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1.
Nat Commun ; 15(1): 6810, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122682

RESUMO

Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate a high-resolution contact map of myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq and HiChIP from myeloma cell lines, patient-derived myeloma cells and normal plasma cells. Our comprehensive transcriptomic and phenomic analyses prioritize candidate genes with biological and clinical implications in myeloma. We show that myeloma cells frequently acquire SE that transcriptionally activate an oncogene PPP1R15B, which encodes a regulatory subunit of the holophosphatase complex that dephosphorylates translation initiation factor eIF2α. Epigenetic silencing or knockdown of PPP1R15B activates pro-apoptotic eIF2α-ATF4-CHOP pathway, while inhibiting protein synthesis and immunoglobulin production. Pharmacological inhibition of PPP1R15B using Raphin1 potentiates the anti-myeloma effect of bortezomib. Our study reveals that myeloma cells are vulnerable to perturbation of PPP1R15B-dependent protein homeostasis, highlighting a promising therapeutic strategy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo , Proteína Fosfatase 1 , Proteostase , Super Intensificadores , Fator de Transcrição CHOP , Animais , Humanos , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , Bortezomib/farmacologia , Linhagem Celular Tumoral , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 2 em Eucariotos/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 1/genética , Super Intensificadores/genética , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-39106958

RESUMO

BACKGROUND: More effective methods are urgently needed for predicting the pathological grade and lymph node metastasis of cT1-stage lung adenocarcinoma. METHODS: We analyzed the relationships between CT quantitative parameters (including three-dimensional parameters) and pathological grade and lymph node metastasis in cT1-stage lung adenocarcinoma patients of our center between January 2015 and December 2023. RESULTS: A total of 343 patients were included, of which there were 233 males and 110 females, aged 61.8 ± 9.4 (30-82) years. The area under the receiver operating characteristic (ROC) curve for predicting the pathological grade of lung adenocarcinoma using the consolidation tumor ratio (CTR) and the solid volume ratio (SVR) were 0.761 and 0.777, respectively. The areas under the ROC curves (AUCs) for predicting lymph node metastasis were 0.804 and 0.873, respectively. Multivariate logistic regression analysis suggested that the SVR is an independent predictor of highly malignant lung adenocarcinoma pathology, while the SVR and pathological grade are independent predictors of lymph node metastasis. The sensitivity of predicting the pathological grading of lung adenocarcinoma based on SVR>5% is 97.2%, with a negative predictive value of 96%. The sensitivity of predicting lymph node metastasis based on SVR>47.1% is 97.3%, and the negative predictive value is 99.5%. CONCLUSIONS: The SVR has greater diagnostic value than the CTR in the preoperative prediction of pathologic grade and lymph node metastasis in stage cT1-stage lung adenocarcinoma patients, and the SVR may replace the diameter and CTR as better criteria for guiding surgical implementation.

