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Pou4f3 plays an important role in the development of hair cells in the inner ear sensory epithelia. Autophagy is related to the auditory damage. However, the role and mechanism of Pou4f3 on drug-induced ototoxicity are incompletely understood. Hence, this study aimed to explore the effects of Pou4f3 on the apoptosis of cochlear hair cells (CHCs) and to explore whether autophagy was involved in this process. The cisplatin was used to produce a loss of CHCs to create a murine model of deafness. The AAV vectors were delivered into the scala media through the lateral wall. Compared with the control mice, the cisplatin-treated mice exhibited significantly enhanced apoptosis and autophagy in the cochleae, accompanied by a notably decreased Pou4f3 levels. Both mutation and knockdown of Pou4f3 promoted the apoptosis- and autophagy-related protein levels, and enhanced the cisplatin-induced levels of apoptosis- and autophagy-related proteins. Furthermore, the autophagy activator rapamycin promoted the apoptosis and autophagy in the cochlea. In addition, the autophagy inhibitor 3-MA overturned the promoting effect of Pou4f3 knockdown on the apoptosis and autophagy. Collectively, in cisplatin-induced deafness mice, the Pou4f3 gene mutation facilitated apoptosis of cochlear hair cells, at least partially, through inducing autophagy.
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Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cisplatino/efeitos adversos , Surdez/induzido quimicamente , Proteínas de Homeodomínio/genética , Fator de Transcrição Brn-3C/genética , Animais , Surdez/genética , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MutaçãoRESUMO
Long noncoding RNAs (lncRNAs) have been reported to play diverse roles in biologic and pathologic processes, including myogenesis. We found that lncRNA AK017368 is highly expressed in skeletal muscle cells. Functional analyses showed that overexpression of AK017368 promoted proliferation and restrained differentiation of myoblasts; whereas inhibition of AK017368 had completely opposite effects in vitro In mice, knockdown of AK017368 promoted muscle hypertrophy in vivo RNA molecules of AK017368 acted mechanistically as competing endogenous RNAs to target micro-RNA (miR)-30c, which was supported by the results of bioinformatics analyses and dual-luciferase reporter assays. It has been shown that lncRNA AK017368 competes with trinucleotide repeat containing-6A (Tnrc6a) for miR-30c. Tnrc6a was previously reported to promote proliferation and inhibit differentiation of myoblast cells, whereas miR-30c targets the 3'-UTR of Tnrc6a mRNA to weaken its function. Taken together, lncRNA AK017368 promotes proliferation and inhibits differentiation of myoblast cells by attenuating function of miR-30c.-Liang, T., Zhou, B., Shi, L., Wang, H., Chu, Q., Xu, F., Li, Y., Chen, R., Shen, C., Schinckel, A. P. lncRNA AK017368 promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c.
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MicroRNAs/genética , Desenvolvimento Muscular/genética , Desenvolvimento Muscular/fisiologia , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo , RNA Longo não Codificante/genética , Animais , Autoantígenos/genética , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/genética , Proliferação de Células/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/química , MicroRNAs/metabolismo , Modelos Biológicos , Músculo Esquelético/citologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , RNA Longo não Codificante/química , RNA Longo não Codificante/metabolismoRESUMO
To characterize the effects of several subtherapeutic antibiotic combinations on the abundance and diversity of fecal microbes, 400 weaned pigs were selected and randomly assigned to 8 groups, where they were continuously fed different antibiotic combinations for 28 days. Then, a total of 48 pigs were randomly selected to collect feces samples for DNA extraction and 16S rRNA high-throughput sequencing. Compared with that of pigs without antibiotic administration, the diversities of fecal microbes were decreased in the pigs fed chlortetracycline (CTC), olaquindox (OLA), and either enramycin (ER) or virginiamycin (VIR), and the relative abundances of members of the phylum Bacteroidetes and the genus Prevotella were increased. Compared with that of pigs without antibiotic administration, the relative abundances of members of the phylum Proteobacteria and the genus Succinivibrio were decreased in the pigs fed CTC, a mixture of zinc bacitracin (ZB) + colistin sulfate (COL), a mixture of CTC+ZB+COL, a mixture of CTC+OLA, or a mixture of CTC+OLA+ER. α-Diversity and ß-diversity were decreased (P < 0.05) in the pigs fed ZB+COL or a mixture of CTC+OLA+ER or CTC+OLA+VIR. This study provides experimental data to deepen our understanding on the effects of antibiotic combinations on intestinal microbes.
