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
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
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
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
As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and ...As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons.However,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still unclear.Here,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal neurons.By whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal neurons.This phenomenon lasts for>10 min after LIPUS exposure.Together with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression.Our work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via LTCCs.This may also explain the multi-activation effects of LIPUS beyond neurons.LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.展开更多
Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser s...Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser speckle contrast imaging(LSCI)is frequently used in neurology to evaluate the effectiveness of treatment.To assess the accuracy of LSCI in predicting the impact of tSCS on PHN,14 adult patients receiving tSCS treatments for spinal nerve-innervated(C6-T2)PHN participated in this observational study.Visual analog scale(VAS)assessments and LSCI bloodflow images of the-ngers were recorded after the tSCS procedure.The results showed that the VAS scores of all patients decreased signi-cantly.Moreover,the bloodflow index(BFI)values were signi-cantly higher than they were before the procedure.Increased bloodflow and pain alleviation were positively correlated.The-ndings indicated that spinal nerve PHN(C6-T2)was signi-cantly reduced by tSCS.Pain alleviation by tSCS was positively correlated with increased bloodflow in the hand.The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.展开更多
BACKGROUND Percutaneous kyphoplasty(PKP)is a pivotal intervention for osteoporotic fractures,pathological vertebral compression fractures,and vertebral bone tumors.Despite its efficacy,the procedure presents challenge...BACKGROUND Percutaneous kyphoplasty(PKP)is a pivotal intervention for osteoporotic fractures,pathological vertebral compression fractures,and vertebral bone tumors.Despite its efficacy,the procedure presents challenges,notably complications arising from intradural cement leakage.Timely and accurate diagnosis,coupled with emergent intervention is imperative to improve patient prognosis.This case report illuminates the intricacies and potential complications associated with PKP,emphasizing the critical need for vigilant monitoring,prompt diagnosis,and immediate intervention to mitigate adverse outcomes.CASE SUMMARY A 58-year-old male patient,experiencing a T7 osteoporosis-related pathological compression fracture,underwent PKP at a local hospital.Two weeks postprocedure,the patient developed paraplegic and dysuric symptoms,necessitating emergency decompression surgery.Gradual improvement was achieved,marked by the restoration of muscle strength,sensation,and mobility.CONCLUSION PKP Intradural cement leakage following PKP is unusual and potentially fatal.Prompt imaging examinations,urgent evaluation,and the decompression surgery are essential,which help alleviate symptoms associated with spinal damage,markedly improving the overall prognosis.展开更多
BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect o...BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect of this procedure on survival and prognosis remains controversial.This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence,guide clinical decision-making,optimize treatment strategies,and improve the survival rate and quality of life of patients.METHODS A retrospective cohort study was performed.Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected.There were 442 males and 210 females.The mean age was 57±12 years.All patients underwent a laparoscopic D2 radical operation for distal GC.The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence,metastasis,and survival.The follow-up period ended in December 2023.Normally distributed data are expressed as the mean±SD,and normally distributed data are expressed as M(Q1,Q3)or M(range).Statistical data are expressed as absolute numbers or percentages;theχ^(2) test was used for comparisons between groups,and the Mann-Whitney U nonparametric test was used for comparisons of rank data.The life table method was used to calculate the survival rate,the Kaplan-Meier method was used to construct survival curves,the log rank test was used for survival analysis,and the Cox risk regression model was used for univariate and multifactor analysis.RESULTS The median overall survival(OS)time for the 652 patients was 81 months,with a 10-year OS rate of 46.1%.Patients with TNM stages II and III had 10-year OS rates of 59.6%and 37.5%,respectively,which were significantly different(P<0.05).Univariate analysis indicated that factors such as age,maximum tumor diameter,tumor diffe-rentiation grade(low to undifferentiated),pathological TNM stage,pathological T stage,pathological N stage(N2,N3),and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer[hazard ratio(HR):1.45,1.64,1.45,1.64,1.37,2.05,1.30,1.68,3.08,and 0.56 with confidence intervals(CIs)of 1.15-1.84,1.32-2.03,1.05-1.77,1.62-2.59,1.05-1.61,1.17-2.42,2.15-4.41,and 0.44-0.70,respectively;P<0.05].Multifactor analysis revealed that a tumor diameter greater than 4 cm,low tumor differentiation,and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients(HR:1.48,1.44,1.81 with a 95%CI:1.19-1.84).Additionally,postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate(HR:0.57,95%CI:0.45-0.73;P<0.05).CONCLUSION A maximum tumor diameter exceeding 4 cm,low tumor differentiation,and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC.Conversely,postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.展开更多
Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body w...Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.展开更多
