient complained of diplopia on the left side for one and a half mo.Computed tomography revealed bilateral SDHs and a midline shift.However,neurotrophic drugs were not effective,and 3 d after admission,he developed a non-orthostatic headache and neck stiffness.Enhanced magnetic resonance imaging revealed dural enhancement as an additional feature,and IH was suspected.Magnetic resonance myelography was then adopted and showed CSF leakage at multiple sites in the spine,confirming the diagnosis of having IH.The patient fully recovered following multiple targeted epidural blood patch(EBP)procedures.CONCLUSION IH is a rare disease,and to the best of our knowledge,IH with diplopia as its initial and primary symptom has never been reported.In this study,we also elucidated that it could be safe and effective to treat IH patients with associated cranial nerve VI palsy and bilateral SDHs using repeated EBP therapy.展开更多
Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Conn...Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.展开更多
<strong>Background</strong>: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. <strong>Objective</strong>: This ...<strong>Background</strong>: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. <strong>Objective</strong>: This study aims to investigate pain and psychological outcomes of ketamine parenteral infusion (0.1 - 0.35 mg/kg/h or maximum 24 mg/hour) for 5 days in patients with chronic refractory pain. The secondary objective is to explore any prognostic pain and psychological factors associated with the successful response to the ketamine treatment. <strong>Methodology</strong>: A prospective longitudinal study of a small cohort (N = 35) of patients with heterogenous chronic refractory pain conditions was conducted from one week to two months follow-up. <strong>Results</strong>: Pain Severity was significantly improved from mean 6.5 to 5.1 (t = 3.77, p < 0.001, d = 0.6) at 1-week and 5.9 (t = 2.14, p = 0.042, d = 0.4) at 2-month;Pain Interference from mean 7.0 to 5.1 (t = 4.99, p < 0.001, d = 0.9) at 1-week and 6.1 (t = 2.16, p = 0.041, d = 0.4) at 2-month;Pain Self-Efficacy Questionnaire (PSEQ) from mean 17 to 24 (t = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>3.37, p = 0.002, d = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>0.6) at 1-week and 23 (t =<span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>2.60, p = 0.016, d =<span style="white-space:nowrap;">−</span><span style="white-space:nowrap;"></span>0.5) at 2-month;Pain Catastrophizing (PCS) from 28 to 23 (t = 3.4, p = 0.002;d = 0.6) at 1-week and 21 (t = 2.45, p = 0.022, d = 0.5) at 2-month;Depression from mean 21 to 16 (t = 2.16, p = 0.038, d = 0.4) at 1-week and 16 (t = 3.53, p = 0.002, d = 0.7) at 2-month;and oral Morphine Equivalent Daily Dose (oMEDD) reduced from mean 191 mg/day on admission to 122 mg/day at 1-week (t = 2.38, p = 0.023;d = 0.4) and 93 mg/day at 2-month (t = 2.59, p = 0.016;d = 0.5). There was no significant difference between responders and non-responders on baseline psychological measures (t<sub>33</sub> < 1.19, p > 0.244) and pain classifications ( <img src="Edit_c68fc9e4-a875-4b79-b0cf-af146ed090fe.png" alt="" /> = 0.610, p = 0.894). <strong>Conclusion</strong>: Ketamine subanaesthetic dose infusion for 5 days was found to be effective in managing chronic refractory pain with significant opioid reduction and small improvements in all chronic pain outcomes, except anxiety, at 1-week and 2-month follow-up and with minimal severe adverse effects.展开更多
BACKGROUND Elsberg syndrome is a type of postinfectious lumbosacral radiculitis typically tri-ggered by neurotropic viruses and manifests as bladder/bowel dysfunction,saddle sensory disturbances(including hypoesthesia...BACKGROUND Elsberg syndrome is a type of postinfectious lumbosacral radiculitis typically tri-ggered by neurotropic viruses and manifests as bladder/bowel dysfunction,saddle sensory disturbances(including hypoesthesia,hyperesthesia,or dyse-sthesia),and variable neurological deficits.Typically self-limiting,it often res-ponds to antiviral and neurotropic therapies.However,in patients with comorbi-dities that confer susceptibility to peripheral neuropathy(e.g.,diabetes mellitus),timely escalation to neuromodulation strategies,such as spinal cord stimulation,may be warranted to optimize functional outcomes when conservative measures are inadequate.CASE SUMMARY A 60-year-old male with diabetes mellitus presented with severe bladder and bowel dysfunction persisting for more than two months,followed by left gluteal and perianal(saddle area)herpes zoster eruption that was accompanied by significant neuropathic pain.Following a suboptimal response to conservative therapy,the patient underwent implantation of a short-term spinal cord stimu-lation.Following a 10-day trial of continuous tonic stimulation,the percutaneous electrode lead was removed.The patients experienced no surgical complications,and after the procedure,the patient achieved complete restoration of bladder and bowel function and significant pain alleviation.Two-month follow-up confirmed sustained full recovery.CONCLUSION Early implementation of short-term spinal cord stimulation represents a pro-mising therapeutic approach for promoting neurological recovery in patients with Elsberg syndrome refractory to conservative management,especially those with predisposing comorbidities such as diabetes mellitus.展开更多
