Complete response of gallbladder cancer treated with gemcitabine and cisplatin chemotherapy combined with durvalumab:A case report and review of literature

BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.

Reflection and operationalization of the common but differentiated responsibilities and respective capabilities principle in the transparency framework under the international climate change regime

“Common but differentiated responsibilities and respective capabilities”(CBDRRC) is the most significant guiding principle in the international climate change regime, created by the United Nations Framework Convention on Climate Change in 1992 and inherited by the Paris Agreement 24 years later. This paper examines the operationalization of the CBDRRC principle in one of the cornerstone rules of the regimedits transparency provisions, both in existing practice under the convention and possible evolvement in negotiations under the Paris Agreement, from the perspectives of both international rule-making and domestic implementation. The authors have found a continuous enhancement of the transparency framework since the 1990s, and gradual consolidation of a bifurcated system between developed and developing countries into a common one. The authors argue that the transparency framework, as part of the procedural rules, should be designed to facilitate transparent information sharing in accordance with substantive commitments under international climate change laws. Thus, it indirectly reflects historical responsibilities for climate change, while the framework should also be designed as feasible and reflective of the respective capabilities of nations. Finally, the evolution of the transparency framework will aim to enact common and enhanced provisions while differentiating between developed and developing countries in the near term, and greater transparency-related capacity-building for developing countries.

Roles and Responsibilities of Stakeholders towards Ensuring Health and Safety at Construction Site

Health and Safety issues in the construction industry are of much concern to stakeholders, particularly because of their impact on the industry. This paper explored the roles and responsibilities of stakeholders in ensuring health and safety at the construction site. A well-structured interview guide was adopted for the qualitative study. Content analysis was adopted for the analysis of the results. The study revealed that the twelve roles identified by the stakeholders are only limited to the few laws and regulations they are aware of. Whereas the Contractors identified provision of welfare facilities, provision of health and safety policy, and health and safety plan as their key roles, the Consultants’ role was mainly limited to provision of competent site agent and provision of site layout. Abiding by the contractors’ instruction was identified by the Construction Workers as their key responsibilities. The local government officials also identified enforcement of CHS laws and regulations and reporting of incidents to the appropriate authorities, whereas the traditional authorities identified the enforcement of CHS laws and regulations including bye laws and enforcement of customs as their key roles. The findings further show that the stakeholders failed to appreciate some key roles and responsibilities enshrined in CHS laws and regulations in Ghana. The findings contribute to knowledge on stakeholders’ responsibilities in ensuring CHS, and provide valuable reference and insight to practitioners on the roles and responsibilities of the various stakeholders. It is recommended to train and educate stakeholders on all the relevant laws and regulations on CHS in order to improve health and safety at the construction site. The government should also set up a body such as Construction Authority to educate, coordinate, monitor and audit the activities of stakeholders to improve CHS at construction sites.

“An integrated system,three separated responsibilities”,a new fever clinic management model,in prevention and control of novel coronavirus pneumonia

BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic,since controlling the spread of disease is an important way to prevent and control the epidemic.METHODS In total,200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups.RESULTS The fever clinic in our hospital operated smoothly,and infection with the novel coronavirus disease(COVID-19)has not been reported in our hospital.Additionally,we did not have any cases of missed diagnosis.The awareness regarding COVID-19 infection sources,transmission routes,early symptoms,and preventive measures was significantly higher in our fever clinic than in those of the pre-management group.CONCLUSION"An integrated system,three separate responsibilities"ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases,which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital,ultimately achieving the maximum effect of epidemic prevention and control.

Framework of Social Responsibilities of Forestry Enterprises

Forestry industry plays a key role in regulating climate and promoting sustainable development of society.Environmental responsibility is the key part of social responsibilities of forestry enterprises.Based on the particularity of forestry industry,the framework of social responsibility reports of forestry enterprises is provided,and major topics of social responsibilities followed by forestry enterprises are analyzed.Meanwhile,the core values of social responsibilities of forestry enterprises are pointed out.It is proposed that the social responsibility reports of forestry enterprises should involve the responsibility to shareholders and creditors,the responsibility to suppliers,customers and consumers,the responsibility to employees,the responsibility to the environment,and the responsibility to communities and charity behavior.

Technology advance and discounting of the historical emission responsibilities

Solving the dispute over historical greenhouse gases emission responsibility is critical for the future climate agreement.This article borrows the methodology from the carbon budget proposal,but further develops this approach by proposing discount of the historical responsibility due to the technology advance.Firstly,it studies the Annex I countries'mitigation and financial responsibilities of the historical emission in the carbon budget proposal;furthermore,it analyzes the results and implications of the discount approach.Results show that the discount method significantly reduces the burden of the mitigation and financial responsibilities of the Annex I countries.Thus,we claim that the discount approach is a systematic,pragmatic,and fair approach to solve the historical responsibility dispute and financial problems for the post-2020international climate institutions.