Objective:To assess the ACP acceptance among patients with malignant tumor in China and factors affecting adoption and timing.Methods:Quantitative study:The convenience sampling method was adopted from October 2020 to...Objective:To assess the ACP acceptance among patients with malignant tumor in China and factors affecting adoption and timing.Methods:Quantitative study:The convenience sampling method was adopted from October 2020 to October 2021 to investigate 200 oncology patients by a general information questionnaire,patient's advance care planning acceptance questionnaire(ACPQ).Multiple linear stepwise regression was used to analyze the influencing factors of ACP acceptance.Qualitative study:A purposive sampling method was used to select 31 oncology patients and 13 clinical nurses for semi-structured interviews.The data were analyzed using Colaizzi's seven steps.Results:The quantitative study revealed that patients with malignancy had an upper-middle acceptance score of(66.15±7.684)for ACP,with attitude(11.26±2.064),feelings(36.64±4.208),and intention(18.25±3.275)scores.Multiple linear regression analysis showed that religious beliefs,education,monthly income,bereavement experience and notification of condition were independent risk factors for acceptance of ACP(P<0.05).The qualitative study showed that(1)oncology patients have low awareness,high demand,and low acceptability of ACP intervention;(2)they preferred to discuss ACP when medical condition or treatment plan changes;(3)family members were usually involved in ACP discussions,followed by medical personnel;(4)economy,environment,companion,and doctor-patient relationship will all influence ACP implementation.As for nurses,they(1)were unsure about the dynamic changes of ACP content and its optimal timing;(2)had limited ACP knowledge;(3)were affected by environmental factors and nurse-patient relationships;(4)were prone to have disagreements due to inadequate organization department assistance.Conclusions:clinical practitioners should discuss ACP with patients in specific conditions to increase patient acceptance.ACP development requires updated legislation,professional training,and a standardized ACP system.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
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 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 National Key Research&Development Program of China(2022YFC3602700 and 2022YFC3602702)the Science and Technology Innovation 2030—Brain Science and Brain-Inspired Intelligence Project(2021ZD0201301)+5 种基金the National Natural Science Foundation of China(32170688,31971159,and 12034015)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07-E00041)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)the ZJ Labthe Shanghai Center for Brain Science and Brain-Inspired Technology,the Program of Shanghai Academic Research Leaders(21XD1403600)the Fundamental Research Funds for the Central Universities(22120230562).
文摘As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons.However,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still unclear.Here,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal neurons.By whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal neurons.This phenomenon lasts for>10 min after LIPUS exposure.Together with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression.Our work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via LTCCs.This may also explain the multi-activation effects of LIPUS beyond neurons.LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.
基金supported by the Clinical Frontier Technology Program of the First A±liated Hospital of Jinan University,China(No.JNU1AFCFTP-2022-a01212)the Clinical Research Funds for the First Clinical Medicine College of Jinan University(Grant No.2018006).
文摘Temporary spinal cord stimulation(tSCS)can effectively reduce the pain and severity of postherpetic neuralgia(PHN).However,there are no effective and objective methods for predicting the effects of tSCS on PHN.Laser speckle contrast imaging(LSCI)is frequently used in neurology to evaluate the effectiveness of treatment.To assess the accuracy of LSCI in predicting the impact of tSCS on PHN,14 adult patients receiving tSCS treatments for spinal nerve-innervated(C6-T2)PHN participated in this observational study.Visual analog scale(VAS)assessments and LSCI bloodflow images of the-ngers were recorded after the tSCS procedure.The results showed that the VAS scores of all patients decreased signi-cantly.Moreover,the bloodflow index(BFI)values were signi-cantly higher than they were before the procedure.Increased bloodflow and pain alleviation were positively correlated.The-ndings indicated that spinal nerve PHN(C6-T2)was signi-cantly reduced by tSCS.Pain alleviation by tSCS was positively correlated with increased bloodflow in the hand.The effect of tSCS on PHN may thus be predicted using an independent and consistent indicator such as LSCI.
文摘BACKGROUND Percutaneous kyphoplasty(PKP)is a pivotal intervention for osteoporotic fractures,pathological vertebral compression fractures,and vertebral bone tumors.Despite its efficacy,the procedure presents challenges,notably complications arising from intradural cement leakage.Timely and accurate diagnosis,coupled with emergent intervention is imperative to improve patient prognosis.This case report illuminates the intricacies and potential complications associated with PKP,emphasizing the critical need for vigilant monitoring,prompt diagnosis,and immediate intervention to mitigate adverse outcomes.CASE SUMMARY A 58-year-old male patient,experiencing a T7 osteoporosis-related pathological compression fracture,underwent PKP at a local hospital.Two weeks postprocedure,the patient developed paraplegic and dysuric symptoms,necessitating emergency decompression surgery.Gradual improvement was achieved,marked by the restoration of muscle strength,sensation,and mobility.CONCLUSION PKP Intradural cement leakage following PKP is unusual and potentially fatal.Prompt imaging examinations,urgent evaluation,and the decompression surgery are essential,which help alleviate symptoms associated with spinal damage,markedly improving the overall prognosis.