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Ração Animal , Antibacterianos/farmacologia , Animais , Antibacterianos/administração & dosagem , Biodiversidade , Quimioterapia Combinada , Fezes/microbiologia , RNA Ribossômico 16S , SuínosRESUMO
Medical image segmentation is a critical task for clinical diagnosis and research. However, dealing with highly imbalanced data remains a significant challenge in this domain, where the region of interest (ROI) may exhibit substantial variations across different slices. This presents a significant hurdle to medical image segmentation, as conventional segmentation methods may either overlook the minority class or overly emphasize the majority class, ultimately leading to a decrease in the overall generalization ability of the segmentation results. To overcome this, we propose a novel approach based on multi-step reinforcement learning, which integrates prior knowledge of medical images and pixel-wise segmentation difficulty into the reward function. Our method treats each pixel as an individual agent, utilizing diverse actions to evaluate its relevance for segmentation. To validate the effectiveness of our approach, we conduct experiments on four imbalanced medical datasets, and the results show that our approach surpasses other state-of-the-art methods in highly imbalanced scenarios. These findings hold substantial implications for clinical diagnosis and research.
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Algoritmos , Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
Ag-Sn-In-Ni-Te alloy ingots were produced through a heating-cooling combined mold continuous casting technique; they were then drawn into wires. However, during the drawing process, the alloy wires tended to harden, making further diameter reduction challenging. To overcome this, heat treatment was necessary to soften the previously drawn wires. The study investigated how variations in heat treatment temperature and holding time affected the microstructure, microhardness and corrosion resistance of the alloy wires. The results indicate that the alloy wires subjected to heat treatment at 700 °C for 2 h not only exhibited a uniform microstructure distribution, but also demonstrated low microhardness and excellent corrosion resistance.
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OBJECTIVE: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults. METHODS: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554. RESULTS: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I2 between the studies was low. CONCLUSIONS: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
To our knowledge, this is the first network meta-analysis comparing the available data on adult patients with episodic tension-type headache (ETTH) treated with different simple analgesics recommended by the current guidelines.Ibuprofen (400 mg) and diclofenac-K (12.5 mg, 25 mg) are potentially the most effective and safe treatment options, supported by high-quality evidence.
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Analgésicos , Ibuprofeno , Metanálise em Rede , Cefaleia do Tipo Tensional , Humanos , Cefaleia do Tipo Tensional/tratamento farmacológico , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Analgésicos/administração & dosagem , Adulto , Ibuprofeno/efeitos adversos , Ibuprofeno/administração & dosagem , Ibuprofeno/uso terapêutico , Acetaminofen/uso terapêutico , Acetaminofen/efeitos adversos , Acetaminofen/administração & dosagem , Teorema de Bayes , Resultado do Tratamento , Diclofenaco/efeitos adversos , Diclofenaco/uso terapêutico , Diclofenaco/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Naproxeno/uso terapêutico , Naproxeno/efeitos adversos , Naproxeno/administração & dosagem , Cetoprofeno/efeitos adversos , Cetoprofeno/uso terapêutico , Cetoprofeno/administração & dosagem , Cetoprofeno/análogos & derivados , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , MasculinoRESUMO
Some HIV-infected individuals receiving ART develop low-level viremia (LLV), with a plasma viral load of 50-1000 copies/mL. Persistent low-level viremia is associated with subsequent virologic failure. The peripheral blood CD4+ T cell pool is a source of LLV. However, the intrinsic characteristics of CD4+ T cells in LLV which may contribute to low-level viremia are largely unknown. We analyzed the transcriptome profiling of peripheral blood CD4+ T cells from healthy controls (HC) and HIV-infected patients receiving ART with either virologic suppression (VS) or LLV. To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV, KEGG pathways of differentially expressed genes (DEGs) were acquired by comparing VS with HC (VS-HC group) and LLV with VS (LLV-VS group), and overlapped pathways were analyzed. Characterization of DEGs in key overlapping pathways showed that CD4+ T cells in LLV expressed higher levels of Th1 signature transcription factors (TBX21), toll-like receptors (TLR-4, -6, -7 and -8), anti-HIV entry chemokines (CCL3 and CCL4), and anti-IL-1ß factors (ILRN and IL1R2) compared to VS. Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription. Finally, we evaluated the effects of 4 and 17 transcription factors that were upregulated in the VS-HC and LLV-VS groups, respectively, on HIV-1 promoter activity. Functional studies revealed that CXXC5 significantly increased, while SOX5 markedly suppressed HIV-1 transcription. In summary, we found that CD4+ T cells in LLV displayed a distinct mRNA profiling compared to that in VS, which promoted HIV-1 replication and reactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV. CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.
