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*

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.
Electrons ; Energy Metabolism ; Glucose ; Glycolysis ; Humans ; Neoplasms

Objective: To investigate the application value of real-time virtual sonography(RVS)in the diagnosis and treatment of complicated hepatolithiasis. Methods: The retrospective and descriptive study was conducted. The clinical data of 10 patients with complicated hepatolithiasis who were admitted to Hunan Provincial People′s Hospital between October 2017 and March 2018 were collected. There were 3 males and 7 females, aged from 40 to 69 years, with an average age of 57 years. Patients received abdominal color Doppler ultrasound examination, magnetic resonance cholangiopancreatography, and upper abdominal spiral computed tomography (CT) thinly scanning + enhanced examination. Data of CT examination were imported into RVS. RVS was used to locate hepatolithiasis, relationship between stones and vessels, anatomy of bile ducts and vessels in hepatic hilus. Surgical methods included RVS-guided hilar cholangiotomy, biliary stricturoplasty, bilateral hepatojejunostomy, hepatic segmentectomy (lobectomy), and hepatolithotomy. Observation indicators: (1) surgical and postoperative situations; (2) typical case analysis; (3) follow-up. Follow-up using outpatient examination was performed to detect residual stones up to June 2019. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results: (1) Surgical and postoperative situations: 10 patients underwent RVS-guided surgeries successfully for complicated hepatolithiasis, with successful match in RVS (difference between CT images and ultrosound images <2 mm). No residual stone was identified by choledochoscope during operation. The operation time and volume of intraoperative blood loss were 285 minutes (range, 210-360 minutes) and 200 mL (range, 100-600 mL), respectively. No blood transfusion was needed during the operations. The duration of hospital stay was 20.5 days (range, 14.0-29.0 days). There was no perioperative death. One patient had postoperative biliary leakage and abdominal infection, and was cured after conservative treatment. (2) Typical case analysis: the tenth patient, female, 60 years old, was diagnosed with complicated hepatolithiasis, and was prepared to undergo hepatolithotomy+ quadrate lobectomy and hilar cholangioplasty+ bilateral hepatojejunostomy. Preoperative CT images and intraoperative color Doppler ultrasound images of the patient were fused and matched on the sagittal section of the portal vein and the cross section of the right branch of portal vein, and stones and important vessels were marked on the images. After accurate positioning, a curette was used to remove the stones. Removal of biliary stones through hepatic parenchyma and peripheral dilated bile ducts was conducted at the site where stones obviously existed. After the stones were removed, the intrahepatic bile duct and hilar bile duct merged. The left end of the bile duct split was confirmed by real-time ultrasound. After location of portal vein was determined by ultrasound, vascular plastic surgery was perfomed to avoid stenosis. (3) Follow-up: 10 patients were followed up for 6-12 months, with a median follow-up time of 8 months. One of 10 patients was suspected residual stones at the right peripheral hepatic anterior lobe by postoperative angiography at 2 months after surgery, and was not removed stones by choledochoscope. The patient had no recurrent symptoms after T-tube removal. The other 9 patients had no residual stones. Conclusion RVS applied in complicated hepatolithiasis is helpful for the precise intraoperative diagnosis, and the surgical treatment can be safe and effective.

Objective To study the incidence,possible risk factors,and influence on patient outcomes of diaphragmatic dysfunction in patients after surgical treatment of type A aortic dissection using ultrasound.Methods Patients who received replacement of hemiarch or total arch with concomitant procedures concerning aortic pathology,and an elephant trunk procedure for the descending aorta were prospectively enrolled in this study from February to May 2017.After surgery,they were transferred to the cardiac surgical intensive care unit.They were divided into two groups based on diaphragmatic excursion:diaphragmatic dysfunction (DD) group and diaphragmatic function normal (DN) grouBilateral diaphragmatic excursions were evaluated using ultrasound during spontaneous breathing trial by T-tube.The differences in demographic characteristics,operation-related variables and outcomes were compared between the two groups.Results A total of 42 patients were enrolled in this study,and 32 of them suffered from diaphragmatic dysfunctions.Compared with DN group,the excursion of the influenced diaphragm in DD group was significantly reduced[(0.450 ± 0.331)cm vs.(1.801 ± 0.616)cm,P＜0.01],while the excursion of the non-influenced diaphragm was not reduced[(2.013±0.655)cm vs.(1.801 ±0.616) cm,P=0.254].Diaphragmatic thickness was comparable [(0.184±0.028)cm vs.(0.189±0.028)cm,P=0.559 ] between the two groups while thickening fraction was significantly reduced in DD group[(4.67％±3.63)％ vs.(23.58％±10.69)％,P＜0.01].Meanwhile,respiratory rate was significantly higher in DD group as compared to DN group [(24.13 ± 4.98)times/min vs.(20.50 ± 3.17)times/min,P=0.037].Patients in DD group showed longer cross-clamp duration[(121.78±27.75)min vs.(93.10±18.84)min,P=0.004] and longer cardiopulmonary bypass duration [(208.09±32.78)min vs.(182.70±24.38)min,P=0.03] than patients in DN grouFurthermore,binary logistic analysis indicated that longer cross-clamp duration was the potential risk factor for diaphragmatic dysfunction after type A aortic dissection surgery.Mechanical ventilation duration was longer in DD group than in DN group (88 h vs.37 h,P=0.194) but without statistical significance.The usage of noninvasive ventilation was significantly increased in DD group as compared to DN group (46.88％ vs.10％,P=0.036).Other outcomes such as post-operative complications,mortality,ICU length of stay were comparable between the two groups.Conclusions Diaphragmatic dysfunction was very common after surgical treatment of type A aortic dissection.Longer duration of cross-clamp was considered as a potential risk factor of diaphragmatic dysfunction.A sequential management of noninvasive ventilation after extubation was feasible for diaphragmatic dysfunction after surgical treatment of type A aortic dissection.

