Innate immunity and hepatocarcinoma:Can toll-likereceptors open the door to oncogenesis?

Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago.Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis.An effective innate immunity response relies on the tolllike receptors(TLR) found in several different liver cells which,through different ligands and many signaling pathways can elicit,not only a pro-inflammatory but also an oncogenic or anti-oncogenic response.Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets.We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015.TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell survival.However,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis.TLR3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or proliferation.TLR4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed.TLR9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more likely.Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported.As therapeutic targets,TLRs are already in use and have a great potential.In conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour influence.TLR4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been described.TLR2 presents a more ambiguous role,possibly depending on the stage of the inflammationHCC axis.

Helicobacter pylori and microRNAs:Relation with innate immunity and progression of preneoplastic conditions

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori(H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. Micro RNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify micro RNA expression in the gastric mucosa and micro RNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. Micro RNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor micro RNAs. Furthermore, micro RNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, micro RNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each micro RNA can control the expression of hundreds to thousands of genes, knowledge of micro RNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of micro RNAs in H. pylori gastric carcinogenesis, identifying the micro RNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

The Effects of Laser Therapy in Treating Hypertrophic Scars and Keloids after Median Sternotomy:A Scoping Review

Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advancements in laser therapy have made it a prominent option for managing these complex scars,yet a com-prehensive understanding of its efficacy is lacking.The aim of this scoping review is to explore the effects of laser therapy in managing hypertrophic scars and keloids after median sternotomy.Methods:This scoping review ana-lyzed studies up to February 2024 from databases including PubMed,EMBASE,CINAHL,Scopus,Web of Science,and the Cochrane Library.We included any study that assessed laser therapy’s effects on hypertrophic scars and keloids following median sternotomy.Studies were selected based on predefined inclusion criteria with-out publication year,design,or origin restrictions.Results:Six studies met the inclusion criteria,involving a total offive RCTs and one review.These studies primarily tested 585 and 595-nm pulsed dye laser(PDL)treatments,focusing on scar appearance,patient symptoms,and treatment satisfaction.Most studies reported significant improvements in scar height reduction and patient symptom relief after treatment,with mixed results for scar erythema and elasticity.Adverse events were generally mild and transient.Conclusions:Laser therapy offers a beneficial approach for improving the appearance and symptoms of hypertrophic scars and keloids post-median sternotomy.However,further research is necessary to optimize treatment parameters and explore the long-term psychosocial impacts of this therapy.This review highlights the need for more comprehensive studies to establish standardized treatment protocols and evaluate their effectiveness.

Management and outcome of recurrent gallstone ileus:A systematic review

AIM: To help the surgeon in decision making whentreating a patient with recurrent gallstone ileus(RGSI). METHODS: A systematic review related to RGSI was performed using the databases CINAHL, EMBASE, MEDLINE via Pub Med from May 1912 to April 2015. All languages were included and the grey literature was also searched. The abstracts were explored for relevance to the topic and full texts obtained as appropriate. A manual search was carried out by scrutinising the reference lists of all the full text articles and further articles were identified and obtained. Total of 903 articles were identified, 656 were excluded after abstract review, 247 full text articles were reviewed and 91 articles selected for final analysis. There were 113 cases of RGSI. RESULTS: There were 113 cases of RGSI reported in 91 articles. The majority of the recurrences, 62.6%, occurred within 6 wk of the index event. The male to female ratio was 1:7. The mean age was 69.6 years(SD 11.2) with a range of 38-95 years. The small bowel was the commonest site of impaction(92.2%). Treatment data was available for 104 patients. The two main operations performed were:(1) Enterolithotomy without repair of biliary fistula in 70.1% of all patients with a procedural mortality rate of 16.4%(12/73) and(2) a single stage surgery approach involving enterolithotomy with cholecystectomy and repair of the biliary enteric fistula in 16.3% with a procedural mortality of 11.7%(2/17). A subset analysis over last 25 years showed mortality from eneterolithotomy was 4.8% while single stage mortality was 22.2%. Enterolithotomy alone was the commonest operation performed for RGSI with four patients(5.4%) having a further recurrence of gallstone ileus. CONCLUSION: Enterolithotomy alone or followed by a delayed two-stage treatment approach is the preferred choice offering low mortality and reduced risk of recurrence.

