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1.
Chinese Acupuncture & Moxibustion ; (12): 1008-1013, 2023.
Article in Chinese | WPRIM | ID: wpr-1007434

ABSTRACT

OBJECTIVE@#To observe the effects of Tiaoshen (regulating the spirit) acupuncture on cognitive function and sleep quality in patients with primary insomnia (PI).@*METHODS@#Sixty patients with PI were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off, 1 case was excluded). The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Sishencong (EX-HN 1), and bilateral Benshen (GB 13), Shenmen (HT 7), Neiguan (PC 6), Sanyinjiao (SP 6). The patients in the control group were treated with shallow needling at non-effective points. Each treatment was provided for 30 min, once every other day, 3 treatments per week for 4 weeks. The Montreal cognitive assessment (MoCA), digit span test (DST), trail making test (TMT)-A, Pittsburgh sleep quality index (PSQI), and fatigue scale-14 (FS-14) were used to assess cognitive function and sleep quality before and after treatment, as well as in follow-up of 4-week after treatment completion. Correlation analysis was conducted between the differences in PSQI scores and differences in MoCA scores before and after treatment in the observation group.@*RESULTS@#Compared with before treatment, the total score, visuospatial and executive function score and delayed memory score of MoCA as well as DST backward score were increased (P<0.01), while TMT-A time, PSQI and FS-14 scores were significantly reduced (P<0.01) after treatment and in follow-up in the observation group. Compared with before treatment, the PSQI score in the control group was reduced (P<0.01, P<0.05). After treatment and in follow-up, the observation group had significantly higher total score, visuospatial and executive function score, delayed memory score of MoCA, and DST backward score compared to the control group (P<0.05, P<0.01). In the observation group, the TMT-A time was significantly shorter than that in the control group (P<0.05, P<0.01), and the PSQI and FS-14 scores were significantly lower than those in the control group (P<0.01). In the observation group, there was a negative correlation between the difference in PSQI scores (post-treatment minus pre-treatment) and the difference in MoCA scores (post-treatment minus pre-treatment) (r=-0.481, P<0.01). A similar negative correlation was found between the difference in PSQI scores (follow-up minus pre-treatment) and the difference in MoCA scores (follow-up minus pre-treatment) (r=-0.282, P<0.05).@*CONCLUSION@#Tiaoshen acupuncture could improve cognitive function, enhance sleep quality, and alleviate daytime fatigue in patients with PI. The improvement in cognitive function in patients with PI is correlated with the improvement in sleep quality.


Subject(s)
Humans , Pilot Projects , Sleep Initiation and Maintenance Disorders/therapy , Acupuncture Therapy , Cognition , Fatigue
2.
Cancer Research on Prevention and Treatment ; (12): 146-150, 2023.
Article in Chinese | WPRIM | ID: wpr-986694

ABSTRACT

Objective To investigate the impact of PD1-TCF1+CD8+ stem-like memory T cells on immunotherapy prognosis and tertiary lymphoid structure in tumors. Methods Pathological tissue sections were collected from 33 patients treated with immunotherapy, 18 cases of NSCLC and 15 cases of ESCC. The expression of PD1-TCF1+CD8+T cells was detected through quantitative analysis by multiplex immunofluorescence. Survival curves were described by the Kaplan-Meier method. Pearson's correlation test was used for correlation analysis. Results The high levels of PD1-TCF1+CD8+T cells had a better PFS in NSCLC and ESCC cohorts. In the NSCLC cohort, high levels of PD1-TCF1+CD8+ T cells were significantly and positively correlated with the number (P=0.0151) and size (P=0.0007) of TLSs. Conclusion In patients with NSCLC and ESCCs, high PD1-TCF1+CD8+ stem-like memory T cell expression indicates improved prognosis and immune response and is associated with the formation of TLSs in the tumor microenvironment of NSCLC.

3.
Cancer Research on Prevention and Treatment ; (12): 58-62, 2023.
Article in Chinese | WPRIM | ID: wpr-986680

ABSTRACT

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.

