Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.

Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.

Temperature and current sensitivity extraction of optical superconducting transition-edge sensors based on a two-fluid model

Optical superconducting transition-edge sensor(TES)has been widely used in quantum information,biological imaging,and fluorescence microscopy owing to its high quantum efficiency,low dark count,and photon number resolving capability.The temperature sensitivity(α_(I))and current sensitivity(β_(I))are important parameters for optical TESs,which are generally extracted from the complex impedance.Here we present a method to extractα_(I)andβ_(I)based on a two-fluid model and compare the calculated current-voltage curves,pulse response,and theoretical energy resolution with the measured ones.This method shows qualitative agreement that is suitable for further optimization of optical TESs.

Abnormal phenomenon of source-drain current of AlGaN/GaN heterostructure device under UV/visible light irradiation

We report an abnormal phenomenon that the source-drain current(I_(D))of AlGaN/GaN heterostructure devices decreases under visible light irradiation.When the incident light wavelength is 390 nm,the photon energy is less than the band gaps of GaN and AlGaN whereas it can causes an increase of ID.Based on the UV light irradiation,a decrease of I_(D) can still be observed when turning on the visible light.We speculate that this abnormal phenomenon is related to the surface barrier height,the unionized donor-like surface states below the surface Fermi level and the ionized donor-like surface states above the surface Fermi level.For visible light,its photon energy is less than the surface barrier height of the AlGaN layer.The electrons bound in the donor-like surface states below the Fermi level are excited and trapped by the ionized donor-like surface states between the Fermi level and the conduction band of AlGaN.The electrons trapped in ionized donor-like surface states show a long relaxation time,and the newly ionized donor-like surface states below the surface Fermi level are filled with electrons from the two-dimensional electron gas(2DEG)channel at AlGaN/GaN interface,which causes the decrease of ID.For the UV light,when its photon energy is larger than the surface barrier height of the AlGaN layer,electrons in the donor-like surface states below the Fermi level are excited to the conduction band and then drift into the 2DEG channel quickly,which cause the increase of ID.

Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Free vibration analysis of a spinning piezoelectric beam with geometric nonlinearities

The linear and non-linear free vibrations of a spinning piezoelectric beam are studied by considering geometric nonlinearities and electromechanical coupling effect. The non-linear differential equations of the spinning piezoelectric beam governing two transverse vibrations are derived by using two Euler angles transformation and extended Hamilton principle, wherein an additional piezoelectric coupling term and different linear terms are present in contrast to the traditional shaft model. Linear frequencies are obtained by solving the standard eigenvalues of the linearized system directly, and the non-linear frequencies and non-linear complex modes are achieved by using the method of multiple scales. For free vibrations analysis of a spinning piezoelectric beam, the non-linear modal motions are investigated as forward and backward precession with different spinning speeds. The responses to the initial conditions for such a gyroscopic system are studied,and a beat phenomenon is found, which are then validated by numerical simulation. The influences of some parameters such as electrical resistance, rotary inertia and spinning speeds to the non-linear dynamics of a spinning piezoelectric beam are investigated.

Anomaly Detection Algorithm for Stay Cable Monitoring Data Based on Data Fusion

In order to improve the accuracy and consistency of data in health monitoring system,an anomaly detection algorithm for stay cables based on data fusion is proposed.The monitoring data of Nanjing No.3 Yangtze River Bridge is used as the basis of study.Firstly,an adaptive processing framework with feedback control is established based on the concept of data fusion.The data processing contains four steps:data specification,data cleaning,data conversion and data fusion.Data processing information offers feedback to the original data system,which further gives guidance for the sensor maintenance or replacement.Subsequently,the algorithm steps based on the continuous data distortion is investigated,which integrates the inspection data and the distribution test method.Finally,a group of cable force data is utilized as an example to verify the established framework and algorithm.Experimental results show that the proposed algorithm can achieve high detection accuracy,providing a valuable reference for other monitoring data processing.

