Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.

Anomalous pancreaticobiliary junction: image analysis and treatment principles

BACKGROUND: Anomalous pancreaticobiliary junction is often associated with biliary tract carcinoma and acute pan- creatitis. We assessed the value of image analysis in the diag- nosis of patients with anomalous pancreaticobiliary junction (APBJ) and the principles for the treatment of APBJ. METHODS: Sixty-four patients with APBJ were subjected to ultrasound imaging, endoscopic retrograde cholangio- pancreatography (ERCP) and magnetic resonance cholan- giopancreatography (MRCP) before surgery. The diagnos- tic accuracy of image analysis and their surgical outcomes were evaluated retrospectively. RESULTS: On ERCP and MRCP, the length of the com- mon channel was calculated to be 15 mm or longer in all patients, and the angle of the junction was more than 75° in 49 (76.6%) of the 64 patients. Of the 64 patients, 28 were defined of pancreatic duct type (P-C) (28/64, 43.75%), 32 bile duct type (C-P) (32/64, 50%), and 4 common chan- nel type (4/64, 6.25%). CONCLUSIONS: Patients with APBJ are often associated with biliary tract and pancreatic diseases, and early detec- tion and correct surgical treatment could avoid serious complications. ERCP and MRCP are accurate in the diag- nosis of APBJ.

Current surgical treatment of esophagogastric junction adenocarcinoma

The incidence of esophagogastric junction(EGJ)adenocarcinoma has shown an upward trend over the past several decades worldwide.In this article,we review previous studies and aimed to provide an update on the factors related to the surgical treatment of EGJ adenocarcinoma.The Siewert classification has implications for lymph node spread and is the most commonly used classification.Different types of EGJ cancer have different incidences of mediastinal and abdominal lymph node metastases,and different surgical approaches have unique advantages and disadvantages.Minimally invasive surgeries have been increasingly applied in clinical practice and show comparable oncologic outcomes.Endoscopic resection may be a good therapy for early EGJ cancer.Additionally,there is still a great need for well-designed,large RCTs to forward our knowledge on the surgical treatment of EGJ cancer.

Optimal treatment for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction: A retrospective cohort study with long-term follow-up

AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes.

Current status and future perspectives for the treatment of resectable locally advanced esophagogastric junction cancer:A narrative review

Incidence rates for esophagogastric junction cancer are rising rapidly worldwide possibly due to the economic development and demographic changes.Therefore,increased attention has been paid to the prevention,diagnosis,and the treatment of esophagogastric junction cancer.Although there are discrepancies in the treatment strategy between Asian and Western countries,surgery remains the mainstay of treatment for esophagogastric junction cancer.Recent developments of perioperative multidisciplinary treatment may lead to better therapeutic effect,higher complete resection rate,and better control of the residual diseases,thus result in prolonged prognosis.In this review,we will focus on the treatment of locally advanced resectable esophagogastric junction cancer,and discuss the current status and future perspectives of the perioperative treatment including chemotherapy,radiation therapy,and immunotherapy,as well as the surgical strategy.Better understanding of the latest treatment strategy and future overlook may enable to standardize and individualize the treatment for esophagogastric junction cancer,thus leading to better prognosis for those patients.

Immune checkpoint inhibitors for treatment of advanced gastric or gastroesophageal junction cancer:Current evidence and future perspectives

Despite the application of conventional therapies,the prognosis of advanced gastric cancer(GC)or gastroesophageal junction cancer(GEJC)is still poor.In recent years,immune checkpoint inhibitors(ICIs)have reshaped the paradigm of cancer therapy.Emerging evidence support the feasibility of programmed cell death-1(PD-1)and its ligand(PD-L1)inhibition in chemo-refractory GC/GEJC.Nivolumab and pembrolizumab have initially been approved in Japan and United States,respectively for the third-line treatment of progressive GC or GEJC.In March 2020,nivolumab has also been licensed in China for treating advanced GC/GEJC who received≥2 lines of systemic therapies.Current studies are moving forward to the first-line application or focusing on combination strategies,though data are insufficient and disputable.In this review,we summarize the recently reported and ongoing clinical trials in ICIs for advanced GC/GEJC.Molecular characteristics and clinical implications of different tumor subtypes are also reviewed.We further discuss the safety profile and biomarkers for predicting the response of ICIs,which has guiding values in clinical practice.

Efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in treatment of advanced gastric cancer or gastroesophageal junction cancer: A meta-analysis

BACKGROUND Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer(GC/GEJC), researchers have turned toward, with the support of promising clinical trials, anti-PD-1/anti-PD-L1 antibody therapy. But there are also different clinical trial results. To better assess its efficacy and safety, we integrated data from 13 eligible studies for a systematic review and meta-analysis.AIM To comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.METHODS PubMed, Web of Science, Cochrane Library,and EMBASE databases were searched to identify eligible articles with outcomes including objective response rate(ORR), disease control rate(DCR), overall survival(OS), progression-free survival(PFS), and adverse events(AEs) of anti-PD-1/anti-PD-L1 antibody therapy.RESULTS Our study encompassed a total of 13 trials totaling 1618 patients. The outcomes showed a pooled ORR and DCR of 15%(95% confidence interval [CI]: 14%-18%) and 40%(95%CI: 33%-46%), respectively. The pooled 6-mo OS and PFS were 54%(95%CI: 45%-64%) and 26%(95%CI: 20%-32%), respectively, and the 12-mo OS and PFS were 42%(95%CI: 21%-62%) and 11%(95%CI: 8%-13%), respectively. In addition, the incidence of any-grade AEs and grade ≥ 3 AEs was 64%(95%CI: 54%-73%) and 18%(95%CI: 16%-20%), respectively. Most importantly, PD-L1 positive patients exhibited a higher ORR rate than PD-L1 negative patients(odds ratio = 2.54, 95%CI: 1.56-4.15).CONCLUSION Anti-PD-1/anti-PD-L1 antibody therapy has shown promising anti-tumor efficacy with manageable AEs in advanced GC/GEJC patients, with PD-L1 overexpressing patients exhibiting a higher ORR. What is more, the clinical efficacy of anti-PD-1/PD-L1 combined with traditional chemotherapy drugs is even better, although the occurrence of AEs still causes considerate concerns.

The extent and value of lymphadenectomy in the surgical treatment of gastroesophageal junction carcinoma

Objective： We studied the extent and value of the lymphadenectomy in surgical treatment of carcinoma of gastroesophageal junction （GEJ）. Methods： 217 patients with GEJ who underwent surgical resection were retrospectively analyzed. The extent of lymphadenectomy was divided into 5 types （DO to D4） and the curability of operation was graded as A, B and C. Results： The patients had been treated as follows： 186 with proximal gastrectomy, 31 with total gastrectomy, 97 with a combined-visceral resection. The patients who underwent D1, D2 and D3 lymphadenectomy were respectively 158, 58 and 1. The patients who were performed with resection of grade A, B and C were 53, 107 and 57 respectively. All patients were performed with a lymphadenectomy and well registered. The lymph node metastasis occurred in 157 cases （72.4%）. The lymph node metastasis rate in the group 1, 2, 3, 4, 7, 9, 12 and 110 as well as in the pulmonary ligament group were higher than other groups. 2868 lymph nodes were removed, in which 655 （22.8%） demonstrated the existence of metastasis. The total lymph node metastatic degree in these groups was higher compared to the other groups. Conclusion： The survival rate in the D1 lymphadenectomy and D2 is similar for all patients, and there may be some differences in the 2nd and 3rd years for the DI lymphadenectomy and D2 in the stage-Ⅲb patients. The survival rate of D2 lymphadenectomy in stage Ⅲb is better than D1 and that of D2 lymphadenectomy is superior to D1 in stage-Ⅳ patients. The survival rate of grade A and B operation is much better than grade C, and the survival rate of grade A is also higher than B.