BACKGROUND Postoperative delirium(POD),an acute neuropsychiatric complication in elderly surgical patients,manifests as attention and cognitive disturbances that may last 24-72 hours after surgery,potentially progress...BACKGROUND Postoperative delirium(POD),an acute neuropsychiatric complication in elderly surgical patients,manifests as attention and cognitive disturbances that may last 24-72 hours after surgery,potentially progressing to dementia.Transcranial direct current stimulation(tDCS),a non-invasive neuromodulation technique,enhances cortical excitability and cognitive function by modulating brain networks and synaptic plasticity.Elderly patients undergoing major laparoscopic surgery face elevated POD risks due to prolonged anesthesia and pneumoperitoneum-induced cerebral hypoperfusion.This study investigates whether pre-anesthesia tDCS can reduce POD incidence in this population.AIM To investigate the effect of preoperative tDCS on reducing the incidence of POD in elderly patients undergoing major laparoscopic surgery.METHODS In this study,we enrolled 220 elderly patients who underwent major laparoscopic surgery between April 2024 and December 2024.Patients were randomly assigned to the active-tDCS(group A)and sham-tDCS(group S)groups.A single session of tDCS or sham stimulation was administered 30 minutes before anesthesia induction.The primary outcome was the incidence of POD during within 3 days postoperatively.RESULTS A total of 201 patients were included in the final analysis,with 100 patients in group A and 101 in group S.The incidence of POD within 3 days postoperatively was 7.0%in group A,which was significantly lower than 22.8%in group S.On postoperative day 1,the Self-Rating Anxiety Scale and Self-Rating Depression Scale scores significantly differed between the two groups,but the pain scores showed no significant difference.CONCLUSION A single session of preoperative tDCS can reduce the incidence of POD in elderly patients undergoing major laparoscopic surgery and can also reduce postoperative anxiety and depression in these patients.展开更多
BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing int...BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.展开更多
OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combinatio...OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.展开更多
Dear Editor,SARS-CoV-2 is the virus that caused the COVID-19 pandemic,leading to more than 774 million cases and 7,037,007 deaths by March 2024(World Health Organization,http://covid19.who.int/).Despite effective trea...Dear Editor,SARS-CoV-2 is the virus that caused the COVID-19 pandemic,leading to more than 774 million cases and 7,037,007 deaths by March 2024(World Health Organization,http://covid19.who.int/).Despite effective treatments,15%-20%of patients experience long-term symptoms,such as breathlessness,fatigue,depression,and cognitive impairment,which are often linked to an excessive immune response[1].All variants of the virus(α,,,Omicron,and BA.1),which can potentially access the brain via the olfactory mucosa,have been found in the brains of Syrian hamsters,triggering inflammation and demonstrating axonal travel[2].展开更多
With the acceleration of China's aging society,elderly patients have become a high-risk group for malignant tumors and exhibit high prevalence of pain.For a long time,the diagnosis,treatment,and management of canc...With the acceleration of China's aging society,elderly patients have become a high-risk group for malignant tumors and exhibit high prevalence of pain.For a long time,the diagnosis,treatment,and management of cancer pain in elderly Chinese patients have been inadequate.This study used"Older adults,geriatric patients,cancer pain,pain assessment,pain management,elderly cancer,geriatric oncology,medication management,palliative care,interdisciplinary pain management,Analgesics,quality of life"as key words.We systematically searched PubMed,Web of Science,CNKI,and Wanfang databases from their inception to September 2024.The search primarily included phase I to III clinical trials,randomized controlled trials,meta-analyses,systematic reviews,and case reports.Elderly patients typically present with complex pain mechanisms,including both cancer-related and non-cancer pain,cognitive dysfunction,comorbidities,and polypharmacy,posing significant challenges for clinical diagnosis and treatment.Notable clinical differences exist between elderly and younger patients in the epidemiology,assessment,diagnosis,and treatment of cancer pain.Currently,the awareness of comprehensive management for elderly cancer pain patients is limited,and specific,implementable clinical guidelines are lacking.Therefore,developing a comprehensive,localized management model for elderly cancer pain patients in China—incorporating factors such as age-related impacts,organ function status,and comorbidities—has become an urgent necessity.展开更多
AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male Sprague...AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.展开更多
Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapopto...Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.展开更多
BACKGROUND Medical robot is a promising surgical tool,but no specific one has been designed for interventional treatment of chronic pain.We developed a computed tomography-image based navigation robot using a new regi...BACKGROUND Medical robot is a promising surgical tool,but no specific one has been designed for interventional treatment of chronic pain.We developed a computed tomography-image based navigation robot using a new registration method with binocular vision.This kind of robot is appropriate for minimal invasive interventional procedures and easy to operate.The feasibility,accuracy and stability of this new robot need to be tested.AIM To assess quantitatively the feasibility,accuracy and stability of the binocularstereo-vision-based navigation robot for minimally invasive interventional procedures.METHODS A box model was designed for assessing the accuracy for targets at different distances.Nine(three sets)lead spheres were embedded in the model as puncture goals.The entry-to-target distances were set 50 mm(short-distance),100 mm(medium-distance)and 150 mm(long-distance).Puncture procedure was repeated three times for each goal.The Euclidian error of each puncture was calculated and statistically analyzed.Three head phantoms were used to explore the clinical feasibility and stability.Three independent operators conducted foramen ovale placement on head phantoms(both sides)by freehand or under the guidance of robot(18 punctures with each method).The operation time,adjustment time and one-time success rate were recorded,and the two guidancemethods were compared.RESULTS On the box model,the mean puncture errors of navigation robot were 1.7±0.9 mm for the short-distance target,2.4±1.0 mm for the moderate target and 4.4±1.4 mm for the long-distance target.On the head phantom,no obvious differences in operation time and adjustment time were found among the three performers(P>0.05).The median adjustment time was significantly less under the guidance of the robot than under free hand.The one-time success rate was significantly higher with the robot(P<0.05).There was no obvious difference in operation time between the two methods(P>0.05).CONCLUSION In the laboratory environment,accuracy of binocular-stereo-vision-based navigation robot is acceptable for target at 100 mm depth or less.Compared with freehand,foramen ovale placement accuracy can be improved with robot guidance.展开更多
BACKGROUND Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia.The anatomical features of the thoracic spine are complex,and puncture ...BACKGROUND Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia.The anatomical features of the thoracic spine are complex,and puncture injury to the pleura,blood vessels,spinal cord,and other tissues may cause serious complications.The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood.AIM To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments.METHODS A total of 88 patients(41 males and 47 females)who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included.Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected.The width of the intertransverse space(D_(P)),the height of the rib neck/head above the lower transverse process(D_(R)),the width of the lateral border of the articular process/lamina(W_(P)),and the width of the posterior border of the vertebral body(W_(V))were measured.At the upper 1/3 of the intervertebral foramina,the horizontal inclination angle(α)from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured.The ratios D_(R)/D_(P) and W_(P)/W_(V) were calculated.The intervertebral foramen parameters were compared between segments.RESULTS No rib head/neck occlusion(D_(R)/D_(P)>0)was found in the intertransverse spaces of T1-2 and T12-L1.The incidence of occlusion for the upper thoracic segments(T1-5,n=138),middle thoracic segments(T5-9,n=116),and lower thoracic segments(T9-L1,n=80)were 76.81%,100%,and 82.50%,respectively.The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).The incidence of>1/2 occlusion(D_(R)/D_(P)>1/2)for the upper,middle,and lower thoracic segments was 7.97%,74.14%,and 32.50%,respectively.The incidence of>1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).W_(P) was longer than W_(V) on T1-2 to T9-10 and shorter than W_(V) on T10-11 to T12-L1.The horizontal puncture angle(α)into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion(left:r=0.772,P<0.01;right:r=0.771,P<0.01),and the horizontal inclination angle for T11-12 and T12-L1 was 90°.CONCLUSION It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.展开更多
