With the advent of big data era, our thinking, technology and methodology are being transformed. Data-intensive scientific discovery based on big data, named “The Fourth Paradigm,” has become a new paradigm of scientific research. Along with the development and application of the Internet information technology in the field of healthcare, individual health records, clinical data of diagnosis and treatment, and genomic data have been accumulated dramatically, which generates big data in medical field for clinical research and assessment. With the support of big data, the defects and weakness may be overcome in the methodology of the conventional clinical evaluation based on sampling. Our research target shifts from the “causality inference” to “correlativity analysis.” This not only facilitates the evaluation of individualized treatment, disease prediction, prevention and prognosis, but also is suitable for the practice of preventive healthcare and symptom pattern differentiation for treatment in terms of traditional Chinese medicine (TCM), and for the post-marketing evaluation of Chinese patent medicines. To conduct clinical studies involved in big data in TCM domain, top level design is needed and should be performed orderly. The fundamental construction and innovation studies should be strengthened in the sections of data platform creation, data analysis technology and big-data professionals fostering and training.

The 2019 novel coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges.

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER=1.95, P=0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

Cellular mechanics, a major regulating factor of cellular architecture and biological functions, responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment. Cellular mechanics also acts as a fundamental mediator in complicated immune responses, such as cell migration, immune cell activation, and pathogen clearance. The principle of atomic force microscopy (AFM) and its three running modes are introduced for the mechanical characterization of living cells. The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves. For a concrete description of AFM capabilities, three AFM applications are discussed. These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils, the immunological functions of macrophages, and the membrane pore formation mediated by perforin, streptolysin O, gasdermin D, or membrane attack complex.

In December 2019, an outbreak of novel coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to ~2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.

Anti-β₂ glycoprotein I (anti-β₂GP I ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β₂GP I antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti-β₂GP I antibodies in complexes with β₂GP I as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I bα) in platelet activation induced by the anti-β₂GP I /β₂GP I complex. The interaction between the anti-β₂GP I /β₂GP I complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GP II b/ III a activation and P-selectin expression and thromboxane B₂ production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β₂GP I /β₂GP I complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β₂GP I /β₂GP I complex induced platelet activation via GP I bα and apoER2', which may then contribute to the prothrombotic tendency in APS patients.

The effect of peripherally administered oxytocin (OT) on gastric ischemia-reperfusion injury (GI-RI) and its possible mechanism were investigated. The Sprague-Dawley (SD) rats were randomly divided into different treatment groups (n = 6). The animal GI-RI model was established by clamping the celiac artery for 30 min to induce ischemia and then released to allow reperfusion for 1 h, and the degree of GI-RI was assessed by scoring the gastric mucosal damage index (GMDI), the gastric fluid output, gastric fluid output, gastric acidity were measured and the surgical preparations of vagotomy and sympathectomy were used to investigate the possible mechanism of OT on GI-RI. The results were as follows. Compared with the control group (NS plus GI-R only, GMDI 121.33±10.40, n = 6), the intra peritoneal (ip) administration of oxytocin (20, 100 μg/0.5 mL) obviously attenuated GI-RI (P<0.05), GMDI were 82.33±14.26, 53.5±5.58 respectively (n = 6); the gastric fluid output and the gastric acidity (evaluated by pH) of the control group were (430.17±87.36) μL, 1.55±0.25 (n = 6), and those of the OT group were (102.45±48.00) μL, 2.65±0.40 (n = 6) res pectively; differences had statistical significance (P<0.01). The effect of oxytocin was reversed by atosiban, a selective oxytocin receptor antagonist. The GMDI of the group given atosiban 10 min before OT was 138.17±24.06 (n = 6), which had no significant difference with the control group. Oxytocin further attenuated GI-RI after vagotomy and sympathectomy (GMDI 6.83±8.89, 29.67±5.54, n = 6), compared with the GI-R group and the oxytocin group (P<0.01). These results indicated that the oxytocin could significantly protect gastric mucosal against injury induced by ischemia-reperfusion, and the oxytocin receptor was involved. This effect of oxytocin may be mediated through the vagus and sympathetic nerve, and then lead to the reduction of gastric juice output and the depression of gastric acidity.

