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OBJECTIVE: The ultrasonographic characteristics of lymph node metastasis in breast cancer patients were retrospectively analyzed, and a predictive nomogram model was constructed to provide an imaging basis for better clinical evaluation. METHODS: B-mode ultrasound was used to retrospectively analyze the imaging characteristics of regional lymph nodes and tumors. Pathological examination confirmed the presence of lymph node metastasis in breast cancer patients. Univariable and multivariable logistic regression analyses were performed to analyze the risk factors for lymph node metastasis. LASSO regression analysis was performed to screen noninvasive indicators, and a nomogram prediction model was constructed for breast cancer patients with lymph node metastasis. RESULTS: A total of 187 breast cancer patients were enrolled, including 74 patients with lymph node metastasis in the positive group and 113 patients without lymph node metastasis in the negative group. Multivariate analysis revealed that pathological type (OR = 4.58, 95% CI: 1.44-14.6, p = 0.01), tumor diameter (OR = 1.37, 95% CI: 1.07-1.74, p = 0.012), spiculated margins (OR = 7.92, 95% CI: 3.03-20.67, p < 0.001), mixed echo of the breast tumor (OR = 37.09, 95% CI: 3.49-394.1, p = 0.003), and unclear lymphatic hilum structure (OR = 16.07, 95% CI: 2.41-107.02, p = 0.004) were independent risk factors for lymph node metastasis. A nomogram model was constructed for predicting breast cancer with lymph node metastasis, incorporating three significantly correlated indicators identified through LASSO regression analysis, namely, tumor spiculated margins, cortical thickness of lymph nodes, and unclear lymphatic hilum structure. The receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.717 (95% CI, 0.614-0.820) for the training set and 0.817 (95% CI, 0.738-0.890) for the validation set. The Hosmer-Lemeshow test results for the training set and the validation set were p = 0.9148 and p = 0.1648, respectively. The prediction nomogram has good diagnostic performance. CONCLUSIONS: B-mode ultrasound is helpful in the preoperative assessment of breast cancer patients with lymph node metastasis. The predictive nomogram model, which is based on logistic regression and LASSO regression analysis, is clinically safe, reliable, and highly practical.
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Neoplasias de la Mama , Ganglios Linfáticos , Metástasis Linfática , Nomogramas , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Metástasis Linfática/diagnóstico por imagen , Estudios Retrospectivos , Persona de Mediana Edad , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Adulto , Pronóstico , Anciano , Factores de Riesgo , Estudios de Seguimiento , Ultrasonografía Mamaria/métodos , Ultrasonografía/métodos , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/secundarioRESUMEN
BACKGROUND: Perioperative bleeding and allogeneic blood transfusion are generally thought to affect the outcomes of patients. This meta-analysis aimed to determine the benefits and risks of several cardiovascular interventions in patients undergoing hepatectomy. METHODS: In this systematic review and meta-analysis, randomised controlled trials (RCTs) were searched in the Cochrane Library, Medline, Embase, and Web of Science to February 02, 2023. RCTs focused on cardiovascular interventions aimed at reducing blood loss or blood transfusion requirements during hepatectomy were included. The primary outcomes were perioperative blood loss amount, number of patients requiring allogeneic blood transfusion and overall occurrence of postoperative complications. The secondary outcomes were operating time, perioperative mortality rate, postoperative liver and kidney function and length of hospital stay. RESULTS: Seventeen RCTs were included in the analysis. A total of 841 patients who underwent hepatectomy in 10 trials were included in the comparative analysis between low central venous pressure (CVP) and control groups. The forest plots showed a low operative bleeding volume [(mean difference (MD): -409.75 mL, 95% confidence intervals (CI) -616.56 to -202.94, P < 0.001], reduced blood transfusion rate [risk ratio (RR): 0.47, 95% CI 0.34 to 0.65, P < 0.001], shortened operating time (MD: -13.42 min, 95% CI -22.59 to -4.26, P = 0.004), and fewer postoperative complications (RR: 0.76, 95% CI 0.58 to 0.99, P = 0.04) in the low CVP group than in the control group. Five and two trials compared the following interventions, respectively: 'acute normovolaemic haemodilution (ANH) vs control' and 'autologous blood donation vs control'. ANH and autologous blood donation could not reduce the blood loss amount but greatly decreased the number of patients requiring allogeneic blood transfusion. No benefits were found in the rate of mortality and length of postoperative hospital stay in any of the comparisons. CONCLUSION: Lowering the CVP seems to be effective and safe in adult patients undergoing hepatectomy. ANH and autologous blood donation should be used as a part of blood management for suitable patients in certain circumstances. TRIAL REGISTRATION: PROSPERO, CRD42022314061.
