Southwest Medical University

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.

Diabetes mellitus is a chronic disease characterized by hyperglycemia. It may cause many complications. According to the growing morbidity in recent years, in 2040, the world's diabetic patients will reach 642 million, which means that one of the ten adults in the future is suffering from diabetes. There is no doubt that this alarming figure needs great attention. With the rapid development of machine learning, machine learning has been applied to many aspects of medical health. In this study, we used decision tree, random forest and neural network to predict diabetes mellitus. The dataset is the hospital physical examination data in Luzhou, China. It contains 14 attributes. In this study, five-fold cross validation was used to examine the models. In order to verity the universal applicability of the methods, we chose some methods that have the better performance to conduct independent test experiments. We randomly selected 68994 healthy people and diabetic patients' data, respectively as training set. Due to the data unbalance, we randomly extracted 5 times data. And the result is the average of these five experiments. In this study, we used principal component analysis (PCA) and minimum redundancy maximum relevance (mRMR) to reduce the dimensionality. The results showed that prediction with random forest could reach the highest accuracy (ACC = 0.8084) when all the attributes were used.

Oxidative stress and inflammation interact in the development of diabetic atherosclerosis. Intracellular hyperglycemia promotes production of mitochondrial reactive oxygen species (ROS), increased formation of intracellular advanced glycation end-products, activation of protein kinase C, and increased polyol pathway flux. ROS directly increase the expression of inflammatory and adhesion factors, formation of oxidized-low density lipoprotein, and insulin resistance. They activate the ubiquitin pathway, inhibit the activation of AMP-protein kinase and adiponectin, decrease endothelial nitric oxide synthase activity, all of which accelerate atherosclerosis. Changes in the composition of the gut microbiota and changes in microRNA expression that influence the regulation of target genes that occur in diabetes interact with increased ROS and inflammation to promote atherosclerosis. This review highlights the consequences of the sustained increase of ROS production and inflammation that influence the acceleration of atherosclerosis by diabetes. The potential contributions of changes in the gut microbiota and microRNA expression are discussed.

In mid-December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus-2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease-2019 (COVID-19) has also increased significantly. Although information regarding the epidemiology of COVID-19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID-19 in children.

The infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is a global threat to public health. Vancomycin remains one of the first-line drugs for the treatment of MRSA infections. However, S. aureus isolates with complete resistance to vancomycin have emerged in recent years. Vancomycin-resistant S. aureus (VRSA) is mediated by a vanA gene cluster, which is transferred from vancomycin-resistant enterococcus. Since the first VRSA isolate was recovered from Michigan, USA in 2002, 52 VRSA strains have been isolated worldwide. In this paper, we review the latest progresses in VRSA, highlighting its resistance mechanism, characteristics of VRSA infections, as well as clinical treatments.

A systematic review and meta-analysis was conducted in an attempt to systematically collect and evaluate the associations of epidemiological, comorbidity factors with the severity and prognosis of coronavirus disease 2019 (COVID-19). The systematic review and meta-analysis was conducted according to the guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Sixty nine publications met our study criteria, and 61 studies with more than 10,000 COVID-19 cases were eligible for the quantitative synthesis. We found that the males had significantly higher disease severity (RR: 1.20, 95% CI: 1.13-1.27, P <0.001) and more prognostic endpoints. Older age was found to be significantly associated with the disease severity and six prognostic endpoints. Chronic kidney disease contributed mostly for death (RR: 7.10, 95% CI: 3.14-16.02), chronic obstructive pulmonary disease (COPD) for disease severity (RR: 4.20, 95% CI: 2.82-6.25), admission to intensive care unit (ICU) (RR: 5.61, 95% CI: 2.68-11.76), the composite endpoint (RR: 8.52, 95% CI: 4.36-16.65,), invasive ventilation (RR: 6.53, 95% CI: 2.70-15.84), and disease progression (RR: 7.48, 95% CI: 1.60-35.05), cerebrovascular disease for acute respiratory distress syndrome (ARDS) (RR: 3.15, 95% CI: 1.23-8.04), coronary heart disease for cardiac abnormality (RR: 5.37, 95% CI: 1.74-16.54). Our study highlighted that the male gender, older age and comorbidities owned strong epidemiological evidence of associations with the severity and prognosis of COVID-19.

