简介：AbstractDiabetic retinopathy (DR) is an important cause of blindness globally, and its prevalence is increasing. Early detection and intervention can help change the outcomes of the disease. The rapid development of artificial intelligence (AI) in recent years has led to new possibilities for the screening and diagnosis of DR. An AI-based diagnostic system for the detection of DR has significant advantages, such as high efficiency, high accuracy, and lower demand for human resources. At the same time, there are shortcomings, such as the lack of standards for development and evaluation and the limited scope of application. This article demonstrates the current applications of AI in the field of DR, existing problems, and possible future development directions.

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简介：AbstractFor the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

简介：AbstractArtificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the "smart lockdown" strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government–public relations.

简介：AbstractObjective:This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods:A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test.Results:The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics.Conclusion:The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

简介：AbstractPurpose:Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE.Methods:A systematic literature review searched "liver trauma" , "hepatic trauma" , "conservative management" , "non operative management" on MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials databases, EMBASE, and Google Scholar, to identify studies published on the conservative management of traumatic liver injuries between January 1990 and June 2020. Patients with traumatic liver injuries (blunt and penetrating) treated by NOM, described at least one outcome of interests and provided morbidity outcomes from NOM were included in this study. Studies reported the outcome of NOM without separating liver from other solid organs; studies reported NOM complications together with those post-intervention; case reports; studies including less than 5 cases; studies not written in English; and studies including patients who had NOM with AE as primary management were excluded. Efficacy of NOM and overall morbidity and mortality were assessed, the specific causes of morbidity were investigated, and the American Association for the Surgery of Trauma classification was used in all the studies analysed. Statistical significance has been calculated using the Chi-square test.Results:A total of 19 studies qualified for inclusion criteria were in this review. The NOM success rate ranged from 85% to 99%. The most commonly reported complications were hepatic collection (3.1%), followed by bile leak (1.5%), with variability between the studies. Other complications included hepatic haematoma, bleeding, fistula, pseudoaneurysm, compartment syndrome, peritonitis, and gallbladder ischemia, all with an incidence below 1%.Conclusion:NOM with simple clinical observation showed an overall low incidence of complications, but higher for bile leak and collections. In patients with grade III and above injuries, the incidence of bile leak, collections and compartment syndrome did not show a statistically significant difference with the AE group. However, the latter result is limited by the small number of studies available and it requires further investigations.

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简介：AbstractThe philosophy of abdominal injury management is currently changing from mandatory exploration to selective non-operative management (NOM). The patient with hemodynamic stability and absence of peritonitis should be managed non-operatively. NOM has an overall success rate of 80%—90%. It also can reduce the rate of non-therapeutic abdominal exploration, preserve organ function, and has been defined as the safest choice in experienced centers. However, NOM carries a risk of missed injury such as hollow organ injury, diaphragm injury, and delayed hemorrhage. Adjunct therapies such as angiography with embolization, endoscopic retrograde cholangiopancreatography with stenting, and percutaneous drainage could increase the chances of successful NOM. This article aims to describe the evolution of NOM and define its place in specific abdominal solid organ injury for the practitioner who faces this problem.

简介：AbstractEndometriosis (EM) is a benign gynecological disease that affects the fertility and health of women of reproductive age; it is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Although several hypotheses have been proposed to explain the underlying cause of EM, its pathogenesis remains obscure. Recently, non-coding RNAs were reported to be involved in the occurrence and development of EM. MicroRNAs and long non-coding RNAs are the main members of the non-coding RNA family that contribute to EM progression in various aspects, such as cell proliferation, apoptosis, invasion, and angiogenesis. Angiogenesis plays a pivotal role in the initiation and development of EM and provides a substantial background for the invasion, proliferation, and long-term growth of endometriotic implants. This review aimed to investigate the role of microRNAs and long non-coding RNAs in regulating angiogenesis in EM and discuss how this mechanism can be used for diagnostic and therapeutic purposes in EM.

简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

简介：AbstractBackground:Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children’s intelligence changes in endemic fluorosis areas has been rarely explored.Methods:A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UFCr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven’s Test was used to evaluate children’s intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children’s UFCr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.Results:In the high fluoride group, children’s IQ scores decreased by 2.502 when the UFCr level increased by 1.0 mg/L (β= –2.502, 95% confidence interval [CI]: –4.411, –0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P < 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05).Conclusion:Our findings suggest that excessive fluoride exposure may have adverse effects on children’s intelligence, and changes in children’s intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.

