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Diabetic peripheral neuropathy （DPN） is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN， one of the most common complications of diabetes mellitus， can lead to disability， foot ulcers， and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage， oxidative stress， mitochondrial disorders， and apoptosis in neural tissues. The p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is a key mechanism mediating the expression of inflammatory factors， oxidative factors， and apoptotic factors of neural tissues in DPN. The inflammatory response， oxidative stress damage， and apoptosis， induced by the activation of p38 MAPK phosphorylation by factors such as high glucose， can cause cell lipid peroxidation， protein modification， and nucleic acid damage， which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years， the research on traditional Chinese medicine （TCM） in the prevention and treatment of DPN has gradually increased， and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN， such as inflammation regulation， oxidative stress， polyol pathway regulation， and Schwann cell apoptosis in the past 10 years. In addition， the literature on Chinese medicine monomers， Chinese patent medicines， and Chinese medicine compounds in inhibiting inflammatory reactions， oxidative injury， and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway， resisting axonal degeneration and demyelination changes， improving sensory and motor abnormalities， relieving peripheral pain sensitization， and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.
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ObjectiveTo explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ， ip） at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK groups， and lipoic acid group （0.026 8 g·kg-1） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4th， 8th， and 12th week of administration. At the 12th week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （P<0.01）. The levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group （P<0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （P<0.01）. Compared with the model group， TBK of the three doses lowered the TWL （P<0.05， P<0.01） and the levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve of rats （P<0.05， P<0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （P<0.05， P<0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.
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ObjectiveTo explore the mechanism of Tangbikang granules （TBK） against diabetic peripheral neuropathy （DPN） based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME， the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN， which were uploaded to Metascape for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin （STZ， ip） were employed to induce diabetes in rats， and then the model rats were respectively treated with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Sensory nerve conduction velocity （SNCV） was evaluated. After hematoxylin and eosin （HE） staining， the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase （AMPK） pathway-related targets in rat sciatic nerve， and Western blot to measure the protein expression of AMPK and phosphorylated （p）-AMPK in rat sciatic nerve. ResultThe main active components of TBK， such as quercetin， kaempferol， β-sitosterol， leech pteridine A， stigmasterol， and baicalein were screened out， mainly acting on interleukin-6 （IL-6）， tumor necrosis factor （TNF）， protein kinase B （Akt）， JUN， and HSP90AA1 and signaling pathways such as AMPK， nuclear factor-κB （NF-κB）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）. Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6， TNF， JUN， and HSP90AA1. As for the animal experiment， compared with the normal group， model group had low SNCV of sciatic nerve （P<0.01）， disordered and loose myelinated nerve fibers with axonotmesis and demyelinization， low mRNA expression of AMPKα， AMPKβ， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， Sirtuin 3 （SirT3）， mitochondrial transcription factor A （TFAM）， and low p-AMPK/AMPK ratio in sciatic nerve （P<0.05， P<0.01）. Compared with the model group， TBK of the three doses raised the SNCV （P<0.01）， restored nerve morphology and nerve compactness， and increased the mRNA expression of AMPKα， AMPKβ， PGC-1α， SirT3， and TFAM （P<0.05， P<0.01）. The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group （P<0.01）， while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling， which lays a basis for further study of TBK in the treatment of DPN.
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ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules（TBK） on type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats， which were then respectively treated （ig） with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Fasting blood glucose （FBG） and body mass were recorded every 4 weeks during the treatment. One week before sampling， the feed intake of rats was detected， and after 12 h night fasting， oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was used to evaluate glucose tolerance， and the homeostatic model assessment for insulin resistance （HOMA-IR） was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes： Fasting serum insulin （FINS）， serum total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， and nonesterified fatty acids （NEFA）. The liver was weighed to calculate the liver index， and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. The protein levels of insulin receptor substrate （IRS）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt） and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group （P<0.01）， and the feed intake the administration groups was lower than that in the model group （P<0.05， P<0.01）. At the 8th and 12th week， the body mass in the model group was lower than that in the normal group （P<0.01）. Compared with the model group， TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group （P<0.01）. The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group， and AUC in the administration groups was significantly different from that in the model group （P<0.01）. The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group （P<0.01）， and they were lower in the TBK groups than in the model group （P<0.01）. Serum levels of TG， TC， HDL-C， NEFA （P<0.05， P<0.01）， and LDL-C were higher in the model group than in the normal group. Serum levels of TG， TC， LDL-C， and NEFA in the TBK groups were lower than those in the model group， and the levels of TG， LDL-C， and NEFA in TBK groups were concentration-dependent （lowest levels in high-dose TBK group）. Compared with the model group， high-dose TBK significantly increased the level of HDL-C （P<0.05）. Liver index of the model group was higher than that in the normal group （P<0.01）. The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver， the model group had unclear structure of liver lobule， enlarged cells of different sizes， and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury， particularly the high dose. For the PAS staining， compared with the normal group， the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein， p-IRS1/IRS1， and p-Akt/Akt in the model group were lower than those in the normal group （P<0.01）， and they were higher in the high-dose TBK group than in the model group （P<0.01）. ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.
