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*

Objective Hypobaric chamber and simulated weightless bed are essential methods for aerospace medical research,and conducting state assessment of volunteers before and after hypobaric chamber and simulated weightless bed tests is an essential guideline for aerospace implementation medicine.To further improve the efficiency of human condition assessment,in addition to the conventional biochemical and physiological indicators,the human oral exhaled gas can be used for condition assessment,and the olfactometry acquisition equipment and analysis software can collect and detect most volatile gases to complete the human oral exhaled gas data acquisition.Conducting comparative analysis of olfactory mapping data from different populations may be a means to assess the status of the body.Methods The olfactometry acquisition equipment was used to collect the oral exhaled breath olfactometry profiles of the general population,hypobaric cabin volunteers,and ambulatory volunteers.The olfactometry analysis software was used to calculate the 12 eigenvalues of the olfactometry profiles and the t-SNE downscaling,and the radar plots were used to analyze the olfactometry profiles of the general population,low-pressure cabin volunteers,and ambulatory volunteers respectively.A comparative analysis of different populations was conducted.Results(1)The t-SNE mapping data of the general population and the ambulatory volunteers were almost indistinguishable;(2)the t-SNE mapping data of the hypobaric cabin volunteers and the general population had a slight overlap,but the distinguishability of the vast majority of the t-SNE mapping data was obvious;(3)the t-SNE mapping data of the hypobaric cabin volunteers and the ambulatory volunteers were distinguishable with no overlap,and the ambulatory t SNE data are highly aggregated,and the distribution of t-SNE data in low-pressure cabin is more discrete;(4)there are 2-3 sensors with large eigenvalues and a large range of variation for both low-pressure cabin volunteers and recumbent volunteers after training activities,and the common sensor with a large range of variation is S6.Conclusion Olfactory diagnostic analysis mapping may be a means to assess the health status of the body and may be useful for spaceflight health status assessment in the future.The analysis and application of flight health state assessment can be a reference in the future.

Objective: To investigate the antidepressant effects of Yuanzhi (Polygalae Radix, PR) aqueous extract on chronic unpredictable mild stress (CUMS)-induced depression rat models and the underlying mechanisms. Methods: A total of 40 male Sprague Dawley (SD) rats were randomly divided into control, model, low dose of PR (PR-L, 0.5 g/kg), high dose of PR (PR-H, 1 g/kg), and fluoxetine (10 mg/kg) groups, with 8 rats in each group. Except for the rats in control group, those in the other four groups underwent CUMS-induced depression modeling. PR and fluoxetine were administered intragastrically once daily, 30 min prior to the CUMS procedure, for 14 consecutive days until the behavioral tests were performed. After CUMS modeling, the sucrose preference test (SPT), open field test (OFT), novelty-suppressed feeding test (NSFT), forced swim test (FST), and tail suspension test (TST) were employed to assess the pharmacological effects of PR on the mitigation of depressive-like behaviors in rat models. Additionally, the enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the rats. Western blot analysis was also conducted to evaluate the protein expression levels of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and caspase-1 in the hippocampal tissues of the rats. Immunofluorescence staining was performed to observe the morphological changes in ionized calcium-binding adapter molecule 1positive (Iba-1+) cells in the dentate gyrus (DG) of rats with CUMS-induced depression. Result: (i) Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests (P < 0.01 and P < 0.05, respectively). Post-administration of PR-H and fluoxetine also led to statistically significant increase in sucrose preference among rats (P < 0.05). Besides, PR-L, PR-H, and fluoxetine treatment markedly decreased the latency of ingestion (P < 0.05, P < 0.05, and P < 0.01, respectively). As observed from the FST, PR-L, PR-H, and fluoxetine presented antidepressant effects on rats with CUMS-induced depression, leading to the reduction in time of their immobility (P < 0.05, P < 0.01, and P < 0.01, respectively). The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well (P < 0.01). (ii) Rats in model group showed an increase in the levels of Iba-1+ microglia in their left and right brains in comparison with control group (P < 0.01). However, such increase was negated post PR treatment (P < 0.01). Treatment with PR-L, PR-H, and fluoxetine considerably reduced the levels of inflammatory factors (TNF-α, IL-1β, and IL-6, P < 0.01). In addition, treatment of PR-L and PR-H effectively counteracted the elevated levels of NLRP3, ASC, and caspase-1, and markedly down-regulated the expression levels of phosphorylated p65 (p-p65), COX-2, and iNOS in rats’ hippocampus (P < 0.01). Conclusion Collectively, these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

