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BACKGROUND: Parkinson's disease (PD) is a serious neurodegenerative disease that brings great stress to the physical and mental health of patients. At the same time, long-term treatment will also bring great economic losses and social burden to the family and society, especially after COVID-19 pandemic. The aim of this study is to analyze the current status of stress perception and anxiety in patients with PD and explore the influencing factors after the COVID-19 pandemic. METHODS: This study used the convenient sampling method to select the research objects of patients with PD who were outpatients or inpatients in a general public hospital in Hangzhou, Zhejiang Province, and the survey time was from February 2023 to March 2023. The measurements included the General information questionnaire, The Perceived Stress Scale (PSS) and The Self Rating Anxiety Scale (SAS). SPSS 21.0 software was used for data statistical analysis. RESULT: 394 out of 420 patients with PD completed the questionnaire. The stress perception score of PD was (16.41 ± 6.435) and the anxiety score was (54.77 ± 10.477). The stress perception scores of patients with PD were significantly different in gender, age, educational, occupation, nature of costs, time of sleep, quality of sleep, duration of disease, way of medical treatment and anxiety level (p < 0.05). Among them, age, duration of disease, public expenses, online remote therapy and anxiety level were the main influencing factors of stress perception in patients with PD (p < 0.05). Besides, there were significant differences in gender, educational, nature of costs, time of sleep, quality of sleep and duration of disease in anxiety among patients with PD (p < 0.05). CONCLUSION: After the COVID-19 pandemic, the level of stress perception and anxiety in patients with PD is high, and the influencing factors are complex.
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Ansiedad , COVID-19 , Enfermedad de Parkinson , Estrés Psicológico , Humanos , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/epidemiología , COVID-19/psicología , COVID-19/epidemiología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Estrés Psicológico/psicología , Anciano , Ansiedad/psicología , Encuestas y Cuestionarios , China/epidemiología , Adulto , Anciano de 80 o más AñosRESUMEN
The genus Rhynchospio has fronto-lateral horns on prostomium, paired branchiae from chaetiger 2 to near the posterior end, capillary notochaetae only, and more than two pairs of pygidial cirri. Rhynchospio species are common in coastal soft bottom communities; nevertheless, many recorded Rhynchospio specimens around the world are currently undescribed. Here we described a Rhynchospio species based on specimens collected from Qingdao, China. Comparison with the reported DNA sequences of four gene markers (16S rRNA, 18S rRNA, 28S rRNA, and Histone H3) and brief morphological description of specimens collected from Jinhae Bay, South Korea, previously reported as Rhynchospio aff asiatica, indicated that they are conspecific. Morphologically, specimens of R. aff. asiatica from Qingdao are characterized by having neuropodial hooded hooks from chaetigers 14-17 (vs. 10-23 in R. asiatica) to near pygidial chaetigers, sperm from chaetiger 11 to 14 (vs. from chaetiger 11 to 21-22 in R. asiatica), oocytes from chaetigers 16-17 to 26-39 (vs. from 22-24 in R. asiatica), and 4-6 (vs. up to 6 in R. asiatica) pygidial cirri. Genetically, Rhynchospio aff. asiatica is most closely related to R. arenincola Hartman, 1936 from California, USA with the interspecific distances of 20.02% (16S rRNA), 4.50% (18S rRNA), 8.44% (28S rRNA), 2.74% (Histone H3), and 6.10% (concatenated sequences). Water flow across the dorsum created by ciliary beating of the branchiae and nototrochs, observed on live specimens, may help transport gametes from reproductive segments in anterior and middle parts to the posterior brooding segments. Phylogenetic trees based on concatenated sequences of four gene markers of 54 spioniform species in 25 genera revealed two clades, covering the two subfamilies Spioninae and Nerininae respectively. Two families (i.e., Poecilochaetidae and Trochochaetidae) in the order Spionida were clustered within Spionidae, supporting a morphology-based proposal that these families bearing a pair of prehensile, grooved palps should be grouped within a more broadly defined family Spionidae. Mapping morphological and reproductive characteristics to the phylogenetic trees indicated that the ancestor of spionids might lack branchiae, broadcast spawn thick-envelop oocytes and ect-aquasperm, and produce planktotrophic larvae.
