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BACKGROUND: Mutations in mitochondrial tRNA (mt-tRNA) genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus (T2DM). We pre-viously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA Trp A5514G and tRNA Ser(AGY) C12237T variants, however, the effects of these mt-tRNA variants on T2DM progression are largely unknown. AIM: To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic, molecular, and biochemical levels. METHODS: Cytoplasmic hybrid (cybrid) cells carrying both m.A5514G and m.C12237T variants, and healthy control cells without these mitochondrial DNA (mtDNA) variants were generated using trans-mitochondrial technology. Mitochondrial features, including mt-tRNA steady-state level, levels of adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mtDNA copy number, nicotinamide adenine dinucleotide (NAD+)/NADH ratio, enzymatic activities of respiratory chain complexes (RCCs), 8-hydroxy-deo-xyguanine (8-OhdG), malondialdehyde (MDA), and superoxide dismutase (SOD) were examined in cell lines with and without these mt-tRNA variants. RESULTS: Compared with control cells, the m.A5514G variant caused an approximately 35% reduction in the steady-state level of mt-tRNA Trp (P < 0.0001); however, the m.C12237T variant did not affect the mt-tRNA Ser(AGY) steady-state level (P = 0.5849). Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells: ATP, MMP, NAD+/NADH ratio, enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells (P < 0.05 for all measures). By contrast, the levels of ROS, 8-OhdG and MDA were significantly increased (P < 0.05 for all measures), but mtDNA copy number was not affected by m.A5514G and m.C12237T variants (P = 0.5942). CONCLUSION: The m.A5514G variant impaired mt-tRNA Trp metabolism, which subsequently caused mitochondrial dysfunction. The m.C12237T variant did not alter the steady-state level of mt-tRNA Ser(AGY), indicating that it may be a modifier of the m.A5514G variant. The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.
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General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.
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Anestésicos Generales , Encéfalo , Oligodendroglía , Oligodendroglía/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Anestésicos Generales/efectos adversos , Anestésicos Generales/toxicidad , Síndromes de Neurotoxicidad/etiología , HumanosRESUMEN
OBJECTIVE: To explore the role of leptin in the onset and development of obesity-associated hypertension. SUBJECTS AND METHODS: A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Leptin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. RESULTS: Serum leptin levels statistically significantly positively correlated with BMI and WC, and negatively with the HDLC (high-density lipoprotein cholesterol), even after adjustment for age and gender. There was no significant difference in the serum leptin levels between the normal healthy group (NH group) and the newly diagnosed untreated just-hypertension group (JH group). And the same is between the newly diagnosed untreated obesity-hypertension group (OH group) and the newly diagnosed untreated just-obesity group (JO group). Multiple linear regression analysis indicated BMI and gender as significant independent correlates of serum leptin. CONCLUSIONS: These results show leptin may not be essential but play an additive effect in the development of obesity-associated hypertension. Leptin may only play an additive effect role in the intricate interwoven network of regulators contributing to the development of hypertension in obese patients.
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Hipertensión , Leptina , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , China , Humanos , Hipertensión/complicaciones , ObesidadRESUMEN
OBJECTIVE: To explore the role of adiponectin-resistin (AR) index as a better indicator of obesity-related hypertension. METHOD(S): This study continued a case control study that had finished recruiting 153 subjects divided as four characteristic groups. Fasting serum resistin levels (FSR) and Fasting serum adiponectin levels (FSA) were tested by ELISA. And, other related anthropometric clinical and metabolic data were collected. Analyzation on correlations between research index and differences between groups were done by SPSS. AR index's performance was also validated by the receiver operating characteristic (ROC) curves, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULT(S): The AR index was defined as 1+ log10(R0)-log10(A0). AUC of the AR index was 0.660 and NRI and IDI indicated AR index outperformed FSA alone. AR index statistically significantly negatively correlated with SB and DB and positively with ALB and SCR. AR index was statistically significantly different between the NH group and OH group and more specific than FSR alone as a biomarker of obesity-related hypertension. CONCLUSION(S): The AR index was more strongly associated with increased risk of obesity-related hypertension than the solely index of FSR or FSA and was useful for early diagnosis of obesity-related hypertension.
