BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Objective:To analyze the clinical features of adrenal metastases and summarize the experience of diagnosis and treatment.Methods:The clinicopathological data of 210 patients with adrenal metastases admitted to Peking Union Medical College Hospital from Jan. 1990 to Jun. 2021 were retrospectively analyzed, and the relevant literature was reviewed. The clinical characteristics, primary tumor types, imaging examination methods and diagnosis and treatment methods of adrenal metastases were summarized.Results:Among 210 patients, 153 were males and 57 were females, with an average age of (60±12) years. The average maximum diameter of the tumor was (4.7±2.6) cm, the maximum was 14.5 cm, and the minimum was 0.5 cm. Tumor occurred in 84 cases on the left, 81 cases on the right, and 44 cases bilateral. The primary tumors of 210 patients were 72 cases of lung cancer, 48 cases of renal cancer, 29 cases of hepatobiliary cancer, 18 cases of colorectal cancer, 11 cases of gastric esophageal cancer, 6 cases of pancreatic cancer, 5 cases of breast cancer, 3 cases of melanoma, and 18 cases of other tumors. 108 patients had no obvious clinical symptoms of discomfort, only found in the review of primary tumor or routine physical examination. 102 were primary disease-related symptoms, and 210 patients had no abnormal endocrine signs such as moon face and buffalo back. The median time from diagnosis of primary tumor to adrenal metastasis was 3 months. 95 cases were diagnosed with primary tumor at the same time. The longest time was 228 months. Of the 210 patients, 203 underwent CT, 99 PET-CT, 74 B-ultrasound and 25 MRI. A total of 122 patients were clinically diagnosed as adrenal metastasis by history and imaging examination. One patient was treated with adrenal photon knife, one patient was treated with adrenal artery embolization chemotherapy, and 21 patients were treated with adrenal radiotherapy or CT-guided adrenal radiofrequency ablation. A total of 88 patients were diagnosed as adrenal metastasis by histopathology. Among them, 12 patients were diagnosed by adrenal puncture under CT guidance, 74 patients were diagnosed by adrenal surgery, and 2 patients were further treated with metastatic tumor resection after adrenal metastasis was diagnosed by puncture. Finally, all patients were diagnosed as adrenal metastasis of malignant tumor by pathology, and they continued to be treated with primary tumor.Conclusions:Lung cancer is the most common type of primary adrenal metastases in our hospital. Most of the elderly men have no obvious endocrine-related symptoms and signs. CT is an effective means of examination, supplemented by B ultrasound or MRI diagnostic accuracy will be further improved, but the diagnosis still depends on histopathological examination. For patients with isolated adrenal metastasis, surgical treatment can significantly improve the prognosis. However, comprehensive treatment should be carried out according to the general situation of patients, the type and biological behavior of primary tumors, and the characteristics of metastatic tumors, so as to achieve the best curative effect.

Objective To optimize the simulation of the pathological characteristics and seizure behavior of medial temporal lobe epilepsy(MTLE),we aimed to establish a chronic epilepsy model of MTLE by unilateral,single hippocampal injection of kainic acid(KA)via stereotactic surgery,and to validate this epilepsy model in terms of behavior,electrophysiology,and pathology.Methods A total of 22 healthy C57BL/6 wild-type male mice were divided randomly into a control group(n=6)and an experimental group,which received KA injections(n=16).Both groups underwent microinjection of equal doses of saline or KA in the hippocampal CA3 area via stereotactic surgery.One week later,all mice were implanted with electrodes in the hippocampal CA3 area to facilitate electroencephalogram(EEG)recording.Seizure frequency and duration were analyzed statistically.The chronic epilepsy model was assessed in terms of behavior,electrophysiology,and pathology.Results No mice in the control group experienced seizures,while all surviving mice in the experimental group developed seizures.Adult model mice exhibited chronic spontaneous seizure behaviors,such as staring,chewing,head and facial muscle twitching,and limb spasms.Two mice died as a result of the surgery,four mice died during the acute seizure phase,and ten model mice were successfully established.EEG recordings showed epileptiform changes consistent with MTLE.Immunofluorescence staining revealed neuronal loss in the CA3 area and astrocytic changes,consistent with characteristic pathological changes of hippocampal sclerosis.Conclusions The model constructed by single unilateral intrahippocampal KA injection demonstrated several advantages such as being time-efficient,easy to operate,and reproducible.This model exhibited EEG,behavioral,and neuropathological changes similar to human MTLE,making it valuable for studying effective treatments for temporal lobe epilepsy and serving as an ideal animal model for predicting outcomes of epilepsy surgery.