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Background & aims: It remains controversial whether patients with advanced-stage hepatocellular carcinoma could be benefit from transarterial chemoembolization (TACE) treatment. The purpose of the present study is to identify predictors of survival following TACE in patients with advanced HCC. Methods: Overall, 303 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who were first treated with TACE from Sun Yat-sen University Cancer Centre between January 2009 and December 2013 were reviewed and enrolled in this study. We carried out Kaplan-Meier and Cox proportional hazard model analyses of prognostic factors. Results: The median survival of the whole cohort was 8.4 months. Multivariable Cox regression analyses confirmed that four risk factors, high serum levels of gamma-glutamyl transpeptidase (GGT), C-reactive protein (CRP), alkaline phosphatase (ALP) and presence of portal vein tumour thrombosis (PVTT), were independent prognostic factors for overall survival. The expected median survival among patients with 0-1 and 2-4 risk factors were 18.1 (95% CI: 15.5-20.7) and 6.8 (95% CI: 5.8-7.8) months, respectively. Objective tumor response among patients with 0-1 and 2-4 risk factors were 38.9% and 17.3%, respectively. Conclusion: We found four risk factors were associated with dismal overall survival for advanced HCC patients: serum GGT level, serum CRP, serum ALP and presence of PVTT. TACE may be recommended for patients with advanced HCC with 0-1 risk factors due to the favourable prognosis.
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The tumor microenvironment is a key determinant of cancer cell biology. The microenvironment is a complex mixture of tumor cells, stromal cells, and proteins, extracellular matrix, oxygen tension, and pH levels surrounding the cells that regulate the tumor progress. This study identified the prognostic factors associated with hepatocellular carcinoma (HCC) and MCT4 and GLUT1 expression levels in HCC specimens. In this study, we analyzed MCT4 and GLUT1 expression levels in tissue samples from 213 patients with HCC by immunohistochemical analyses and in HCC tumor tissues and matched adjacent nonneoplastic tissues by quantitative real-time PCR. We conducted a prognostic analysis of the overall survival (OS) and time to recurrence (TTR) using immunoreactivity and other common clinical and pathological parameters. All variables with prognostic impact were further analyzed by multivariate analysis. We found that MCT4 and GLUT1 expression levels were significantly higher in tumor tissues than in adjacent nontumor tissues, and they were positively correlated with tumor size. Survival analysis showed that patients with high expression levels of MCT4 or GLUT1 had a poor OS and TTR. In patients with HCC, MCT4 expression was an independent negative prognostic factor for OS (hazard ratio [HR] = 1.617; 95% confidence interval [CI] = 1.102-2.374; P = 0.014), and metabolic indicators were independent prognostic factors for OS (HR = 1.617, 95% CI = 1.102-2.374, P = 0.006) and TTR (HR = 1.348, 95% CI = 1.079-1.685, P = 0.009). Interestingly, patients with positive metabolic indicator expression in tumor cells had a significantly shorter OS and earlier TTR than those with negative metabolic indicator expression in tumor cells in the ≤5 cm and >5 cm subgroups. In summary, using the expression of MCT4 and GLUT1 and their metabolic parameters to determine the metabolic status of tumors is promising for predicting the prognosis of patients with HCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Neoplasias Hepáticas/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Adolescente , Adulto , Anciano , Carcinoma Hepatocelular/cirugía , Femenino , Hepatectomía , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results. METHODS: Thirty five patients were treated with sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m2 HAI on day 1, leucovorin 400 mg/m2 HAI on days 1, and 5-fluorouracil 2800 mg/m2 on days 1 and 2, repeated every 21 days. The primary end point was the 3-month PFS rate. RESULTS: The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%, respectively. The median PFS and overall survival was 6.7 and 13.2 months, respectively. The objective response rate was 40%, and the disease control rate was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to complete resection after the study treatment, and one of them experienced a pathological complete response. Treatment-related deaths did not occur. Grade 3-4 toxicities consisted of increases in aspartate aminotransferase (31.4%), hand-foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%). CONCLUSIONS: The combination treatment met the pre-specified end point of a 3-month progression free survival rate exceeding 65% and was clinical tolerable. The merits of this approach need to be established with a phase III trial. Clinical trial number http://ClinicalTrials.gov (No. NCT02981498).
