Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice

AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic mice.After 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western blotting.The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence.The mechanisms underlying the effects of MSC-Shh was investigated.RESULTS:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp.Significant downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp.The extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp.Brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh administration.CONCLUSION:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice.The ERK1/2,AKT and PI3K pathways are involved in this process.MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma

AIM:To assess the performance of macular ganglion cell-inner plexiform layer thickness(mGCIPLT)and 10-2 visual field(VF)parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma.METHODS:Totally 127 eyes from 89 participants(36 eyes of 19 healthy participants,45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients)were included.The relationships between the optical coherence tomography(OCT)-derived parameters and VF sensitivity were determined.Patients with early glaucoma were divided into eyes with or without central 10°of the VF damages(CVFDs),and the diagnostic performances of OCT-derived parameters were assessed.RESULTS:In early glaucoma,the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation(PSD;with average mGCIPLT:β=-0.046,95%CI,-0.067 to-0.024,P<0.001).In advanced glaucoma,the mGCIPLT was related to the 24-2 VF mean deviation(MD;with average mGCIPLT:β=0.397,95%CI,0.199 to 0.595,P<0.001),10-2 VF MD(with average mGCIPLT:β=0.762,95%CI,0.485 to 1.038,P<0.001)and 24-2 VF PSD(with average mGCIPLT:β=0.244,95%CI,0.124 to 0.364,P<0.001).Except for the minimum and superotemporal mGCIPLT,the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs.The area under the curve(AUC)of the average mGCIPLT(AUC=0.949,95%CI,0.868 to 0.982)was greater than that of the average circumpapillary retinal nerve fiber layer thickness(cpRNFLT;AUC=0.827,95%CI,0.674 to 0.918)and rim area(AUC=0.799,95%CI,0.610 to 0.907)in early glaucomatous eyes with CVFDs versus normal eyes.CONCLUSION:The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF,cpRNFLT and ONH parameters,especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

Ultrasound-guided sphenopalatine ganglion block for effective analgesia during awake fiberoptic nasotracheal intubation: A case report

BACKGROUND Awake fiberoptic nasotracheal intubation(AFNI)is the preferred airway ma-nagement strategy for patients with difficult airways.However,this procedure can cause significant physical and psychological distress.This case report explores the application of a sphenopalatine ganglion(SPG)block as an alternative anal-gesic modality to mitigate the discomfort associated with AFNI.CASE SUMMARY A 63-year-old female with a history of right maxillary osteosarcoma underwent craniotomy for a suspected malignant brain lesion.The patient’s medical history included prior surgery,chemotherapy,and radiation therapy,resulting in signi-ficant jaw impairment and limited neck mobility.Considering the anticipated air-way challenges,AFNI was planned.A SPG block was performed under real-time ultrasound guidance,providing effective analgesia during nasotracheal intuba-tion.CONCLUSION The SPG block represents a promising analgesic approach in AFNI,offering po-tential benefits in alleviating pain involving the nasal and nasopharyngeal regions as well as improving patient cooperation.

Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition

Objective This study aimed to determine whether lipopolysaccharide(LPS)induces the loss of corneal nerve fibers in cultured trigeminal ganglion(TG)cells,and the underlying mechanism of LPS-induced TG neurite damage.Methods TG neurons were isolated from C57BL/6 mice,and the cell viability and purity were maintained for up to 7 days.Then,they were treated with LPS(1µg/mL)or the autophagy regulator(autophibib and rapamycin)alone or in combination for 48 h,and the length of neurites in TG cells was examined by the immunofluorescence staining of the neuron-specific proteinβ3-tubulin.Afterwards,the molecular mechanisms by which LPS induces TG neuron damage were explored.Results The immunofluorescence staining revealed that the average length of neurites in TG cells significantly decreased after LPS treatment.Importantly,LPS induced the impairment of autophagic flux in TG cells,which was evidenced by the increase in the accumulation of LC3 and p62 proteins.The pharmacological inhibition of autophagy by autophinib dramatically reduced the length of TG neurites.However,the rapamycin-induced activation of autophagy significantly lessened the effect of LPS on the degeneration of TG neurites.Conclusion LPS-induced autophagy inhibition contributes to the loss of TG neurites.

Transcriptional regulatory network during axonal regeneration of dorsal root ganglion neurons:laser-capture microdissection and deep sequencing

The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.

