1.Analysis of syncopal DRVR in blood donors: multicenter hemovigilance data (2020—2023)
Junhong YANG ; Qing XU ; Wenqin ZHU ; Fei TANG ; Ruru HE ; Zhenping LU ; Zhujiang YE ; Fade ZHONG ; Gang WU ; Guoqiang FENG ; Xiaojie GUO ; Jia ZENG ; Xia HUANG
Chinese Journal of Blood Transfusion 2025;38(8):1071-1076
Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.
2.Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion
Zhong-You ZENG ; Ping-Quan CHEN ; Xing ZHAO ; Hong-Fei WU ; Jian-Qiao ZHANG ; Xiang-Qian FANG ; Yong-Xing SONG ; Wei YU ; Fei PEI ; Shun-Wu FAN ; Guo-Hao SONG ; Shi-Yang FAN
China Journal of Orthopaedics and Traumatology 2024;37(1):33-44
Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4%.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P<0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)%to the latest follow-up(11.30±3.27)%,and there was statistically significant different.The complication rate was 31.3%(45/144),and the reoperation rate was 9.72%(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14%(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.
3.Reasons and strategies of reoperation after oblique lateral interbody fusion
Zhong-You ZENG ; Deng-Wei HE ; Wen-Fei NI ; Ping-Quan CHEN ; Wei YU ; Yong-Xing SONG ; Hong-Fei WU ; Shi-Yang FAN ; Guo-Hao SONG ; Hai-Feng WANG ; Fei PEI
China Journal of Orthopaedics and Traumatology 2024;37(8):756-764
Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P<0.05).The ODI recovered from(40.60±7.01)%preoperatively to(9.14±2.66)%postoperatively(P<0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.
4.Clinical Observation on the Tiaodu Lijin Acupuncture Combined with Thumb-tack Needling for Subcutaeous Embedding in the Treatment of Lumbar Disc Herniation
Yun-Fei WANG ; Jing YANG ; Wen-Zhong WU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(7):1805-1812
Objective To observe the clinical efficacy of Tiaodu Lijin Acupuncture combined with thumb-tack needling for subcutaeous embedding in the treatment of lumbar disc herniation.Methods A total of 98 patients with lumbar disc herniation were randomly divided into observation group and control group,49 cases in each group.The control group was treated with Tiaodu Lijin Acupuncture,and the observation group was treated with thumb-tack needling for subcutaeous embedding on the basis of the control group.Both groups were treated for one month.After one month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Japanese Orthopaedic Association(JOA)score and Visual Analogue Scale(VAS)of pain were observed before and after treatment in the two groups,as well as the activity of lumbar spine and the expressions of ERK protein and ERK mRNA.The levels of β-endorphin(β-EP),neuropeptide Y(NPY),5-hydroxytryptamine(5-HT),substance P(SP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)were compared between the two groups before and after treatment.The safety of the two groups was evaluated.Results(1)The total effective rate was 93.88%(46/49)in the observation group and 79.59%(39/49)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the JOA and VAS scores of the two groups were significantly improved(P<0.05),and the improvement of JOA and VAS scores in the observation group was significantly superior to that in the control group,the difference was statistically significant(P<0.05).(3)After treatment,the levels of β-EP,NPY,5-HT and SP in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the levels of β-EP,NPY,5-HT and SP,the difference was statistically significant(P<0.05).(4)After treatment,the levels of IL-6,IL-1β and TNF-α in the two groups were significantly improved(P<0.05),and the levels of IL-6,IL-1β and TNF-α in the observation group were significantly superior to those in the control group(P<0.05).(5)After treatment,the lumbar flexion and extension activities of the two groups were significantly improved(P<0.05),and the improvement of lumbar flexion and extension activities in the observation group was significantly superior to that in the control group,the difference was statistically significant(P<0.05).(6)After treatment,the expressions of ERK protein and the level of ERK mRNA in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the expressions of ERK protein and the level of ERK mRNA,the difference was statistically significant(P<0.05).(7)The incidence of adverse reactions in the observation group was 8.16%(4/49),while the control group was 4.08%(2/49).There was no significant difference between the observation group and the control group(P>0.05).Conclusion Tiaodu Lijin Acupuncture combined with thumb-tack needling for subcutaeous embedding exerts certain effect in the treatment of lumbar disc herniation.It can significantly improve the pain symptoms of patients,reduce the levels of serum pain mediators and inflammatory factors,and improve lumbar function.The mechanism may be related to the inhibition of ERK signaling pathway.
