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We elucidate grapevine evolution and domestication histories with 3525 cultivated and wild accessions worldwide. In the Pleistocene, harsh climate drove the separation of wild grape ecotypes caused by continuous habitat fragmentation. Then, domestication occurred concurrently about 11,000 years ago in Western Asia and the Caucasus to yield table and wine grapevines. The Western Asia domesticates dispersed into Europe with early farmers, introgressed with ancient wild western ecotypes, and subsequently diversified along human migration trails into muscat and unique western wine grape ancestries by the late Neolithic. Analyses of domestication traits also reveal new insights into selection for berry palatability, hermaphroditism, muscat flavor, and berry skin color. These data demonstrate the role of the grapevines in the early inception of agriculture across Eurasia.

Cardiac inflammation is generally accompanied by hypoxia, while myocardial injury and an abnormal microenvironment caused by hypoxia tend to suppress the efficacy of common anti-inflammatory drugs. To improve the anti-inflammatory effect under hypoxia, a hypoxia-activated prodrug HAP1 consisting of a cyclooxygenase-2 (COX-2) inhibitor Ind and a carbonic anhydrase (CA) inhibitor Ace was synthesized. HAP1 was found to be activated by nitroreductase (NTR) under hypoxia to release two pharmacophores and achieve the combinatory medication intensively at the hypoxic site, better than Ind or Ace alone. When NTR activity was inhibited by Na

BackgroundFamily physicians play a key role in responding to the growing demand for primary healthcare due to aging. The work attitude of family physician team members (FPTMs) impacts their work efficiency and quality. Knowing how satisfied they are with their jobs can help identify potential directions and entry points for incentives. The purpose of this study is to analyze the job satisfaction status and influencing factors of grassroots health service personnel after the implementation of the family physician contract system in China.MethodsThe study conducted a cross-sectional survey with 570 FPTMs in three prefecture-level cities in the Shandong Province. Satisfaction was measured using 30 items across seven dimensions. Responses were recorded on a 5-point Likert scale. Descriptive statistical analysis was used to analyze the general information and satisfaction of FPTMs. Multiple linear regression analysis was used to analyze the factors influencing job satisfaction.ResultsThe overall job satisfaction among FPTMs was not high. Among the seven dimensions, interpersonal relationships had the highest satisfaction (4.10 ± 0.78), while workload had the lowest satisfaction (3.08 ± 0.56). The satisfaction levels of the three sample regions were different, and the results were opposite to their regional economic development levels. The results of the multifactor analysis showed that gender, income level, educational background, working years, daily working hours, number of training sessions per year and the proportion of performance pay had significant impact on overall job satisfaction.ConclusionsThe development of a family physician contract system has increased the workload of FPTMs. In addition to the implementation of the new policy, attention should be paid to the workload and working attitude of family physicians. The fundamental measures should focus on attracting more personnel to work at the grassroots level by accelerating education and training to solve the problem of insufficient health personnel at the grassroots level. Simultaneously, attention should be paid to the improvement of the medical staff's salary level and the need for self-promotion, such as training.

To analyze the trend of disease burden of stroke attributable to ambient PM_(2.5) exposure among Chinese residents from 1990 to 2019.On the basis of the data of global burden of disease study 2019(GBD 2019) in China, the burden of stroke attributable to the ambient PM_(2.5) exposure in China from 1990 to 2019 were analyzed using the number and rate of deaths, disability adjusted life year(DALY), DALY rate and its standardized rate and estimated annual percentage change(EAPC).In 2019, 24.7% of stroke deaths among people aged 15 years and above in China were due to ambient PM_(2.5) exposure. Compared with 1990, in China the number of stroke deaths and mortality attributable to ambient PM_(2.5) exposure increased to 541 800 and 39.08/100 000, respectively in 2019, and the attributable DALY and DALY rates increased by 2.07% and 1.56%, respectively, in 2019. And the attributable DALY and DALY in males were higher than those in females, and they were all increasing with aging. The attributed standardized mortality and DALY rates in China were higher than those of the global and different socio-demographic index(SDI) regions, and showed an increasing trend, with EAPCs of 1.11(95% CI 0.47-1.75) and 1.11(95% CI 0.53-1.69), respectively.The burden of stroke disease due to ambient PM_(2.5) exposure is heavy in China, with differences in gender and age, and is higher than those of the global and different SDI regions.

PurposeThis study aimed to determine the prevalence of myopia among school-aged children and adolescents at the whole city level of Weifang, China.MethodsThis study was a large scale school-based cross-sectional study among children and adolescents aged 5–20 years old. Participants were selected by the school-based registration system in 2020. All the subjects underwent spherical equivalent (SE) error with non-cycloplegic autorefraction measurement. Myopia was defined as an SE refraction of ≤-0.75 diopters (D) and graded into low myopia (−0.75 to −3.00 D), moderate myopia (−3.01 to −5.99 D), and high myopia (≤-6.00 D).ResultsA total of 1,059,838 participants were eligible for this survey and 1,013,206 (95.6% participation rate) were selected through data quality control, which comprised 17 districts/counties and 1,254 schools, including 861 elementary schools, 313 middle schools, and 80 high schools. The mean age of participants was 11.57 ± 3.36 years (5–20 years), and the male-to-female ratio was 1.11. The whole city-level prevalence of total myopia was 75.35%. The prevalence of total myopia among the students in the Hanting District was 45.47%, but ≈82.37% of students living in Changyi have myopia. The overall prevalence of low myopia in elementary, middle, and high school students was 48.56, 47.30, and 31.62%, respectively, while high myopia (SE ≤ −6.00 D) prevalence was 1.12, 8.89, and 20.12%, respectively. The overall prevalence of myopia increased fastest in children aged 7–9 years old. The prevalence of high myopia was 7.59% for girls and 6.43% for boys, respectively (p < 0.001). The prevalence of myopia increased with increasing age and grade, but SE decreased with increasing age and grade.ConclusionsThe current investigation demonstrated a high proportion of myopia among school students in the city of Weifang, and gradually increased with age, and the prevalence of myopia was the highest in Changyi areas. The high myopia prevalence for girls was higher than that in boys.

