Repetitive transcranial magnetic stimulation in Alzheimer's disease: effects on neural and synaptic rehabilitation.

Alzheimer's disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis. The Alzheimer's disease brain tends to be hyperexcitable and hypersynchronized, thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life, leaving patients incapacitated. Repetitive transcranial magnetic stimulation is a cost-effective, neuro-modulatory technique used for multiple neurological conditions. Over the past two decades, it has been widely used to predict cognitive decline; identify pathophysiological markers; promote neuroplasticity; and assess brain excitability, plasticity, and connectivity. It has also been applied to patients with dementia, because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult. However, its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies. This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment, evaluate its effects on synaptic plasticity, and identify the associated mechanisms. This review essentially focuses on changes in the pathology, amyloidogenesis, and clearance pathways, given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer's disease. Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription, which are closely related to the neural regeneration process, are also highlighted. Finally, we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation, with the aim to highlight future directions for better clinical translations.

Altered connectivity between frontal cortex and supplementary motor area in various types of Parkinson's disease.

BACKGROUND: Tremor-dominant (TD) and postural instability/gait difficulty (PIGD) are common subtypes of Parkinson's disease, each with distinct clinical manifestations and prognoses. The neural mechanisms underlying these subtypes remain unclear. This study aimed to investigate the altered connectivity of the frontal cortex and supplementary motor area (SMA) in different types of Parkinson's disease. METHODS: Data of 173 participants, including 41 TD patients, 65 PIGD patients, and 67 healthy controls, were retrospectively analyzed. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical assessments. Differences in amplitude of low frequency fluctuation (ALFF), voxel-wise functional connectivity (FC), and functional network connectivity (FNC) among the three groups were compared, followed by partial correlation analysis. RESULTS: Compared to healthy controls, the left dorsolateral superior frontal gyrus (DLSFG) ALFF was significantly increased in both PIGD and TD patients. The FC between the left DLSFG and the left SMA, as well as between the left paracentral lobule and the right DLSFG, was significantly decreased. Similarly, the FNC between the visual network and the auditory network was reduced. Compared to TD patients, PIGD patients showed a significantly higher ALFF in the left DLSFG and a notably reduced FC between the left DLSFG and left SMA. Additionally, the FC of the left DLSFG-SMA was inversely correlated with the PIGD score exclusively in PIGD patients. The FNC of the visual-auditory network was inversely associated with the tremor score only in TD patients. CONCLUSION: Decreases in the left DLSFG-SMA connectivity may be a key feature of the PIGD subtype, while reduced VN-AUD connectivity may characterize the TD subtype.

Differential symptom cluster responses and predictors to repetitive transcranial magnetic stimulation treatment in Parkinson's disease: A retrospective study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective noninvasive neuromodulation technique for Parkinson's disease (PD). However, the efficacy of rTMS varies widely between individuals. This study aimed to investigate the factors related to the response to rTMS in PD patients. Methods: We retrospectively analyzed the response of 70 idiopathic PD patients who underwent rTMS for 14 consecutive days targeting the supplementary motor area (SMA) in either an open-label trail (n = 31) or a randomized, double-blind, placebo-controlled trial (RCT) (n = 39). The motor symptoms of PD patients were assessed by the United Parkinson's Disease Rating Scale Part III (UPDRSIII). Based on previous studies, the UPDRSIII were divided into six symptom clusters: axial dysfunction, resting tremor, rigidity, bradykinesia affecting right and left extremities, and postural tremor. Subsequently, the efficacy of rTMS to different motor symptom clusters and clinical predictors were analyzed in these two trails. Results: After 14 days of treatment, only the total UPDRSIII scores and rigidity scores improved in both the open-label trial and the RCT. The results of multiple linear regression analysis indicated that baseline rigidity scores (ß = 0.37, p = 0.047) and RMT (ß = 0.30, P = 0.02) positively predicted the improvement of UPDRSIII. The baseline rigidity score (ß = 0.55, P < 0.0001) was identified as an independent factor to predict the improvement of rigidity. Conclusion: This study demonstrated significant improvements in total UPDRSIII scores and rigidity after 14-day treatment, with baseline rigidity scores and RMT identified as predictors of treatment response, underscoring the need for individualized therapy.