AIM： TO explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture. METHODS： Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile ...AIM： TO explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture. METHODS： Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into four groups according to the fentanyl concentration： control group （0 ng/mL）, group I （0.3 ng/mL）, group I （3.0 ng/mL）, and group III （30 ng/mL）. In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl ＋ 0.1 μg/mL naloxone or fentanyl ＋ 1.0 μg/mL naloxone. Cell viability was assessed by the MTT assay. Insulin release in response to low and high concentrations （2.8 mmol/L and 16.7 mmol/L, respectively） of glucose was investigated and electron microscopy morphological assessment was performed. RESULTS： Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups I and II （62.33 ± 9.67 μIU vs 47.75 ± 8.47 μIU, 39.67 ± 6.18 μIU and 125.5 ± 22.04 μIU vs 96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P 〈 0.01） and was lowest in group III （P 〈 0.01）. After adding 1 μg/mL naloxone, insulin release in groups II and II was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/ml fentanyl. CONCLUSION： Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged β-cells of rat islets.展开更多
Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers p...Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.展开更多
The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation a...The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation and creep properties of the optic nerve change after injury.Moreover,human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal.To validate this hypothesis,a rabbit model of optic nerve injury was established using a clamp approach.At 7 days after injury,the vitreous body received a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells.At 30 days after injury,stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly,with pathological changes in the injured optic nerve also noticeably improved.These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves,and thereby contributes to nerve recovery.展开更多
文摘Background: The long-term outcomes of patients with chronic pain treated in a multidisciplinary pain management center remain variable. Objective: This study aims to evaluate the changes in outcomes of patient’s self-reported pain, psychosocial status, health related quality of life and gender differences following treatment in amultidisciplinary pain management centre. Design: A prospective longitudinal cross-sectional study uses questionnaires. Treatment Setting: A pragmatic and individualized patient centered approach in a tertiary level multidisciplinary pain management center. Subjects: Patients with chronic pain referred to the centre from 2004-2010. Outcome Measures: Pain Numerical Rating Scale (NRS), Pain Temporal Description (1 - 6), Pain Self- Efficacy Questionnaire (PSEQ), Depression Anxiety Stress Scales (DASS-21) and Short Form-36 (SF- 36). Follow-up questionnaires were sent at 6 and 12 months after initial assessment. Results: Mean duration of baseline chronic pain was 8.1 years and 61% of chronic pains were involving the musculoskeletal system. At 6 and 12 month follow-ups, 273 and 180 participants had been surveyed respectively. At 6-month follow-up, there were significant improvements on pain intensity (Cohen’s d = 0.8), pain self-efficacy (Cohen’s d = 0.47), depression and stress scores (Cohen’s d = 0.16) and six out of eight domains of SF-36 (Cohen’s d = 0.2 - 0.4). At 12-month follow-up, improvements were maintained on pain intensity, self-efficacy and three out of eight domains of SF-36. There were distinctive pre- and post-treatment gender differences in these outcomes and overall females showed better short- and long-term outcomes than males. Conclusion: Multidisciplinary pain management using an individualized patient centered approach remains an effective treatment for chronic pain in both the short- (6 month) and long-term (12 month). The distinctive pre- and post-treatment gender differences particularly in the psychological outcomes, suggest that it may be beneficial to further delineate and better manage vulnerable patient subgroups.
基金supported by STI2030-Major Projects(2022ZD0204700)the National Natural Science Foundation of China(32030048,32200817,and 82271256).
文摘Neuropathic pain,a debilitating condition caused by dysfunction of the somatosensory nervous system,remains difficult to treat due to limited understanding of its molecular mechanisms.Bioinformatics analysis identified cerebellin 2(CBLN2)as highly enriched in human and murine proprioceptive and nociceptive neurons.We found that CBLN2 expression is persistently upregulated in dorsal root ganglia(DRG)following spinal nerve ligation(SNL)in mice.In addition,transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription.SNL also induced SOX11 upregulation,with SOX11 and CBLN2 co-localized in nociceptive neurons.The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia.High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes,including upregulation of numerous NF-κB downstream targets.Consistently,CBLN2 activated NF-κB signaling,and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity,proinflammatory cytokines and chemokines production,and neuronal hyperexcitability.Together,these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
基金supported by STI2030-Major Projects(2022ZD0204700)the National Natural Science Foundation of China(32030048,31700899,and 32200817)+1 种基金the Graduate Student Scientific Research Innovation Projects of Jiangsu Province(KYCX18-2397)the Startup Foundation for Doctors of the Affiliated Hospital of Nantong University(Tdb1906).