Background Doctors play an important role in smoking control. This study aimed to assess doctors’ smoking control knowledge, attitudes and practices to help doctors raise awareness of smoking control assistance. Methods This cross-sectional study recruited 1046 doctors from Shandong Province, China, by using multistage sampling. Participants’ information was collected by questionnaire. Pearson’s χ2 test and Fisher’s exact probability method were used to compare the distributions of categorical variables between/among groups. Results Among the participants, 14.7% were current smokers. Approximately 50.3% of participants had heard of smoking cessation drugs and 59.2% of participants thought that low-tar and low-nicotine cigarettes were as harmful to health as common cigarettes. Approximately 98.2 and 60.9% of participants agreed that smoking was related to lung cancer and male sexual dysfunction, respectively. Although 72.0% of participants believed that doctors should actively provide smoking cessation assistance, only 58.1% of participants considered that doctors should be responsible for providing smoking cessation assistance. Similarly, 85.2% of participants often asked about the smoking history of patients or their family members, while only 4.9% of participants had prescribed smoking cessation drugs for patients. Pediatricians had a higher proportion of “Agree” responses to the assessment items than doctors in other departments. Conclusions The results showed that doctors in Shandong Province did not have sufficient knowledge of smoking control. Slightly more than half of doctors thought that providing smoking cessation assistance was their responsibility. Only a few participants had prescribed smoking cessation drugs.

This study aimed to evaluate the cost-effectiveness of donafenib compared to sorafenib and lenvatinib as first-line treatments for patients with advanced hepatocellular carcinoma (HCC) in China.A partitioned survival model was developed to estimate the clinical and economic outcomes of donafenib, sorafenib, and lenvatinib for advanced HCC. The key clinical data of these targeted therapies were assessed through a network meta-analysis. The cost and health utilities were mainly collected from the literature. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICER) were the primary outcomes. Model uncertainty was tested with one-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses (PSA).For health outcomes, donafenib gained the highest QALYs among the three treatments, followed by lenvatinib and sorafenib (1.106, 0.999, and 0.915 QALYs, respectively). For cost, donafenib was the cheapest option, followed by sorafenib and lenvatinib ($42,116, $43,193, and $44,261). The PSA indicated that the probability of being cost-effective for donafenib was 86.98% and 93.56% when the willingness-to-pay thresholds were one and three times the gross domestic product per capita in China, respectively. The one-way sensitivity analyses and scenario analyses also found the results to be robust.Compared to sorafenib and lenvatinib, donafenib was likely to be a cost-effective treatment with the highest QALYs and the lowest cost for patients with advanced HCC in China.

Background Ischemic heart disease (IHD) is the leading cause of premature death which poses public health challenges worldwide. Previous studies focused on the overall population in China. However, variations in temporal and spatial patterns across subgroups remain unknown. This study was to analyze how the IHD burden among Chinese and subgroup populations changes in response to temporal and spatial trends from 1990 to 2016. Methods Based on data from the updated estimate in the 2016 Global Burden of Disease (GBD) study, we used years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) to describe the IHD burden. The percentage and annual average percentage changes were applied to illustrate temporal and spatial variations of the IHD burden stratified by age, sex, and province, over the periods 1990–2016, 1990–2005, and 2005–2016. We estimate population-attributable fraction (PAF) for 24 modifiable risk factors at the provincial level in 2016. Results YLD rates, YLL rates, and DALY rates for IHD underwent a notable increase among all age groups and increased by 119.4, 83.3, and 84.5% nationally from 1990 to 2016. In YLD rates, a greater increase was seen in females (124.4%) compared to males (114.0%), while males experienced a more substantial increase than that in females in YLL rates (99.3% vs. 60.5%) and DALY rates (99.7% vs. 63.2%) from 1990 to 2016. Compared with 1990–2005, annual average changes in the overall population in YLL rates (3.5% vs. 1.8%) and DALY rates (3.5% vs. 1.9%) showed a tardier increase whereas an opposite increasing trend of YLD rates (3.5% vs. 4.0%) was observed between 2005 and 2016. Geographically, all provinces saw declines in the YLLs/YLDs ratio from 2005 to 2016, with seventeen of thirty-three provinces showing an upward trend between 1990 and 2005. Most provinces witnessed a remarkable upsurge in the age-standardised DALY rate from 1990 to 2016 whereas the economically advantaged region Macao (52.2%) saw the most marked reduction. High systolic blood pressure and high LDL cholesterol remained the two leading risk factors of IHD in all provinces in 2016. Diet high in sodium was the leading behavioral risks in twenty-eight provinces with smoking heading the list in five provinces. Conclusions China has made significant achievements in preventing premature death from IHD along with the increased risk of disability. Substantial disparities in temporal and spatial trends of the IHD burden emphasize concerns for elderly men and those in economically disadvantaged regions with resource constraints. Regional differences in the IHD burden can be partly explained by modifiable risk factors. By having identified these disparities, targeted IHD prevention and control strategies will help to bridge these gaps.