4.
Chinese Pharmacological Bulletin ; (12): 1565-1572, 2022.
Article in Chinese | WPRIM | ID: wpr-1014001

ABSTRACT

Aim To explore the main active ingredients of Tripterygium wilfordii and the mechanism in treat-ment of breast cancer based on network pharmacology.Methods The active components and targets of Tripterygii Wilfordii were searched by TCMSP.GeneCard database was used to screen the potential targets of Tripterygii Wilfordii in treatment of breast cancer.The two were matched to obtain the core components and targets of Tripterygii Wilfordii.Cytoscape3.6.0 and AutoDock Vina were used to draw the drug-target network diagram, and GO enrichment analysis, KEGG pathway enrichment analysis, and molecular docking between the core target and the components were carried out.CCK8 and qPCR were used to verify the effect of optimal core component tripterine on breast cancer cells.Results Seven kinds of active anti-breast cancer components and twenty-five core therapeutic targets of Tripterygii Wilfordii were obtained.Tripterine, which significantly inhibited the growth of breast cancer cells, was the most valuable component of Tripterygii Wilfordii for breast cancer.QPCR results showed that tripterine decreased the expression of core therapeutic targets.Conclusions The effectiveness of Tripterygii Wilfordii has multiple pathways, and tripterine may play an important role in treatment of breast cancer.

5.
Journal of International Oncology ; (12): 678-682, 2021.
Article in Chinese | WPRIM | ID: wpr-907599

ABSTRACT

The emergence of immune checkpoint inhibitors (ICIs) has greatly changed the treatment strategy of non-small cell lung cancer (NSCLC). Although ICIs are effective, there are still many patients who cannot benefit from immunotherapy alone. The current research direction focuses on the combination of multiple treatment schemes. Radiotherapy can upregulate immunogenic cell surface markers, and regulate the expressions of immune checkpoints. A large number of preclinical and clinical studies are exploring the efficacy and safety of ICIs combined with radiotherapy in various clinical stages of NSCLC, including radiotherapy timing, optimal dose, dose distribution and so on.

6.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 117-123, 2021.
Article in Chinese | WPRIM | ID: wpr-906278

ABSTRACT

Objective:To investigate the chemical constituents and antioxidant activities of Violae Herba from the Violaceae. Method:The 5 kg of Violae Herba was refluxing extracted with 3 times the amount of 95% ethanol for three times, then the extracting solution was combined, filtrated, concentrated under vacuum to get the total extract. Seven corresponding fractions were eluted with petroleum ether, dichloromethane, dichloromethane-methanol (50∶1, 10∶1, 5∶1, 2∶1) and methanol by silica gel column chromatography (60-100 mesh) on the total extract. Each fraction was isolated and purified by normal phase silica gel column chromatography, octadecylsilane chemically bonded silica (ODS) column chromatography, Sephadex LH-20 column chromatography and preparative high performance liquid chromatography (HPLC), respectively. The structures of the obtained compounds were identified by spectroscopic methods of nuclear magnetic resonance (NMR), mass spectroscopy (MS) and infrared spectroscopy (IR). Meanwhile, some of these compounds isolated from Violae Herba were carried on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging experiment. Result:Fourteen compounds were isolated from the 95% ethanol extract of Violae Herba, including <italic>N</italic>-acetyl-1-ethyl ester glutamic acid (<bold>1</bold>), <italic>N</italic>-acetyl glutamic acid-1-ethyl-5-methyl ester (<bold>2</bold>), aurantiamide (<bold>3</bold>), <italic>rel</italic>-(2<italic>α</italic>,3<italic>β</italic>)-7-<italic>O</italic>-methylcedrusin (<bold>4</bold>), oleanolic acid (<bold>5</bold>), <italic>α</italic>-tocopherol-quinone (<bold>6</bold>), tectochrysin (<bold>7</bold>), isoscopoletin (<bold>8</bold>), esculetin (<bold>9</bold>), 24-ethylcholesta-4,24(28)<italic>Z</italic>-dien-3-one (<bold>10</bold>), stigmasta-4,25-dien-3-one (<bold>11</bold>), <italic>β</italic>-sitostenone (<bold>12</bold>), <italic>β</italic>-sitosterol (<bold>13</bold>), (24<italic>R</italic>)-3<italic>β</italic>-hydroxy-ethylcholest-5-en-7-one (<bold>14</bold>). Conclusion:Compound <bold>2</bold> is a new natural product, compounds <bold>1</bold>, <bold>4</bold>, <bold>6</bold>, <bold>7</bold>, <bold>10</bold>-<bold>12 </bold>are isolated from the genus <italic>Viola</italic> for the first time. Compound <bold>9</bold> has significant antioxidant activity, while compounds <bold>2</bold>, <bold>6 </bold>and<bold> 8</bold> have certain DPPH free radical scavenging activity.