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Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Linfócitos T , Viremia/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , Carga Viral , Fatores de Transcrição/genética , Perfilação da Expressão Gênica , Linfócitos T CD4-Positivos , Fármacos Anti-HIV/farmacologia , Proteínas de Ligação a DNA/genéticaRESUMO
Copper-coated graphite and copper mixture powders were deposited on AZ31B magnesium alloy and 6061 T6 aluminum alloy substrates under different process parameters by a solid-state cold spray technique. The microstructure of the copper-coated graphite and copper composite coatings was visually examined using photographs taken with an optical microscope and a scanning electron microscope. The surface roughness of the coatings was investigated with a 3D profilometer. The thickness of the coatings was determined through the analysis of the microstructure images, while the adhesion of the coatings was characterized using the scratch test method. The results indicate that the surface roughness of the coatings sprayed on the two different substrates gradually decreases as gas temperature and gas pressure increase. Additionally, the thickness and adhesion of the coatings deposited on the two different substrates both increase with an increase in gas temperature and gas pressure. Comparing the surface roughness, thickness, and adhesion of the coatings deposited on the two different substrates, the surface roughness and adhesion of the coatings on the soft substrate are greater than those of the coatings on the hard substrate, while the thickness of the coatings is not obviously affected by the hardness of the substrate. Furthermore, it is noteworthy that the surface roughness, thickness, and adhesion of the copper-coated graphite and copper composite coatings sprayed on the two different substrates exhibit a distinct linear relationship with particle velocity.
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INTRODUCTION: Hearing loss is one of the most common sensory disorders. Recent findings have shown that the apoptotic program and autophagy are related to hearing loss. The aim of the study was to explore the effects of noise and cisplatin exposure on apoptosis and autophagy in the hair cells of the cochleae. MATERIAL AND METHODS: C57BL/6 mice were randomly divided into 3 groups (n = 10 for each): the control group, the noise model group and the cisplatin model group. Auditory brainstem response (ABR) measurements were used to detect the hearing thresholds. TUNEL assay was used to evaluate cell apoptosis. Western blot and immunofluorescence were performed to examine the apoptosis- and autophagy-related proteins. RESULTS: The mice exhibited substantial hearing loss after noise and cisplatin exposure. Additionally, more TUNEL positive cells were observed in the mice after noise and cisplatin exposure compared with the control group. Moreover, the protein expression levels of Beclin-1, LC3-II, Bax and cleaved caspase-3 were significantly increased, while the expression of Bcl-2 was notably decreased in the cochlea after noise (p = 0.0278, 0.0075, 0.0142, 0.0158, 0.0131 respectively) and cisplatin (p = 0.0220, 0.0075, 0.0024, 0.0161, 0.0452 respectively) exposure compared with the control group. Besides, the ratio of LC3-II/LC3-I was substantially higher in the mice treated by cisplatin (p = 0.0046) and noise (p = 0.0220) compared with the control group. CONCLUSIONS: Our findings demonstrated for the first time that noise and cisplatin exposure promoted apoptosis and autophagy in the hair cells of the cochleae. This study provides new insights into the mechanisms of noise- or cisplatin-induced hearing loss.