Although much progress has been made in the diagnosis and treatment of thoracic aortic dissection (TAD), the overall morbidity and mortality rates of TAD are still high. Therefore, the molecular pathogenesis and etiology of TAD need to be elucidated. In this study, we found that histone deacetylase 1 (HDAC1) expression is dramatically higher in the aortic wall of patients with TAD (than that in a normal group) and negatively correlates with the levels of the vascular smooth muscle cell (SMC) contractile-phenotype markers. Knockdown of HDAC1 upregulated both smooth muscle 22 α (SM22α) and α-smooth muscle actin (α-SMA) in platelet-derived growth factor (PDGF)-BB-treated and -untreated SMCs. In addition, the knockdown of HDAC1 markedly decreased SMC viability and migration in contrast to the control group under the conditions of quiescence and PDGF-BB treatment. We also showed that the expression of polycystic kidney disease 1 (PKD1) is decreased in the aortic wall of patients with TAD and negatively correlates with HDAC1 expression. Overexpressed PKD1 obviously increased SM22α and α-SMA expression and reduced the viability and migration of SMCs, but these effects were attenuated by HDAC1. Furthermore, we demonstrated that HDAC1 serves as an important modulator of the migration and phenotypic switch of SMCs by suppressing the PKD1- mammalian target of the rapamycin signaling pathway. HDAC1 downregulation inhibited media degeneration and attenuated the loss of elastic-fiber integrity in a mouse model of TAD. Our results suggest that HDAC1 might be a new target for the treatment of a macrovascular disease such as TAD.

This study aimed to investigate the functional roles of kinesin family member 18B (KIF18B) in hepatocellular carcinoma (HCC) development, as well as the related molecular mechanisms. Tissue specimens were collected from 105 patients with HCC, and the messenger RNA (mRNA) and protein levels of KIF18B were detected using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The χ2 test was performed to estimate the association of KIF18B with clinical characteristics of patients with HCC. Effects of KIF18B expression on biological behaviors of HCC cells were detected by clone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and transwell assays. The expression patterns of proteins were investigated using Western blot analysis. HCC tissues and cell lines showed significant upregulation of KIF18B at both mRNA and protein levels (p > .05, for all). Furthermore, the elevated KIF18B expression was positively correlated with the tumor-node-metastasis stage (p = .015) and lymph node metastasis (p = .007). Knockdown of KIF18B might suppress HCC cell clone formation, proliferation, migration, and invasion in vitro. Besides, the activity of Wnt/β-catenin pathway was also significantly inhibited after the KIF18B knockdown. However, the antitumor actions caused by KIF18B knockdown might be reversed by lithium chloride treatment, which was the inducer of Wnt/β-catenin-signaling pathway. KIF18B may serve as an oncogene in HCC through enhancing the activity of Wnt/β-catenin pathway.

Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial–mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

Background Alcohol use disorders (AUD) has long been one of the most disability mental disorders and a major cause of health loss. Methods Based on open access data from the 2019 Global Burden of Disease (GBD 2019) study, we extracted data of years lived with disability (YLD), years of life lost (YLL) and disability-adjusted life years (DALY) to describe the changes of AUD burden over the period of 1990-2019 stratified by sex in globe, high-income countries (HICs), upper-middle income countries (UMCs), lower-middle income countries (LMCs), low-income countries (LICs) and China. We used Joinpoint regression model to fit the changing trend of years. And pairwise comparison was applied to test the coincidence parallelism and judge whether the difference of the trend among different regions is statistically significant. Results LMCs experienced the largest changes in the YLD rate of AUD from 1990 to 2019 (average annual percent change (AAPC) = -0.7, 95% confidence interval (CI) = -0.8, -0.7, P

Purpose The objectives of this study were to examine the patterns of antihyperglycemic drug (AHD) therapy among patients with newly diagnosed type 2 diabetes mellitus (T2DM) in the general Chinese population, stratified by initial hemoglobin (Hb) A1c level, and to assess whether treatment patterns are consistent with the recommendations published in the China Diabetes Society's clinical treatment guideline. Methods A retrospective database analysis was conducted, and data were obtained from the SuValue database. Prescribing patterns for diabetes treatments were determined from data obtained from the Nanhai District-based electronic medical records database, a subset of the SuValue database. Data from patients newly diagnosed with T2DM who also had at least 2 prescriptions for AHD medications after diagnosis and at least 1 HbA1c test result during the 12 months prior to AHD treatment initiation, between January 1, 2004, and July 22, 2018, were included in the analysis. ANOVA, χ2 test, and Kaplan-Meier survival analysis were used to examine differences between 4 initial-HbA1c groups ( Findings A total of 4712 patients were included, with women accounting for 47.8%; the mean age (SD) of the study population was 56.44 (12.57) years. Men were more likely to have had a higher HbA1c level at initial AHD treatment (P Implications The findings from the present study depict a comprehensive overview of AHD-treatment patterns in patients stratified by HbA1c level. The current treatment practices observed were inconsistent the published guideline, in terms of recommendations on metformin monotherapy and insulin use in first-line therapy.

Few studies have examined the attributable fraction (AF) of temperature to mortality and Years of Life Lost (YLL), especially in developing countries. This study aims to explore the short-term effect of the cold and hot temperatures on the cause-specific YLL and mortality, discover the attributable contributions from the temperature variations, and identify the vulnerable populations in Weifang, China. Daily registered death information and meteorological data over the period 2010-2016 were obtained in Weifang, a northern Chinese city. Generalized additive Poisson and Gaussian regression models were used to assess the impacts of temperatures on both mortality and YLL, explore the AF of the temperature variations on mortality, after adjusting for other covariates. Both hot and cold temperatures have had significant negative impacts on cause-specific mortality counts and YLL, with heat presented an acute and short effect and the cold temperatures had delayed effects and lasted for several days. In terms of the attributable fraction calculations, the contributions from cold effects was higher than that of hot effects on non-accidental, cardiovascular, and respiratory deaths (YLL 10.88 vs. 1.23%, 19.58 vs. 1.71%, and 14.47 vs. 3.05%; mortality 13.97 vs. 1.65%, 19.20 vs. 1.59%, and 14.89 vs. 3.09%), respectively. The elderly and women and people with low education level were the most vulnerable. The findings will provide important scientific evidences and policy implications for developing adaptation strategies to reduce the adverse effect of cold and hot exposure in Weifang, in terms of resource allocation, healthcare workforce capacity building, and community health education, especially for the vulnerable groups.