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Objective:To evaluate the performance of a novel master-slave transurethral surgical robot system and test its safety and effectiveness.Methods:In September 2021, two urologists (A and B) applied transurethral surgery robot prototype on simulate human tissue model experiments. The transurethral surgical robotic systems used in this study include: master-end control platform, slave-end surgical platform, and end-effector. The main end control platform adopted Omega7 force feedback main hand as the main controller, and the degrees of freedom include: up and down translation, left and right translation, front and back translation, end rotation, end pitch, end swing, end operation. The end-operated surgical platform adopts the Med 7 seven-degree-of-freedom medical collaborative robotic arm to apply precision through the end effector operated resectoscope. The end effectors were modular in design for maximum compatibility with existing surgical instruments. The two doctors routinely assembled the resectoscope and the transurethral surgical robot 20 times each to calculate the assembly time. The routine assembly time of the resectoscope included the time when the lens and light source were connected after the resectoscope had been installed, and the doctor entered the experimental module with the resectoscope in hand. The time to assemble the surgical robot included the time to install the resectoscope with the end effector and connect the lens and light source to enter the experimental module. Two doctors performed 25 simulated prostate resection and 5 simulated bladder resection procedures. The small intestine, heart and stomach of pigs were sutured to construct urethra, prostate and bladder structures that simulated human body: urethra (pig small intestine) was 16-18 cm long, prostate (pig heart) size was about 5 cm×5 cm×6 cm, and bladder (pig stomach) capacity was 250-300 ml. The model was placed in a 3D printed sleeve to simulate the fitting of the urethra to the silicone penis. Prostate resection surgery: the doctor operated the handle on the main end control platform, controld the slave actuator through human-computer interaction, and excisesed the "prostate" around the fixed point under direct vision, simulating standard transurethral prostatectomy, the resection ranges from the bladder neck to the tip of the prostate, and the two lobes and middle lobes were removed. Each operation lasted 40 minutes and the weight of the removed tissue was recorded. Transurethral esection of the bladder: each procedure involved removal of the triangle, bilateral walls, and apical area of the bladder to record the occurrence of perforation. The accuracy of master-slave operating distance, operation attitude accuracy, master-slave operation attitude repeatability, fixed point accuracy, master-slave control start delay time and master-slave control following delay time, robotic arm swing range, limit site and other indicators of the robot were verified by surgery.Results:The positioning accuracy of the end effector of transurethral surgical robot was less than 0.5 mm, the accuracy of master-slave operation distance was ≤0.5 mmthe repeatability distance was ≤0.2 mm, the accuracy of master-slave operation attitude was a≤0.30°, the angle b≤0.30°, the angle C≤0.15°, the accuracy of the fixed point ≤is 0.6 mm, the maximum activity space of the robotic arm was a hemispherical space with a radius of (1 493±5)mm. The delay time of master-slave control startup and master-slave control follow-up delay time did not exceed 100ms; When the end of the manipulator was collided by an external force during the movement, the system could automatically stop the movement of the manipulator, at this time the external force was(70±7) N, and the fixed point setting range was 30-170 mm. The assembly time of transurethral surgery robot by Doctor A and Doctor B was (111.35±57.88) s and (111.70±58.30), respectively.The time of routine assembly resectoscope was (44.90±4.89) s and (44.90±5.16) s, respectively, and the difference between the routine assembly time and robot assembly time of Doctor A and Doctor B were not statistically significant( P=0.679 and P=0.996), the assembly time of the two doctor robots was more than the conventional assembly time( P=0.001 and P=0.001). The average weight of prostate tissue resection in experiments was (43.60±12.42)g and (43.45±12.63)g, respectively. No significant difference was found between them( P=0.954). During the simulated bladder electrosurgery, the robot system could successfully complete the resection of the triangular region, bilateral walls, and top tissues of the bladder. In the surgical experiment, the system operated smoothly, without mechanical failure, module damage, perforation, and other complications. Conclusions:The transurethral surgery robot might be a choice for transurethral surgery.