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Hipertensión , Resistencia a la Insulina , Adiponectina , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , China/epidemiología , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Obesidad/complicaciones , ResistinaRESUMEN
INTRODUCTION: Pancreatic arteriovenous malformation (P-AVM) is a rare vascular malformation. Fewer than 200 cases have been reported. The clinical manifestations lack specificity. Common symptoms include abdominal pain, gastrointestinal hemorrhage, and jaundice, which is easily confused with other disorders. PATIENT CONCERNS: A 42-year-old man received TAE due to abdominal pain caused by P-AVM in a local hospital, melena and abdominal pain occurred in a short time after TAE. DIAGNOSIS: The patient was diagnosed as P-AVM which was confirmed by computed tomography and digital subtraction angiography. INTERVENTIONS: A pylorus-preserving pancreatoduodenectomy was successfully performed after diagnosis was made. OUTCOMES: The patient recovered with no complications two weeks after surgery, and no sign of recurrence was found during the 4-mo follow-up period. CONCLUSION: In our experience, TAE may have limitations in the treatment of P-AVM and surgical resection should be considered as the treatment of choice.
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Dolor Abdominal/etiología , Malformaciones Arteriovenosas/cirugía , Embolización Terapéutica/métodos , Páncreas/irrigación sanguínea , Pancreaticoduodenectomía , Dolor Abdominal/diagnóstico por imagen , Adulto , Angiografía , Angiografía de Substracción Digital , Malformaciones Arteriovenosas/diagnóstico por imagen , Humanos , Malformaciones Arteriovenosas Intracraneales/cirugía , Masculino , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Objective: To explore the role of resistin in the onset and development of obesity-related hypertension.Methods: Resistin serum levels were tested by ELISA in 153 adult subjects among four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Following, correlations between research index and differences between groups were analyzed using SPSS.Results: Serum resistin levels statistically significantly negatively correlated with SB, DB and BMI, but statistically significantly positively correlated with serum creatinine (SCR) and serum albumin (ALB), even after adjustment for age and/or gender. The serum level of resistin in the normal healthy subject group (NH) was higher than in other groups.Conclusions: Resistin's role in the onset of obesity-related hypertension may be more important than what has been previously assumed. More pathway substances in the early onset of obesity-related hypertension should be tested.Abbreviations: WC, waist circumference; GGT, Gamma-glutamyltransferase; ALB, Albumin; ALT, Alanine aminotransferase; LDL, Low density lipoprotein cholesterol; TG, Triglyceride; HDLC, High density lipoprotein cholesterol; FA Fructosamine; SCR, serum creatinine; IB, Indirect bilirubin; ALP, Alkaline phosphatase; CB, Conjugated bilirubin; UREA, Urea; Ua, Uric acid; FBG, fasting blood glucose; TC, Total cholesterol; TB, Total bilirubin; TP, Total protein; TC/HDLC, TC/HDLC ratio; SB, systolic blood pressure; DB, diastolic blood pressure.
