Non-invasive biomarkers for liver inflammation in non-alcoholic fatty liver disease: present andfuture

Inflammation is the key driver of liver fibrosis progression in non-alcoholic fatty liver disease (NAFLD). Unfortunately, it is often challenging to assess inflammation in NAFLD due to its dynamic nature and poor correlation with liver biochemical markers. Liver histology keeps its role as the standard tool, yet it is well-known for substantial sampling, intraobserver, and interobserver variability. Serum proinflammatory cytokines and apoptotic markers, namely cytokeratin-18, are well-studied with reasonable accuracy, whereas serum metabolomics and lipidomics have been adopted in some commercially available diagnostic models. Ultrasound and computed tomography imaging techniques are attractive due to their wide availability; yet their accuracies may not be comparable with magnetic resonance imaging-based tools. Machine learning and deep learning models, be they supervised or unsupervised learning, are promising tools to identify various subtypes of NAFLD, including those with dominating liver inflammation, contributing to sustainable care pathways for NAFLD.

Association between wrist pain and awkward postures among workers in 10 key industries / 环境与职业医学

Background Prolonged awkward postures during occupational activities can lead to excessive musculoskeletal load on the wrist of workers and symptoms such as wrist pain or discomfort. Objective To survey the prevalence of wrist pain among workers in 10 key industries and analyze its correlation with wrist working postures. Methods By using stratified cluster sampling method, workers from 10 key industries, such as footwear manufacturing industry, shipbuilding manufacturing industry, and automobile manufacturing industry, were selected from seven regions in North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China. The demographic information, wrist working postures, pain in wrist of the workers were collected through a cross-sectional survey. Pearson χ2 test was used to compare prevalence by selected factors, trend χ2 test for between group comparison, and unconditional logistic regression models for the association of wrist working postures with wrist pain. Results There were 64052 workers enrolled in this survey, and 56286 provided valid questionnaires (the effective rate was 87.8%). According to the survey, the prevalence of wrist pain was 23.3% (13112/56286), and the industries with higher prevalences were footwear manufacturing (27.1%, 1927/7106), automobile manufacturing (24.9%, 5378/21560), and shipbuilding and related equipment manufacturing (24.4%, 850/3488) industries. Finger pinching (OR=2.09, 95%CI: 1.95-2.24), frequent wrist bending (OR=2.03, 95%CI: 1.92-2.15), fixed wrist bending (OR=1.77, 95%CI: 1.69-1.85), wrist on hard edge (OR=1.34, 95%CI: 1.28-1.40), and arms over shoulders (OR=1.11, 95%CI: 1.05-1.17) increased the risk of reporting wrist pain. Conclusion Awkward postures are related to wrist pain among workers in selected 10 key industries. The related factors are wrist on hard edge, frequent wrist bending, finger pinching, fixed wrist bending, and arms over shoulders.

Non-invasive tests of non-alcoholic fatty liver disease / 中华医学杂志(英文版)

For 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.

Disease-dependent interaction policies to support health and economic outcomes during the COVID-19 epidemic

Lockdowns and stay-at-home orders have partially mitigated the spread of Covid-19. However, the indiscriminate nature of mitigation -- applying to all individuals irrespective of disease status -- has come with substantial socioeconomic costs. Here, we explore how to leverage the increasing reliability and scale of both molecular and serological tests to balance transmission risks with economic costs involved in responding to Covid-19 epidemics. First, we introduce an optimal control approach that identifies personalized interaction rates according to an individuals test status; such that infected individuals isolate, recovered individuals can elevate their interactions, and activity of susceptible individuals varies over time. Critically, the extent to which susceptible individuals can return to work depends strongly on isolation efficiency. As we show, optimal control policies can yield mitigation policies with similar infection rates to total shutdown but lower socioeconomic costs. However, optimal control policies can be fragile given mis-specification of parameters or mis-estimation of the current disease state. Hence, we leverage insights from the optimal control solutions and propose a feedback control approach based on monitoring of the epidemic state. We utilize genetic algorithms to identify a switching policy such that susceptible individuals (both PCR and serological test negative) return to work after lockdowns insofar as recovered fraction is much higher than the circulating infected prevalence. This feedback control policy exhibits similar performance results to optimal control, but with greater robustness to uncertainty. Overall, our analysis shows that test-driven improvements in isolation efficiency of infectious individuals can inform disease-dependent interaction policies that mitigate transmission while enhancing the return of individuals to pre-pandemic economic activity.

