Despite the availability of different treatments for advanced NSCLC, all of them have a palliative intention and a cure for the disease is unlikely. Thus, advanced lung cancer remains as an unmet medical need. Chemoth...Despite the availability of different treatments for advanced NSCLC, all of them have a palliative intention and a cure for the disease is unlikely. Thus, advanced lung cancer remains as an unmet medical need. Chemotherapy has been used as the therapy of choice for advanced NSCLC patients, but it is mainly limited by the patient’s performance status. More recently, targeted therapies have introduced more specific treatment options that show efficacy in specific niche of patients, but precisely due to their target specificity, they usually provoke early resistance. In addition to these limitations, most of the best drugs currently used for treatment of advanced NSCLC show small increases in patient survival with severe associated toxicity. Novel drugs with low toxicity that could be given chronically to control the advanced disease can make a difference. They could allow the management of advanced cancer as a chronic disease that, even when not cured, it can be controlled for long periods of time offering patients a good quality of life. Active-specific immunotherapy is an area of oncology that is rapidly expanding with encouraging results. Cancer vaccines against many potential targets have shown to increase patient survival in clinical trials at all stages NSCLC, when included as first-line, maintenance, or second-line therapy. Safety of cancer vaccines supposes a new hope for cancer therapy, and this unique characteristic makes it possible to be used in sub-sets of patients that cannot receive other approved treatments because of their high toxicity. In this paper, authors propose how active immunotherapy could be included in the current algorithm for treatment of advanced NSCLC patients.展开更多
Objective To investigate the effect of active immunotherapy on unexplained recurrent spontaneous abortion (URSA ) during the process of gestation and delivery period. Methods We collected the data of the women with ...Objective To investigate the effect of active immunotherapy on unexplained recurrent spontaneous abortion (URSA ) during the process of gestation and delivery period. Methods We collected the data of the women with URSA and their offsprings. The women were treated by immunization with paternal lymphocytes and then had a successful pregnancy. The fore mentioned group of women were compared with those who had a normal pregnancy and then delivered in the same period. Results The incidences of premature rupture of membranes, adherent placenta, and residual cauls in the group of URSA patients were statistically higher than those in the normal group. Correspondingly, gestational age at delivery and birth weight of the newborns of the group of URSA patients were lower, but there were no significant differences between the two groups. Conclusion These results indicate that paternal lymphocyte immunotherapy is effective on the maintenance of pregnancy in women with URSA, and has no deleterious effects on the fetus or newborns. However, in case of the higher incidence of premature rupture of membranes, adherent placenta, and residual cauls, more attention should be paid to the treated patients to avoid intrauterine growth retardation and postpartum hemorrhage.展开更多
The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic d...The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic devices have undergone significant advancements,thereby facilitating the study of electrophysiology.The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale.In this paper,we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electroexcitable cells,focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals.Looking forward to the possibilities,challenges,and wide prospects of active micro-nano-devices,we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers wor...Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.展开更多
Since the discovery of insulin over 100 years ago,the focus of research in the management of type 1 diabetes(T1D)has centered around glycemic control and management of complications rather than the prevention of autoi...Since the discovery of insulin over 100 years ago,the focus of research in the management of type 1 diabetes(T1D)has centered around glycemic control and management of complications rather than the prevention of autoimmune destruc-tion of pancreaticβcells.Fortunately,in recent years,there has been significant advancement in immune-targeted pharmacotherapy to halt the natural progres-sion of T1D.The immune-targeted intervention aims to alter the underlying pa-thogenesis of T1D by targeting different aspects of the immune system.The im-munotherapy can either antagonize the immune mediators like T cells,B cells or cytokines(antibody-based therapy),or reinduce self-tolerance to pancreaticβcells(antigen-based therapy)or stem-cell treatment.Recently,the US Food and Drug Administration approved the first immunotherapy teplizumab to be used only in stage 2 of T1D.However,the window of opportunity to practically implement this approved molecule in the selected target population is limited.In this Edito-rial,we briefly discuss the various promising recent developments in the field of immunotherapy research in T1D.However,further studies of these newer thera-peutic agents are needed to explore their true potential for prevention or cure of T1D.展开更多
Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high c...Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.展开更多
The virtual synchronous generator(VSG)technology has been proposed to address the problem of system frequency and active power oscillation caused by grid-connected new energy power sources.However,the traditional volt...The virtual synchronous generator(VSG)technology has been proposed to address the problem of system frequency and active power oscillation caused by grid-connected new energy power sources.However,the traditional voltage-current double-closed-loop control used in VSG has the disadvantages of poor disturbance immunity and insufficient dynamic response.In light of the issues above,a virtual synchronous generator voltage outer-loop control strategy based on improved linear autonomous disturbance rejection control(ILADRC)is put forth for consideration.Firstly,an improved first-order linear self-immunity control structure is established for the characteristics of the voltage outer loop;then,the effects of two key control parameters-observer bandwidthω_(0)and controller bandwidthω_(c)on the control system are analyzed,and the key parameters of ILADRC are optimally tuned online using improved gray wolf optimizer-radial basis function(IGWO-RBF)neural network.A simulationmodel is developed using MATLAB to simulate,analyze,and compare the method introduced in this paper.Simulations are performed with the traditional control strategy for comparison,and the results demonstrate that the proposed control method offers superior anti-interference performance.It effectively addresses power and frequency oscillation issues and enhances the stability of the VSG during grid-connected operation.展开更多
Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of im...Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.展开更多
Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream...Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。展开更多
BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of ...BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.展开更多
Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death p...Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.展开更多
In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent...In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.展开更多
Metasurfaces have opened the door to next-generation optical devices due to their ability to dramatically modulate electromagnetic waves at will using periodically arranged nanostructures.However,metasurfaces typicall...Metasurfaces have opened the door to next-generation optical devices due to their ability to dramatically modulate electromagnetic waves at will using periodically arranged nanostructures.However,metasurfaces typically have static optical responses with fixed geometries of nanostructures,which poses challenges for implementing transition to technology by replacing conventional optical components.To solve this problem,liquid crystals(LCs)have been actively employed for designing tunable metasurfaces using their adjustable birefringent in real time.Here,we review recent studies on LCpowered tunable metasurfaces,which are categorized as wavefront tuning and spectral tuning.Compared to numerous reviews on tunable metasurfaces,this review intensively explores recent development of LC-integrated metasurfaces.At the end of this review,we briefly introduce the latest research trends on LC-powered metasurfaces and suggest further directions for improving LCs.We hope that this review will accelerate the development of new and innovative LC-powered devices.展开更多
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monocl...Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.展开更多
The active layer,acting as an intermediary of water and heat exchange between permafrost and atmosphere,greatly influences biogeochemical cycles in permafrost areas and is notably sensitive to climate fluctuations.Uti...The active layer,acting as an intermediary of water and heat exchange between permafrost and atmosphere,greatly influences biogeochemical cycles in permafrost areas and is notably sensitive to climate fluctuations.Utilizing the Chinese Meteorological Forcing Dataset to drive the Community Land Model,version 5.0,this study simulates the spatial and temporal characteristics of active layer thickness(ALT)on the Tibetan Plateau(TP)from 1980 to 2020.Results show that the ALT,primarily observed in the central and western parts of the TP where there are insufficient station observations,exhibits significant interdecadal changes after 2000.The average thickness on the TP decreases from 2.54 m during 1980–1999 to 2.28 m during 2000–2020.This change is mainly observed in the western permafrost region,displaying a sharp regional inconsistency compared to the eastern region.A persistent increasing trend of ALT is found in the eastern permafrost region,rather than an interdecadal change.The aforementioned changes in ALT are closely tied to the variations in the surrounding atmospheric environment,particularly air temperature.Additionally,the area of the active layer on the TP displays a profound interdecadal change around 2000,arising from the permafrost thawing and forming.It consistently decreases before 2000 but barely changes after 2000.The regional variation in the permafrost active layer over the TP revealed in this study indicates a complex response of the contemporary climate under global warming.展开更多
BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A...BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.展开更多
Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and othe...Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.展开更多
High-static-low-dynamic-stiffness(HSLDS)vibration isolators with buckling beams have been widely used to isolate external vibrations.An active adjustable device composed of proportion integration(PI)active controllers...High-static-low-dynamic-stiffness(HSLDS)vibration isolators with buckling beams have been widely used to isolate external vibrations.An active adjustable device composed of proportion integration(PI)active controllers and piezoelectric actuators is proposed for improving the negative stiffness stroke of buckling beams.A nonlinear output frequency response function is used to analyze the effect of the vibration reduction.The prototype of the active HSLDS device is built,and the verification experiment is conducted.The results show that compared with the traditional HSLDS vibration isolator,the active HSLDS device can broaden the isolation frequency bandwidth,and effectively reduce the resonant amplitude by adjusting the active control parameters.The maximum vibration reduction rate of the active HSLDS vibration isolator can attain 89.9%,and the resonant frequency can be reduced from 31.08 Hz to 13.28 Hz.Therefore,this paper devotes to providing a new design scheme for enhanced HSLDS vibration isolators.展开更多
文摘Despite the availability of different treatments for advanced NSCLC, all of them have a palliative intention and a cure for the disease is unlikely. Thus, advanced lung cancer remains as an unmet medical need. Chemotherapy has been used as the therapy of choice for advanced NSCLC patients, but it is mainly limited by the patient’s performance status. More recently, targeted therapies have introduced more specific treatment options that show efficacy in specific niche of patients, but precisely due to their target specificity, they usually provoke early resistance. In addition to these limitations, most of the best drugs currently used for treatment of advanced NSCLC show small increases in patient survival with severe associated toxicity. Novel drugs with low toxicity that could be given chronically to control the advanced disease can make a difference. They could allow the management of advanced cancer as a chronic disease that, even when not cured, it can be controlled for long periods of time offering patients a good quality of life. Active-specific immunotherapy is an area of oncology that is rapidly expanding with encouraging results. Cancer vaccines against many potential targets have shown to increase patient survival in clinical trials at all stages NSCLC, when included as first-line, maintenance, or second-line therapy. Safety of cancer vaccines supposes a new hope for cancer therapy, and this unique characteristic makes it possible to be used in sub-sets of patients that cannot receive other approved treatments because of their high toxicity. In this paper, authors propose how active immunotherapy could be included in the current algorithm for treatment of advanced NSCLC patients.
文摘Objective To investigate the effect of active immunotherapy on unexplained recurrent spontaneous abortion (URSA ) during the process of gestation and delivery period. Methods We collected the data of the women with URSA and their offsprings. The women were treated by immunization with paternal lymphocytes and then had a successful pregnancy. The fore mentioned group of women were compared with those who had a normal pregnancy and then delivered in the same period. Results The incidences of premature rupture of membranes, adherent placenta, and residual cauls in the group of URSA patients were statistically higher than those in the normal group. Correspondingly, gestational age at delivery and birth weight of the newborns of the group of URSA patients were lower, but there were no significant differences between the two groups. Conclusion These results indicate that paternal lymphocyte immunotherapy is effective on the maintenance of pregnancy in women with URSA, and has no deleterious effects on the fetus or newborns. However, in case of the higher incidence of premature rupture of membranes, adherent placenta, and residual cauls, more attention should be paid to the treated patients to avoid intrauterine growth retardation and postpartum hemorrhage.
基金The work is supported in part by the National Natural Science Foundation of China(Grant Nos.62171483,82061148011)Zhejiang Provincial Natural Science Foundation of China(Grant No.LZ23F010004)+1 种基金Hangzhou Agricultural and Social Development Research Key Project(Grant No.20231203A08)Doctoral Initiation Program of the Tenth Affiliated Hospital,Southern Medical University(Grant No.K202308).