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Pueblo Asiatico , Hipertensión/sangre , Obesidad/sangre , Resistina/sangre , Adulto , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , China , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Circunferencia de la CinturaRESUMEN
Certain mutations in mitochondrial DNA (mtDNA) are associated with Leber's hereditary optic neuropathy (LHON). In particular, the wellknown NADH dehydrogenase 4 (ND4) m.11778G>A mutation is one of the most common LHONassociated primary mutations worldwide. However, how specific mtDNA mutations, or variants, affect LHON penetrance is not fully understood. The aim of the current study was to explore the relationship between mtDNA mutations and LHON, and to provide useful information for early detection and prevention of this disease. Following the molecular characterization of a Han Chinese family with maternally inherited LHON, four out of eight matrilineal relatives demonstrated varying degrees of both visual impairment and age of onset. Through PCR amplification of mitochondrial genomes and direct Sanger sequencing analysis, a homoplasmic mitochondrialencoded ND4 m.11778G>A mutation, alongside a set of genetic variations belonging to human mtDNA haplogroup B5b1 were identified. Among these sequence variants, alanine transfer RNA (tRNA)Ala m.5601C>T was of particular interest. This variant occurred at position 59 in the TψC loop and altered the base pairing, which led to mitochondrial RNA (mtRNA) metabolism failure and defects in mitochondrial protein synthesis. Bioinformatics analysis suggested that the m.5601C>T variant altered tRNAAla structure. Therefore, impaired mitochondrial functions caused by the ND4 m.11778G>A mutation may be enhanced by the mttRNAAla m.5601C>T variant. These findings suggested that the tRNAAla m.5601C>T variant might modulate the clinical manifestation of the LHONassociated primary mutation.
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ADN Mitocondrial/genética , Mitocondrias/genética , NADH Deshidrogenasa/genética , Atrofia Óptica Hereditaria de Leber/genética , ARN de Transferencia de Alanina/genética , Adolescente , Adulto , Pueblo Asiatico/genética , Niño , Biología Computacional , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Atrofia Óptica Hereditaria de Leber/sangre , Atrofia Óptica Hereditaria de Leber/metabolismo , Atrofia Óptica Hereditaria de Leber/patología , Linaje , Penetrancia , Filogenia , Polimorfismo Genético , ARN de Transferencia de Alanina/químicaRESUMEN
Monolayer MoSe2 is a transition metal dichalcogenide with a narrow bandgap, high optical absorbance and large spin-splitting energy, giving it great promise for applications in the field of optoelectronics. Producing monolayer MoSe2 films in a reliable and scalable manner is still a challenging task as conventional chemical vapor deposition (CVD) or exfoliation based techniques are limited due to the small domains/nanosheet sizes obtained. Here, based on NaCl assisted CVD, we demonstrate the simple and stable synthesis of sub-millimeter size single-crystal MoSe2 monolayers with mobilities ranging from 38 to 8 cm2 V-1 s-1. The average mobility is 12 cm2 V-1 s-1. We further determine that the optical responsivity of monolayer MoSe2 is 42 mA W-1, with an external quantum efficiency of 8.22%.
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Ghost imaging technologies acquire images through intensity correlation of reference patterns and bucket values. Among them, an interesting method named correspondence imaging can generate positive-negative images by only conditionally averaging reference patterns, but still requires full/over sampling to treat the ensemble average of bucket values as a selection criteria, causing a long acquisition time. Here, we propose a sequential-deviation ghost imaging approach, which can realize real-time reconstructions of positive-negative images with a high image quality close to that of differential ghost imaging. Since it is no longer necessary to compare with the ensemble average, this method can improve the real-time performance. An explanation of its essence is also given here. Both simulation and experimental results have demonstrated the feasibility of this technique. This work may complement the theory of ghost imaging.