Brain functional specialization and cooperation in Alzheimer's disease.

BACKGROUND: Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. OBJECTIVE: This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty-four clinically diagnosed AD patients and 52 age- and sex-matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). RESULTS: In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging-cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine-based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave-one-out cross-validation. CONCLUSION: This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD.

A Study on the Effect of Executive Control Network Functional Connection on the Therapeutic Efficacy of Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by brain network dysfunction. Few studies have investigated whether the functional connections between executive control networks (ECN) and other brain regions can predict the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS). Objective: The purpose of this study is to examine the relationship between the functional connectivity (FC) within ECN networks and the efficacy of rTMS. Methods: We recruited AD patients for rTMS treatment. We established an ECN using baseline period fMRI data and conducted an analysis of the ECN's FC throughout the brain. Concurrently, the support vector regression (SVR) method was employed to project post-rTMS cognitive scores, utilizing the connectional attributes of the ECN as predictive markers. Results: The average age of the patients was 66.86±8.44 years, with 8 males and 13 females. Significant improvement on most cognitive measures. We use ECN connectivity and brain region functions in baseline patients as features for SVR model training and fitting. The SVR model could demonstrate significant predictability for changes in Montreal Cognitive Assessment scores among AD patients after rTMS treatment. The brain regions that contributed most to the prediction of the model (the top 10% of weights) were located in the medial temporal lobe, middle temporal gyrus, frontal lobe, parietal lobe and occipital lobe. Conclusions: The stronger the antagonism between ECN and parieto-occipital lobe function, the better the prediction of cognitive improvement; the stronger the synergy between ECN and fronto-temporal lobe function, the better the prediction of cognitive improvement.

Design, synthesis, biological evaluation of novel piperidine-based derivatives as potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a crucial member of DNA repair enzymes responsible for repairing DNA single-strand breaks. Developing PARP inhibitors based on synthetic lethality strategies is an effective approach for treating breast cancer and other diseases. In this study, a series of novel piperidine-based benzamide derivatives were designed and synthesized using structure-based drug design principles. The anticancer activities of these compounds were evaluated against five human cancer cell lines (MDA-MB-436, CAPAN-1, SW-620, HepG2, SKOV3, and PC3) and the preliminary structure-activity relationships were delineated. Among the compounds, 6a and 15d demonstrated potent antiproliferative effects against MDA-MB-436 cells with IC50 values of 8.56 ± 1.07 µM and 6.99 ± 2.62 µM, respectively. Furthermore, both compounds exhibited excellent inhibitory activity against PARP-1, with IC50 values of 8.33 nM and 12.02 nM, respectively. Mechanistic investigations revealed that 6a and 15d effectively inhibited colony formation and cell migration of HCT116 cells. Moreover, they induced apoptosis by upregulating the expression of Bax and cleaved Caspase-3, while downregulating the expression of Caspase-3 and Bcl-2 in HCT116 cells. Based on its impressive pharmacodynamic data in vitro, we conducted a study to evaluate the efficacy of 15d in a xenograft tumor model in mice when used in combination with cytotoxic agents. Collectively, these findings suggest that 15d could be promising drug candidates worthy of further investigation.

Abnormal EEG microstates in Alzheimer's disease: predictors of ß-amyloid deposition degree and disease classification.