Intervention Serology and Interaction Substitution: Modeling the Role of 'Shield Immunity' in Reducing COVID-19 Epidemic Spread

The COVID-19 pandemic has precipitated a global crisis, with more than 690,000 confirmed cases and more than 33,000 confirmed deaths globally as of March 30, 2020 [1-4]. At present two central public health control strategies have emerged: mitigation and suppression (e.g, [5]). Both strategies focus on reducing new infections by reducing interactions (and both raise questions of sustainability and long-term tactics). Complementary to those approaches, here we develop and analyze an epidemiological intervention model that leverages serological tests [6, 7] to identify and deploy recovered individuals as focal points for sustaining safer interactions via interaction substitution, i.e., to develop what we term shield immunity at the population scale. Recovered individuals, in the present context, represent those who have developed protective, antibodies to SARS-CoV-2 and are no longer shedding virus [8]. The objective of a shield immunity strategy is to help sustain the interactions necessary for the functioning of essential goods and services (including but not limited to tending to the elderly [9], hospital care, schools, and food supply) while decreasing the probability of transmission during such essential interactions. We show that a shield immunity approach may significantly reduce the length and reduce the overall burden of an outbreak, and can work synergistically with social distancing. The present model highlights the value of serological testing as part of intervention strategies, in addition to its well recognized roles in estimating prevalence [10, 11] and in the potential development of plasma-based therapies [12-15].

Preliminary study on the international distribution of phase Ⅰ clinical trials and the characteristics of research institutions / 中华医学科研管理杂志

Objective:To analysis the construction of the world's top PhaseⅠclinical trial registration agencies, compare their size, composition, operation and funding, to provide further reference for the construction of clinical trial agency in China.Methods:Search for PhaseⅠclinical trial research agencies by region on clinicaltrials.gov. Collecting information about the agency’s management, staffing, implementation in Asia, America and Europe. Descriptive analysis was carried out to explore the type, proportion and operation among different regions, the organizational structure, operational management and effectiveness of each agency from different regions were compared.Results:The United States, Europe and East Asia are dense areas of PhaseⅠclinical research around the world. The types of agencies in the United States, Britain, France, Germany, South Korea, Japan, and Israel are mainly enterprises. Among other types of agencies, the organizational models are diversified. The agencies have different spatial distances from medical institutions, but possess relatively consistent scale and institutional operation. All the agencies have a stable source of funding.Conclusions:In order to strengthen the construction of clinical trial agencies in China, we should speed up the establishment of a close connection mechanism to promote deep cooperation in clinical trials. Control the construction scale and maintain stable input of the agency. Meanwhile, establish and strengthen international exchanges and cooperation.

Preliminary study on the pathway of scientific and technological achievements of clinical hospitals transferred by medical device enterprises in the Yangtze River Delta / 中华医学科研管理杂志

Objective:To provide references for promoting clinical hospital technology transfer, through on-site investigations of medical device manufacturers and sorting out the situation of the participation of enterprises in technology transfer.Methods:Purposive sampling and questionnaire are used; the study analyzed the collected data by quantitative and qualitative research on the selected 5 enterprises in the Yangtze River Delta, and introduced the procedures of enterprises purchasing scientific payoffs.Results:It shows that the medical device enterprises have strong demand for the technology innovation, and the cooperation between enterprises and researchers at an earlier stage are conducive to technology transfer. At present, the overall technology readiness level for the hospitals is generally not high. The commercialization of scientific and research findings could achieve the win-win situation for both the hospitals and enterprises.Conclusions:To further promote the transformation of scientific and technological achievements in China, We should establish a more diversified achievement promotion platform to push forward the hospital-enterprise cooperation to improve the technology readiness level, and meanwhile, accelerate the application-oriented clinical scientific research.

Activation of mammaLian target of rapamycin signaLing pathway in pLacentaL tissues of gravidas with gestationaL diabetes meLLitus / 中华围产医学杂志