Handgrip strength and health outcomes: Umbrella review of systematic reviews with meta-analyses of observational studies

Purpose:The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes.Methods:An umbrella review of systematic reviews with meta-analyses of observational studies was conducted.We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values,95%prediction intervals,heterogeneity,small-study effects,and excess significance.We graded the evidence from convincing(Class I)to weak(Class IV).Results:From 504 articles returned in a search of the literature,8 systematic reviews were included in our review,with a total of 11 outcomes.Overall,nine of the 11 of the outcomes reported nominally significant summary results(p<0.05),with 4 associations surviving the application of the more stringent p value(p<106).No outcome presented convincing evidence.Three associations showed Class II evidence(i.e.,highly suggestive):(1)higher handgrip values at baseline were associated with a minor reduction in mortality risk in the general population(n=34 studies;sample size=1,855,817;relative risk=0.72,95%confidence interval(95%CI):0.670.78),(2)cardiovascular death risk in mixed populations(n=15 studies;relative risk=0.84,95%CI:0.780.91),and(3)incidence of disability(n=7 studies;relative risk=0.76,95%CI:0.660.87).Conclusion:The present results show that handgrip strength is a useful indicator for general health status and specifically for early all-cause and cardiovascular mortality,as well as disability.To further inform intervention strategies,future research is now required to fully understand mechanisms linking handgrip strength scores to these health outcomes.

Inclusion complexes between sildenafil citrate and cyclodextrins enhance drug solubility

Sildenafil citrate is a potent and selective phosphodiesterase-5inhibitor. It is effectively used in the treatment of erectile dysfunction and pulmonary arterial hypertension. The drug is rapidly absorbed and pharmacologically acts within30 min to 1 h after oral administration. However, it has a relatively low absolute bioavailability of 41%because its limited solubility in water is the major problem (1)To improve the oral bioavailability of poorly water-soluble drugs.

Current trends in outcome studies for children with hearing loss and the need to establish a comprehensive framework of measuring outcomes in children with hearing loss in China

Since the 1970s, outcome studies for children with hearing loss expanded from focusing on assessing auditory awareness and speech perception skills to evaluating language and speech development. Since the early 2000s, the multi-center large scale research systematically studied outcomes in the areas of auditory awareness, speech-perception, language development, speech development, educational achievements, cognitive development, and psychosocial development. These studies advocated the establishment of baseline and regular follow-up evaluations with a comprehensive framework centered on language development. Recent research interests also include understanding the vast differences in outcomes for children with hearing loss, understanding the relationships between neurocognitive development and language acquisition in children with hearing loss, and using outcome studies to guide evidence-based clinical practice. After the establishment of standardized Mandarin language assessments, outcomes research in China's Mainland has the potential to expand beyond auditory awareness and speech perception studies.

Intervention for reducing stigma: Assessing the influence of gender and knowledge

AIM: To evaluate the effectiveness in reducing social stigma of an intervention and to assess the influence of gender and knowledge.METHODS: The program consisted in providing information and contact with users of mental health in order to reduce social stigma in the school environment. A total of 62 secondary school students(age 14-16 years) were evaluated with the Opinions on Mental Illness(OMI) questionnaire before and after the intervention. The subscales of the OMI were: authoritarianism, interpersonal etiology, benevolence, restrictiveness and negativism. The analysis was performed over the total sample, separating by gender and knowledge of someone with a mental disorder. t-test for repeated measures was used in the statistical analysis.RESULTS: All the OMI subscales showed a significant change after the intervention(P < 0.001), except for benevolence. Women presented significant changes in the subscales of authoritarianism and restrictiveness, while men presented changes in negativism and interpersonal etiology rather than restrictiveness(P < 0.001-0.003). Students that knew someone with a mental disorder presented significant changes in authoritarianism, interpersonal etiology, and negativism(P < 0.001-0.003) and students that do not know anyone with a mental disorder improved in restrictiveness and authoritarianism(P < 0.001-0.001). In all the subscales of the instrument the students improved their perception of mental disorders, reducing their levels of stigma.CONCLUSION: The intervention designed to reduce social stigma was effective, especially in the area of authoritarianism. The whole sample showed improved attitudes towards mental illness, although the areas were different depending on gender and knowledge.

