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1.
Ultrasound Med Biol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39097493

RESUMO

OBJECTIVE: To explore the performance of ultrasound image-based radiomics in predicting World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading of clear-cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted via histopathological examination on participants with ccRCC from January 2021 to August 2023. Participants were randomly allocated to a training set and a validation set in a 3:1 ratio. The maximum cross-sectional image of the lesion on the preoperative ultrasound image was obtained, with the region of interest (ROI) delineated manually. Radiomic features were computed from the ROIs and subsequently normalized using Z-scores. Wilcoxon test and least absolute shrinkage and selection operator (LASSO) regression were applied for feature reduction and model development. The performance of the model was estimated by indicators including area under the curve (AUC), sensitivity and specificity. RESULTS: A total of 336 participants (median age, 57 y; 106 women) with ccRCC were finally included, of whom 243 had low-grade tumors (grade 1-2) and 93 had high-grade tumors (grade 3-4). A total of 1163 radiomic features were extracted from the ROIs for model construction and 117 informative radiomics features selected by Wilcoxon test were submitted to LASSO. Our ultrasound-based radiomics model included 51 features and achieved AUCs of 0.90 and 0.79 for the training and validation sets, respectively. Within the training set, the sensitivity and specificity measured 0.75 and 0.92, respectively, whereas in the validation set, the sensitivity and specificity measured 0.65 and 0.84, respectively. In the subgroup analysis, for the training and validation sets Philips AUCs were 0.91 and 0.75, Toshiba AUCs were 0.82 and 0.90, and General Electric AUCs were 0.95 and 0.82, respectively. CONCLUSION: Ultrasound-based radiomics can effectively predict the WHO/ISUP grading of ccRCC.

2.
BMC Urol ; 24(1): 131, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909202

RESUMO

OBJECTIVE: The incidence of recurrent hernia after radical resection of prostate cancer is high, so this article discusses the incidence and risk factors of inguinal hernia after radical resection of prostate cancer. METHODS: This case control study was conducted in The First People's Hospital of Huzhou clinical data of 251 cases underwent radical resection of prostate cancer in this hospital from March 2019 to May 2021 were retrospectively analyzed. According to the occurrence of inguinal hernia, the subjects were divided into study group and control group, and the clinical data of each group were statistically analyzed, Multivariate Logistic analysis was performed to find independent influencing factors for predicting the occurrence of inguinal hernia. The Kaplan-Meier survival curve was drawn according to the occurrence and time of inguinal hernia. RESULTS: The overall incidence of inguinal hernia after prostate cancer surgery was 14.7% (37/251), and the mean time was 8.58 ± 4.12 months. The average time of inguinal hernia in patients who received lymph node dissection was 7.61 ± 4.05 (month), and that in patients who did not receive lymph node dissection was 9.16 ± 4.15 (month), and there was no significant difference between them (P > 0.05). There were no statistically significant differences in the incidence of inguinal hernia with age, BMI, hypertension, diabetes, PSA, previous abdominal operations and operative approach (P > 0.05), but there were statistically significant differences with surgical method and pelvic lymph node dissection (P < 0.05). The incidence of pelvic lymph node dissection in the inguinal hernia group was 24.3% (14/57), which was significantly higher than that in the control group 11.8% (23/194). Logistic regression analysis showed that pelvic lymph node dissection was a risk factor for inguinal hernia after prostate cancer surgery (OR = 0.413, 95%Cl: 0.196-0.869, P = 0.02). Kaplan-Meier survival curve showed that the rate of inguinal hernia in the group receiving pelvic lymph node dissection was significantly higher than that in the control group (P < 0.05). CONCLUSION: Pelvic lymph node dissection is a risk factor for inguinal hernia after radical resection of prostate cancer.


Assuntos
Hérnia Inguinal , Complicações Pós-Operatórias , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Hérnia Inguinal/epidemiologia , Hérnia Inguinal/cirurgia , Neoplasias da Próstata/cirurgia , Fatores de Risco , Incidência , Estudos de Casos e Controles , Idoso , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Excisão de Linfonodo , Correlação de Dados
3.
Signal Transduct Target Ther ; 9(1): 91, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627387

RESUMO

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.


