[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Measuring quality of reporting in systematic reviews of diagnostic test accuracy studies in medical imaging: comparison of PRISMA-DTA and PRISMA.

OBJECTIVES: To compare the reporting quality measured by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy studies (PRISMA-DTA) vs the original PRISMA checklist for systematic reviews of diagnostic test accuracy studies in imaging and survey the use of PRISMA-DTA by researchers and endorsement by journals. METHODS: Systematic reviews of DTA studies published in 2020 and 2021 in Quartile 1 and Quartile 3 medical imaging journals (defined by Journal Citation Reports) were identified through PubMed. The reporting of each systematic review was assessed using PRISMA-DTA, PRISMA-2009 and PRISMA-2020. The item scores and overall score were compared among the three checklists. We also examined checklist adoption by the included systematic reviews and surveyed checklist endorsement from author instructions of included journals. RESULTS: A total of 173 systematic reviews from 66 journals were included. The use of PRISMA-DTA, compared with PRISMA-2009 and PRISMA-2020, identified more issues in the reporting of title (proportion of systematic reviews with proper reporting, 27.2% vs 98.8% vs 98.8%), abstract (39.3% vs 97.1% vs 64.7%), eligibility criteria (67.6% vs 94.2% vs 94.2%), search (28.9% vs 72.3% vs 28.9%), definitions for data extraction (14.5% vs 91.9% vs 91.9%), diagnostic accuracy measures (38.2% vs 93.6% vs 93.6%), synthesis of results (28.9% vs 89.6% vs 73.4%) and results of individual studies (40.5% vs 80.3% vs 80.3%). The overall median reporting score measured by PRISMA-DTA (72.0% (interquartile range (IQR), 66.7-77.8%)) was lower than that measured by PRISMA-2009 (88.9% (IQR, 84.0-92.6%)) and similar to that measured by PRISMA-2020 (74.1% (IQR, 66.7-77.8%)). Additionally, PRISMA-DTA was used by only 43 (24.9%) systematic reviews and endorsed by two (3.0%) journals. These trends remained consistent for reviews published in journals with diverse scientific impact. CONCLUSIONS: The use of PRISMA-DTA may identify more reporting inadequacies compared with the original PRISMA checklists when assessing diagnostic test accuracy systematic reviews, especially in critical sections such as title, abstract and methods. However, this tool is not commonly used by researchers and is inadequately endorsed by imaging journals. Our findings suggest a strong need to use PRISMA-DTA for reporting of diagnostic test accuracy systematic reviews by authors and its endorsement by journals. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

[Current situation and prospect of primary prevention of cancer in China].

Cancer is a major public health issue that seriously endangers the public health and social development of China. Future initiatives for cancer prevention and control should continue to adhere to the principle of prioritizing prevention, and comprehensively implement related prevention activities nationwide. This is critical to reducing cancer burden in Chinese residents, especially in the low- and middle-income populations and those living in areas that are less economically developed. In the past several decades, the international community has significantly reduced the incidence of related cancers through primary prevention measures such as tobacco control, improved occupational hygiene, and vaccination. China has also implemented a series of exploratory primary prevention measures among high-risk groups of cancer in specific areas including Xuanwei, Qidong, and Linxian, and achieved encouraging results. However, due to the low level of systematic awareness of cancer risk factors and the lack of awareness and ability of self-health management in Chinese residents, it is urgent to develop novel research tools and methods to further reveal the causes of cancer, and establish innovative mechanisms and systems of primary prevention of cancer at population and individual levels. Based on current status of the transformation of cancer spectrum and the development of digital intelligence, it would be beneficial to establish a smart digital system for primary cancer prevention service that can cover the entire population, integrating authoritative popular science education on primary prevention of cancer, individualized cancer risk assessment, and personalized health management assistant. This will improve primary cancer prevention among the Chinese general population and can help the sustainable development of cancer prevention and control in China.

[Exploration of construction mode of real-world data system].

Real-world data study evidence, as an important part of evaluating the safety and effectiveness of drugs and devices, has attracted increasing attention from regulatory agencies and scholars both at home and abroad, and has become an essential source of evidence to support the development and review of drugs and devices. This paper systematically discusses the process and mode of real-world data system construction based on the preliminary practical study of real-world data according to the guidelines/technical specifications issued by regulatory agencies and academic research results. This study result provides not only reference for the generation of clinical evaluation evidence to meet the regulatory requirements for innovative drugs and devices, but also reference for researchers, sponsors and regulators to carry out real-world data studies successfully.

