The Institute of Basic Medical Sciences(IBMS)is a global leader in biomedical research and advanced medical education.This year(2023)marks the 65^(th)anniversary of its foundation at the Chinese Academy of Medical Sci...The Institute of Basic Medical Sciences(IBMS)is a global leader in biomedical research and advanced medical education.This year(2023)marks the 65^(th)anniversary of its foundation at the Chinese Academy of Medical Sciences(CAMS)and School of Basic Medicine(SBM)of the Peking Union Medical College(PUMC).In the beginning,the IBMS and SBM incorporated the premedical departments of the PUMC,which was established by the Rockefeller Foundation in 1917.Since then,these departments have been committed to undertakingrstrate medical science research in China.展开更多
There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Addition...There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health services, medical training and future medical research programs. We also discuss the characteristics of modern naval combat, medical rescue challenges, medical treatment highlights and future developments of medical rescue at sea.展开更多
The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development ...The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.展开更多
To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip...To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.展开更多
Original statement in the caption of Fig.5:Fig.5.JinMaiTong(JMT)treatment restored the perturbed central carbohydrate metabolism in the circulation and sciatic nerve of diabetic peripheral neuropathy(DPN)rats.Dash lin...Original statement in the caption of Fig.5:Fig.5.JinMaiTong(JMT)treatment restored the perturbed central carbohydrate metabolism in the circulation and sciatic nerve of diabetic peripheral neuropathy(DPN)rats.Dash line arrows indicate the direct metabolic reactions,and solid line arrows indicate the indirect reactions.*P<0.05 and**P<0.01.ns:no significant difference.CON:control;TCA:tricarboxylic acid cycle;ADP:adenosine diphosphate:ATP:adenosine triphosphate;GDP:guanosine diphosphate;GTP:guanosine triphosphate.展开更多
Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q...Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes.Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.展开更多
Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located...Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located in ZIKV 5'UTR and virus production.Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining,Subsequently,liquid chromatographytandem mass spectrometry(LC-MS/MS),bioinformatics analysis,and Western blot were used to identify the candidate proteins binding to ZIKV 5'UTR.Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production,respecitvely.Results tRSA RNA pull-down assay,LC-MS/MS,and Western blot analysis showed that polypyrimidine tractbinding protein(PTB)bound to the ZIKV 5'UTR.Furthermore,dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV(t=10.220,P<0.001),while PTB knockdown had the opposite effect(t=4.897,P<0.01).Additionally,virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer(t=6.400,P<0.01),whereas reducing PTB expression level weakened virus infectivity(t=5.055,P<0.01).Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.展开更多
Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pr...Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
Cause of death surveillance data is most important for developing effective health policies,whose quality is crucially affected by the accuracy of the underlying cause of death(UCOD)provided in death certificates.The ...Cause of death surveillance data is most important for developing effective health policies,whose quality is crucially affected by the accuracy of the underlying cause of death(UCOD)provided in death certificates.The World Health Organization(WHO)has clearly defined a UCOD as“the disease or injury which initiated the train of morbid events leading directly to death,or the circumstance of the accident or violence which produced the fatal injuries”[1].展开更多
Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells...Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that β-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.展开更多
AIM: To investigate the role of opioid p-receptor subtype in opiate-induced constipation (OIC).METHODS: The effect of Ioperamide on intestinal transit was investigated in mice. Ileum strips were isolated from 12-w...AIM: To investigate the role of opioid p-receptor subtype in opiate-induced constipation (OIC).METHODS: The effect of Ioperamide on intestinal transit was investigated in mice. Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension. The ileum strips were precontracted with 1 μmol/L acetylcholine (ACh). Then, decrease in muscle tone (relaxation) was characterized after cumu- lative administration of 0.1-10μ~mol/L Ioperamide into the organ bath, for a concentration-dependent study. Specific blockers or antagonists were used for pretreat- ment to compare the changes in Ioperamide-induced relaxation.RESULTS: In addition to the delay in intestinal transit, Ioperamide produced a marked relaxation in isolated ileum precontracted with ACh, in a dose-dependent manner. This relaxation was abolished by cyprodime,a selective opioid p-receptor antagonist, but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors. Also, treatment with opioid μ-1 receptor agonist failed to modify the muscle tone. Moreover, the relaxation by Ioperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K^+ (KATP) channels, and by protein kinase A (PKA) inhibitor, but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate (cAMP).CONCLUSION: Loperamide induces intestinal relaxa- tion by activation of opioid μ-2 receptors via the cAMP- PKA pathway to open KATp channels, relates to OIC.展开更多