7.
China Journal of Chinese Materia Medica ; (24): 5064-5071, 2021.
Article in Chinese | WPRIM | ID: wpr-921645

ABSTRACT

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.


Subject(s)
Animals , Rats , Cardiomegaly/genetics , Isoproterenol , Myocardium , Myocytes, Cardiac , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology
8.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 141-147, 2020.
Article in Chinese | WPRIM | ID: wpr-873261

ABSTRACT

Objective::To isolate and identify the chemical constituents from the 95%, 75%ethanol extracts of the stems of Zanthoxylum bungeanum. Method::The 25 kg stems of Z. bungeanum were extracted with 95%, 75%ethanol for three times, and the combined filtrates were concentrated under vacuum to get the extracts. The 95%extracts were then extracted by petroleum ether, dichloromethane, ethyl acetate and n-butanol successively to obtain corresponding fractions. Such fractions and 75%extracts were isolated and purified by silicagel, Sephadex LH-20, ODS, preparation HPLC and recrystallization to obtain compounds. Their structures were identified by mass spectroscopy (MS), and nuclear magnetic resonance (NMR). Result::Sixteen compounds were isolated from the stems of Z. bungeanum and identified as dictamnine(1), decarine(2), zanthobungeanine(3), pseudocolumbamine(4), skimmianine(5), norchelerythrine(6), osthenol(7), dimethylfraxetin(8), 3, 4, 5-trimethoxycinnamylalcohol(9), asarinin(10), yangambin(11), syringaresinol(12), ashantin(13), bis(2-ethylhexyl) benzene-1, 2-dicarboxylate(14), 24-propylcholesterol(15), and sucrose(16). Conclusion::Compounds pseudocolumbamine(4), 3, 4, 5-trimethoxycinnamylalcohol(9), and 24-propylcholesterol(15)were isolated from the genus of Zanthoxylum for the first time and compounds dictamnine(1), osthenol(7), dimethylfraxetin(8), asarinin(10), yangambin(11), syringaresinol(12), ashantin(13), and bis(2-ethylhexyl) benzene-1, 2-dicarboxylate(14)were isolated from this plant for the first time.

9.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 152-157, 2020.
Article in Chinese | WPRIM | ID: wpr-872998

ABSTRACT

Objective::To investigate the chemical constituents from Paeonia veitchii. Method::P. veitchii samples (30 kg) were extracted with 95% ethanol for four times and then filtrated, and the combined filtrates were concentrated under vacuum to get the extracts. After suspension with water, exaction was conducted with petroleum ether, dichloromethane, ethyl acetate, n-butanol and water successively to obtain five corresponding fractions. The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography and prep-HPLC, and the structures of these compounds were determined by such spectrum technologies as infrared spectroscopy (IR), mass spectroscopy (MS), and nuclear magnetic resonance (NMR). Result::Sixteen compounds were isolated and their structures were identified as follows (1S, 5R, 6R)-1, 8-dihydroxypin-2-en-4-one (1), (2-hydroxyl)-phenyl-methyl-β-D-xylopyranoside (2), flufuran (3), 6′-O-vanillylpaeoniflorin (4), methyl 2, 5-dihydroxycinnamate (5), (1S, 2S, 5R, 6R)-1, 8-dihydroxypin-4-one (6), palbinone (7), 4-O-methylpaeoniflorin (8), 4-O-ethylpaeoniflorin (9), benzoyloxypaeoniflorin (10), benzoic acid (11), gallic acid (12), methyl gallate (13), ethyl gallate (14), β-sitosterol (15), and 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucopyranose (16). Conclusion::Compounds 1, 2 were new natural compounds; compound 3 was isolated from genus Paeonia for the first time, and compounds 4-7 were isolated from this plant for the first time.