[Real-world data studies of medical products in the context of special healthcare policy: study designs and key considerations].

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.

[Electromyography analysis in 13 patients with acute trimethyltin chloride poisoning].

Objective: To investigate the electromyography (EMG) characteristics and clinical significance in patients with acute trimethyltin chloride (TMT) poisoning. Methods: Retrospectively analyze the EMG results of major limb nerves and muscles of 13 patients with acute TMT poisoning. Results: Among the 13 patients, 10 cases had abnormal and the abnormal rate was 76.9%. The same degree of involvement of upper and lower limbs is the most common. And distal peripheral nerve damage is the most common, mainly manifested as sensory damage or mixed sensory and motor damage, with axonal injury and demyelinating lesions to almost the same degree. The peroneal nerve and median nerve were the most vulnerable, with an abnormal rate of 39.1% and 35.9%, respectively. The peroneal nerve and median nerve were damaged first but recovered slowly.The ulnar nerve first appeared damaged and recovered quickly. The sural nerve was damaged later. Conclusion: Acute TMT poisoning can cause limb peripheral nerve damage. This damage is a slow, gradual process, and its recovery is also a slow process.

Progress in the 16S rRNA Gene Sequencing in Forensic Science.

Forensic microorganism is one of the hotspots of forensic science research. Due to its conservatism and specificity, the 16S rRNA gene is found to be an ideal marker for forensic identification. With the rapid development of high throughput sequencing technology, the research on microorganisms has been gradually applied to many fields such as environment and health care. In the field of forensic science, the results of forensic microbiology research, represented by 16S rRNA gene sequencing, are also gradually applied to forensic practice, such as biological samples identification, individual identification, postmortem interval estimation, and regional inference, which not only provide clues for the investigation of cases but also complement and assist traditional methods. This paper describes the research methods and related sequencing technologies of 16S rRNA gene sequencing, summarizes its research progress, and discusses the application value and potential of 16S rRNA in forensic science.

[Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGM™ Platform].

OBJECTIVES: To analyze and detect the whole genome sequence of human mitochondrial DNA （mtDNA） by Ion Torrent PGM™ platform and to study the differences of mtDNA sequence in different tissues. METHODS: Samples were collected from 6 unrelated individuals by forensic postmortem examination, including chest blood, hair, costicartilage, nail, skeletal muscle and oral epithelium. Amplification of whole genome sequence of mtDNA was performed by 4 pairs of primer. Libraries were constructed with Ion Shear™ Plus Reagents kit and Ion Plus Fragment Library kit. Whole genome sequencing of mtDNA was performed using Ion Torrent PGM™ platform. Sanger sequencing was used to determine the heteroplasmy positions and the mutation positions on HVⅠ region. RESULTS: The whole genome sequence of mtDNA from all samples were amplified successfully. Six unrelated individuals belonged to 6 different haplotypes. Different tissues in one individual had heteroplasmy difference. The heteroplasmy positions and the mutation positions on HVⅠ region were verified by Sanger sequencing. After a consistency check by the Kappa method, it was found that the results of mtDNA sequence had a high consistency in different tissues. CONCLUSIONS: The testing method used in present study for sequencing the whole genome sequence of human mtDNA can detect the heteroplasmy difference in different tissues, which have good consistency. The results provide guidance for the further applications of mtDNA in forensic science.

Expressions of IL-1α and MMP-9 in degenerated lumbar disc tissues and their clinical significance.

OBJECTIVE: To observe the expression levels of interleukin-1α (IL-1α) and matrix metalloproteinase-9 (MMP-9) in degenerated lumbar disc tissues and to investigate their clinical significance. PATIENTS AND METHODS: Fifty patients with lumbar disc degeneration received the operative treatment were divided into three groups according to the magnetic resonance imaging (MRI) results: protrusion group, extrusion group, and free group. The degenerated intervertebral disc tissues were taken, and the normal intervertebral disc tissues of 20 patients received the operative treatment due to lumbar bursting fracture, and were selected as the control group. The bone mineral densities of all patients were measured. The mRNA and protein expression levels of MMP-9 and IL-1α were detected via Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: The bone mass of patients with lumbar disc degeneration was significantly decreased compared with that of the control group, and the bone mass was decreased more significantly in a free group than that in protrusion group. The mRNA and protein levels in IL-1α and MMP-9 of patients with lumbar disc degeneration were significantly increased compared with those in control group; the mRNA and protein levels in IL-1α and MMP-9 of extrusion group and free group were significantly higher than those in protrusion group, and the mRNA and protein levels in IL-1α and MMP-9 of free group were significantly higher than those in extrusion group. CONCLUSIONS: The levels of IL-1α and MMP-9 in degenerated lumbar disc tissues are higher than normal levels, and the increasing levels are positively correlated with the disease condition.

Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients

Circulating tumor cell (CTC) count and the host inflammatory response are two independent predictors for patients with various malignant disease. Several inflammation-based indicators have been demonstrated to have prognostic value in many malignant solid tumors, including systemic immune-inflammation index (SII), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutrition index (PNI). The aim of this study was to evaluate the predictive value of the inflammation-based indexes including SII, NLR PLR, and PNI for CTC detection of gastric cancer patients before surgery. Methods. CTCs were measured using the isolation method by size of epithelial tumor cells and Wright staining for 60 patients with gastric cancer who underwent surgery. The indicators of SII, NLR, PLR, and PNI were calculated based on clinical laboratory testing. Results. The detected CTC number was correlated with extension of tumor invasion (p = 0.037), lymph node metastasis (p < 0.001), and TNM stage (p < 0.001). The CTC detection ratio was significantly correlated with T stage (p = 0.041), lymph node metastasis (p = 0.001), nerve fiber invasion of tumor outside the lymph nodes (p = 0.017), and TNM stage (p < 0.001). Statistical analysis showed that SII (p < 0.001), NLR (p < 0.001), PLR (p < 0.001), and PNI (p < 0.001) were significantly associated with positive CTC count and CTC detection rate. Conclusions. This study provides evidence that preoperative indicators consisting of SII, NLR, PLR, and PNI are robust predictors for CTC detection in gastric cancer patients undergoing tumor resection (AU)

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Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients.

PURPOSE: Circulating tumor cell (CTC) count and the host inflammatory response are two independent predictors for patients with various malignant disease. Several inflammation-based indicators have been demonstrated to have prognostic value in many malignant solid tumors, including systemic immune-inflammation index (SII), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutrition index (PNI). The aim of this study was to evaluate the predictive value of the inflammation-based indexes including SII, NLR PLR, and PNI for CTC detection of gastric cancer patients before surgery. METHODS: CTCs were measured using the isolation method by size of epithelial tumor cells and Wright staining for 60 patients with gastric cancer who underwent surgery. The indicators of SII, NLR, PLR, and PNI were calculated based on clinical laboratory testing. RESULTS: The detected CTC number was correlated with extension of tumor invasion (p = 0.037), lymph node metastasis (p < 0.001), and TNM stage (p < 0.001). The CTC detection ratio was significantly correlated with T stage (p = 0.041), lymph node metastasis (p = 0.001), nerve fiber invasion of tumor outside the lymph nodes (p = 0.017), and TNM stage (p < 0.001). Statistical analysis showed that SII (p < 0.001), NLR (p < 0.001), PLR (p < 0.001), and PNI (p < 0.001) were significantly associated with positive CTC count and CTC detection rate. CONCLUSIONS: This study provides evidence that preoperative indicators consisting of SII, NLR, PLR, and PNI are robust predictors for CTC detection in gastric cancer patients undergoing tumor resection.

Potential benefits of diagnosis and treatment on health outcomes among elderly people with symptoms of overactive bladder.