Experiences of Screening for Abdominal Aortic Aneurysm—In and Out on Five Minutes

Background: The purpose of AAA screening is to prevent rupture and mortality. Screening for life-threatening diseases is a double-edged sword. The aim of this study is to describe 65-year-old men’s experiences of health related quality of life and anxiety after screening for Abdominal Aortic Aneurysm, and experiences of information and reasons for not participating. Methods: 368 men answered Short Form 36 (SF-36), and anxiety and depression scale (HAD). 72 telephone interviews were conducted with the participants and 77 with those who declined to take part in the screening programme. Results: The SF-36 domains of Physical Function and Role limitations due to emotional health problems were significantly better for men who had undergone screening compared to a matched population. Compared to non-smokers, smokers had lower values in the SF-36 domains of general health perceptions, social functioning, role limitations due to emotional health problems and mental health. 80% of patients did not experience any form of anxiety/panic in connection with the screening invitation. Of the men who did not participate, 56% stated that they would like to be screened or had already undergone the examination. Conclusion: The men who underwent the investigation were healthier in some of the SF-36 domains than the general population. The participants did not experience any great anxiety before the screening and despite the short duration of the examination.

Clinical and Epidemiological Evolution of Sheep Pox in Morocco

Sheep pox is an infectious viral disease that affects specifically sheep and it is caused by the Capripoxvirus genus.The clinical signs include fever,diarrhea,difficulty breathing,nodules,lung lesions and death.In Morocco,the 2010 epidemic of sheep pox was characterized by the emergence of a nodular form of the disease.The local strain was isolated and the analysis of affected animals was positively confirmed by virus isolation and real-time polymerase chain reaction(RT-PCR).The epidemiological analysis of 911 data records showed that the virus is endemic in the country;an average of 350 cases per year with an epizootic evolution was observed in 2010.The incidence varies depending on provinces and the disease appears confined to the central and the eastern regions of the country where a very intensive sheep breeding activity is taking place.The statistical analysis showed that there is a positive correlation between the endemicity and the significant factor of the rural market(p=0.006).The annual average morbidity and mortality rates were 2.96%(1.26%to 4.32%)and 0.71%(0.41%to 0.94%),respectively.The clinical findings associated to the epidemiological data analysis confirmed the presence of sheep pox in its nodular form and suggest that new pathogenic strains may have been introduced from Mauritania.The purpose of this work was to provide a better description of the spatiotemporal evolution of sheep pox disease based on some epidemiological indicators and to put forward plausible hypotheses regarding the emergence of the virus in order to implement an adequate control strategy.

COVID-19 Vaccine Priority Access for Adults and Children with Congenital Heart Disease: A Statement of the Italian Society of Pediatric Cardiology

COVID-19 pandemic continues to strike across the world with increasing number of infected patients,severe morbidity and mortality,social life and economy disruption.Universal access to vaccine prophylaxis will be pivotal in controlling this infection and providing individual level protection.However,mismatch between vaccine request and vaccine availability,as well as constraints in logistics of vaccine campaign is creating a transition phase of progressive but still incomplete inclusion of group of individuals in the vaccination process.Selected patients living with chronic and multisystemic disease may present increased propensity of adverse outcome,should Sars-Cov-2 infection develop.In these patients,expedite access to COVID-19 vaccination may be considered.The Italian Society of Pediatric Cardiology National Board is providing a viewpoint to inform policy makers and public authorities during vaccine allocation strategies development,to consider higher priority and expedite access for selected groups of patients living with congenital heart disease.