Influence of hypoxia on retinal progenitor and ganglion cells in human induced pluripotent stem cell-derived retinal organoids

AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were used for the experiments.Generated embryoid bodies(EBs)were randomly and equally divided into hypoxic and normoxic groups.Photographs of the EBs were taken on days 38,45,and 52,and the corresponding volume of EBs was calculated.Simultaneously,samples were collected at these three timepoints,followed by fixation,sectioning,and immunofluorescence.RESULTS:The proportion of Ki67-positive proliferating cells increased steadily on day 38;this proliferationpromoting effect tended to increase tissue density rather than tissue volume.On days 45 and 52,the two groups had relatively similar ratios of Ki67-positive cells.Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52(P<0.05).In contrast,the percentage of PAX6-and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints(P<0.01),except for CHX10 at day 45(P>0.05).Moreover,the proportion of PAX6-/TUJ1+cells within the neural retinas increased considerably(P<0.01,<0.05,<0.05 respectively).CONCLUSION:Low oxygen promotes stemness and proliferation of neural retinas,suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.

Detection of macular ganglion cell complex loss and correlation with choroidal thickness in chronic and recurrent central serous chorioretinopathy

AIM:To investigate the association of ganglion cell complex thickness(GCCt),global loss volume percentage(GLV%),and focal loss volume percentage(FLV%)with structural and functional findings among patients with chronic central serous chorioretinopathy(CCSC)and recurrent central serous chorioretinopathy(RCSC)by optical coherence tomography(OCT).METHODS:Among 29 patients with monocular affected central serous chorioretinopathy(CSC),15 had CCSC,and 14 had RCSC.The GCCt,FLV%,GLV%,and subfoveal choroidal thickness(SFCT)and sublesional choroidal thickness(SLCT)values were determined using OCT,and the association of these characteristics with neural structure parameters,choroidal morphology,features and functional alterations were estimated for the CCSC and RCSC patients.RESULTS:In CCSC,the affected eyes had significantly lower GCCt values than the fellow eyes in the macular regions(all P<0.05),with the highest GCCt observed in the inferior area.A significant association was found between the GCCt in different regions and the change in best corrected visual acuity(BCVA;r=-0.696;-0.695;-0.694,P<0.05)in CCSC patients.A statistically significant moderate negative correlation indicated that long-term CCSC was associated with greater differences in the GCCt in different regions between affected and fellow eyes(r=-0.562;r=-0.556;r=0.525,P<0.05).Additionally,observation of thickened SFCT was associated with a worse FLV%(r=0.599;r=0.546,P<0.05)in both groups.Similarly,thickened SLCT was associated with FLV%in RCSC patients(r=0.544,P<0.05).CONCLUSION:The distribution and GCCt are associated with the duration and visual outcomes of CCSC,whereas there is no correlation among RCSC patients.FLV%may be instrumental in differentiating the various outer choroidal vessels(pachyvessels)in long-term CSC.These results suggest that neural structure parameters may aid in estimating and predicting the recovery of altered morphology and function in CCSC and RCSC patients.

Valproate reduces retinal ganglion cell apoptosis in rats after optic nerve crush

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

Intraoperative sudden arrhythmias in cervical spine surgery adjacent to the stellate ganglion:A case report

BACKGROUND Atrial arrhythmias such as paroxysmal supraventricular tachycardia(PSVT)and atrial flutter(AF)are common in the perioperative setting.They commonly resolve spontaneously.However,occasionally,they may continually progress to fatal arrhythmias or cause complications.Therefore,prompt and appropriate management is important.CASE SUMMARY A 46-year-old female patient diagnosed with cervical C6-7 radiculopathy characterized by decreased sensation in the right third,fourth and fifth fingers underwent C6-7 anterior cervical disc fusion surgery.Electrocardiography showed PSVT and ventricular tachycardia during C6-7 disc retraction.However,the patient remained stable.Initial treatment with esmolol and lidocaine for ventricular tachycardia was ineffective.Carotid massage and Valsalva maneuver were attempted but PSVT did not resolve.The surgery was paused,and the patient’s fraction of inspired oxygen was set to 100%.Adenosine was administered for pharmacological management of PSVT.The arrhythmia temporarily resolved.However,it then transformed into AF.Diltiazem was administered,which briefly decreased blood pressure,which immediately recovered.Surgery resumed while the patient was in normal sinus rhythm.She was discharged safely on postoperative day 6 without complications or abnormalities.Currently,she is living a healthy life without arrhythmia recurrence.CONCLUSION Ganglia associated with cardiac arrhythmias in the surgical site should be identified during cervical spine surgery.