A theory for three-dimensional response of micropolar plates

Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Shouldering responsibilities & chasing dreams

This special issue of Petroleum Science celebrates not only the 60th anniversary of China University of Petroleum（CUP）,but also the 60th anniversary of China’s higher education and scientific research in petroleum science.As the first petroleum university in the People’s Republic of China,CUP played the major role in the development of the country’s petroleum higher education from a humble start to its successes today.

Thermo-hydro-poro-mechanical responses of a reservoir-induced landslide tracked by high-resolution fiber optic sensing nerves

Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Probiotics: Shaping the gut immunological responses

Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate amounts.Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and yeasts.Most of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological responses.Chronic intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal damage.Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue microenvironment.This influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential nutrients.We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.

Diphylleia Grayi-Inspired Intelligent Temperature-Responsive Transparent Nanofiber Membranes

Nanofiber membranes(NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent(TRT) membranes,which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 ℃, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance(> 90%), and fast response(5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.

Inflammation: Complexity and significance of cellular and molecular responses

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

Shoulder New Responsibilities in All-around Opening-up——Interview with CPPCC member and CCPIT Chairperson Gao Yan

'We shall promote opening-up in an all around way and develop new competitive edge in international economic cooperation.'This year’s government report has laid out a blueprint for China’s opening-up.What role shall the CPPIT play in this process? What will the CCPIT do to support the stability of foreign trade and investment, cope with international economic conflicts and promote the Belt and Road projects?Our reporter was honored to interview Ms. Gao Yan, CPPCC member and Chairperson of the CPPIT.

Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

Coral records of Mid-Holocene sea-level highstands and climate responses in the northern South China Sea

High-resolution sea-level data and high-precision dating of corals in the northern South China Sea(SCS)during the Holocene provide a reference and historical background for current and future sea-level changes and a basis for scientific assessment of the evolutionary trend of coral reefs in the SCS.Although sporadic studies have been performed around Hainan Island in the northern SCS,the reconstructed sea level presents different values or is controversial because the indicative meaning of the sea-level indicators were neither quantified nor uniform criteria.Here,we determined the quantitative relationship between modern living coral and sea level by measuring the top surfaces of 27 live Porites corals from the inner reef flat along the east coast of Hainan Island and assessed the accuracy of results obtained using coral as sea-level indicators.Additionally,three in situ fossil Porites corals were analyzed based on elevation measurements,digital X-ray radiography,and U-Th dating.The survey results showed that the indicative meanings for the modern live Porites corals is(146.09±8.35)cm below the mean tide level(MTL).It suggested that their upward growth limit is constrained by the sea level,and the lowest low water is the highest level of survival for the modern live Porites corals.Based on the newly defined indicative meanings,6 new sea-level index points(SLIPs)were obtained and 19 published SLIPs were recalculated.Those SLIPs indicated a relative sea level fluctuation between(227.7±9.8)cm to(154.88±9.8)cm MTL between(5393±25)cal a BP and(3390±12)cal a BP,providing evidences of the Mid-Holocene sea-level highstand in the northern SCS.Besides that,our analysis demonstrated that different sea-level histories may be produced based on different indicative meanings or criteria.The dataset of 276 coral U-Th ages indicates that coral reef development in the northern SCS comprised the initial development,boom growth,decline,and flourishing development again.A comparison with regional records indicated that synergistic effects of climatic and environmental factors were involved in the development of coral reefs in the northern SCS.Thus,the cessation of coral reef development during the Holocene in the northern SCS was probably associated with the dry and cold climate in South China,as reflected in the synchronous weakening of the ENSO and East Asian summer monsoon induced by the reduction of the 65°N summer insolation,which forced the migration of the Intertropical Convergence Zone.

Time-domain dynamic constitutive model suitable for mucky soil site seismic response

Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modulus and combining the dynamic skeleton curve and the damping degradation coefficient,the constitutive equation of the logarithmic dynamic skeleton can be obtained,which considers the damping effect in a soil dynamics problem.Based on the finite difference method and the multi-transmitting boundary condition,a 1D site seismic response analysis program called Soilresp1D has been developed herein and used to analyze the time-domain seismic response in three types of sites.At the same time,this study also provides numerical simulation results based on the hyperbolic constitutive model and the equivalent linear method.The results verify the rationality of the new soil dynamic constitutive model.It can analyze the mucky soil site nonlinear seismic response,reflecting the deformation characteristics and damping effect of the silty soil.The hysteresis loop area is more extensive,and the residual strain is evident.

Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

The Fulfillment of Government Responsibilities in the Collaborative Governance of Rural Water Pollution

Rural environmental pollution is becoming more and more serious, which has become an important problem to be solved urgently in our country under the background of the new era. Protecting the ecological environment is one of the important functions of the government, and protecting the rural water environment is the unshirkable responsibility of the local governments. As the main body of rural water pollution control, how to define and fulfill the local governments’ responsibilities is of great significance to the advancement of the overall governance work. This paper starts from the local governments, which are the important main body of rural environmental governance. By comparing the similarities and differences between the performance of government responsibilities under the traditional governance model and the collaborative governance model, clarifies the governance responsibilities of the local governments. And further explores the effective measures for the government to play the main role, fulfill the main responsibilities, and participate in the collaborative governance of rural water pollution.