[Abstract] Objective： ：To study the effects of IL-34 over-expression on malignant biological behavior of acute monocytic leukemia (AMoL) cells. Methods: The lentiviral vector pCDH-GFP for over-expressing IL-34 was constructed and infected into AMoL cell lines (THP1 and MOLM-13). Then its effects on proliferation, colony forming and cell cycle as well as apoptosis were tested by the MTS, colony formation assay and Annexin-V/PI staining, respectively. The cell differentiation phenotypes were assessed by fflow cytometry. Nude mice xenograft model was established to observe the tumor size and mass as well as the macrophages recruitment. Results: qPCR analysis showed that the expression of IL-34 mRNAin THP1-IL-34 and MOLM-13-IL-34 cells was nearly 4 000 and 3 000 folds higher than their respective control cells (all P<0.01), indicating that AMoL cell lines over-expressing IL-34 were successfully established. In vitro study showed that over-expression of IL-34 in AMoL cell lines promoted their proliferation potential(72 h:[0.738±0.003] vs [0.646±0.008]; [0.290±0.004] vs [0.247±0.004]; all P<0.01) and colony formation ([127.00 ± 3.37] vs [86.00±4.08]; [160.70±4.70] vs [116.70±3.93]; all P<0.01), whereas had little effect on apoptosis (all P>0.05). Over-expression of IL-34 promotedAMoLcell differentiation towards monocyte-macrophage lineage as the expressions of the monocyte-macrophage markers, CD11b and CD14, were increased whereas the expression of immature marker, CD71, was decreased in AMoL cell lines over-expressing IL-34(all P<0.05). Nude mice xenograft model showed that IL-34 over-expression stimulated macrophage recruitment in tumor tissues (P<0.01). Conclusion: Over-expression of IL-34 in human AMoL cell lines promotes their proliferation, colony forming potential and differentiation towards monocyte-macrophage lineage. Furthermore, IL-34 participates in the process of macrophages recruitment in vivo.

Objective To evaluate the imaging changes of the arterial wall and lumen at the site of intracranial large artery lesions with high-resolution magnetic resonance imaging (HR-MRI) before and after Wingspan stent implantation.Methods From December 2013 to December 2014,9 patients with symptomatic intracranial arterial stenosis (stenosis rate:70%-99%) admitted to the Department of Interventional Neuroradiology,Xuanwu Hospital,Capital Medical University were enrolled retrospectively.The sites of the lesions included middle cerebral arteries,basilar artery,and intracranial segment of vertebral artery.Head 3D HR-MRI technique was used to analyze and compare the changes of the tube-wall enhancement areas in the lesion sites through image registration and matching.The consistency of stenosis rates measured by HR-MRI and DSA was compared through Pearson correlation analysis and Bland-Altman Plot.Results The success rate of technique was 100% without related complications.(1) After Wingspan stent implantation,the gadolinium enhancement in the vascular walls of the stenosis sites was decreased significantly compared with that before procedure.The area of enhancement decreased was 87±16% after stent implantation compared with before implantation,and the difference was statistically significant (t=2.325,P=0.049).(2) Before stent implantation,the mean stenosis rates of the HR-MRI and DSA measurements were 82±6% and 82±8% respectively,and the difference was not statistically significant (t=0.051,P=0.961);after procedure,the mean stenosis rates of HR-MRI and DSA measurements were 16±12% and 21±12% respectively,and the difference was not statistically significant (t=1.345,P=0.216).(3) The Pearson correlation coefficients of HR-MRI and DSA for stenosis rate measurement before and after stent implantation were 0.347 (P=0.361) and 0.545 (P=0.129) respectively.Bland-Altman statistical images showed that most of the data points were within the consistency limit (x-±1.96 s).Conclusions As an in vivo noninvasive imaging means,HR-MRI can be used to assess the changes of vascular walls of the lesion sites,the vascular lumen,and the original plaques after the intracranial stent release.It can also be used to evaluate the reconstruction of intracranial arterial walls.