The aim of this paper was to investigate the effects of resistin on human umbilical vein endothelial cells (HUVECs), and to explore its role and mechanism of action in atherosclerosis. HUVECs were incubated with recombinant human resistin (0, 50, 100 ng/mL) for 24 h. ICAM-1, VCAM-1 and reactive oxygen species (ROS) were assayed by flow cytometer. ET-1, eNOS and iNOS mRNA expression were measured by semi-quantitative RT-PCR. Incubation of HUVECs with resistin resulted in an increase in ICAM-1 expression and ET-1 mRNA expression. However, resistin had no effect on VCAM-1 expression and ROS release. eNOS and iNOS mRNA expression were not altered by resistin stimulation. Adipokine resistin exerted a direct effect in promoting HUVEC dysfunction by promoting ICAM-1 and ET-1 expression. These data suggest that adipocyteendothelium cross-talk might play an important role in the pathogenesis of cardiovascular disease in diabetes mellitus.

Dyspnea is one of the most common manifestations of patients with pulmonary disease, myocardial dysfunction, and neuromuscular disorder, among other conditions. Identifying the causes of dyspnea in clinical practice, especially for the general practitioner, remains a challenge. This pilot study aimed to develop a computer-aided tool for improving the efficiency of differential diagnosis. The disease set with dyspnea as the chief complaint was established on the basis of clinical experience and epidemiological data. Differential diagnosis approaches were established and optimized by clinical experts. The artificial intelligence (AI) diagnosis model was constructed according to the dynamic uncertain causality graph knowledge-based editor. Twenty-eight diseases and syndromes were included in the disease set. The model contained 132 variables of symptoms, signs, and serological and imaging parameters. Medical records from the electronic hospital records of Suining Central Hospital were randomly selected. A total of 202 discharged patients with dyspnea as the chief complaint were included for verification, in which the diagnoses of 195 cases were coincident with the record certified as correct. The overall diagnostic accuracy rate of the model was 96.5%. In conclusion, the diagnostic accuracy of the AI model is promising and may compensate for the limitation of medical experience.

Coronavirus disease 2019 (COVID-19) is currently under a global pandemic trend. The efficiency of containment measures and epidemic tendency of typical countries should be assessed. In this study, the efficiency of prevention and control measures in China, Italy, Iran, South Korea, and Japan was assessed, and the COVID-19 epidemic tendency among these countries was compared. Results showed that the effective reproduction number(Re) in Wuhan, China increased almost exponentially, reaching a maximum of 3.98 before a lockdown and rapidly decreased to below 1 due to containment and mitigation strategies of the Chinese government. The Re in Italy declined at a slower pace than that in China after the implementation of prevention and control measures. The Re in Iran showed a certain decline after the establishment of a national epidemic control command, and an evident stationary phase occurred because the best window period for the prevention and control of the epidemic was missed. The epidemic in Japan and South Korea reoccurred several times with the Re fluctuating greatly. The epidemic has hardly rebounded in China due to the implementation of prevention and control strategies and the effective enforcement of policies. Other countries suffering from the epidemic could learn from the Chinese experience in containing COVID-19.

New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR⁺/HER2^-- advanced breast cancer (ABC). We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR⁺/HER2^-- ABC. PUBMED and EMBASE databases were searched for eligible trials. Hazard ratios (HRs) for progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), clinical benefit rate (CBR), and toxicity were meta-analyzed. Twenty-six studies with data on 10 347 patients were included and pooled. The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR= 0.547, P<0.001), overall survival (pooled HR= 0.755, P<0.001), and tumor response rates (ORR, pooled OR= 1.478, P<0.001; CBR, pooled OR= 1.201, P<0.001) with manageable toxicities (pooled OR= 3.280, P<0.001). The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients. Moderate improvement in PFS (pooled HR= 0.686, P<0.001) yet pronounced toxicities (pooled OR=2.154, P<0.001) were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant. Future studies are warranted to optimize the population and the dosing sequence of these available options.

p53 mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type p53 or the functional activation of mutant-type p53 might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant p53 and KYSE 150 with wild-type p53, p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type p53, KYSE 70 with mutant p53, and EC9706 with unknown p53 genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the p53 genotype.

Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

NES1 gene is thought to be a tumor-suppressor gene. Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate, associated with a mild decrease in BCL-2 expression. The BCL-2 decrease could increase the sensitivity of radiotherapy to tumors. Thus, we supposed to have an “enhanced firepower” effect by combining overexpressed NES1 gene therapy and ¹³¹I radiation therapy uptake by overexpressed hNIS protein. We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake. By overexpressing hNIS in PC3, the radioactive iodine uptake ability was significantly increased. Results of in vitro and in vivo tumor proliferation experiments and ¹⁸F-fluorothymidine (¹⁸F-FLT) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging showed that the combined NES1 gene therapy and ¹³¹I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect. Immunohistochemistry showed an obvious decrease of Ki-67 expression and the lowest BCL-2 expression. These data suggest that via inhibition of BCL-2 expression, overexpressed NES1 might enhance the effect of radiation therapy of ¹³¹I uptake in hNIS overexpressed PC3 cells.

The effects of heat stress on the neurons in hippocampal CA1 region of brain ischemia/reperfusion were explored. The mice were pretreated with heat stress followed by ischemia/reperfusion by clipping bilateral cervical commo n arteries for 7 min. Mice were divided randomly into four groups as follows: (1) normal control group; (2) heat stress pretreated subsequent to ischemia/reperfusion group (HS/IR); (3) ischemia/reperfusion group (IR); and (4) heat stress group (HS). Animals in the last three groups were subdivided into three subgroups: 1 d, 4 d, 14 d respectively. The Morris water maze was used to test the ability of learning and memorizing, Nissl staining was used to count the average number of survived neurons in hippocampal CA1 region, and immunohistochemistry combined with image analysis system to detect the changes of Microtubule associated protein 2 (MAP-2) expression. The results showed that mice in IR group exhibited increased escape latency when compared with that of normal, HS and HS/IR groups (P<0.01), and the mice in IR group adopted an inefficient search strategy, major in circling and restricted searching manners. Nissl staining results showed a significant reduction in the number of pyramidal neurons in hippocampal CA1 regions in HS/IR and IR groups, with a decrease in IR group (P<0.01). Compared with normal group, the expression of MAP-2 in hippocampal CA1 region obviously decreased in IR group (P<0.05). The present results indicate that heat stress pretreatment can improve the spatial learning and memorizing function through protection to hippocampal neurons.

Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. Meanwhile, the H7N9 virus continues to accumulate mutations, and its affinity for the human respiratory epithelial sialic acid 2-6 receptor has increased. Therefore, a pandemic is still possible. In the past 6 years, we have accumulated rich experience in dealing with H7N9, especially in terms of virus tracing, epidemiological research, key site mutation monitoring, critical disease mechanisms, clinical treatment, and vaccine development. In the research fields above, significant progress has been made to effectively control the spread of the epidemic and reduce the fatality rate. To fully document the research progress concerning H7N9, we reviewed the clinical and epidemiological characteristics of H7N9, the key gene mutations of the virus, and H7N9 vaccine, thus providing a scientific basis for further monitoring and prevention of H7N9 influenza epidemics.

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P<0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

Recent studies have shown that acute blood glucose elevation in patients with ST-segment elevation myocardial infarction (STEMI) suggests a poor prognosis. To investigate the effect of fasting blood glucose (FBG) on the risk of heart failure (HF) and left ventricular systolic dysfunction (LVSD) in non-diabetic patients undergoing primary percutaneous coronary intervention (PCI) for acute STEMI, we retrospectively recruited consecutive non-diabetic patients who underwent primary PCI for STEMI in our hospital from February 2003 to March 2015. The patients were divided into two groups according to the FBG level. A total of 623 patients were recruited with an age of 61.3±12.9 years, of whom 514 (82.5%) were male. The HF risk (odds ratio 3.401, 95% confidence interval (CI) 2.144–5.395, P <0.001) was significantly increased in patients with elevated FBG than those with normal FBG. Elevated FBG was also independently related to LVSD (β 1.513, 95%CI 1.282–1.785, P <0.001) in a multiple logistics regression analysis. In conclusion, elevated FBG was independently associated with 30-day HF and LVSD risk in non-diabetic patients undergoing primary PCI for STEMI.

Diabetes mellitus is one of the major public health problems worldwide. Considerable recent evidence suggests that the cellular reduction–oxidation (redox) imbalance leads to oxidative stress and subsequent occurrence and development of diabetes and related complications by regulating certain signaling pathways involved in β-cell dysfunction and insulin resistance. Reactive oxide species (ROS) can also directly oxidize certain proteins (defined as redox modification) involved in the diabetes process. There are a number of potential problems in the clinical application of antioxidant therapies including poor solubility, storage instability and non-selectivity of antioxidants. Novel antioxidant delivery systems may overcome pharmacokinetic and stability problem and improve the selectivity of scavenging ROS. We have therefore focused on the role of oxidative stress and antioxidative therapies in the pathogenesis of diabetes mellitus. Precise therapeutic interventions against ROS and downstream targets are now possible and provide important new insights into the treatment of diabetes.