Assuntos
NF-kappa B , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Regulação para Baixo/genética , Cirrose Hepática/metabolismo , Macrófagos/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores de Quimiocinas , Proteína A4 de Ligação a Cálcio da Família S100
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1018741

RESUMO

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1031438

RESUMO

Based on the view of "spleen deficiency generating turbidity", it is believed that the main pathology of irritable bowel syndrome diarrhea-predominant (IBS-D) is spleen deficiency and turbidity excess, with spleen deficiency as the root and turbidity stagnating intestines as the branch, and the treatment principle of draining turbidity and transporting the center was proposed. In the acute stage, turbidity excess is the main cause, the treatment should unblock the bowels and discharge turbidity, commonly with modified Zhishi Daozhi Decoction (枳实导滞汤); in the remission stage, spleen deficiency is the main cause, the treatment should boost qi and fortify the spleen, commonly with modified Qiwei Baizhu Powder (七味白术散). Treating the branch in acute conditions, and treating the root in moderate conditions, so as to help restore the conduction function of the intestines and bowels, the transportation and transformation function of the spleen and stomach, then the water and grains have their own way, clear and turbid each in its own way.

6.
World J Psychiatry ; 13(10): 714-723, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-38058685

RESUMO

BACKGROUND: Cognitive dysfunction in epileptic patients is a high-incidence complication. Its mechanism is related to nervous system damage during seizures, but there is no effective diagnostic biomarker. Neuronal pentraxin 2 (NPTX2) is thought to play a vital role in neurotransmission and the maintenance of synaptic plasticity. This study explored how serum NPTX2 and electroencephalogram (EEG) slow wave/fast wave frequency ratio relate to cognitive dysfunction in patients with epilepsy. AIM: To determine if serum NPTX2 could serve as a potential biomarker for diagnosing cognitive impairment in epilepsy patients. METHODS: The participants of this study, conducted from January 2020 to December 2021, comprised 74 epilepsy patients with normal cognitive function (normal group), 37 epilepsy patients with cognitive dysfunction [epilepsy patients with cognitive dysfunction (ECD) group] and 30 healthy people (control group). The mini-mental state examination (MMSE) scale was used to evaluate cognitive function. We determined serum NPTX2 levels using an enzyme-linked immunosorbent kit and calculated the signal value of EEG regions according to the EEG recording. Pearson correlation coefficient was used to analyze the correlation between serum NPTX2 and the MMSE score. RESULTS: The serum NPTX2 level in the control group, normal group and ECD group were 240.00 ± 35.06 pg/mL, 235.80 ± 38.01 pg/mL and 193.80 ± 42.72 pg/mL, respectively. The MMSE score was lowest in the ECD group among the three, while no significant difference was observed between the control and normal groups. In epilepsy patients with cognitive dysfunction, NPTX2 level had a positive correlation with the MMSE score (r = 0.367, P = 0.0253) and a negative correlation with epilepsy duration (r = -0.443, P = 0.0061) and the EEG slow wave/fast wave frequency ratio value in the temporal region (r = -0.339, P = 0.039). CONCLUSION: Serum NPTX2 was found to be related to cognitive dysfunction and the EEG slow wave/fast wave frequency ratio in patients with epilepsy. It is thus a potential biomarker for the diagnosis of cognitive impairment in patients with epilepsy.

7.
J Integr Med ; 21(6): 528-536, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37957088

RESUMO

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Avaliação de Resultados em Cuidados de Saúde , Padrões de Referência , Reprodutibilidade dos Testes , Projetos de Pesquisa , Ensaios Clínicos como Assunto
8.
Zhonghua Nan Ke Xue ; 29(1): 38-42, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-37846830

RESUMO

OBJECTIVE: To investigate the clinical effect of a modified vascular blocking technique in intrafascial nerve-sparing laparoscopic radical prostatectomy (INLRP). METHODS: We retrospectively studied the clinical data on 13 cases of INLRP completed via a modified vascular blocking technique between July 2021 and August 2022. The patients ranged in age from 64 to 73 (68.8 ± 3.15) years, with elevated PSA of 4.71-16.12 (9.71 ± 3.50) µg/L preoperatively. Prostate cancer was confirmed in all the cases by ultrasound-guided perineal prostate needle biopsy, with Gleason 6 in 7 cases and Gleason 7 in 6 cases. MRI revealed no preoperative tumor breakthrough in the prostatic capsule or pelvic lymph node metastasis. All the patients received INLRP with a modified superficial suture dorsal vein complex (DVC) combined with lateral prostatic pedicle vascular blocking. RESULTS: Prostatic capsule rupture occurred in 1 case during the operation, with positive resection margin indicated by rapid intraoperative frozen biopsy, so the lateral fascia resection was modified. No positive resection margin was found in any of the cases in postoperative pathological examinations. Urinary continence was restored in 8 cases immediately after surgery and in the other 5 within 2 weeks after catheter removal. At 1 month after surgery, all the patients were medicated with low-dose tadalafil (5 mg qd), and IIEF-5 scores of >15 were achieved in 4 cases (31%) at 1 month and in another 8 (62%) at 3 months postoperatively. CONCLUSION: INLRP via modified vascular blocking showed the advantages of desirable intraoperative bleeding control and postoperative tumor control, restoration of urinary continence and relatively satisfactory recovery of erectile function. However, due to the small sample size, short follow-up time and lack of control, our findings need to be further verified by more clinical studies.


