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This paper investigates the structure and aggregation stability of acrylic acid-acrylamide-diethyldiallylammonium chloride (FA367), followed by an investigation into the impact of acidic CO2 environments on the interaction between FA367 and cement slurry. The results showed that FA367 formed stable flocculation in cement slurry filtrate, which was not affected by acid gas CO2. With an FA367 concentration of 0.6%, the fluidity of the cement slurry measures 18.1 cm, but this fluidity is lost upon introducing CO2. At 90 °C, the compressive strength after 1, 3, and 7 days is 10.23, 77.48, and 62.97%, respectively, compared to pure cement. However, with the addition of CO2, the compressive strength increases to 27.03, 99.59, and 75.47%, respectively. The interaction between FA367 and cement slurry impedes cement hydration without altering hydration product composition. Instead, it fosters needle-like aggregations between hydration products, affecting the cement stone's compact structure. Upon CO2 introduction, these needle-like structures diminish, resulting in an overall more intact cement stone structure.
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OBJECTIVE: To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty (PKP) of vertebrae following local anesthesia. METHODS: From August 2019 to June 2021, 118 patients with thoraco lumbar osteoporotic fractures were treated and divided into observation group and control group, with 59 patients in each gruop. In observation group, there were 26 males and 33 females, aged from 57 to 80 years old with an average of (67.69±4.75)years old;14 patients on T11, 12 patients on T12, 18 patients on L1, 15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group. In control group, there were 24 males and 35 females, aged from 55 to 77 years old with an average of (68.00±4.43) years old;19 patients on T11, 11 patients on T12, 17patients on L1, 12 patients on L2;the same amount of normal saline was injected intramuscularly in control group. Observation indicators included operation time, intraoperative bleeding, visual analogue scale (VAS) evaluation and recording of preoperative (T0), intraoperative puncture(T1), and working cannula placement (T2) between two groups of patients, at the time of balloon dilation (T3), when the bone cement was injected into the vertebral body (T4), 2 hours after the operation (T5), and the pain degree at the time of discharge(T6);adverse reactions such as dizziness, nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery. RESULTS: All patients were successfully completed PKP via bilateral pedicle approach, and no intravenous sedative and analgesic drugs were used during the operation. There was no significant difference in preoperative general data and VAS(T0) between two groups (P>0.05). There was no significant difference in operation time and intraoperative blood loss between the two groups (P>0.05). VAS of T1, T2, T3, T4 and T5 in observation group were all lower than those in control group(P<0.05), and there was no significant difference in T6 VAS (P>0.05). T6 VAS between two groups were significantly lower than those of T0, and the difference was statistically significant (P<0.05). There was no significant difference in incidence of total adverse reactions between two groups (P>0.05). There was a statistically significant difference in the acceptance of repeat PKP surgery (P<0.05). CONCLUSION: Half an hour before operation, intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia, which could increase the comfort of patients during operation and 2 hours after operation, and improve patients satisfaction with surgery.
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Anestesia Local , Cifoplastia , Vértebras Lombares , Fraturas por Osteoporose , Vértebras Torácicas , Tramadol , Humanos , Feminino , Masculino , Idoso , Tramadol/administração & dosagem , Pessoa de Meia-Idade , Cifoplastia/métodos , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Fraturas por Osteoporose/cirurgia , Vértebras Lombares/cirurgia , Anestesia Local/métodos , Idoso de 80 Anos ou mais , Analgesia/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Fraturas da Coluna Vertebral/cirurgia , Analgésicos Opioides/administração & dosagemRESUMO
A new species of Papaveraceae, Corydalis sunhangii, in the section Trachycarpae, is described and illustrated from Nyingchi City, Xizang, China. The new species has some resemblance to Corydalis kingdonis, but differs by radical leaves prominent, usually several, blade tripinnate (vs. insignificant, few, blade bi- to triternate); cauline leaf usually one, much smaller than radical leaves, usually situated in lower half of stem (vs. usually two, larger than radical leaves, concentrated in upper third of stem); racemes densely 13-35-flowered (vs. rather lax, 4-11-flowered); claw of lower petal shallowly saccate (vs. very prominently and deeply saccate); capsule oblong, with raised lines of dense papillae (vs. broadly obovoid, smooth). Phylogenetic analysis, based on 68 protein-coding plastid genes of 49 samples, shows that C. sunhangii is not closely related to any hitherto described species, which is consistent with our morphological analysis.
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BACKGROUND: CD2-associated protein (CD2AP) is a podocyte-associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC. METHODS: Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT-qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan-Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP-related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor-infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells. RESULTS: We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration. CONCLUSIONS: Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression.