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BACKGROUND: Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with both syndromic and non-syndromic hearing impairment. However, the pathophysiology underlying mt-tRNA mutations in clinical expression of hearing loss remains poorly understood. OBJECTIVE: The aim of this study was to explore the potential association between mttRNA mutations and hearing loss. METHODS AND RESULTS: We reported here the molecular features of a pedigree with maternally transmitted non-syndromic hearing loss. Among 12 matrilineal relatives, five of them suffered variable degree of hearing impairment, but none of them had any medical history of using aminoglycosides antibiotics (AmAn). Genetic screening of the complete mitochondrial genomes from the matrilineal relatives identified the coexistence of mt-tRNAHis G12192A and mt-tRNAThr G15927A mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup B5b1b. Interestingly, the G12192A mutation occurred 2-bp from the 3' end of the TψC loop of mt-tRNAHis, which was evolutionarily conserved from various species. In addition, the well-known G15927A mutation, which disrupted the highly conserved C-G base-pairing at the anticodon stem of mt-tRNAThr, may lead to the failure in mt-tRNA metabolism. Furthermore, a significant decreased in ATP production and an increased ROS generation were observed in polymononuclear leukocytes (PMNs) which were isolated from the deaf patients carrying these mt-tRNA mutations, suggested that the G12192A and G15927A mutations may cause mitochondrial dysfunction that was responsible for deafness. However, the absence of any functional mutations/variants in GJB2, GJB3, GJB6 and TRMU genes suggested that the nuclear genes may not play important roles in the clinical expression of non-syndromic hearing loss in this family. CONCLUSION: Our data indicated that mt-tRNAHis G12192A mutation may increase the penetrance and expressivity of deafness-associated m-tRNAThr G15927A mutation in this family.
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Pueblo Asiatico/genética , Sordera/genética , Sordera/fisiopatología , Mitocondrias/genética , Mutación , ARN de Transferencia de Histidina/genética , ARN de Transferencia de Treonina/genética , Adulto , Secuencia de Bases , ADN Mitocondrial/análisis , Femenino , Genes Mitocondriales , Humanos , Masculino , Persona de Mediana Edad , Linaje , Penetrancia , FenotipoRESUMEN
Premature ovarian insufficiency (POI) is a common endocrine disorder featured by the triad constituting of amenorrhea for at least four months, to date, the molecular pathogenesis of POI is largely undetermined. Despite several investigations have reported an increase in reactive oxygen species (ROS) content in idiopathic POI, the role of mitochondrial DNA (mtDNA) mutations/variants in the progression of POI has not been widely investigated. The current study aimed to explore the association between mt-tRNA mutations/variants and POI; we first used the PCR-Sanger sequencing to detect the mutations/variants in mt-tRNA genes from 50 POI patients and 30 healthy subjects. In addition, we evaluated the mitochondrial functions by using trans-mitochondrial cybrid cells containing these potential pathogenic mt-tRNA mutations. Consequently, five mutations: tRNALeu(UUR) C3303T, tRNAMet A4435G, tRNAGln T4363C, tRNACys G5821A and tRNAThr A15951G were identified. Notably, these mutations occurred at the extremely conserved nucleotides of the corresponding mt-tRNAs and may result the failure in mt-tRNA metabolism and subsequently lead to the impairment in mitochondrial protein synthesis. Furthermore, biochemical and molecular analyses of the cybrid cells containing these mutations showed a significantly lower level of ATP production when compared with the controls, whereas the ROS levels were much higher in POI patients carrying these mt-tRNA mutations, strongly indicated that these mt-tRNA mutations may cause the mitochondrial dysfunction, and play active roles in the progression and pathogensis of POI. Together, this study shaded additional light on the molecular mechanism of POI that was manifestated by mt-tRNA mutations.
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Insuficiencia Ovárica Primaria/genética , ARN Mitocondrial/genética , ARN de Transferencia/genética , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Mutación , Adulto JovenRESUMEN
Gene expression divergence is an important evolutionary driving force for the retention of duplicate genes. In this study, we identified three CYP78A subfamily genes in soybean, GmCYP78A70, GmCYP78A57 and GmCYP78A72, which experienced different duplication events. GmCYP78A70 was mainly expressed in leaf tissue and the vegetative phase, whereas GmCYP78A57 was mainly expressed in floral tissue and seed, i.e., the reproductive phase. Expression of GmCYP78A72 could be detected in all the tissues and phases mentioned above. The expression levels of GmCYP78A70 and GmCYP78A57 in different soybean cultivars showed positive correlations with leaf size and 100-seed weight, respectively. The population genetics analysis indicated that the three genes had experienced different selective pressures during domestication and improved breeding of soybean. Deciphering the function of this subfamily of genes may well prove useful to breeders for improving soybean's agronomic traits.