Experimental and Numerical Study on the Gas Explosion in Urban Regulator Station

Regulator station is an important part in the urban gas transmission and distribution system.Once gas explosion occurs,the real explosion process and consequences of methane gas explosion in the regulator station were not revealed systematically.In this study,a full-scale experiment was carried out to simulate the regulator station explosion process,and some numerical simulations with a commercial CFD software called FLACS were conducted to analyze the effect of ignition and vent conditions on the blast overpressure and flame propagation.The experimental results demonstrated that the peak overpressure increased as the distance from the vent increased within a certain distance.And the maximum overpressure appeared 3 m away from the door,which was about 36.6 kPa.It was found that the pressure-time rising curves obtained from the simulation are basically the same as the ones from the experiment,however,the time of reaching the peak pressure was much shorter.The numerical simulation results show that the peak overpressures show an increase trend as the ignition height decreased and the vent relief pressure increased.It indicates that the damage and peak overpressure of gas explosion could be well predicted by FLACS in different styles of regulator station.In addition,the results help us to understand the internal mechanism and development process of gas explosion better.It also offers technical support for the safety protection of the urban regulator station.

铁路货运票据电子化优化策略研究

阐述铁路货运票据电子化涵盖的票据和系统,从互联网应用、大数据分析、管理等方面分析铁路货运票据电子化的不足。从"前店"系统和"后厂"系统的功能整合、作业流程、货运票据电子化管理制度以及货物运价体系等方面提出铁路货运票据电子化优化策略。通过优化铁路货运票据电子化,进一步完善相关业务的互联网办理,打破地域限制,通过铁路局集团公司建立受理和制单核算中心、开发手持机操作平台等,切实发挥铁路货运票据电子化优势,提高货运作业效率和市场竞争力。

Pigment epithelium-derived factor protects retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction

AIM： To investigate the potential of pigment epitheliumderived factor（PEDF） to protect the immortalized rat retinal ganglion cells-5（RGC-5） exposed to Co Cl2-induced chemical hypoxia. METHODS： After being differentiated with staurosporine（SS）, RGC-5 cells were cultured in four conditions： control group cells cultured in Dulbecco ＇s modified eagle medium（DMEM） supplemented with 10% fetal bovine serum, 100 μmol/m L streptomycin and penicillin（named as normal conditions）; hypoxia group cells cultured in DMEM containing 300 μmol/m L Co Cl2; cells in the group protected by PEDF were first pretreated with 100 ng/m L PEDF for 2h and then cultured in the same condition as hypoxia group cells; and PEDF group cells that were cultured in the presence of 100 ng/m L PEDF under normal conditions. The cell viability was assessed by MTT assay, the percentage of apoptotic cells was quantified using Annexin V-FITC apoptosis kit, and intra-cellar reactive oxygen species（ROS） was measured by dichloro-dihydro-fluorescein diacetate（DCFH-DA） probe. The mitochondria-mediated apoptosis was also examined to further study the underlying mechanism of the protective effect of PEDF. The opening of mitochondrial permeability transition pores（m PTPs） and membrane potential（Δψm） were tested as cellular adenosine triphosphate（ATP） level and glutathione（GSH）. Also, the expression and distribution of Cyt C and apoptosis inducing factor（AIF） were observed.RESULTS： SS induced differentiation of RGC-5 cells resulting in elongation of their neurites and establishing contacts between outgrowths. Exposure to 300 μmol/m L Co Cl2 triggered death of 30% of the total cells in cultures within 24 h. At the same time, pretreatment with 100 ng/m L PEDF significantly suppressed the cell death induced by hypoxia（P〈0.05）. The apoptosis induced by treatment of Co Cl2 was that induced cell death accompanied with increasing intracellar ROS and decreasing GSH and ATP level. PEDF pretreatment suppressed these effects（P〈0.05）. Additionally, PEDF treatment inhibited the opening of m PTPs and suppressed decreasing of Δψm in RGC-5 cells, resulting in blocking of the mitochondrial apoptotic pathway.CONCLUSION： Pretreatment of RGC-5 cells with 100 ng/m L PEDF significantly decreases the extent of apoptosis. PEDF inhibits the opening of m PTPs and suppresses decreasing of Δψm. Moreover, PEDF also reduces ROS production and inhibits cellular ATP level＇s reduction. Cyt C and AIF activation in PEDF-pretreated cultures are also reduced. These results demonstrate the potential for PEDF to protect RGCs against hypoxic damage in vitro by preventing mitochondrial dysfunction.

