Human Factors/Ergonomics (HFE) in Leadership and Management: Organizational Interventions to Reduce Stress in Healthcare Delivery

Clinician Burnout is a personal and public health issue. Most occupational stressors contributing to clinician burnout are systemic. The combination of organizational interventions along with individual interventions is necessary to make significant lasting difference in reducing burnout, improving clinician and patient satisfaction and reducing latent error in healthcare delivery. Application of Human Factors/Ergonomics (HFE) science in healthcare leadership and management is a gap in current training for leaders. HFE uses concepts from organizational, educational and cognitive science, systems science and industrial engineering. HFE application is especially necessary in a fast changing highly stressful healthcare environment which impacts the wellbeing of clinicians and the safety of patients under care. Practical suggestions for working with various healthcare leadership styles and organizational dynamics, while aligning wellness efforts with institutional mission are discussed. Concrete examples of decreasing extraneous mental load on clinicians to preserve their brainpower to achieve quality patient care are illustrated. Organizational interventions in combination with individual interventions to reduce and manage burnout have enormous potential to improve clinician wellbeing and satisfaction in taking care of patients, reduce costs, risk of error and create the safe working environment needed to sustainably give high quality care to patients.

From Digital Human Modeling to Human Digital Twin: Framework and Perspectives in Human Factors

The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulating human physical and cognitive aspects to support ergonomic analysis.However,it has limitations in real-time data usage,personalized services,and timely interaction.The emerging HDT concept offers new possibilities by integrating multi-source data and artificial intelligence for continuous monitoring and assessment.Hence,this paper reviews the evolution from DHM to HDT and proposes a unified HDT framework from a human factors perspective.The framework comprises the physical twin,the virtual twin,and the linkage between these two.The virtual twin integrates human modeling and AI engines to enable model-data-hybrid-enabled simulation.HDT can potentially upgrade traditional ergonomic methods to intelligent services through real-time analysis,timely feedback,and bidirectional interactions.Finally,the future perspectives of HDT for industrial applications as well as technical and social challenges are discussed.In general,this study outlines a human factors perspective on HDT for the first time,which is useful for cross-disciplinary research and human factors innovation to enhance the development of HDT in industry.

INTEGRATION OF HUMAN FACTORS ENGINEERING AND QUALITY MANAGEMENT

Human factors engineering and quality management are different research branches in the field of industrial engineering.A basis for interaction based on the concepts and techniques of human factors engineering and quality management with some practical examples of cooperative effect is defined in this paper.The specific challenges about the quality management in manufacturing and service are presented to demonstrate that the human factors analysis of quality problems leads to new tends for integrated development.

Disinfection Byproducts and Their Precursors in Drinking Water Sources:Origins,Influencing Factors,and Environmental Insights

Tracing the contamination origins in water sources and identifying the impacts of natural and human processes are essential for ecological safety and public health.However,current analysis approaches are not ideal,as they tend to be laborious,time-consuming,or technically difficult.Disinfection byproducts(DBPs)are a family of well-known secondary pollutants formed by the reactions of chemical disinfectants with DBP precursors during water disinfection treatment.Since DBP precursors have various origins(e.g.,natural,domestic,industrial,and agricultural sources),and since the formation of DBPs from different precursors in the presence of specific disinfectants is distinctive,we argue that DBPs and DBP precursors can serve as alternative indicators to assess the contamination in water sources and identify pollution origins.After providing a retrospective of the origins of DBPs and DBP precursors,as well as the specific formation patterns of DBPs from different precursors,this article presents an overview of the impacts of various natural and anthropogenic factors on DBPs and DBP precursors in drinking water sources.In practice,the DBPs(i.e.,their concentration and speciation)originally present in source water and the DBP precursors determined using DBP formation potential tests—in which water samples are dosed with a stoichiometric excess of specific disinfectants in order to maximize DBP formation under certain reaction conditions—can be considered as alternative metrics.When jointly used with other water quality parameters(e.g.,dissolved organic carbon,dissolved organic nitrogen,fluorescence,and molecular weight distribution)and specific contaminants of emerging concern(e.g.,certain pharmaceuticals and personal care products),DBPs and DBP precursors in drinking water sources can provide a more comprehensive picture of water pollution for better managing water resources and ensuring human health.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Assessment of Dependent Performance Shaping Factors in SPAR-H Based on Pearson Correlation Coefficient

