Comparative Efficacy of Lifestyle Modifications versus Pharmacotherapy on Weight Loss and Metabolic Health Outcomes: A Comprehensive Review

Background: Obesity has become a serious global public health challenge, given that it leads to various adverse health outcomes that include cardiovascular illnesses, diabetes, and certain types of cancer. The World Health Organization (WHO) has estimated that, at the end of 2022, 1 out of every 8 individuals were obese, and that the global adult obesity rates have over doubled since 1990, even as the adolescent obesity rates have quadrupled. Thus, as of 2022, nearly 2.5 billion adults, aged 18 years and above, were overweight, with 890 million being obese. Obesity and overweight incidence rate has been gradually increasing over the years, presenting significant challenges to the healthcare systems throughout the globe. In this regard, the objective of this systematic review was to evaluate the effectiveness and safety of lifestyle modifications (diet and physical activity) and pharmacotherapy in promoting weight loss and improving metabolic health in overweight adults. Methodology: To attain the above stated study objective, a systematic evaluation of previous studies was carried out, particularly studies that assessed the effectiveness and safety of lifestyle modifications (diet and physical activity) and pharmacotherapy in promoting weight loss and improving metabolic health in overweight adults. The authors have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in the selection of eligible studies for inclusion in the study. Results: The findings indicate that lifestyle interventions resulted in 5% - 10% weight reduction and significant improvements in metabolic indicators, while pharmacotherapy (GLP-1 receptor agonists) achieved up to 15% weight reduction and considerable metabolic health benefits. Further, comparative studies show lifestyle modifications provide overall health benefits, while medication is necessary for non-responders. Conclusion: Individualized treatment strategies are crucial, and further research is needed on long-term consequences and combination therapies.

精准医学开拓个体化医疗领域“蓝海市场”的进程

大科学、大数据时代,精准医学(precision medicine,PM)在概念、规模、技术手段、应用范围等各方面已有质的飞跃,正在为高科技研发提供源源不断的动力。与传统医学所提倡的辩证施治相比,作为循证医学加强版的PM力求标本兼治,且百发百中,强调个体生命的生物学、个体行为、生活方式和生存环境等相关因素的动态互作,并以此为基石量身定制全方位的个性化医疗与健康服务。乘势而为的一大批学术机构、研究联盟以及资金充裕的生物技术、生物制药项目也在各自的创新之路取得了令人鼓舞的佳绩;其宏伟蓝图是推动多维度、全方位的医疗保健产品与服务,逐渐将可预判(Predictive)、可预防(Preventive)、可个性化(Personalized)、可参与/分享(Participatory)的“4P医学”一一落到实处。如果将PM视为未来医学发展的标杆并藉此满足全人类对整体福祉和健康、富足生活的渴望,那么该如何去客观衡量该领域的进展与成效?相信《中国医药导刊》的读者们在浏览2024年1月PM专刊时,这一现实问题会在脑海中反复涌现。鉴于此,为协助读者深入了解PM领域的主要发展历程,凸显该领域后续发展的任重道远,本述评主要以最近十年为坐标,回顾性梳理和探讨几个PM相关重要里程碑事件以及抢滩失败的教训来捕捉一些核心路径。作为人类与各种疾病激烈抗争的前沿阵地,PM既需要跨学科、综合性理论与高新技术手段的支持,也需要多边合作、互利共赢之策略。更为重要的是,PM除了引以为傲的科学价值、社会价值与大众吸引力以外,还需要依赖可行的商业模式来实现其崇高使命。

Analysis of Transportation Users’ Preferences and Attitudes for Identifying Micro-Level Determinants of Transportation Network Companies’ (TNCs) Growth

