Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

Objective:To investigate the application value of the Nottingham Hip Fracture Score (NHFS) in China and establish a formula specifically designed to assess the risk for 30-day mortality after surgery for hip fracture patients in China.Methods:A retrospective study was conducted to analyze the clinical data of 824 hip fracture patients who had been treated at Department of Orthopaedics, The First Hospital Affiliated to Zhengzhou University from August 2019 to May 2022. There were 312 males and 512 females with a median age of 73 (63, 82) years. The clinical data were compared between patients with different survival outcomes. The 30-day mortality was calculated by the formula according to the patients' NHFS, and compared with the actual one to validate the effectiveness of the original prediction model. The patients were divided into a training group ( n=577) and a validation group ( n=247). Binary logistic regression analysis was performed to establish a new prediction model for the patients in the training group. The discrimination, calibration, and clinical effectiveness of the predictive model were assessed in both the training and validation groups. Results:Multivariate logistic regression analysis showed that advanced age (≥86 years old) ( OR=3.775, 95% CI: 1.099 to 12.972, P=0.035), male ( OR=3.151, 95% CI: 1.574 to 6.306, P=0.001), admission hemoglobin concentration ≤100 g/L ( OR=2.402, 95% CI: 1.189 to 4.850, P=0.015), dependence on others for care before admission ( OR=2.673, 95% CI: 1.298 to 5.505, P=0.008), and comorbidities ≥2 ( OR=4.988, 95% CI: 1.874 to 13.274, P=0.001) were identified as risk factors for postoperative 30-day mortality (all P<0.05). In validation of the original prediction model, the C-index was found to be 0.764, indicating good discrimination. However, there was a significant discrepancy between the mortality forecast by the original prediction model and the actual mortality ( P<0.05), indicating poor calibration. After the prediction model was recalibrated, 30-day mortality (%) = 100/[1 + e (5.818-NHFS×0.599)]. After the new prediction model was validated in both the training and validation groups, the C-indexes were 0.762 and 0.780, indicating a good level of discrimination. The predicted 30-day mortality by the prediction model was closely aligned with the actual mortality ( P>0.05), demonstrating good calibration. When the threshold probabilities of the training and the validation groups were 0 to 26% and 0 to 35%, respectively, the patients might benefit from clinical intervention, showing clinical effectiveness of the model. Conclusions:The NHFS can predict the risk for 30-day mortality after hip fracture surgery. The new NHFS prediction model after calibration has a good predictive value for 30-day mortality after hip fracture surgery in Chinese population.

Objective:To evaluate the personalized 3D printed guide template used in the osteotomy for malunion of tibial fracture.Methods:A retrospective analysis was conducted of the 30 patients who had been treated for malunion of tibial fracture at Department of Orthopaedics, The First Affiliated Hospital to Zhengzhou University from January 2010 to January 2018. Of them, 15 used a personalized 3D printed guide template in the osteotomy (3D printing group). They were 9 males and 6 females, with an age of 46.3 year±8.2 years. The fracture malunion was located in the upper and middle tibia in 11 cases, in the lower tibia in 4 cases, on the left side in 6 cases and on the right side in 9 ones. There were 8 cases of varus deformity and 7 ones of valgus deformity. Their preoperative fracture deformity angle was 24.3°±5.5°. The other 15 patients were treated with conventional surgery (conventional group). They were 10 males and 5 females, with an age of 47.1 years±6.0 years. The fracture was located in the upper and middle tibia in 12 cases, in the lower tibia in 3 cases, on the left side in 5 cases and on right side in 10 cases. There were 7 cases of varus deformity and 8 ones of valgus deformity. Their preoperative fracture deformity angle was 22.5°±5.4°. The 2 groups were compared in terms of preoperative baseline data, operation time, intraoperative blood loss and postoperative recovery of the alignment of lower limb.Results:There were no significant differences in the preoperative baseline data between the 2 groups, showing comparability ( P>0.05). The 3D printing group was followed up for an average of 12 months while the conventional group for an average of 10 months. The operation time for the 3D printing group was significantly shorter than that for the conventional group(102.2 min±13.0 min versus 137.9 min ±10.5 min), the intraoperative blood loss for the former significantly less than that for the latter (77.3 mL ± 39.7 mL versus 163.3 mL ± 35.2 mL), and the postoperative malunion angle in the former significantly smaller than that in the latter (1.9°±0.4° versus 3.2°±0.9°) (all P< 0.05). The last follow-ups revealed no implant failure or re-malunion but fine healing of the osteotomy sites and good recovery of the alignment of lower limb in the 2 groups. Conclusion:A personalized 3D printed guide template used in the osteotomy for malunion of tibial fracture is an effective aid because it can facilitate precise osteotomy, reduce operation time and intraoperative blood loss and help correct the alignment of lower limb, leading to good short-term surgical outcomes.