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Proteínas Adaptadoras de Transdução de Sinal , Carcinoma de Células Renais , Carcinoma , Proteínas do Citoesqueleto , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Variações do Número de Cópias de DNA , Prognóstico , Neoplasias Renais/genética , BiomarcadoresRESUMO
Studying the physicochemical properties and biological activities of Lycium barbarum polysaccharides(LBPs) is of great significance. The previous study had extracted LBPs(LBP-1, LBP-2, LBP-3, LBP-4, and LBP-5) by five different methods(cold water extraction, boiling water reflux extraction of the residue after cold water extraction, ultrasonic extraction with 50% ethanol, ultrasonic extraction with 25% ethanol of the residue after 50% ethanol extraction, and hot water extraction). In this study, the structures of the obtained five LBPs were characterized by UV spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the antioxidant, blood lipid-lowering, nitrosation-inhibting, acetylcholinesterase-inhibiting, and tyrosinase-inhibiting activities of the five LBPs were measured in vitro. The results showed that high-temperature extraction destroyed the polysaccharide structure, while ultrasound-assisted extraction ensured the structural integrity. The thermal stability and degradation behaviors differed among the five LBPs. However, the UV spectroscopic results of the five LBPs did not show significant differences, and all of the five LBPs showed the characteristic absorption peaks of proteins. LBP-3 and LBP-4 exhibited strong antioxidant activity, while LBP-3 had the strongest blood lipid-lowering activity. In addition, LBP-3 outperformed other LBPs in inhibiting nitrosation and acetylcholineste-rase, and LBP-2 showed the strongest inhibitory effect on tyrosinase. This study explored the effects of different extraction methods on the physicochemical properties and biological activities of LBPs, with a view to providing a basis for the selection of suitable extraction methods to obtain LBPs with ideal biological activities.
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Medicamentos de Ervas Chinesas , Lycium , Lycium/química , Monofenol Mono-Oxigenase , Acetilcolinesterase , Antioxidantes/farmacologia , Antioxidantes/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Lipídeos , Etanol , ÁguaRESUMO
PURPOSE: Diabetes is a chronic disease in metabolic disorder, and the pathology is characterized by insulin resistance and insulin secretion disorder in blood. In current, many studies have revealed that polysaccharides extracted from natural sources with significant anti-diabetic effects. Natural polysaccharides can ameliorate diabetes through different action mechanisms. All these polysaccharides are expected to have an important role in the clinic. METHODS: Existing polysaccharides for the treatment of diabetes are reviewed, and the mechanism of polysaccharides in the treatment of diabetes and its structural characteristics are described in detail. RESULTS: This article introduced the natural polysaccharide through different mechanisms of action in the treatment of diabetes, including oxidative stress, apoptosis, inflammatory response and regulation of intestinal bacteria. Natural polysaccharides can treat of diabetes by regulating signaling pathways is also a research hotspot. In addition, the structural characteristics of polysaccharides were explored. There are some structure-activity relationships between natural polysaccharides and the treatment of diabetes.
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Diabetes Mellitus , Resistência à Insulina , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Diabetes Mellitus/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Estresse OxidativoRESUMO
Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.
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Antineoplásicos , Imunoconjugados , Anticorpos de Domínio Único , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Moléculas de Adesão Celular , Citotoxinas , Ensaios Antitumorais Modelo de Xenoenxerto , Antígeno Carcinoembrionário , Proteínas Ligadas por GPIRESUMO
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
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Objective:To construct a scientific and technological evaluation system based on the needs of the pilot program for building a national high-quality hospital and establishing a national medical center.Methods:Xiangya Hospital of Central South University gradually improved its academic evaluation system by following the guidelines outlined in national authorities′ documents regarding "abolishing the five only" and "setting new standards", adhering to the guiding principles of "quality, contribution, efficiency, and impact" and employing the principles of "high-standard evaluation, quantitative evaluation, representative work evaluation, and third-party evaluation" .Results:The hospital established a comprehensive, scientific, and quantifiable indicator pool. These indicators were applied to various aspects of medical innovation evaluation, including awarding incentives, discipline assessment, professional promotion, personnel assessment, mentor selection for graduates, and excellence evaluation. Simultaneously, the hospital developed an intelligent platform for medical innovation evaluation and assessment in university-affiliated hospitals based on performance management theory.Conclusions:Through the construction and practice of the Xiangya technology evaluation system, the hospital further improved and optimized its academic evaluation work, guiding researchers to high-quality innovation and efficient translational research, ultimately promoting the high-quality development of the hospital.