Over the last decade, the popularity of Transportation Network Companies (TNCs) as a mode of travel has been increasing at a steady pace. This trend highlights the importance of identifying the determinants that influence transportation users to adopt TNCs as a preferred mode choice and the impacts of such preferences on their travel patterns and transportation network operation. This paper reports on a recent study undertaken in Birmingham, AL aiming at understanding and documenting the factors that influence transportation users to select TNCs (such as Uber/Lyft) for completing typical day trips. In doing so, a travel diary questionnaire survey was developed in accordance with the Institute of Transportation Engineers (ITE) Manual on Transportation Engineering Studies using the Qualtrics Research Core platform. The questionnaire was used to survey over 450 transportation users in the Birmingham Metro area. The survey participants provided detailed trip information for a typical 24-hr day along with demographic data and travel preference information. The survey responses provide high-resolution micro-level indicators of travel preferences and behaviors in a TNC-served area, which is a much-needed type of information for researchers and transportation planning agencies.

Breast Imaging Experiences at Academic Medical Centers during COVID-19: Restructuring, Reopening, and Preparing for Possible Resurgence

Severe acute respiratory syndrome coronavirus 2 has thoroughly reshaped the medical landscape. Much has been written and discussed of the adaptations required by this pandemic, particularly in the realm of elective medical care. While some areas of the country have, in recent weeks, seen a plateau or even a decrease in coronavirus 2019 case-burden, others remain face-to-face with significant ongoing morbidity and mortality. Furthermore, given eased restrictions across numerous states and municipalities, a widespread resurgence of the disease is not precluded. To that end, we have attempted to summarize experiences and best practices in the handling of breast imaging against the backdrop of the novel coronavirus, and we consider future directions.

Induced Differentiation of Epithelioid Carcinoma Cell Lines: Evidence for Tumor Cell Quantal Mitosis

The effects of growth factors and calcium concentrations present in different culture media on induction of terminal differentiation were investigated for four different epidermoid carcinoma cell lines, Hela, KB, A431, and SCC-25, and their responses determined relative to those elicited by normal human keratinocytes subjected to these culture conditions. Differentiation status was determined cyto-chemically by a validated keratin protein staining method, and by autoradiographic analyses. Growth and differentiation promoting factors that influenced the direction of integrated control of growth and differentiation in normal human keratinocytes were found to be effective for some cell lines but not others. The factors examined were 1) high density arrest in serum-free and serum-containing media, 2) media shifts from high density culture in serum-containing media to low density growth factor-depleted or supplemented serum-free medium, and 3) the concentration of calcium in the media. The extent and degree of differentiation achieved varied among different cell lines depend on the presence or absence of serum, EGF and insulin protein growth factors. Certain growth media appear to sponsor keratin protein, cyto-chemically-detected differentiation, and evidence of quantal mitotic division in low density HeLa cell and SCC25 cell cultures. Epidermoid carcinoma cell lines retain limited capacity to commit to early stages of cell differentiation.

Potential Benefits of Increased Public Transit Ridership in Medium Sized Cities: A Case Study

At the beginning of the twentieth century, the United States was leading in the public transit sector, but following World War II, private automobiles became more affordable and gained popularity. Transportation infrastructure investments that increased road capacity further facilitated the increase in automobile use at the expense of reduced public transit ridership. With the increase of dependency on automobiles and the continuing growth of private automobile ownership and use, various problems became major challenges in big cities of USA. These include traffic congestion, air pollution, road and parking infrastructure costs, energy consumption, traffic safety, fewer mobility options for the non-drivers, and a decline in the image and use of public transit. This study uses a medium sized city, Birmingham as a case study to investigate the potential of public transit to reduce automobile trips and in turn improve the overall performance of the road network by addressing the abovementioned challenges. An agent-based simulation model was developed for the Birmingham metropolitan region using the Multi-agent Transport Simulation (MATSim) platform. Three scenarios were considered with gradually increased transit ridership to identify the benefits of increased public transit. Traffic volume, network average speed, and travel times were used as performance measures for the evaluation of the designated scenarios. Results suggest that modal shifts toward public transit and reduction in travel demand for an automobile can result in improvements in speed and travel time for all users. Therefore, investments for improving transit quality and frequency of service, as well as campaigns to improve the image of public transit and make it a mode of choice for transportation users can increase transit ridership and, in turn, improve network operations, thus are deemed worthy for medium sized cities.