简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.

简介：AbstractObjective:The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined.Methods:PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models.Results:Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], -0.126-0.609) and dropout rate of 2.1% (95% CrI, 0.007-0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017-0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76-0.96) for the achievement of progression-free survival and overall survival, respectively.Conclusion:In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.

简介：AbstractPreimplantation genetic testing (PGT) is a widely adopted screening method that can be performed to identify and select embryos with normal ploidy; however, PGT relies on embryo biopsy, that is, polar body, embryo cells, or trophectoderm biopsy, to obtain embryonic DNA, increase its technical limitations. Studies have indicated that biopsy may have an influence on the quality and development of embryos, and increase the chance of abnormal epigenetic modifications. Therefore, non-invasive PGT (niPGT) detection of cell-free DNA (cfDNA) has gradually become a hot research topic in the field of assisted reproduction. Studies showed cfDNA could be detected in blastocyst fluid and spent culture medium (SCM) in vitro cultured embryos. The cfDNA collection requires less skill and makes lower risk to embryos. Some studies have been conducted to evaluate the feasibility of SCM-based niPGT approaches. When comparing the ploidy consistency of cfDNA in SCM, its consistency to the conventional PGT for aneuploidies results fluctuated widely, it is critical to recognize the factors influencing accuracy. These contradictory results may be related to factors such as the difference in SCM sampling methods and sampling time, and the definition of consistency. In this review, we aimed to comprehensively summarize how researchers use embryonic cfDNA to conduct niPGT detection. It also systematically reviews the factors affecting the accuracy of the test and its underlying issues, as well as prospective applications. We hope to provide a basis for future niPGT research and a useful reference for the standardized operation of niPGT that can be widely applied in clinical practice.

简介：AbstractImmune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

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简介：AbstractBackground:While malaria morbidity and mortality have declined since 2000, viral central nervous system infections appear to be an important, underestimated cause of coma in malaria-endemic Eastern Africa. We aimed to describe the etiology of non-traumatic comas in young children in Benin, as well as their management and early outcomes, and to identify factors associated with death .Methods:From March to November 2018, we enrolled all HIV-negative children aged between 2 and 6 years, with a Blantyre Coma Score ≤ 2, in this prospective observational study. Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol, including blood cultures, malaria diagnostics, and cerebrospinal fluid analysis using multiplex PCR. To determine factors associated with death, univariate and multivariate analyses were performed.Results:From 3244 admissions, 84 children were included: malaria was diagnosed in 78, eight of whom had a viral or bacterial co-infection. Six children had a non-malarial infection or no identified cause. The mortality rate was 29.8% (25/84), with 20 children dying in the first 24 h. Co-infected children appeared to have a poorer prognosis. Of the 76 children who consulted a healthcare professional before admission, only 5 were prescribed adequate antimalarial oral therapy. Predictors of early death were jaundice or increased bilirubin [odd ratio (OR)= 8.6; 95% confidential interval (CI): 2.03–36.1] and lactate > 5 mmol/L (OR= 5.1; 95% CI: 1.49–17.30). Antibiotic use before admission (OR = 0.1; 95% CI: 0.02–0.85) and vaccination against yellow fever (OR= 0.2, 95% CI: 0.05–0.79) protected against mortality.Conclusions:Infections were found in all children who died, and cerebral malaria was by far the most common cause of non-traumatic coma. Missed opportunities to receive early effective antimalarial treatment were common. Other central nervous system infections must be considered in their management. Some factors that proved to be protective against early death were unexpected.

简介：AbstractThe phosphosphatidylinositol-3-kinase (PI3K) signaling pathway is one of the most important intracellular signal transduction pathways affecting cell functions, such as apoptosis, translation, metabolism, and angiogenesis. Lung cancer is a malignant tumor with the highest morbidity and mortality rates in the world. It can be divided into two groups, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for >85% of all lung cancers. There are currently many clinical treatment options for NSCLC; however, traditional methods such as surgery, chemotherapy, and radiotherapy have not been able to provide patients with good survival benefits. The emergence of molecular target therapy has improved the survival and prognosis of patients with NSCLC. In recent years, there have been an increasing number of studies on NSCLC and PI3K signaling pathways. Inhibitors of various parts of the PI3K pathway have appeared in various phases of clinical trials with NSCLC as an indication. This article focuses on the role of the PI3K signaling pathway in the occurrence and development of NSCLC and summarizes the current clinical research progress and possible development strategies.