Objective To develop a Traditional Chinese Medicine(TCM)syndrome diagnosis scale suitable for evaluating the overall health status of participants in long-term simulated weightlessness experiments,and preliminarily evaluate its reliability and validity.Methods Based on the understanding of the pathogenesis of TCM in different stages of long-term manned spaceflight,a scale was developed through literature research and expert consultation.Test-retest reliability and internal consistency coefficient were used to test the reliability of the scale.Item analysis and factor principal component analysis were used to evaluate the validity of the scale,and a rotating component matrix was used to analyze the correlation between each item and dimension using 36 volunteers in a 90 days head down bed rest experiment as the research subjects.Results The scale contains eight dimensions and 57 items.The reliability analysis showed that the correlation coefficient of the total score of the scale for the first and second tests of 30 participants was 0.889,indicating high stability of the scale.The Cronbach coefficient of the scale was 0.934,indicating very good internal consistency.The split half reliability after correction was 0.858,indicating a high reliability of the scale.The validity analysis showed that the difference between the high score group and the low score one for each of the 57 items was statistically significant(P<0.01),and the Pearson correlation coefficient between each item and the total score of the scale was greater than 0.4(P<0.001).The cumulative contribution rate of 8 common factors extracted using principal component factor analysis was 55.293%,and the results of rotating component matrix analysis,after applying TCM theory and expert feedback,had a coincidence of up to 87.5%with the initial 8 dimensions,indicating good structural validity of the scale.Conclusion The scale has good reliability and validity,and can diagnose TCM syndromes.It is suitable for long-term simulated weightlessness experiment and provides an objective and quantitative new method for evaluating the subjective feelings of participants.

Objective To study traditional Chinese medicine(TCM)syndrome pattern of astronauts in long term spaceflight,and to summarize and elucidate the characteristics and evolvement of their holistic functional status based on TCM Pattern Identification and Classification System.Methods The Digital TCM Diagnostic Instrument and TCM Syndrome Diagnosis Scale were used to collect information from 9 astronauts in three manned missions of China Space Station,through diagnostic methods of observation,palpation and inquiry according to CM theory.Data collection was performed at various stages before,during,and after spaceflight,a total of 32 person-time digital images of tongues and facial complexion and over 2 000 data were collected.Through data mining and analysis using four diagnostic feature fusion methods,the distribution characteristics of TCM pattern among astronauts at different stages of flight and with different physical constitutions were proposed,and the health status and evolution trend of astronauts were evaluated based on the health concept of TCM.Results ⑴The astronauts showed related manifestations of 8 TCM syndromes during long term flight,among which 4 syndromes had higher scores,including Liver Depression Transforming into Fire,Liver and Kidney Yin Deficiency,Heart Kidney Disharmony,and Spleen and Kidney Yang Deficiency.However,their syndrome differentiation were mainly based on Yin and Yang in equilibrium,with only a few individuals showing a brief deviation from the equilibrium state at a certain stage.After long-term adaptation and adjustment,they almost had returned to a state of Yin-Yang equilibrium reestablishment.⑵As the flight time increased,the proportion of Liver Depression Transforming into Fire and Qi and Blood Deficiency in Heart and Spleen syndrome increased month by month,indicating that the psychological and emotional changes and insufficient Qi and blood status during long term flight need to be focused on.⑶Physical constitution had a certain impact on the syndrome patterns during flight,the astronauts with biased constitutions had significantly higher total scores for all syndrome patterns than that of individuals with Normal-constitution,astronauts with Yin deficiency had slightly higher scores for Heart Kidney Disharmony than those with Yang(Qi)deficiency,indicating that personalized TCM conditioning measures should be developed based on the pathogenesis of TCM syndrome during different flight periods,combined with factors such as physical constitution,etc.Conclusion The research has verified the scientific nature and effectiveness of TCM pattern analysis based on"four diagnostic"methods,which could be used for achieving quantitative and comprehensive evaluation of astronaut health status from the perspective of TCM in long-term space flight.