Electroencephalography (EEG) microstates are used to study cognitive processes and brain disease-related changes. However, dysfunctional patterns of microstate dynamics in Alzheimer's disease (AD) remain uncertain. To investigate microstate changes in AD using EEG and assess their association with cognitive function and pathological changes in cerebrospinal fluid (CSF). We enrolled 56 patients with AD and 38 age- and sex-matched healthy controls (HC). All participants underwent various neuropsychological assessments and resting-state EEG recordings. Patients with AD also underwent CSF examinations to assess biomarkers related to the disease. Stepwise regression was used to analyze the relationship between changes in microstate patterns and CSF biomarkers. Receiver operating characteristics analysis was used to assess the potential of these microstate patterns as diagnostic predictors for AD. Compared with HC, patients with AD exhibited longer durations of microstates C and D, along with a decreased occurrence of microstate B. These microstate pattern changes were associated with Stroop Color Word Test and Activities of Daily Living scale scores (all P < 0.05). Mean duration, occurrences of microstate B, and mean occurrence were correlated with CSF Aß 1-42 levels, while duration of microstate C was correlated with CSF Aß 1-40 levels in AD (all P < 0.05). EEG microstates are used to predict AD classification with moderate accuracy. Changes in EEG microstate patterns in patients with AD correlate with cognition and disease severity, relate to Aß deposition, and may be useful predictors for disease classification.

Using scalp EEG to predict seizure recurrence and electrical status epilepticus in children with idiopathic focal epilepsy.

PURPOSE: Some individuals with idiopathic focal epilepsy (IFE) experience recurring seizures accompanied by the evolution of electrical status epilepticus during sleep (ESES). Here, we aimed to develop a predictor for the early detection of seizure recurrence with ESES in children with IFE using resting state electroencephalogram (EEG) data. METHODS: The study group included 15 IFE patients who developed seizure recurrence with ESES. There were 17 children in the control group who did not experience seizure recurrence with ESES during at least 2-year follow-up. We used the degree value of the partial directed coherence (PDC) from the EEG data to predict seizure recurrence with ESES via 6 machine learning (ML) algorithms. RESULTS: Among the models, the Xgboost Classifier (XGBC) model achieved the highest specificity of 0.90, and a remarkable sensitivity and accuracy of 0.80 and 0.85, respectively. The CATC showed balanced performance with a specificity of 0.85, sensitivity of 0.73, and an accuracy of 0.80, with an AUC equal to 0.78. For both of these models, F4, Fz and T4 were the overlaps of the top 4 features. CONCLUSIONS: Considering its high classification accuracy, the XGBC model is an effective and quantitative tool for predicting seizure recurrence with ESES evolution in IFE patients. We developed an ML-based tool for predicting the development of IFE using resting state EEG data. This could facilitate the diagnosis and treatment of patients with IFE.

Deep Brain Stimulation Modulates the Visual Pathway to Improve Freezing of Gait in Parkinson's Disease Patients.

OBJECTIVE: To investigate the involvement of the visual cortex in improving freezing of gait (FoG) after subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients using whole-brain seed-based functional connectivity. METHODS: A total of 66 PD patients with FoG who underwent bilateral STN-DBS were included in our study. Patients were divided into a FoG responder group and an FoG nonresponder group according to whether FoG improved 1 year after DBS. We compared the differences in clinical characteristics, brain structural imaging, and seed-based functional connectivity between the 2 groups. The locations of active contacts were further analyzed. RESULTS: All PD patients benefited from STN-DBS. No significant differences in the baseline characteristics or brain structures were found between the 2 groups. Seed-based functional connectivity analysis revealed that better connectivity in bilateral primary visual areas was associated with better clinical improvement in FoG (P < 0.05 familywise error corrected). Further analysis revealed that this disparity was associated with the location of the active contacts within the rostral region of the sensorimotor subregion in the FoG responder group, in contrast to the findings in the FoG nonresponder group. CONCLUSIONS: This study suggested that DBS in the rostral region of the STN sensorimotor subregion may alleviate FoG by strengthening functional connectivity in primary visual areas, which has significant implications for guiding surgical strategies for FoG in the future.

A Zeolitic Octahedral Metal Oxide with Ultrahigh Porosity for High-temperature and High-humidity Alkyne/Alkene Separation.

