1.Potassium channel Kv1.3 mediates neurodysfunction and neuroin-flammation after traumatic brain injury
Xingxing CHEN ; Zhengxun CHEN ; Die ZHANG ; Haopeng JIANG ; Jie TAO ; Lele TANG ; Yi YUAN
Chinese Journal of Pharmacology and Toxicology 2025;39(6):401-411
OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.
2.Potassium channel Kv1.3 mediates neurodysfunction and neuroin-flammation after traumatic brain injury
Xingxing CHEN ; Zhengxun CHEN ; Die ZHANG ; Haopeng JIANG ; Jie TAO ; Lele TANG ; Yi YUAN
Chinese Journal of Pharmacology and Toxicology 2025;39(6):401-411
OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.
3.Association of triglyceride glucose index and risk of incident hypertension: a prospective cohort study
Xi CHEN ; Manman WEI ; Zhengxun ZHANG ; Ge LIU ; Ruoshan WANG ; Xinyuan YOU ; Dongsheng HU ; Yang ZHAO
Chinese Journal of Cardiology 2024;52(4):413-419
Objective:To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults.Methods:A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk.Results:The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles ( Ptrend<0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 ( RR=1.11, 95% CI 1.01-1.22, P=0.023), TyG 8.6-8.9 ( RR=1.16, 95%CI 1.06-1.27, P=0.023), and TyG≥9.0 ( RR=1.20, 95%CI 1.10-1.31, P=0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions:The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.
4.Clinical efficacy analysis of arthroscopic treatment for hallux ganglion cyst deriving from ankle joint
Qinglin ZHANG ; Lei CHEN ; Mingtong HAN ; Baoqiang XU ; Yong HU ; Zhengxun LI
Chinese Journal of Surgery 2023;61(11):982-988
Objective:To investigate the pathogenesis and clinical efficacy of arthroscopic treatment for hallux ganglion cyst deriving from ankle joint.Methods:The clinical data of 21 patients with ankle arthroscopic in the Department of Hand and Foot Surgery,Affiliated Hospital of Jining Medical College from January 2019 to March 2021 were analyzed retrospectively.There were 15 male cases and 6 female cases,aged (52.6±8.2) years (range:42 to 70 years).There were 9 cases of primary operation and 12 cases of recurrence after operation in other hospital.All the patients were examined by ankle arthrography and MRI before operation.The synovial membrane of the ankle was debrided and the tendon sheath of flexor longus was removed at the ankle canal.One year after operation,MRI was performed,and the American Orthopedic Foot and Ankle Society(AOFAS) score of forefoot function and visual analogue scale (VAS) before and after operation were compared by the paired t test or Mann-Whitney U test.The postoperative complications and recurrence were recorded. Results:All patients were operated successfully.The joint capsule at the back of the ankle joint of the patients were ruptured and communicated with the tendon sheath of the flexor longus tendon at the ankle canal.No wound infection,vascular and nerve injury occurred.The follow-up period was (15.0±2.2) months (range:12 to 18 months).During the follow-up period,there was no recurrence of toe appearance and MRI.At the last follow-up,the AOFAS score (90.8±4.3) was significantly higher than that before operation (72.8±6.3) ( t=-10.810, P<0.01),and the VAS score( M(IQR)) was significantly lower than that before operation,the difference was significant (1.0(1.0) vs. 3.0(0.5), Z=-4.081, P<0.01). Conclusions:The possible mechanism of hallux ganglion cyst deriving from ankle joint is that the joint capsule at the back of the ankle joint ruptures and communicates with the tendon sheath of the flexor longus tendon at the ankle canal,and the intra-articular synovial fluid through the cylinder effect generated by sliding with the flexor tendon of the flexor longus tendon in the tendon sheath sac leads to the heel valange cyst.Ankle-synovial cleansing of the ankle joint under ankle arthroscopy and resection of the flexor tendon sheath of the flexor longus tendon at the ankle canal are effective and less invasive.