Modeling Freight Truck Trips in Birmingham Using Tour-Based Approach

This research study explores the use of an innovative freight tour-based approach to model truck trips as an alternative to the conventional trip-based approach. The tour-based approach is more realistic as it captures the intermediate stops of each truck and reflects the implications of those stops on vehicle miles traveled (VMT). The paper describes the truck tour-based model concept, and presents the framework of a truck tour-based travel demand forecasting approach. As a case study, Global Positioning System (GPS) truck data are used to determine origin, destination, and truck stops for trucks moving within the Birmingham, Alabama region. Such information is then utilized to model truck movements within the study region as individual truck tours. The tour-based model is ran, and the resulting performance measures are contrasted to those obtained from the conventional trip-based planning model used by the Regional Planning Commission of Greater Birmingham (RPCGB). This case study demonstrates the feasibility of using a tour-based freight demand forecasting model as an alternative to the conventional 4-step process currently used to estimate truck trips in the Birmingham region. The results and lessons learned from the Birmingham case study are expected to improve truck movement modeling practices in the region and advance the accuracy of truck travel demand forecasting models at other locations in the future.

Cancer Chemopreventive Retinoids: Validation and Analysis of in Vivo and in Vitro Bioassay Results

Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC);2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC);3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC);4) the mouse skin papilloma (MPA) assay;and 5) a novel retinoid bioassay in which retinoids display IC50 values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED50 values in the HTOC system and reduction in TPA-induced ODC enzyme activity;2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity;and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.

Adult Cleft Lip Repair under Local Anaesthesia: The Ghana Experience

Background: Unlike developed countries where adult primary cleft lip and palate cases are barely nonexistent, developing countries still have a backlog of adults with unrepaired cleft lip and palate. Method: A retrospective review of adult/adolescent cleft lip repair under local anesthesia was performed between 2012 and 2015. Results: Fifty six (56) adolescent and adults were seen comprising 35 females and 21 males. Forty two patients presented with unrepaired unilateral cleft lip of which only 6 were complete;4 were unrepaired bilateral cleft lip and 10 were revisions. The lowest age was 13 years (two patients) and the highest age was 66 years (one patient). The mean weight was 54 kg. The mean anaesthetic time including waiting time was 12.94 minutes and mean operation time was 56.52 minutes. Majority of the patients were discharged same day except for five who needed to stay overnight because of distance from their home. There were no reported early postoperative complications and wound healing was uneventful for all the patients. Conclusion: Cleft lip repair in adults under local anesthesia is safe, effective and less expensive. A modification in technique with minimal dissection and efficiency is essential in such cases.

转移抑制与metastamiR调节的联系

BRMS1:乳腺癌转移抑制因子1;HDAC:组蛋白去乙酰化酶;EGFR:表皮生长因子受体;miRNA:小分子RNA;miR:小分子RNA;pri-miRNA:初始小分子RNA;

Contaminated open fracture and crush injury: a murine model

Modern warfare has caused a large number of severe extremity injuries, many of which become infected. In more recent conflicts, a pattern of co-infection with Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus has emerged. We attempted to recreate this pattern in an animal model to evaluate the role of vascularity in contaminated open fractures. Historically, it has been observed that infected bones frequently appear hypovascular, but vascularity in association with bone infection has not been examined in animal models. Adult rats underwent femur fracture and muscle crush injury followed by stabilization and bacterial contamination with A. baumannii complex and methicillin-resistant Staphylococcus aureus.Vascularity and perfusion were assessed by micro CT angiography and SPECT scanning, respectively, at 1, 2 and 4 weeks after injury. Quantitative bacterial cultures were also obtained. Multi-bacterial infections were successfully created, with methicillin-resistant S. aureus predominating. There was overall increase in blood flow to injured limbs that was markedly greater in bacteria-inoculated limbs. Vessel volume was greater in the infected group. Quadriceps atrophy was seen in both groups, but was greater in the infected group. In this animal model, infected open fractures had greater perfusion and vascularity than non-infected limbs.