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Carcinoma Hepatocelular/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos Organoplatinos/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Trombosis de la Vena/complicaciones , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/complicaciones , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales/métodos , Leucovorina/administración & dosificación , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Compuestos de Fenilurea/administración & dosificación , Vena Porta/patología , Estudios Prospectivos , Sorafenib , Resultado del TratamientoRESUMEN
The clinical significance of the sodium-potassium ATPase regulator FXYD domain-containing ion transport regulator 3 (FXYD3) has been demonstrated in a number of types of cancer. However, the role of this protein in human hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, 217 HCC tissue samples were analyzed to evaluate the expression and prognostic significance of FXYD3 in HCC. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA expression of FXYD3 in 80 primary HCC specimens and paired non-cancerous liver tissue samples, while western blotting was used to analyze the protein expression level of FXYD3 in another 24 pairs. These analyses demonstrated that the expression level of FXYD3 was significantly increasedb at the mRNA and protein levels in HCC tumor tissues compared with adjacent non-cancerous tissues. Immunohistochemical analysis of 137 paraffin-embedded HCC tissue samples indicated that the expression of FXYD3 was associated with HCC clinicopathological characteristics. Kaplan-Meier analysis demonstrated that patients with high FXYD3 protein expression (n=60) experienced significantly poorer overall survival time compared with patients with low FXYD3 protein expression (n=77) (P<0.001). Multivariate analysis demonstrated that FYXD3 protein expression level (hazard ratio, 2.137; 95% confidence interval, 1.224-3.732; P=0.008) was an independent prognostic factor in patients with HCC. Overall, the results indicated that FXYD3 expression levels were higher in HCC tumor tissues than in adjacent non-cancerous tissues, and that the FXYD3 protein may serve as a prognostic marker for HCC.
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Hepatocellular carcinoma (HCC) is among the most fatal types of cancer worldwide due to its high rates of recurrence and metastasis. The molecular processes involved in HCC progression require further investigation to identify biomarkers for use in diagnosis and treatment. In the present study, the significance and prognostic value of matrix metallopeptidase 12 (MMP12) expression in human HCC was investigated. MMP12 mRNA expression was investigated using reverse transcription-quantitative polymerase chain reaction analysis of 42 pairs of tumor and non-tumor liver tissues obtained from patients with HCC following surgical treatment. Immunohistochemical staining was used to detect MMP12 and forkhead box P3 (FOXP3) expression in 158 paraffin-embedded HCC tissues. The prognostic value of MMP12 expression was determined using Kaplan-Meier analysis and the Cox proportional hazards model. MMP12 mRNA levels were significantly higher in liver tumor tissues compared with matched non-tumor liver tissues. MMP12 expression and FOXP3+ regulatory T cell (Treg) infiltration was positively correlated (r=0.302; P<0.001). MMP12 protein overexpression was positively correlated with tumor size (P=0.018), high serum alpha-fetoprotein levels (P=0.005) and poor overall survival time (P=0.012) in patients with HCC. Furthermore, MMP12 protein level was an independent predictive factor for overall survival time of patients with HCC who underwent curative resection. In conclusion, these results suggest that MMP12 may increase FOXP3+ Treg infiltration into tumor tissues, and promote tumor progression and immune evasion of HCC. The overexpression of MMP12 protein is, therefore, a valuable prognostic indicator in patients with HCC.