10.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 161-166, 2019.
Article in Chinese | WPRIM | ID: wpr-802215

ABSTRACT

Objective:To isolate and identify the chemical constituents from 95%ethanol extracts from stems of Zanthoxylum bungeanum. Method:The stems (25 kg) were extracted with 95%ethanol under reflux for three times and then filtrated,and the combined filtrates were concentrated under vacuum to get the extracts. After suspension with water,the extracts were extracted with petroleum ether,dichloromethane,ethyl acetate and n-butanol successively,and five corresponding parts were obtained. The parts of petroleum ether,dichloromethane,ethyl acetate were separated in a similar way to get pure compounds. By the method the subjects were first chromatographed on silica gel column respectively,then the selected sub-fractions were further separated by Sephadex LH-20, and finally purified on preparation HPLC to get the monomer compound. The n-butanol part was first treated with macroporous resin D101,and then the sub-fractions were further purified by almost the same method as mentioned above. The structures of these compounds were determined by spectrum technology as IR,MS,1H-NMR,13 C-NMR. Result:Ten compounds were isolated from Z. bungeanum stems and identified as follows:(+)-magnoflorine(1),(-)-marmesin(2),(-)-columbianetin(3),(-)-decursinol(4),lupeol(5),α-amyrin(6),β-amyrin(7),δ-amyrin(8),quercetin(9),rutin(10). Among them, 1 was alkaloid, 2,3,4 were coumarin, 5,6,7,8 were triterpenoid, 9,10 were flavonoids. Conclusion:Compounds 1-8 were isolated from this plant for the first time.

11.
West China Journal of Stomatology ; (6): 544-551, 2018.
Article in Chinese | WPRIM | ID: wpr-772461

ABSTRACT

Human papillomavirus (HPV) is a major causative agent of head and neck squamous cell carcinomas (HNSCC). Over the past several decades, an increasing number of studies established the strong association of HPV with the invasion and metastasis of HNSCC. In the present study, we reviewed the gene mutations in HPV-associated HNSCC and the unique mechanism of E6- and E7-mediated carcinogenesis via interactions with an array of cellular elements. We further discussed the progress in the mechanisms of invasion and metastasis; these mechanisms include non-coding RNAs, deregulating cellular energetics, tumor microenvironment, cancer stem cells, angiogenesis, and lymphangiogenesis.


Subject(s)
Humans , Head and Neck Neoplasms , Pathology , Virology , Neoplasm Invasiveness , Neoplasm Metastasis , Papillomaviridae , Papillomavirus Infections , Squamous Cell Carcinoma of Head and Neck , Pathology , Virology
12.
China Medical Equipment ; (12): 105-108, 2017.
Article in Chinese | WPRIM | ID: wpr-667786

ABSTRACT

Objective: To design a clock synchronization system for multi-functional monitor so as to apply objective and accurate technical means to realize automatic synchronization for clock of bedside multi-functional monitor. Methods: The simple network time protocol(SNTP) which was defined in the standard of consistent time(CT) from integrating the healthcare enterprise(IHE) were chosen and clock synchronization source which suited to medical organization were adopted, and all of them were applied to design clock synchronization system based on Windows platform. Results: The clock synchronization system can be integrated to connect with the original monitor system, and 7 central station monitor systems were integrated and connected, and total of 58 multi-functional monitors were joined up. Except manual synchronization mode, both of satellite and internet can achieve real time synchronization of clock for 58 bedside monitors. Conclusion: The clock synchronization system of bedside multi-functional monitor can effectively realize clock synchronization of monitor system, and it can avoid the potential risks caused by time inconsistency. At the same time, it can connect with more emergency equipment to realize clock synchronization.

13.
Shanghai Journal of Acupuncture and Moxibustion ; (12): 1387-1390, 2017.
Article in Chinese | WPRIM | ID: wpr-663243

ABSTRACT

Objective To observe the clinical efficacy of wheat-sized moxibustion in assisting the treatment of mild—to-moderate persistent chronic bronchial asthma in the elderly with Salmeterol xinafoate and fluticasone propionate aerosol. Method Eighty-four old patients with mild—to-moderate persistent chronic bronchial asthma were randomized into an observation group and a control group by using the random number table, 42 each. The control group was given Salmeterol xinafoate and fluticasone propionate aerosol, 1 inhalation each time, twice a day;the observation group was additionally given wheat-sized moxibustion by selecting Pishu (BL20), Feishu (BL13) and Geshu (BL17), twice a week. The two groups were both treated for 2 months. Before and after the intervention, Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), and pulmonary function parameters [peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC)] were observed, and the clinical efficacies were compared. Result The total effective rate was 92.9% in the observation group versus 78.6% in the control group, and the difference was statistically significant (P<0.05); the ACT and AQLQ scores, as well as PEF, FEV1 and FVC were significantly increased after the intervention in both groups (P<0.05); after the treatment, the improvement in the observation group was significantly superior to that in the control group (P<0.05). Conclusion Wheat-sized moxibustion is effective in assisting the treatment of mild-to-moderate persistent chronic bronchial asthma in the elderly with Salmeterol xinafoate and fluticasone propionate aerosol. It can effectively controlasthma and enhance the quality of life.