P1B-ATPases are a group of proteins that can transport heavy metal ions across membranes by hydrolyzing ATP and they are a subclass of the P-type ATPase family. It was found that P1B-ATPases are mainly responsible for the active transport of heavy metal ions in plants and play an important role in the regulation of heavy metal homeostasis in plants. In this paper, we dissusses the mechanism of P1B-ATPases from the structure and classification of P1B-ATPases, and review the current research progress in the function of P1B-ATPases, in order to provide reference for future research and application of P1B-ATPases in improving crop quality and ecological environment management.
Adenosine Triphosphatases/metabolism* ; Biological Transport ; Metals, Heavy ; Plants/enzymology*

Objective: To construct a scientific behavioral research of pasta matrix reaching task (PMRT) and comprehensively evaluate sensory-motor dysfunction caused by brain injury. Methods: Twenty-one SD rats were subjected to 14-days pasta matrix grasping training and then were randomly divided into model group (11 rats) and sham group (6 rats). Motor cortex ischemia was induced by injection of endothelin-1 in SD rats. The number of pasta grabed by the injured forelimb and the location in matrix were evaluated daily 7 days after surgery. The infarct volume was measured by Nissl staining at the 7 days, 14 days, and 28 days after stroke. Results: The number of pasta obtained by rats was reduced from (33.43±1.02) to (20.57±0.57) at 7 days post stroke in model group, and then increased to (26.85±0.98) at 28 days post stroke, although there was a significant difference between sham group(32.33±1.45) and ischemic group (t=3.198, P<0.05). The frequency of retrieval from each slot of the pasta matrix represented that sham group demonstrated a significant gain in performance in the antero quadrant of the matrix compared to ischemic rats by the fourth week after stroke.The stroke volume was decreased from (37.82±1.17)mm³ at 7 days post-stroke to (24.35±0.38)mm³ at 28 days post-stroke, indicating brain recovery from ischemic injury. Conclusion The pasta matrix reaching task can function as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies and focused rehabilitative training after stroke.

Objective To evaluate the effect of mitotane as a preoperative adjuvant therapy in advanced adrenocortical carcinoma.Methods Mitotane was used in 2 patients as preoperative adjuvant therapy.Case 1,a 24-year-old woman had Cushing's symptom for 1 year and presented with edema in both legs for 1 month.Computed tomography (CT) showed a solid mass in the right adrenal.It was about 10.0 cm×7.8 cm with calcification,and the boundary of tumor was not clear.Enhanced CT scan showed heterogeneous enhancement and there was a suspicious filling defect in the inferior vena cava.Biopsy of adrenal neoplasm was made and pathological result was adrenocortical tissue.The patient was diagnosed as right adrenocortical carcinoma with tumor thrombus in vena cava.Mitotane was used for 6 months.Case 2,a 42-year-old woman who underwent left adrenal adenoma resection 9 years ago,presented with Cushing's syndrome for 2 years,and found masses in left retroperitoneal and abdominal wall for 6 months.CT showed multiple nodular soft tissues with pitting calcification and fusion in it,locating between retroperitoneal spleen and kidney.The biggest section was approximately 8 cm× 12 cm,with a largest diameter of 14 cm.Enhanced scan showed uneven density wiht CT value of about 32 HU.Nodule shadows which were obviously strengthened were found in front of the right side of the diaphragmatic muscle.And some heterogeneous enhanced nodule shadows could be seen in front of the right abdominal peritoneal and muscle layer.The patient was diagnosed as right adrenocortical carcinoma with multiple metastases.Mitotane was used for treatment for 5 months.Results Both of their Cushing's symptom were significantly improved by taking drugs.The main side effects were nausea,vomiting,dizziness,fatigue,diarrhea and so on,but all could be alleviated after drug dosage adjustment.CT reexamination showed the volume of the primary lesion and metastases were significantly reduced.The postoperative pathological report after remove of the tumor and metastases showed adrenocortical carcinoma.Followed up for 42 and 7 months,the patients had no recurrence.Conclusions Mitotane is effectiveas preoperative adjuvant therapy in adrenocortical carcinoma and metastases.It can reduce the lesions significantly,relieve the Cushing's symptom,and provide opportunity for surgical treatment.