Objective To investigate the efficacy of dexmedetomidine on sedation in post-cardiac surgery patients with NIV intolerance.The changes of respiratory function and hemodynamics of the patients as well as non-invasive ventilation (NIV) failure rate were also under evaluation.Methods Thirty-five post-cardiac surgery patients with NIV intolerance and hypoxemia were enrolled in this prospective study.All patients were sedated with dexmedetomidine.NIV was standardized according to the uniform protocol.The main outcome was NIV success (avoiding endotracheal intubation) or NIV failure (requiring endotracheal intubation or die).The cardiorespiratory parameters (BP,HtR and RR) and artery blood gas analysis were prospectively recorded before and after sedation.The respiratory function and hemodynamics changes in both groups (NIV success group and NIV failure group) were then evaluated.Factors independently associated with NIV failure were identified using a logistic regression model.Results Twenty out of 35 patients (57.14％) survived while 15 (42.86％) patients failed NIV.After 1 h and 4 h of NIV with dexmedetomidine sedation,respiratory rate in both groups were decreased compared with baseline,especially in NIV success group.The PaO2/FiO2 was also improved after 1h and 4h of NIV treatment compared with baseline.The improvement was more significantly in NIV success group.The heart rate was decreased compared with baseline with no differences between two groups.There were no significant changes on PaCO2 and mean arterial pressure (MAP) during the treatment.The respiratory and hemodynamics variables identified as predictors of NIV failure were included in a multivariate logistic regression.RR ＞ 23 time/min (OR =3.2,95％ CI:2.043 ～ 4.301,P ＜ 0.01) 1 h after NIV,RR ＞ 20 time/min (OR =2.1,95％ CI:1.659～3.231,P=0.025) 4 h after NIV,PaO2/FiO2 ＜178 mmHg (OR=2.4,95％CI:1.892 ～ 3.287,P ＜0.01) 1 h after NIV and PaO2/FiO2 ＜ 185 mmHg (OR =1.7,95％ CI:1.243 ～ 2.365,P =0.041) 4 h after NIV independendy predicted NIV failure.Conclusions Dexmedetomidine might be considered as an effective and safe sedative for post-cardiac surgery patients with NIV intolerance.Early identification of predictors of NIV failure may facilitate early intervention.

Objective To investigate the relationship between renal vascular resistance index( RI) and serum Apelin level in type 2 diabetic mellitus ( T2DM )?Methods Seventeen cases newly diagnosed T2DM patients with RI increased but without microalbuminuraia in Minhang Hospital Affiliated to Fudan University from December 2011 to December 2014 were selected as observation group,17 newly diagnosed T2DM patients with RI normal during the same period were selected as control group?Fasting plasma glucose(FPG),glycosylated hemoglobin A1C(HbAlC),blood lipids and fasting insulin(FINS),hepatic functional and renal function were tested in all the subjects?Serum Apelin level was detected by enzyme?linked immunosorbent assay?Results Compared with control group,serum Apelin level was significantly higher in observation group((179?2±122?4)μg/L vs?(56?7±50?6) μg/L,t=3?814,P<0?05)?Partial correlation analysis showed that the RI was positive correlated with Apelin ( r= 0?364, P= 0?040 )?Conclusion The serum Apelin levels elevated in newly diagnosed T2DM patients with RI increased, and RI is positively correlated with Apelin, which indicate that Apelin play an important role in the pathophysiology of early renal damage in patients with TsDM.

Objective To analyze the separation and displacement of bone fragments in sagittal fracture of the mandibular condyle (SFMC),understand the motion type and guide clinical treatment and development of related surgical instruments.Methods Forty-five patients (52 sides) with SFMC treated between October 2008 and October 2012 were enrolled; 32 patients (36 sides) were males and 13 patients (16 sides) were females.According to the Neff classification,there were 20 sides with type A,28 sides type B and 4 sides type M.All the patients underwent CT scan and were classified based on measurements of distance and angle of displaced bone fragments.Results Patients were categorized into type Ⅰ on 20 sides (type Ⅰ A on 14 sides and type Ⅰ B on 6 sides),type Ⅱ on 27 sides (type Ⅱ A on 11 sides and type ⅡB on 16 sides),type ⅢB in 1 side and type Ⅳ in4 sides.Mean displacement of bone fragments was 12 mm (range,4-16 mm) ; mean deviation angle was 34°(range,11°-43°) ; mean descending distance was 13 mm (range,6-18 mm).Conclusion CT analysis results show that,mast bone fragments in SFMC move slightly.