Assuntos
Laparoscopia , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Próstata/cirurgia , Próstata/patologia , Margens de Excisão , Estudos Retrospectivos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Laparoscopia/métodos
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-969983

RESUMO

Based on data mining technology, the acupoints compatibility rules of acupuncture for depression diseases were explored. The randomized controlled trial (RCT) articles regarding acupuncture for depression diseases published from establishment of database to September 2nd, 2022 were searched in CNKI database, Wangfang database, VIP database, SinoMed database, PubMed, EMbase, Web of Science and Cochrane Library. The use frequency of acupoints, meridian tropism, selection of special acupoints and acupoint association rules for five common depression diseases, including primary depression, post-stroke depression, menopausal syndrome, psychoneurosis and anxiety disorder, were analyzed by Python programming language. Cytoscape software was used to analyze the acupoint association and the disease-acupoint co-occurrence network. As a result, totally 387 articles were included, and 319 acupoints prescriptions for the above five common depression diseases were extracted, involving 159 acupoints. The use frequency of acupoints was 2 574 times in total. The frequently-used acupoints were Baihui (GV 20), Sanyinjiao (SP 6), Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Yintang (GV 24+), Zusanli (ST 36), Hegu (LI 4), Sishencong (EX-HN 1) and Taixi (KI 3), etc. The frequently involved meridians were the governor vessel, foot-taiyang bladder meridian, foot-taiyin spleen meridian, and foot-jueyin liver meridian. The frequency of the special acupoints from high to low was crossing points, five-shu points, yuan-primary points, back-shu points, luo-connecting points, and eight confluent points, etc, which were often used in combination with "Baihui (GV 20)-Yintang (GV 24+)" (the highest degree of association). At the same time, the analysis of the co-occurrence network of depression diseases and acupoints showed that the core acupoints group of acupuncture for depression diseases were Baihui (GV 20), Taichong (LR 3), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6) and Sanyinjiao (SP 6). In conclusion, acupuncture treatment for depression diseases has gradually formed a rule of acupoint compatibility, with special acupoint as the main body and "unblocking the governor vessel, and regulating the spirit and qi " as the main therapeutic principle.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Mineração de Dados , Depressão , Meridianos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
JOURNAL OF RARE DISEASES ; (4): 50-54, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005060

RESUMO

  Objective  Mohr-Tranebjaerg syndrome (MTS) is a rare X-linked neurodegenerative disorder which usually involving hearing impairment, gradual dystonia, and other symptoms. In this study, we perform analyzed the genetic makeup of a family with this rare Mohr-Tranebjaerg syndrome.  Methods  We collected the clinical data of the family, did the whole exome sequencing on the proband Ⅲ6 with a rare mutation, and verified the mutation in another affected family member Ⅲ5 and unaffected members Ⅰ1, Ⅰ2, Ⅱ1, Ⅱ5, Ⅱ7, Ⅱ8, Ⅲ7.  Results  The patients in the family all showed early-onset deafness. More than a couple of affected male members have dystonia with/without mental disorders. Genetic testing results showed the proband Ⅲ6 had a c.133-2delA in TIMM8A (NM_ 004085.3, DDP1), highly likely pathogenic(LP). This variation was detected in affected Ⅲ5 as well as the unaffected females Ⅰ1, Ⅱ5, Ⅱ7.  Conclusions  MTS caused by the rare TIMM8A mutation, the molecular etiology of the family with this rare disease, is highly consistent with the clinical manifestations and segregation. Other than the deafness, other symptoms varied among the affected family members. Genetic diagnosis for such X-linked diseases can also identify female heterozygotes. Genetic and reproduction counseling can help families in the family planning.