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OBJECTIVE: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study. MATERIALS AND METHODS: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology. RESULTS: The zeta potential of the mPEG-PCL-ART-NPs was about -38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM. CONCLUSION: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.
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Artemisininas/administração & dosagem , Artemisininas/farmacologia , Gentamicinas/efeitos adversos , Perda Auditiva/tratamento farmacológico , Hidrogéis/administração & dosagem , Animais , Artemisininas/farmacocinética , Sistemas de Liberação de Medicamentos , Etilenoglicóis/química , Gelatina , Cobaias , Células HeLa , Perda Auditiva/induzido quimicamente , Humanos , Hidrogéis/química , Metacrilatos/química , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/químicaRESUMO
To evaluate effects of tail docking and/or teeth clipping on sows and their piglets, a total of 24 sows and their 302 piglets at 3 days of age were randomly allocated to one of four treatments: teeth clipping and tail docking (TCTD), teeth clipping (TC), tail docking (TD), or intact teeth and tail (Intact). Behavior of piglets and sows, lesions on the body and tail of piglets and sows' teats were inspected. Heart rates of processed piglets were increased (p < .01) during the procedures. Teeth clipping decreased body surface temperature (p < .01) of piglets during and after the procedures but tail docking did not (p > .01). Processed piglets spent more (p < .05) time lying alone and playing/fighting than sham-processed piglets. Tail docked piglets spent less (p < .01) time standing than tail sham-docked piglets. Intact teeth increased (p < .05) the avoidance behaviors of sows. Teeth clipping decreased (p < .05) the lesion scores on the anterior, middle, and posterior teats. Taken together, piglet teeth clipping had more impact on sows and their piglets than tail docking did in the lactation period based on our findings.
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Criação de Animais Domésticos , Comportamento Animal/fisiologia , Glândulas Mamárias Animais/lesões , Animais , Feminino , Masculino , Suínos , Cauda/cirurgia , Dente/cirurgiaRESUMO
Liver cancer is the second leading cause of cancer mortality worldwide. Safer and more effective diagnostic methods for liver cancer are desirable, and biomarkers represent a potentially alternative method for diagnosis. The present study was designed to identify liver cancer biomarkers. We quantified the changes in serum protein levels between liver transplantation and healthy (control) females using isobaric tags for relative and absolute quantitation (iTRAQ) as well as proteomic analysis. A total of 1399 proteins were identified; of these, three proteins showed significantly different concentrations between the before transplantation group and the control group. These proteins may thus be relevant to liver cancer and constitute potential liver cancer biomarkers.
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Estrus expression by gilts and sows is hereditable and important for heat detection. To better understand the molecular biological mechanisms of estrus expression in gilts, the mRNA expression profiles of follicular tissue from Large White gilts in diestrus (LD, n = 3) and estrus (LE, n = 3), and Chinese indigenous Mi gilts in diestrus (MD, n = 2) and estrus (ME, n = 3) were investigated using RNA sequencing. We detected 122,804-335,295 SNPs, 6,140-14,947 InDel and 12 types of AS events (39.57% TSS, 34.90% TTS) in 11 samples. A total of 2,838 differentially expressed genes (DEGs) were found in LD vs MD, LE vs ME, LE vs LD, or ME vs MD comparisons. Two DEGs (ACP5 and PIGS) were observed in all comparisons. Two new genes (ENSSSCG00000028235 and ENSSSCG00000021903) were exclusively expressed in Mi and Large White gilts, respectively. Bioinformatics analyses indicate that these DEGs are involved in single-organism process, catalytic activity, cell adhesion and enriched in ECM-receptor interaction, olfactory transduction, ovarian steroidogenesis, steroid biosynthesis and CAMs signaling pathways. These results of RNA-Seq have provided important information for screening the key functional genes or molecular markers of estrus expression in gilts.