OBJECTIVES: This study examined potential benefits of diagnosing and treating elderly adults with overactive bladder (OAB) symptoms. METHODS: Data were analysed from the OAB Re-Contact Study (N = 2750), a cross-sectional, self-reported Internet survey. Elderly respondents (65+ years old) with OAB were identified according to current medication use to control OAB symptoms or by scores > 14 (men) or > 16 (women) on the OAB Awareness Tool. Treated were those currently using prescription medication and never treated were those who never used prescription medication for OAB. Outcome measures included health-related quality of life, activity impairment, OAB-related severity and symptoms, and healthcare resource use (e.g. hospitalisations). Generalised linear models predicted health outcomes as a function of diagnosis or treatment, adjusting for covariates. RESULTS: Diagnosed vs. not diagnosed elderly respondents had higher mental component summary (MCS) scores and SF-6D health utilities, and less activity impairment. Treated vs. never treated elderly respondents had higher MCS and SF-6D health utilities, less activity impairment, fewer OAB symptoms, lower OAB Awareness Tool scores, and lower odds of having bladder problems or incontinence. There were no significant differences in healthcare resource use. Further analysis by age group (middle-aged vs. elderly respondents) revealed significantly greater diagnosis- and treatment-related benefits on MCS (2.93 and 4.49 points more, respectively) and activity impairment (1.24 and 1.37 times as much, respectively) among elderly respondents. CONCLUSIONS: Diagnosis and treatment were each associated with a lower health burden for elderly adults with OAB symptoms. These findings highlighted the importance of diagnosis and treatment in alleviating OAB symptoms and their impact on health outcomes.

Risk and protective factors for falls on stairs in young children: multicentre case-control study.

AIM: To investigate risk and protective factors for stair falls in children aged <5 years. METHODS: Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated. RESULTS: Cases' most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%). CONCLUSION: Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries.

Source Identification of Human Biological Materials and Its Prospect in Forensic Science.

Source identification of human biological materials in crime scene plays an important role in reconstructing the crime process. Searching specific genetic markers to identify the source of different human biological materials is the emphasis and difficulty of the research work of legal medical experts in recent years. This paper reviews the genetic markers which are used for identifying the source of human biological materials and studied widely, such as DNA methylation, mRNA, microRNA, microflora and protein, etc. By comparing the principles and methods of source identification of human biological materials using different kinds of genetic markers, different source of human biological material owns suitable marker types and can be identified by detecting single genetic marker or combined multiple genetic markers. Though there is no uniform standard and method for identifying the source of human biological materials in forensic laboratories at present, the research and development of a series of mature and reliable methods for distinguishing different human biological materials play the role as forensic evidence which will be the future development direction.

[Identification of Vaginal Fluid Using Microbial Signatures].

OBJECTIVES: To investigate the specific microbial signatures in vaginal fluid. METHODS: Vaginal fluid （16 samples）, saliva （16 samples）, feces （16 samples）, semen （8 samples）, peripheral blood （8 samples）, urine （5 samples）, and nasal secretion （4 samples） were collected respectively. The 16S rRNA genes of Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus iners, and Atopobium vaginae were amplified. PCR production was detected via a 3130xl Genetic Analyzer. RESULTS: The detected number of Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus iners, and Atopobium vaginae were 15, 5, 8, 14, and 3 in all vaginal fluid samples, respectively. Lactobacillus crispatus and Lactobacillus jensenii existed specifically in vaginal fluid. CONCLUSIONS: There is a potential application value to detect Lactobacillus crispatus and Lactobacillus jensenii for the identification of vaginal fluid.

[Research Progress on Gene Alterations of Amelogenin Locus in Gender Identification].

There are two kinds of amelogenin gene mutation, including mutation in primer-binding region of amelogenin gene and micro deletion of Y chromosome encompassing amelogenin gene, and the latter is more common. The mechanisms of mutation in primer-binding region of amelogenin gene is nucleotide point mutation and the mechanism of micro deletion of Y chromosome encompassing amelogenin gene maybe non-allelic homologous recombination or non-homologous end-joining. Among the population worldwide, there is a notably higher frequency of amelogenin gene mutations in Indian population, Sri Lanka population and Nepalese population which reside within the Indian subcontinent. Though amelogenin gene mutations have little impact on fertility and phenotype, they might cause incorrect result in gender identification. Using composite-amplification kit which including autosomal STR locus, amelogenin gene locus and multiple Y-STR locus, could avoid wrong gender identification caused by amelogenin gene mutation.

Prevalence, management and outcomes of medically complex vulnerable elderly patients with urinary incontinence in the United States.