3.
World J Gastrointest Surg ; 16(6): 1558-1570, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983340

RESUMO

BACKGROUND: Rectal cancer ranks as the second leading cause of cancer-related mortality worldwide, necessitating surgical resection as the sole treatment option. Over the years, there has been a growing adoption of minimally invasive surgical techniques such as robotic and laparoscopic approaches. Robotic surgery represents an innovative modality that effectively addresses the limitations associated with traditional laparoscopic techniques. While previous studies have reported favorable perioperative outcomes for robot-assisted radical resection in rectal cancer patients, further evidence regarding its oncological safety is still warranted. AIM: To conduct a comparative analysis of perioperative and oncological outcomes between robot-assisted and laparoscopic-assisted low anterior resection (LALAR) procedures. METHODS: The clinical data of 125 patients who underwent robot-assisted low anterior resection (RALAR) and 279 patients who underwent LALAR resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to November 2022 were retrospectively analyzed. After performing a 1:1 propensity score matching, the patients were divided into two groups: The RALAR group and the LALAR group (111 cases in each group). Subsequently, a comparison was made between the short-term outcomes within 30 d after surgery and the 3-year survival outcomes of these two groups. RESULTS: Compared to the LALAR group, the RALAR group exhibited a significantly earlier time to first flatus [2 (2-2) d vs 3 (3-3) d, P = 0.000], as well as a shorter time to first fluid diet [4 (3-4) d vs 5 (4-6) d, P = 0.001]. Additionally, the RALAR group demonstrated reduced postoperative indwelling catheter time [2 (1-3) d vs 4 (3-5) d, P = 0.000] and decreased length of hospital stay after surgery [5 (5-7) d vs 7(6-8) d, P = 0.009]. Moreover, there was an observed increase in total cost of hospitalization for the RALAR group compared to the LALAR group [10777 (10780-11850) dollars vs 10550 (8766-11715) dollars, P = 0.012]. No significant differences were found in terms of conversion rate to laparotomy or incidence of postoperative complications between both groups. Furthermore, no significant disparities were noted regarding the 3-year overall survival rate and 3-year disease-free survival rate between both groups. CONCLUSION: Robotic surgery offers potential advantages in terms of accelerated recovery of gastrointestinal and urologic function compared to LALAR resection, while maintaining similar perioperative and 3-year oncological outcomes.

4.
J Thorac Dis ; 16(4): 2472-2481, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38738243

RESUMO

Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.

5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 11-18, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433625

RESUMO

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.


Assuntos
Neoplasias Ósseas , Cicloexilaminas , Eliptocitose Hereditária , Ferroptose , Osteossarcoma , Fenilenodiaminas , Animais , Humanos , Camundongos , Sistema y+ de Transporte de Aminoácidos , Endonucleases , Camundongos Nus , Nuclease do Micrococo , Domínio Tudor
6.
Nutr Metab Cardiovasc Dis ; 34(5): 1283-1294, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38494368

RESUMO

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.


Assuntos
Infarto do Miocárdio , Deficiência de Vitamina D , Humanos , Feminino , Pandemias , Fatores de Risco , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologia , Vitamina D , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Itália/epidemiologia
7.
World J Gastroenterol ; 30(2): 115-127, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38312115

RESUMO

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.


Assuntos
Neoplasias Colorretais , RNA Nucleolar Pequeno , Humanos , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Prognóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia
8.
Front Mol Neurosci ; 16: 1164426, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396788

RESUMO

Background: Neuropathic pain (NP) takes a heavy toll on individual life quality, yet gaps in its molecular characterization persist and effective therapy is lacking. This study aimed to provide comprehensive knowledge by combining transcriptomic and proteomic data of molecular correlates of NP in the anterior cingulate cortex (ACC), a cortical hub responsible for affective pain processing. Methods: The NP model was established by spared nerve injury (SNI) in Sprague-Dawley rats. RNA sequencing and proteomic data from the ACC tissue isolated from sham and SNI rats 2 weeks after surgery were integrated to compare their gene and protein expression profiles. Bioinformatic analyses were performed to figure out the functions and signaling pathways of the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) enriched in. Results: Transcriptomic analysis identified a total of 788 DEGs (with 49 genes upregulated) after SNI surgery, while proteomic analysis found 222 DEPs (with 89 proteins upregulated). While Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the DEGs suggested that most of the altered genes were involved in synaptic transmission and plasticity, bioinformatics analysis of the DEPs revealed novel critical pathways associated with autophagy, mitophagy, and peroxisome. Notably, we noticed functionally important NP-related changes in the protein that occurred in the absence of corresponding changes at the level of transcription. Venn diagram analysis of the transcriptomic and proteomic data identified 10 overlapping targets, among which only three genes (XK-related protein 4, NIPA-like domain-containing 3, and homeodomain-interacting protein kinase 3) showed concordance in the directions of change and strong correlations between mRNA and protein levels. Conclusion: The present study identified novel pathways in the ACC in addition to confirming previously reported mechanisms for NP etiology, and provided novel mechanistic insights for future research on NP treatment. These findings also imply that mRNA profiling alone fails to provide a complete landscape of molecular pain in the ACC. Therefore, explorations of changes at the level of protein are necessary to understand NP processes that are not transcriptionally modulated.

