The 4th summer camp for AIDS-orphaned children was held in Beijing from August 2-8, 2007. Co-sponsored by the China Youth Concern Commission and China Foundation for the Prevention and Control of STDs （sexually trans...The 4th summer camp for AIDS-orphaned children was held in Beijing from August 2-8, 2007. Co-sponsored by the China Youth Concern Commission and China Foundation for the Prevention and Control of STDs （sexually transmitted disease） and AIDS, the event was attended by 80 AIDS-orphaned children aged 8- 16 from 18 counties and cities of 8 provinces of Shanxi, Yunnan, Henan, Jilin, Liaoning, Guizhou, Sichuan and Anhui.展开更多
At 26, Li Dan could have a promising career as an astronomy major at Beijing Normal University for undergraduate studies and a solar physics major at the National Astronomical Observatory under the Chinese Academy of ...At 26, Li Dan could have a promising career as an astronomy major at Beijing Normal University for undergraduate studies and a solar physics major at the National Astronomical Observatory under the Chinese Academy of Sciences for graduate studies. Few people would anticipate that the young man with such a strong science background would give up science to devote himself completely to children orphaned by AIDS.展开更多
This study aimed to research the living status and support system of children orphaned by AIDS in rural Henan Province. The approach of face-to-face questionnaires research was used to assess 501 children’s current s...This study aimed to research the living status and support system of children orphaned by AIDS in rural Henan Province. The approach of face-to-face questionnaires research was used to assess 501 children’s current situation while in-depth interview was conducted for the support system research. The age range of the children orphaned by AIDS was 2 - 15 years old and the mean age was 11.10 years. Most children among 2 - 6 years had communication skills with temper control and psychological problems. Children of 7 - 15 years old had the ability to take care of themselves and family members but could not do self-regulation. The support system for children orphaned by AIDS included social support, policies support, education support, and health care support but improvement are needed in the future. Support system can be improved through much more feasible and concrete policies and strategies to guarantee these children’s basic needs and comprehensive development.展开更多
The Human Immunodeficiency Virus and the resultant disease—Acquired Immune Deficiency Syndrome are global epidemics in recent times. Although the effects of the epidemic have been curtailed somewhat in the developed ...The Human Immunodeficiency Virus and the resultant disease—Acquired Immune Deficiency Syndrome are global epidemics in recent times. Although the effects of the epidemic have been curtailed somewhat in the developed world, it is not so in developing countries. As such it affects not only the infected but those directly dependent on them. Some of the affected people have been identified as children, who turn out to be unprepared for and defenceless against the imminent hardship prevalent as a consequence of the disease. The effects of the epidemic are felt more in the developing world than in developed countries and this is because the attitude of the developed world to the epidemic is positive, enhanced by awareness of the disease;whereas in the developing countries, a lot of myths are attached to it, affecting the requisite attitude needed to combat the epidemic and its effects. This paper seeks to examine the effects of this epidemic on children in Nigeria, comparing the effects on children in other African countries. The paper also looks at structures in place to cater for these children, and then seeks to proffer improved means of protecting their rights.展开更多
Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and...Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.展开更多
Objective To evaluate the clinical value of siltuximab in the treatment of Castleman disease based on multicriteria decision analysis(MCDA)and evidence and value:Impact on decision making(EVIDEM)framework.Methods The ...Objective To evaluate the clinical value of siltuximab in the treatment of Castleman disease based on multicriteria decision analysis(MCDA)and evidence and value:Impact on decision making(EVIDEM)framework.Methods The evidence matrix for quantitative analysis of MCDA was extracted through literature research,and the weight of each evaluation index was calculated by the maximum differentiation measure in conjoint analysis.Besides,the clinical value of siltuximab in the treatment of Castleman disease was analyzed quantitatively and qualitatively based on the results of expert questionnaire surveys.Results and Conclusion The clinical value score of siltuximab was 0.491,and the weight ratio of“therapeutic benefit”(15.39%),“drug effectiveness”(14.46%)and“drug safety”(11.43%)were the three largest.Among the indexes of“drug effectiveness”“drug safety”“patient reported outcome”“therapeutic benefit”and“non-medical cost”,siltuximab for Castleman disease was considered to be a more valuable treatment option than other first-line therapies.By qualitative analysis,57%experts believed that siltuximab was a better treatment option.The indexes that contribute the most to the overall clinical value of siltuximab are“therapeutic benefit”“drug effectiveness”and“quality of evidence”,while the indexes that have a negative impact on the clinical value of siltuximab is“drug treatment cost”.展开更多
Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was...Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.展开更多
Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It ha...Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.展开更多
Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortal...Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortality in infancy compared to children of surviving mothers. Motherless children mostly suffer a lot due to lack of day-to-day care, isolation, lack of motivation as well as economic cost associated with mother’s death. Thus, the purpose of this study was to ascertain the lives of children whose mothers passed away during childbirth at the Sagnarigu Municipality. Methods: This quantitative cross-sectional study was carried out at the Sagnarigu Municipal. The study recruited 297 respondents. To assess the effects of maternal death on the lives of children, families that experienced maternal death were assessed. The number of pregnancies experienced by the deceased woman, pregnancy-related complaints experienced, determinants of maternal death, number of children alive, and their standard of living were assessed with the aid of a structured questionnaire. Results: The data showed that negligence, illiteracy, poor road access, poverty, ignorance, delays in recognizing the problem, delays in making appropriate decisions, delays in the health facility, delays in giving the appropriate treatments, and traditional beliefs were some of the factors that led to maternal death in the Sagnarigu Municipality. Conclusion: The study concluded that determinants of maternal death in the Sagnarigu Municipal included the following;negligence, illiteracy, poverty, and delays in recognizing the problem. The study findings also demonstrated that the effects of maternal death on children are diverse and cut across different areas of a child’s life including livelihood sustenance, healthcare, education, and emotional and psychological development.展开更多
Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception eme...Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.展开更多
Introduction: IgG4 disease is an orphan, fibro-inflammatory autoimmune disease of recent discovery whose thoracic involvement is rarer. We report a case of Pulmonary and orbital bifocal IgG4 disease with a review of t...Introduction: IgG4 disease is an orphan, fibro-inflammatory autoimmune disease of recent discovery whose thoracic involvement is rarer. We report a case of Pulmonary and orbital bifocal IgG4 disease with a review of the literature. Observation: This is a 71-year-old patient with a history of hypertension, dyslipidemia, smoking cessation at 15 PA, with progressive dyspnoea, weight loss of 4 kg with PS = 0 for 2 months. The thoracic CT scan revealed 3 pseudotumoral lung lesions of the LIG, LID and LM. The histology of the two CT-guided lung biopsies and the LIG wedge had objectified inflammatory lesions without signs of malignancy. The evolution was marked by the occurrence of a right orbital edema. The cerebral scanner found a voluminous right orbital inflammatory pseudotumor. Biopsy with histology found fibroinflammatory lesions with lymphoplasmacytic infiltrates and positive immunolabeling with anti-IgG4 antibodies. The PET scanner had objectified pulmonary and pleural parenchymal consolidations and moderately hypermetabolic mediastinal ADP with max SUV between 3 and 6. The patient was put on corticosteroid therapy with a favorable outcome. Conclusion: IgG4 disease is rare and difficult to diagnose despite well-defined and consensual diagnostic criteria and classification. The discovery of new biomarkers facilitates the diagnosis and monitoring of patients. Well-codified corticosteroid therapy is effective but possibility of recurrence. The current challenge remains the lack of data on the follow-up of these patients to assess the risk of neoplasia (lymphoma).展开更多
Apelin受体APJ是加拿大学者O＇Dowd等于1993年发现的一种孤儿G蛋白偶联受体（orphan GPCRs,o GPCRs）,因其与血管紧张素Ⅱ1型受体（angiotensinl I typel receptor,ATI）有30%~50%的同源性,故取名为血管紧张素Ⅱ1型受体相关蛋白（putati...Apelin受体APJ是加拿大学者O＇Dowd等于1993年发现的一种孤儿G蛋白偶联受体（orphan GPCRs,o GPCRs）,因其与血管紧张素Ⅱ1型受体（angiotensinl I typel receptor,ATI）有30%~50%的同源性,故取名为血管紧张素Ⅱ1型受体相关蛋白（putative receptor protein related to the angiotensin II typel receptor,APJ）（[1]）。为探寻APJ内源性配体,日本学者Tatemoto于1998年用反向药理学方法,展开更多
AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtain...AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Rot2, 13-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3＇-diaminobenzidine tetrahydrochloride （DAB） before brief counterstaining with Mayer＇s hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Rot2 was examined by real time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 and Wnt5a protein expressions in the majority of HCC patients （63% and 77%, respectively） was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% （58/85） of the HCC cases, the expression of IB-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression （P = 0.016, P = 0.007, respectively）.CONCLUSION： Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.展开更多
Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic fail...Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.展开更多
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well ...Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.展开更多
The influence of social upbringing on the activity pattern of lion Panthera leo cubs was investigated at three sites. In this study, stimulus objects such as sticks, grass, fresh dung （elephant Loxondota africana, ze...The influence of social upbringing on the activity pattern of lion Panthera leo cubs was investigated at three sites. In this study, stimulus objects such as sticks, grass, fresh dung （elephant Loxondota africana, zebra Equus quagga, impala Aepyceros melampus, duiker Sylvicapra grimmia, kudu Tragelaphus strepsiceros, giraffe Giraffa camelopardalis and wildebeest Connochaetes taurinus） and cardboard boxes, were utilized in an enrichment program aimed at encouraging active behaviors of captive lion cubs at Antelope Park and Masuwe. Lion cubs at Chipangali were not behaviorally enriched. Activity patterns were recorded for 10 days at each site. We recorded moving, resting, playing, grooming, visual exploration and display of hunting instincts. We found that behavioral enrichment enhanced the active behaviors of captive lion cubs. Orphan-raised cubs spent more time moving, playing and displaying hunting instincts than mother-raised cubs, but the time spent grooming was similar across areas and suggests that grooming is not influenced by enrichment. Mother-raised cubs spent more time engaged in visual exploration than orphan-raised cubs and this could be a behavior acquired from mothers or a result of confidence to explore because of their presence. Activity patterns were different among time treatments across our three study sites. Based on these findings, we suggest that lion cubs raised in captivity could benefit from behavioral enrichment to encourage active behaviors essential for eventual reintroduction into the wild展开更多
According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, w...According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.展开更多
文摘The 4th summer camp for AIDS-orphaned children was held in Beijing from August 2-8, 2007. Co-sponsored by the China Youth Concern Commission and China Foundation for the Prevention and Control of STDs （sexually transmitted disease） and AIDS, the event was attended by 80 AIDS-orphaned children aged 8- 16 from 18 counties and cities of 8 provinces of Shanxi, Yunnan, Henan, Jilin, Liaoning, Guizhou, Sichuan and Anhui.
文摘At 26, Li Dan could have a promising career as an astronomy major at Beijing Normal University for undergraduate studies and a solar physics major at the National Astronomical Observatory under the Chinese Academy of Sciences for graduate studies. Few people would anticipate that the young man with such a strong science background would give up science to devote himself completely to children orphaned by AIDS.
文摘This study aimed to research the living status and support system of children orphaned by AIDS in rural Henan Province. The approach of face-to-face questionnaires research was used to assess 501 children’s current situation while in-depth interview was conducted for the support system research. The age range of the children orphaned by AIDS was 2 - 15 years old and the mean age was 11.10 years. Most children among 2 - 6 years had communication skills with temper control and psychological problems. Children of 7 - 15 years old had the ability to take care of themselves and family members but could not do self-regulation. The support system for children orphaned by AIDS included social support, policies support, education support, and health care support but improvement are needed in the future. Support system can be improved through much more feasible and concrete policies and strategies to guarantee these children’s basic needs and comprehensive development.