A Comparison of Two Macroinvertebrate Multi-Plate Sampling Methods to Inform Great Lakes Monitoring and Remediation Efforts

Hester-Dendy (HD) multi-plate samplers have been widely used by state and federal government agencies for bioassessment of water quality through use of macroinvertebrate community data. To help guide remediation and restoration efforts at the Niagara River Great Lakes Area of Concern site, a multi-agency study was conducted in 2014 to assess the contribution of seven major urban tributaries on the US side of the river toward the impairment of the Niagara River. As part of this study, macroinvertebrate communities were sampled using two co-located versions of HD samplers: one version used by the New York State Department of Environmental Conservation (NYSDEC) and another by the US Environmental Protection Agency Office of Research and Development. Samplers were deployed in tributaries in highly developed watersheds with high percent impervious surface. The two sampling methods varied in terms of number and size of plates, between-plate spacing, and deployment method. Comparison of the similarity/grouping of communities with multivariate ordination techniques, Nonmetric Multidimensional Scaling and Multi-Response Permutation Procedure, showed that both methods were able to detect differences in communities at stations, despite some grouping by month and method. The indices and metrics derived from the two HD methods were found to give comparable but not identical assessments of water quality. Despite their differences, the methods were robust with respect to water quality categories derived from indices used nationally (HBI) and by NY state (BAP). For the common richness metrics, total taxa and EPT richness, there was no statistical difference between means from 3 samplings. Some metrics, especially percent tolerant collector-gatherer individuals, did show significant differences at certain stations. Indicator Species Analysis showed some taxa associated with each method. The observed community differences were thought mostly due to the difference in sampler deployment position. .

Differences in Pandemic-Related Factors Associated with Alcohol and Substance Use among Korean Adolescents:Nationwide Representative Study

The coronavirus disease 2019(COVID-19)pandemic has raised concerns about the mental health and social well-being of youth,including its potential to increase or exacerbate substance use behaviors[1].Among adolescents,the COVID-19pandemic has resulted in limited face-to-face school contact and thus missed milestones in preventing alcohol and substance use.

Implementation of evidence-based practice by standardized care plans: A study protocol

Background: Patient records should both transfer and create knowledge about patients and their health care. A standardized care plan could be a way to implement evidence-based care directly in practice and improve the documentation in patient records. The aim of this study is to investigate and compare the development and implementation process of a standardized care plan in hospital and primary health care. A further aim is to evaluate the effects on the quality of documentation and the care given in two contexts. Methods and Analysis: Realistic evaluation will be used as a framework to investigate the implementation process. According to this framework, possible contexts, mechanisms, and outcomes in the study will be considered. The study will be performed in two contexts: an orthopedic clinic and primary health care centers. In both contexts, the two key mechanisms will be the same: the implementation process will be driven by internal facilitators (practitioners at the units) and the process will be guided by the Rules and Regulations for interoperability in the Health and Social Care specification, “National information structure for standardized care plans”. Two outcomes of the study will be studied: to investigate the development and implementation process by an evaluation of fidelity and to evaluate how a standardized care plan affects the quality of documentation and the use of evidence-based care. Discussion: Implementation of the SCP will probably meet the same resistance as implementation of guidelines. Documentation of care is an important but resource-consuming requirement in health care, a more standardized method of documenting is requested by health professionals. This project can provide insight into the complex process of developing and implement an SCP in different contexts, which will be useful in further implementation processes.