9.
Front Endocrinol (Lausanne) ; 14: 1134643, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967802

RESUMO

Background: The prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and to determine the prognostic predictors of overall and progression-free survival. Methods: Medical records of patients, who were diagnosed with ACC at Taipei Veterans General Hospital between January 1992 and June 2021, were reviewed. Patient demographics, tumor characteristics, and subsequent treatment were analyzed with regard to overall survival and progression-free survival using Kaplan-Meier methods and a Cox regression model. Results: Sixty-seven patients were included. Females (65.7%) were more susceptible to ACC, with a younger onset and active hormonal secretion. One-half of the patients exhibited distant metastases at the time of diagnosis. The European Network for the Study of Adrenal Tumours (ENSAT) stage (hazard ratio [HR] 3.60 [95% confidence interval (CI) 1.25-10.38]; p=0.018), large vessel invasion (HR 5.19 [95% CI 1.75-15.37]; p=0.003), and mitotane use (HR 0.27 [95% CI 0.11-0.70]; p=0.007) were significantly associated with overall survival (OS). There was no single factor independently associated with progression-free survival. Conclusion: ENSAT stage had a substantial impact on overall survival though there was no difference in OS between patients with stage II and stage III ACC. Large vessel invasion portended poor prognosis and influenced OS significantly. Moreover, mitotane only improved clinical outcomes of patients with stage IV disease.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Feminino , Humanos , Carcinoma Adrenocortical/terapia , Carcinoma Adrenocortical/tratamento farmacológico , Prognóstico , Mitotano , Neoplasias do Córtex Suprarrenal/terapia , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico
10.
BMC Urol ; 23(1): 52, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997995

RESUMO

INTRODUCTION: Neobladder urolithiasis is a rare but important delaying complication of orthotopic urinary diversion. We report a case of Hem-o-Lok (HOLC) migration into the neobladder with giant stone formation after orthotopic neobladder cystectomy. CASE REPORT: We report a case of a 57-year-old man with frequent urination and occasional discharge of stones 3 years after a laparoscopic orthotopic neobladder cystectomy. Computed tomography revealed a large round 3.5 cm calculus. An endoscopic neocystolitholapaxy was performed, and a Hem-o-Lok was found in the center of the stone. CONCLUSION: We described the case presentation, treatment and analysis of etiology of stone formation to avoid such complication.


Assuntos
Cálculos , Laparoscopia , Derivação Urinária , Masculino , Humanos , Pessoa de Meia-Idade , Cistectomia , Instrumentos Cirúrgicos
11.
Transl Lung Cancer Res ; 12(1): 150-157, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36762064

RESUMO

Background: With the popularity of high-resolution computed tomography (HRCT), more and more pulmonary nodules are being discovered. Video-assisted thoracoscopic surgery (VATS) has become the first choice for surgical treatment of pulmonary nodules. The use of accurate preoperative localization is crucial for successful resection in VATS. At present, there are many kinds of preoperative localization methods, but there are certain disadvantages. This study aimed to evaluate the feasibility and safety of mixed reality (MR)-guided pulmonary nodules localization, which is a new method that can benefit patients to a greater extent. Methods: By constructing an animal model of pulmonary nodules localization, 28 cases of pulmonary nodules were located by MR-guided localization. We recorded the localization accuracy, localization time, insertion attempts, and incidence of complications related to localization under MR-guidance. Results: All 28 nodules were successfully located: the deviation of MR-guided localization was 5.71±2.59 mm, localization time was 8.07±1.44 min, and insertion attempts was 1. A pneumothorax and localizer dislodgement occurred in 1 case, respectively. Conclusions: Since preoperative localization is critical for VATS resection of pulmonary nodules, we investigated a new localization method. As indicated by our study, MR-guided localization of pulmonary nodules is feasible and safe, which is worthy of further research and promotion. We have also registered corresponding clinical trials to further investigate and help to improve our understanding of this technique.