5.Current situation of in-flight bladder relief device for US fighter pilots and implications for Chinese PLA
Xiao LUO ; Xiao-Li ZHANG ; Fei CHANG ; Fei-Fei WU ; Fang-Hu ZHONG
Chinese Medical Equipment Journal 2024;45(6):71-76
The whole developing history of the in-flight bladder relief device for US fighter pilots from the first generation to the third generation was introduced.The optimized design of the third-generation product was described in terms of male use and female use.It's pointed out the US Air Force developed the in-flight bladder relief device with the mode of integration and innovation,the idea closely following the troops'needs and the key technology upgrading thought introducing the newest achievements,and references were provided for the technical improvement of this type of device for the PLA.[Chinese Medical Equipment Journal,2024,45(6):71-76]
6.Mechanism of miR-125a-3p targeting FOXM1 in regulating skin injury and inflammatory response in psoriasis rats
Zhao JIN ; Zhong LIU ; Jing PENG ; Rongyi HU ; Juan WU ; Qinsi HUANG ; Fei WANG
Chinese Journal of Immunology 2024;40(12):2531-2536,2542
Objective:To explore effect of miR-125a-3p on skin injury and inflammatory response in psoriasis rats and its mechanism.Methods:SD rats were randomly divided into control group,psoriasis group,miR-NC group and miR-125a-3p group.Psoriasis Area and Severity Index(PASI)score and Baker score were measured on rats;levels of IL-6,IL-1β and TNF-α in rat skin tissue were detected by ELISA;qRT-PCR was used to detect miR-125a-3p expression;mRNA and protein expressions of forkhead box protein M1(FOXM1)in rat skin tissue were detected by qRT-PCR and Western blot.Keratinocytes from psoriasis rats were isolated and cultured,targeting relationship between miR-125a-3p and FOXM1 was verified by dual-luciferase reporter gene assay.Inhibiting or overexpressing miR-125a-3p and FOXM1 was overexpressed on basis of overexpressing miR-125a-3p,respectively.miR-125a-3p,FOXM1 mRNA and protein expressions in cells and IL-6,IL-1β,TNF-α levels in cell culture supernatants were detected,CCK-8 method was applied to detect cell viability,and flow cytometry was used to detect apoptosis rate.Results:Compared with control group,miR-125a-3p expression in skin tissue of rats in psoriasis group was decreased,PASI score,Baker score,IL-6,IL-1β,TNF-α levels,and FOXM1 mRNA and protein expressions were increased(P<0.05);compared with psoriasis group and miR-NC group,expression of miR-125a-3p in skin tissue of rats in miR-125a-3p group was increased,PASI score,Baker score,IL-6,IL-1β,TNF-α levels,and expressions of FOXM1 mRNA and protein were decreased(P<0.05).There was a targeting relationship between miR-125a-3p and FOXM1.After inhibiting miR-125a-3p expression,FOXM1 mRNA and protein expressions in cells,cell viability and IL-6,IL-1β,TNF-α levels in cell culture supernatant were increased,and apoptosis rate was decreased(P<0.05),while overexpression of miR-125a-3p had opposite effect.Overexpression of FOXM1 attenuated effects of overexpression of miR-125a-3p on cell viability,apopto-sis rate and inflammatory response.Conclusion:miR-125a-3p is lowly expressed in skin lesions of psoriasis rats,whose overexpression may inhibit proliferation of keratinocytes and promote apoptosis by targeting FOXM1,improve skin injury and reduce inflammatory response in psoriasis rats.
