Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis

BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal lives.Microglial cells are as-sociated with NP.Excessive inflammatory responses,especially the secretion of large amounts of pro-inflammatory cytokines,ultimately lead to neuroinflam-mation.Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.METHODS Two models,an in vitro lipopolysaccharide(LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments,were used.Key proteins in the pyroptosis signaling pathway,NLRP3-GSDMD,were assessed using western blotting,real-time quantitative polymerase chain reaction,and immunofluorescence.Inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α]were assessed using enzyme-linked immuno-sorbent assay.We also evaluated microglial cell proliferation and apoptosis.Furthermore,we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.RESULTS The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α,IL-6,and IL-1βwere enhanced in LPS-treated microglia.Furthermore,SPP1 expression was also induced in LPS-treated microglia.Notably,BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia.Additionally,depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia,whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin(sh)RNA in LPS-treated microglia.Finally,SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N,NLPRP3,and ASC and suppressed the production of inflammatory factors.CONCLUSION Notably,BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death.It improves pain perception and inhibits microglial activation in rats with selective nerve pain.

Laser speckle contrast imaging to predict the effect of temporary spinal cord stimulation in postherpetic neuralgia patients: A prospective observational study

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.

Mechanism of Huanglian Detoxification Soup Relieving Postherpetic Neuralgia by Enhancing IL-2 Levels in Rats

[Objectives]To explore the mechanism of Huanglian detoxification soup improving pain behavior by affecting serum IL-2 levels in postherpetic neuralgia(post herpes neuralgia,PHN)model rats.[Methods]20 PHN rats were randomly divided into model group(PHN group)and detoxification decoction group(n=10).In the group,10%Huanglian detoxification soup(0.4 mL/0.1 kg)was given once in the morning and evening for 14 d.The PHN group was filled with an equal volume of 0.9%sodium chloride solution.Tail vein serum inflammatory factor interleukin-2(IL-2),IL-βand IL-6 levels were measured using ELISA kits at 7 and 21 d.[Results]IL-2 increased at 14 and 21 d in IL group,while IL-βand IL-6 decreased compared with the PHN group(P<0.05).[Conclusions]Huanglian detoxification soup may raise IL-2 levels after VZV infection to promote the differentiation of cells of the immune system,so as to relieve the pain caused by IL-βand IL-6 inflammatory factors.

The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

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.

Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study

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.

Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

A study of current status of acceptance and influencing factors of advance care planning for patients with malignant tumors

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.

Trend Analysis of the Burden of Hypertensive Heart Disease in China from 1990 to 2021

Objective:To quantitatively analyze the burden of hypertensive heart disease(HHD)in China and provide a scientific basis for prevention and control strategies.Methods:Data from the Global Burden of Disease 2021 database were used to assess the disease burden,deaths,years lived with disability(YLDs),and risk factors for HHD in the Chinese population from 1990 to 2021.Results:From 1990 to 2021,HHD cases in China increased from 1.5 million to 3.9 million,with an average annual growth rate of 2.83%.Prevalence rose from 127.76/100,000 to 259.00/100,000,while age-standardized prevalence decreased by 0.68%annually.HHD deaths increased from 232,478 to 320,247,with a mortality rate rise from 19.76/100,000 to 22.56/100,000,though age-standardized mortality decreased by 2.68%annually.YLDs rose from 124,386 to 301,426,with the rate increasing by 2.20%annually,while age-standardized YLDs decreased by 0.67%annually.High sodium intake and low fruit consumption were key risk factors for HHD deaths.Deaths related to low vegetable intake decreased until 2005 and then rose,while deaths from lead exposure showed a similar pattern.Conclusion:HHD cases and prevalence increased significantly,but age-standardized prevalence and mortality rates declined,reflecting the impact of an aging population and improved health interventions.The rise in YLDs highlights the long-term impact on patients’quality of life.Key risk factors included high sodium intake and low fruit consumption,emphasizing the importance of dietary improvements in HHD prevention.HHD remains a significant public health challenge in China,requiring continuous research and targeted prevention strategies.