12.
J Clin Immunol ; 43(4): 835-845, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36807221

RESUMO

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.


Assuntos
Adenosina Desaminase , Peptídeos e Proteínas de Sinalização Intercelular , Humanos , Adenosina Desaminase/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Estudos de Coortes , Estudos Retrospectivos , Mutação
13.
Comput Assist Surg (Abingdon) ; 28(1): 1-5, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36622864

RESUMO

To explore the safety and feasibility of wireless thoracoscope in thoracic surgery. A retrospective analysis was made of all the clinical data of 90 patients with thoracoscope lung resection, from April to August 2021, Shanghai changzheng hospital thoracic minimally invasive center. Compared the thoracoscope preparation time, picture resolution, picture delay, surgeon comfort level, assistant comfort level between the wireless thoracoscope group and wired thoracoscope group. The thoracoscopic preparation time of the wireless thoracoscope group was significantly shorter than that of the wired group (26.66 ± 6.04 vs 62.14 ± 10.07, p < 0.0001). Comfort level of the surgeon (4.64 ± 0.48 vs 3.77 ± 0.42, p < 0.001) and the comfort level of the assistant (4.85 ± 0.36 vs 3.88 ± 0.32, p < 0.001) of the wireless thoracoscope group were higher than that of the wired thoracoscope group. There were no statistically significant differences in video sharpness (4.64 ± 0.48 vs 4.74 ± 0.44, p = 0.31). Although there was one case picture delay in wireless group, it was caused by low power which could be dealt with by a good charge before surgery. The wireless thoracoscope has the advantages of short preparation time, high comfort for the surgeon and the assistant, no less than the wired thoracoscope in picture resolution and picture delay. Wireless connection is more convenient and portability, which is worthy of further application in clinical practice.


Assuntos
Cirurgia Torácica , Humanos , Estudos Retrospectivos , China , Toracoscopia , Toracoscópios
14.
Metab Brain Dis ; 37(8): 2903-2914, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36070047

RESUMO

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).


Assuntos
Depressão , Fosfatidilinositol 3-Quinases , Pós , Simulação de Acoplamento Molecular , Depressão/tratamento farmacológico , Ligantes , Proteínas Proto-Oncogênicas c-akt , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico
15.
World J Clin Cases ; 10(18): 6039-6049, 2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35949849

RESUMO

BACKGROUND: Most complex renal stones are managed primarily with percutaneous nephrolithotomy (PCNL). However, PCNL is still a great challenge for surgeons because of poor comprehension on complex adjacent structures. Novel techniques are required to assist in planning and navigation. AIM: To apply and evaluate the Hisense computer-assisted surgery (CAS) system in PCNL. METHODS: A total of 60 patients with complex renal stones were included. Thirty patients in the CAS group had three-dimensional (3D) virtual models constructed with the CAS system. The model assisted in planning and navigating in the CAS system. Thirty patients in the control group planned and navigated as standard PCNL, without the application of the CAS system. Success rate of one attempt, operation time, initial stone-free rate, decrease in hemoglobin, and complications were collected and analyzed. RESULTS: There were no statistically significant differences in the baseline characteristics or planning characteristics. The success rate of one puncturing attempt (90% vs 67%, P = 0.028) and the initial stone-free rate (87% vs 63%, P = 0.037) were significantly higher in the CAS group. However, there were no statistically significant differences in the operation time (89.20 ± 29.60 min vs 92.33 ± 33.08 min, P = 0.859) or in the decrease in hemoglobin (11.07 ± 8.32 g/L vs 9.03 ± 11.72 g/L, P = 0.300) between the CAS group and the control group. No statistically significant differences in the incidence of complications (Clavien-Dindo grade ≥ 2) were found. CONCLUSION: Compared with standard PCNL, CAS-assisted PCNL had advantages in terms of the puncturing success rate and stone-free rate. The Hisense CAS System was recommended to assist in preoperative planning and intraoperative navigation for an intuitive, precise and convenient PCNL.