Objective To investigate the clinical efficacy of our self-designed sight used to guide thoracic vertebroplasty.Methods A retrospective analysis was conducted of the 52 patients (70 thoracic vertebrae) who had undergone percutaneous vertebroplasty (PVP) (n =36)or percataneous kyphoplasty (PKP) (n =34) of T1-T4 vertebral bodies at Department of Orthopaedics,The First Affiliated Hospital to Zhengzhou University form August 2012 to October 2013.The operation time,intraoperative bleeding,intraoperative radiation by C-arm roentgenography,and visual analogue scale (VAS) were compared between the patients whose surgery had been guided by our self-designed sight and those whose surgery had been not.Results All the patients were followed up for 18 to 36 months (average,22.3 months).Compared with those who had not used the sight,the patients who had used the sight incurred significantly shorter operation time (16.5 ± 3.2 min versus 26.5 ± 3.7 min),significantly less intraoperative bleeding (2.8 ± 1.3 mL versus 6.3 ± 1.7 mL) and significantly less radiation by C-arm roentgenography (5.6 ± 3.3 times versus 9.4 ± 3.1 times) (P ＜0.05).The VAS scores at postoperative 3 days and final follow-up were significantly decreased than the preoperative values in all the patients (P ＜ 0.05).There were no significant differences between the patients who had used the sight and those who had not in the the VAS scores at postoperative 3 days or final follow-up (P ＞ 0.05).Conclusions The upper thoracic PVP or PKP guided by our self-designed sight has theadvantages of short operation time,less intraoperative bleeding and less frequency of C-arm radiation.The sight is suitable for various vertebroplasties.

PURPOSETo investigate the changes of cerebral hemodynamics pre- and post-ventricular drainage in patients with posttraumatic acute diffuse brain swelling.

METHODSTwenty-four cases of traumatic diffuse brain swelling were analyzed retrospectively. Patients in nonsurgical group were treated by medicine therapy. Patients in surgical group were treated by external ventricular drainage plus medicine therapy. The first CT perfusion scan was completed within 4-5 h after trauma and scanned again after 7 days. The changes of perfusion parameters in area-of-interest in two groups were analyzed and compared before and after treatment.

RESULTSCompared with the nonsurgical group, the value of cerebral blood volume, cerebral blood flow and mean transit time in bilateral frontal temporoparietal grey matter, basal ganglia, cerebellum, and brain stem at pre- and post-therapy were increased significantly (p < 0.05) in surgical group, and consequently the prognosis of patients undergoing surgery was also better than that of nonsurgical group.

CONCLUSIONExternal ventricular drainage can improve cerebral perfusion and increase survival quality for the patients with posttraumatic acute diffuse brain swelling.

Adult ; Aged ; Brain ; physiopathology ; Brain Edema ; physiopathology ; therapy ; Brain Injuries ; complications ; Cerebrovascular Circulation ; Drainage ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Retrospective Studies

Mild traumatic brain injury (MTBI) is defined as a mild brain trauma resulting in a short loss of consciousness and alteration of mental status. It may also occasionally develop persistent and pro-gressive symptoms. It has been confirmed that MTBI causes changes of anatomic structures in central nervous systemand biomarkers in the body fluid. How ever, there is no sufficient research on relevance among threshold for the brain injury, individual vulnerability and duration of disturbance of conscious-ness. Furthermore, there are no reliable diagnostic methods to establish w hether a blow to the head is sufficient to cause the brain injury. T his review provides references for biomarkers in cerebrospinal fluid and blood associated w ith T B I. It also provides application status and potential prospects for further as-sessment and diagnosis of MTBI.

BACKGROUND:Tissue-engineered bone in the treatment of large bone defects has obvious advantages especial y when the autologous ilium transplantation is limited, which can effectively fil bone defects.
OBJECTIVE:To investigate the rationality of intramedul ary nailing support and tissue-engineered bone fil ing in the treatment of fibrous dysplasia of the proximal femur and the biocompatibility of the tissue-engineered bone.
METHODS:Seven patients with fibrous dysplasia of the proximal femur were subjected to intramedul ary nailing support and tissue-engineered bone fil ing.
RESULTS AND CONCLUSION:Al of the seven patients underwent more than 8 months of fol ow-up, no rejection reaction and other complications occurred. After 4-6 weeks of fixation, al the seven patients removed hip spica braces, with a good hip mobility. After 10-12 weeks, X-ray review showed no pathological fracture, internal fixation loosening and narrow neck stem angle. Using the Harris hip score evaluation of the hip function, the affected side of the seven patients was optimized. After 16-18 weeks, X-ray films reviewed good creeping substitution in the affected area treated with the intramedul ary nailing support and bone graft. After 24-26 weeks, new bone appeared within the scope of lesions. After 1.0-1.5 years, bone creeping substitution was basical y completed in the intertrochanteric region, and original lesions were invisible on X-ray films. These findings confirmed that intramedul ary nailing support and tissue-engineered bone fil ing for treating fibrous dysplasia of the proximal femur has good effectiveness, exhibiting stable internal fixation and avoiding resection of autogenous iliac bone. Tissue-engineered bone has a good biocompatibility in the medium-term fol ow-up, with good hip function activities.

Objective To investigate the family burden of patients with severe mental illness. Methods 148 patients with schizophrenia and bipolar disorder were assessed with Family Burden Scale of disease (FBS). Results Family burden broadly exists among those patients with schizophrenia and bipolar disorder, and the burden tends to involve several dimensions, including family relations (51%), home entertainment (50%), daily routine (45%), economic burden (43%), mental health of family members (36%) and physical health of family members (32%). Conclusion Integrated psychological and social intervention should be made to reduce the family burden of patients with schizophrenia and bipolar disorder.