11.
Journal of Integrative Medicine ; (12): 528-536, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010962

RESUMO

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Avaliação de Resultados em Cuidados de Saúde , Padrões de Referência , Reprodutibilidade dos Testes , Projetos de Pesquisa , Ensaios Clínicos como Assunto
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-982700

RESUMO

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.


Assuntos
Flavonoides/química , Cajanus , Estrutura Molecular , Chalconas/química
13.
Hepatol Commun ; 7(2): e0046, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345896

RESUMO

NAFLD is a series of liver disorders, and it has become the most prevalent hepatic disease to date. However, there are no approved and effective pharmaceuticals for NAFLD owing to a poor understanding of its pathological mechanisms. While emerging studies have demonstrated that m6A modification is highly associated with NAFLD. In this review, we summarize the general profile of NAFLD and m6A modification, and the role of m6A regulators including erasers, writers, and readers in NAFLD. Finally, we also highlight the clinical significance of m6A in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Metilação de RNA
14.
BMC Urol ; 22(1): 120, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922856

RESUMO

OBJECTIVE: To investigate the expression intensity of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma and its predictive value for the recurrence after transurethral resection of bladder tumor. METHODS: A retrospective analysis was made of 194 specimens who underwent transurethral resection of bladder tumors in our hospital from January 2014 to January 2016 and completed follow-up. The expression intensity of CA-IX and the clinical data of the patients were analyzed, and the subjects were divided into positive group and negative group according to the expression intensity of CA-IX. The age, gender, T stage, degree of differentiation, tumor number, tumor diameter, recurrence of each group was analyzed. Logistic univariate and multivariate analysis was used successively to find independent influencing factors for predicting the recurrence of bladder urothelial carcinoma after resection. The Kaplan-Meier survival curve was drawn according to the relationship between CA-IX expression intensity and postoperative recurrence. RESULTS: The positive expression rates of CA-IX in bladder urothelial carcinomas were 68.1% (132/194). The positive expression of CA-IX had no statistical significance with age, gender and tumor diameter (P > 0.05), while the positive expression of CA-IX had statistical significance with tumor T stage, tumor differentiation, tumor number and recurrence (P < 0.05); Logistic regression analysis showed that clinical T stage, tumor differentiation, tumor number, and CA-IX expression intensities were independent risk factors for predicting recurrence of bladder urothelial carcinoma after resection (P < 0.05); There were 59 cases of recurrence in the positive expression of CA-IX group, with a recurrence rate of 44.69% (59/132), and 17 cases of recurrence in the negative expression group, with a recurrence rate of 27.41% (17/62). The mean recurrence time of CA-IX positive group was 29.93 ± 9.86 (months), and the mean recurrence time of CA-IX negative group was 34.02 ± 12.44 (months). The Kaplan-Meier survival curve showed that the recurrence rate and recurrence time of patients with positive expression of CA-IX in bladder urothelial carcinomas were significantly higher than those of patients with negative expression of CA-IX. CONCLUSION: CA-IX is highly expressed in bladder urothelial carcinoma, is a good tumor marker, and can be used as a good indicator for predicting the recurrence of bladder urothelial carcinoma after transurethral resection of bladder tumor.


Assuntos
Anidrases Carbônicas , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Anidrase Carbônica IX , Anidrases Carbônicas/metabolismo , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
15.
Theranostics ; 12(9): 4163-4180, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35673582

RESUMO

Rationale: Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant disease with the complex immune microenvironment, which ultimately influence clinic outcomes of patients. However, the spatial expression patterns of diverse immune cells among tumor microenvironment remain to be further deciphered. Methods: Spatial transcriptomics sequencing (ST) was implemented on two portions of HCC specimens. Differentially expressed genes, cell cycle phases, epithelial-mesenchymal features, pseudo-time and immune infiltration analysis were applied to demonstrate the intratumor heterogeneity and define the specific immune-related regions, and the results were further validated by a second analysis on another ST study. In vitro and in vivo experiments were conducted to confirm the functional mechanisms of key molecules such as CCL15, CCL19 and CCL21. Clinical tissue samples were used to assess their potential prognostic and therapeutic values. Results: Totally, 7553 spots were categorized into 15 subsets by hierarchical clustering, and malignant subsets with intratumor heterogeneity phenotypes were identified. Spatial heterogeneity from distinct sectors highlights specific chemokines: CCL15 is remarkable in the core region of the carcinoma sector and facilitates the immunosuppressive microenvironment by recruiting and polarizing M2-like macrophages in vitro and in vivo; High expression of CCL15 and CD163 respectively predicts poor prognosis of HCC patients, and the combined application of them has better predictive value. CCL19 and CCL21, sharing similar spatial expression patterns, are highly-correlated and prominent in the immune infiltration enrichment and recruit CD3+ T cells and CD20+ B cells to inhibit the growth of HCC, indicating a good prognosis of HCC patients. Conclusions: Taken together, our studies preliminarily reveal intratumor heterogeneity of HCC based on ST techniques and unravel the previously unexplored spatial expression patterns in the immune microenvironment. We also highlight the clinical significance and spatial discrepancy of key molecules, providing novel insight for further developing therapeutic strategies in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Transcriptoma/genética , Microambiente Tumoral/genética
16.
Microbiol Spectr ; 10(3): e0229621, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35499324