Differences in brain structure in patients with distinct sites of chronic pain:A voxel-based morphometric analysis

A reduction in gray matter volume is common in patients with chronic back pain, and different types of pain are associated with gray matter abnormalities in distinct brain regions. To examine differ- ences in brain morphology in patients with low back pain or neck and upper back pain, we investi- gated changes in gray matter volume in chronic back pain patients having different sites of pain using voxel-based morphometry. A reduction in cortical gray matter volume was found primarily in the left postcentral gyrus and in the left precuneus and bilateral cuneal cortex of patients with low back pain. In these patients, there was an increase in subcortical gray matter volume in the bilateral putamen and accumbens, right pallidum, right caudate nucleus, and left amygdala. In upper back pain patients, reduced cortical gray matter volume was found in the left precentral and left postcen- tral cortices. Our findings suggest that regional gray matter volume abnormalities in low back pain patients are more extensive than in upper back pain patients. Subcortical gray matter volume in- creases are found only in patients with low back pain.

Effect of Preemptive Ketamine Administration on Postoperative Visceral Pain after Gynecological Laparoscopic Surgery

The pain following gynecological laparoscopic surgery is less intense than that following open surgery; however, patients often experience visceral pain after the former surgery. The aim of this study was to determine the effects of preemptive ketamine on visceral pain in patients undergoing gynecological laparoscopic surgery. Ninety patients undergoing gynecological laparoscopic surgery were randomly assigned to one of three groups. Group 1 received placebo. Group 2 was intravenously injected with preincisional saline and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. Group 3 was intravenously injected with preincisional ketamine（0.3 mg/kg） and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. A standard anesthetic was used for all patients, and meperidine was used for postoperative analgesia. The visual analogue scale（VAS） scores for incisional and visceral pain at 2, 6, 12, and 24 h, cumulative analgesic consumption and time until first analgesic medication request, and adverse effects were recorded postoperatively. The VAS scores of visceral pain in group 3 were significantly lower than those in group 2 and group 1 at 2 h and 6 h postoperatively（P〈0.05 and P〈0.01, respectively）. At 2 h and 6 h, the VAS scores of incisional pain did not differ significantly between groups 2 and 3, but they were significantly lower than those in group 1（P〈0.01）. Groups 1 and 2 did not show any differences in visceral pain scores at 2 h and 6 h postoperatively. Moreover, the three groups showed no statistically significant differences in visceral and incisional pain scores at 12 h and 24 h postoperatively. The consumption of analgesics was significantly greater in group 1 than in groups 2 and 3, and the time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistically significant difference between groups 2 and 3. However, the three groups showed no significant difference in the incidence of shoulder pain or adverse effects. Preemptive ketamine may reduce visceral pain in patients undergoing gynecological laparoscopic surgery.

Determination of vitamin D and analysis of risk factors for osteoporosis in patients with chronic pain

BACKGROUND Vitamin D deficiency is common in patients with chronic pain and healthy people,but the difference between the two has not been reported;thus,whether there is a relationship between vitamin D deficiency and chronic pain remains to be confirmed.Osteoporosis is a common disease in chronic pain disorders.Understanding the relationship between vitamin D and osteoporosis will provide a basis for the rational supplementation of vitamin D to prevent osteoporosis,and to understand the risk factors of bone mass change to provide a new treatment plan for early prevention of osteoporosis.AIM To determine 25 hydroxy vitamin D(25OHD)level in patients with chronic pain to clarify its clinical significance.The relationship between vitamin D and bone mineral density(BMD)and the risk factors for bone mass change were also evaluated.METHODS In this study,184 patients with chronic pain were included in the study group,and 104 healthy individuals who underwent routine health checkups during the same period were included in the control group.25OHD level was detected in both groups by enzyme-linked immunosorbent assay.According to the BMD test results,the patients in the study group were further classified into three subgroups:Normal BMD group,reduced BMD group,and osteoporosis group.Age,sex,ethnicity,living altitude,body mass index,25OHD level,parathyroid hormone(PTH),calcium(Ca)and phosphorus levels were analyzed statistically in both groups.RESULTS The vitamin D level in the study group was lower than that in the control group at 53.8%vs 57.7%,with no significant difference between the two groups.The proportion of patients with severe vitamin D deficiency in the study group was higher than that in the control group.The mean age was greater in the osteoporosis subgroup,and the youngest in the normal BMD subgroup.Vitamin D level in the osteoporosis subgroup was lower than that in the other two subgroups,and was not specific for the diagnosis of bone mass reduction and osteoporosis.The above results were analyzed statistically and showed significant differences(P<0.05).There was a positive correlation between age and BMD in patients with chronic pain(R=0.567,P<0.001).Age,PTH and Ca were risk factors for bone mass reduction,while age,ethnicity and altitude were risk factors for osteoporosis.CONCLUSION Vitamin D deficiency is a common phenomenon in patients with chronic pain,and severe vitamin D deficiency is not uncommon.Vitamin D level is not a risk factor for bone mass reduction and osteoporosis.Bone mass reduction is correlated with age,PTH and Ca,while osteoporosis is correlated with age,ethnicity and altitude.