With the improvement of equipment reliability,human factors have become the most uncertain part in the system.The standardized Plant Analysis of Risk-Human Reliability Analysis(SPAR-H)method is a reliable method in the field of human reliability analysis(HRA)to evaluate human reliability and assess risk in large complex systems.However,the classical SPAR-H method does not consider the dependencies among performance shaping factors(PSFs),whichmay cause overestimation or underestimation of the risk of the actual situation.To address this issue,this paper proposes a new method to deal with the dependencies among PSFs in SPAR-H based on the Pearson correlation coefficient.First,the dependence between every two PSFs is measured by the Pearson correlation coefficient.Second,the weights of the PSFs are obtained by considering the total dependence degree.Finally,PSFs’multipliers are modified based on the weights of corresponding PSFs,and then used in the calculating of human error probability(HEP).A case study is used to illustrate the procedure and effectiveness of the proposed method.

Abnormal Expression of Eukaryotic Translation Factors in Malignant Transformed Human Bronchial Epithelial Cells Induced by Crystalline Nickel Sulfide

Objective To study the oncogenic potential of mouse translation initiation factor 3 （TIF3） and elongation factor-1δ （TEF-1δ） in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide （NiS）. Methods Abnormal expressions of human TIF3 and TEF-1δ genes in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were investigated and analyzed by the reverse transcript polymerase chain reaction （RT-PCR） and fluorescent quantitative polymerase chain reaction （FQ-PCR）, respectively. Results RT-PCR analysis primarily showed that both human TIF3 and TEF-1δ mRNA expressions in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were increased as compared with controls. FQ-PCR assay showed that the levels of TIF3 expressions in the transformed cells and tumorigenic cells were 3 and 4 times higher respectively, and the elevated expressions of TEF-16 eDNA copies were 2.7- to 3.5-fold in transformed cells and 4.1- to 5.2-fold in tumorigenic cells when compared with non-transformed cells, indicating that the over-expressions of human TIF3 and TEF-1δ genes were related to malignant degree of the cells induced by nickel. Conclusions These findings demonstrate that there are markedly abnormal expressions of TIF3 and TEF-1δ genes during malignant transformation of human bronchial epithelial cell lines induced by crystalline NiS. They seem to be the molecular mechanisms potentially responsible for human carcinogensis due to nickel.

Addressing Human Factors in Burnout and the Delivery of Healthcare: Quality & Safety Imperative of the Quadruple Aim

Human factors in the delivery of service are considered in many occupations of high impact on others such as airline industry and nuclear power industry, but not sufficiently in healthcare delivery. A common administrative framework of healthcare involves focus upon costs, quality and patient satisfaction (The Triple Aim). Many industries which support healthcare and healthcare administrators do not have firsthand knowledge of the complexities in delivering care. As a result, the experience and human factors of providing care are often overlooked at high level decision-making unless incorporated into the healthcare delivery framework, proposed as the fourth aim of The Quadruple Aim framework. Research is pointing to consequent negative effects on quality, safety, joy, meaning and sustainability of healthcare practice. High acute occupational stress and chronic occupational stress can cause direct and indirect effects on safety and quality of care. The biological, psychological and social consequences of burnout from excessive acute and chronic occupational stress are more of a threat to healthcare than commonly acknowledged. Patient safety, quality of care and clinician well-being are inextricably linked. This report will describe the process of transition from The Triple Aim to The Quadruple Aim administrative framework of healthcare delivery at the University of Rochester Medical Center. Developing the fourth aim of improving the experience of providing care, had high acceptability and aligned with other health system goals of optimization of safety, quality, and performance by applying a human factors/ergonomic (HFE) framework that considers human capabilities and human limitations. The goal of HFE is to fit the healthcare system to the human instead of the human to the healthcare system. Concepts include removal of extraneous cognitive load, using clinician neural resource (brain power) optimally for highest order decision making in patient care. An integrative model of patient safety and clinician wellbeing is a product of this effort.

