RESUMO
This study aims to investigate the mechanism of Mailuo Shutong Pills(MLST) on posterior limb muscle swelling caused by femoral fracture(SCFF) through network pharmacology and animal experiments. The plasma components of MLST were analyzed by LC-MS, and the target and signal pathway of SCFF were predicted by network pharmacology and verified by molecular docking. SCFF model rats were established through animal experiments, and different doses of MLST were administered to detect the degree of limb swelling. Hematoxylin-eosin(HE) staining was used to observe pathological changes in muscle tissue, and interleukin-6(IL-6), interleukin-1ß(interleukin-1ß), and tumor necrosis factor-α(TNF-α) in peripheral blood were determined by enzyme-linked immunosorbent assay(ELISA). The expression of relevant signaling pathways was measured by Western blot. Network pharmacological results showed that MLST and SCFF had a total of 153 disease targets, and the key targets were IL-6, TNF, etc., involving mitogen-activated protein kinase(MAPK) signaling pathway, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, etc. The binding energies of the main components and key targets were lower than-7.0 kcal·mol~(-1), indicating that the network analysis results were reliable. The results of animal experiments showed that MLST could reduce the swelling degree and pathological damage of the posterior limb muscles of SCFF rats compared with the model group. ELISA results showed that MLST could reduce the levels of IL-6, IL-1ß, and TNF-α in the serum of SCFF rats. Western blot results showed that MLST can reduce the expression of p-AKT, p-PI3K, p-NF-κB, p-p38 MAPK, and p-ERK in SCFF rats. MLST may reduce the content of inflammatory factors in serum by regulating the expression of PI3K/AKT and MAPK-related signaling pathway protein and improving posterior limb muscle SCFF in rats.
Assuntos
Medicamentos de Ervas Chinesas , Fraturas do Fêmur , Farmacologia em Rede , Animais , Ratos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Simulação de Acoplamento Molecular , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genéticaRESUMO
This study aimed to investigate the protective effect and underlying mechanism of Mailuo Shutong Pills(MLST) on posterior limb swelling caused by femur fracture in rats. The rats were randomly divided into a sham operation group, a model group, a low-dose MLST group(1.8 g·kg~(-1)·d~(-1)), a high-dose MLST group(3.6 g·kg~(-1)·d~(-1)), and a positive drug group(60 mg·kg~(-1)·d~(-1) Maizhiling Tablets). The femur in the sham operation group was exposed and the wound was sutured, while the other four groups underwent mechanical damage to cause femur fracture. The rats were treated with corresponding drugs by gavage 7 days before modeling and 5 days after modeling, while those in the sham operation group and the model group were given an equivalent dose of distilled water by gavage. Hematoxylin-eosin(HE) staining was used to detect the pathological injury of the posterior limb muscle tissues in rats, and the degree of hind limb swelling was measured. The enzyme-linked immunosorbent assay(ELISA) kit was used to detect the expression levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. The activity of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and glutathione peroxidase(GSH-Px) in rat serum was also measured. Western blot was used to detect the protein expression levels of heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), and nuclear transcription factor E2-related factor 2(Nrf2) in rat posterior limb muscle tissues. The changes in the intestinal flora and intestinal metabolites in rats were detected by 16S rDNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), respectively, to explore the underlying mechanism of MLST in treating posterior limb swelling caused by femur fracture in rats. Compared with the model group, MLST significantly improved the degree of posterior limb swelling in rats, reduced the levels of serum inflammatory factors, and alleviated oxidative stress injury. The HE staining results showed that the inflammatory infiltration in the posterior limb muscle tissues of rats in the MLST groups was significantly improved. Western blot results showed that MLST significantly increased the protein expression of HO-1, NQO1, and Nrf2 in rat posterior limb muscle tissues compared with the model group. The 16S rDNA sequencing results showed that MLST improved the disorder of intestinal flora in rats after femur fracture. The UPLC-MS/MS results showed that MLST significantly affected the bile acid biosynthesis and metabolism pathway in the intestine after femur fracture, and the Spearman analysis confirmed that the metabolite deoxycholic acid involved in bile acid biosynthesis was positively correlated with the abundance of Turicibacter. The metabolite cholic acid was positively correlated with the abundance of Papilibacter, Staphylococcus, and Intestinimonas. The metabolite lithocholic acid was positively correlated with Papilibacter and Intestinimonas. The above results indicated that MLST could protect against the posterior limb swelling caused by femur fracture in rats. This protective effect may be achieved by improving the pathological injury of the posterior limb muscle, reducing the expression levels of inflammatory and oxidative stress-related factors in serum, reducing the oxidative injury of the posterior limb muscle, improving intestinal flora, and balancing the biosynthesis of bile acids in the intestine.