miR-141-3p对腰椎间盘突出症大鼠背根神经节炎症及下肢疼痛的抑制和改善作用

背景:研究表明,胰岛素样生长因子1/血小板源性生长因子有抑制纤维环细胞凋亡的作用。miR-141-3p微小RNA在骨髓基质细胞中随着年龄的增加而增加,且与炎症信号通路的活化存在一定关系,提示其可能成为腰椎间盘突出症的治疗靶点。目的:探究miR-141-3p通过调控胰岛素样生长因子1/血小板源性生长因子对腰椎间盘突出症大鼠背根神经节炎症及下肢疼痛的影响。方法:选取50只SPF级SD雄性大鼠,随机分为正常组、模型组、miR-NC组、miR-141-3p inhibitor组、miR-141-3p mimics组,每组10只。除正常组外,其余大鼠采用自体髓核移植法进行腰椎间盘突出症建模。建模成功后,对miR-NC组、miR-141-3p inhibitor组和miR-141-3p mimics组大鼠鞘内分别注射10μL 20μmol/L miR-NC,miR-141-3p inhibitor,miR-141-3p mimics,均每天注射1次,连续注射28 d;正常组、模型组同期同位置注射同体积生理盐水。采用热缩足潜伏期阈值评价大鼠下肢疼痛,实时荧光定量PCR检测背根神经节组织miR-141-3p mRNA表达,ELISA法检测背根神经节组织炎症因子,免疫印迹法检测背根神经节组织胰岛素样生长因子1/血小板源性生长因子蛋白表达,并分析miR-141-3p与胰岛素样生长因子1/血小板源性生长因子的相关性。结果与结论:miR-NC组各项指标与模型组比较,差异均无显著性意义。①大鼠热缩足潜伏期阈值:模型组明显低于正常组(P<0.05),miR-141-3p inhibitor组明显低于miR-NC组(P<0.05),miR-141-3p mimics组明显高于miR-141-3p inhibitor组(P<0.05)。②背根神经节组织miR-141-3p mRNA表达:模型组明显低于正常组(P<0.05),miR-141-3p inhibitor组明显低于miR-NC组(P<0.05),miR-141-3p mimics组明显高于miR-141-3p inhibitor组(P<0.05)。③背根神经节组织肿瘤坏死因子α、白细胞介素1β、白细胞介素1含量:模型组明显高于正常组(P<0.05),miR-141-3p inhibitor组明显高于miR-NC组(P<0.05),miR-141-3p mimics组明显低于miR-141-3p inhibitor组(P<0.05)。④背根神经节组织胰岛素样生长因子1、血小板源性生长因子蛋白表达:模型组明显低于正常组(P<0.05),miR-141-3p inhibitor组明显低于miR-NC组(P<0.05),miR-141-3p mimics组明显高于miR-141-3p inhibitor组(P<0.05)。⑤胰岛素样生长因子1与miR-141-3p呈正相关(r=0.904,P<0.001),血小板源性生长因子与miR-141-3p呈正相关(r=0.879,P<0.001)。⑥结论:miR-141-3p可显著改善腰椎间盘突出症大鼠下肢疼痛,抑制背根神经节炎症,其机制可能与促进胰岛素样生长因子1/血小板源性生长因子表达有关。

经颅磁声电刺激对健康与帕金森病大鼠神经回路中beta振荡的影响

背景:经颅磁声电刺激是一种基于磁声耦合电效应的无创、高精度脑神经聚焦刺激方法,可调节神经节律振荡活动,从而影响大脑的运动、认知等功能。目的:探究经颅磁声电刺激对健康与帕金森病大鼠神经回路中beta振荡的影响。方法:①动物实验:采用随机数字表法将24只Wistar大鼠随机分为4组,每组6只:正常对照组不进行任何干预;正常刺激组大脑前额叶皮质接受经颅磁声电刺激(空间峰值脉冲平均强度为13.33 W/cm^(2),基波频率为0.4 MHz,基波周期数为1000,脉冲重复频率为200 Hz);模型对照组、模型刺激组通过腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶建立帕金森病模型,造模成功后,模型对照组大脑前额叶皮质接受经颅磁声电假刺激,模型刺激组大脑前额叶皮质接受经颅磁声电刺激,每天刺激时长2.0 min,刺激结束停留8-10 min后,采集大鼠执行T迷宫过程中局部场电位信号并同时记录行为学正确率,对比分析各组局部场电位信号能量的时频分布情况和行为差异,当大鼠正确率连续3 d高于80%后停止刺激实验和T迷宫实验。②建模仿真实验:构建经颅磁声电刺激下皮质-基底神经节回路模型,分别改变超声发射周期(5,10,20 ms)、超声发射占空比(30%,50%,90%)和感应电流密度(20,50,100μA/cm^(2)),比较不同刺激参数下健康与帕金森病大鼠beta振荡的功率谱密度值。结果与结论:①动物实验:正常对照组大鼠的空间学习能力强于模型对照组(P<0.001),正常刺激组大鼠的空间学习能力强于正常对照组(P<0.05),模型刺激组大鼠的空间学习能力强于模型对照组(P<0.01);正常对照组beta振荡能量分布较为集中,正常刺激组较正常对照组beta振荡信号能量有所降低,模型对照组与模型刺激组beta振荡能量广泛分布且能量值显著高于正常对照组、正常刺激组,并且模型刺激组beta振荡信号能量明显低于模型对照组;②建模仿真实验:不加刺激时,健康大鼠beta频段功率谱密度峰值(30 dB)显著低于帕金森病大鼠(55 dB);施加经颅磁声电刺激后,两组大鼠beta频段功率谱密度值普遍降低;beta频段功率谱密度峰值与超声发射周期呈正相关、与感应电流密度呈负相关,当超声发射占空比为50%时功率谱密度峰值最低;③结果表明:经颅磁声电刺激可抑制健康与帕金森病大鼠的beta振荡,进而改善大鼠的运动功能与决策认知功能。