文摘The cytochrome P450 proteins(CYP450s)have been implicated in catalyzing numerous important biological reactions and contribute to a variety of diseases.CYP26A1,a member of the CYP450 family,carries out the oxidative metabolism of retinoic acid(RA),the active metabolite of vitamin A.Here we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation(SNL).CYP26A1 was mainly expressed in spinal neurons and astrocytes.HPLC analysis displayed that the content of all-trans-RA(at-RA),the substrate of CYP26A1,was reduced in the spinal cord on day 7 after SNL.Inhibition of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic pain.Talarozole also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine(IL-10)production.The RA receptors RARα,RXRβ,and RXRγwere expressed in spinal neurons and glial cells.The promoter of Il-10 has several binding sites for RA receptors,and at-RA directly increased Il-10 mRNA expression in vitro.Finally,intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and microglia.Collectively,the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial activation.CYP26A1 may be a potential therapeutic target for the treatment of neuropathic pain.
文摘Lumbar synovial cysts are benign fluid collections thought to form in a background of facet joint degeneration, allowing for fluid to leak from the joint capsule and form cysts in the synovium. Although often asymptomatic, patients with symptomatic synovial cysts will present with low back pain and possibly an associated radiculopathy. Clinicians can consider conservative management, epidural steroid injection, surgical intervention, or facet joint block with aspiration and rupture. This case describes a 59-year-old male facilities manager with intermittent low back pain for one year with worsening right-sided radicular symptoms secondary to a lumbar facet joint synovial cyst in the context of severe facet arthropathy and microinstability. The patient’s low back pain and radicular symptoms were refractory to conservative treatment. Imaging demonstrated a lumbar synovial cyst and subsequent management included transforaminal epidural steroid injection and facet joint block with cyst aspiration and rupture. The patient’s radicular pain resolved but axial lumbar pain returned after 3 weeks of relief. Follow-up imaging demonstrated decreased cyst size with fluid accumulation and joint space widening. Although the cyst was successfully decompressed with resolution of radicular pain, the underlying facet arthropathy remains contributing to persistent axial low back pain and potential for continued degenerative changes including cyst recurrence.
文摘BACKGROUND Intracranial hypotension(IH)is a disorder involving cerebrospinal fluid(CSF)hypovolemia due to spontaneous or traumatic spinal CSF leakage and is easily being misdiagnosed or missed,especially in these patients without the prototypical manifestation of an orthostatic headache.At present,the management of IH with both cranial nerve VI palsy and bilateral subdural hematomas(SDHs)is still unclear.CASE SUMMARY A 67-year-old male Chinese patient complained of diplopia on the left side for one and a half mo.Computed tomography revealed bilateral SDHs and a midline shift.However,neurotrophic drugs were not effective,and 3 d after admission,he developed a non-orthostatic headache and neck stiffness.Enhanced magnetic resonance imaging revealed dural enhancement as an additional feature,and IH was suspected.Magnetic resonance myelography was then adopted and showed CSF leakage at multiple sites in the spine,confirming the diagnosis of having IH.The patient fully recovered following multiple targeted epidural blood patch(EBP)procedures.CONCLUSION IH is a rare disease,and to the best of our knowledge,IH with diplopia as its initial and primary symptom has never been reported.In this study,we also elucidated that it could be safe and effective to treat IH patients with associated cranial nerve VI palsy and bilateral SDHs using repeated EBP therapy.
基金the National Natural Science Foundation of China(81971056,31600852,81771202,and 81873101)the Innovative Research Team of Highlevel Local Universities in Shanghai+3 种基金the Foundation of Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180302153701406)the National Key R&D Program of China(2017YFB0403803)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab。
文摘Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.