Objectives Tumor necrosis factor-α (TNF-α) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-α...Objectives Tumor necrosis factor-α (TNF-α) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis (TB) among patients with coal worker's pneumoconiosis (CWP). Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP). Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher's exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls (2,2=5.44, P=-0.07). But difference in frequency of the TNF-α-308 A allele was identified between them (2,2-5.14, P=0.02). No significant difference in frequencies of the TNF-α-238 genotype and allele (P=0.23 and P=0.09, respectively) was found between cases and controls either, with combined (GG and AA) OR of 3.96 (95% confidence interval of 1.30-12.09) at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 (95% CI of 1.06-3.71) for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index (OR=4.92), as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.展开更多
Background: Mortality outcomes in trials of low-dose computed tomography(CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung canc...Background: Mortality outcomes in trials of low-dose computed tomography(CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect.Methods: A decision tree model with three scenarios(low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort(100,000 smokers aged45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality(primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables.Results: Among the 100,000 subjects, there were 448,541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively(17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, lowdose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths(relative numbers) with low-dose CT screening in the worst and optimal cases were16(5.4%) and 288(40.2%) over no screening, respectively.Conclusions: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China.However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.展开更多
Objective To compare the characteristics of suicides in the four main demographic groups: urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in Chin...Objective To compare the characteristics of suicides in the four main demographic groups: urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China. Methods A detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country. Results Pesticide ingestion accounted for 58% (519) of all suicides and 61% (3181519) of deaths were due to unsuccessful medical resuscitation. A substantial proportion (37%) of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% (76/563) received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion (79%), the lowest prevalence of mental illness (39%), and the highest acute stress from precipitating life events just prior to the suicide. Contusion Many suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.展开更多
AIM To investigate the effects of Xiangbin prescription(XBP), a Chinese herbal concoction, on gastrointestinal motility.METHODS Forty healthy volunteers were recruited for this randomized controlled trial of XBP. Antr...AIM To investigate the effects of Xiangbin prescription(XBP), a Chinese herbal concoction, on gastrointestinal motility.METHODS Forty healthy volunteers were recruited for this randomized controlled trial of XBP. Antroduodenojejunal manometry was used to monitor gastrointestinal motility in these subjects. After the subjects had fasted for at least 12 h, XBP(n = 30) or placebo(n = 10) was orally administrated and gastrointestinal motility was recorded for 4 h. Plasma motilin and ghrelin were measured by enzyme-linked immunosorbent assay.RESULTS Oral administration of XBP significantly increased the amplitude of duodenal contractions [19.5(13.0-26.7) vs 16.9(12.3-23.9), P < 0.05], jejunal contractions [18.3(15.3-25.0) vs 15.4(11.7-23.9), P < 0.01], and the motility index of duodenal contractions [522.0(146.0-139.0) vs 281.0(76.5-1006.0), P < 0.01] in phase Ⅱ of the migratory motor complex(MMC), which subsequently initiated the MMC cycle [74.0(30.0-118.0) vs 116.5(24.0-219.0), P < 0.05], shortened the duration of phase I of the MMC [42.0(0.0-90.0) vs 111.5(42.0-171.0), P < 0.01], and lengthened the duration of phase Ⅱ of the MMC [120(21-240) vs 58(16-170), P < 0.01] compared to the duration before XBP administration. There were significant differences in the amplitude of jejunal contractions [19.8(14.0-30.0) vs 18.0(13.0-28.5), P < 0.05], the motility index of duodenal contractions [236.0(115.0-306.0) vs 195.0(109.0-310.0), P < 0.05], and jejunal contractions [214.0(95.0-403.0) vs 178.0(55.0-304.0), P < 0.01] in phase Ⅲ of the MMC. Oral administration of XBP greatly increased plasma motilin(57.69 ± 9.03 vs 49.38 ± 8.63, P < 0.01) and ghrelin(279.20 ± 104.31 vs 238.73 ± 115.59, P < 0.01) concentrations compared to concentrations after oral administration of the placebo.CONCLUSION XBP can stimulate duodenal and jejunal motility and increase the concentrations of plasma motilin and ghrelin. The clinical applicability of XBP in treating GDIM deserves investigation.展开更多
Objective To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-KB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metallop...Objective To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-KB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). Methods Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFa-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants. Results it was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFa for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFa for 24 h. The stimulatory effect of TNFa just on proMMP-9 was counteracted significantly by CAPE. Conclusion NF-KB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFa (a pro-apoptotic factor). Therefore, therapeutic NF-KB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.展开更多