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Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.
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The majority patients of differentiated thyroid carcinoma (DTC) with indolent progression have general good prognosis after standard primary treatments including surgery, thyroid stimulating hormone (TSH) suppression and radioactive iodine (RAI) therapy. However, there are still some patients suffered from recurrence or distant metastasis after initial treatment. They may lose the ability of uptaking iodine during their natural course of disease or treatment and could not benefit from subsequent RAI treatment, which will result in radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Options are very limited for RAIR-DTC patients, which is associated with a poor prognosis. Recently, with the research advances on the molecular mechanism of RAIR-DTC, redifferentiation combined with RAI therapy have been increasingly used to treat RAIR-DTC, and some outcomes are quite encouraging. This paper reviews the progress of signaling pathway inhibitors, histone deacetylase inhibitors, DNA methyltransferase inhibitors, retinoids and peroxisome proliferator-activated receptor agonists in redifferentiating therapy of RAIR-DTC.
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Objective To construct a grading nursing care system at public hospitals based on the severity of illness and activities of daily living ( ADL). Methods Multi-center stratified random sampling was used to investigate the general adult patients hospitalized in 12 wards of six tertiary-level hospitals in the eastern, central and western parts of China from January to December of 2016. The Barthel index and simple clinical score ( SCS) were used to evaluate their ADL and severity of illness, while a customized direct nursing hour scale was applied to record the direct nursing time needed by patients in 24 hours. Nursing grades were defined according to different conditions and ADL and to the difference of patient needs of 24 h direct nursing hours. Results 7 200 patients were investigated in total, and 7 073 effective questionnaires were collected (98. 24% ). Seven new grades of nursing care were defined based on patients′ severity of illness, ADL and different 24 h direct nursing time. These grades match the existing four grading nursing care levels to become refined sub-levels. Conclusions Patients can be graded according to their conditions, ADL and the 24 h direct nursing time needed. Such a new method is more objective, specific and quantitative than before, conducive to upgrading fine management level of nursing.
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@#The genome, replication mode and nosogenesis of duck hepatitis B virus are similar to those of human hepatitis B virus. In addition, the natural host of duck hepatitis B virus is readily available, cheap and has a high success rate of infection. Therefore, duck hepatitis B virus-infected models have been widely used for drug screening, pharmacological and pathological studies. For drug screening, the model is easy to obtain with high infection success rate and good stability. In the pharmacological research, the model can maintain high levels of viral DNA replication in the hepatocytes and exhibit significant damaged liver phenotypes which can reflect the pharmacological effects of drugs with different mechanisms. Also in the pathologic mechanisms research, the model has entire virus life cycle and maintains a pool of covalent closed-loop DNA in the hepatocytes, which can help scientific researchers better understand human hepatitis B virus. This article reviews the applications of duck hepatitis B animal model in drug screening, pharmacological and pathological studies, also outlooks the application prospect of this model.
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DNA typing of biological samples is an important step in performing individual identification and paternity testing in forensic applications. In practice, the detection of complex biological samples and the identification of complex kinships are challenging current biological technologies. Novel DNA technologies are also introduced into forensic genetics to improve the power of analysis. Next-generation sequencing (NGS) has several advantages, such as high-throughput and low cost, and can obtain detailed DNA sequences and relative contents of targeted regions, which will improve the detection of biological samples to help the analysis of forensic cases. The application of NGS in forensic genetics has received extensive attention and reports on the application of NGS in forensic genetics are increasing. In this study, we summarized the progress in the application research of NGS in the forensic genetics including the detection of genetic markers and their analytical methods. This will provide guides for related studies and forensic applications.