文摘BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect of this procedure on survival and prognosis remains controversial.This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence,guide clinical decision-making,optimize treatment strategies,and improve the survival rate and quality of life of patients.METHODS A retrospective cohort study was performed.Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected.There were 442 males and 210 females.The mean age was 57±12 years.All patients underwent a laparoscopic D2 radical operation for distal GC.The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence,metastasis,and survival.The follow-up period ended in December 2023.Normally distributed data are expressed as the mean±SD,and normally distributed data are expressed as M(Q1,Q3)or M(range).Statistical data are expressed as absolute numbers or percentages;theχ^(2) test was used for comparisons between groups,and the Mann-Whitney U nonparametric test was used for comparisons of rank data.The life table method was used to calculate the survival rate,the Kaplan-Meier method was used to construct survival curves,the log rank test was used for survival analysis,and the Cox risk regression model was used for univariate and multifactor analysis.RESULTS The median overall survival(OS)time for the 652 patients was 81 months,with a 10-year OS rate of 46.1%.Patients with TNM stages II and III had 10-year OS rates of 59.6%and 37.5%,respectively,which were significantly different(P<0.05).Univariate analysis indicated that factors such as age,maximum tumor diameter,tumor diffe-rentiation grade(low to undifferentiated),pathological TNM stage,pathological T stage,pathological N stage(N2,N3),and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer[hazard ratio(HR):1.45,1.64,1.45,1.64,1.37,2.05,1.30,1.68,3.08,and 0.56 with confidence intervals(CIs)of 1.15-1.84,1.32-2.03,1.05-1.77,1.62-2.59,1.05-1.61,1.17-2.42,2.15-4.41,and 0.44-0.70,respectively;P<0.05].Multifactor analysis revealed that a tumor diameter greater than 4 cm,low tumor differentiation,and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients(HR:1.48,1.44,1.81 with a 95%CI:1.19-1.84).Additionally,postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate(HR:0.57,95%CI:0.45-0.73;P<0.05).CONCLUSION A maximum tumor diameter exceeding 4 cm,low tumor differentiation,and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC.Conversely,postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.
基金supported by National Natural Science Foundation of China[grant number U21A20399]Liaoning Revitalization Talents Program[grant number XLYC1802059]+2 种基金the Key R&D Program of Liaoning Province[grant number2019JH2/10300044]the Key Laboratory Program of Liaoning Province[grant number 2018225113]the Key Laboratory Program of Shenyang City[grant number 21-103-0-16]。
文摘Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.
基金supported by Zhou's Nursing Research Project(No.HLYJ-Z-2018-07).
文摘Objective:To assess the ACP acceptance among patients with malignant tumor in China and factors affecting adoption and timing.Methods:Quantitative study:The convenience sampling method was adopted from October 2020 to October 2021 to investigate 200 oncology patients by a general information questionnaire,patient's advance care planning acceptance questionnaire(ACPQ).Multiple linear stepwise regression was used to analyze the influencing factors of ACP acceptance.Qualitative study:A purposive sampling method was used to select 31 oncology patients and 13 clinical nurses for semi-structured interviews.The data were analyzed using Colaizzi's seven steps.Results:The quantitative study revealed that patients with malignancy had an upper-middle acceptance score of(66.15±7.684)for ACP,with attitude(11.26±2.064),feelings(36.64±4.208),and intention(18.25±3.275)scores.Multiple linear regression analysis showed that religious beliefs,education,monthly income,bereavement experience and notification of condition were independent risk factors for acceptance of ACP(P<0.05).The qualitative study showed that(1)oncology patients have low awareness,high demand,and low acceptability of ACP intervention;(2)they preferred to discuss ACP when medical condition or treatment plan changes;(3)family members were usually involved in ACP discussions,followed by medical personnel;(4)economy,environment,companion,and doctor-patient relationship will all influence ACP implementation.As for nurses,they(1)were unsure about the dynamic changes of ACP content and its optimal timing;(2)had limited ACP knowledge;(3)were affected by environmental factors and nurse-patient relationships;(4)were prone to have disagreements due to inadequate organization department assistance.Conclusions:clinical practitioners should discuss ACP with patients in specific conditions to increase patient acceptance.ACP development requires updated legislation,professional training,and a standardized ACP system.
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.