Epidemiological profiles of human immunodeficiency virus and hepatitis C virus infections in Malian women:Risk factors and relevance of disparities

AIM:To document the epidemiologic patterns and risk factors of human immunodeficiency virus(HIV)and hepatitis C virus(HCV)infections in Mali in order to develop prevention means for both diseases.METHODS:Two prospective studies were conducted in Bamako in 2009 among 1000 pregnant women(i.e.,young women)who consulted six reference health centers,and in 2010,among 231 older women who attended general practice in two hospitals.Antibody tests and molecular analysis(performed only for HCV)were used to quantify the frequencies of both infections.The data were collected from patients recruited through a questionnaire.Transmission risk factors of both diseases were identified by univariate and multivariate analysis.RESULTS:HCV seroprevalence was 0.2% for young and 6.5% for older women.HIV prevalence was similar in both populations(4.1% vs 6.1%).In older women,the analysis of risk factors highlighted an association between HCV infection and episodes of hospitalization(P < 0.01).The study did not show an association between HIV infection and the variables such as hospitalization,transfusion,tattoo,dental care,and endoscopy.A significant decrease of HIV seroprevalence was detected in young women who used condoms for contraception more than for other purposes(P < 0.01).By contrast,HIV seroprevalence was significantly increased in young women using condoms mainly to prevent sexual infections rather than for contraception(P < 0.01).No HCV/HIV coinfection was detected in our study.CONCLUSION:Risk factors and epidemiologic data of HIV and HCV as well as the absence of co-infection strongly suggest epidemiological disparities between these diseases.

Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study

BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodeficiency virus(HIV)-negative patients with Talaromyces marneffei(T. marneffei) infection.METHODS: We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis.RESULTS: Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat(ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suff ered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen(BUN), alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactic dehydrogenase(LDH), myoglobin(Mb), procalcitonin(PCT), and galactomannan were related to poor prognosis(hazard ratio [HR]>1, P<0.05).CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

Intervention decision-making in MAV/UAV cooperative engagement based on human factors engineering

Aiming at the intervention decision-making problem in manned/unmanned aerial vehicle（MAV/UAV） cooperative engagement, this paper carries out a research on allocation strategy of emergency discretion based on human factors engineering（HFE）.Firstly, based on the brief review of research status of HFE, it gives structural description to emergency in the process of cooperative engagement and analyzes intervention of commanders. After that,constraint conditions of intervention decision-making of commanders based on HFE（IDMCBHFE） are given, and the mathematical model, which takes the overall efficiency value of handling emergencies as the objective function, is established. Then, through combining K-best and variable neighborhood search（VNS） algorithm, a K-best optimization variable neighborhood search mixed algorithm（KBOVNSMA） is designed to solve the model. Finally,through three groups of simulation experiments, effectiveness and superiority of the proposed algorithm are verified.