The feelings and thoughts of mental health nurses concerning the management of distressed and disturbed in-patients: A comparative qualitative European study

High levels of distress and disturbance amongst those experiencing acute mental illness can be a major problem for mental health nurses. The feelings experienced by these nurses when caring for and supporting disturbed and/or distressed patients along with their concurrent thoughts are not well described in the literature. To date, this complex issue has not been explored within a comparative European context. The objective of this qualitative study was to explore the feelings and thoughts of mental health nurses when supporting and caring for distressed and/or disturbed patients in 6 European countries. Methods: Focus groups were used to collect data from 130 mental health nurses working in acute inpatient psychiatric settings. Results: Data were analysed using content analysis. Findings highlighted 6 broad themes: 1) Mixed emotions: expressive and responsive, 2) Procedure for caring for and supporting disturbed and/or distressed patients, 3) Use of guidelines for caring and supporting disturbed and/or distressed patients, 4) Team and organisational support, 5) Ethical concerns: Cognitive dissonance and 6) Education and training. Commonalities and differences were?found across all themes. Approaches to care, nurses’ role and education, clinical guidelines and/or standards vary from country to country, therefore the care, treatment and management of distressed and/or disturbed patients are various. As a result, mental health nurses have different experiences, various emotional quandaries concurrent with cognitive dissonance and different coping strategies when caring for and supporting distressed and disturbed patients. Conclusions: More emphasis needs to be given to the emotional quandaries and concurrent cognitive dissonance experienced by mental health nurses caring for distressed and/or disturbed inpatients in acute psychiatric settings. Increased access to education and training with particular attention to interpersonal communication and relationship building within clinical teams needs to be a priority given the experiences described by mental health nurses.

Advancing the Understanding of Environmental Transformations, Bioavailability and Effects of Nanomaterials, an International US Environmental Protection Agency—UK Environmental Nanoscience Initiative Joint Program

Nanotechnology has significant economic, health, and environmental benefits, including renewable energy and innovative environmental solutions. Manufactured nanoparticles have been incorporated into new materials and products because of their novel or enhanced properties. These very same properties also have prompted concerns about the potential environmental and human health hazard and risk posed by the manufactured nanomaterials. Appropriate risk management responses require the development of models capable of predicting the environmental and human health effects of the nanomaterials. Development of predictive models has been hampered by a lack of information concerning the environmental fate, behavior and effects of manufactured nanoparticles. The United Kingdom (UK) Environmental Nanoscience Initiative and the United States (US) Environmental Protection Agency have developed an international research program to enhance the knowledgebase and develop risk-predicting models for manufactured nanoparticles. Here we report selected highlights of the program as it sought to maximize the complementary strengths of the transatlantic scientific communities by funding three integrated US-UK consortia to investigate the transformation of these nanoparticles in terrestrial, aquatic, and atmospheric environment. Research results demonstrate there is a functional relationship between the physicochemical properties of environmentally transformed nanomaterials and their effects and that this relationship is amenable to modeling. In addition, the joint transatlantic program has allowed the leveraging of additional funding, promoting transboundary scientific collaboration.

意大利语版护理管理者胜任力测评工具的信效度检验

目的旨在翻译Chase护理管理者胜任力测评工具(the Chase Nurse Manager Competency Instrument,CNMCI)为意大利语,并对其进行信度和效度检验。方法对英文版CNMCI进行翻译,并通过横断面研究验证其信效度。采用预翻译(建立等效)、初始翻译、预测试、审查和管理5个步骤的问卷翻译方法,将英文版工具翻译为意大利语版。于2022年8月到2023年6月,选取意大利3个地区31所医疗机构349名护理管理者进行调查。采用内容效度、结构效度评估工具的效度;采用Cronbach'sα系数、重测信度评估工具的信度。结果意大利语版CNMCI,包括“知识理解”和“实施和/或使用能力”两个分量表,每个分量表包括53个条目。工具的条目内容效度指数(I-CVI)为0.83~1.00,两个分量表的内容效度指数(S-CVI)均为0.97。经验证性因子分析显示该工具各项拟合指数表现良好。工具中“知识理解”分量表的Cronbach'sα系数为0.978,“实施和/或使用能力”分量表的Cronbach'sα系数为0.976。各个维度之间的相关系数为0.494~0.908重测信度为0.820,表明工具的一致性较好。结论意大利语版CNMCI在测量护理管理者胜任力方面显示出良好的信度和效度,并支持该工具的多维度结构。此外,研究结果支持了这些因素的层次性质,进一步支持了该工具的有效性。