Zeolitic octahedral metal oxide is a newly synthesized all-inorganic zeolitic material and has been used for adsorption, separation, and catalysis. Herein, a new zeolitic octahedral metal oxide was synthesized and characterized. The porous framework was established through the assembly of [P2Mo13O50] clusters with PO4 linkers. Guest molecules occupied the framework, which could be removed through heat treatment, thereby opening the micropores. The pore characteristics were controlled by the cations within the micropore, enabling the adjustment of the interactions with alkynes and alkenes. This resulted in good separation performance of ethylene/acetylene and propylene/propyne even under high temperature and humidity conditions. The high stability of the material enabled the efficient recovery and reuse without discernible loss in the separation performance. Due to the relatively weak interaction between the adsorbed alkyne and the framework, the adsorbent facilitated the recovery of a highly pure alkyne. This feature enhances the practical applicability of the material in various industrial processes.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Metagenome reveals the possible mechanism that microbial strains promote methanogenesis during anaerobic digestion of food waste.

For better understanding the mechanism of microbial strains promoting methane production, four strains Hungatella xylanolytica A5, Bacillus licheniformis B1, Paraclostridium benzoelyticum C2 and Advenella faeciporci E1 were inoculated into anaerobic digestion systems. After bioaugmentation, the cumulative methane production of A5, B1, C2 and E1 groups elevated by 11.68%, 8.20%, 18.21% and 15.67% compared to CK group, respectively. The metagenomic analysis revealed that the species diversity and uniformity of the experimental groups was improved, and hydrolytic acidifying bacteria, represented by Clostridiaceae, Anaerolineaceae and Oscillospiraceae, and methanogens, such as Methanotrichaceae and Methanobacteriaceae, were enriched. Meanwhile, the abundance of key genes in carbohydrate, pyruvate and methane metabolism was increased in the inoculated groups, providing reasonable reasons for more methane production. The strengthening mechanism of microbial strains in this study offered a theoretical foundation for selecting a suitable bioaugmentation strategy to solve the problems of slow start-up and low methane production in anaerobic digestion.

A pig model of symptomatic spinal epidural hematoma.

PURPOSE: The purpose of this study was to establish an animal model capable of simulating the development and decompression process of symptomatic spinal epidural hematoma (SSEH). METHODS: A total of 16 male Bama miniature pigs were included in this study and randomly allocated into four groups: Group A (4 h 20 mmHg hematoma compression), Group B (4 h 24 mmHg hematoma compression), Group C (4 h 28 mmHg hematoma compression), and Group Sham (control). Real-time intra-wound hematoma compression values were obtained using the principle of connectors. Electrophysiological analyses, including the latency and amplitude of somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP), along with behavioral observations (Tarlov score), were performed to assess this model. RESULTS: ANOVA tests demonstrated significant differences in the latency and relative amplitude of SSEP and MEP between Groups C and Sham after 4 h of hematoma compression and one month after surgery (P < 0.01). Behavioral assessments 8 h after surgery indicated that animals subjected to 28 mmHg hematoma compression suffered the most severe spinal cord injury. Pearson correlation coefficient test suggested a negative correlation between the epidural pressure and Tarlov score (r = -0.700, p < 0.001). With the progression of compression and the escalation of epidural pressure, the latency of SSEP and MEP gradually increased, while the relative amplitude gradually decreased. CONCLUSIONS: When the epidural pressure reaches approximately 24 mmHg, the spinal cord function occurs progressive dysfunction. Monitoring epidural pressure would be an effective approach to assist to identify the occurrence of postoperative SSEH.