Background Climate change may lead to emerging and re-emerging infectious diseases and pose public health challenges to human health and the already overloaded healthcare system. It is therefore important to review current knowledge and identify further directions in China, the largest developing country in the world. Methods A comprehensive literature review was conducted to examine the relationship between climate variability and infectious disease transmission in China in the new millennium. Literature was identified using the following MeSH terms and keywords: climatic variables [temperature, precipitation, rainfall, humidity, etc.] and infectious disease [viral, bacterial and parasitic diseases]. Results Fifty-eight articles published from January 1, 2000 to May 30, 2018 were included in the final analysis, including bacterial diarrhea, dengue, malaria, Japanese encephalitis, HFRS, HFMD, Schistosomiasis. Each 1 °C rise may lead to 3.6%–14.8% increase in the incidence of bacillary dysentery disease in south China. A 1 °C rise was corresponded to an increase of 1.8%–5.9% in the weekly notified HFMD cases in west China. Each 1 °C rise of temperature, 1％ rise in relative humidity and one hour rise in sunshine led to an increase of 0.90%, 3.99% and 0.68% in the monthly malaria cases, respectively. Climate change with the increased temperature and irregular patterns of rainfall may affect the pathogen reproduction rate, their spread and geographical distribution, change human behavior and influence the ecology of vectors, and increase the rate of disease transmission in different regions of China. Conclusion Exploring relevant adaptation strategies and the health burden of climate change will assist public health authorities to develop an early warning system and protect China's population health, especially in the new 1.5 °C scenario of the newly released IPCC special report.

Study design A retrospective review of clinical and radiological parameters. Objective To evaluate the therapeutic efficacy of transpedicular impaction bone grafting (TIBG) with long segmental posterior instrumentation for the treatment of stage III Kummell disease. Summary of background data The optimal treatment for stage III Kummell disease remains controversial and unclear. Theoretically, transpedicular bone grafting can reconstruct anterior column support and reduce the failure of internal fixation, which is an intuitive method for the treatment of Kummell disease. However, the use of this technique has rarely been reported for the treatment of this disease. This study reported the clinical and radiological results of TIBG with long segmental posterior instrumentation for the treatment of stage III Kummell disease. Methods Between August 2011 and December 2017, we retrospectively analyzed 24 patients with stage III Kummell disease who underwent TIBG with long segmental posterior instrumentation. Anterior vertebral heights, kyphotic Cobb angle, visual analog scale (VAS), Oswestry disability index (ODI), and American Spinal Injury Association (ASIA) impairment scale were used to evaluate the effects of surgery. Results The mean time to follow-up was 38.1 ± 10.2 months. The average operative duration was 136 ± 16.5 minutes, and the average intraoperative blood loss was 293 ± 41.3 mL. The VAS, ODI, anterior vertebral heights, and kyphotic Cobb angles were improved significantly at 1 week after surgery compared the preoperative examinations, and were well maintained at the final follow-up evaluation. Fourteen patients (58%) had mild neurological impairments before surgery, with neurological function returning to normal at the final follow-up evaluation. There was no instance of instrumentation failure. Conclusion TIBG combined with long segmental posterior instrumentation is a safe and effective surgical option for stage III Kummell disease.Level of Evidence: 4.

To improve the salt tolerance/sensitivity of cellulose nanofibrils (CNFs), zwitterionic cellulose nanofibrils (ZCNFs) were prepared from softwood bleached kraft pulp fibers via a sequential process of anionic modification with 2,2,6,6-tetramethylepiperidin-1-oxyl (TEMPO)-mediated oxidation, cationic modification with (2,3-epoxypropyl) trimethylammonium chloride (EPTMAC), and high-pressure homogenization. To produce ZCNFs with different contents of cation group, EPTMAC loadings of 0.15 to 1.15 g/g fiber were explored during cationization. The obtained ZCNFs were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectra (XPS), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and rheological measurements. The salt tolerance of the ZCNFs was investigated by adding mixed salts into the ZCNF dispersions. The results demonstrated that the ZCNFs with both anionic and cationic charges were produced. Compared with the TEMPO-mediated oxidized cellulose nanofibrils (TOCNFs), the ZCNFs exhibited an excellent "salt-thickening" behavior under the studied salt concentrations (2-24% w/w). Moreover, increasing the content of the cation group increased the salt tolerance/sensitivity of ZCNFs. This work demonstrated that introducing cationic charges to the anionic charged TOCNFs imparts the produced ZCNFs with excellent salt sensitivity and tolerance, which could expand the application of nanocellulose in oil recovery or wastewater treatment.

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl4)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl4 (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl4 also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100 μg/mL effectively relieved CCl4-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400 mg/kg BW) were administered via gavage daily for 14 days before CCl4 treatment. The high serum ALT and AST levels induced by CCl4 were dose-dependently suppressed by pretreatment of TFs (200 and 400 mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl4-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl4-induced liver damage.

BACKGROUND Cryoablation of hepatocellular carcinoma (HCC) close to major organs or viscus is challenging because it can cause complications. This retrospective study aimed to investigate the safety and efficacy of percutaneous argon-helium cryoablation of small HCC located adjacent to major organs or viscus. MATERIAL AND METHODS Ninety-two patients who underwent percutaneous argon-helium cryoablation between February 2012 and December 2018 at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital were included. Treatment efficacy was evaluated by magnetic resonance imaging or triphasic computed tomography scan within 1 week after each cryoablation procedure. Local tumor progression, distant recurrence, and overall survival were analyzed using the Kaplan-Meier method and log-rank test. RESULTS A total of 92 patients with small HCC located adjacent to major organs or viscus who underwent cryoablation were retrospectively reviewed. The number of patients with tumors adjacent to the gallbladder, portal or hepatic vein, diaphragm, stomach, heart, and intestine was 22, 1, 39, 6, 8, and 16, respectively. Cumulative local tumor progression rates at 1 and 2 years were 2.8% and 7.3%, respectively. Cumulative distant recurrence rates at 1, 2, and 3 years were 11.1%, 17.6%, and 20.7%, respectively. The overall survival rates at 1, 2, and 4 years were 100%, 93.6%, and 74.9%, respectively. Major complications were observed in 5 (5.4%) patients. Minor complications were observed in 85 (92.4%) patients. CONCLUSIONS This experience from a single center showed that percutaneous argon-helium cryoablation was safe and effective in the management of small HCC that is located adjacent to major organs or viscus.