Objective : To evaluate the effect of platelet-rich fibrin (PRF) on orthodontic tooth movement (OTM) and to provide a basis for clinical application. Methods: Literature searches were conducted in 7 electronic databases supplemented with a hand search. Randomized controlled trials focusing on OTM with PRF were included. The risk of bias was assessed by the Cochrane tool. Finally, due to the heterogeneity of patient clinical characteristics and research methods, the results in every study were qualitatively described. Results: Six studies were included. Five studies were split-mouth designs, and 1 was a two-arm parallel design. Two studies used leukocyte- and platelet-rich fibrin, while the other 4 used injectable PRF. The risk of bias of 3 studies was graded as “Some concerns”, and 3 were graded as “Low risk”. The trials lasted from 4 weeks to 5 months. Four studies supported that PRF could accelerate OTM, 1 study demonstrated that PRF had no effect on OTM, and 1 study reported that PRF decreased OTM. There is moderate-quality evidence that PRF accelerates OTM in the first 3 months after application, while low-quality evidence supports that PRF loses its tooth-acceleration effect after 4 months. Conclusion Limited clinical evidence suggests that PRF could accelerate OTM in the early stages, but its long-term effect needs clarification.

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 discuss the diagnostic value of a diagnostic strategy combining D-dimer and aortic dissection detection risk score (ADDRS) for patients with acute aortic dissection (AAD). Methods The clinical data of 750 patients with suspected AAD in emergency department of Zhongda Hospital Affiliated to Southeast University from January 2016 to January 2018 were retrospectively analyzed, including medical history, gender, age, chief complaint, physical examination, diagnostic imaging data and D-dimer levels on admission. ADDRS = 0 was defined as low risk group, ADDRS = 1 as medium risk group, ADDRS≤1 as non-high risk group,whereas ADDRS > 1 as high risk group. The clinical characteristics of AAD and non-AAD patients, ADDRS, D-dimer, and the diagnostic ability of D-dimer (the cutoff value of 500 μg/L) for AAD in different risk groups were observed. Results AAD was diagnosed in 79 of 750 (10.53%) patients. Of the 256 (34.13%) patients in low risk group, 5 patients were diagnosed with AAD. The medium risk group had 337 (44.93%) patients, including 44 cases with AAD. The high risk group had 157 (20.93%) patients, including 30 cases with AAD. In AAD patients, the proportion of male and hypertension, the incidence of ADDRS risk markers (including abrupt onset of pain, severe pain intensity, ripping or tearing pain, pulse deficit or systolic blood pressure differential of upper limb, focal neurological deficit, recent aortic manipulation, known thoracic aortic aneurysm) and the D-dimer levels in AAD group were significantly higher than those of non-AAD patients [male: 82.28% (65/79) vs. 59.76% (401/671), hypertension: 81.01% (64/79) vs. 41.43% (278/671), abrupt onset of pain: 78.48% (62/79) vs. 39.94% (268/671), severe pain intensity: 78.48% (62/79) vs. 50.52% (339/671), ripping or tearing pain: 32.91% (26/79) vs. 0.75% (5/671), pulse deficit or systolic blood pressure differential of upper limb: 15.19% (12/79) vs. 0.15% (1/671), focal neurological deficit: 7.59% (6/79) vs. 1.64% (11/671), recent aortic manipulation: 6.33% (5/79) vs. 0.30% (2/671), known thoracic aortic aneurysm: 15.19% (12/79) vs. 0.30% (2/671), D-dimer (μg/L): 1 160 (588, 3 340) vs 135 (56, 478), all P < 0.05], the proportion of diabetics was significantly lower than that of non-AAD patients [7.59% (6/79) vs. 18.78% (126/671), P < 0.05]. The positive predictive values of D-dimer for AAD diagnosis in the low risk group and the non-high-risk groups (including low and medium risk groups) were lower than that in the high risk group (8.62%, 26.32% vs. 40.91%), the negative predictive values of D-dimer were higher in the low risk group and non-high-risk groups than that in the high risk group (100.00%, 99.05% vs. 96.70%), missed diagnosis rates were higher than that in high risk group (0, 0.95%, vs. 3.30%). Conclusion In the high risk group, D-dimer≥500 μg/L is helpful for diagnosis of AAD; and in low risk group or non-high-risk group, D-dimer < 500 μg/L can efficiently and accurately exclude AAD.