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Objective To explore the clinical characteristics and treatment scheme of periprosthetic joint infection(PJI)caused by Cutibacterium avidum(C.avidum).Methods The diagnosis and treatment process of a patient with PJI caused by C.avidum was summarized,and relevant literatures in the database were retrieved for review.Results A 65-year-old female patient with body mass index(BMI)of 31.1 kg/m2 underwent left humeral head prosthesis replacement surgery following a left proximal humerus fracture.Ten months after the surgery,the pa-tient exhibited poor wound healing and oozing,along with limited movement of the left shoulder joint,and was diag-nosed infection following shoulder arthroplasty.Patient underwent debridement of the infected lesion and removal of the prosthesis.The tissue,bone cement and prosthesis were cultured for C.avidum.Four literatures were re-trieved and screened,a total of 30 patients with PJI(28 cases hip joint infection and 2 cases shoulder joint infection)caused by C.avidum were reported through literature retrieval,and 78.6%(n=22)total hip arthroplasty(THA)surgeries were performed using direct anterior approach(DAA).The positive rate of preoperative joint fluid culture was 71.4%,29 cases underwent surgical combined with sensitive antimicrobials treatment.Except for one patient who had repeated infection and underwent three surgeries,other patients had a good prognosis.Conclusion PJI caused by C.avidum is mostly seen in THA patients who are obese and undergo DAA,with a few cases reported after shoulder arthroplasty.The high sensitivity of preoperative joint fluid culture provides an important basis for the development of surgical strategies and anti-infection protocols.
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AIM:To rapidly evaluate the effective-ness,safety and economy of dienogest in the treat-ment of endometriosis so as to provide evidence-based reference for clinical drug selection and deci-sion.METHODS:Retrieved from PubMed,Embase,Cochrane Library,CNKI,SinoMed,Wanfang and health technology assessment(HTA)organization websites,HTA report,systematic review/Meta-anal-ysis and pharmacoeconomic study were included during the inception to Sep 2023.Data extraction and quality evaluation were carried out for the lit-erature that met the inclusion and exclusion crite-ria,and the research results were summarized and analyzed qualitatively.RESULTS:Nine systematic re-view/Meta-analyses,and 2 pharmacoeconomic studies were included.The quality of Meta-analysis literatures was low,and the quality of economic re-search was good.In terms of effectiveness,com-pared with no treatment,dienogest can significant-ly reduce postoperative recurrence rate,VAS score,and improve pregnancy rate and effective rate;Di-enogest has similar therapeutic effects in terms of recurrence rate as GnRHa and COC;With regard to recurrence rate and pregnancy rate,dienogest is superior to danazol,gestrinone,and mifepristone.In terms of safety,compared with placebo,the inci-dence of vaginal bleeding and headache was signifi-cantly increased with dienogest,and there was no difference in bone loss;The incidence of vaginal bleeding caused by dienogest was significantly high-er than that of GnRHa,but the incidence of hot flashes and bone loss was lower.In terms of econo-my,dienogest has a more cost-effective advantage comparing with GnRHa,but does not have econom-ic benefits comparing with COC.CONCLUSION:Di-enogest has good effectiveness and safety in the treatment of endometriosis,and economically su-perior to GnRHa,but inferior to COC.
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OBJECTIVE@#To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.@*METHODS@#The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups.@*RESULTS@#A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison.@*CONCLUSION@#Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.
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Humanos , Fíbula/cirurgia , Fraturas Ósseas/complicações , Tíbia/cirurgia , Consolidação da Fratura , Fixação Interna de Fraturas , Resultado do TratamentoRESUMO
OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
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Ratos , Animais , Eletroacupuntura , Ratos Sprague-Dawley , Serotonina , Pontos de Acupuntura , Dor Referida , Peptídeo Relacionado com Gene de Calcitonina , Transdução de Sinais , Colite/terapia , Indóis , SulfonamidasRESUMO
IRF family genes have been shown to be crucial in tumorigenesis and tumour immunity. However, information about the role of IRF in the systematic assessment of pan-cancer and in predicting the efficacy of tumour therapy is still unknown. In this work, we performed a systematic analysis of IRF family genes in 33 tumour samples, including expression profiles, genomics and clinical characteristics. We then applied Single-Sample Gene-Set Enrichment Analysis (ssGSEA) to calculate IRF-scores and analysed the impact of IRF-scores on tumour progression, immune infiltration and treatment efficacy. Our results showed that genomic alterations, including SNPs, CNVs and DNA methylation, can lead to dysregulation of IRFs expression in tumours and participate in regulating multiple tumorigenesis. IRF-score expression differed significantly between 12 normal and tumour samples and the impact on tumour prognosis and immune infiltration depended on tumour type. IRF expression was correlated to drug sensitivity and to the expression of immune checkpoints and immune cell infiltration, suggesting that dysregulation of IRF family expression may be a critical factor affecting tumour drug response. Our study comprehensively characterizes the genomic and clinical profile of IRFs in pan-cancer and highlights their reliability and potential value as predictive markers of oncology drug efficacy. This may provide new ideas for future personalized oncology treatment.