Dual-cloud point extraction (dCPE) was successfully developed for simultaneous extraction of trace sulfonamides (SAs) including sulfamerazine (SMZ), sulfadoxin (SDX), sulfathiazole (STZ) in urine and water samples. Several parameters affecting the extraction were optimized, such as sample pH, concentration of Triton X-114, extraction temperature and time, centrifugation rate and time, back-extraction solution pH, back-extraction temperature and time, back-extraction centrifugation rate and time. High performance liquid chromatography (HPLC) was applied for the SAs analysis. Under the optimum extraction and detection conditions, successful separation of the SAs was achieved within 9 min, and excellent analytical performances were attained. Good linear relationships (R2 ≥ 0.9990) between peak area and concentration for SMZ and STZ were optimized from 0.02 to 10 μg/mL, for SDX from 0.01 to 10 μg/mL. Detection limits of 3.0–6.2 ng/mL were achieved. Satisfactory recoveries ranging from 85 to 108% were determined with urine, lake and tap water spiked at 0.2, 0.5 and 1 μg/mL, respectively, with relative standard deviations (RSDs, n = 6) of 1.5–7.7%. This method was demonstrated to be convenient, rapid, cost-effective and environmentally benign, and could be used as an alternative tool to existing methods for analysing trace residues of SAs in urine and water samples.

Intervertebral disc (IVD) disease, the most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to analyze the potential of thalidomide for the treatment of IVD disease, through identifying and explaining its anti-inflammatory and anti-catabolic activity in both in vitro IVD cell culture and in vivo animal model. Inflammatory response was induced by IL-1β, then the activity and expression of inflammatory mediators and pathways were assessed in the presence or absence of thalidomide. The p38 inhibitor SB203580 was also used to investigate the involvement of the MAPK pathway in the observed effects. Moreover the analgesic properties of thalidomide were analyzed by the von Frey filament test in Sprague-Dawley rats. Our results indicated that thalidomide significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB. Our current study strongly supports the potential of thalidomide for the treatment of pain and inflammation in degenerative disc disease.

This study aimed to explore whether the depression of offspring caregivers can be affected by the intergenerational disagreements on preferred living arrangements for the elderly, and the extent of this influence.A total of 875 participants from five urban neighborhoods were investigated in a cross-sectional survey in Jinan, China. Depressive symptoms were assessed by the Self-rating Depression Scale (SDS). Multiple stratification was performed based on participants' characteristics, then generalized linear models (GLM) were used to adjust confounding factor and analyze the effect of the intergenerational disagreements on depressive symptoms among participants with different characteristics.The intergenerational disagreements on preferred living arrangements for the elderly greatly impact on offspring caregivers' depressive symptoms. Especially in the following two situations: (1) in the case of older adults were relatively independent and offspring caregivers had to co-reside with older adults against their own will, the max mean difference on the depression measures was up to 10.603 (p0.001), in comparison with both parties were willing to co-reside. (2) In the case of older adults were fully dependent and offspring caregivers had not to hire a maid to care older adults against their own will, the max mean difference on the depression measures was up to 8.937 (p0.001), in comparison with both parties were willing not to hire a maid.Intergenerational disagreements on preferred living arrangement for the elderly have negative effect on offspring caregivers' depressive symptoms.

The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-β p, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief.

Thalidomide was introduced to the market in 1957 as a sedative and antiemetic agent, and returned to the market for the treatment of myelodysplastic syndrome and multiple myeloma. There are reports and studies of thalidomide as an analgesic or analgesic adjuvant in clinic. However, the underlying mechanism is quite elusive. Many studies suggest that the analgesic effect of thalidomide may be due to its immunomodulatory and anti-inflammatory properties as it suppresses the production of tumor necrosis factor α (TNF-α) selectively. However, it is not clear whether any other mechanisms are implicated in the pain relief. In this study, we demonstrated that the peripheral vanilloid receptor 1 (TRPV1) channel was also involved in the analgesic effect of thalidomide in different cell and animal models. During the activation by its agonist capsaicin, the cation inward influx through TRPV1 channels and the whole-cell current significantly decreased after TRPV1-overexpressed HEK293 cells or dorsal root ganglion (DRG) neurons were pre-treated with thalidomide for 20 minutes. And such attenuation in the TRPV1 activity was in a dose-dependent manner of thalidomide. In an acetic acid writhing test, pre-treatment of thalidomide decreased the writhing number in the wild type mice, while it did not happen in TRPV1 knockout mice, suggesting that the TRPV1 channel was involved in the pain relief by thalidomide. Taken together, the study showed that TRPV1 channels were involved in the analgesic effects of thalidomide. Such alteration in the action of TRPV1 channels by thalidomide may help understand how thalidomide takes analgesic effect in the body in addition to its selective inhibition of TNF-α production.