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BACKGROUND: The obesity-hypertension pathogenesis is complex. From the phenotype to molecular mechanism, there is a long way to clarify the mechanism. To explore the association between obesity and hypertension, we correlate the phenotypes such as the waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), and diastolic blood pressure (DB) with the clinical laboratory data between four specific Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group), and the results may show something. OBJECTIVE: To explore the mechanisms from obesity to hypertension by analyzing the correlations and differences between WC, BMI, SB, DB, and other clinical laboratory data indices in four specific Chinese adult physical examination groups. METHODS: This cross-sectional study was conducted from September 2012 to July 2014, and 153 adult subjects, 34 women and 119 men, from 21 to 69 years, were taken from four characteristic Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group). The study was approved by the ethics committee of Hangzhou Center for Disease Control and Prevention. WC, BMI, SB, DB, and other clinical laboratory data were collected and analyzed by SPSS. RESULTS: Serum levels of albumin (ALB)ï¼alanine aminotransferase (ALT), low density lipoprotein cholesterol (LDLC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), alkaline phosphatase (ALP), uric acid (Ua), and TC/HDLC (odds ratio) were statistically significantly different between the four groups. WC statistically significantly positively correlated with BMI, ALT, Ua, and serum levels of glucose (GLU), and TC/HDLC, and negatively with ALB, HDLC, and serum levels of conjugated bilirubin (CB). BMI was statistically significantly positively related to ALT, Ua, LDLC, WC, and TC/HDLC, and negatively to ALB, HDLC, and CB. DB statistically significantly positively correlated with ALP, BMI, and WC. SB was statistically significantly positively related to LDLC, GLU, serum levels of fructosamine (FA), serum levels of the total protein (TC), BMI, and WC. CONCLUSION: The negative body effects of obesity are comprehensive. Obesity may lead to hypertension through multiple ways by different percents. GGT, serum levels of gamma glutamyltransferase; ALB, serum levels of albumin; ALT, serum levels of alanine aminotransferase; LDLC, serum levels of low density lipoprotein cholesterol; TG, serum levels of triglyceride; HDLC, serum levels of high density lipoprotein cholesterol; FA, serum levels of fructosamine; S.C.R, serum levels of creatinine; IB, serum levels of indirect bilirubin; ALP, serum levels of alkaline phosphatase; CB, serum levels of conjugated bilirubin; UREA, Urea; Ua, serum levels of uric acid; GLU, serum levels of glucose; TC, serum levels of the total cholesterol; TB, serum levels of the total bilirubin; TP, serum levels of the total protein; TC/HDLC, TC/HDLC ratio.
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Presión Sanguínea , Índice de Masa Corporal , Hipertensión/fisiopatología , Obesidad/fisiopatología , Circunferencia de la Cintura , Adulto , Anciano , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Bilirrubina/sangre , Glucemia/metabolismo , China , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Diástole , Femenino , Fructosamina/sangre , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Fenotipo , Factores de Riesgo , Albúmina Sérica/metabolismo , Sístole , Triglicéridos/sangre , Ácido Úrico/sangre , Adulto Joven , gamma-Glutamiltransferasa/sangreRESUMEN
Mutations in mitochondrial genome have been found to be associated with hearing loss. Of these, the mitochondrial 12S rRNA and tRNASer(UCN) are the hot spots for pathogenic mutations associated with deafness. To understand the putative role of mitochondrial DNA (mtDNA) mutations in hearing loss, we recently initiated a mutational screening for the mtDNA mutations in Hangzhou area from Zhejiang Province. In this study, we described a maternally inherited Han Chinese family with high penetrance of hearing loss, notably, the penetrances of hearing loss in this family were 80% and 40%, when the aminoglycoside was included or excluded. Three matrilineal relatives in this pedigree exhibited different levels of hearing loss with different age at onset. In addition, sequence analysis of the complete mitochondrial genome showed the presence of the well-known C1494T mutation in 12S rRNA gene and the G7444A mutation in the COI/tRNASer(UCN). The C1494T mutation had been reported to be a pathogenic mutation associated with aminoglycoside-induced and non-syndromic hearing loss. While the G7444A mutation was considered as a secondary mutation associated with deafness. However, the lack of functional variants in GJB2 and TRMU genes suggested that nuclear modified genes may not play important roles in deafness expression. Thus, the combination of G7444A and C1494T mutations in mitochondrial genome may account for the high penetrance of hearing loss in this Chinese family.