Objective: To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors (RFs, including nulliparity, mean number of children, age at first birth and breastf...Objective: To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors (RFs, including nulliparity, mean number of children, age at first birth and breastfeeding), use of oral contraceptives (OCs, restricted to the age group of 15-49 years), and hormone replacement therapy (HRT), as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods: We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results: Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer (712 cases, 294 deaths). The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction (PAF) of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion: RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.展开更多
Objective:To investigate the bioactive-constituents of Shemamruthaa(SM),a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation(LPO),antioxidant status,citr...Objective:To investigate the bioactive-constituents of Shemamruthaa(SM),a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation(LPO),antioxidant status,citric acid cycle enzymes and electron transport chain enzymes in mammary tissues of 7,12-dimethylbenz(a)-anthracene(DMBA)induced mammary carcinoma in rat model.Methods:Adult Female Sprague-Dawley rats were used for the study and were divided into four groups.CroupⅠserved as control and CroupⅡrats were induced mammary carcinoma by administration of DMBA(25 mg/kg b.w.)orally.The normal and cancer-induced rats(GroupⅢ)were treated with SM(400 mg/kg b.w./day)orally by gastric incubation for 14days.CroupⅣrats served as SM-treated control animals.Results:Cancer-induced rats showed a considerably increased level of LPO with concomitant decreased levels of antioxidants,citric acid cycle enzymes,electron transport chain enzymes and cytochrome contents in the mammary tissue.Treatment with SM brought back the aforementioned biochemical parameters to near normal.Conclusions:From the results,it can be inferred that Shemamruthaa possesses significant anticancer effect through its role in attenuation of LPO,prevention of membrane damage and restoring membrane integrity.展开更多
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(No.2022-I2M-2-001)
文摘The Institute of Basic Medical Sciences(IBMS)is a global leader in biomedical research and advanced medical education.This year(2023)marks the 65^(th)anniversary of its foundation at the Chinese Academy of Medical Sciences(CAMS)and School of Basic Medicine(SBM)of the Peking Union Medical College(PUMC).In the beginning,the IBMS and SBM incorporated the premedical departments of the PUMC,which was established by the Rockefeller Foundation in 1917.Since then,these departments have been committed to undertakingrstrate medical science research in China.
文摘There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health services, medical training and future medical research programs. We also discuss the characteristics of modern naval combat, medical rescue challenges, medical treatment highlights and future developments of medical rescue at sea.
文摘The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.
基金sponsored by the National Natural Science Foundation of China (Grant Nos.61960206012,62121003,T2293731,62171434,61975206,61971400,and 61973292)the National Key Research and Development Program of China (Grant Nos.2022YFB3205602 and 2022YFC2402501)+1 种基金Major Program of Scientific and Technical Innovation 2030 (Grant No.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences (Grant No.GJJSTD20210004).
文摘To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.
文摘Original statement in the caption of Fig.5:Fig.5.JinMaiTong(JMT)treatment restored the perturbed central carbohydrate metabolism in the circulation and sciatic nerve of diabetic peripheral neuropathy(DPN)rats.Dash line arrows indicate the direct metabolic reactions,and solid line arrows indicate the indirect reactions.*P<0.05 and**P<0.01.ns:no significant difference.CON:control;TCA:tricarboxylic acid cycle;ADP:adenosine diphosphate:ATP:adenosine triphosphate;GDP:guanosine diphosphate;GTP:guanosine triphosphate.
基金supported by grants from the National Key Research and Development Program of China(2022YFC2703700 and 2022YFC2703900)National Natural Science Foundation of China(30871367)CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-018 and CIFMS 2021-I2M-1-051).
文摘Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes.Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.
文摘Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located in ZIKV 5'UTR and virus production.Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining,Subsequently,liquid chromatographytandem mass spectrometry(LC-MS/MS),bioinformatics analysis,and Western blot were used to identify the candidate proteins binding to ZIKV 5'UTR.Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production,respecitvely.Results tRSA RNA pull-down assay,LC-MS/MS,and Western blot analysis showed that polypyrimidine tractbinding protein(PTB)bound to the ZIKV 5'UTR.Furthermore,dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV(t=10.220,P<0.001),while PTB knockdown had the opposite effect(t=4.897,P<0.01).Additionally,virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer(t=6.400,P<0.01),whereas reducing PTB expression level weakened virus infectivity(t=5.055,P<0.01).Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.