Cryoablation is a less prevalent percutaneous ablative therapy for hepatocellular carcinoma (HCC), and current evidence about its usefulness is limited. We report our experience in treating 1595 HCC cases with percutaneous cryoablation to give a comprehensive profile about the effectiveness, safety and long-term outcome of this therapy. From January 2003 to December 2013, 1595 patients with 2313 HCC nodules were ablated with 2958 cryoablation sessions in our center. Complete ablation was achieved in 1294 patients for 1893 nodules with a mean diameter of 3.4 ± 2.2 cm. The complete ablation rate was 81.2%, 99.4%, 94.4%, and 45.6% in all tumors, tumors3 cm, tumors5 cm, and tumors5 cm, respectively. Major complications were observed after 80 (3.4%) of the 2958 cryoablations and minor complications were observed after 330 cryoablations with no treatment-related deaths. After a median follow-up of 33.4 months, 937 patients developed different types of recurrence. The 5- and 10-year overall survival was 25.7% and 9.2%, respectively. Cryoablation showed reliable safety and efficacy and should be considered as a promising technique, particularly when a large zone of ablation is required.

Background Epigenetic alterations are well documented in hepatocarcinogenesis. However, hypomethylation of long interspersed nuclear element 1(LINE-1) promoter and its relationship with clinicopathological features in hepatocellular carcinoma (HCC) remain unknown. Methods The bisulfite-specific PCR and DNA sequencing analysis was performed to assess the methylation status of LINE-1 promoter in a pilot cohort of 71 patients with HCC. Additionally, methylation levels of two hot CpG sites of LINE-1 promoter, site 7 and 18 were measured by real-time PCR and compared with clinicopathological parameters in a cohort of 172 HCC. All the patients included were in BCLC stage A or B. Results Most patients with HCC (87.3%) showed hypomethylation of LINE-1 promoter compared with HBV-related cirrhosis and normal controls (P

Widespread interest in the mechanism of transcriptional regulation by the androgen receptor (AR) has been stimulated by the finding that AR signaling is critically important in the progression of human prostate cancers. Co-factors, the co-repressors, or the co-activators are responsible for the regulation of AR activation. The pro-oncogene human Long Interspersed Nucleotide acid Element-1 (LINE-1) encodes LINE-1 ORF-1p and plays important roles in the development and progression of several human carcinomas. In this study, the results showed that LINE-1 ORF-1p increased the AR transcriptional activity and in turn enhanced the expression of prostate specific antigen (PSA) in the presence of R1881. A physical protein-protein interaction between the AR signaling and the LINE-1 ORF-1p was identified by the immunoprecipitation assays and GST pull-down assays. Furthermore, LINE-1 ORF-1p would function as a novel AR positive co-regulator through modulating its cytoplasm/nucleus translocation and the recruitment to the androgen response element in the PSA gene promoter. Our date also showed that the LINE-1 ORF-1p promoted the proliferation and anchor-independent growth of LNCaP (ligand dependent) and PC-3 (ligand independent) human prostatic carcinoma cells. By investigating a novel role of the LINE-1 ORF-1p in the androgen/androgen receptor signaling pathway regulation, our study identifies that LINE-1 ORF-1p may be a novel AR co-regulator and molecular target for human prostate carcinoma therapy.

We describe a case of cardiac cavernous hemangioma with coexisting pulmonary cavernous hemangiomas and hepatic hemangioma. A 35-year-old woman who had previously received a living donor liver transplant to cure giant hepatic hemangioma was seen because of chest pain. A cardiac neoplasm and multiple pulmonary nodules were detected. The tumor was surgically removed, and biopsy specimens were taken from the lung nodules. Histopathologic examination confirmed that both lesions were cavernous hemangiomas. The patient was discharged without adverse events postoperatively. Cardiac hemangioma is an extremely rare entity; the present case is unique for its multiorgan involvement. Suspicion of this entity should be aroused if the imaging manifestation suggests a vascular nature.

We assessed the safety and efficacy of sorafenib with cryotherapy (cryoRx) in advanced hepatocellular carcinoma (HCC). One hundred four HCC patients were enrolled, who met the following criteria: (i) Barcelona Clinic Liver Cancer stage C; (ii) HCC without distant metastasis; (iii) the presence of portal vein thrombosis (PVT); (iv) Child-Pugh class A or B; and (v) life expectancy of at least 12 weeks. The patients were randomly divided into sorafenib-cryoRx and sorafenib (control) groups. Primary endpoint was time to progression (TTP); secondary endpoints included overall survival (OS) and tolerability. Microvessel density (MVD) was assessed by CD34-immunostaining. After a median 10.5 (4–26) months follow-up, the data showed that median TTP was 9.5 (8.4–13.5) months in combinatorial therapy group vs. 5.3 (3.8–6.9) months in sorafenib group (P = 0.02). The median OS was 12.5 (95 % CI 10.6–16.4) months in combination therapy group vs. 8.6 (7.3–10.4) months in sorafenib group (P = 0.01). Low MVD patients in combination therapy exhibited significantly longer median TTP and OS than controls. High MVD was predictive of poor responses to sorafenib. CryoRx did not increase frequency/degree of sorafenib-related adverse events. Therefore, it was concluded that the addition of cryoRx significantly improved clinical outcomes of Sorafenib therapy in advanced HCC with acceptable tolerance and similar safety profiles as previously reported.

We carried out this study to evaluate the association between regulatory T cells (Treg) and prognosis and progression after cryoablation in patients with hepatitis-B virus-related hepatocellular carcinoma.Peripheral Treg frequency in 111 patients with hepatocellular carcinoma (HCC) was detected by flow cytometry. Treg frequency and function were re-examined during patient follow up. A possible association between Treg and α-fetoprotein (AFP) was also analyzed, and the distribution of resident CD4(+) and CD8(+) T cells and FoxP3(+) T cells in the liver tissue of patients with HCC was examined by immunohistochemistry.Treg frequency significantly increased with disease progression. Our longitudinal study showed that Treg frequency had significantly decreased in 17 patients with HCC regression following cryoablation, but the frequency had dramatically increased in 14 patients with HCC recurrence or progression. Furthermore, AFP levels varied in a way comparable with Treg frequency in patients with elevated AFP recorded before therapy. Significantly increased suppressive effects of Treg on proliferation and cytokine secretion of CD8(+) and CD4(+) T cells were observed during follow up in patients with tumor progression, but not in patients with tumor response. Moreover, the numbers of CD8(+), CD4(+), and FoxP3(+) cells infiltrating the tumors around the cryotherapeutic zones were significantly decreased after argon-helium cryoablation, and this was associated with a reduction in the FoxP3/CD8 ratio. Importantly,increased quantities of circulating CD4(+)CD25(+)FoxP3(+) Treg and tumor infiltrating FoxP3(+) cells before cryoablation were associated with high recurrence or risk of progression in HCC patients after cryoablation.Treg variation is associated with tumor regression or progression in HCC following cryoablation and may be used as a marker to estimate HCC progression.