Decreased uncoupling protein 2 expression in aging retinal pigment epithelial cells

AIM: To analyze the expression of uncoupling protein 2(UCP2) in retinal pigment epithelium(RPE) cells at the different human age, further explore the possible new target of RPE cells protection.METHODS: Adult retinal pigment epithelial-19(ARPE-19) cells and the primary RPE cells at the different age(9-20 y,50-55 y, 60-70 y, >70 y) were cultured and harvested. The expression of UCP2 in these cells was detected by reverse transcription-polymerase chain reaction(RT-PCR), Western blot and confocal microscopy.RESULTS: Cells from the donors more than 60 y are larger and more fibroblastic in appearance compared to ARPE-19 cells and those primary cultures obtained from the younger individuals by using phase-contrast micrographs. Results of RT-PCR, Western blot and confocal microscopy all showed that UCP2 was highly expressed in ARPE-19 cells and in the younger primary cultured human RPE cells at the age of 9-20 y and 50-55 y, whereas lower expression of UCP2 was measured in the older primary cultured human RPE cells at the age more than 60 y.CONCLUSION: Expression of UCP2 gene is decreased in aged RPE cells, promoting the lower ability of anti-oxidation in these cells. It is indicated that UCP2 gene might be a new target for protecting the cells from oxidative stress damage.

Effects of butylphthalide on bronchial asthma in guinea pigs and involvement of endothelin

Objective: To study the effects of butylphthalide on bronchial asthma in guinea pigs, and investigate the involvement of endothelin. Methods: In guinea pigs, bronchial asthma was induced by injection of ovalbumin(OVA) and provoked by inhalation of OVA, and the effects of butylphthalide on asthma were evaluated through the changes it induced by OVA, pulmonary function, endothelin-1(ET-1) contents and activity of endothelin converting enzyme-1(ECE-1) in bronchoalveolar lavage fluid(BALF), serum and lung tissue, and the gene expression of ET-1 in lung tissue. Results: Butylphthalide significantly improved pulmonary function, lowered asthmatic behavior score, inhibited the activity of ECE-1, and reduced ET-1 gene expression level in lung tissue. Conclusion: Butylphthalide has an anti-asthma effect and the mechanisms involve inhibition of ECE-1 activity and lowering of ET-1geng expression.

Establishment and evaluation of a mouse model of bronchial asthma with Yin deficiency syndrome

Objective: To establish and evaluate a mouse model of bronchial asthma with Yin deficiency syndrome. Methods: The mouse model of bronchial asthma with Yin deficiency syndrome was established by the treatment with injecting ovalbumin(OVA) two times to sensitize, inhaling OVA 14 times to stimulate, and using thyroxin through lavage during late stimulation. This model was evaluated through body weight, asthmatic behaviors, respiratory function, autonomous activity, lung pathology, and pulmonary fluid clearance. Results: OVA combined with thyroxin was an appropriate method to induce the mouse model with increased food and water intake, autonomous activity, asthmatic behaviors score, and respiratory rate, decreased body weight, tidal volume, and wet/dry ratio of lung, and changed with pathology of lung tissue. The changes of the above mentioned parameters indicated that the model was the bronchial asthma with Yin deficiency syndrome. Conclusion: The OVA combined with thyroxin is a good pattern to establish a mouse model of bronchial asthma with Yin deficiency syndrome successfully, which can highly simulate the clinical symptoms of this disease.