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Cruzamento , Estro/genética , Perfilação da Expressão Gênica , Genoma , Folículo Ovariano/metabolismo , Sus scrofa/genética , Processamento Alternativo/genética , Animais , Feminino , Ontologia Genética , Mutação INDEL/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Transcriptoma/genéticaRESUMO
The presence of antibiotic resistance genes (ARGs) is one of the most important public health concerns. Six tetracycline resistance genes (TRGs-tetA, tetC, tetL, tetO, tetW, and tetX) were quantified using real-time quantitative polymerase chain reaction (qPCR) in the fecal microorganisms of weaned pigs. Two hundred 35-day-old weaned pigs were fed different dietary antibiotics for 28 days: (1) no antibiotic as the control treatment (CT); (2) chlortetracycline, bacitracin zinc and colistin sulfate (CBC); (3) bacitracin zinc and colistin sulfate (BC); and (4) chlortetracycline (CTC). The detection frequencies (DFs) of tetC, tetL, and tetW were 100 %; and the DFs of tetA, tetD, tetM, tetO, and tetX were 65 %. The relative abundances (tet/16S rRNA gene copy numbers) of six tet genes (tetA, tetC, tetL, tetO, tetW and tetX) were between 1.5 × 10(-4) and 2.0 × 10(-1). In the group CTC, the relative abundances of tetC (P < 0.01), tetL (P < 0.01), tetO (P < 0.05), tetW (P < 0.01), and tetX (P < 0.01) were greater than those of the group CT. Compared with the group CTC, the relative abundances of tetC (P < 0.01), tetL (P < 0.01), and tetW (P < 0.01) were decreased in the CBC and BC groups. These results indicate that a combination of different antibiotics suppressed the abundance increase of a part of tet genes, which suggests that a combination of antibiotics produces multiple selection pressures on fecal microorganism of pigs.
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Antibacterianos/análise , Fezes/microbiologia , Resistência a Tetraciclina , Animais , Genes Bacterianos , RNA Ribossômico 16S/genética , Suínos , Tetraciclina/farmacologiaRESUMO
Observation of gravity erosion in the field with strong sunshine and wind poses a challenge. Here, a novel topography meter together with a movable tent addresses the challenge. With the topography meter, a 3D geometric shape of the target surface can be digitally reconstructed. Before the commencement of a test, the laser generator position and the camera sightline should be adjusted with a sight calibrator. Typically, the topography meter can measure the gravity erosion on the slope with a gradient of 30°-70°. Two methods can be used to obtain a relatively clear video, despite the extreme steepness of the slopes. One method is to rotate the laser source away from the slope to ensure that the camera sightline remains perpendicular to the laser plane. Another way is to move the camera farther away from the slope in which the measured volume of the slope needs to be corrected; this method will reduce distortion of the image. In addition, installation of tent poles with concrete columns helps to surmount the altitude difference on steep slopes. Results observed by the topography meter in real landslide experiments are rational and reliable.
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AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis (XGC) clinically. METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma (GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section (FS) analysis and surgical procedure data of these patients were collected and analyzed. RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven (17%) cases presented with mild jaundice without choledocholithiasis. Thirty-five (83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29 (69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40 (95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon's macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon's macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups (21% vs 20%, P > 0.05). CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide a practical and effective standard in the differential diagnosis between XGC and GBC.
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Colecistite/diagnóstico , Erros de Diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Vesícula Biliar/patologia , Granuloma/diagnóstico , Xantomatose/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistite/diagnóstico por imagem , Colecistite/patologia , Colecistite/cirurgia , Diagnóstico Diferencial , Feminino , Secções Congeladas , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Granuloma/diagnóstico por imagem , Granuloma/patologia , Granuloma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Procedimentos Desnecessários , Xantomatose/diagnóstico por imagem , Xantomatose/patologia , Xantomatose/cirurgiaRESUMO
Objective. To determine the association between Yang-Deficient Constitution and the clinical outcomes of HIV/AIDS patients who have initiated highly active antiretroviral therapy (HAART). Method. A total of 197 antiretroviral-naive adults who initiated HAART between 2009 and 2011 were recruited. The participants were asked to complete a questionnaire twice to assess their Yang-Deficient Constitution status before HAART. During the study, signs and symptoms and CD4 or CD8 T cell counts were recorded. Routine blood and biochemical tests were conducted. For the patients who were found to have infections, pathologic examination was performed. Statistical test of association of clinical attributes and demographic factors with Yang-Deficient Constitution was conducted. Result. Good test-retest reliability was observed for Yang-Deficient Constitution scoring. The median Yang-Deficient Constitution score of 142 eligible participants was 25. Female (score = 32.14, P < 0.05), hepatotoxicity (32.14, P < 0.1), nephrotoxicity (37.50, P < 0.1), total number of adverse events (P < 0.1), and mortality (39.29, P < 0.05) were associated with Yang-Deficient Consitution, while annual changes or nadir values of CD4 or CD8 T lymphocytes, and newly acquired infections after starting HAART were not. Mortality was also associated with total number of adverse events (P < 0.05), hepatotoxicity (P < 0.05), and nephrotoxicity (P < 0.05). Conclusion. Yang-Deficient Constitution score has a potential to be developed as a predictor for early HIV-related mortality and side effects. The interrelation and underlying mechanisms should be further investigated for evidence-based design of a more appropriate treatment strategy.
