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The aim of this paper is to study the malonyl ginsenosides in the fresh roots of Panax ginseng. D101 macroporous adsorption resin, ODS, and preparative HPLC were employed to separate the chemical components from the 70% ethanol extract of the fresh roots of P. ginseng, and the structures of the separated compounds were identified based on the data of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Two malonyl ginsenosides were isolated from the fresh roots of P. ginseng and identified as 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1â2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1â4)-α-L-arabinopyranosyl-(1â6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(1) and 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1â2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1â2)-α-L-arabinofuranosyl-(1â6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(2), respectively. Compounds 1 and 2 are new compounds isolated from fresh roots of P. ginseng for the first time and named as malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2, respectively.
Assuntos
Ginsenosídeos , Panax , Raízes de Plantas , Panax/química , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Raízes de Plantas/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificaçãoRESUMO
BACKGROUND: Laparoscopic pancreaticoduodenectomy(LPD) has become the goal of lots of minimally invasive surgical centers in recent years. Postoperative pancreatic fistula(POPF) is still the barrier to attaining the above goal. Thus, improving anastomosis techniques to reduce the rate of POPF has been a hotspot of surgery. Blumgart pancreaticojejunostomy is considered one of the best anastomosis procedures, with low rates of POPF. However, the original Blumgart pancreaticojejunostomy method is not easy for laparoscopic operation. In consequence, we modified a Blumgart pancreaticojejunostomy technique with a simple and practicable procedure and applied to LPD. METHODS: We collected and retrospectively analyzed the perioperative clinical data of patients who underwent modified Blumgart anastomosis from February 2017 to September 2022. The above patients included 53 cases in open pancreaticojejunostomy(OPD) and 58 cases in LPD. After propensity score matching, 44 cases were included for comparison in each group. RESULTS: After propensity score matching, the average time for pancreaticojejunostomy was about 30 min in the LPD group. The Clinically relevant POPF(CR-POPF) rate was 9.1%. The length of postoperative hospitalization was 13.1 days. Compared with the OPD group, The CR-POPF rate in the LPD group are not significant differences. But the postoperative length of hospital stay was significantly shorter in the LPD group. Besides, there were no other severely postoperative complications between two groups. CONCLUSION: The modified Blumgart anastomosis technique applied to LPD in our Center not only has simple and convenient properties but also low rate of CR-POPF. And this method may be a good choice for surgeons to begin to carry out LPD.
Assuntos
Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Anastomose Cirúrgica/métodos , Pancreaticojejunostomia/métodos , Fístula Pancreática/etiologia , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologiaRESUMO
There is a lack of information on the compound profile of Cornus officinalis Sieb. et Zucc. seeds. This greatly affects their optimal utilization. In our preliminary study, we found that the extract of the seeds displayed a strong positive reaction to the FeCl3 solution, indicating the presence of polyphenols. However, to date, only nine polyphenols have been isolated. In this study, HPLC-ESI-MS/MS was employed to fully reveal the polyphenol profile of the seed extracts. A total of 90 polyphenols were identified. They were classified into nine brevifolincarboxyl tannins and their derivatives, 34 ellagitannins, 21 gallotannins, and 26 phenolic acids and their derivatives. Most of these were first identified from the seeds of C. officinalis. More importantly, five new types of tannins were reported for the first time: brevifolincarboxyl-trigalloyl-hexoside, digalloyl-dehydrohexahydroxydiphenoyl (DHHDP)-hexdside, galloyl-DHHDP-hexoside, DHHDP-hexahydroxydiphenoyl(HHDP)-galloyl-gluconic acid, and peroxide product of DHHDP-trigalloylhexoside. Moreover, the total phenolic content was as high as 79,157 ± 563 mg gallic acid equivalent per 100 g in the seeds extract. The results of this study not only enrich the structure database of tannins, but also provide invaluable aid to its further utilization in industries.