Relative importance of climate factors and human activities in impacting vegetation dynamics during 2000–2015 in the Otindag Sandy Land,northern China

In recent years, there has been increasing research interests in differentiating the relative importance of climate factors and human activities in impacting vegetation dynamics. In this study, based on residual trend method, we used MOD13A3（MODIS vegetation index product）, MCD12Q1（MODIS land cover product） and meteorological datasets to differentiate the relative importance of climate factors and human activities in impacting vegetation dynamics during 2000–2015 in the Otindag Sandy Land, northern China. Results show that during the study period（2000–2015）, the overall vegetation condition had improved in the Otindag Sandy Land. The driving forces of vegetation dynamics differed spatially in the whole study area over the study period. The area with vegetation degradation solely resulted from human activities accounted for 8.23% of the study area, while the area with vegetation degradation resulted from others（including climate factors and combination of climate factors and human activities） occupied 1.53%. The area with vegetation recovery benefitted from human activities occurred over 26.02% of the study area; the area benefitted from climate factors accounted for 23.69%; and the area benefitted from both climate factors and human activities occupied 37.74%. All in all, impacts of climate factors and human activities on vegetation dynamics varied at the county/city/banner scales and locality-specific measures should be adopted to protect the environments.

Management of human factors engineering-associated hemochromatosis: A 2015 update

This review focuses on the management of iron metabolism and iron overload experienced in the hereditary condition, human factors engineering(HFE)-associated hemochromatosis. Hemochromatosis refers to a group of genetic diseases that result in iron overload; the major one globally is HFE-associated hemochromatosis. The evolution in understanding of the most common form of hereditary hemochromatosis, being the substation of cysteine to a tyrosine at position 282 in the HFE gene, has been extensively studied Novel mutations in both HFE and non-HFE genes have been indicated in this disease which hold significance in its application for the Asia-Pacific region. In conditions with iron overload, the storage of excess iron in various body tissues leads to complications and toxic damage. The most common presenting complaint for this disease is malaise, lethargy and other non-specific symptoms. In order to diagnose hereditary hemochromatosis, there are biochemical, imaging and genetic testing options. Currently, cascade screening of affected families is preferred over population-level screening. The mainstay of treatment is venesection and the appropriate approach to treatment has been consolidated over the years. Recently, the indications for venesection therapy of hemochromatosis have been challenged and are the subject of ongoing research.

Mapping of liver-enriched transcription factors in the human intestine

AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels. CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.

Quantitative Analysis of Natural and Human Factors of Oasis Change in the Tail of Shiyang River over the Past 60 Years

The human and natural factors complicit in the driving forces of oasis change have always received considerable interest from the international research community. In this study, we used principal component analysis of natural and socio-economic statistical factors to quantitatively analyze the causal relationships and their contributions to the observed periodic expansion or shrinkage of the Minqin Oasis over almost 60 years. Our results show that human factors were the dominant factors governing expansion or shrinkage, with average contributions of 69.38% and 76.16%, respectively. Moreover, policy decisions have been the pivotal human factors. Under the influence of various policies, we have found that water resource utilization, land reclamation, population explosion, ecological protection and economic development have each played leading roles in different periods. This study provides a scientific basis for modelling the dynamics of an oasis for sustainable management.

Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors"(RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus(HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell's intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16(IFI16)(a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and h Daxx; the latter three being the keys elements of nuclear domain 10(ND10). IFI16 inhibits the synthesis of virus DNA by downregulating UL54 transcription- a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65(p UL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents.

Risk factors for liver fibrosis among human immunodeficiency virus monoinfected patients using the FIB4 index in Morocco