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Traditional Chinese medicine shows good hypoglycemic effect with mild efficacy, long duration and few adverse reac-tions. In recent years, the researches on the hypoglycemic effect of Ruikang Hospital Affilliated to traditional Chinese medicine mainly started from the mechanism of new target protein and pathway, for example, Chinese medicine monomers or compounds including as-tragalus polysaccharide, curcumin, berberine, emodin, total saponins of momordicacharantia, total saponins of momordicacharantia, Yitangkang, Jiangtang Sanhuang tablets, Jianpixiaokefang and Tangnaikang granule can activate Adenosine monophosphate ( AMP)-activated protein kinase ( AMPK) to play hypoglycemic effect.
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RNA has received m ore attention in the field of forensic m edicine and the developm ent of the new biological m arkers based on RNA show s great significance in the analysis of com plex cases. circular RNA (circRNA ) is a kind of non-coding RNA w hich is w idely reported recently. A lthough the regulatory m echanism s of generation and expression are not fully clear, the existing research indicates that circRNA has im portant biological functions. C ircRNA has a cell-type-specific expression w ith great stability and a high expression level, w hich m akes it m eaningful in forensic applications potentially. In this paper, the research progress, the generation and regulation of circRNA as w ell as its biological characteristics and functions are sum m arized, w hich w ill provide references for related studies and foren-sic applications.
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Objective To conduct a single-center retrospective analysis on the distribution characteristics and prevalence of idiopathic membranous nephropathy (IMN) patients diagnosed with pathology for the past 16 years,to investigate diagnostic and differential diagnostic value of serum antiphospholipase A2 receptor antibodies (PLA2R-Ab),and to evaluate the correlation between PLA2R-Ab and clinical disease activity.Methods (1) 6996 biopsy-proven primary glomerular nephropathy (PGN) patients,including 1567 IMN cases,admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2015 were involved.Demographics and pathological type were gathered from all patients.(2) 433 cases receiving renal biopsy and testing PLA2R-Ab from June 2015 to December 2015 were involved,with their clinical and laboratorial data being collected.During the period patients' follow-up time,therapeutic schedule and laboratory results were recorded.Results (1) IMN accounted for 22.4％ of primary glomerular disease,and patients above 40 years old accounted for more than 60％ of the IMN.(2) The sensitivity and specificity of serological PLA2R-Ab were 58.1％(95％CI 47.0％-68.5％) and 98.6％(95％CI 95.6％-99.6％) respectively.PLA2R-Ab positive rate was affected by immunosuppression therapy.(3) The PLA2R-Ab titers wasn't correlated with 24-hour urinary protein (r=-0.017,P=0.887),serum albumin (r=-0.072,P=0.549) and urinary red blood cell count (r=-0.030,P=0.802).There was no difference between PLA2R-Ab positive positive and PLA2R-Ab negative on proportion of IMN pathological stage Ⅰ-Ⅱ (P ＞ 0.05).Thirteen cases of patients with PLA2R-Ab positive were all prescribed glucocorticoid combined with immunosuppressant.After (2.21± 1.09) months,the decrease of PLA2R-Ab titers was in accordance with 24-hour urinary protein quantity descending and serum albumin ascending (P ＜ 0.05).Condusions The incidence of IMN increase year by year,especially in the mid-aged and the elderly.Serum PLA2R-Ab correlates not with IMN pathological stage,but with the development of IMN.Monitoring PLA2R-Ab titers individually may access the efficiency of treatment.
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@#The purpose of this study was to investigate the formation thermodynamics of baicalein(BE)-nicotinamide(NCT)cocrystals in three solvents including ethyl acetate, acetone and trichloromethane. The solubilities of BE, NCT and BE-NCT in the above solvents at 25 °C were measured. Ternary phase diagrams(TPDs)of the BE-NCT-solvent systems were established. The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT cocrystals demonstrated a good correlation between calculated and experiment data. ΔG0< 0 suggested that BE-NCT cocrystal formation was a spontaneous process. Among the organic solvents studied, the absolute value of ΔG0 in trichloromethane was significantly lower than that in the other two solvents. In addition, the cocrystallization zone in trichloromethane was far away from stoichiometric line. This study provides a theoretical foundation for solvent selection and preparation-condition optimization of BE-NCT cocrystals.