Assuntos
Cornus , Medicamentos de Ervas Chinesas , Taninos/química , Cornus/química , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Taninos Hidrolisáveis , Polifenóis , Sementes , Medicamentos de Ervas Chinesas/químicaRESUMO
Plants have a memory function for the environmental stress they have suffered. When they are subjected to repeated environmental stress, they can quickly and better activate the response and adaptation mechanism to environmental stress, thus realizing long-term stable reproduction. However, most of the relevant studies are applied to crops and Arabidopsis thaliana rather than medicinal plants about the improvement of plant growth status and the effect on phytoalexin biosynthesis. In this study, yeast extract(YE) was used as an elicitor to simulate biotic stress, and the changes in biomass and the content of some secondary metabolites were measured by giving repeated stresses to Sorbus aucuparia suspension cell(SASC). The results showed that the accumulation levels of biomass and some secondary metabolites in SASC subjected to repeated stress are significantly increased at some time points compared with single stress. A phenomenon that SASC can memorize biotic stress is confirmed in this study and influences phytoalexin accumulation in SASC. Furthermore, the work laid the groundwork for research into the transgenerational stress memory mechanism of medicinal plant.
Assuntos
Sorbus , Células Cultivadas , Metabolismo Secundário , Estresse FisiológicoRESUMO
A series of scarce amino-substituted cyclopentafullerenes instead of the expected N-alkyl-2,5-disubstituted fulleropyrrolidines were synthesized in moderate to excellent yields via the simple one-step reaction of [60]fullerene with cheap and easily available ß-substituted propionaldehydes and secondary amines in the absence/presence of magnesium perchlorate. The in situ generation of allylic amines from ß-substituted propionaldehydes and secondary amines played a crucial role in the successful preparation of amino-substituted cyclopentafullerenes without additional carbons. With the addition of magnesium perchlorate, secondary amines containing ethyl group(s) could produce novel amino-substituted cyclopentafullerenes with two additional carbons. All the obtained cyclopentafullerenes displayed high stereoselectivity with cis isomers as the exclusive or major products. Plausible reaction mechanisms are proposed to elucidate the above-mentioned reaction process.
RESUMO
The preparation of carbon materials usually involves the decomposition of precursors and the reorganization of the as-generated fragments. However, the cleavage of bonds and the simultaneous formation of new bonds at nearly the same positions prevents effective yet precise fabrication. Herein, a supramolecular precursor, cucurbit[6]uril, that contains multiple bonds with distinct bond strengths is proposed to decouple the twin problem of simultaneous bond cleavage and formation, allowing multistage transformations to hierarchical porous carbon and metal-doped carbon in a single yet effective pyrolysis step without the need of a template or additional purification. As a proof-of-concept, the Fe-doped carbon electrocatalysts realized a Pt/C-like half-wave potential of 0.869â V vs. RHE and small Tafel slope of 51.3â mV dec-1 in oxygen reduction reaction.
RESUMO
Studies on the characteristic chemical markers of sulfur fumigation have become an effective auxiliary way for quality control of traditional Chinese medicine. This study established a quantitative analysis method for the determination of p-hydroxybenzyl hydrogen sulfite (p-HS) in Gastrodiae Rhizoma (GR) based on UPLC-MS/MS. Then, 37 batches of GR were screened, and the results showed that 27 batches of them were sulfur-fumigated. Especially, the GR samples in Yunnan producing areas were sulfur-fumigated more seriously. Based on the stability of p-HS after different storage time and heat treatment methods, it was found that the content of p-HS was stable and reliable in the storage period of 8 months and under normal heat treatment (50, 60, 70, 80 °C) conditions. In conclusion, this study shows a high sensitivity, good selectivity and good stability of p-HS, which can provide reference for the quality control and sulfur fumigation screening of GR.