RESUMO

Sponge microbiomes are typically profiled by analyzing the community DNA of whole tissues, which does not distinguish the taxa residing within sponge cells from extracellular microbes. To uncover the endosymbiotic microbiome, we separated the sponge cells to enrich the intracellular microbes. The intracellular bacterial community of sponge Euryspongia arenaria was initially assessed by amplicon sequencing, which indicated that it hosts three unique phyla not found in the extracellular and bulk tissue microbiomes. These three phyla account for 66% of the taxonomically known genera in the intracellular microbiome. The shotgun metagenomic analysis extended the taxonomic coverage to viruses and eukaryotes, revealing the most abundant signature taxa specific to the intracellular microbiome. Functional KEGG pathway annotation demonstrated that the endosymbiotic microbiome hosted the greatest number of unique gene orthologs. The pathway profiles distinguished the intra- and extracellular microbiomes from the tissue and seawater microbiomes. Carbohydrate-active enzyme analysis further discriminated each microbiome based on their representative and dominant enzyme families. One pathway involved in digestion system and family esterase had a consistently higher level in intracellular microbiome and could statistically differentiate the intracellular microbiome from the others, suggesting that triacylglycerol lipases could be the key functional component peculiar to the endosymbionts. The identified higher abundance of lipase-related eggNOG categories further supported the lipid-hydrolyzing metabolism of endosymbiotic microbiota. Pseudomonas members, reported as lipase-producing bacteria, were only in the endosymbiotic microbiome, meanwhile Pseudomonas also showed a greater abundance intracellularly. Our study aided a comprehensive sponge microbiome that demonstrated the taxonomic and functional specificity of endosymbiotic microbiota. IMPORTANCE Sponges host abundant microbial symbionts that can produce an impressive number of novel bioactive metabolites. However, knowledge on intracellular (endosymbiotic) microbiota is scarce. We characterize the composition and function of the endosymbiotic microbiome by separation of sponge cells and enrichment of intracellular microbes. We uncover a noteworthy number of taxa exclusively in the endosymbiotic microbiome. We unlock the unique pathways and enzymes of endosymbiotic taxa. This study achieves a more comprehensive sponge microbial community profile, which demonstrates the structural and functional specificity of the endosymbiotic microbiome. Our findings not only open the possibility to reveal the low abundant and the likely missed microbiota when directly sequencing the sponge bulk tissues, but also warrant future in-depth exploration within single sponge cells.


Assuntos
Microbiota , Poríferos , Animais , Lipase/genética , Filogenia , Poríferos/genética , Poríferos/microbiologia , RNA Ribossômico 16S/genética
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-929244

RESUMO

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.


Assuntos
Antivirais/farmacologia , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Illicium/química , Éteres Fenílicos
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-954628

RESUMO

Non-recurrent laryngeal nerve (NRLN) is a rare anatomic variation of the recurrent laryngeal nerve, which is often associated with right subclavian artery variation on the right side and more rare on the left side, usually accompanied with visceral inversion. Injury will lead to permanent paralysis of the vocal cord, bilateral nerve injury will even contribute to dyspnea in patients, breathing only with the aid of ventilator, in which case postoperative tracheotomy treatment is needed, leading to obvious influence on the daily life of patients. We reviewed the progress of NRLN in terms of histology and embryology development, anatomical classification, improvement and identification of related preoperative examination, intraoperative nerve identification, exploration and protection, and postoperative injury response, with the aim to provide some reference for improvement of thyroid surgery in clinical diagnosis and treatment.

20.
Acta Pharmaceutica Sinica ; (12): 2101-2107, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-936574

RESUMO

This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC50) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.

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