文摘The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic devices have undergone significant advancements,thereby facilitating the study of electrophysiology.The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale.In this paper,we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electroexcitable cells,focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals.Looking forward to the possibilities,challenges,and wide prospects of active micro-nano-devices,we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金Supported by The Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil(Luz MS and Pinheiro SLR),No.6511185733054315 and No.3748771590681149The coauthor Lemos,FFB is supported by the Scientific Initiation Scholarship Programme(PIBIC)of Bahia State Research Support Foundation,FAPESB,Brazil,No.19.573.301.5418and the CNPq Research Productivity Fellow(de Melo FF),No.4357511882624145.
文摘Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.
文摘Since the discovery of insulin over 100 years ago,the focus of research in the management of type 1 diabetes(T1D)has centered around glycemic control and management of complications rather than the prevention of autoimmune destruc-tion of pancreaticβcells.Fortunately,in recent years,there has been significant advancement in immune-targeted pharmacotherapy to halt the natural progres-sion of T1D.The immune-targeted intervention aims to alter the underlying pa-thogenesis of T1D by targeting different aspects of the immune system.The im-munotherapy can either antagonize the immune mediators like T cells,B cells or cytokines(antibody-based therapy),or reinduce self-tolerance to pancreaticβcells(antigen-based therapy)or stem-cell treatment.Recently,the US Food and Drug Administration approved the first immunotherapy teplizumab to be used only in stage 2 of T1D.However,the window of opportunity to practically implement this approved molecule in the selected target population is limited.In this Edito-rial,we briefly discuss the various promising recent developments in the field of immunotherapy research in T1D.However,further studies of these newer thera-peutic agents are needed to explore their true potential for prevention or cure of T1D.
基金This work is supported by National Key Research and Development Program of China(No.2022YFC3501905)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)+2 种基金National Natural Science Foundation of China(NSFC,No.82104076)Science and Technology Commission of Shanghai Municipal(STCSM,No.22S21902400,China)Medicine-Engineering joint foundation of Shanghai Jiao Tong University(No.YG2022QN025 and YG2022QN050,China).
文摘Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.
基金supported by the Lanzhou Jiaotong University-Southwest Jiaotong University Joint Innovation Fund(LH2024027).
文摘The virtual synchronous generator(VSG)technology has been proposed to address the problem of system frequency and active power oscillation caused by grid-connected new energy power sources.However,the traditional voltage-current double-closed-loop control used in VSG has the disadvantages of poor disturbance immunity and insufficient dynamic response.In light of the issues above,a virtual synchronous generator voltage outer-loop control strategy based on improved linear autonomous disturbance rejection control(ILADRC)is put forth for consideration.Firstly,an improved first-order linear self-immunity control structure is established for the characteristics of the voltage outer loop;then,the effects of two key control parameters-observer bandwidthω_(0)and controller bandwidthω_(c)on the control system are analyzed,and the key parameters of ILADRC are optimally tuned online using improved gray wolf optimizer-radial basis function(IGWO-RBF)neural network.A simulationmodel is developed using MATLAB to simulate,analyze,and compare the method introduced in this paper.Simulations are performed with the traditional control strategy for comparison,and the results demonstrate that the proposed control method offers superior anti-interference performance.It effectively addresses power and frequency oscillation issues and enhances the stability of the VSG during grid-connected operation.
基金supported by grants from the National Natural Science Foundation of China (Grant No. U20A20369)GuangDong Basic and Applied Basic Research Foundation (Grant No. 2022B1515120085)。
文摘Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.
文摘Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。
基金This study has been reviewed and approved by the Clinical Medical Ethics Committee(Approval No.2021HN26A).
文摘BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.
基金Supported by Natural Science Foundation of Fujian Province,No.2021J011259.
文摘Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
文摘In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.
基金supported by the POSCO-POSTECH-RIST Convergence Research Center program funded by POSCO,the Samsung Research Funding&Incubation Center for Future Technology grant(SRFC-IT1901-52)funded by Samsung Electronicsthe National Research Foundation(NRF)grants(NRF-2022M3C1A3081312,NRF-2022M3H4A1A-02074314,NRF-2022M3H4A1A02046445,NRF-2021M3H4A1A04086357,NRF-2019R1A5A8080290,RS-2024-00356928,RS-2023-00283667)funded by the Ministry of Science and ICT of the Korean governmentthe Korea Evaluation Institute of Industrial Technology(KEIT)grant(No.1415185027/20019169,Alchemist project)funded by the Ministry of Trade,Industry and Energy(MOTIE)of the Korean government.H.Kim and J.Kim acknowledge the POSTECH Alchemist fellowship,the Asan Foundation Biomedical Science fellowship,and Presidential Science fellowship funded by the MSIT of the Korean government.