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Neoplasias , Humanos , Biomarcadores , Carcinogênese , Transformação Celular Neoplásica , Imunoterapia , Reprodutibilidade dos Testes , Microambiente Tumoral , Fatores Reguladores de InterferonRESUMO
RATIONALE: Gefitinib is a potent and selective orally active growth factor receptor (EGFR)-tyrosine kinase inhibitor that is commonly used to treat advanced non-small cell lung cancer patients with activating EGFR mutations. Hearing impairment with gefitinib was sparsely reported. In this report, we describe a case of sensorineural deafness associated with the administration of gefitinib, with a Naranjo score of 7. PATIENT CONCERNS: An 81-year-old female was diagnosed with lung adenocarcinoma with bone metastasis and an EGFR-activating mutation. The patient was prescribed gefitinib tablets at a daily dose of 250 mg for lung adenocarcinoma treatment. However, the patient experienced moderate to severe bilateral sensorineural deafness, primarily in her right ear, after taking gefitinib. Following the cessation of gefitinib administration, the patient exhibited partial restoration of auditory function. Upon resuming the medication, she experienced a worsening of deafness. DIAGNOSES: The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness. INTERVENTIONS: The otolaryngologist recommended bilateral hearing aids to enhance hearing function. OUTCOMES: Throughout our follow-up period, the patient did not receive a hearing aid implant. LESSONS: This article first reported the ototoxicity caused by gefitinib. While rare, our report highlights that gefitinib-induced sensorineural deafness is possible and its mechanisms are still unclear. This adverse reaction should be monitored closely during clinical application of gefitinib to improve patient outcomes.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Surdez , Perda Auditiva Neurossensorial , Neoplasias Pulmonares , Humanos , Feminino , Idoso de 80 Anos ou mais , Gefitinibe/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/patologia , Perda Auditiva Neurossensorial/induzido quimicamente , Receptores ErbB/metabolismo , MutaçãoRESUMO
Although hepatocellular carcinoma (HCC) is rather frequent, little is known about the molecular pathways underlying its development, progression, and prognosis. In the current study, we comprehensively analyzed the deferentially expressed metabolism-related genes (MRGs) in HCC based on TCGA datasets attempting to discover the potentially prognostic genes in HCC. The up-regulated MRGs were further subjected to analyze their prognostic values and protein expressions. Twenty-seven genes were identified because their high expressions were significant in OS, PFS, DFS, DSS, and HCC tumor samples. They were then used for GO, KEGG, methylation, genetics changes, immune infiltration analyses. Moreover, we established a prognostic model in HCC using univariate assays and LASSO regression based on these MRGs. Additionally, we also found that SLC38A1, an amino acid metabolism closely related transporter, was a potential prognostic gene in HCC, and its function in HCC was further studied using experiments. We found that the knockdown of SLC38A1 notably suppressed the growth and migration of HCC cells. Further studies revealed that SLC38A1 modulated the development of HCC cells by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism. In conclusion, this study identified the potentially prognostic MRGs in HCC and uncovered that SLC38A1 regulated HCC development and progression by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism, which might provide a novel marker and potential therapeutic target in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Glutamina/metabolismo , Neoplasias Hepáticas/patologia , Proliferação de Células/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Metabolismo Energético , Linhagem Celular Tumoral , Sistema A de Transporte de Aminoácidos/metabolismoRESUMO
AIMS: Our study focused on exploring the feasible prognostic laboratory parameters of HCC and establishing a score model to estimate individualized overall survival (OS) in HCC after resection. METHODS: Four hundred and sixty-one patients with HCC who underwent hepatectomy between January 2010 and December 2017 was enrolled in this investigation. Cox proportional hazards model was conducted to analyze the prognostic value of laboratory parameters. The score model construction was based on the forest plot results. Overall survival was evaluated by Kaplan-Meier method and the log-rank test. The novel score model was validated in an external validation cohort from a different medical institution. RESULTS: We identified that alpha fetoprotein (AFP), total bilirubin (TB), fibrinogen (FIB), albumin (ALB), and lymphocyte (LY) were independent prognostic factors. High AFP, TB, FIB (HR > 1, p < 0.05), and low ALB, LY (HR < 1, p < 0.05) were associated with the survival of HCC. The novel score model of OS based on these five independent prognostic factors achieved high C-index of 0.773 (95% confidence interval [CI]: 0.738-0.808), which was significantly higher than those of the single five independent factors (0.572-0.738). The score model was validated in the external cohort whose C-index was 0.7268 (95% CI: 0.6744-0.7792). CONCLUSION: The novel score model we established was an easy-to-use tool which could enable individualized estimation of OS in patients with HCC who underwent curative hepatectomy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas , Fibrinogênio , Bilirrubina , Prognóstico , Albuminas , Hepatectomia , Linfócitos/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury. METHODS: To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity. RESULTS: Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism. CONCLUSION: Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.