BACKGROUND: On average, 570 million users, 93% in China's first-tier cities, log on to WeChat every day. WeChat has become the most widely and frequently used social media in China, and has been profoundly integrated into the daily life of many Chinese people. A variety of health-related information may be found on WeChat. The objective of this study is to understand how the general public views the impact of the rapidly emerging social media on health information acquisition. METHODS: A self-administered questionnaire was designed, distributed, collected, and analyzed utilizing the online survey tool Sojump. WeChat was adopted to randomly release the questionnaires using convenience sampling and collect the results after a certain amount of time. RESULTS: (1) A total of 1636 questionnaires (WeChat customers) were collected from 32 provinces. (2) The primary means by which respondents received health education was via the Internet (71.79%). Baidu and WeChat were the top 2 search tools utilized (90.71% and 28.30%, respectively). Only 12.41% of respondents were satisfied with their online health information search. (3) Almost all had seen (98.35%) or read (97.68%) health information; however, only 14.43% believed that WeChat health information could improve health. Nearly one-third frequently received and read health information through WeChat. WeChat was selected (63.26%) as the most expected means for obtaining health information. (4) The major concerns regarding health information through WeChat included the following: excessively homogeneous information, the lack of a guarantee of professionalism, and the presence of advertisements. (5) Finally, the general public was most interested in individualized and interactive health information by managing clinicians, they will highly benefit from using social media rather than Internet search tools. CONCLUSIONS: The current state of health acquisition proves worrisome. The public has a high chance to access health information via WeChat. The growing popularity of interactive social platforms (e.g. WeChat) presents a variety of challenges and opportunities with respect to public health acquisition.

Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy.

Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATP-binding cassette (ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics.

When the production of reactive oxygen species (ROS) is overloaded surpassing the capacity of the reductive rheostat, mammalian cells undergo a series of oxidative damage termed oxidative stress (OS). This phenomenon is ubiquitously detected in many human pathological conditions. Wound healing program implicates continuous neovascularization, cell proliferation, and wound remodeling. Increasing evidence indicates that reactive oxygen species (ROS) have profound impacts on the wound healing process through regulating a series of the physiological and pathological program including inflammatory response, cell proliferation, angiogenesis, granulation as well as extracellular matrix formation. In most pathological wound healing processes, excessive ROS exerts a negative role on the wound healing process. Interestingly, the moderate increase of ROS levels is beneficial in killing bacteria at the wound site, which creates a sterile niche for revascularization. In this review, we discussed the physiological rhythms of wound healing and the role of ROS in this progress, aim to explore the potential manipulation of OS as a promising therapeutic avenue.

Depression is the most common mental disorder and a leading cause of disability worldwide. Despite abundant research, the precise mechanisms underlying the pathophysiology of depression remain elusive. Accumulating evidence from preclinical and clinical studies suggests that alterations in the gut microbiota, microbe-derived short-chain fatty acids, D-amino acids and metabolites play a key role in the pathophysiology of depression via the brain-gut-microbiota axis, including the neural and immune systems. Notably, the brain-gut-microbiota axis might play a crucial role in susceptibility versus resilience in rodents exposed to stress. Vagotomy is reported to block depression-like phenotypes in rodents after fecal microbiota transplantation of "depression-related" microbiome, suggesting that the vagus nerve influences depression through the brain-gut-microbiota axis. In this article, we review recent findings regarding the brain-gut-microbiota axis in depression and discuss its potential as a therapeutic target for depression.

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.

miRNAs (microRNAs) participate in many diseases including cardiovascular disease. In contrast with our original hypothesis, miRNAs exist in circulating blood and are relatively stable due to binding with other materials. The aim of the present translational study is to establish a method of determining the absolute amount of an miRNA in blood and to determine the potential applications of circulating cell-free miR-1 (microRNA-1) in AMI (acute myocardial infarction). The results revealed that miR-1 is the most abundant miRNA in the heart and is also a heart- and muscle-specific miRNA. In a cardiac cell necrosis model induced by Triton X-100 in vitro, we found that cardiac miR-1 can be released into the culture medium and is stable at least for 24 h. In a rat model of AMI induced by coronary ligation, we found that serum miR-1 is quickly increased after AMI with a peak at 6 h, in which an increase in miR-1 of over 200-fold was demonstrated. The miR-1 level returned to basal levels at 3 days after AMI. Moreover, the serum miR-1 level in rats with AMI had a strong positive correlation with myocardial infarct size. To verify further the relationship between myocardial size and miR-1 level, an IP (ischaemic preconditioning) model was used. The results showed that IP significantly reduced circulating miR-1 levels and myocardial infract size induced by I/R (ischaemia/reperfusion) injury. Finally, the levels of circulating cell-free miR-1 were significantly increased in patients with AMI and had a positive correlation with serum CK-MB (creatine kinase-MB) levels. In conclusion, the results suggest that serum miR-1 could be a novel sensitive diagnostic biomarker for AMI.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1β and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen species (ROS) levels in A549 and H1299 cells, and N-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.