5.Clinical efficacy analysis of arthroscopic treatment for hallux ganglion cyst deriving from ankle joint
Qinglin ZHANG ; Lei CHEN ; Mingtong HAN ; Baoqiang XU ; Yong HU ; Zhengxun LI
Chinese Journal of Surgery 2023;61(11):982-988
Objective:To investigate the pathogenesis and clinical efficacy of arthroscopic treatment for hallux ganglion cyst deriving from ankle joint.Methods:The clinical data of 21 patients with ankle arthroscopic in the Department of Hand and Foot Surgery,Affiliated Hospital of Jining Medical College from January 2019 to March 2021 were analyzed retrospectively.There were 15 male cases and 6 female cases,aged (52.6±8.2) years (range:42 to 70 years).There were 9 cases of primary operation and 12 cases of recurrence after operation in other hospital.All the patients were examined by ankle arthrography and MRI before operation.The synovial membrane of the ankle was debrided and the tendon sheath of flexor longus was removed at the ankle canal.One year after operation,MRI was performed,and the American Orthopedic Foot and Ankle Society(AOFAS) score of forefoot function and visual analogue scale (VAS) before and after operation were compared by the paired t test or Mann-Whitney U test.The postoperative complications and recurrence were recorded. Results:All patients were operated successfully.The joint capsule at the back of the ankle joint of the patients were ruptured and communicated with the tendon sheath of the flexor longus tendon at the ankle canal.No wound infection,vascular and nerve injury occurred.The follow-up period was (15.0±2.2) months (range:12 to 18 months).During the follow-up period,there was no recurrence of toe appearance and MRI.At the last follow-up,the AOFAS score (90.8±4.3) was significantly higher than that before operation (72.8±6.3) ( t=-10.810, P<0.01),and the VAS score( M(IQR)) was significantly lower than that before operation,the difference was significant (1.0(1.0) vs. 3.0(0.5), Z=-4.081, P<0.01). Conclusions:The possible mechanism of hallux ganglion cyst deriving from ankle joint is that the joint capsule at the back of the ankle joint ruptures and communicates with the tendon sheath of the flexor longus tendon at the ankle canal,and the intra-articular synovial fluid through the cylinder effect generated by sliding with the flexor tendon of the flexor longus tendon in the tendon sheath sac leads to the heel valange cyst.Ankle-synovial cleansing of the ankle joint under ankle arthroscopy and resection of the flexor tendon sheath of the flexor longus tendon at the ankle canal are effective and less invasive.
6.Pathological changes in the preparation of bone-skin flap with allogeneic bone induction
Qingluan HAN ; Wei LI ; Hongjin FAN ; Bo ZHANG ; Zhengxun LI
Chinese Journal of Tissue Engineering Research 2013;(44):7733-7738
BACKGROUND:Autologous bone-skin flap transplantation is the best method for the repair of composite tissue defect, but the repair ability is limited, with big trauma, new tissue defect and a certain dysfunction. Al ogeneic bone has the osteoinductive capacity, which can be used to prepare the bone-skin flap. OBJECTIVE:To research the pathological change of the al ogenic bone during the prefabrication of bone-skin flap with al ogeneic bone implant. METHODS:The experimental animals were Bama miniature pigs. Deep-frozen al ogenic bone was implanted in iliac artery-supported tissue flap compartment of miniature pigs. After operation, the local reactions were observed, the al ogenic bone were studied by general observation and histological analysis at 4, 8, 12 and 16 weeks after implantation respectively. RESULTS AND CONCLUSION:Obvious inflammation reaction was not observed in the surgical zone. The al ogeneic bone was vascularized at 4 weeks after implanted into the flap tissue without obvious osteoblast-like cells. The vascularization, bone resorption and uneven distributed osteoblast-like cells and osteoclast-like cells were observed at 8 weeks after implantation, and new bone formation was observed. At 12 weeks after implantation, new bone formation and bone absorption was strengthened, and the morphology of the bone graft was changed. At 16 weeks after implantation, al ogenic bone turned into fragments and absorbed, and no new bone formation was observed. The results indicated that during the prefabrication of bone-skin flap with al ogeneic bone implantation, the pathological changes of the al ogeneic bone was observed with time prolonging, and the bone-skin flap should be transplanted in time.

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