AIM: To study the prevalence and risk factors of significant hepatic fibrosis in Moroccan human immunodeficiency virus(HIV) monoinfected patients.METHODS: We conducted a cross-sectional study among HIV monoinfected patients(negative for hepatitis B surface antigen and hepatitis C antibody). Clinical and laboratory data were collected from the data base of the Infectious Diseases Unit in Ibn Rochd Hospital Center [age, gender, duration of HIV infection, CD4 T lymphocyte count, HIV viral load, glycemia and current or prior use of antiretroviral and antiretroviral therapy(ART) duration]. The primary outcome was a FIB4score > 1.45. Multivariable logistic regression identifiedindependent risk factors for FIB4 > 1.45.RESULTS: A FIB4 score > 1.45 was identified in 96among 619(15.5%). HIV monoinfected patients followed up between September 1990 and September2012. Multivariate analysis showed that only a viral load > 75(OR = 2.23, 95%CI: 1.36-3.67), CD4 > 200cells/mm3(OR = 0.39, 95%CI: 0.21-0.72) and age at FIB4 index calculation(OR = 1.10, 95%CI: 1.07-1.13)were independently associated with the occurrence of FIB4 index(> 1.45). Gender, duration of HIV infection,glycemia, use of antiretroviral therapy and ART duration were not associated with significant fibrosis by FIB4.CONCLUSION: FIB4 score > 1.45 was found in 15.5%of Moroccan HIV monoinfected patients. Age, HIV viremia > 75 copies/mL and CD4 count > 200 cells/mm3are associated with liver fibrosis. Further studies are needed to explore mechanisms for fibrosis in HIV monoinfected patients.

Promoting Clinician Well-Being and Patient Safety Using Human Factors Science: Reducing Unnecessary Occupational Stress

Our healthcare delivery system has accumulated complexity of payment, regulation systems, expectations and requirements. Often these are not designed to align with clinical thinking process flow of patient care. As a result, clinicians are utilizing enormous mental (cognitive) resource to comply with these complexities, over and above the baseline mental effort required to give good care to the patient. Recent studies suggest a significant number of physicians, advanced practice providers and nurses no longer want to stay in healthcare due to difficult work expectations and conditions that have become unreasonable. Technology has benefitted healthcare delivery, but also is a conduit of many expectations that have been grafted upon clinician workloads, exceeding the resources provided to accomplish them. Cognitive load is a measure of mental effort and is divided into Intrinsic, Germane and Extraneous Cognitive Load. Extraneous Cognitive Load (ECL) is what is not necessary and can be removed by better design. High cognitive load is associated with increased risk of both medical error and clinician burnout. Chronic high level occupational stress occurs from dealing with this job/resource imbalance and is showing serious personal health impact upon clinicians and the quality of the work they can provide for patients. Since organizational systems have become more complex, leadership methods, clinician wellbeing and patient safety efforts need to adjust to adapt and succeed. Safety efforts have tended to predominantly follow methods of a few decades ago with predominant focus upon how things go wrong (Safety I) but are now being encouraged to include more of the study of how things go right (Safety II). Human Factors/Ergonomics (HFE) science has been used in many industries to preserve worker wellbeing and improve system performance. Patient safety is a product of good system performance. HFE science helps inform mechanisms behind Safety I and II approach. HFE concepts augment existing burnout and safety interventions by providing a conceptual roadmap to follow that can inform how to improve the multiple human/technology, human/system, and human/work environment interfaces that comprise healthcare delivery. Healthcare leaders, by their influence over culture, resource allocation, and implementation of requirements and workflows are uniquely poised to be effective mitigators of the conditions leading to clinician burnout and latent medical error. Basic knowledge of HFE science is a strategic advantage to leaders and individuals tasked with achieving quality of care, controlling costs, and improving the experiences of receiving and providing care.

Trans-acting factors from the human fetal liver bindingto the human ε-globin gene silencer

The developmental stage-specific silencing of the human ε-globin gene during embryonic life is controlled, inpart, by the silencer (-392bp～-177bp) upstream of thisgene. In order to elucidate its role, the nuclear extractfrom the human fetal liver has been prepared and the interactions between trans-acting factors and this silencerelement have been examined. By using DNasel footprinting assay, a major protected region from -278bp to -235bpwithin this silencer element was identified. Furthermore,we found in gel mobility shift assay and Southwestern blotting assay that there were at least four trans-acting factors (MW ≈ 32, 28, 26 and 22kD) in the nuclear extractisolated from the human fetal liver, which could specifically bind to this region. Our results suggested that thesetrans-acting factors might play an important role in silencing the human embryonic ε-globin gene expression at thefetal stage through the interactions with this silencer.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.