Development and validation of a machine learning-based predictive model for assessing the 90-day prognostic outcome of patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is associated with significant mortality and morbidity. Predicting the prognosis of patients with sICH remains an important issue, which significantly affects treatment decisions. Utilizing readily available clinical parameters to anticipate the unfavorable prognosis of sICH patients holds notable clinical significance. This study employs five machine learning algorithms to establish a practical platform for the prediction of short-term prognostic outcomes in individuals afflicted with sICH. METHODS: Within the framework of this retrospective analysis, the model underwent training utilizing data gleaned from 413 cases from the training center, with subsequent validation employing data from external validation center. Comprehensive clinical information, laboratory analysis results, and imaging features pertaining to sICH patients were harnessed as training features for machine learning. We developed and validated the model efficacy using all the selected features of the patients using five models: Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), XGboost and LightGBM, respectively. The process of Recursive Feature Elimination (RFE) was executed for optimal feature screening. An internal five-fold cross-validation was employed to pinpoint the most suitable hyperparameters for the model, while an external five-fold cross-validation was implemented to discern the machine learning model demonstrating the superior average performance. Finally, the machine learning model with the best average performance is selected as our final model while using it for external validation. Evaluation of the machine learning model's performance was comprehensively conducted through the utilization of the ROC curve, accuracy, and other relevant indicators. The SHAP diagram was utilized to elucidate the variable importance within the model, culminating in the amalgamation of the above metrics to discern the most succinct features and establish a practical prognostic prediction platform. RESULTS: A total of 413 patients with sICH patients were collected in the training center, of which 180 were patients with poor prognosis. A total of 74 patients with sICH were collected in the external validation center, of which 26 were patients with poor prognosis. Within the training set, the test set AUC values for SVM, LR, RF, XGBoost, and LightGBM models were recorded as 0.87, 0.896, 0.916, 0.885, and 0.912, respectively. The best average performance of the machine learning models in the training set was the RF model (average AUC: 0.906 ± 0.029, P < 0.01). The model still maintains a good performance in the external validation center, with an AUC of 0.817 (95% CI 0.705-0.928). Pertaining to feature importance for short-term prognostic attributes of sICH patients, the NIHSS score reigned supreme, succeeded by AST, Age, white blood cell, and hematoma volume, among others. In culmination, guided by the RF model's variable importance weight and the model's ROC curve insights, the NIHSS score, AST, Age, white blood cell, and hematoma volume were integrated to forge a short-term prognostic prediction platform tailored for sICH patients. CONCLUSION: We constructed a prediction model based on the results of the RF model incorporating five clinically accessible predictors with reliable predictive efficacy for the short-term prognosis of sICH patients. Meanwhile, the performance of the external validation set was also more stable, which can be used for accurate prediction of short-term prognosis of sICH patients.

Report of Citrus tristeza virus in Diaphorina citri (Hemiotera: Liviidae) insects of different sexes, color morphs, and developmental stages.

Diaphorina citri, also known as the Asian citrus psyllid, is the main vector of 'Candidatus Liberibacter asiaticus' (CLas) associated with citrus Huanglongbing. It has been reported that D. citri could also be infected by Citrus tristeza virus (CTV), a virus that has been previously reported to be vectored by certain aphid species. In this study, the CTV and CLas profiles in different organs, color variants, developmental stages, or sexes of D. citri insects were analyzed. Although no significant differences were found between nymphs and adults in CTV titers, we found that the third instar nymph of D. citri was more efficient in CTV and CLas acquisition compared to the fourth and fifth instars and adults. With the instars of D. citri development, the relationship between the acquiring of CTV and CLas by D. citri seemed to follow an inverse trend, with the titer of CLas increased and the titer of CTV decreased. No significant differences were observed between the 2 sexes of D. citri in acquiring either CTV or CLas titers in the field. However, no differences were drawn among the 3 color morph variants for CTV titers. CTV titers in the midguts of adult D. citri were significantly higher than those in the salivary glands. Both CTV-positive incidence and CTV titers in the midguts of adult D. citri increased with increasing exposure periods. This study provides new data to deepen our understanding of the CTV-involved interaction between D. citri and CLas.

Patients with episodic migraine without aura have an increased rate of delayed discounting.