文摘<strong>Background</strong>: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. <strong>Objective</strong>: This study aims to investigate pain and psychological outcomes of ketamine parenteral infusion (0.1 - 0.35 mg/kg/h or maximum 24 mg/hour) for 5 days in patients with chronic refractory pain. The secondary objective is to explore any prognostic pain and psychological factors associated with the successful response to the ketamine treatment. <strong>Methodology</strong>: A prospective longitudinal study of a small cohort (N = 35) of patients with heterogenous chronic refractory pain conditions was conducted from one week to two months follow-up. <strong>Results</strong>: Pain Severity was significantly improved from mean 6.5 to 5.1 (t = 3.77, p < 0.001, d = 0.6) at 1-week and 5.9 (t = 2.14, p = 0.042, d = 0.4) at 2-month;Pain Interference from mean 7.0 to 5.1 (t = 4.99, p < 0.001, d = 0.9) at 1-week and 6.1 (t = 2.16, p = 0.041, d = 0.4) at 2-month;Pain Self-Efficacy Questionnaire (PSEQ) from mean 17 to 24 (t = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>3.37, p = 0.002, d = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>0.6) at 1-week and 23 (t =<span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>2.60, p = 0.016, d =<span style="white-space:nowrap;">−</span><span style="white-space:nowrap;"></span>0.5) at 2-month;Pain Catastrophizing (PCS) from 28 to 23 (t = 3.4, p = 0.002;d = 0.6) at 1-week and 21 (t = 2.45, p = 0.022, d = 0.5) at 2-month;Depression from mean 21 to 16 (t = 2.16, p = 0.038, d = 0.4) at 1-week and 16 (t = 3.53, p = 0.002, d = 0.7) at 2-month;and oral Morphine Equivalent Daily Dose (oMEDD) reduced from mean 191 mg/day on admission to 122 mg/day at 1-week (t = 2.38, p = 0.023;d = 0.4) and 93 mg/day at 2-month (t = 2.59, p = 0.016;d = 0.5). There was no significant difference between responders and non-responders on baseline psychological measures (t<sub>33</sub> < 1.19, p > 0.244) and pain classifications ( <img src="Edit_c68fc9e4-a875-4b79-b0cf-af146ed090fe.png" alt="" /> = 0.610, p = 0.894). <strong>Conclusion</strong>: Ketamine subanaesthetic dose infusion for 5 days was found to be effective in managing chronic refractory pain with significant opioid reduction and small improvements in all chronic pain outcomes, except anxiety, at 1-week and 2-month follow-up and with minimal severe adverse effects.
基金Supported by the Science and Technology Department of Sichuan Province,No.2023YFS0255。
文摘BACKGROUND Elsberg syndrome is a type of postinfectious lumbosacral radiculitis typically tri-ggered by neurotropic viruses and manifests as bladder/bowel dysfunction,saddle sensory disturbances(including hypoesthesia,hyperesthesia,or dyse-sthesia),and variable neurological deficits.Typically self-limiting,it often res-ponds to antiviral and neurotropic therapies.However,in patients with comorbi-dities that confer susceptibility to peripheral neuropathy(e.g.,diabetes mellitus),timely escalation to neuromodulation strategies,such as spinal cord stimulation,may be warranted to optimize functional outcomes when conservative measures are inadequate.CASE SUMMARY A 60-year-old male with diabetes mellitus presented with severe bladder and bowel dysfunction persisting for more than two months,followed by left gluteal and perianal(saddle area)herpes zoster eruption that was accompanied by significant neuropathic pain.Following a suboptimal response to conservative therapy,the patient underwent implantation of a short-term spinal cord stimu-lation.Following a 10-day trial of continuous tonic stimulation,the percutaneous electrode lead was removed.The patients experienced no surgical complications,and after the procedure,the patient achieved complete restoration of bladder and bowel function and significant pain alleviation.Two-month follow-up confirmed sustained full recovery.CONCLUSION Early implementation of short-term spinal cord stimulation represents a pro-mising therapeutic approach for promoting neurological recovery in patients with Elsberg syndrome refractory to conservative management,especially those with predisposing comorbidities such as diabetes mellitus.
文摘BACKGROUND Postoperative delirium(POD),an acute neuropsychiatric complication in elderly surgical patients,manifests as attention and cognitive disturbances that may last 24-72 hours after surgery,potentially progressing to dementia.Transcranial direct current stimulation(tDCS),a non-invasive neuromodulation technique,enhances cortical excitability and cognitive function by modulating brain networks and synaptic plasticity.Elderly patients undergoing major laparoscopic surgery face elevated POD risks due to prolonged anesthesia and pneumoperitoneum-induced cerebral hypoperfusion.This study investigates whether pre-anesthesia tDCS can reduce POD incidence in this population.AIM To investigate the effect of preoperative tDCS on reducing the incidence of POD in elderly patients undergoing major laparoscopic surgery.METHODS In this study,we enrolled 220 elderly patients who underwent major laparoscopic surgery between April 2024 and December 2024.Patients were randomly assigned to the active-tDCS(group A)and sham-tDCS(group S)groups.A single session of tDCS or sham stimulation was administered 30 minutes before anesthesia induction.The primary outcome was the incidence of POD during within 3 days postoperatively.RESULTS A total of 201 patients were included in the final analysis,with 100 patients in group A and 101 in group S.The incidence of POD within 3 days postoperatively was 7.0%in group A,which was significantly lower than 22.8%in group S.On postoperative day 1,the Self-Rating Anxiety Scale and Self-Rating Depression Scale scores significantly differed between the two groups,but the pain scores showed no significant difference.CONCLUSION A single session of preoperative tDCS can reduce the incidence of POD in elderly patients undergoing major laparoscopic surgery and can also reduce postoperative anxiety and depression in these patients.