7. Regulation of Yes associated protein in diabetic nephropathy mice by Yishen Huashi Granule
Xiao-Fan CAI ; Yue XING ; Xin-Yi FU ; Yue-Yi DENG ; Yi-Fei ZHONG ; Jie-Bo HUANG ; Hui-Juan WU
Chinese Pharmacological Bulletin 2023;39(10):1944-1949
Aim To explore the protective effect of Yishen Huashi Granule (YSHS) on streptozotocin (STZ) - indueed diabetes nephropathy (DN) in mice and its possible mechanism. Methods The STZ induced DN mice model was established, which was randomly divided into model group, YSHS group and YAP inhibitor Vertepofin group, and the eontrol group was also established. The intervention was started eight weeks after the successful modeling with the course of four weeks. Urine protein concentration before and after intervention in each group as well as serum creatinine (Scr) and blood urea nitrogen (Bun) levels after intervention were measured. After the treatment, the mice were sacrificed, and the pathological changes of glomeruli were observed by light microscope HE staining. The protein expression of YAP, p-YAP S127 and CTGF were detected by Western blot, and the mRNA expressions of YAP, CTGF and podocyte functional proteins nephrin, podophyxin and WT1 were detected by RT-PCR. Results The biochemical indexes of YSHS group were better than those of model group, and HE staining showed that the pathological injury of glomeruli was improved. In the model group the protein expression of YAP, p-YAP (S127) and CTGF as well as the mRNA expression of YAP and CTGF increased, while the mRNA expression of nephrin, podocalyxin and WT1 decreased. After YSHS treatment, the protein expression of YAP, p-YAP S127, CTGF and the mRNA expression of YAP and CTGF decreased, while the mRNA expression of nephrin, podocalyxin and WT1 increased. Conclusions YSHS can reduce urinary protein, protect renal function and alleviate glomerular pathological injury in DN mice. Its possible mechanism may be related to the down-regulation of YAP in renal tissue, the reduction of CTGF expression level and the up-regulation of podocyte protein mRNA expression.
8.Clinicopathological features and prognosis of anorectal melanoma: A report of 68 cases.
Yu Mei LAI ; Zhong Wu LI ; Huan LI ; Yan WU ; Yun Fei SHI ; Li Xin ZHOU ; Yu Tong LOU ; Chuan Liang CUI
Journal of Peking University(Health Sciences) 2023;55(2):262-269
OBJECTIVE:
To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors.
METHODS:
A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging.
RESULTS:
(1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm2. The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival.
CONCLUSION
The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.
Humans
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Male
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Female
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Middle Aged
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Neoplasm Staging
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Retrospective Studies
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Proto-Oncogene Proteins B-raf
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Prognosis
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Melanoma/surgery*
9.Age-adjusted Charlson comorbidity index predicts mortality in patients with acute type A aortic dissection
Wendan WANG ; Lei WANG ; Chen CHAI ; Xiaowei ZHANG ; Fei LV ; Suting ZHONG ; Tiantian WANG ; Long WU ; Zehai TANG
Chinese Journal of Emergency Medicine 2023;32(1):76-81
Objective:To evaluate the predictive value of age-adjusted Charlson comorbidity index (ACCI) for in-hospital mortality and 1-year mortality in patients with acute type A aortic dissection (ATAAD).Methods:This was a retrospective cohort study, and the clinical data of ATAAD patients admitted to Wuhan Union Hospital from January 1, 1999 to December 31, 2018 were collected for analysis. All the patients were confirmed by computed tomography angiography or magnetic resonance imaging of the aorta and the onset time was less than 14 days. Patients who survived at discharge were followed up to obtain 1-year survival information. The ACCI score was calculated for patients based on their comorbidities and age at admission, and they were divided into three groups of 0, 1 and ≥2 according to the ACCI score. The in-hospital mortality and 1-year mortality of the three groups were compared. Logistic regression analysis was applied to determine the independent predictors for in-hospital mortality and 1-year mortality.Results:Among 1 133 ATAAD patients, 383, 357 and 393 patients had ACCI score of 0, 1, and ≥2, respectively. The in-hospital mortality and 1-year mortality of patients with ACCI score ≥2 were significantly higher than those of patients with ACCI score of 0 (25.4% vs. 17.0%, 30.0% vs. 19.6%, both P<0.05). Multivariate Logistic regression analysis showed that ACCI score ≥2 was an independent risk factor for in-hospital mortality ( OR=1.670, 95% CI: 1.176-2.370, P=0.004) and 1-year mortality ( OR=1.762, 95% CI: 1.264-2.456, P<0.001). Age (per 10-year increase) and cerebrovascular diseases were independent risk factors for in-hospital mortality and 1-year mortality, while diabetes mellitus was a protective factor for in-hospital mortality. Conclusions:ACCI can predict the in-hospital mortality and 1-year mortality of ATAAD patients, and patients with ACCI score ≥2 have a poorer prognosis.
10.Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy
Lin YANG ; Qi ZHANG ; Xueqing WU ; Xiaoyun QIU ; Fan FEI ; Nanxi LAI ; Yuyi ZHENG ; Mengdi ZHANG ; Qingyang ZHANG ; Yu WANG ; Fei WANG ; Cenglin XU ; Yeping RUAN ; Yi WANG ; Zhong CHEN
Chinese Journal of Pharmacology and Toxicology 2023;37(7):482-483
OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

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