This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson’s disease (PD) reflected by fractional anisotropy (FA), addressing clinical profiles and methodology-related heterogeneity. Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls (HC) using the anisotropic effect size–signed differential mapping. A total of 808 patients with PD and 760 HC coming from 27 databases were finally included. Subgroup analyses were conducted considering heterogeneity with respect to medication status, disease stage, analysis methods, and the number of diffusion directions in acquisition. Compared with HC, patients with PD had decreased FA in the left middle cerebellar peduncle, corpus callosum (CC), left inferior fronto-occipital fasciculus, and right inferior longitudinal fasciculus. Most of the main results remained unchanged in subgroup meta-analyses of medicated patients, early stage patients, voxel-based analysis, and acquisition with ˂30 diffusion directions. The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex. The cerebellum and CC, associated with typical motor impairment, showed the most consistent FA decreases in PD. Medication status, analysis approaches, and the number of diffusion directions have an important impact on the findings, needing careful evaluation in future meta-analyses.

Bone mass is a key determinant of osteoporosis and fragility fractures. Epidemiologic studies have shown that a 10% increase in peak bone mass (PBM) at the population level reduces the risk of fracture later in life by 50%. Low PBM is possibly due to the bone loss caused by various conditions or processes that occur during adolescence and young adulthood. Race, gender, and family history (genetics) are responsible for the majority of PBM, but other factors, such as physical activity, calcium and vitamin D intake, weight, smoking and alcohol consumption, socioeconomic status, age at menarche, and other secondary causes (diseases and medications), play important roles in PBM gain during childhood and adolescence. Hence, the optimization of lifestyle factors that affect PBM and bone strength is an important strategy to maximize PBM among adolescents and young people, and thus to reduce the low bone mass or osteoporosis risk in later life. This review aims to summarize the available evidence for the common but important factors that influence bone mass gain during growth and development and discuss the advances of developing high PBM.

With the transformation of modern medicinal pattern, medical studies are confronted with methodological challenges. By analyzing two methodologies existing in the study of physical matter system and information system, the article points out that traditional Chinese medicine (TCM), especially the treatment based on syndrome differentiation, embodies information conception of methodological positions, while western medicine represents matter conception of methodological positions. It proposes a new way of thinking about combination of TCM and western medicine by combinating two kinds of methodological methods.

Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes. However, blood pressure (BP) responses to potassium supplementation vary among individuals. This study was designed to examine the association between 12 single nucleotide polymorphisms (SNPs) in the adducin 1 alpha (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to potassium-supplementation. We conducted a 7-day high-sodium intervention (307.8&#8201;mmol sodium/day) followed by a 7-day high-sodium with potassium-supplementation (60&#8201;mmol potassium/day) among 1906 Han Chinese participants from rural north China. BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer. We identified significant associations between ADD1 variant rs17833172 and SBP, DBP, and MAP responses to potassium-supplementation (all P&lt;0.0001) that remained significant after adjustment for multiple comparisons. In participants that were heterozygous or homozygous for the G allele of this marker, SBP, DBP, and MAP response to potassium-supplementation were &#8722;3.52 (&#8722;3.82, &#8722;3.21), &#8722;1.41 (&#8722;1.66, &#8722;1.15) and &#8722;2.12 (&#8722;2.37, &#8722;1.87), respectively, as compared to the corresponding responses of 1.99 (0.25, 3.73), &#8722;0.65 (&#8722;0.10, &#8722;0.21), and &#8722;0.23 (&#8722;0.37, 0.83), respectively, for those who were homozygous for A allele. In addition, participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation (P = 0.0041 and 0.01, respectively), which was also significant after correction for multiple testing. DBP and MAP responses to potassium-supplementation were &#8722;1.36 (&#8722;1.63, &#8722;1.10) and &#8722;2.07 (&#8722;2.32, &#8722;1.82) for those with at least G allele compared to corresponding responses of 0.86 (&#8722;0.68, 2.40) and &#8722;0.45 (&#8722;1.74, 0.84) for those who were homozygous for A allele. In summary, our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation, which could have important clinical and public health implications. Future studies aimed at replicating these novel findings are warranted.