基金Supported by the National Natural Science Foundation of China,No.81971814Pudong New Area Health Talent Training Program,No.2025PDWSYCBJ-04Shanghai’s 2023“Technology Innovation Action Plan”Medical Innovation Research Project,No.23Y11908300。
文摘BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.
基金National Natural Science Foundation of China Youth Found Project:Anti-Colorectal Cancer Metastasis Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)According to the Hypoxia-Inducible Factor 2 Alpha/β-Catenin Cross-Talk Which Influence the Colon Tumor Stem Cells in Hypoxia Microenvironment(No.82003961)National Natural Science Foundation of China Youth Found Project:the Mechanism of the Compatibility of Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis)on the Early Metastasis of Hepatocellular Carcinoma Mediated by Cancer Associated Fibroblasts(82104408)+1 种基金Science Foundation of China Project:Involvement of Hypoxia Inducible Factor-1αSignal in Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Combination Induced Remolding of Tumor Hypoxic Microenvironment(No.82074035)Science and Technology Development Project of Traditional Chinese Medicine in Jiangsu Province:Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Herb Pair on the Inhibition of Colon Cancer Metastasis Through the Wnt/β-catenin Pathway(No.YB201921)。
文摘OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.
基金sponsored by the National Key Research&Development Program of China(2022YFC3602700 and 2022YFC3602702)the Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0201301)+1 种基金the National Natural Science Foundation of China(32170688 and 82172109)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01),and ZJLab.
文摘Dear Editor,SARS-CoV-2 is the virus that caused the COVID-19 pandemic,leading to more than 774 million cases and 7,037,007 deaths by March 2024(World Health Organization,http://covid19.who.int/).Despite effective treatments,15%-20%of patients experience long-term symptoms,such as breathlessness,fatigue,depression,and cognitive impairment,which are often linked to an excessive immune response[1].All variants of the virus(α,,,Omicron,and BA.1),which can potentially access the brain via the olfactory mucosa,have been found in the brains of Syrian hamsters,triggering inflammation and demonstrating axonal travel[2].
文摘With the acceleration of China's aging society,elderly patients have become a high-risk group for malignant tumors and exhibit high prevalence of pain.For a long time,the diagnosis,treatment,and management of cancer pain in elderly Chinese patients have been inadequate.This study used"Older adults,geriatric patients,cancer pain,pain assessment,pain management,elderly cancer,geriatric oncology,medication management,palliative care,interdisciplinary pain management,Analgesics,quality of life"as key words.We systematically searched PubMed,Web of Science,CNKI,and Wanfang databases from their inception to September 2024.The search primarily included phase I to III clinical trials,randomized controlled trials,meta-analyses,systematic reviews,and case reports.Elderly patients typically present with complex pain mechanisms,including both cancer-related and non-cancer pain,cognitive dysfunction,comorbidities,and polypharmacy,posing significant challenges for clinical diagnosis and treatment.Notable clinical differences exist between elderly and younger patients in the epidemiology,assessment,diagnosis,and treatment of cancer pain.Currently,the awareness of comprehensive management for elderly cancer pain patients is limited,and specific,implementable clinical guidelines are lacking.Therefore,developing a comprehensive,localized management model for elderly cancer pain patients in China—incorporating factors such as age-related impacts,organ function status,and comorbidities—has become an urgent necessity.
基金Supported by National Natural Science Foundation of China,No.81230024,No.81471137(to GYX)and No.31400947(to HHZ)Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.
基金supported by the National Natural Science Foundation of China,No.81200851(to DL)the National Institutes of Health of the USA,No.NS 040723(to QL)
文摘Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.