Assuntos
Medicamentos de Ervas Chinesas/normas , Fumigação , Gastrodia/química , Sulfitos/análise , China , Cromatografia Líquida , Medicamentos de Ervas Chinesas/química , Controle de Qualidade , Rizoma/química , Enxofre , Espectrometria de Massas em TandemRESUMO
To study the effect of different storage time on the chemical compositions and sulfur dioxide residues of sulfur-fumigated Gastrodiae Rhizoma (GR), and provide scientific basis for solving the quality and safety issues of sulfur-fumigated traditional Chinese medicinal materials. GR, sulfur-fumigated GR and its medicinal slices were stored under the same conditions, and then 8 active ingredients and sulfur dioxide residues were measured respectively. The results showed that the content of gastrodins in sulfur-fumigated GR and its medicinal slices was significantly lower than that in the non-fumigated GR. Moreover, the content of sulfur dioxide residue in sulfur-fumigated GR was significantly higher than that in its medicinal slices. That is to say, sulfur fumigation degree had significantly higher effect on GR quality as compared with its medicinal slices. During the whole storage time (8 months), the content of the eight chemical components in GR was not changed greatly in general. However, after the storage for 4 months, the content of 8 components and sulfur dioxide residues in all of GR samples were significantly changed. In particular, the content of sulfur dioxide residue in GR medicinal materials decreased up to 50% or more.
Assuntos
Armazenamento de Medicamentos , Medicamentos de Ervas Chinesas/química , Fumigação , Gastrodia/química , Dióxido de Enxofre/análise , Rizoma/química , EnxofreRESUMO
The thermal reaction of C60 with aromatic aldehydes and inactive secondary amines for the stereoselective synthesis of trans-1,2,5-trisubstituted fulleropyrrolidines has been developed. Moreover, when an o-hydroxyl group was located at the phenyl ring of the generated fulleropyrrolidines, the Cu(OAc)2-promoted regioselective intramolecular C-O coupling reaction occurred to generate unique tricycle-fused fullerene derivatives.
RESUMO
A series of scarce N-unsubstituted 2,5-diaryl fulleropyrrolidines as cis isomers could be prepared via the facile one-step reaction of [60]fullerene with N-unsubstituted arylmethanamines promoted by cheap and easily available ferric perchlorate. Nevertheless, the reaction of N-substituted arylmethanamines with [60]fullerene under the same conditions gave different experimental results. N-Methylbenzylamine formed N-methyl 2,5-diphenyl fulleropyrrolidine as a trans isomer, and N,N-dibenzylamine unexpectedly afforded the N-unsubstituted 2,5-diphenyl fulleropyrrolidine as a cis isomer. Intriguingly, high stereoselectivity for all 2,5-diaryl fulleropyrrolidines could be observed although both cis and trans isomers were possibly formed. N-Unsubstituted fulleropyrrolidine could be further converted to N-substituted fulleropyrrolidines under the assistance of an acid chloride or an isocyanate. A possible reaction pathway leading to 2,5-diaryl fulleropyrrolidines is also proposed.
RESUMO
The facile one-step reaction of [60]fullerene with aldehydes and primary amines in the presence of cheap and easily available Cu(OAc)2·H2O afforded a series of new types of fulleropyrrolines with trisubstituted CâC bonds in good to excellent yields, which would be difficult to prepare by known methods. The formed fulleropyrroline under the assistance of Pd(OAc)2 and CuCl2·2H2O could be further converted to 1-fulleropyrrolidine by the chlorohydroxylation reaction of CâC bond. Subsequent elimination reaction of 1-fulleropyrrolidine with the aid of TsOH·H2O generated the scarce 1-fulleropyrroline derivative.
RESUMO
The Cu(OAc)2-promoted reaction of C60 with easily available primary amines allows the concise preparation of aziridinofullerenes. Both alkyl and aryl amines are suitable in this reaction. Moreover, the Cu(OAc)2-promoted reaction of C60 with diamines affords C60-fused cyclic 1,2-diaminated fullerenes.
RESUMO
The Lewis base-catalyzed double nucleophilic substitution reaction of N-tosylaziridinofullerene with various ureas allows the easy preparation of fulleroimidazolidinones with a high tolerance for functional groups. Alkyl-substituted ureas show better reactivity than aryl-substituted ureas.