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Pérdida de Sangre Quirúrgica , Hepatectomía , Adulto , Humanos , Hepatectomía/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea , Cuidados Preoperatorios , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Although laparoscopic pancreaticoduodenectomy (LPD) has been accepted worldwide for treating pancreatic ductal adenocarcinoma (PDA), it is a very technical and challenging procedure. Also, it is unclear whether LPD is superior to open pancreaticoduodenectomy (OPD). This study summarized the experience and efficacy of LPD for treating PDA in our medical center. METHODS: This retrospective cohort study included patients with PDA admitted at the Affiliated Hospital of Jiangnan University from October 2019 and January 2021. Patients received either LPD or OPD. Clinical outcomes (operation time, duration of anesthesia, intraoperative hemorrhage), postoperative complications, and short-term outcomes were compared. Cox proportional hazard model and Kaplan-Meier method were used to analyze overall survival (OS) and progression-free survival (PFS). RESULTS: Among the PDA patients, 101 patients underwent surgical treatment, 4 patients converted from LPD to OPD, and 7 of them received conservative treatment. Forty-six patients were cured of LPD, and 1 of them died shortly after the operation. Moreover, 44 patients received OPD, and there were 2 postoperative deaths. There were significant differences in the location of the operation time, duration of anesthesia, postoperative hemorrhage, abdominal infections, and postoperative pneumonia between the two groups (all p < 0.05). Multivariate analysis showed that LPD was an independent factor negatively correlated with the incidence of pneumonia (relative risk (RR) = 0.072, 95%CI: 0.016-0.326, p = 0.001) and abdominal infection (RR = 0.182, 95%CI: 0.047-0.709, p = 0.014). Also, there were no differences in OS (hazard ratio (HR) = 1.46, 95%CI: 0.60-3.53, p = 0.40) and PFS (HR = 1.46, 95%CI: 0.64-3.32, p = 0.37) at 12 months between the two groups. CONCLUSIONS: LPD could be efficacy and feasible for managing selected PDA patients. Also, LPD has a better effect in reducing postoperative pneumonia and abdominal infection compared to OPD.
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Carcinoma Ductal Pancreático , Laparoscopía , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomía/métodos , Estudios Retrospectivos , Pronóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de Internación , Neoplasias PancreáticasRESUMEN
Metabolic stress causes activation of the cJun NH2-terminal kinase (JNK) signal transduction pathway. It is established that one consequence of JNK activation is the development of insulin resistance and hepatic steatosis through inhibition of the transcription factor PPARα. Indeed, JNK1/2 deficiency in hepatocytes protects against the development of steatosis, suggesting that JNK inhibition represents a possible treatment for this disease. However, the long-term consequences of JNK inhibition have not been evaluated. Here we demonstrate that hepatic JNK controls bile acid production. We found that hepatic JNK deficiency alters cholesterol metabolism and bile acid synthesis, conjugation, and transport, resulting in cholestasis, increased cholangiocyte proliferation, and intrahepatic cholangiocarcinoma. Gene ablation studies confirmed that PPARα mediated these effects of JNK in hepatocytes. This analysis highlights potential consequences of long-term use of JNK inhibitors for the treatment of metabolic syndrome.
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Ácidos y Sales Biliares/metabolismo , Colangiocarcinoma/enzimología , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Proteína Quinasa 9 Activada por Mitógenos/metabolismo , Animales , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/fisiopatología , Homeostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Quinasa 8 Activada por Mitógenos/genética , Proteína Quinasa 9 Activada por Mitógenos/genética , PPAR alfa/genética , PPAR alfa/metabolismoRESUMEN
A novel optimal control problem is considered for multiple input multiple output (MIMO) stochastic systems with mixed parameter drift, external disturbance and observation noise. The proposed controller can not only track and identify the drift parameters in finite time but, furthermore, drive the system to move towards the desired trajectory. However, there is a conflict between control and estimation, which makes the analytic solution unattainable in most situations. A dual control algorithm based on weight factor and innovation is, therefore, proposed. First, the innovation is added to the control goal by the appropriate weight and the Kalman filter is introduced to estimate and track the transformed drift parameters. The weight factor is used to adjust the degree of drift parameter estimation in order to achieve a balance between control and estimation. Then, the optimal control is derived by solving the modified optimization problem. In this strategy, the analytic solution of the control law can be obtained. The control law obtained in this paper is optimal because the estimation of drift parameters is integrated into the objective function rather than the suboptimal control law, which includes two parts of control and estimation in other studies. The proposed algorithm can achieve the best compromise between optimization and estatimation. Finally, the effectiveness of the algorithm is verified by numerical experiments in two different cases.