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BACKGROUND: Transarterial chemoembolization (TACE) is recommended as the standard care for unresectable hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) stage A-B. However, the efficacy of TACE on large (≥ 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy (HAIC) might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX (mFOLFOX) regimen and those of TACE in patients with massive unresectable HCC. METHODS: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen (oxaliplatin, 85 mg/m2 intra-arterial infusion; leucovorin, 400 mg/m2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m2 continuous infusion) every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression (TTP), and safety were assessed. RESULTS: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group (52.6% vs. 9.8%, P < 0.001; 83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months (hazard radio [HR] = 2.35, 95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection (10 vs. 3, P = 0.033). The proportions of grade 3-4 adverse events (AE) and serious adverse events (SAE) were lower in the HAIC group than in the TACE group (grade 3-4 AEs: 13 vs. 27, P = 0.007; SAEs: 6 vs. 15, P = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent (10 vs. 2, P = 0.026). CONCLUSIONS: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Arteria Hepática , Humanos , Infusiones Intraarteriales , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Resultado del TratamientoRESUMEN
Quantitative study on macrobenthos was carried out in 8 transects along intertidal zone of Rushan Bay in May, 2011. In total, 116 macrobenthic species were identified, among which 58 were polychaetes, 15 were mollusks, 27 were crustaceans, 3 were echinoderms and 13 were other groups. The average abundance and biomass of macrobenthos were 872.6 ind · m(-2) and 9.37 g · M(-2), respectively. By IRI index, Mediomastus sp., Helice sheni, Nemertinea and Neanthes sp. were ranked as the top 4 dominant species in the study area. Average Margalef's species richness diversity (d), Shannon diversity (H) and Pielou's evenness index (J) of macrobenthos were 2.119, 2.384 and 0.608, respectively, indicating slight pollution in the study area. Based on 30% similarity level, 8 transects could be grouped into 3 different communities. Compared with other intertidal zones in similar latitude, macrobenthos of Rushan Bay intertidal zone were characterized by higher species number, smaller body size and higher abundance. Besides the macrobenthic community structure and diversities, more exhaustive studies were needed to reveal the possible influence of shellfish culture on intertidal macrobenthic community.
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Bahías , Biota , Estaciones del Año , Animales , Biomasa , Braquiuros , Crustáceos , Moluscos , PoliquetosRESUMEN
The Bohai Sea is a large semi-enclosed shallow water basin, which receives extensive river discharges of various terrestrial and anthropogenic materials such as sediments, nutrients and contaminants. How these terrigenous inputs may influence the diversity, community structure, biogeographical distribution, abundance and ecophysiology of the sediment anaerobic ammonium oxidation (anammox) bacteria was unknown. To answer this question, an investigation employing both 16S rRNA and hzo gene biomarkers was carried out. Ca. Scalindua bacteria were predominant in the surface sediments of the Bohai Sea, while non-Scalindua anammox bacteria were also detected in the Yellow River estuary and inner part of Liaodong Bay that received strong riverine and anthropogenic impacts. A novel 16S rRNA gene sequence clade was identified, putatively representing an anammox bacterial new candidate species tentatively named "Ca. Scalindua pacifica". Several groups of environmental factors, usually with distinct physicochemical or biogeochemical natures, including general marine and estuarine physicochemical properties, availability of anammox substrates (inorganic N compounds), alternative reductants and oxidants, environmental variations caused by river discharges and associated contaminants such as heavy metals, were identified to likely play important roles in influencing the ecology and biogeochemical functioning of the sediment anammox bacteria. In addition to inorganic N compounds that might play a key role in shaping the anammox microbiota, organic carbon, organic nitrogen, sulfate, sulfide and metals all showed the potentials to participate in the anammox process, releasing the strict dependence of the anammox bacteria upon the direct availability of inorganic N nutrients that might be limiting in certain areas of the Bohai Sea. The importance of inorganic N nutrients and certain other environmental factors to the sediment anammox microbiota suggests that these bacteria were active for the in situ N transforming process and maintained a versatile life style well adapted to the varying environmental conditions of the studied coastal ocean.