电针舌三针辅助星状神经节阻滞对脑梗死后吞咽障碍患者吞咽功能的影响

目的探讨电针舌三针辅助星状神经节阻滞(Stellate ganglion block,SGB)对脑梗死后吞咽障碍患者吞咽功能的影响。方法选取2022年1月—2023年1月期间河北北方学院附属第二医院收治的90例脑梗死后吞咽障碍患者,依据简单随机数字表法分为对照组和研究组,每组各45例。对照组采取SGB治疗,研究组在对照组基础上采取电针舌三针疗法,共治疗14 d。统计两组患者治疗前后舌骨移动度、吞咽用时、吞咽功能(Standardized swallowing assessment,SSA)及生活质量(Swallowing Quality-of-Life Instrument,SWAL-QOL)评分、营养状态指标[白蛋白(Prealbumin,PA)、转铁蛋白(Transferrin,TRF)、白蛋白(Albumin,ALB)]平及不良事件发生情况。结果治疗后两组患者舌骨上、下移动度较治疗前增大,差异有统计学意义(P<0.05);且研究组优于对照组,差异有统计学意义(P<0.05)。治疗后两组患者喉关闭用时、咽运送用时、口腔运送用时、吞咽反应用时较治疗前缩短,差异有统计学意义(P<0.05);且研究组优于对照组,差异有统计学意义(P<0.05)。治疗后两组患者SSA评分较治疗前降低、SWAL-QOL评分较治疗前升高,差异有统计学意义(P<0.05);且研究组SSA评分低于对照组,SWAL-QOL评分高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者PA、ALB、TRF水平较治疗前升高,差异有统计学意义(P<0.05);且研究组高于对照组,差异有统计学意义(P<0.05)。治疗期间,研究组不良事件发生率4.44%(2/45)明显低于对照组17.78%(8/45),差异有统计学意义(P<0.05)。结论采取电针舌三针辅助SGB治疗脑梗死后吞咽障碍可增大舌骨移动度,缩短吞咽用时,利于改善吞咽功能及营养状态,提升生活质量,并降低不良事件发生风险。

星状神经节阻滞用于慢性主观性耳鸣困扰的辅助干预效果及预测指标初析

【目的】探讨星状神经节阻滞(SGB)用于慢性主观性耳鸣困扰的辅助干预效果,及相应的预测指标,为SGB应用于耳鸣的临床干预累积经验。【方法】回顾因其他干预方案效果不理想而在中山大学附属第三医院耳鼻咽喉-头颈外科接受SGB干预的慢性主观性耳鸣患者资料。SGB干预前进行耳鸣残疾量表(THI)评估、纯音听阈测试、耳鸣响度评估,部分患者接受了睡眠质量(PSQI)评估。SGB干预后复测THI,以评价SGB的干预效果。随后,通过相关分析及线性回归方程探寻预测SGB干预效果的潜在指标。数据的统计分析采用SPSS 24.0进行,P<0.05表示存在统计学意义。【结果】至2023年04月,共有107名慢性主观性耳鸣患者接受了SGB干预,其中男性患者67名,女性患者40名,平均(45.32±11.40)周岁,耳鸣持续(20.32±24.64)月[16(12~20)]。有7名患者因个人原因中途退组,退组率6.54%,干预依从性良好。所有患者均未出现穿刺部位感染、血肿、神经损伤、局麻药中毒等不良反应,安全性良好。SGB干预后,有77名患者的THI得分下降至36分及以下,剩余的患者中有12名的THI得分下降幅度达到10分及以上,有效率为89%;配对样本t检验显示,SGB干预前后的THI得分有显著的统计学差异(t=15.575,P<0.001),干预效果良好。皮尔逊相关分析显示,干预前的THI得分和耳鸣主观响度与THI的改善水平呈显著的正相关关系(P<0.05);进一步的逐步线性回归分析发现,“干预前THI得分”具有显著的统计学意义(P<0.001),回归系数为0.308,预测了THI改善水平的17.4%。【结论】SGB干预慢性主观性耳鸣困扰的短期效果良好、安全性高,可用于常规干预方案不理想时(尤其是THI得分较高患者)的补充方案,但后续研究需要明确长期疗效及内在机制,为SGB应用于主观性耳鸣的干预奠定更为扎实的理论基础。