Objective To analyze the electrophysiological characteristics of Charcot-Marie-Tooth (CMT) disease 1A,1X,2A and myelin protein zero (MPZ)-related CMT in Chinese patients.Methods Baseline electrophysiological data from 36 CMT1A patients,78 CMT1X patients,31 CMT2A patients and 10 MPZ-related CMT patients in the Third Xiangya Hospital and Xiangya Hospital of Central South University during 2004-2018 were analyzed.Electrophysiological recordings were taken from the upper limbs (median nerve,ulnar nerve) and lower limbs (tibial nerve,peroneal nerve).Demyelination in different nerve segments was assessed by measurement of distal motor latency,motor nerve conduction velocity (MNCV),sensory nerve conduction velocity and F-wave latency,and calculation of conduction block,terminal latency index (TLI) and modified F ratio (MFR);Axonal degeneration was assessed by measuring compound motor action potential (CMAP) and sensory nerve action potential.The relationship between the gender,age at onset,duration,Overall Neuropathy Limitation Scale (ONLS) score and indexes of peripheral nerve electrophysiology was statistically analyzed.Results The peripheral nerves of CMT1A patients were characterized by uniform demyelination and axonal degeneration.MNCV ((21.39± 6.72) m/s) and CMAP amplitude (2.40 (3.50) mY) of median nerve of CMT1A patients were decreased.The peripheral nerves of CMT1X patients were also characterized by uniform demyelination and axonal degeneration.MNCV (35.20 (6.77) m/s) and CMAP amplitude (2.60 (3.79) mY) of median nerve of CMT1X patients were decreased.CMT2A patients showed axonal degeneration of the peripheral nerves and CMAP amplitude ((4.75 ±2.38) mV) of median nerve of CMT2A patients was decreased.The electrophysiological data in MPZ-related CMT patients demonstrated variability.The TLI and MFR for the median and ulnar nerves in these four subtypes were normal.MNCV (r=0.423,P=0.025) of median nerve in CMT1A patients was positively correlated with age at onset.MNCV (r=0.782,P=-0.013) of median nerve in MPZ-related CMT patients was positively correlated with age at onset.CMAP amplitude (r=0.652,P＜0.01) of median nerve in CMT2A patients was positively correlated with age at onset.Demyelination and axonal degeneration in male CMT1X patients were relatively more severe than those in female patients,and MNCV (Z=-3.300,P＜0.01) and CMAP amplitude (Z=-3.960,P＜0.01) of median nerve,MNCV (Z=-2.56,P=0.011) and CMAP amplitude (Z=-2.311,P=0.048) of ulnar nerve of male patients were lower than those of female patients.The ONLS score of CMT1A (r=-0.494,P＜0.01),CMT1X (r=-0.596,P＜0.01) and CMT2A patients (r=-0.494,P=0.012) was inversely associated with CMAP amplitude.Conclusions The electrophysiological characteristics of CMT1A,CMT1X,CMT2A and MPZ-related CMT are different.Electrophysiological examinations are the basis of clinical classification and could provide guidance for further genetic testing and diagnosis.CMAP amplitude may serve as an objective index to assess the severity of functional disability in CMT patients.

OBJECTIVE： To investigate the formulation of therapy plan and pharmaceutical care for a penicillin allergic patient with necrotizing fasciitis combined with diabetes mellitus. METHODS： A penicillin allergic patient with necrotizing fasciitis combined with diabetes mellitus was admitted to Ordos central hospital on March 30， 2018. According to the disease characteristics of the patient， clinical pharmacists conducted pharmaceutical care during the treatment process from the aspects of antiinfective drugs selection， monitoring points of necrotizing fasciitis， blood glucose monitoring， effects of hypoproteinemia on antibiotic pharmacokinetics-pharmacodynamics， and assisted the physician to develop a more reasonable and effective individualized therapentic regimen. RESULTS： For diabetes mellitus， the patient adjusted Insulin lispro injection （insulin pump）， Acarbose tablets， Metformin hydrochloride tablets and Glimepiride tablets successively. For rapid atrial fibrillation with intraventricular differential conduction and ST-T changes， Metoprolol tartrate tablets were used to reduce heart rate. For necrotizing fasciitis， when choosing drugs to ensure the anti-infective effect， considering that the patient had penicillin allergic and hypoproteinemia， clinical pharmacists chose drugs with low protein binding rates and different from the mother nucleus and side chain of penicillin. Imipenem cilastatin for injection， Aztreonam for injection， Levofloxacin lactate and sodium chloride injection were used successively. Voriconazole for injection was adopted for anti-fungal treatment. Physicians adopted the suggestions of clinical pharmacists. Debridement through early thorough drainage and rational drug use， the patient’s condition was effectively controlled. CONCLUSIONS： Clinical pharmacists assist physicians to formulate and optimize whole course therapentic regimen so as to improve the safety and effectiveness of drug treatment.