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Baicalein-nicotinamide(BE-NCT)co-crystal was chosen as model drug to investigate the thermody-namic characteristics.Solubilities of BE in NCT solutions in ethyl acetate at different temperatures were deter-mined in order to explain the complexation behavior of BE-NCT co-crystal.Thermodynamic parameters of co-crys-tal formation progress were calculated.Ternary phase diagrams (TPDs)of the BE-NCT-ethyl acetate systems at various temperatures were established.The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT co-crystal demonstrated a good correlation between calculated and experimental data (R2 >0.98). Co-crystal formation is a spontaneous process(ΔG°<0).Increase in temperature resulted in the increase of Ksp;decrease of K11 and a narrowed co-crystal zone.The degree of spontaneous reaction also decreased with increased temperature.The spontaneous reaction no longer carried out if the temperature reached T* =315 K sinceΔG°=0(ΔH°=-6.314 ×10 -2 kJ/mol;ΔS°=-0.200 5 J/mol.K).A drop in temperature favors the complexation between BE and NCT in ethyl acetate.Since NCT has higher solubility than BE in ethyl acetate;the TPDs of co-crystal was asymmetric.The DSC diagrams of products prepared via three presupposed methods confirmed that the BE-NCT co-crystal could be generated in solutions of nonstoichiometric compositions.
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The negative experience such as burden and positive experience such as benefits may engender in caregivers in the process of caring for stroke patients,which present both mutual independence and coexistence.Negative experience was paid more attention,but positive experience received less.The article analyzed the current situation of assessment in care burden of stroke patients' caregivers,summarized the shortcomings,made suggestions.Based on these summaries,the care benefits were suggested to do research on three levels (individual,family and social).
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Objective To investigate the restricting factors of long-term care of stroke survivors in community.Methods The phenomenological methodology was adopted in the study.Sixteen stroke survivors were interviewed.Data were analyzed by Colaizzi's method.Results Three themes were found,including physical barriers,incorrect attitude towards disease,and defects of community health service.Conclusions On the basis of improving technology and ability,medical workers in community should consider of supporting the patients with information of disease and useful resources in a variety of ways,and improving the patients health literacy.
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Objective To investigate the relationship between positive experience and social support of spouses' of community stroke patients.Methods 100 stroke patients and their spouses in two communities were conveniently selected and investigated about their positive experience and social support with General Information Questionnaire (GIQ),Modified Barthel Index(MBI),Positive Aspects of Caregiver (PAC),Perceived Social Support Scale (PSSS).Results The mean score of the spouses' positive experience was (22.74±5.85); the dimension of serf-affirmation was (15.82±3.84),higher than the dimension of life expectation(6.92±2.95).The scores of the spouses' positive experience were significantly different among age,gender,education of spouses and age and ability of daily life of stroke patients; the score of the spouses' positive experience was positively correlated with social support,subjective support,utility of support;multiple linear regression showed that age of spouses,ability of daily life of stroke patients and utility of support were influential important factors of spouses' positive experience.Conclusions The spouses' positive experience was below average level,we must pay more attention to improve it,utility of support can improve spouses' positive experience.
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Objective To compare the efficacy of percutaneous radiofrequency ablation (PRFA) and repeat hepatectomy for solitary recurrent hepatocellular carcinoma (HCC) with the diameter≤3 cm. Methods The clinical data of 151 patients with recurrent HCC (diameter≤3 cm) who were admitted to the Cancer Center of Sun Yat-Sen University from January 1999 to December 2009 were retrospectively analyzed. Of all the patients, 79received PRFA (PRFA group) and 72 received repeat hepatectomy (repeat hepatectomy group). The survival rate, morbidity and recurrence of the tumor between the two groups were compared. All data were analyzed using t test, chi-square test or Log-rank test, and the survival of the patients were analyzed using the Kaplan-Meier method. Results The mobidities of the PRFA group and repeat hepatectomy group were 13% (10/79) and 36%(26/72), respectively, with a significant difference between the two groups (x2=11.411, P＜0.05). The cumulative 1-, 2-, 3-, 4-, 5-year survival rates were 89.7%, 75.2%, 67.1%, 61.5%, 56.6% in the PRFA group, and 86.0%, 67.6%, 53.6%, 44.1%, 40.2% in the repeat hepatectomy group, with no significant difference between the two groups (x2=1.610, P＞0.05). The cumulative 4-, 5-year survival rates of the PRFA group were significant higher than those in the repeat hepatectomy group (x2=4.682, 4. 196, P ＜ 0.05). The local tumor recurrence rate of the PRFA group was 5% (4/79), and the incisal margin recurrence rate was 3% (2/72) in the repeat hepatectomy group, with no significant difference between the two groups (x2=0.565, P＞0.05). Conclusion As a less invasive treatment method, PRFA is superior to repeat hepatectomy for solitary recurrent HCC with the diameter≤3 cm.