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BACKGROUND: Transarterial chemoembolization (TACE) is commonly used to treat advanced hepatocellular carcinoma (HCC), but less is known regarding safety and efficacy of TACE in patients with HCC and portal vein tumour thrombosis (PVTT). The objective of this study was to evaluate the effect of TACE treatment on 1-year survival in patients with HCC and PVTT. METHODS: Medline, EMBASE, CENTRAL databases (until July 2013) were searched for studies that evaluated the efficacy of TACE with regard to survival in patients with HCC and PVTT. One-year survival rate, the primary end point, was compared between patients who received TACE and those who received control treatment. RESULTS: Five prospective studies were identified that assessed the efficacy of TACE on survival. These studies included 600 patients: 335 received TACE therapy and 226 received control treatments. Three of the five studies reported 1-year survival data and were used in the meta-analysis. The combined odds ratio (3.079, 95% confidence interval = 1.094-8.662) indicated that patients who received TACE had a significantly better 1-year survival rate compared with patients in the control group (P = 0.033). CONCLUSIONS: There are several limitations to this analysis that should be considered when interpreting the findings. The studies used different treatment regimens as controls or with TACE. These differences across the studies may have altered the 1-year survival outcomes in each study and confounded our analysis. This meta-analysis showed that TACE improves the 1-year survival of patients with HCC and PVTT. However, additional prospective controlled trials are required to further substantiate these findings.
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Vena Porta , Trombosis de la Vena/etiología , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
AIM: To investigate the simplicity, reliability, and safety of the application of single-layer mucosa-to-mucosa pancreaticojejunal anastomosis in pancreaticoduodenectomy. METHODS: A retrospective analysis was performed on the data of patients who received pancreaticoduodenectomy completed by the same surgical group between January 2011 and April 2014 in the General Hospital of the People's Liberation Army. In total, 51 cases received single-layer mucosa-to-mucosa pancreaticojejunal anastomosis and 51 cases received double-layer pancreaticojejunal anastomosis. The diagnoses of pancreatic fistula and clinically relevant pancreatic fistula after pancreaticoduodenectomy were judged strictly by the International Study Group on pancreatic fistula definition. The preoperative and intraoperative data of these two groups were compared. χ(2) test and Fisher's exact test were used to analyze the incidences of pancreatic fistula, peritoneal catheterization, abdominal infection and overall complications between the single-layer anastomosis group and double-layer anastomosis group. Rank sum test were used to analyze the difference in operation time, pancreaticojejunal anastomosis time, postoperative hospitalization time, total hospitalization time and hospitalization expenses between the single-layer anastomosis group and double-layer anastomosis group. RESULTS: Patients with grade A pancreatic fistula accounted for 15.69% (8/51) vs 15.69% (8/51) (P = 1.0000), and patients with grades B and C pancreatic fistula accounted for 9.80% (5/51) vs 52.94% (27/51) (P = 0.0000) in the single-layer and double-layer anastomosis groups. Although there was no significant difference in the percentage of patients with grade A pancreatic fistula, there was a significant difference in the percentage of patients with grades B and C pancreatic fistula between the two groups. The operation time (220.059 ± 60.602 min vs 379.412 ± 90.761 min, P = 0.000), pancreaticojejunal anastomosis time (17.922 ± 5.145 min vs 31.333 ± 7.776 min, P = 0.000), postoperative hospitalization time (18.588 ± 5.285 d vs 26.373 ± 15.815 d, P = 0.003), total hospitalization time (25.627 ± 6.551 d vs 33.706 ± 15.899 d, P = 0.002), hospitalization expenses (116787.667 ± 31900.927 yuan vs 162788.608 ± 129732.500 yuan, P = 0.001), as well as the incidences of pancreatic fistula [13/51 (25.49%) vs 35/51 (68.63%), P = 0.0000], peritoneal catheterization [0/51 (0%) vs 6/51 (11.76%), P = 0.0354], abdominal infection [1/51 (1.96%) vs 11/51 (21.57%), P = 0.0021], and overall complications [21/51 (41.18%) vs 37/51 (72.55%), P = 0.0014] in the single-layer anastomosis group were all lower than those in the double-layer anastomosis group. CONCLUSION: Single-layer mucosa-to-mucosa pancreaticojejunal anastomosis appears to be a simple, reliable, and safe method. Use of this method could reduce the postoperative incidence of complications.