Assuntos
Aziridinas/síntese química , Fulerenos/química , Imidazolidinas/síntese química , Bases de Lewis/química , Ureia/química , Aziridinas/química , Catálise , Imidazolidinas/química , Modelos Moleculares , Estrutura MolecularRESUMO
BF3·Et2O-catalyzed double nucleophilic substitution reaction of N-tosylaziridinofullerene with sulfamides has been exploited for the easy preparation of cyclic sulfamide-fused fullerene derivatives. Moreover, the Lewis base catalyzed double amination of N-tosylaziridinofullerene, with amidines as the diamine source, is demonstrated for the first time. The present methods provide new routes to cyclic 1,2-diaminated [60]fullerenes.
RESUMO
The aim of this study is to assess alterations in heart function and structure in patients diagnosed with non-ST segment elevation acute myocardial infarction (NSTEAMI), unstable angina (UA), and stable angina (SA) 1 year after undergoing off-pump coronary artery bypass grafting (OPCABG) performed without extracorporeal circulation. A total of 182 patients who underwent OPCABG were included and classified into 3 groups based on their preoperative diagnosis: the NSTEAMI group (nâ =â 68), the UA group (nâ =â 64), and the SA group (nâ =â 50). Cardiac ultrasonography data were collected for all groups both preoperatively and 1 year postoperatively. Clinical data were subjected to statistical analysis. In the NSTEAMI group, postoperative observations revealed increases in left ventricular stroke volume and left ventricular end-systolic diameter, along with reductions in left ventricular end-diastolic volume (LVEDV) and left ventricular end-diastolic diameter (LVEDD) 1-year post-surgery. The UA group demonstrated decreases in LVEDV and LVEDD 1-year post-surgery. Similarly, the SA group exhibited an increase in left ventricular ejection fraction (LVEF) and reductions in LVEDV and LVEDD 1-year post-surgery. Comparative analysis of cardiac ultrasonography data revealed that the NSTEAMI group displayed significantly lower left ventricular stroke volume and notably higher left ventricular end-systolic diameter and volume compared to the UA and SA groups 1-year post-surgery. Furthermore, the SA group exhibited significantly elevated LVEF compared to the UA and NSTEAMI groups 1-year post-surgery. Cardiac ultrasonography findings indicate that all 3 groups exhibited improvements in cardiac function and left ventricular structure 1-year post-surgery. However, the NSTEAMI group demonstrated more substantial improvements in comparison to the UA and SA groups.
Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Idoso , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Ecocardiografia/métodos , Angina Instável/cirurgia , Angina Instável/fisiopatologia , Angina Instável/diagnóstico por imagem , Angina Estável/cirurgia , Angina Estável/fisiopatologia , Angina Estável/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Ponte de Artéria Coronária/métodosRESUMO
Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan-Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the "ssGSEA" algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.
Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Mapas de Interação de Proteínas , Curva ROCRESUMO
The Japanese pine sawyer, Monochamus saltuarius, as a beetle vector of Bursaphelenchus xylophilus (pine wood nematode), is an economically important forest pest in Eurasia. To feed on the phloem and xylem of conifers, M. saltuarius needs to overcome various stress factors, including coping with entomopathogenic bacteria and also various plant secondary compounds (PSCs). As an important adaptation strategy to colonize host trees, M. saltuarius deposit eggs in oviposition pits to shield their progeny. These pits harbor bacterial communities that are involved in the host adaptation of M. saltuarius to the conifers. However, the composition, origin, and functions of these oviposition pit bacteria are rarely understood. In this study, we investigated the bacterial community associated with M. saltuarius oviposition pits and their ability to degrade PSCs. Results showed that the bacterial community structure of M. saltuarius oviposition pits significantly differed from that of uninfected phloem. Also, the oviposition pit bacteria were predicted to be enriched in PSC degradation pathways. The microbial community also harbored a lethal strain of Serratia, which was significantly inhibited. Meanwhile, metatranscriptome analysis indicated that genes involved in PSCs degradation were expressed complementarily among the microbial communities of oviposition pits and secretions. In vitro degradation showed that bacteria cultured from oviposition pits degraded more monoterpenes and flavonoids than bacteria cultured from uninfected phloem isolates. Disinfection of oviposition pits increased the mortality of newly hatched larvae and resulted in a significant decrease in body weight in the early stages. Overall, our results reveal that M. saltuarius construct oviposition pits that harbor a diverse microbial community, with stronger PSCs degradation abilities and a low abundance of entomopathogenic bacteria, resulting in the increased fitness of newly hatched larvae.