PBL结合图形勾画在进修医师颅底卵圆孔定位教学的应用效果研究

目的探讨基于问题的教学法(problem-based learning,PBL)结合图形勾画在进修医师颅底卵圆孔定位教学的应用效果。方法选择2022年1-12月,在首都医科大学宣武医院疼痛科进修的医生共60名作为研究对象,采用随机数字表法分为试验组(n=30)和对照组(n=30)。在三叉神经半月节球囊压迫术中实施X射线影像定位颅底卵圆孔教学,试验组采用PBL结合图形勾画教学方式,对照组采用传统教学方式。通过理论考试和问卷调查评价教学效果。结果与对照组相比,试验组的理论考试总成绩、影像成绩和操作成绩均高于对照组(85.8±8.5 vs.69.3±13.7,P<0.001;24.7±3.9 vs.21.8±5.2,P=0.020;35.8±3.7 vs.23.7±6.1,P<0.001)。问卷调查检查结果显示,在提高学习兴趣、提升学习能力、解决困惑迷茫、理解重点难点和满意度评分方面,试验组分别优于对照组(96.7±3.1 vs.80.1±6.9,P<0.001;95.2±4.5vs.76.7±6.2,P<0.001;96.0±4.1vs.72.7±7.9,P<0.001;93.8±5.3vs.69.7±7.4,P<0.001;97.2±3.7 vs.75.0±7.3,P<0.001)。结论在X射线影像定位颅底卵圆孔教学的应用中,PBL结合图形勾画取得良好的教学效果,提高学生学习兴趣和学习能力。

红景天苷改善顺铂引起的小鼠耳蜗毛细胞和螺旋神经节神经元损伤的机制

目的探究红景天苷(SAL)改善顺铂(CIS)引起的耳蜗毛细胞(CHC)和螺旋神经节神经元(SGN)损伤的作用及其与环磷腺苷(cAMP)/蛋白激酶A(PKA)/cAMP效应元件结合蛋白(CREB)通路的关系。方法分离新生C57BL/6小鼠的耳蜗基底膜,分为对照组(C组)、CIS组、SAL组、SAL+SQ22536(cAMP抑制剂)组和SAL+H-89(PKA抑制剂)组,每组20条。C组仅加入无血清BME培养液;CIS组在培养液中加入15μmol/L CIS;SAL组在CIS组基础上加入5μmol/L SAL;SAL+SQ22536组在CIS组基础上加入5μmol/L SAL和5μmol/L SQ22536;SAL+H-89组在CIS组基础上加入5μmol/L SAL和30μmol/L H-89。各组在培养箱中孵育48 h后,免疫荧光染色观察各组CHC和SGN损伤;试剂盒检测各组耳蜗基底膜中ROS和cAMP含量;Western blot检测各组PKA、p-CREB、CREB、Bcl-2、BDNF、NF-M蛋白水平。结果CIS组CHC排列混乱、体积肿大,SGN细胞核破碎、神经突缺失,SAL可减轻CHC和SGNs损伤。与C组相比,CIS组CHC、SGN数量较少(P<0.05),ROS、cAMP含量、PKA、BDNF、NF-M、Bcl-2蛋白及p-CREB/CREB水平较高(P<0.05);与CIS组相比,SAL组CHC、SGN数量较多(P<0.05),ROS含量较低(P<0.05),cAMP含量、PKA、BDNF、NF-M、Bcl-2蛋白及p-CREB/CREB水平较高(P<0.05)。SQ22536和H-89均可逆转SAL对CHC和SGN的保护作用。结论SAL可能通过激活cAMP/PKA/CREB通路,促进抗凋亡蛋白和神经保护因子表达,缓解CIS引起的CHC和SGN损伤。