Assuntos
Microbioma Gastrointestinal , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Cromatografia Líquida , Tipagem de Sequências Multilocus , Espectrometria de Massas em Tandem , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Fêmur , Ácidos e Sais Biliares , DNA Ribossômico , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1ß(IL-1ß) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-ß(TGF-ß), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1ß in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-ß, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-ß/Smad4 signaling pathway.
Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Camundongos , Masculino , Animais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Azeite de Oliva/metabolismo , Azeite de Oliva/farmacologia , Azeite de Oliva/uso terapêutico , Tetracloreto de Carbono/efeitos adversos , Tetracloreto de Carbono/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fígado , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1ß were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1ß proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1ß and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1ß positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1ß protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1ß signaling pathway.
Assuntos
NF-kappa B , Urticária , Animais , Masculino , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ovalbumina , Hidróxido de Alumínio/farmacologia , Transdução de Sinais , Caspase 1/genética , Caspase 1/metabolismo , PruridoRESUMO
This study aims to clarify the effect of Jingfang Mixture on the treatment of chronic urticarial and its mechanism, and investigate the regulatory effect of chronic urticaria on the metabolic disorder of endogenous metabolites in the blood. The mice were randomly divided into normal group, model group, and Jingfang Mixture group, and modeling and administration continued for 21 d. The changes in endogenous small molecules in rat serum were determined by ultra-high performance liquid chromatography-electrospray ionization-Q Exactive-Orbitrap-mass spectrometry(UHPLC-ESI-QE-Orbitrap-MS) metabolomics technology. The change trend of endogenous metabolites in rat serum was analyzed to find potential biomarkers. The results showed that Jingfang Mixture regulate 16 biomarkers, mainly including taurine, glutamate, succinic acid, docosahexaenoic acid, and arachidonic acid. Metabolic pathway analysis was carried out by MetaboAnalyst, and P<0.01 was taken as the potential key metabolic pathway. Ten metabolic pathways were closely related to the treatment of chronic urticarial by Jingfang Mixture, mainly involved in the glutamate metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, arachidonic acid metabolism, tricarboxylic acid cycle, unsaturated fatty acid biosynthesis, glutathione metabolism, phenylalanine metabolism, alanine, aspartic acid, and glutamate metabolism, and butyric acid metabolism. Glutamate metabolism and butyric acid metabolism involved more metabolic pathways than others. Therefore, it was speculated that Jingfang Mixture had a balanced regulating effect on the related metabolic pathways which caused the serum disorder in the rats with urticaria, and tended to regulate the metabolic differential to the normal level in the rats with urticaria. This paper provides references for studying the mechanism of Jingfang Mixture from the perspective of endogenous metabolites and metabolic pathways in vivo. At the same time, the endogenous substances explored in this paper can be used as important biomarkers for the prevention of urticaria.
Assuntos
Urticária Crônica , Ratos , Camundongos , Animais , Ácido Araquidônico , Ácido Butírico , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Biomarcadores/metabolismo , Taurina , GlutamatosRESUMO
In this study, a rapid and highly sensitive fluorescence-linked immunosorbent assay for puerarin determination was developed by the conjugation of quantum dots with an antibody against puerarin. The linear range and detection limit of the fluorescence-linked immunosorbent assay were validated. The detection curve (y = -1041ln(x)+5366, R² = 0.999) was linear in the range of 7.8-125 ng/mL. The 50% inhibitory concentration determined by fluorescence-linked immunosorbent assay was 33.8 ng/mL puerarin in water. The limit of detection for PUE was 6.1 ng/mL. To our knowledge, this is the first report on the quantitative detection of a natural product using quantum dots as fluorescent markers. Furthermore, the newly developed fluorescence-linked immunosorbent assay was successfully applied to determine puerarin in several commercial Gegen Qinlian tablets, with a higher sensitivity than that of conventional enzyme-linked immunosorbent assays.