Evidence-based approach to the treatment of esophagogastric junction tumors

The incidence of esophagogastric junction(EGJ)adenocarcinoma is increasing in developed nations due to the rising prevalence of obesity and gastroesophageal reflux disease.Due to the peculiar location in a histological transition zone between the esophagus and the stomach,the management of EGJ tumors is controversial.Two main surgical approaches exist:total gastrectomy with distal esophagectomy or esophagectomy by either transhiatal or transthoracic approach.These operations differ significantly in the extent of lymphadenectomy.In addition,patients with locally advanced disease can receive either preoperative chemoradiation or perioperative chemotherapy.This evidence-based review analyzes current evidence regarding the management of EGJ tumors in order to help defining the best surgical and systemic treatment of these patients.

Versatile control of concentration gradients in non-fullerene acceptor-based bulk heterojunction films using solvent rinse treatments

Solvent rinse treatments using polar methanol(Me OH)and nonpolar n-hexane have been developed for controlling material concentration gradients along the longitudinal direction of non-fullerene acceptor-based bulk heterojunction(BHJ)films comprised of electron donor polymer,PBDB-T and acceptor,ITIC-m.Before the used solvents(chlorobenzene with 1 vol%DIO)were completely evaporated,ITIC-m rich domains were formed at the top surface of the BHJ films after they were rinsed with Me OH,as evidenced by water contact angle,atomic force microscopy,time-of-flight secondary ion mass spectroscopy,which led to enhanced electron transport in the conventional structure of organic solar cells(OSCs).In contrast,after rinsing with n-hexane,ITIC-m rich domains were formed at the bottom surface of the films,which improved electron transport in the inverted structure OSCs.The enhanced carrier transports increased the PCEs(11.80%and 11.15%)in both conventional and inverted OSCs by 10.29%and 10.35%compared with control devices.The versatile control of material concentration gradients is determined to be feasible owing to the chemical interaction of the used substrates(glass,PEDOT:PSS,and Zn O)and rinsing solvents.

Treatment of esophagogastric junction carcinoma:An unsolved debate

The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening programs to individuate and eradicate BE represent the best way to reduce AEG cancer. Several endoscopic approaches are here discussed. Surgicalstrategies for different types of AEG cancer are now fairly standardized, and multidisciplinary strategies u s i n g c h e m o t h e ra py o r c h e m o ra d i o t h e ra py m ay improve the outcome of these patients. Here we briefly discuss the keypoints, main topics, and critical issues, according to accumulating evidence and taking into account our own experience.

A new approach to endoscopic treatment of tumors of the esophagogastric junction with individually designed self-expanding metal stents

The incidence of adenocarcinoma of the esophago-gastric junction is constantly increasing. Curative treatment is no longer possible at the time of diagnosis in more than 50% of patients with esophageal carcinoma,and palliative treatment focusing on eliminating dysphagia is required. Endoscopic therapy with stent implantation is an established method of achieving this. It can be carried out quickly,with a low rate of early complications,and leads to fast symptomatic improvement,assessed using the dysphagia score. The relatively high rate of late complications such as stent migration,hemorrhage,and gastroesophageal mucosal prolapse has led to recent debate on the role of metal stents in palliative therapy. We present here a new type of stent design for transcardial application,which is intended to prevent bleeding due to mechanical mucosal lesions caused by the distal end of the stent extending into the stomach. The further intention of this case report is to force the discussion on individually designed nitinol stents in special anatomic conditions.

Constructing Built-In Electric Fields with Semiconductor Junctions and Schottky Junctions Based on Mo-MXene/Mo-Metal Sulfides for Electromagnetic Response