文摘Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
基金supported by State Key Laboratory Special Fund(2060204)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2023-I2M-2-001)+1 种基金The Collaborative Innovation Team Project:Health Effect of Environmental Factors and Gut Microbiome on Digestive Tract-Related Diseases:Population-Based Cohort Studies(2016-12M-3-001)supported by CAMS Innovation Fund for Medical SciencesStrengthen Capacity of Study and Application on the Burden of Disease in Health Care Systems in China:Establishment and Development of Chinese Burden of Disease Research and Dissemination Center(15-208)supported by the China Medical Board(CMB).
文摘Cause of death surveillance data is most important for developing effective health policies,whose quality is crucially affected by the accuracy of the underlying cause of death(UCOD)provided in death certificates.The World Health Organization(WHO)has clearly defined a UCOD as“the disease or injury which initiated the train of morbid events leading directly to death,or the circumstance of the accident or violence which produced the fatal injuries”[1].
基金This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2007CB914800 to Xiaodong Zhang), National Natural Science Foundation of China (No. 30570698 to Xiaodong Zhang) and Tianjin Natural Scientific Foundation (No. 033801211 to Xiaodong Zhang).
文摘Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that β-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.
基金Supported by A grant from E-Da Hospital (in part)
文摘AIM: To investigate the role of opioid p-receptor subtype in opiate-induced constipation (OIC).METHODS: The effect of Ioperamide on intestinal transit was investigated in mice. Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension. The ileum strips were precontracted with 1 μmol/L acetylcholine (ACh). Then, decrease in muscle tone (relaxation) was characterized after cumu- lative administration of 0.1-10μ~mol/L Ioperamide into the organ bath, for a concentration-dependent study. Specific blockers or antagonists were used for pretreat- ment to compare the changes in Ioperamide-induced relaxation.RESULTS: In addition to the delay in intestinal transit, Ioperamide produced a marked relaxation in isolated ileum precontracted with ACh, in a dose-dependent manner. This relaxation was abolished by cyprodime,a selective opioid p-receptor antagonist, but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors. Also, treatment with opioid μ-1 receptor agonist failed to modify the muscle tone. Moreover, the relaxation by Ioperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K^+ (KATP) channels, and by protein kinase A (PKA) inhibitor, but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate (cAMP).CONCLUSION: Loperamide induces intestinal relaxa- tion by activation of opioid μ-2 receptors via the cAMP- PKA pathway to open KATp channels, relates to OIC.
基金supported by grants from China National Programs for Science and Technology Development (Grant No. 2003BA712A11-24)Scientific Research Fund of North China Coal Medical College (Grant No. 2005-14)
文摘Objectives Tumor necrosis factor-α (TNF-α) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis (TB) among patients with coal worker's pneumoconiosis (CWP). Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP). Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher's exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls (2,2=5.44, P=-0.07). But difference in frequency of the TNF-α-308 A allele was identified between them (2,2-5.14, P=0.02). No significant difference in frequencies of the TNF-α-238 genotype and allele (P=0.23 and P=0.09, respectively) was found between cases and controls either, with combined (GG and AA) OR of 3.96 (95% confidence interval of 1.30-12.09) at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 (95% CI of 1.06-3.71) for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index (OR=4.92), as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.
基金supported by Peking Union Medical College Youth Fund and the Fundamental Research Funds for the Central Universities(No.2017310049)
文摘Background: Mortality outcomes in trials of low-dose computed tomography(CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect.Methods: A decision tree model with three scenarios(low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort(100,000 smokers aged45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality(primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables.Results: Among the 100,000 subjects, there were 448,541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively(17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, lowdose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths(relative numbers) with low-dose CT screening in the worst and optimal cases were16(5.4%) and 288(40.2%) over no screening, respectively.Conclusions: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China.However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.
基金This project was supported by grants from the Ford Foundation, the Save the Children Fund, and Befrienders International.
文摘Objective To compare the characteristics of suicides in the four main demographic groups: urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China. Methods A detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country. Results Pesticide ingestion accounted for 58% (519) of all suicides and 61% (3181519) of deaths were due to unsuccessful medical resuscitation. A substantial proportion (37%) of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% (76/563) received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion (79%), the lowest prevalence of mental illness (39%), and the highest acute stress from precipitating life events just prior to the suicide. Contusion Many suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.