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Despite advances in the detection and treatment of hepatocellular carcinoma (HCC), the prognosis remains poor partly due to recurrence or extra/intrahepatic metastasis. Stemlike cancer cells are considered the source of malignant phenotypes including metastasis in various types of cancer. HCC side population (SP), considered as stemlike cancer cells, plays an important role in the migration and invasion in HCC, while the mechanisms involved remain unknown. In the present study, high levels of STAT3 and phosphoSTAT3 were observed in MHCC97H SP cells compared with the main population (MP) cells. Inhibition of phosphoSTAT3 led to a reduction of miR21 expression, an increase of PTEN, RECK, and programmed cell death 4 (PDCD4) expression as well as the migration and invasion of SP cells. A set of rescue experiments was performed using different combinations of STAT3 inhibitor, miR21 mimics and siRNAs to observe the expression of miR21 targets, cell migration and invasion alterations. Data indicated that the alterations induced by STAT3 inhibition were partly reversed by the upregulation of miR21. Additionally, the cells migration and invasion when silencing the targets of miR21 were also reversed by STAT3 inhibition. In conclusion, the present study revealed the aberrant expression of STAT3 and miR21 in HCC SP cells. Targeting STAT3 may limit HCC migration and invasion, which is likely to involve the regulation of miR21 and its targets PTEN, RECK and PDCD4. Strategies directed towards STAT3 may therefore be a novel approach for the treatment of HCC.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/biosíntesis , Células Madre Neoplásicas/patología , Factor de Transcripción STAT3/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/biosíntesis , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quimiocina CXCL12/farmacología , Proteínas Ligadas a GPI/biosíntesis , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Invasividad Neoplásica , Recurrencia Local de Neoplasia/genética , Fosfohidrolasa PTEN/biosíntesis , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño , Proteínas de Unión al ARN/biosíntesis , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Triterpenos/farmacologíaRESUMEN
AIM: To explore the morbidity and risk factors of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy. METHODS: The data from 196 consecutive patients who underwent pancreaticoduodenectomy, performed by different surgeons, in the General Hospital of the People's Liberation Army between January 1(st), 2013 and December 31(st), 2013 were retrospectively collected for analysis. The diagnoses of POPF and clinically relevant (CR)-POPF following pancreaticoduodenectomy were judged strictly by the International Study Group on Pancreatic Fistula Definition. Univariate analysis was performed to analyze the following factors: patient age, sex, body mass index (BMI), hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pancreatic duct diameter, pylorus preserving pancreaticoduodenectomy, pancreatic drainage and pancreaticojejunostomy. Multivariate logistic regression analysis was used to determine the main independent risk factors for POPF. RESULTS: POPF occurred in 126 (64.3%) of the patients, and the incidence of CR-POPF was 32.7% (64/196). Patient characteristics of age, sex, BMI, hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pylorus preserving pancreaticoduodenectomy and pancreaticojejunostomy showed no statistical difference related to the morbidity of POPF or CR-POPF. Pancreatic duct diameter was found to be significantly correlated with POPF rates by univariate analysis and multivariate regression analysis, with a pancreatic duct diameter ≤ 3 mm being an independent risk factor for POPF (OR = 0.291; P = 0.000) and CR-POPF (OR = 0.399; P = 0.004). The CR-POPF rate was higher in patients without external pancreatic stenting, which was found to be an independent risk factor for CR-POPF (OR = 0.394; P = 0.012). Among the entire patient series, there were three postoperative deaths, giving a total mortality rate of 1.5% (3/196), and the mortality associated with pancreatic fistula was 2.4% (3/126). CONCLUSION: A pancreatic duct diameter ≤ 3 mm is an independent risk factor for POPF. External stent drainage of pancreatic secretion may reduce CR-POPF mortality and POPF severity.