Assuntos
Isoflavonas , Pontos Quânticos , Ensaio de Imunoadsorção Enzimática , Imunoadsorventes , Limite de DetecçãoRESUMO
BACKGROUND: The objective of this study was to analyze the association between tooth loss and uncontrolled diabetes among US adults. METHODS: The authors used National Health and Nutrition Examination Survey data from 2011 through 2018. The sample included 16,635 participants 20 years and older who represent 187,596,215 people in the United States in a probability weighted sample. The authors used bivariate analysis and multiple regressions to analyze factors associated with edentulism and number of missing teeth. RESULTS: The multiple logistic regression model significantly predicted edentulism using diabetes status (adjusted odds ratio controlled diabetes, 1.44 [95% CI, 1.12 to 1.86]; adjusted odds ratio uncontrolled diabetes, 2.26 [95% CI, 1.33 to 3.85]), missing annual dental visits, seeing a dentist only for treatment, family income below 200% of the federal poverty guideline, being female, being 65 years or older, tobacco smoking, and no college education. After controlling for the same covariates, multiple Poisson regression analysis showed that dentate adults with controlled and uncontrolled diabetes had higher relative risk of tooth loss than those without diabetes (adjusted risk ratio controlled diabetes, 1.52 [95% CI, 1.35 to 1.71]; adjusted risk ratio uncontrolled diabetes, 1.57 [95% CI, 1.35 to 1.83]). CONCLUSIONS: US adults with uncontrolled (glycated hemoglobin ≥ 9%) and controlled diabetes (glycated hemoglobin < 9%) were more likely to be edentulous and experience tooth loss than adults without diabetes. PRACTICAL IMPLICATIONS: US health policy officials should adopt benefits policies to provide regular dental examinations to people who have diabetes, have low income (< 200% of the federal poverty guideline), or are 65 years or older to reduce tooth loss and improve their quality of life. Dentists should work with physicians to help patients control glycemic levels.
Assuntos
Diabetes Mellitus , Perda de Dente , Adulto , Diabetes Mellitus/epidemiologia , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Inquéritos Nutricionais , Qualidade de Vida , Perda de Dente/complicações , Perda de Dente/epidemiologia , Estados Unidos/epidemiologiaRESUMO
PURPOSE: Chronic obstructive pulmonary disease (COPD), a progressive and irreversible respiratory disease, becomes the third leading cause of death and results in enormous economic burden on healthcare costs and productivity loss worldwide by 2020. Thus, it is urgent to develop effective anti-COPD drugs. MATERIALS AND METHODS: In the present study, two published GEO profiles were used to re-analyze and ascertain the relationships between circulating miRNAs and bronchial epithelial cells (BECs) mRNAs in COPD. The microRNA levels of miR-361-5p and miR-196-5p in plasma of COPD patients and healthy volunteers were detected by qRT-PCR. Next, the effects of γ-sitosterol (GS) on the expression of miR-361-5p and miR-196-5p and cell proliferation were investigated in BEC and H292 cell lines. Finally, whether specific miRNA-mRNA pathways involved in the effect of GS on BECs was assayed using Western Blot, real-time PCR and immunofluorescence. RESULTS: miR-196-5p and miR-361-5p were, respectively, up- and down-regulated in COPD patients compared with healthy controls. Luciferase assays demonstrated that miR-361-5p and miR-196-5p were, respectively, targeting abca1 and arhgef12 3'UTR in BEAS-2B cells. GS significantly suppressed miR-196-5p and promoted miR-361-5p levels in BEAS-2B cells and inhibited BECs proliferation in vitro. GS promoted miR-361-5p expression, which inhibited BCAT1 mRNA and protein levels and weaken mTOR-pS6K pathway, resulted in anti-proliferation in BEAS-2B cells. In addition, RhoA was activated by ARHGEF12 due to the inhibitory effect of miR-196-5p on arhgef12-3'UTR which was partially abolished by GS suppressing miR-196-5p expression. Activated RhoA further activated ROCK1-PTEN pathway and finally inhibited mTOR pathway, resulting in induced BECs proliferation. The anti-proliferation effect of GS was not observed in H292 cells. CONCLUSION: These findings indicate that miR-361-5p/abca1 and miR-196-5p/arhgef12 axis mediated GS inducing dual anti-proliferation effects on BECs.
Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Transportador 1 de Cassete de Ligação de ATP/genética , Células Epiteliais , Humanos , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Sitosteroides , Transaminases , Quinases Associadas a rhoRESUMO
BACKGROUND: As an inodilator, milrinone is commonly used for patients who undergo coronary artery bypass graft (CABG) surgery because of its effectiveness in decreasing the cardiac index and mitral regurgitation. The aim of this study was to perform a systematic review and meta-analysis of existing studies from the past 20 years to evaluate the impact of milrinone on mortality in patients who undergo CABG surgery. METHODS: We performed a systematic literature search on the application of milrinone in patients who underwent CABG surgery in studies published between 1997 and 2017 in BioMed Central, PubMed, EMBASE, and the Cochrane Central Register. The included studies evaluated milrinone groups compared to groups receiving either placebo or standard treatment and further compared the systemic administration. RESULTS: The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significant difference in mortality between the milrinone group and the placebo/standard care group when patients underwent CABG surgery. In addition, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmia was lower in the milrinone group than in the placebo/standard care group. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction, myocardial ischemia, and arrhythmia was significantly different. However, the occurrence of stroke and renal failure, the duration of inotropic support (h), the need for an intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences. CONCLUSIONS: Based on the current results, compared with placebo, milrinone might be unable to decrease mortality in adult CABG surgical patients but can significantly ameliorate the occurrence of MI, myocardial ischemia, and arrhythmia. These results provide evidence for the further clinical application of milrinone and of therapeutic strategies for CABG surgery. However, along with milrinone application in clinical use, sufficient data from randomized clinical trials need to be collected, and the potential benefits and adverse effects should be analyzed and reevaluated.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/cirurgia , Milrinona/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Fármacos Cardiovasculares/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Milrinona/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Implants with platform-switching (PS) design have been demonstrated to reduce marginal bone loss. However, the influence on peri-implant soft tissue healing is unclear. This study was designed to investigate its effect on peri-implant soft tissue healing after implant uncovery. METHODS: Non-smokers needing two implants in different quadrants were recruited in this study. For each individual, one PS and one platform-matching (PM) implants were placed using two-stage protocol. Following 2 to 8 months of healing, all implants were uncovered and connected to the corresponding healing abutments. Clinical measurements and peri-implant crevicular fluid (PICF) were taken at 1-, 2-, 4-, and 6-week after 2nd stage surgery. The cytokine concentrations in PICF were analyzed. Peri-implant mucosa (1 × 2 × 2 mm) was harvested around the healing abutment for the analysis of gene expression at uncovery and 6-week post-uncovery. RESULTS: Eighteen participants (nine males; 51.7 ± 14.9 years) were recruited. Compared to PM, PS showed significantly lower probing depth (PD) at 1- and 2-week as well as modified sulcus bleeding index (mSBI) at 1-, 4-, and 6-week (P < 0.05). Over time, a decrease in osteoprotegerin and interleukin-1ß concentrations in PICF along with an increase in receptor activator of unclear factor kappa-B ligand, periostin, and peroxidasin gene expressions in peri-implant mucosa were noted within both groups (P < 0.05) without significant intergroup differences. CONCLUSION: Within the limits, implants with PS design rendered significant benefits over PM design in PD and mSBI reduction during a 6-week healing. However, molecular changes within PICF and peri-implant mucosa as a response to PM and PS appear negligible.
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Implantes Dentários , Citocinas , Implantação Dentária Endóssea , Masculino , CicatrizaçãoRESUMO
PURPOSE: To compare the efficacy and safety profile of S-1-based versus non-S-1-based chemotherapy as first-line treatment in mCRC. METHODS: Relevant randomized controlled trials (RCTs) were obtained from PubMed, Embase, and Ovid databases and the Cochrane library from database set up in May 2018. The RCTs of S-1-based monotherapy or combination therapy as first-line treatment were selected. The impact of S-1-based chemotherapy on progression-free survival (PFS) and overall survival (OS) was assessed by pooling data via RevMan 5.3. RESULTS: Meta-analysis of 10 RCTs showed that S-1-based chemotherapy significantly improved PFS (HR 0.90, 95% CI 0.84-0.97, P = 0.006). In subgroup analysis, there was a statistically significant increase in PFS when S-1-based chemotherapy was compared with 5-FU-based (HR 0.92, 95% CI 0.84-1.00, P = 0.04) or capecitabine-based chemotherapy (HR 0.85, 95% CI 0.73-0.99, P = 0.04). The meta-analysis of OS (HR 0.95, 95% CI 0.86-1.05, P = 0.36), overall response rate (ORR) (HR 0.99, 95% CI 0.84-1.17, P = 0.90), and disease control rate (DCR) (HR 1.61, 95% CI 0.87-3.00, P = 0.13) showed no statistical significance between S-1-based and non-S-1-based chemotherapy. The statistically significant differences in the meta-analysis indicated less incidence of graded 3-4 leucopenia (OR = 0.30, 95% CI 0.13-0.71, P = 0.006) and hand-foot syndrome (HFS) (OR = 0.24, 95% CI 0.10-0.58, P = 0.001) in the S-1-based chemotherapy, and there was no statistically significant difference for other adverse events. CONCLUSIONS: S-1-based chemotherapy in mono or combined therapy was an attractive alternative to standard first-line regimen for patients of mCRC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , HumanosRESUMO