14.
Chinese Acupuncture & Moxibustion ; (12): 53-57, 2012.
Article in Chinese | WPRIM | ID: wpr-230502

ABSTRACT

<p><b>OBJECTIVE</b>To explore the anti-aging effect of artemisia burning products (ie. smoke of moxibustion) and its proper intervention parameters.</p><p><b>METHODS</b>According to factorial experiment design, 70 SAMP8 mice were randomly divided into one model group (group M) and 6 intervention groups: low concentration with 15 min group (group A1), low concentration with 30 min group (group A2), middle concentration with 15 min group (group B1), middle concentration with 30 min group (group B2), high concentration with 15 min group (group C1), high concentration with 30 min group (group C1). There were 10 cases in each group. Ten age-matched SAMR1 mice were used as normal group (group Z). All the mice in the 6 intervention groups were fumed with artemisia burning products of different concentration and time. The content of serum malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and glutathione reductase (GSH-Px) were tested.</p><p><b>RESULTS</b>MDA content in group M was significantly higher than that in group Z (both P < 0.05), while SOD and GSH-Px activity were significantly lower in group M than that in group Z (both P < 0.05). Results of MDA, SOD and GSH-Px in 6 intervention groups were either of no statistically significant differences, or better than that in group M. Among 6 intervention groups, results of MDA and GSH-Px were better in group B1, while the result of SOD was better in group B2. Time factor didn't make any difference, while concentration of artemisia burning products is meaningful. As to SOD and GSH-Px, there's a strong interaction between the two factors.</p><p><b>CONCLUSION</b>With certain concentration and time period, the intervention of artemisia burning products can exert anti-aging effect by increasing antioxydative capability and reducing metabolites of free radicals. Middle concentration and 30 minutes are recommended when intervened with artemisia burning products.</p>


Subject(s)
Animals , Humans , Male , Mice , Aging , Blood , Metabolism , Antioxidants , Metabolism , Artemisia , Chemistry , Disease Models, Animal , Glutathione Peroxidase , Blood , Glutathione Reductase , Blood , Malondialdehyde , Blood , Moxibustion , Superoxide Dismutase , Blood
15.
Acta Academiae Medicinae Sinicae ; (6): 645-649, 2003.
Article in Chinese | WPRIM | ID: wpr-327017

ABSTRACT

<p><b>OBJECTIVE</b>To study the role and prospect of 18FDG PET imaging in patients with malignant lymphoma.</p><p><b>METHODS</b>Forty-four patients (73 studies) with malignant lymphoma underwent 18FDG PET imaging. Final diagnoses were proved histopathologically. Images obtained were analyzed using visual and semiquantitative analysis (SUV).</p><p><b>RESULTS</b>Either nodal or extranodal tumor foci showed high 18FDG uptake. 18FDG PET led to correct diagnosis in 5 of 6 cases except 1 false negative case. PET imaging changed the staging in 4 of 6 cases pretherapeutically. Of the 16 cases in which either residual tumor mass or suspicious recurrence suggested by other imaging modalities, 18FDG PET confirmed relapse in 5, detected more lesions in 2 and showed no evidence of active tumor mass in 9. For the 3 patients with comparison between pre- or post-treatment PET imaging and 16 patients who only underwent post-treatment PET follow-up studies, therapeutic response was correctly evaluated.</p><p><b>CONCLUSIONS</b>18FDG PET is a valuable non-invasive metabolic imaging modality in facilitating diagnosis and staging, evaluating therapeutic response, assessing clinical outcome and predicting prognosis in patients with lymphoma.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Follow-Up Studies , Lymphoma, Non-Hodgkin , Diagnostic Imaging , Neoplasm Recurrence, Local , Diagnostic Imaging , Neoplasm Staging , Prognosis , Radiopharmaceuticals , Retrospective Studies , Tomography, Emission-Computed
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