The exploration of novel multivariate heterostructures has emerged as a pivotal strategy for developing high-performance electromagnetic wave(EMW)absorption materials.However,the loss mechanism in traditional heterostructures is relatively simple,guided by empirical observations,and is not monotonous.In this work,we presented a novel semiconductor-semiconductor-metal heterostructure sys-tem,Mo-MXene/Mo-metal sulfides(metal=Sn,Fe,Mn,Co,Ni,Zn,and Cu),including semiconductor junctions and Mott-Schottky junctions.By skillfully combining these distinct functional components(Mo-MXene,MoS_(2),metal sulfides),we can engineer a multiple heterogeneous interface with superior absorption capabilities,broad effective absorption bandwidths,and ultrathin matching thickness.The successful establishment of semiconductor-semiconductor-metal heterostructures gives rise to a built-in electric field that intensifies electron transfer,as confirmed by density functional theory,which collaborates with multiple dielectric polarization mechanisms to substantially amplify EMW absorption.We detailed a successful synthesis of a series of Mo-MXene/Mo-metal sulfides featuring both semiconductor-semiconductor and semiconductor-metal interfaces.The achievements were most pronounced in Mo-MXene/Mo-Sn sulfide,which achieved remarkable reflection loss values of-70.6 dB at a matching thickness of only 1.885 mm.Radar cross-section calculations indicate that these MXene/Mo-metal sulfides have tremendous potential in practical military stealth technology.This work marks a departure from conventional component design limitations and presents a novel pathway for the creation of advanced MXene-based composites with potent EMW absorption capabilities.

Trimodality treatment in gastric and gastroesophageal junction cancers:Current approach and future perspectives

Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Western countries.These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses.Accordingly,the understanding of phenotypic and genotypic correlations/classifications has been improved.Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone,with the incorporation of other treatment modalities,such as radiation and chemotherapy(including biologics).Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival.Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate,which is associated with improved long-term outcomes.Several studies have defined various chemotherapy regimens to accompany radiation(before and after surgery).Recently,addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval.Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results.The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers,highlight the remaining questions and present the current research effort addressing them.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Systematic treatment in gastric cancer patients with overt bleeding:A propensity score matching analysis

BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety of chemotherapy as an initial therapy for GC/GEJC patients with overt bleeding(OB).AIM To investigate the impact of OB on the survival and treatment-related adverse events(TRAEs)of GC/GEJC patients.METHODS Patients with advanced or metastatic GC/GEJC who received systematic treatment at Peking University Third Hospital were enrolled in this study.Propensity score matching(PSM)analysis was performed.RESULTS After 1:2 PSM analysis,93 patients were assessed,including 32 patients with OB before treatment(OBBT)and 61 patients without OBBT.The disease control rate was 90.6%in the group with OBBT and 88.5%in the group without OBBT,and this difference was not statistically significant.There was no difference in the incidence of TRAEs between the group with OBBT and the group without OBBT.The median overall survival(mOS)was 15.2 months for patients with OBBT and 23.7 months for those without OBBT[hazard ratio(HR)=1.101,95%confidence interval(CI):0.672-1.804,log rank P=0.701].The mOS was worse for patients with OB after treatment(OBAT)than for those without OBAT(11.4 months vs 23.7 months,HR=1.787,95%CI:1.006-3.175,log rank P=0.044).CONCLUSION The mOS for GC/GEJC patients with OBBT was similar to that for those without OBBT,but the mOS for patients with OBAT was worse than that for those without OBAT.

Electron-distribution control via Pt/NC and MoC/NC dual junction:Boosted hydrogen electro-oxidation and theoretical study

The scarcity,high cost and susceptibility to CO of Platinum severely restrict its application in alkaline hydrogen oxidation reaction(HOR).Hybridizing Pt with other transition metals provides an effective strategy to modulate its catalytic HOR performance,but at the cost of mass activity due to the coverage of modifiers on Pt surface.Herein,we constructed dual junctions'Pt/nitrogen-doped carbon(Pt/NC)andδ-MoC/NC to modify electronic structure of Pt via interfacial electron transfer to acquire Pt-MoC@NC catalyst with electron-deficient Pt nanoparticles,simultaneously endowing it with high mass activity and durability of alkaline HOR.Moreover,the unique structure of Pt-MoC@NC endows Pt with a high COtolerance at 1,000 ppm CO/H_(2),a quality that commercial Pt-C catalyst lacks.The theoretical calculations not only confirm the diffusion of electrons from Pt/NC to Mo C/NC could occur,but also demonstrate the negative shift of Pt d-band center for the optimized binding energies of*H,*OH and CO.