MicroRNA-153 (miR-153) is considered to be a tumor regulator. Silencing of miR-153 expression induced apoptosis in breast cancer cells. Data on mechanism suggest that up-regulation of miR- 153 level promotes cell proliferation via the down regulation of the expression of PTEN or FOXO1, which attenuates the proliferation of cancerous cells. This study aims to identify the effect of miR-153 on the activity of chemotherapeutic and targeted agents in HCC cells and to investigate the mechanisms involved. MTT, soft agar, trans-well and flow cytometry assays were performed to examine whether miR-153 down-regulated the activity of the chemotherapeutic and targeted drugs, Sorafenib, Etoposide and Paclitaxel in HCC cells. The rate of proliferation inhibition, relative survival rates and IC 50 values of each drug were calculated. Western blot and luciferase assays were performed to assess whether miR-153 modulates the expression of important genes related to cell proliferation, apoptosis or survival. Results showed that miR-153 attenuated the effect of Etoposide, Paclitaxel and Sorafenib on HepG2 cells; the IC 50 value increased from 0.25±0.01μmol/L to 1.02±0.14μmol/L, 0.05±0.01μmol/L to 0.14±0.02μmol/L and from 1.09±0.15μmol/L to 5.18±0.99μmol/L, respectively. In addition, miR-153 also reduced the effect of these drugs on MHCC- 97H, MHCC-97 L and L-02 cells; and it also reduced the effects of Sorafenib, Etoposide and Paclitaxel on anchorindependent growth of HepG2 cells. Over-expression of miR-153 down-regulated the activity of Etoposide and Paclitaxel on cell cycle arrest of HepG2 cells and the effect of Sorafenib on the invasion and migration of HepG2 cells. Furthermore, overexpression of miR-153 also enhanced the growth of HepG2, MHCC-97H, MHCC-97 L and L-02 cells. Mechanisms data showed that overexpression of miR-153 down regulated the activity of luciferase reporters, p15-Luc and p21-Luc; and enhanced the protein level of pro-survival or anti-apoptosis proteins Survivin and BCL-2. These results show that overexpression of miR-153 protects HepG2 cells against the effects of these drugs via multiple mechanisms, and miR-153 may be a novel target for HCC in future diagnostic and therapeutic interventions.

Background Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. Methods/design This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. Discussion Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. Trial registration ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013

Since 2009, health reform had launched in China and essential public health services were provided for all residents to ensure service equity and accessibility, and to achieve sustained population-wide health improvement. This study aimed to investigate the differences and determinants among populations with different characteristics access to essential public health services in China, especially hypertension people and children aged 0-6 years.A cross-sectional study with socio-demographic data analysis was undertaken to estimate distribution characteristics of receiving essential public health services of hypertension patients and children. Regular follow-ups and effective blood pressure control reflected the effective management for hypertension patients, and for children, public services provided were vaccination on schedule and regular physical check-up. Logistic regression was used to determine the predictors for effective management.A total of 1 505 hypertension patients and 749 children were involved; 39.14% of hypertension participants could control their blood pressure in the normal range, and the rate in urban areas (43.61%) was higher than that in rural (31.88%). And 34.68% of them could receive more than 4 times follow-ups by the medical technician. Of 754 children, 79.84% could receive the periodic physical examination and 98.40% had vaccinated regularly. Children living in rural areas were more likely to have regular check-ups (83.96%) and regular vaccination (nearly 99%). Overall, geographic location and education level were the determinants of people access to essential public health services.Implementation of the health reform since 2009 has headed China's public health system in the right direction and promoted the improvement of public health system development. Our study highlights the growing needs for more public health services in China, and China's public health system needs to be greatly improved in terms of its quality and accessibility.

Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro-oncogene LINE-1. It is involved in the development and progression of several human carcinomas, such as hepatocellular carcinoma and lung and breast cancers. The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in regulation of cancer cell proliferation, metastasis and invasion. The biological function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling pathway in regulation of human breast cancer proliferation remains largely unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional activity and increased expression of downstream genes of ETS-1. Interaction between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays. LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1 ORF-1p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated that LINE-1 ORF-1p may be a novel ETS-1 coactivator and molecular target for therapy of human triple negative breast cancer.

Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the following groups: fatty acid transport and β-oxidation, gluconeogenesis, and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of five metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis.

Objective To discuss the experience of combining extra-corporeal membrane oxygenation (ECMO) with intra-aortic balloon pump (IABP) for the treatment of acute heart failure in critically ill adults. Methods The clinical data of 54 patients who received ECMO combined with IABP due to acute heart failure between January 2008 and July 2012 were retrospectively analysed. Thirty-eight of the patients were male, and 16 were female; the mean age was 57±11. Thirty-nine of the patients received IABP first but were still unable to maintain adequate circulation, and were then given ECMO; the other 15 underwent ECMO first, but due to increased left ventricular load, the opening of the aortic valve was restricted and IABP was then introduced. Results Thirty-four patients (63%) were successfully weaned from ECMO; 21 patients (38.9%) survived to discharge. Major complications that occurred were renal failure (27 cases), infection (20 cases), blood plasma leakage in the oxygenator (13 cases), bleeding (18 cases), limb ischaemia (eight cases), and neurological complications (seven cases); in the group of patients who did not survive, the rates of bleeding occurrence, infection and renal failure were markedly higher than in the survived patients group. In both groups, the longer the patients were on support, the more improvement they showed in terms of MAP, CVP, Lac, SvO 2 and IS. Conclusion ECMO and IABP may have synergistic effects and play complementary roles in the treatment of acute cardiac failure; with timely administration, active prevention and treatment of complications, they can improve treatment outcome.