16.
Front Oncol ; 12: 959484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992851

RESUMO

Objective: To investigate the safety and efficacy of glasses-free three-dimensional (3D) thoracoscopic surgery in minimally invasive esophagectomy (MIE). Methods: The clinical data of 98 patients, including 81 men and 17 women aged 45-77 years, with esophageal squamous cell carcinoma who underwent minimally invasive thoracoscopic esophagectomy from January 2017 to December 2019 [3 years, with clinical follow-up time: 1 year~4 years (2017.01-2020.12)] were retrospectively analyzed. Patients were divided into two groups according to different surgical methods including a glasses-free 3D thoracoscopic group (G-3D group: 38 patients) and a two-dimesional (2D) thoracoscopic group (2D group: 60 patients). The clinical outcome of the two groups were compared. Results: The operation time of the thoracoscopic part in the G-3D group was significantly shorter than that in the 2D group (P<0.05). The total number of lymph node dissection in the G-3D group was more than that in the 2D group (P<0.05). The thoracic indwelling time, postoperative hospital stay, severe pulmonary infection, arrhythmia, anastomotic leakage, chylothorax, and recurrent laryngeal nerve injury were not significantly different between the two groups (P>0.05). There was also no significant difference between the two groups on the progression-free survival (P>0.05). Conclusion: Glasses-free 3D thoracoscopic surgery for esophageal cancer is a safe and effective surgical procedure. Compared with 2D thoracoscopic MIE, glasses-free 3D thoracoscopic MIE for esophageal cancer has higher safety, more lymph node dissection, and higher operation efficiency through the optimized surgical operations. We believe that glasses-free 3D thoracoscopy for MIE is worthy of clinical promotion.

17.
Front Nutr ; 9: 842856, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811963

RESUMO

Aim: The aim of the study was to examine the relationship between coffee, tea, caffeine consumption and risk of all-cause death and cardiovascular disease (CVD) death in CVD population. Methods: This cohort study included 626 CVD participants aged ≥18 years old who derived from the National Health and Nutrition Examination Surveys (NHANES) database 2003-2006. The end time of follow-up was 2015, and with a median follow-up time of 113.5 (63, 133) months. CVD death was defined as a death caused by congestive heart failure (CHF), coronary heart disease (CHD), angina pectoris, heart attack or stroke. Cox model and competitive-risk model were used to explore the relationship of coffee, tea, caffeine, decaffeinated coffee/tea on the risk of the all-cause death and CVD death for CVD population, respectively. Additionally, we explored the effect of urinary caffeine and caffeine metabolites on all-cause death. Results: All patients were divided into survival group (n = 304), non-CVD death group (n = 223), and CVD death group (n = 99). The incidence of all-cause death and CVD death was ~51.44 and 15.81% in the study. After adjusting age, body mass index (BMI), cancer, estimated glomerular filtration rate (eGFR), energy, the history of CVD medications, carbohydrate and family income to poverty ratio (PIR), the results suggested coffee, caffeine, iced tea and hot tea consumption (≥4 cups per day) were associated with an increased risk of the all-cause death in CVD patients; while hot tea (1-3 cups per day), decaffeinated coffee/iced tea/hot tea could reduce the risk of the all-cause death. Likewise, coffee, caffeine, iced tea (≥4 cups per day), hot tea, decaffeinated iced tea/ hot tea (Always) could enhance the risk of the CVD death in CVD population. We also found that 1-methylxanthine showed a significant positive association on the risk of all-cause death in CVD population. Conclusion: Our study indicated that higher consumption of coffee, tea and caffeine could increase the risk of all-cause and CVD death for CVD patients.