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Bacterias/clasificación , Bacterias/genética , Sedimentos Geológicos/microbiología , Tipificación Molecular , Océanos y Mares , Compuestos de Amonio Cuaternario/metabolismo , Anaerobiosis , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Biodiversidad , China , ADN Bacteriano/genética , Contaminantes Ambientales/toxicidad , Genes Bacterianos/genética , Metagenoma/efectos de los fármacos , Metagenoma/genética , Oxidación-Reducción , Filogenia , ARN Ribosómico 16S/genética , Análisis EspacialRESUMEN
An investigation was made on the standing crop, spatial distribution, sediment environment of meiofauna at 33 stations (including 22 stations in cold water mass area and 9 stations in Enteromorpha prolifera bloom area) in the Yellow Sea at the late stage of E. prolifera bloom in summer 2008. In this southern Yellow Sea area which was seriously impacted by the green algal bloom, the silt and clay contents in the sediments in 2008 had an obvious increase, compared with those in 2007, and the sediment chlorophyll-a and phaeophytin a contents in 2008 did not show obvious changes in cold water mass area but distinctly decreased in southern Jiangsu inshore area and Yangtze River estuary. Within the total 16 meiofaunal groups sorted, no marked variation was observed in their vertical distribution and in the contribution of each group to the total meiofauna. In 2008, the average abundance of meiofauna was (1375 +/- 793) ind x 10 cm(-2), and the biomass was (1203 +/- 707) micro x 10 cm(-2), both of which were decreased by about 1/3, compared with those in 2007. The meiofaunal standing crop was decreased more obviously in the stations heavily affected by the E. prolifera bloom, while that in the Yellow Sea cold water mass area was slightly increased, resulting in an unusual trend of meiofaunal standing crop decreasing from the central area of cold water mass to the inshore area in the southern Yellow Sea. By contrast, and as usual, the meiofaunal standing crop was increased from the cold water mass area to the inshore area in the northern Yellow Sea. Statistical analyses suggested that only the meiofaunal abundance had positive correlation with the salinity in the stations heavily affected by the green algal bloom. Our study indicated that macroalgal bloom obviously inhibited the standing crop of meiofauna in the inshore area. The decrease was not due to the deficiency of food concentration, but likely caused by the deposition and degradation of the E. prolifera bloom.
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Chlorophyta/crecimiento & desarrollo , Crustáceos/crecimiento & desarrollo , Nematodos/crecimiento & desarrollo , Contaminación del Agua/análisis , Animales , China , Eutrofización , Océanos y MaresRESUMEN
A comprehensive seafloor biomass and abundance database has been constructed from 24 oceanographic institutions worldwide within the Census of Marine Life (CoML) field projects. The machine-learning algorithm, Random Forests, was employed to model and predict seafloor standing stocks from surface primary production, water-column integrated and export particulate organic matter (POM), seafloor relief, and bottom water properties. The predictive models explain 63% to 88% of stock variance among the major size groups. Individual and composite maps of predicted global seafloor biomass and abundance are generated for bacteria, meiofauna, macrofauna, and megafauna (invertebrates and fishes). Patterns of benthic standing stocks were positive functions of surface primary production and delivery of the particulate organic carbon (POC) flux to the seafloor. At a regional scale, the census maps illustrate that integrated biomass is highest at the poles, on continental margins associated with coastal upwelling and with broad zones associated with equatorial divergence. Lowest values are consistently encountered on the central abyssal plains of major ocean basins The shift of biomass dominance groups with depth is shown to be affected by the decrease in average body size rather than abundance, presumably due to decrease in quantity and quality of food supply. This biomass census and associated maps are vital components of mechanistic deep-sea food web models and global carbon cycling, and as such provide fundamental information that can be incorporated into evidence-based management.
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Biomasa , Biología Marina/métodos , Algoritmos , Animales , Inteligencia Artificial , Biodiversidad , Carbono/química , Biología Computacional/métodos , Ecosistema , Modelos Biológicos , Océanos y Mares , Análisis de RegresiónRESUMEN
From September 2003 to September 2004, seven cruises bimonthly survey was conducted on the macrobenthos at five research stations in the Jiaozhou Bay, and the abundance, biomass, secondary productivity, and P/B value of the macrobenthos were studied by using Brey' s empirical formula. The results showed that the secondary productivity of the macrobenthos was averagely 47.34 g x m(-2) x a(-1), and the mean P/B value was 0.58. Correlation analysis indicated that Chl-a was the important environmental factor affecting the secondary productivity. A comparative study on the southern Yellow Sea, Bohai Bay and other areas also proved that on local scale, Chl-a was the important factor affecting the secondary productivity of the benthic community, but on regional scale, water depth was more determinative, i.e., this productivity was decreased with increasing water depth. The greatest contributor to the secondary productivity of macrobenthos in studied areas was Ruditapes philippinarum, the most important economic bivalve in the Jiaozhou Bay, and its population was dominated by the individuals with the ages of less than one year, one year, and two years.