We present the case of one 58-year-old man with advancd hepatocellular carcinoma and hepatitis-B virus-related liver cirrhosis who received hepatic cryoablation. Magnetic resonance imaging (MRI) showed multiple liver tumors and the diameter of the largest tumor was more than 10cm. The patient received 2 percutaneous cryoablations in December 2009 and January 2010. Ten months later, MRI showed that not only the treated areas underwent necrosis but also the non-treated area decreased. The a-fetoprotein (AFP) level and the frequency of circulated regulatory T cell (Treg) before treatment were 13,800ng/mL and 15.6%, respectively. Following the cryoablations they dropped to 436ng/mL and 7.6%, respectively, 10 months later. The patient remains in good condition until now.

Peptides Count (SC) was widely used for protein abundance estimation in proteomics. On the basis of that, Mann and co-workers corrected the SC by dividing spectrum counts by the number of observable peptides per protein and named it PAI. Here we present modified spectral count index (mSCI) for protein abundance estimation, which was defined as the number of observed peptides divided by protein relative identification possibility (RIPpro). RIPpro was derived from 6788 mRNA and protein expression data (collected from human liver samples) and related to proteins' three physical and chemical properties (MW/pI/Hp). For 46 proteins in mouse neuro2a cells, mSCI shows a linear relationship with the actual protein concentration, similar or better than PAI abundance. Also, multiple linear regressions were performed to quantitative assess several factors' impact on the mRNA/protein abundance correlation. Our results shown that the primary factor affecting protein levels was mRNA abundance (32-37%), followed by variability in protein measurement, MW and protein turnover (7-12%,7-9% and 2-3%, respectively). Interestingly, we found that the concordance between mRNA transcripts and protein expression was not consistent among all protein functional categories. This correlation was lower for signaling proteins as compared to metabolism genes. It was determined that RIPpro was the primary factor affecting signaling protein abundance (23% on average), followed by mRNA abundance (17%). In contrast, only 5% (on average) of the variability of metabolic protein abundance was explained by RIPpro, much lower than mRNA abundance (40%). These results provide the impetus for further investigation of the biological significance of mechanisms regulating the mRNA/protein abundance correlation and provide additional insight into the relative importance of the technological parameter (RIPpro) in mRNA/protein correlation research.

Hepatic angiomyolipoma (HAML) is a rare mesenchymal tumor of the liver with marked histological diversity. The present study was to review the magnetic resonance imaging (MRI) and clinical pathological features of HAML resembling hepatocellular carcinoma (HCC). Nine patients who underwent surgical resection and had pathological diagnosis of HAML were retrospectively analyzed. All of 9 patients (5 males and 4 females) had a solitary hepatic mass with a median size of 4 cm (from 1.4 cm to 15.3 cm). Seven cases were identified as incidental liver tumors during health screening and 2 patients were diagnosed for hepatic mass when visited hospitals with unspecific abdominal discomfort. Before resection, 6 cases were diagnosed as HCC on MRI. MRI on chemical shift imagings showed a large amount of lipids in 5 cases. The enhancement pattern of MRI was classified into 2 types: in 2 cases, lesions with small or no vessels that demonstrated prolonged enhancement (1 mixed subtype and 1 myomatous subtype) and in 7 cases, lesions with abundant central vessels that show rapid washout (3 mixed subtypes and 4 myomatous subtypes) in the portal venous/delayed phase. All patients underwent resection of hepatic tumor and no recurrence was observed during follow-up (range: 2–24 months) of median 10 months. By immunohistochemistry, the tumor cells demonstrated positive immunostaining for human melanoma black-45, smooth muscle actin, and CD34. In conclusion, all of 9 patients with HAML presented with none or nonspecific clinical manifestations. The diagnosis of HAML relies on disease and immunohistochemistry, but not MRI due to its resemblance to HCC.

Objective To find an association between basic characteristics, seasons as well as disease types and 25-Hydroxyvitamin D serum concentrations in Chinese patients. Methods We randomly selected 5470 Chinese patients with various diseases, who were hospitalized between May 2012 and August 2013 in Shanghai and analyzed their serum 25-Hydroxyvitamin D2 (25 (OH)D2) and 25-Hydroxyvitamin D3 (25(OH)D3) concentrations with liquid chromatography-tandem mass spectrometry (LC-MS/MS) as well as their parathyroid hormone (PTH) and serum creatinine blood levels. The resulting data were analyzed by linear regression and variance analyses or multivariate analysis with covariance. Results The 25(OH)D serum concentrations were lowest in December. Among the subjects with a median age of 83.0±16.0, the median 25(OH)D2, 25(OH)D3 and total 25(OH)D serum concentrations were 1.00±1.80 ng/ml, 12.20±8.50 ng/ml and 14.80±9.80 respectively, indicating a prevalent 25(OH)D deficiency. According to our multivariate analysis of covariance, the factors affecting 25(OH)D2 and 25(OH)D3 serum concentrations included age, creatinine, PTH, season and type of disease, whereas gender correlated only with 25(OH)D2 and 25(OH)D2 and D3 values correlated negatively with each other. Our results further revealed that 25(OH)D3 levels were low while 25(OH)D2 levels were high among patients with lung diseases, dyskinesia and coronary heart diseases. In addition, participants with diabetes and cerebral infarction had higher 25(OH)D3 serum concentrations compared with lung disease patients. Conclusion Vitamin D intake particularly during winter and summer seasons is important especially for elderly lung disease, dyskinesia and coronary heart disease patients to improve their quality of life.