基金Supported by Guangdong Provincial Department of Science and Technology,No.[2013]173
文摘AIM To investigate the effects of Xiangbin prescription(XBP), a Chinese herbal concoction, on gastrointestinal motility.METHODS Forty healthy volunteers were recruited for this randomized controlled trial of XBP. Antroduodenojejunal manometry was used to monitor gastrointestinal motility in these subjects. After the subjects had fasted for at least 12 h, XBP(n = 30) or placebo(n = 10) was orally administrated and gastrointestinal motility was recorded for 4 h. Plasma motilin and ghrelin were measured by enzyme-linked immunosorbent assay.RESULTS Oral administration of XBP significantly increased the amplitude of duodenal contractions [19.5(13.0-26.7) vs 16.9(12.3-23.9), P < 0.05], jejunal contractions [18.3(15.3-25.0) vs 15.4(11.7-23.9), P < 0.01], and the motility index of duodenal contractions [522.0(146.0-139.0) vs 281.0(76.5-1006.0), P < 0.01] in phase Ⅱ of the migratory motor complex(MMC), which subsequently initiated the MMC cycle [74.0(30.0-118.0) vs 116.5(24.0-219.0), P < 0.05], shortened the duration of phase I of the MMC [42.0(0.0-90.0) vs 111.5(42.0-171.0), P < 0.01], and lengthened the duration of phase Ⅱ of the MMC [120(21-240) vs 58(16-170), P < 0.01] compared to the duration before XBP administration. There were significant differences in the amplitude of jejunal contractions [19.8(14.0-30.0) vs 18.0(13.0-28.5), P < 0.05], the motility index of duodenal contractions [236.0(115.0-306.0) vs 195.0(109.0-310.0), P < 0.05], and jejunal contractions [214.0(95.0-403.0) vs 178.0(55.0-304.0), P < 0.01] in phase Ⅲ of the MMC. Oral administration of XBP greatly increased plasma motilin(57.69 ± 9.03 vs 49.38 ± 8.63, P < 0.01) and ghrelin(279.20 ± 104.31 vs 238.73 ± 115.59, P < 0.01) concentrations compared to concentrations after oral administration of the placebo.CONCLUSION XBP can stimulate duodenal and jejunal motility and increase the concentrations of plasma motilin and ghrelin. The clinical applicability of XBP in treating GDIM deserves investigation.
文摘Objective To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-KB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). Methods Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFa-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants. Results it was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFa for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFa for 24 h. The stimulatory effect of TNFa just on proMMP-9 was counteracted significantly by CAPE. Conclusion NF-KB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFa (a pro-apoptotic factor). Therefore, therapeutic NF-KB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.
基金supported by International Agency for Research on Cancer (Lyon, France) (No. CRA No GEE/08/19)supported in part by the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988)
文摘Objective: To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors (RFs, including nulliparity, mean number of children, age at first birth and breastfeeding), use of oral contraceptives (OCs, restricted to the age group of 15-49 years), and hormone replacement therapy (HRT), as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods: We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results: Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer (712 cases, 294 deaths). The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction (PAF) of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion: RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.
基金supported by the Department of Medical Biochemistry.University of Madras.Chennai-600113.Tamil Nadu,India
文摘Objective:To investigate the bioactive-constituents of Shemamruthaa(SM),a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation(LPO),antioxidant status,citric acid cycle enzymes and electron transport chain enzymes in mammary tissues of 7,12-dimethylbenz(a)-anthracene(DMBA)induced mammary carcinoma in rat model.Methods:Adult Female Sprague-Dawley rats were used for the study and were divided into four groups.CroupⅠserved as control and CroupⅡrats were induced mammary carcinoma by administration of DMBA(25 mg/kg b.w.)orally.The normal and cancer-induced rats(GroupⅢ)were treated with SM(400 mg/kg b.w./day)orally by gastric incubation for 14days.CroupⅣrats served as SM-treated control animals.Results:Cancer-induced rats showed a considerably increased level of LPO with concomitant decreased levels of antioxidants,citric acid cycle enzymes,electron transport chain enzymes and cytochrome contents in the mammary tissue.Treatment with SM brought back the aforementioned biochemical parameters to near normal.Conclusions:From the results,it can be inferred that Shemamruthaa possesses significant anticancer effect through its role in attenuation of LPO,prevention of membrane damage and restoring membrane integrity.