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OBJECTIVE: To explore the correlation between the incidence of birth defects and the contents of soil elements so as to provide a scientific basis for screening the related pathogenic factors that inducing birth defects for the development of related preventive and control strategies. METHODS: MapInfo 7.0 software was used to draw the maps on spatial distribution regarding the incidence rates of birth defects and the contents of 11 chemical elements in soil in the 33 studied areas. Variables on the two maps were superposed for analyzing the spatial correlation. SAS 8.0 software was used to analyze single factor, multi-factors and principal components as well as to comprehensively evaluate the degrees of relevance. RESULTS: Different incidence rates of birth defects showed in the maps of spatial distribution presented certain degrees of negative correlation with anomalies of soil chemical elements, including copper, chrome, iodine, selenium, zinc while positively correlated with the levels of lead. Results from the principal component regression equation indicating that the contents of copper(0.002), arsenic(-0.07), cadmium(0.05), chrome (-0.001), zinc (0.001), iodine(-0.03), lead (0.08), fluorine(-0.002)might serve as important factors that related to the prevalence of birth defects. CONCLUSION: Through the study on spatial distribution, we noticed that the incidence rates of birth defects were related to the contents of copper, chrome, iodine, selenium, zinc, lead in soil while the contents of chrome, iodine and lead might lead to the occurrence of birth defects.
Assuntos
Anormalidades Congênitas/epidemiologia , Monitoramento Ambiental , Solo/química , Pré-Escolar , Anormalidades Congênitas/prevenção & controle , Geografia , Humanos , PrevalênciaRESUMO
PURPOSE: In our previous publication, we have shown that dihydroartemisinin could significantly inhibit the growth of CML K562 cells by its anti-proliferative and inducing apoptotic effects. Given the pivotal effect of Bcr/Abl tyrosine kinase and its downstream signal factors on CML cell proliferation and survival, we extend our study to investigate the effect of DHA on Bcr/Abl and related signal factors to further illuminate the possible mechanisms of the effect of DHA on CML cells. METHODS: The expression of Bcr/Abl was analyzed with PCR and Western blotting methods at both mRNA and protein levels. Measurement of protein expression and tyrosine phosphorylation activity of Bcr/Abl, AKT, ERK1/2, NF-κB and cytochrome c were performed with Western blotting and immunoprecipitation methods. Using the activity kits analyzed the activity of caspase 9 and caspase 3. RESULTS: The treatment with DHA results in a significant suppression on Bcr/Abl expression and leads to a concentration-dependent reduction on the Bcr/Abl tyrosine activity. Moreover, it also results in a strong influence on the downstream signal factors of Bcr/Abl, which includes inhibition of tyrosine kinase activity of AKT and ERK1/2, suppression of NF-κB protein expression, promotion of the cytochrome c release and the consequential activation of caspase 3/9 in CML K562 cells. CONCLUSIONS: Together with our previous report, our data show that the growth inhibitory effect of DHA on CML cells might be due to the influence on Bcr/Abl expression and its downstream signal factors. DHA might be a potential novel anti-CML drug candidate and worthy of further study.