成年大鼠心肌细胞高效激光共聚焦显微镜钙成像方法

目的建立高效易行的测定心肌细胞钙成像方法。方法 Langendorff灌流获取成年大鼠心室肌细胞。大鼠心肌细胞经Fluo-4染色后分别加入玻璃底的6孔培养板中,连接Ion C-PaceEP刺激器,于激光共聚焦显微镜下测定胞内钙离子浓度的动态变化。结果约80%的细胞跟随所设频率规律的收缩。激光共聚焦显微镜记录到与刺激器频率相同的有规则的细胞钙瞬变。加入咖啡因后钙释放增加,提示此为钙库的钙释放。结论利用新型的刺激装置,结合激光共聚焦显微技术,我们成功地获得了高效易行的成年大鼠心肌细胞Ca2+成像方法。此法也可用于其他实验动物心肌细胞,易于记录细胞内钙离子浓度的动态变化。

Nocardia infections among immunomodulated inflammatory bowel disease patients:A review

Human nocardiosis,caused by Nocardia spp.,an ubiquitous soil-borne bacteria,is a rare granulomatous disease close related to immune dysfunctions.Clinically can occur as an acute life-threatening disease,with lung,brain and skin being commonly affected.The infection was classically diagnosed in HIV infected persons,organ transplanted recipients and long term corticosteroid treated patients.Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario.Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings.We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals.Eleven cases of nocardiosis associated with anti-tumor necrosis factor(TNF) prescription(9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease(IBD),4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients,lung disease in 4 patients,hepatic in one and disseminated disease in 3 patients.From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine.In conclusion,nocardiosis requires high levels of clinical suspicion and experience of laboratory staff,in order to establish a timely diagnosis and by doing so avoid worst outcomes.Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential.The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated.

Midkine secretion protects Hep3B cells from cadmium induced cellular damage

AIM： To evaluate role Cadmium （Cd） exposure line Hep3B cells. of midkine secretion during in the human hepatocyte cell METHODS： Different dosages of Cd （0.5-1-5-10 μg/mL） were applied to Hep3B cells and their effects to apoptosis, lactate dehydrogenase （LDH） leakage and midkine secretion were evaluated as time dependent manner. Same experiments were repeated with exogenously applied midkine （250-5000 pg/mL） and/or 5 t^g/mL Cd. RESULTS： Cd exposure induced prominent apoptosis and LDH leakage beginning from lower dosages at the 48^th. Cd induced midkine secretion with higher dosages （P 〈 0.001）, （control, Cd 0.5-1-5-10μg/mL respectively： 1123 ± 73, 1157 ± 63, 1242 ± 90, 1886 ± 175, 1712 ± 166 pg/mL）. Exogenous 500-5000 pg/mL midkine application during 5 μg/mL Cd toxicity prevented caspase-3 activation （control, Cd toxicity, 250, 500, 1000, 2500, 5000 pg/mL midkine＋ Cd toxicity, respectively： 374 ± 64, 1786 ± 156, 1545 ± 179, 1203 ± 113, 974 ± 116, 646 ± 56, 556 ± 63 cfu） LDH leakage and cell death in Hep3B cells （P 〈 0.001）. CONCLUSION： Our results showed that midkine secretion from Hep3B cells during Cd exposure protects liver cells from Cd induced cellular damage. Midkine has anti-apoptotic and cytoprotective role during Cd toxicity. Further studies are needed to explain the mechanism of midkine secretion and cytoprotective role of midkine during Cd exposure. Midkine may be a promising theurapatic agent in different toxic hepatic diseases.