文摘The Human Immunodeficiency Virus and the resultant disease—Acquired Immune Deficiency Syndrome are global epidemics in recent times. Although the effects of the epidemic have been curtailed somewhat in the developed world, it is not so in developing countries. As such it affects not only the infected but those directly dependent on them. Some of the affected people have been identified as children, who turn out to be unprepared for and defenceless against the imminent hardship prevalent as a consequence of the disease. The effects of the epidemic are felt more in the developing world than in developed countries and this is because the attitude of the developed world to the epidemic is positive, enhanced by awareness of the disease;whereas in the developing countries, a lot of myths are attached to it, affecting the requisite attitude needed to combat the epidemic and its effects. This paper seeks to examine the effects of this epidemic on children in Nigeria, comparing the effects on children in other African countries. The paper also looks at structures in place to cater for these children, and then seeks to proffer improved means of protecting their rights.
文摘Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
文摘Objective To evaluate the clinical value of siltuximab in the treatment of Castleman disease based on multicriteria decision analysis(MCDA)and evidence and value:Impact on decision making(EVIDEM)framework.Methods The evidence matrix for quantitative analysis of MCDA was extracted through literature research,and the weight of each evaluation index was calculated by the maximum differentiation measure in conjoint analysis.Besides,the clinical value of siltuximab in the treatment of Castleman disease was analyzed quantitatively and qualitatively based on the results of expert questionnaire surveys.Results and Conclusion The clinical value score of siltuximab was 0.491,and the weight ratio of“therapeutic benefit”(15.39%),“drug effectiveness”(14.46%)and“drug safety”(11.43%)were the three largest.Among the indexes of“drug effectiveness”“drug safety”“patient reported outcome”“therapeutic benefit”and“non-medical cost”,siltuximab for Castleman disease was considered to be a more valuable treatment option than other first-line therapies.By qualitative analysis,57%experts believed that siltuximab was a better treatment option.The indexes that contribute the most to the overall clinical value of siltuximab are“therapeutic benefit”“drug effectiveness”and“quality of evidence”,while the indexes that have a negative impact on the clinical value of siltuximab is“drug treatment cost”.
基金supported by Medical and Health Research Project of Nanjing Health Science and Technology Development Special Fund(ZKX21040).
文摘Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
基金Supported by the Hangzhou Medical Health Science and Technology Project,No.B20220173the Public Welfare Technology Project of Zhejiang Province,No.LGF21H160033Zhejiang Medical Technology Plan Project,No.2021KY047.
文摘Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.
文摘Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortality in infancy compared to children of surviving mothers. Motherless children mostly suffer a lot due to lack of day-to-day care, isolation, lack of motivation as well as economic cost associated with mother’s death. Thus, the purpose of this study was to ascertain the lives of children whose mothers passed away during childbirth at the Sagnarigu Municipality. Methods: This quantitative cross-sectional study was carried out at the Sagnarigu Municipal. The study recruited 297 respondents. To assess the effects of maternal death on the lives of children, families that experienced maternal death were assessed. The number of pregnancies experienced by the deceased woman, pregnancy-related complaints experienced, determinants of maternal death, number of children alive, and their standard of living were assessed with the aid of a structured questionnaire. Results: The data showed that negligence, illiteracy, poor road access, poverty, ignorance, delays in recognizing the problem, delays in making appropriate decisions, delays in the health facility, delays in giving the appropriate treatments, and traditional beliefs were some of the factors that led to maternal death in the Sagnarigu Municipality. Conclusion: The study concluded that determinants of maternal death in the Sagnarigu Municipal included the following;negligence, illiteracy, poverty, and delays in recognizing the problem. The study findings also demonstrated that the effects of maternal death on children are diverse and cut across different areas of a child’s life including livelihood sustenance, healthcare, education, and emotional and psychological development.
文摘Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.