Thiocyanate Oxidation by Coculture from a Coke Wastewater Treatment Plant

Bacterial strains in an activated sludge aerobic reactor from a coke wastewater were found to be able to utilize thiocyanate as carbon source when the thiocyanate-containing wastewater was deprived of carbon source. This study showed that three thiocyanate-oxidizing bacterial strains, Burkholderia sp., Chryseobacterium sp., and Ralstonia sp. were isolated from the activated sludge of a coke wastewater treatment plant as evidenced by the fact that complete decomposition of thiocyanate was achieved either by coculture or individual pure culture. The thiocyanate biodegradation by the coculture occurred with an optimal pH range between 6.5 and 8.5 and an optimal temperature range between 30°C and 40°C. The biodegradation kinetics of thiocyanate was well fitted with the Andrew-Haldane model, which demonstrated a distinct substrate concentration-inhibited bacterial growth pattern. The effects of different types of additional carbon, nitrogen or sulfur sources on thiocyanate biodegradation were also investigated. Analysis of the end-products indicated that thiocyanate degradation by these strains should proceed via two pathways.

Fluorescence Emission Mediated by Metal-Dielectric-Metal Fishnet Metasurface: Spatially Selective Excitation and Double Enhancement

Enhancement of uorescent radiation is of great importance for applications including biological imaging,high-sensitivity detectors,and integrated light sources.Strong electromagnetic elds can be created around metallic nanoparticles or in gap of nanostructures,where the local state density of radiating mode is then dramatically enhanced.While enhanced uorescent emission has been demonstrated in many metallic nanoparticles and nanoparticle pairs,simultaneous mediation of absorption and emission processes of uorescent emitters remains challenging in metallic nanostructures.Here,we investigate uorescent emission mediated by metal-dielectric-metal fishnet metasurface,in which localized surface plasmon(LSP)and magnetic plasmon polaritons(MPPs)modes are coupled with absorption and emission processes,respectively.For absorption process,coupling of the LSP mode enables spatially-selective excitation of the uorescent emitters by rotating the polarization of the pump laser beam.In addition,the polarization-dependent MPP mode enables manipulation of both polarization and wavelength of the uorescent emission by introducing a rectangular fishnet structure.All the experimental observations are further corroborated by nite-difference time-domain simulations.The structure reported here has great potential for application to color light-emitting devices and nanoscale integrated light sources.

数字化背景下高职院校文化建设:演进逻辑、时代内涵及实践路径

高职院校文化建设是职业教育高质量发展的内在要求,是铸牢社会主义意识形态的前沿阵地,也是践行社会主义核心价值观的辐射场域。从演进逻辑出发体悟高职院校文化建设的政策逻辑;从时代内涵出发审视主流意识形态文化的核心地位和其他文化的协同发展重要作用;从建设路径出发明确立德树人教育目标,以文化育人为导向,拓展文化组织形式,实施文化创新研究,提高高职院校文化建设主体能力,全面提升实践成效。

An Atomic Magnetometer with Spin-Projection Noise Proportional to (T_2)^(1/2)

There is a comm on sense view for atomic magnetometers that their spin-projection-noises(SPNs) are inversely proportional to (T_2)^(1/2), where (T_2)^(1/2) is the transverse relaxation time. We analyze the current atomic magnetometer types and give a counter-example of this common sense, which is the all-optical spin precession modulated threeaxis atomic magnetometer proposed by our group in 2015. Unlike the other atomic magnetometers, the SPN of this kind of atomic magnetometers is proportional to (T_2)^(1/2) due to the fact that the scale factor between P_x and B can be unrelated to the transverse relaxation time T_2. We demonstrate this irrelevance experimentally and analyze the SPN theoretically. Using short-pulse ultra-high power laser to fully polarize the atoms, the phenomenon that SPN decreases with T_2 may also be demonstrated experimentally and a new tool for researching SPN in atomic magnetometers may be realized.