OBJECTIVE: This study aimed to explore decision-making impulsivity and its neural mechanisms in patients with episodic migraine without aura (EMoA). BACKGROUND: Previous evidence indicates increased impulsivity and altered reward processing in patients with chronic migraine and medication overuse; however, whether the same holds true for those with EMoA is unclear. METHODS: Patients newly diagnosed with EMoA (n = 51) and healthy controls (HC, n = 45) were recruited. All participants completed delay discounting task, cognitive assessments, a questionnaire for headache profile, and resting-state function magnetic resonance imaging scans. Resting-state functional connectivity (RSFC) between the regions of interest and the entire brain was explored. RESULTS: Patients with EMoA showed a steeper subjective discount rate than HCs (F = 4.74, p = .032), which was positively related to a history of migraines (r = .742, p < .001). RSFC among the ventral striatum (vSTR), ventromedial prefrontal cortex, and occipital cortex was lower in patients with EMoA than in control groups, which was correlated with history (r' = .294, p = .036) and subjective discount rate (r' = .380, p = .006). Additionally, discounting rates and RSFC between the vSTR and occipital regions were significantly abnormal in the triptan group than the non-triptan group. Mediating effect analysis indicated a significant mediating effect in the change in RSFC between the vSTR and occipital status, history of triptan use, and subjective discount rate. CONCLUSION: This study further elucidated that an increase in delayed discounting rate exists in patients with EMoA and is related to the abnormality of the value processing network.

MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder.

Background: Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive. Aims: To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression. Methods: Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression. Results: The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity. Conclusions: Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

[Clinical outcomes of 3D-printing stand-alone artificial vertebral body in anterior cervical surgeries].

OBJECTIVE: To explore the short-term outcomes of 3D-printing stand-alone artificial vertebral body (AVB) in the surgical procedure of anterior cervical corpectomy and fusion (ACCF). METHODS: Following the proposal of IDEAL (idea, development, exploration, assessment, and long-term follow-up) framework, we designed and conducted this single-armed, retrospective cohort study. The patients with cervical spondylotic myelopathy were recruited, and these patients exclusively received the surgical procedure of single-level ACCF in our single center. After the process of corpectomy, the size was tailored using different trials and the most suitable stand-alone AVB was then implanted. This AVB was manufactured by the fashion of 3D-printing. Two pairs of screws were inserted in an inclined way into the adjacent vertebral bodies, to stabilize the AVB. The participants were regularly followed-up after the operation. Their clinical data were thoroughly reviewed. We assessed the neurological status according to Japanese Orthopedic Association (JOA) scale. We determined the fusion based on imaging examination six months after the operation. The recorded clinical data were analyzed using specific software and they presented in suitable styles. Paired t test was employed in comparison analysis. RESULTS: In total, there were eleven patients being recruited eventually. The patients were all followed up over six months after the operation. The mean age of the cohort was (57.2±10.2) years. The mean operation time was (76.1±23.1) min and the median bleeding volume was 150 (100, 200) mL. The postoperative course was uneventful for all the cases. Dysphagia, emergent hematoma, and deterioration of neurological function did not occur. Mean JOA scores were 13.2±2.2 before the operation and 16.3±0.8 at the final follow-up, which were significantly different (P < 0.001). The mean recovery rate of neurological function was 85.9%. By comparing the imaging examinations postoperatively and six months after the operation, we found that the average subsidence length was (1.2±1.1) mm, and that there was only one cases (9.1%) of the severe subsidence (>3 mm). We observed significant improvement of cervical lordosis after the operation (P=0.013). All the cases obtained solid fusion. CONCLUSION: 3D-printing stand-alone AVB presented favorable short-term outcome in one-level ACCF in this study. The fusion rate of this zero-profile prosthesis was satisfactory and the complication rate was relatively low.

Comparison of En Bloc Resection and Intralesional Excision for Re-resection of Giant Cell Tumors of the Spine.

OBJECTIVE: Re-resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re-resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re-resection for giant cell tumors of the spine. METHODS: This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression-free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan-Meier estimator was used for survival analysis. RESULTS: A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19-63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p < 0.05). The 5- and 10-year local progression-free survival rates were both 90% in the en bloc resection group, while in the intralesional excision group, the 5-year local progression-free survival rate was 80% with a 10-year rate of 45.7%. The en bloc resection group had a lower local tumor recurrence rate than that of the intralesional excision group (p < 0.05), but the former had a higher rate of complications (p = 0.015). CONCLUSIONS: This study revealed a low local recurrence rate in patients who underwent en bloc resection for giant cell tumors, while the perioperative complication rate was high.

The targeting of DAPK1 with miR-190a-3p promotes autophagy in trophoblast cells.

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.