基金Supported by Jiangsu Provincial Department of Science and Technology,No.BE2017603 and No.BE2017675。
文摘BACKGROUND Medical robot is a promising surgical tool,but no specific one has been designed for interventional treatment of chronic pain.We developed a computed tomography-image based navigation robot using a new registration method with binocular vision.This kind of robot is appropriate for minimal invasive interventional procedures and easy to operate.The feasibility,accuracy and stability of this new robot need to be tested.AIM To assess quantitatively the feasibility,accuracy and stability of the binocularstereo-vision-based navigation robot for minimally invasive interventional procedures.METHODS A box model was designed for assessing the accuracy for targets at different distances.Nine(three sets)lead spheres were embedded in the model as puncture goals.The entry-to-target distances were set 50 mm(short-distance),100 mm(medium-distance)and 150 mm(long-distance).Puncture procedure was repeated three times for each goal.The Euclidian error of each puncture was calculated and statistically analyzed.Three head phantoms were used to explore the clinical feasibility and stability.Three independent operators conducted foramen ovale placement on head phantoms(both sides)by freehand or under the guidance of robot(18 punctures with each method).The operation time,adjustment time and one-time success rate were recorded,and the two guidancemethods were compared.RESULTS On the box model,the mean puncture errors of navigation robot were 1.7±0.9 mm for the short-distance target,2.4±1.0 mm for the moderate target and 4.4±1.4 mm for the long-distance target.On the head phantom,no obvious differences in operation time and adjustment time were found among the three performers(P>0.05).The median adjustment time was significantly less under the guidance of the robot than under free hand.The one-time success rate was significantly higher with the robot(P<0.05).There was no obvious difference in operation time between the two methods(P>0.05).CONCLUSION In the laboratory environment,accuracy of binocular-stereo-vision-based navigation robot is acceptable for target at 100 mm depth or less.Compared with freehand,foramen ovale placement accuracy can be improved with robot guidance.
基金Supported by The Key R&D Project in Jiangsu Province,No.BE2017603 and No.BE2017675the Key Program of Medical Science and Technology Development Projects in Nanjing,No.ZKX19016.
文摘BACKGROUND Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia.The anatomical features of the thoracic spine are complex,and puncture injury to the pleura,blood vessels,spinal cord,and other tissues may cause serious complications.The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood.AIM To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments.METHODS A total of 88 patients(41 males and 47 females)who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included.Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected.The width of the intertransverse space(D_(P)),the height of the rib neck/head above the lower transverse process(D_(R)),the width of the lateral border of the articular process/lamina(W_(P)),and the width of the posterior border of the vertebral body(W_(V))were measured.At the upper 1/3 of the intervertebral foramina,the horizontal inclination angle(α)from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured.The ratios D_(R)/D_(P) and W_(P)/W_(V) were calculated.The intervertebral foramen parameters were compared between segments.RESULTS No rib head/neck occlusion(D_(R)/D_(P)>0)was found in the intertransverse spaces of T1-2 and T12-L1.The incidence of occlusion for the upper thoracic segments(T1-5,n=138),middle thoracic segments(T5-9,n=116),and lower thoracic segments(T9-L1,n=80)were 76.81%,100%,and 82.50%,respectively.The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).The incidence of>1/2 occlusion(D_(R)/D_(P)>1/2)for the upper,middle,and lower thoracic segments was 7.97%,74.14%,and 32.50%,respectively.The incidence of>1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).W_(P) was longer than W_(V) on T1-2 to T9-10 and shorter than W_(V) on T10-11 to T12-L1.The horizontal puncture angle(α)into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion(left:r=0.772,P<0.01;right:r=0.771,P<0.01),and the horizontal inclination angle for T11-12 and T12-L1 was 90°.CONCLUSION It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.
文摘AIM： TO explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture. METHODS： Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into four groups according to the fentanyl concentration： control group （0 ng/mL）, group I （0.3 ng/mL）, group I （3.0 ng/mL）, and group III （30 ng/mL）. In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl ＋ 0.1 μg/mL naloxone or fentanyl ＋ 1.0 μg/mL naloxone. Cell viability was assessed by the MTT assay. Insulin release in response to low and high concentrations （2.8 mmol/L and 16.7 mmol/L, respectively） of glucose was investigated and electron microscopy morphological assessment was performed. RESULTS： Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups I and II （62.33 ± 9.67 μIU vs 47.75 ± 8.47 μIU, 39.67 ± 6.18 μIU and 125.5 ± 22.04 μIU vs 96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P 〈 0.01） and was lowest in group III （P 〈 0.01）. After adding 1 μg/mL naloxone, insulin release in groups II and II was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/ml fentanyl. CONCLUSION： Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged β-cells of rat islets.
基金supported by grants from National Natural Science Foundation of China(No.81071307,No.30872440,No.81171259)
文摘Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.
基金supported by a grant from High-Tech Research and Development Program of Jilin Province of China,No.20110492
文摘The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation and creep properties of the optic nerve change after injury.Moreover,human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal.To validate this hypothesis,a rabbit model of optic nerve injury was established using a clamp approach.At 7 days after injury,the vitreous body received a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells.At 30 days after injury,stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly,with pathological changes in the injured optic nerve also noticeably improved.These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves,and thereby contributes to nerve recovery.