文摘Metasurfaces have opened the door to next-generation optical devices due to their ability to dramatically modulate electromagnetic waves at will using periodically arranged nanostructures.However,metasurfaces typically have static optical responses with fixed geometries of nanostructures,which poses challenges for implementing transition to technology by replacing conventional optical components.To solve this problem,liquid crystals(LCs)have been actively employed for designing tunable metasurfaces using their adjustable birefringent in real time.Here,we review recent studies on LCpowered tunable metasurfaces,which are categorized as wavefront tuning and spectral tuning.Compared to numerous reviews on tunable metasurfaces,this review intensively explores recent development of LC-integrated metasurfaces.At the end of this review,we briefly introduce the latest research trends on LC-powered metasurfaces and suggest further directions for improving LCs.We hope that this review will accelerate the development of new and innovative LC-powered devices.
文摘Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(STEP)program[grant number 2019QZKK0102]the Youth Innovation Promotion Association CAS[grant number 2021073]the special fund of the Yunnan University“double firstclass”construction.
文摘The active layer,acting as an intermediary of water and heat exchange between permafrost and atmosphere,greatly influences biogeochemical cycles in permafrost areas and is notably sensitive to climate fluctuations.Utilizing the Chinese Meteorological Forcing Dataset to drive the Community Land Model,version 5.0,this study simulates the spatial and temporal characteristics of active layer thickness(ALT)on the Tibetan Plateau(TP)from 1980 to 2020.Results show that the ALT,primarily observed in the central and western parts of the TP where there are insufficient station observations,exhibits significant interdecadal changes after 2000.The average thickness on the TP decreases from 2.54 m during 1980–1999 to 2.28 m during 2000–2020.This change is mainly observed in the western permafrost region,displaying a sharp regional inconsistency compared to the eastern region.A persistent increasing trend of ALT is found in the eastern permafrost region,rather than an interdecadal change.The aforementioned changes in ALT are closely tied to the variations in the surrounding atmospheric environment,particularly air temperature.Additionally,the area of the active layer on the TP displays a profound interdecadal change around 2000,arising from the permafrost thawing and forming.It consistently decreases before 2000 but barely changes after 2000.The regional variation in the permafrost active layer over the TP revealed in this study indicates a complex response of the contemporary climate under global warming.
基金Supported by Department of Health of Zhejiang Province,No.2019-KY1-001-138Zhejiang Provincial Natural Science Foundatio,No.LTGY24H160016。
文摘BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.
基金2021 Key Topic of Qinghai Provincial Health System–Guiding Plan Topic,No.2021-WJZDX-43.
文摘Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.
基金Project supported by the National Natural Science Foundation of China(Nos.62188101,12272103,12022213)。
文摘High-static-low-dynamic-stiffness(HSLDS)vibration isolators with buckling beams have been widely used to isolate external vibrations.An active adjustable device composed of proportion integration(PI)active controllers and piezoelectric actuators is proposed for improving the negative stiffness stroke of buckling beams.A nonlinear output frequency response function is used to analyze the effect of the vibration reduction.The prototype of the active HSLDS device is built,and the verification experiment is conducted.The results show that compared with the traditional HSLDS vibration isolator,the active HSLDS device can broaden the isolation frequency bandwidth,and effectively reduce the resonant amplitude by adjusting the active control parameters.The maximum vibration reduction rate of the active HSLDS vibration isolator can attain 89.9%,and the resonant frequency can be reduced from 31.08 Hz to 13.28 Hz.Therefore,this paper devotes to providing a new design scheme for enhanced HSLDS vibration isolators.