Asunto(s)
Conductos Pancreáticos/cirugía , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Anciano , Distribución de Chi-Cuadrado , China , Drenaje/instrumentación , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Conductos Pancreáticos/patología , Fístula Pancreática/diagnóstico , Fístula Pancreática/mortalidad , Fístula Pancreática/prevención & control , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Stents , Resultado del TratamientoRESUMEN
Previously known as a first-response protein upon viral infection and other stress signals, double-stranded RNA-dependent protein kinase (PKR, also termed EIF2AK2) has been found to be differentially expressed in multiple types of tumor, including hepatocellular carcinoma, suggesting that PKR may be involved in tumor initiation and development. However, whether and how PKR promotes or suppresses the development of hepatocellular carcinoma remains controversial. In the present study, PKR expression was investigated using qPCR and western blot analysis, which revealed that PKR expression was upregulated in liver tumor tissues, when compared to that of adjacent normal tissues, which were obtained from four primary liver cancer patients. Furthermore, in vitro cellular assays revealed that PKR exerts a key role in maintaining the proliferation and migration of HepG2 human hepatocellular carcinoma cells. Mouse models with xenograft transplantations also confirmed a tumorigenic role of PKR in HepG2 cells. Furthermore, a transcription factor, signal transducer and activator of transcription 3 (STAT3), was revealed to mediate the tumor-promoting function of PKR in HepG2 cells, as shown by in vitro cellular proliferation and migration assays. In conclusion, the results suggested a tumorigenic role of PKR in liver cancer and a detailed mechanism involving an oncogenic transcription factor, STAT3, is described. Therefore, PKR may present a potential novel therapeutic target for the treatment of liver cancer.
RESUMEN
BACKGROUND: Various malignant tumors can obstruct the extrahepatic biliary tract. Two major techniques for restoring bile flow in this circumstance are endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD).We conducted a meta-analysis to compare the effectiveness and safety of the two techniques. METHODS: Medline, EMBASE and the Cochrane Library database were searched for articles published between January 1980 and December 2013. The outcome measures were therapeutic success rate (primary), 30-day mortality rate and overall complications. RESULTS: Of 264 screened articles, 3 randomized controlled trialscomprising an aggregate total of 183 cancer patients were included in the meta-analysis. Our analysis showed no significant difference in restoration of bile flow between patients treated with EBD and those treated with PTBD (odds ratio (OR) = 2.34, 95% confidence interval (CI) = 0.32 to 17.16, P = 0.401).However, the result of sensitivity analysis indicated that the study conducted by Speer et al. influenced the pooled estimates. After the Speer et al. study was excluded, the therapeutic success rate of patients treated with PTBD was significantly greater than that of those who underwent EBD (OR = 5.48, 95% CI: 2.26 to 13.28, P < 0.001). The 30-day mortality and complication rates were similar in the EBD and PTBD groups. CONCLUSIONS: The results of our meta-analysis indicate that PTBD had a higher therapeutic success rate than EBD in the treatment of malignancy-induced biliary obstruction. The mortality and complication rates of the two techniques were similar.