Improvement in Radicular Symptoms but Continued Facet Arthropathy and Axial Back Pain Following Rupture of a Facet Joint Synovial Cyst

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.

Minimally invasive interventional therapy for pain

Pain interventional therapy,known as the most promising medical technology in the 21st century,refers to clinical treatment technology based on neuroanatomy,neuroimaging,and nerve block technology to treat pain diseases.Compared with traditional destructive surgery,interventional pain therapy is considered a better and more economical choice of treatment.In recent years,a variety of minimally invasive pain interventional therapy techniques,such as neuroregulation,spinal cord electrical stimulation,intervertebral disc ablation,and intrasheath drug infusion systems,have provided effective solutions for the treatment of patients with post-herpetic neuralgia,complex regional pain syndrome,cervical/lumbar disc herniation,and refractory cancer pain.

Motor cortex transcranial magnetic stimulation to reduce intractable postherpetic neuralgia with poor response to other threapies:Report of two cases

BACKGROUND Postherpetic neuralgia(PHN)is a typical neuropathic pain condition that appears in the lesioned skin regions following the healing of shingles.The pain condition tends to persist,which is often accompanied by negative emotions(e.g.,anxiety and depression)and substantially reduces the quality of life.In addition to analgesia(e.g.,pregabalin and gabapentin),nerve radiofrequency technology is an effective treatment for intractable PHN.However,there is still a significant portion of patients who do not benefit from this treatment.As a non-invasive form of brain stimulation,repetitive transcranial magnetic stimulation(rTMS)targeting the motor cortex is able to reduce neuropathic pain with grade A evidence.CASE SUMMARY Here we report two cases in which motor cortex rTMS was used to treat intractable PHN that did not respond to initial drug and radiofrequency therapies.Moreover,we specifically investigated rTMS efficacy at 3 mo following treatment.CONCLUSION Motor cortex rTMS can treat intractable PHN that did not respond to initial drug and radiofrequency therapies.

A Prospective Study of Inpatient Ketamine Subanaesthetic Dose Infusion in Chronic Refractory Pain

Background: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. Objective: 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. Methodology: 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. Results: 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 = −3.37, p = 0.002, d = −0.6) at 1-week and 23 (t =−2.60, p = 0.016, d =−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 (t33 < 1.19, p > 0.244) and pain classifications ( = 0.610, p = 0.894). Conclusion: 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.

Unloading and successful treatment with bioresorbable stents during percutaneous coronary intervention:A case report

BACKGROUND With the development of percutaneous coronary intervention(PCI),the number of interventional procedures without implantation,such as bioresorbable stents(BRS)and drug-coated balloons,has increased annually.Metal drug-eluting stent unloading is one of the most common clinical complications.Comparatively,BRS detachment is more concealed and harmful,but has yet to be reported in clinical research.In this study,we report a case of BRS unloading and successful rescue.This is a case of a 59-year-old male with the following medical history:“Type 2 diabetes mellitus”for 2 years,maintained with metformin extended-release tablets,1 g PO BID;“hypertension”for 20 years,with long-term use of metoprolol sustained-release tablets,47.5 mg PO QD;“hyperlipidemia”for 20 years,without regular medication.He was admitted to the emergency department of our hospital due to intermittent chest pain lasting 18 hours,on February 20,2022 at 15:35.Electrocardiogram results showed sinus rhythm,ST-segment elevation in leads I and avL,and poor R-wave progression in leads V1–3.High-sensitivity troponin I level was 4.59 ng/mL,indicating an acute high lateral wall myocardial infarction.The patient’s family requested treatment with BRS,without implanta-tion.During PCI,the BRS became unloaded but was successfully rescued.The patient was followed up for 2 years;he had no episodes of angina pectoris and was in generally good condition.CONCLUSION We describe a case of a 59-year-old male experienced BRS unloading and successful rescue.By analyzing images,the causes of BRS unloading and the treatment plan are discussed to provide insights for BRS release operations.We discuss preventive measures for BRS unloading.

Cytochrome P45026A1 Contributes to the Maintenance of Neuropathic Pain

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.

Thoracic spinal cord injury and paraplegia caused by intradural cement leakage after percutaneous kyphoplasty: A case report

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.

TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity

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.