Lower Concentrations of Glucose or Insulin Decrease the Risk of Various Types of Cancer in the Long-Lived Ames Dwarf Mouse by Increasing the Expression of p27Kip1, a Cell-Cycle Repressor Protein

Introduction. The molecular biological mechanism of the increased incidence of the various types of cancer in obesity or type 2 diabetes in rodents or humans has largely been resolved in recent years. By contrast, the molecular biological mechanism of the decreased, not increased, incidence of the various types of cancer in the homozygous long-lived Ames dwarf mice still remains unresolved. Objective. The first objective of the present study was to investigate whether the decrease in the incidence of cancer in the homozygous long-lived Ames dwarf mice is due to the increase, not decrease, in the expression of p27Kip1, a cell cycle repressor protein. The second objective was to investigate whether the decrease in the incidence of cancer in the homozygous long-lived Ames dwarf mice is due to the decrease, not increase, in the levels of glucose or insulin. Methods. To achieve these objectives, we first performed western immunoblot analysis of the hepatic expression of p27Kip1 protein. We then performed, using a human breast cancer cell line in vitro, the luciferase reporter plasmid assay to determine whether the translation initiation activity of the p27Kip1 mRNA is increased when the concentrations of either glucose or insulin are decreased. Results and Conclusion. The results of the first objective indicated that the hepatic expression of p27Kip1 protein was up-regulated in the homozygous long-lived Ames dwarf mice as expected. We also found that the lower concentrations of glucose or insulin increased the translation initiation activity of the p27Kip1 mRNA.

Transportation Users’ Attitudes and Choices of Ride-Hailing Services in Two Cities with Different Attributes

The rapid technological developments in the 21st century created new opportunities for shared-use economy applications around the globe. Among other services, Transportation Network Companies (TNCs) like Uber and Lyft emerged in the US as a transportation alternative that offered a higher level of availability, reliability, and convenience than traditional modes. However, TNCs deployment was also blamed for increases in vehicle miles traveled (VMT) in large cities that embraced TNC services early on. Concerns about TNC adoption are also magnified by the current controversy in policy and legislation as to the regulation of TNCs. These new realizations create a need to examine the transportation users’ attitudes and perceptions regarding ride-hailing service, after nearly a decade of service in the Unites States market. In doing so, this paper compares and contrasts results from two recently completed studies aiming at creating links between socio-demographic factors and TNC use. The paper describes the methods employed to collect the data and presents findings from the analysis of 790 users’ responses in the Birmingham, AL and Miami Beach, FL markets. The study documents preferences and attitudes toward TNCs and highlights similarities and differences in travel behaviors related to local considerations. Moreover, the study uses the Least Absolute Shrinkage and Selection Operator (Lasso) method to identify predictors for TNC use based on the users’ responses in Birmingham and Miami Beach case studies. Vehicle availability and waiting time emerged as the only significant predictors for the Birmingham region whereas vehicle ownership, vehicle use, residency, and prior use of transit and TNC where some of the predictors identified for the Miami Beach area. Understanding the characteristics of TNC users and the leading reasons that drive people towards the use of TNCs services is expected to help transportation agencies and TNC providers in their efforts to plan for transportation services that meet customer needs in the future.

免疫检查点抑制剂治疗晚期头颈部恶性肿瘤的研究进展

免疫检查点抑制剂通过去除T细胞的抑制信号，增强T细胞活性，杀灭肿瘤细胞。该疗法被认为是继手术、放化疗后，用于癌症患者的又一重要治疗方法。近年来，免疫检查点抑制剂用于晚期头颈部恶性肿瘤的治疗取得了大量有价值的研究成果，但合适个体的选择，判断该治疗效果标记物的鉴别仍在探索中，需要开展更深入的研究。本文对近几年国内外学者在该领域取得的成果做一简要概述，并对免疫检查点抑制剂在治疗晚期头颈部恶性肿瘤中的机制、安全性、联合应用以及不良反应等方面进行阐述，以期为该疗法在临床中的应用提供一些新的认识。