Hearing impairment is considered as the most prevalent impairment worldwide. Almost 600 million people in the world suffer from mild or moderate hearing impairment, an estimated 10% of the human population. Genetic factors play an important role in the pathogenesis of this disorder. Hereditary hearing loss is divided into syndromic hearing loss (associated with other anomalies) and non-syndromic hearing loss (not associated with other anomalies). Approximately 80% of genetic deafness is non-syndromic. On the basis of the frequency of hearing loss, hereditary non-syndromic hearing loss can be divided into high-, mid-, low-, and total-frequency hearing loss. An audiometric finding of mid-frequency sensorineural hearing loss, or a “bowl-shaped” audiogram, is uncommon. Up to now, merely 7 loci have been linked to mid-frequency hearing loss. Only four genetic mid-frequency deafness genes, namely, DFNA10 (EYA4), DFNA8/12 (TECTA), DFNA13 (COL11A2), DFNA44 (CCDC50), have been reported to date. This review summarizes the research progress of the four genes to draw attention to mid-frequency deafness genes.

This article presents a synopsis of the current data on the mechanisms of blood--brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationship between the severity of immunobiochemical changes and clinical outcome of acute ischemic stroke. Ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. To date, BBB is not considered the border between the immune system and central nervous system, and the local immune subsystems are found within and behind the BBB. BBB disruption contributes to the leakage of brain autoantigens and induction of secondary autoimmune response to neuronal antigens and long-term inflammation. Glymphatic system function is altered and jeopardized both in hemorrhagic and ischemic stroke types. The receptors of innate immunity (toll-like receptor-2 and toll-like receptor-4) are also involved in acute ischemia--reperfusion injury. Immune response is related to the key processes of blood clotting and fibrinolysis. At the same time, the stroke-induced immune activation may promote reparation phenomena in the brain. Subsequent research on the reduction of the acute ischemic brain injury through the target regulation of the immune response is promising.

The purpose of this article is to determine the effect of a well-designed combined aerobic, resistance, and extension exercise program on bone mineral density (BMD) in postmenopausal women. The population comprised 45 postmenopausal women, who exercised over 12&#59976;months (exercise group), and 36 women who served as a non-training control group. BMD of the hip, and lumbar spine was measured at the baseline and 12th month. Repeated measurement analysis of variance and nonparametric test were utilized to compare differences between the exercise group and controls. Thirty-six out of 45 persons in the exercise group and 36 controls completed the study. Average compliance was 82.2% for the whole exercise group at the 12th month. All the subjects had decreased BMD, but the rate of bone loss was lower in the exercise group than in the control group at the L4 and hip. Although the exercise program in this study may probably reduce the rate of bone loss in weight-bearing skeletal sites, we do not suggest the exercise by itself be viewed as prevention or treatment for osteoporosis. Further, the exact dose-response relationship of exercise and bone mass in early postmenopause is not clear.

Given the rapid development in precision medicine, tremendous efforts have been devoted to discovering new biomarkers for disease diagnosis and treatment. Esophageal cancer-related gene-4 (ECRG4), which is initially known as a new candidate tumor suppressor gene, is emerging as a sentinel molecule for gauging tissue homeostasis. ECRG4 is unique in its cytokine-like functional pattern and epigenetically-regulated gene expression pattern. The gene can be released from the cell membrane upon activation and detected in liquid biopsy, thus offering considerable potential in precision medicine. This review provides an updated summary on the biology of ECRG4, with emphasis on its important roles in cancer diagnosis and therapy. The future perspectives of ECRG4 as a potential molecular marker in precision medicine are also discussed in detail.

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.

Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30–32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1, 2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.

Minimally invasive surgery, including laparoscopic and thoracoscopic procedures, benefits patients in terms of improved postoperative outcomes and short recovery time. The challenges in hand–eye coordination and manipulation dexterity during the aforementioned procedures have inspired an enormous wave of developments on surgical robotic systems to assist keyhole and endoscopic procedures in the past decades. This paper presents a systematic review of the state-of-the-art systems, picturing a detailed landscape of the system configurations, actuation schemes, and control approaches of the existing surgical robotic systems for keyhole and endoscopic procedures. The development challenges and future perspectives are discussed in depth to point out the need for new enabling technologies and inspire future researches.