18.
Front Surg ; 9: 874983, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846962

RESUMO

Background: With uniportal video-assisted thoracoscopic surgery (VATS) becoming mainstream, how to make the incision cosmetic has attracted much attention. This study aimed to introduce a new traceless method for cosmetic closure of the incision and a special procedure for chest tube fixation after uniportal VATS and to evaluate the feasibility, effectiveness, and safety of this new technique. Methods: In this retrospective study, a total of 258 consecutive patients who underwent uniportal VATS were included. Among them, 127 patients were treated with a conventional method, and 131 patients were treated with a new method. Results: Patients in the new method group had a significantly less incidence of subcutaneous emphysema after the chest tube was removed. The incidence of pneumothorax after the chest tube was removed and fat liquefaction of chest incision was not significantly different between the two groups. No differences in the incidence of pneumothorax after chest tube removal and fat liquefaction of postsurgical incision were found between the two groups. Additionally, there was also no significant difference in follow-up items. Conclusions: Taken together, our results showed that this new method for minimally invasive incision closure and chest tube fixation after uniportal VATS was as feasible, effective, and safe as the conventional one but more cosmetic.

19.
Front Surg ; 9: 925003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711706

RESUMO

Background: It still remains unclear whether subxiphoid video-assisted thoracoscopic surgery (SVATS) thymectomy is safe and reasonable. This meta-analysis aims at assessing the effectiveness and safety of SVATS for thymoma in comparison with that of intercostal video-assisted thoracoscopic surgery (IVATS) thymectomy. Methods: All the relevant data systematically analyzed in this thesis were retrieved from PubMed, the Cochrane Library, web of science, EMBASE, and ClinicalTrials.gov. The time span for data retrieval was from the date of database establishment to March 2022. The outcome indicators include operation time, intraoperative blood loss, duration of postoperative drainage, postoperative hospital days, visual analogue scale (VAS) score on the day of operation, VAS score on postoperative day 3, and VAS score on postoperative day 7; postoperative complications were analyzed in our meta-analysis. Results: In 13 studies of this paper, there were 1,198 cases included. Among them, 563 cases were treated by SVATS thymectomy and 635 cases by IVATS thymectomy. There was no significant difference in the operation time [113.38 vs. 119.91  min, 95% confidence interval (CI): -0.70-0.15, p = 0.20) and the incidence of intraoperative and postoperative complications (RR = 0.82, 95% CI: 0.58-1.15, p = 0.25) between SVATS thymectomy and IVATS thymectomy. However, SVATS thymectomy significantly reduced the amount of intraoperative blood loss (47.68 vs. 66.69  mL, SMD = -0.57, 95% CI: -0.95 to -0.18, p = 0.004), postoperative drainage days (2.12 vs. 2.72 days, SMD = -0.46, 95% CI: -0.74 to -0.18, p = 0.001), postoperative hospital stays (4.53 vs. 5.91 days, SMD = -0.64, 95% CI: -0.96 to -0.31, p = 0.0001), and VAS scores after the operation. Discussion: SVATS thymectomy is safe and feasible, and the perioperative effect is better than IVATS thymectomy to a certain extent, which is worthy of popularization and further research.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

20.
Front Pharmacol ; 13: 769751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517799

RESUMO

Anthracycline is a first-line chemotherapy drug used to treat childhood acute leukemia, which may cause cardiac toxicity including common arrhythmia, valve disease, pericardial effusion, and even rare cardiomyopathy and cardiac failure. We reported a 2-year-old boy who was treated irregularly for acute lymphoblastic leukemia with daunorubicin. After 26 months, his left ventricular ejection fraction decreased to 40% and progressively decreased to 20-30%. Then he successfully received a heart transplant and the myocardium was confirmed with dilated cardiomyopathy. Eight months after cardiac transplantation, he was admitted again for left neck mass and was diagnosed with monomorphic diffuse large B cell lymphoma associated with Epstein-Barr virus infection by biopsy. We present this case to highlight the importance of standard chemotherapy of daunorubicin, clinical prevention, and monitoring of anthracycline-induced cardiotoxicity in acute lymphoblastic leukemia children to ensure their good prognosis and long-term life quality.

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