OBJECTIVES: To assess the prevalence, patient-physician communication, treatment and health outcomes associated with urinary incontinence (UI) among the medically complex vulnerable elderly (MCVE) in the United States (US). METHODS: Data from the 2006 to 2012 Medicare Health Outcomes Survey (HOS) were used. MCVE patients were aged 65+ years with a HOS VE score ≥ 3. UI was reported as a small, big or no problem. Descriptive statistics were used to assess patient-physician communication and treatment. Multivariable regression analyses were performed to assess the association of small or big UI problems with various outcomes. RESULTS: The annual UI prevalence increased among MCVE [from 35.8% (2006) to 38.6% (2012)]. MCVE with big UI problems communicated with their physicians more often than those with small UI problems (77.9% and 49.6%, respectively); however, treatment of UI remained low (48.5% and 29.1%, respectively). Physical component summary (PCS) and mental component summary (MCS) scores were lower among MCVE with small or big UI problems compared with those with no UI problems, respectively. The decrements in PCS and MCS scores associated with big UI problems were greater than the decrements associated with any of the other assessed conditions. MCVE with small or big UI problems, respectively, were more likely to report past falls, depression and activity daily living limitations vs. those without UI. The odds of having experienced these outcomes were greater for those with big UI vs. small UI problems. CONCLUSIONS: Urinary incontinence prevalence in the USA increased among MCVE from 2006 to 2012, although treatment of UI remained low. UI problems, particularly big UI problems, adversely impact health outcomes. Efforts to better identify and manage UI among the MCVE are needed.

Live Combined Bacillus subtilis and Enterococcus faecium Ameliorate Murine Experimental Colitis by Immunosuppression.

Live combined Bacillus subtilis and Enterococcus faecium ameliorate murine experimental colitis by immunosuppression manifested by downregulation of TLRs, macrophages, Th1, and Th2 but upregulation of Tregs.

Direct and indirect cost of urge urinary incontinence with and without pharmacotherapy.

OBJECTIVE: To evaluate the impact of treating urge urinary incontinence (UUI), including mixed urinary incontinence (MUI), on healthcare resource utilisation, productivity, activity impairment and associated costs. METHODS: The study used data from the 2011 U.S. National Health and Wellness Survey, an Internet-based questionnaire of a nationwide sample of adults. UUI or MUI respondents were identified via three Incontinence Questions. Respondents with stress urinary incontinence only, prostate cancer or (medication for) benign prostatic hyperplasia were excluded. UUI/MUI respondents were categorised as Rx users for overactive bladder (OAB) and non-Rx users (who never used Rx and whose condition reportedly interfered with life activities or was difficult to manage). Outcome measures included healthcare utilisation and Work Productivity and Activity Impairment questionnaire-based scores. Direct and indirect costs were estimated using 2010 labour and 2008 medical expenditure data sources. Generalised linear models predicted resource use and productivity as a function of treatment status, adjusting for covariates (e.g. sociodemographics, OAB severity, comorbid status) that may also predict impairment. RESULTS: Rx (vs. non-Rx) users were more likely to be female (80.7% vs. 70.0%), older (mean = 62.7 vs. 53.1) and reporting more moderate-to-severe OAB (70.9% vs. 52.6%; all p < 0.05). Adjusting for covariates, Rx (vs. non-Rx) users had significantly lower activity impairment (41.1% vs. 46.8%), more provider visits (7.42 vs. 5.60) and costs ($18,175 vs. $13,679), and higher total direct costs ($27,291 vs. $21,493), all p < 0.01. CONCLUSIONS: Urge urinary incontinence patients using, vs. never using, prescription medication reported lower activity impairment but higher direct costs. These findings may inform the degree to which UUI pharmacotherapy affects health outcomes.

Transport studies of dual-gated ABC and ABA trilayer graphene: band gap opening and band structure tuning in very large perpendicular electric fields.

We report on the transport properties of ABC and ABA stacked trilayer graphene using dual, locally gated field effect devices. The high efficiency and large breakdown voltage of the HfO(2) top and bottom gates enable independent tuning of the perpendicular electric field and the Fermi level over an unprecedentedly large range. We observe a resistance change of 6 orders of magnitude in the ABC trilayer, which demonstrates the opening of a band gap. Our data suggest that the gap saturates at a large displacement field of D ~ 3 V/nm, in agreement with self-consistent Hartree calculations. In contrast, the ABA trilayer remains metallic even under a large perpendicular electric field. Despite the absence of a band gap, the band structure of the ABA trilayer continues to evolve with increasing D. We observe signatures of two-band conduction at large D fields. Our self-consistent Hartree calculation reproduces many aspects of the experimental data but also points to the need for more sophisticated theory.