Down regulation of UCP2 expression in retinal pigment epithelium cells under oxidative stress: an in vitro study

AIM: To evaluate the expression of uncoupling protein 2(UCP2) in a retinal pigment epithelium cell line(ARPE-19), under oxidative stress(OS).METHODS: ARPE-19 cells were divided into groups treated with various concentrations of hydrogen peroxide(H2 O2;0, 150, 300, 500, 700, and 900 μmol/L) for 24 h, to induce oxidative damage and cell viability was assessed by MTT assay. UCP2 mRNA expression in cells treated with H2 O2 was investigated by reverse transcription-polymerase chain reaction(RT-PCR). UCP2 protein expression was assessed by Western blotting and ROS levels analyzed by flow cytometry(FCM). Further, UCP2-siRNA treated cultures were exposed to H2 O2(0, 75, 150, and 300 μmol/L) for 2 h and cell viability determined by MTT assay.RESULTS: Cells treated with higher concentrations of H2 O2 appeared shrunken;their adhesion to adjacent cells was disrupted, and the number of dead cells increased. The results of cell viability assays demonstrated that the numbers of cells were decreased in a dose-dependent manner following treatment with H2 O2. Compared with untreated controls, cell viability was significantly reduced after treatment with >300 μmol/L H2 O2(P<0.05). Cell metabolic activity was decreased with increased concentrations of H2 O2 as detected by MTT assay. Levels of OS were further decreased in cells treated with UCP2-siRNA compared with those treated with H2 O2 alone(P<0.05). The results of RT-PCR and Western blotting demonstrated that UCP2 expression was reduced in H2 O2-treated groups compared with controls(P<0.05). FCM analysis showed that cell reactive oxygen species(ROS) levels were increased in H2 O2-treated groups and further upregulated by UCP2-si RNA treatment(P<0.05).CONCLUSION: Expression levels of UCP2 are decreased in ARPE-19 cells treated with H2 O2. ROS levels are further increased in cells treated with UCP2-siRNA relative to those treated with H2 O2 alone. UCP2 may have a protective role in ARPE-19 cells during oxidative injury.

Improvement of energy resolution of x-ray transition-edge sensor using K-means algorithm and Wiener filter

We develop an x-ray Ti/Au transition-edge sensor(TES)with an Au absorber deposited on the center of TES and improved its energy resolution using the K-means clustering algorithm in combination with Wiener filter.We firstly extract the main parameters of each recorded pulse trace,which are adopted to classify these traces into several clusters in the K-means clustering algorithm.Then real traces are selected for energy resolution analysis.Following the baseline correction,the Wiener filter is used to improve the signal-to-noise ratio.Although the silicon underneath the TES has not been etched to reduce the thermal conductance,the energy resolution of the developed x-ray TES is improved from 94 eV to 44 eV at 5.9 keV.

Linear,nonlinear dynamics,and sensitivity analysis of a vibratory ring gyroscope

The linear and nonlinear dynamic responses of a vibratory ring gyroscope are investigated in this study focusing on the response mechanism of such a vibratory gyroscope. It is found that the nonlinear equations governing the drive and sense directions are coupled through both inertial linear and geometric nonlinear terms. Nonlinear responses are studied based on the full coupled nonlinear dynamic equations. The varying amplitude on the sense direction is analyzed for different input angular rates. The effect of nonlinearity on the ring gyroscope system is performed by comparing the results of nonlinear responses to those of linear responses. The contributions of some parameters to the amplitude responses and gyroscope sensitivity are analyzed, the conclusions of which provide guidelines to improve the sensitivity of the vibratory ring gyroscopes.