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Doença Hepática Induzida por Substâncias e Drogas , Polygonum , Animais , Camundongos , Polygonum/química , Lipidômica , Fígado , Lipídeos/farmacologia , Glicerofosfolipídeos/metabolismo , Glicerofosfolipídeos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
In this study, five polysaccharides from Lycium barbarum(LBPs)(LBP-1-LBP-5) were selectively extracted by different extraction methods, and the chemical composition, structural characteristics, and biological activities of LBPs were explored. The results of chemical composition analysis showed that alkaloids were not detected in the five LBPs. The total polysaccharide content was(81.95%±1.6%)-(92.96%±0.76%), the uronic acid content was(8.26%±0.46%)-(24.81%±0.46%), and the protein content was(0.06%±0.03%)-(1.35%±0.13%). The monosaccharide compositions of the five LBPs were basically same, mainly including glucose, xylose, and galactose. However, there was significant difference in the content ratio of different monosaccharide. The results of infrared spectra analysis indicated that the five LBPs had typical infrared spectral characteristics of polysaccharides. The results of nuclear magnetic resonance characteristic spectrum analysis revealed that the five LBPs had two configurations of α and ß. Meanwhile, there were triple helix structures in LBP-2, LBP-3, and LBP-4, which enhanced the activities of polysaccharides. The results of activities screening suggested that the biological activities of the five LBPs were significantly different. LBP-3 showed the highest lipid oxidation clearance rate, and its antioxidant activity was equivalent to that of the positive control group. The inhibitory rate of LBP-4 on α-amylase and its activation rate of alcohol dehydrogenase were better than those of other fractions, and the inhibitory rate of LBP-4 on α-amylase was slightly higher than that of the positive control group when the mass concentration was 10 g·L~(-1). LBP-2 showed stronger inhibitory activity against α-glucosidase and hyaluronidase. This study provides references for the precise development and utilization of LBPs.
Assuntos
Medicamentos de Ervas Chinesas , Lycium , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Lycium/química , Antioxidantes/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/química , MonossacarídeosRESUMO
BACKGROUND: Pneumatic tube system (PTS) may be associated with preanalytical hemolysis. The objective of this study was to evaluate the effects of PTS on biochemical and immunological tests susceptible to hemolysis and try to find ways to reduce the result bias caused by PTS. METHODS: Laboratory parameters were compared between PTS without centrifuging group, PTS after centrifuging group, PTS with serum group, and hand-delivered (HD) group. Studies were performed to access the influence of different PTS transport frequencies on laboratory assays. RESULTS: PTS transportation resulted in obviously increase in LDH (lactate dehydrogenase) and NSE (neuron-specific enolase) results (LDH: Bias = 17.95%, 95% confidence interval (CI) = -3.13-39.02; p < 0.001; NSE: Bias = 64.26%, 95% CI = -21.29-149.82; p < 0.001; respectively). After pre-centrifugation, no statistical difference was observed in LDH results (Bias = 2.83%, 95% CI = -13.00-18.65; p = 0.737). However, the bias of NSE still reach 19.16% (95% CI = -41.78-80.11), which exceeded the clinical acceptable range (p = 0.017). Both LDH(p = 0.931) and NSE(p > 0.999) show no statistical difference between PTS with serum group and HD group (LDH: Bias = -1.60%, 95% CI = -6.00-2.81; NSE: Bias = -3.68%, 95% CI = -11.35-3.99). CONCLUSION: PTS can lead to falsely increased LDH and NSE test results. Only loading the centrifuged upper serum in new tubes during PTS transport can eliminate the results bias of NSE.