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Objective: To analyze the therapeutic effect of repeated hepatectomy on recurrent hepatocellu-lar carcinoma and prognostic factors. Methods: We retrospectively analyzed the clinicopathologic data of 48 patients who underwent repeated hepatectomy for recurrent hepatocellular carcinoma between July 1995 and July 2003. Overall survival rate and disease-free survival (DFS) rate were calculated by Kaplan-Meier meth-od. Prognostic factors were analyzed by univariate and multivariate analysis. Results: The median survival of 48 patients was 36.4 months. The overall 1-, 3-, and 5-year survival rates were 81.3%, 45.8%, and 27.1%, re-spectively. The disease-free 1-, 3-, and 5-year survival rates were 70.8%, 25.0%, and 16.7%, respectively. Univariate analysis showed that TNM stage of primary tumor, TNM stage of the recurrent tumor, vascular in-vasion, recurrent tumor size (>5cm) and recurrence-free interval were prognostic risk factors for overall surviv-al. While TNM stage of primary tumor, recurrent tumor size (>5cm), TNM stage of recurrent tumor, vascular in-vasion, pathological grading of recurrent tumor, preoperative AFP and recurrence-free interval were prognos-tic risk factors for DFS. Multivariate analysis showed that recurrence-free interval and TNM stage of recurrent tumor were independent prognostic risk factors for overall survival. While recurrence-frae interval and recur-rent tumor size (>5cm) were independent prognostic risk factors for DFS. Conclusion: Short recurrence-free in-terval (≤24 months), recurrent tumor size (>5cm) and TNM stage of recurrent tumor indicate poor prognosis of patients who received repeated hepatectomy for recurrent hepatocellular carcinoma.
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<p><b>OBJECTIVE</b>To study the micrometastasis distribution in liver tissue surrounding hepatocellular carcinoma (HCC), and provide reference for appropriate surgical safety margin.</p><p><b>METHODS</b>Thirty-six patients with HCC but without clinical metastasis underwent hepatectomy. Their specimens showing ample surgical margin were made into giant sections. Tumor micrometastasis in liver tissue around the primary tumor were examined microscopically. In each specimen, the surrounding tissue was divided into proximal(p) and distal(d) areas. In either area, three lines of demarcation 0.5 cm, 1.0 cm, and 2.0 cm away from the margin of the primary tumor were designated as L(0.5), L(1.0) and L(2.0). Therefore, the surrounding tissue was divided into six zones - Z(p0.5), Z(p1.0), Z(p2.0) and Z(d0.5), Z(d1.0), Z(d2.0). The maximum micrometastasis spread distance (MMSD) and density (D(p0.5), D(p1.0), D(p2.0) and D(d0.5), D(d1.0), D(d2.0)) in each zone were analyzed after search for micrometastasis in the giant sections.</p><p><b>RESULTS</b>72.5% (111/153) micrometastases were found in form of microscopic tumor emboli. Their spread distance could be up to 6.1 cm. In 66.7% (24/36) specimens, micrometastases were found in the surrounding tissue. In 91.7% (22/24) of them, the distal MMSD was less than 3 cm. The proximal MMSD was less than 1.5 cm in 92.3% (12/13). The comparison of micrometastasis density in the different zones were D(d0.5) > D(d1.0) > D(d 2.0); D(p0.5) > D(p1.0) > D(p2.0); D(d1.0) > D(p1.0); D(d2.0) > D(p2.0) with significant differences.</p><p><b>CONCLUSION</b>(1) Micrometastases of HCC exist mainly in form of microscopic tumor emboli, (2) The longer the distance from the primary focus, the lower the micrometastasis incidence, (3) In zones more than 0.5 cm away from the primary focus, tumor micrometastasis incidence is significantly lower in the proximal zones than that in the distal zones and (4) For HCC patients without clinical metastasis, a surgical margin of 3 cm wide in the distal area and 1.5 cm wide in the proximal area may reduce the rate of postoperative recurrence.</p>