Assuntos
Besouros , Pinus , Feminino , Animais , Besouros/microbiologia , Larva , Serratia , Árvores , Monoterpenos , Pinus/microbiologiaRESUMO
BACKGROUND: Cysteine-rich protein 2 (CSRP2) is discovered as oncogene. The study aims to investigate the clinical significance and potential mechanism of CSRP2 in head and neck squamous cell carcinoma (HNSCC). METHODS: CSRP2 expression was explored by immunohistochemistry tissue microarrays and Western blotting in HNSCC. The effect of CSRP2 on the cancer stemness and epithelial-to-mesenchymal transition (EMT) of HNSCC cells was investigated by sphere formation, wound healing, and transwell assays. The vitro and vivo experiments revealed that CSRP2 modulated cancer stemness and EMT phenotypes in HNSCC. RESULTS: CSRP2 was overexpressed in HNSCC patients and presented poor prognosis. CSRP2 knockdown inhibited the migration and invasion ability of the HNSCC cells. And CSRP2 expression was closely associated with CSCs markers, EMT-transcription factor, new oncoprotein, and immune checkpoint. CONCLUSION: The overexpression of CSRP2 indicates poor prognosis and plays a key role in maintaining the cancer cell stemness and EMT.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/genética , Fatores de Transcrição/genética , Fenótipo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/farmacologia , Proteínas Nucleares/genética , Proteínas com Domínio LIM/genéticaRESUMO
Medicinal plants constitute a source for designing clinically useful drugs targeting diseases through various mechanisms. Plant secondary metabolites can be used as lead compounds of drugs. Corynanthe alkaloids are highly abundant natural bioactive substances of various core structures possessing important properties such as nerve excitation and antimalarial and analgesic effects. In this review, we summarize and review the state-of-the-art corynanthe-type alkaloid research focusing on phytochemistry, pharmacology, and structural chemistry. Approximately 120 articles reporting 231 alkaloids classified into simple corynanthe, yohimbine, oxindole corynanthe, mavacurane, sarpagine, akuammiline, strychnos, and ajmaline-type groups were compiled. Relevant biological properties discussed include antiviral, antibacterial, anti-inflammatory, antimalarial, muscle-relaxant, vasorelaxant, and analgesic activities and activities affecting the main nervous and cardiac systems, as well as NF-κB inhibitory and Na+-glucose cotransporter inhibitory properties. This review provides insights and a reference for future studies, thus paving the way for the discovery of drugs based on corynanthe alkaloids.
Assuntos
Alcaloides , Antimaláricos , Plantas Medicinais , Pausinystalia , Alcaloides/farmacologia , Analgésicos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologiaRESUMO
In the present paper, a kind of noninvasive determination for human serum protein concentration of albumin, globulin and total protein was explored based on the technology of near-infrared reflectance spectra. Reflectance spectra on the tongue tip of 58 volunteers were collected. Because these is an nonlinear mapping relationship induced by the individual differences between these spectra data and serum protein concentration, SVM was used to establish quantitative regression models of 3 kinds of protein concentration respectively after the normalized spectral reflectance was calculated and the protein content statistics distribution of the sample set was analyzed. In addition, results of SVM were compared with that of PLS. The results show that the predictive effect for calibrated model of SVM is obviously better than that of PLS. Using SVM model to predict the prediction set, the correlation coefficients of ALB, GLB and TP are respectively 0.894, 0.931 and 0.863, and root mean square errors are 2.19, 1.93 and 4.38. So SVM can resist the impact of nonlinear factors among in-vivo determinations, and enhance the robustness of the models. Meanwhile it was also showed that the near infrared spectral information for tongue can relatively objectively reflect changes in human physiological and biochemical indexes, and this technology for noninvasive determination of serum protein concentration is highly feasible.