INTRODUCTION: This case report introduces a technique for managing oroantral communication (OAC) using a collagen membrane strip to repair the perforated sinus membrane and simultaneously graft the alveolar ridge. CASE PRESENTATION: A 55-year-old Asian male presented for a second-opinion consultation regarding an endosseous dental implant that had been placed overly subcrestal at #13 edentulous site. The 8 mm fixture had been placed 3 to 4 mm subcrestally with more than half the implant length into the maxillary sinus. The patient stated that no sinus augmentation procedure had been performed. The implant was considered to be non-restorable and treatment planned for explantation with ridge preservation. Explantation revealed a sinus perforation with OAC. A collagen membrane strip (30 × 6 mm) was folded into a U-shape, to hold bone allograft for ridge preservation, and placed with the bottom of the U-shape level with the sinus floor and the ends extending to the buccal and palatal, beyond the crest. A second collagen membrane covered the graft at ridge crest level, followed by primary closure. Implant placement (4.1 × 10 mm) with indirect sinus augmentation was performed in 6 months. The implant was uncovered and subsequently restored following a 5-month osseointegration period. The 13-month follow-up examination revealed successful outcomes, with normal clinical and radiographic parameters. CONCLUSION: This novel technique achieved the dual goals of ridge preservation and repair of a sinus membrane perforation simultaneously after implant explantation in the posterior maxilla. It further allowed a successful implant placement with simultaneous sinus augmentation and subsequent restoration.
Assuntos
Aumento do Rebordo Alveolar , Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Colágeno , Implantação Dentária Endóssea/efeitos adversos , Implantes Dentários/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: TGF-ß-induced alveolar epithelial cells apoptosis were involved in idiopathic pulmonary fibrosis (IPF). This study aimed to explore potential targets and mechanisms of IPF. MAIN METHODS: mRNA and microRNA arrays were used to analyze differentially expressed genes and miRNAs. Several essential targets of TGF-ß-SMADs and TGF-ß-PI3K-AKT pathways were detected. KEY FINDINGS: miR-31 and miR-184 expression levels were positively correlated with smad6 and smad2/akt expression levels in IPF patients. TGF-ß could induce miR-31 and suppress miR-184 levels in A549 cells. miR-31 was confirmed to bind to the smad6-3'UTR and functionally suppress its expression. Down-regulated SMAD6 enhanced SMAD2/SMAD4 dimer formation and translocation due to its failure to prevent SMAD2 phosphorylation. In contrast, anti-fibrotic functions of miR-184 were abolished due to TGF-ß directly suppressing miR-184 levels in A549 cells. When A549 was stimulated by TGF-ß combined with or without miR-31 inhibitor/miR-184 mimic, it was showed that depleted miR-31 and/or increased miR-184 significantly ameliorated TGF-ß-induced viability of A549 cells, as well as inhibited the expression of profibrotic factors, MMP7 and RUNX2. SIGNIFICANCE: Inhibiting miR-31 and/or promoting miR-184 protect against TGF-ß-induced fibrogenesis by respectively repressing the TGF-ß-SMAD2 and TGF-ß-PI3K-AKT signaling pathways, implying that miR-31/184 are potential targets and suggesting a new management strategy for IPF.
Assuntos
Células A549/metabolismo , Apoptose/efeitos dos fármacos , Fibrose Pulmonar Idiopática/metabolismo , MicroRNAs/fisiologia , Fator de Crescimento Transformador beta/farmacologia , Imunofluorescência , Humanos , Imunoprecipitação , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Proteína Smad2/metabolismoRESUMO
BACKGROUND: Treatment of furcation-involved molars presents a clinical challenge. This study retrospectively investigates the demographic parameters affecting treatment decisions and outcomes of root-resected molars using a nationwide population-based dataset. METHODS: De-identified data from 471 eligible patients were obtained from a representative cohort composed of 1 million of Taiwan's population. Demographic factors that influence treatment decisions and outcomes of root-resected teeth were examined. Cox regression was performed to statistically analyze the factors. RESULTS: The overall survival rate for root-resected molars was 91.1%. The survival times of the extracted and surviving teeth were 303.0 ± 274.6 and 551.8 ± 327.2 days, respectively (P <0.001). The analyzed patient-related factors, such as living district, urbanization level, medical institution, and monthly income, have remarkable influence on treatment decisions; however, there is no statistically significant difference in survival rate between root-resected molars receiving flap surgery and those that do not (P = 0.504). After adjusting for other factors, patients aged >74 years have 3.33 times (hazard ratio = 3.33; 95% CI = 1.04 to 10.66; P = 0.043) higher rates of molar extraction than younger counterparts. CONCLUSIONS: The overall survival rate of root-resected molars was satisfactory. Patients with advanced age (>74 years) had a higher risk of extraction occurrence on resected molars. Patient-related factors may influence the treatment decision of whether molars receive flap surgery. These findings suggest that demographic factors should be carefully evaluated before and after performing root-resection procedures because these factors may eventually impact the outcome of root-resected molars.