文摘Introduction: IgG4 disease is an orphan, fibro-inflammatory autoimmune disease of recent discovery whose thoracic involvement is rarer. We report a case of Pulmonary and orbital bifocal IgG4 disease with a review of the literature. Observation: This is a 71-year-old patient with a history of hypertension, dyslipidemia, smoking cessation at 15 PA, with progressive dyspnoea, weight loss of 4 kg with PS = 0 for 2 months. The thoracic CT scan revealed 3 pseudotumoral lung lesions of the LIG, LID and LM. The histology of the two CT-guided lung biopsies and the LIG wedge had objectified inflammatory lesions without signs of malignancy. The evolution was marked by the occurrence of a right orbital edema. The cerebral scanner found a voluminous right orbital inflammatory pseudotumor. Biopsy with histology found fibroinflammatory lesions with lymphoplasmacytic infiltrates and positive immunolabeling with anti-IgG4 antibodies. The PET scanner had objectified pulmonary and pleural parenchymal consolidations and moderately hypermetabolic mediastinal ADP with max SUV between 3 and 6. The patient was put on corticosteroid therapy with a favorable outcome. Conclusion: IgG4 disease is rare and difficult to diagnose despite well-defined and consensual diagnostic criteria and classification. The discovery of new biomarkers facilitates the diagnosis and monitoring of patients. Well-codified corticosteroid therapy is effective but possibility of recurrence. The current challenge remains the lack of data on the follow-up of these patients to assess the risk of neoplasia (lymphoma).
文摘Apelin受体APJ是加拿大学者O＇Dowd等于1993年发现的一种孤儿G蛋白偶联受体（orphan GPCRs,o GPCRs）,因其与血管紧张素Ⅱ1型受体（angiotensinl I typel receptor,ATI）有30%~50%的同源性,故取名为血管紧张素Ⅱ1型受体相关蛋白（putative receptor protein related to the angiotensin II typel receptor,APJ）（[1]）。为探寻APJ内源性配体,日本学者Tatemoto于1998年用反向药理学方法,
基金Supported by The fund of Nature Science Foundation of Shandong Province,No.ZR2009CM041
文摘AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Rot2, 13-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3＇-diaminobenzidine tetrahydrochloride （DAB） before brief counterstaining with Mayer＇s hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Rot2 was examined by real time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 and Wnt5a protein expressions in the majority of HCC patients （63% and 77%, respectively） was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% （58/85） of the HCC cases, the expression of IB-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression （P = 0.016, P = 0.007, respectively）.CONCLUSION： Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.
文摘Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.
基金Supported by Fondo per gli Investimenti della Ricerca di Base(FIRB)(RBAP10MY35_002)by Ente Cassa di Risparmio di Firenzeby FiorGen ONLUS to Galli A
文摘Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.
文摘The influence of social upbringing on the activity pattern of lion Panthera leo cubs was investigated at three sites. In this study, stimulus objects such as sticks, grass, fresh dung （elephant Loxondota africana, zebra Equus quagga, impala Aepyceros melampus, duiker Sylvicapra grimmia, kudu Tragelaphus strepsiceros, giraffe Giraffa camelopardalis and wildebeest Connochaetes taurinus） and cardboard boxes, were utilized in an enrichment program aimed at encouraging active behaviors of captive lion cubs at Antelope Park and Masuwe. Lion cubs at Chipangali were not behaviorally enriched. Activity patterns were recorded for 10 days at each site. We recorded moving, resting, playing, grooming, visual exploration and display of hunting instincts. We found that behavioral enrichment enhanced the active behaviors of captive lion cubs. Orphan-raised cubs spent more time moving, playing and displaying hunting instincts than mother-raised cubs, but the time spent grooming was similar across areas and suggests that grooming is not influenced by enrichment. Mother-raised cubs spent more time engaged in visual exploration than orphan-raised cubs and this could be a behavior acquired from mothers or a result of confidence to explore because of their presence. Activity patterns were different among time treatments across our three study sites. Based on these findings, we suggest that lion cubs raised in captivity could benefit from behavioral enrichment to encourage active behaviors essential for eventual reintroduction into the wild
文摘According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.