Objective To investigate the activation of mammalian target of rapamycin (mTOR) signaling pathway in placental tissues of gestational diabetes mellitus (GDM) women and in JEG3 cells after high glucose treatment. Methods Placental tissues were collected from 60 singleton pregnant women at term, who underwent elective cesarean section in Peking University First Hospital from December 2016 to June 2017, including 30 GDM women (GDM group) and 30 normal glucose tolerance (NGT) women (NGT group). Expressions of mTOR, Rictor, Raptor, S6 kinase (S6K) and phosphorylated-S6K (p-S6K), which were mTOR signaling pathway-related molecules in those placental tissues were detected by real-time fluorescence quantitative polymerase chain reaction, Western blotting and immunohistochemistry. At the same time, JEG3 cells were treated with glucose of different concentrations (5.5, 10.0, 15.0, 25.0 and 50.0 mmol/L) for 24 h, and the expressions of mTOR, S6K and p-S6K were detected by Western blotting. Two independent samples t-test, one-way analysis of variance test and Spearman correlation analysis were used for statistical analysis. ResuLts Compared with the NGT group, the pre-pregnancy body mass index(BMI), neonatal birth weight, fasting blood glucose(FBG), and 1 h and 2 h post-load blood glucose in oral glucose tolerance test (OGTT) of the GDM group were significantly increased [pre-pregnant BMI: (21.6±2.7) vs (23.4±3.5) kg/m2, t= － 2.192; neonatal birth weight: (3 337.5±347.7) vs (3 618.3±580.9) g, t=－2.727; FBG: (4.6±0.4) vs (5.2±0.8) mmol/L, t=－3.947; 1 h glucose level: (7.4±1.2) vs (9.6±1.9) mmol/L, t=－5.332; 2 h glucose level: (6.3±1.0) vs (8.1±1.5) mmol/L, t=－5.314; all P<0.05]. The mRNA expressions of mTOR, Rictor and Raptor were significantly higher in the GDM group than in the NGT group (0.051±0.015 vs 0.031±0.011, t=－5.635; 0.038±0.017 vs 0.026±0.010, t=－3.485; 0.036±0.012 vs 0.025±0.011, t=－3.312; all P<0.05). The expression of mTOR, Rictor, Raptor and p-S6K protein in the GDM group were enhanced as compared with those in the NGT group (0.834±0.432 vs 0.386±0.361, t= － 2.249;0.589±0.236 vs 0.262±0.075, t= － 3.726; 0.767±0.345 vs 0.323±0.109, t= － 3.472; 1.847±1.025 vs 0.834±0.432, t=－2.575; all P<0.05). The results of immunohistochemistry also showed that the p-S6K in the placental tissues of the GDM group was higher than that of the NGT group (0.29±0.09 vs 0.18±0.08, t=－3.122, P=0.004). The expressions of mTOR protein (0.190±0.085, 0.301±0.089, 0.419±0.065, 0.562±0.108, 0.412±0.058, F=18.351, P<0.05) and p-S6K protein (0.753±0.150, 1.146±0.289, 2.148±0.188, 2.248±0.115, 2.134±0.214, F=66.242, P<0.05) in JEG3 cells treated with different concentrations of glucose (5.5, 10.0, 15.0, 25.0 and 50.0 mmol/L) were significantly different and increased with increasing concentrations of glucose (r=0.314, P=0.035; r=0.457, P=0.002). ConcLusions The up-regulated expressions of mTOR signaling pathway-related molecules in GDM placenta and high glucose-treated trophoblast cells (JEG3 cells) indicate a possible correlation between mTOR signaling pathway and GDM. However, the specific mechanisms need further study.

Literature Analysis of Pediatric Drug-induced Liver Injury in China from 2007 to 2016 / 中国药房

OBJECTIVE:To investigate the characteristics of pediatric drug-induced liver injury (DILI) in China,and to provide reference for reducing ADR.METHODS:Using"liver injury liver damage hepatotoxicity hepatitis liver disease""drug induced children" as keywords,related domestic literatures were retrieved from CNKI and Wanfang database during 2007-2016,clinical information of DILI children in literatures were recorded in detail and analyzed comprehensively.RESULTS:A total of 363 literatures were retrieved,including 13 effective literatures and 665 children in total.There were 424 boys (63.76％)and 241 girls (36.24％),with ratio of 1.76 ∶ 1.The youngest child was 1 month old,the oldest child was 14 years old;the average age was 7.87 years,337 children aged more then 7 years old,accounting for 50.68％.Top 3 primary diseases were respiratory tract infection (40 cases,31.50％),hematologic diseases (29 cases,22.83％) and tumor (14 cases,11.02％).Top 3 pediatric DILI-inducing drug types were antibiotics (245 cases,34.41％),TCM (143 cases,20.08％) and antipyretic analgesics (113 cases,15.87％).DILI usually happened within 4 weeks (332 cases,82.18％).The most common clinical classification was hepatocellular type (382 cases,65.30％).The severity of liver injury was mainly mild and moderate (505 cases,86.32％),and 80 cases were severe (13.68％),including 31 cases of hepatic failure (5.30％).Clinical symptoms mainly manifested as anorexia,jaundice,nausea,vomiting,hypodynamia and abdominal discomfort.After drug withdreawd and treatment,96.54％ of the patients were recovered or cured,and 4 cases died (0.60％).CONCLUSIONS:Under the premise of rational use of drugs,it is necessary to carry out medication education and supervision for antibiotics,TCM and antipyretic analgesics which mainly induce pediatric DILI,pay attention to allergic history and evaluate the progress of extrahepatic symptoms.When ADR occurred,the timely and drug withdrawal intervention are conducted to improve good prognosis.