Assuntos
Tomada de Decisões , Defeitos da Furca/cirurgia , Dente Molar/cirurgia , Planejamento de Assistência ao Paciente , Raiz Dentária/cirurgia , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Hospitais/estatística & dados numéricos , Humanos , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prática Privada/estatística & dados numéricos , Modelos de Riscos Proporcionais , Características de Residência/estatística & dados numéricos , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgia , Taxa de Sobrevida , Taiwan , Extração Dentária/estatística & dados numéricos , Resultado do Tratamento , UrbanizaçãoRESUMO
PURPOSE: To assess the effective distribution of blood supply in jejunal graft with the 3rd intestinal artery as pedicle and to afford a reliable theoretic base for clinical esophageal reconstruction. METHODS: Thirty-two formalin-preserved and 21 fresh cadaver specimens were studied with anatomic measurement, acetic ester perfusion, and Acrylonitrile butadiene styrene (ABS) vascular casting specimen. RESULTS: Results demonstrate there is no significant variation of vascular in the two groups. The inner diameter of the 3rd intestinal artery is comparatively larger among five intestinal arteries. There is a wider distribution of efficient blood supply in the 3rd intestinal artery. The mean (SD) length of homogenously stained jejunum segment, and the mean (SD) ABS effective distributing length of extended arches are 142.2 (62.3) cm and 30.8 (7.3) cm, respectively. CONCLUSIONS: The 3rd intestinal artery as pedicle can afford adequate blood supply to the jejunum segment and has effective arterial arch with enough length; thus it meets the need of esophageal reconstruction.
Assuntos
Jejuno/irrigação sanguínea , Jejuno/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/transplante , Adulto , Cadáver , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: To study the reconstruction of partial defects at the end of the thumbs and other fingers with microsurgical free toe flaps. METHODS: 21 partial defects (19 cases) at the end of thumbs and other fingers were reconstructed with microsurgical free toe flaps taking from the corresponding toe part. RESULTS: All the free flaps survived. The patients were followed up for 3 - 6 months. The aesthetic and functional results were both satisfactory. The two-point-discrimination distance was 4 - 6 mm. CONCLUSIONS: The microsurgical free toe flaps have good therapeutic effect for the reconstruction of partial defects at the end of the fingers.
Assuntos
Traumatismos dos Dedos/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Transplante de Pele , Retalhos Cirúrgicos , Polegar/lesões , Polegar/cirurgia , Dedos do Pé/cirurgia , Adulto JovemRESUMO
OBJECTIVE: In partial loss of distal finger segment, a corresponding part of the toe tissue compound is harvested and transplanted for repair or reconstruction. This new procedure gives forth a new concept and is called decorative repair or reconstruction. METHODS: In a series of 77 patients with 88 thumb and/or finger subtotal defects in forms of lateral half, dorsal half or volar half composite tissue defects were reconstructed with lateral nail-skin flap, dorsal skin-nail flap or pulp flap taken from corresponding part of the toes. The blood circulations were re-established by anastomosing digital arteries of the toe transplants and fingers. RESULTS: In this series 75 patients with 78 fingers reconstructed are successful. The overall survival rate is 97.5%. Follow-up examinations made half to 12 years postoperatively showed the fingers are having a normal length, outward appearance and function. There are nails preserved. The pulps are full. Sweating function are present. Two-point-discrimination tests are between 4-6 mm. CONCLUSION: By decorative reconstruction of subtotal dorsal, lateral, or volar halves defect of thumb and/or fingers by transplanting corresponding part of soft tissue taken from the toe has the merit of repair of any parts of tissue loss precisely what is needed. This procedure is better than any traditional toe-to-hand transfer and realizing the exact meaning of decorative reconstruction.