New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.

Aim: This study aims to clarify the risk factors for falls to prevent severe consequences in older adults. Methods: We searched the PubMed, Web of Science, Embase, and Google Scholar databases using the terms "risk factors" OR "predicting factors" OR "predictor" AND "fall" OR "drop" to identify all relevant studies and compare their results. The study participants were divided into two groups, the "fall group" and the "control group", and differences in demographic characteristics, lifestyles, and comorbidities were compared. Results: We included 34 articles in the analysis and analyzed 22 factors. Older age, lower education level, polypharmacy, malnutrition, living alone, living in an urban area, smoking, and alcohol consumption increased the risk of falls in the aging population. Additionally, comorbidities such as cardiac disease, hypertension, diabetes, stroke, frailty, previous history of falls, depression, Parkinson's disease, and pain increased the risk of falls. Conclusion: Demographic characteristics, comorbidities, and lifestyle factors can influence the risk of falls and should be taken into consideration.

BACKGROUND: Wearable devices have attracted much attention from the market in recent years for their fitness monitoring and other health-related metrics; however, the accuracy of fitness tracking results still plays a major role in health promotion. OBJECTIVE: The aim of this study was to evaluate the accuracy of a host of latest wearable devices in measuring fitness-related indicators under various seminatural activities. METHODS: A total of 44 healthy subjects were recruited, and each subject was asked to simultaneously wear 6 devices (Apple Watch 2, Samsung Gear S3, Jawbone Up3, Fitbit Surge, Huawei Talk Band B3, and Xiaomi Mi Band 2) and 2 smartphone apps (Dongdong and Ledongli) to measure five major health indicators (heart rate, number of steps, distance, energy consumption, and sleep duration) under various activity states (resting, walking, running, cycling, and sleeping), which were then compared with the gold standard (manual measurements of the heart rate, number of steps, distance, and sleep, and energy consumption through oxygen consumption) and calculated to determine their respective mean absolute percentage errors (MAPEs). RESULTS: Wearable devices had a rather high measurement accuracy with respect to heart rate, number of steps, distance, and sleep duration, with a MAPE of approximately 0.10, whereas poor measurement accuracy was observed for energy consumption (calories), indicated by a MAPE of up to 0.44. The measurements varied for the same indicator measured by different fitness trackers. The variation in measurement of the number of steps was the highest (Apple Watch 2: 0.42; Dongdong: 0.01), whereas it was the lowest for heart rate (Samsung Gear S3: 0.34; Xiaomi Mi Band 2: 0.12). Measurements differed insignificantly for the same indicator measured under different states of activity; the MAPE of distance and energy measurements were in the range of 0.08 to 0.17 and 0.41 to 0.48, respectively. Overall, the Samsung Gear S3 performed the best for the measurement of heart rate under the resting state (MAPE of 0.04), whereas Dongdong performed the best for the measurement of the number of steps under the walking state (MAPE of 0.01). Fitbit Surge performed the best for distance measurement under the cycling state (MAPE of 0.04), and Huawei Talk Band B3 performed the best for energy consumption measurement under the walking state (MAPE of 0.17). CONCLUSIONS: At present, mainstream devices are able to reliably measure heart rate, number of steps, distance, and sleep duration, which can be used as effective health evaluation indicators, but the measurement accuracy of energy consumption is still inadequate. Fitness trackers of different brands vary with regard to measurement of indicators and are all affected by the activity state, which indicates that manufacturers of fitness trackers need to improve their algorithms for different activity states.

The 0.65(NBT-BKT)–0.35SBT ceramic possesses an ultra-high recoverable energy storage density (<italic>W</italic>_rec ∼ 4.06 J cm⁻³) and maintains a relatively high efficiency (<italic>η</italic> = ∼87.3%).