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Algoritmos , Ruido , Simulación por ComputadorRESUMEN
BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a devastating disease often detected at advanced stages when surgery cannot be performed. Conventional and targeted systemic therapies perform poorly, and therefore effective drugs are urgently needed. Different epigenetic modifications occur in CCA and contribute to malignancy. Targeting epigenetic mechanisms may thus open therapeutic opportunities. However, modifications such as DNA and histone methylation often coexist and cooperate in carcinogenesis. We tested the therapeutic efficacy and mechanism of action of a class of dual G9a histone-methyltransferase and DNA-methyltransferase 1 (DNMT1) inhibitors. APPROACH AND RESULTS: Expression of G9a, DNMT1, and their molecular adaptor, ubiquitin-like with PHD and RING finger domains-1 (UHRF1), was determined in human CCA. We evaluated the effect of individual and combined pharmacological inhibition of G9a and DNMT1 on CCA cell growth. Our lead G9a/DNMT1 inhibitor, CM272, was tested in human CCA cells, patient-derived tumoroids and xenograft, and a mouse model of cholangiocarcinogenesis with hepatocellular deletion of c-Jun-N-terminal-kinase (Jnk)-1/2 and diethyl-nitrosamine (DEN) plus CCl4 treatment (JnkΔhepa + DEN + CCl4 mice). We found an increased and correlative expression of G9a, DNMT1, and UHRF1 in CCAs. Cotreatment with independent pharmacological inhibitors G9a and DNMT1 synergistically inhibited CCA cell growth. CM272 markedly reduced CCA cell proliferation and synergized with Cisplatin and the ERBB-targeted inhibitor, Lapatinib. CM272 inhibited CCA tumoroids and xenograft growth and significantly antagonized CCA progression in JnkΔhepa + DEN + CCl4 mice without apparent toxicity. Mechanistically, CM272 reprogrammed the tumoral metabolic transcriptome and phenotype toward a differentiated and quiescent status. CONCLUSIONS: Dual targeting of G9a and DNMT1 with epigenetic small molecule inhibitors such as CM272 is a potential strategy to treat CCA and/or enhance the efficacy of other systemic therapies.
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Neoplasias de los Conductos Biliares , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma , ADN (Citosina-5-)-Metiltransferasa 1 , Inhibidores Enzimáticos/farmacología , Antígenos de Histocompatibilidad , N-Metiltransferasa de Histona-Lisina , Animales , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Línea Celular Tumoral , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN/efectos de los fármacos , Metilación de ADN/fisiología , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antígenos de Histocompatibilidad/metabolismo , Código de Histonas/efectos de los fármacos , Código de Histonas/fisiología , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Ratones , Resultado del Tratamiento , Ubiquitina-Proteína Ligasas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
BACKGROUND: The treatment of hepatic injury can be complex. Medical clinical centers are often the first line hospitals for the diagnosis and treatment of hepatic trauma in China. The aim of the study is to summarize the experience in the diagnosis and treatment of hepatic trauma in one medical clinical center in China. METHODS: This retrospective study included patients with hepatic trauma admitted between January 2002 and December 2019 at the Xishan People's Hospital of Wuxi. The outcomes were cure rate and death within 14 days post-discharge. RESULTS: Among the 318 patients with hepatic trauma, 146 patients underwent surgical treatment, and 172 received conservative treatment; three patients were transferred to other hospitals for further treatment; 283 patients were cured, and 35 died. Severe hepatic trauma occurred in 74 patients, with a mortality rate of 31.1% and accounting for 65.7% of total mortality. American Association for the Surgery of Trauma (AAST) grading ≥ III (OR = 3.51, 95%CI: 1.32-9.37, P = 0.012) and multiple organ injury (OR = 7.51, 95%CI: 2.51-22.46, P < 0.001) were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death (OR = 0.08, 95%CI: 0.01-0.45, P = 0.004). Among patients with ASST ≥ III and who underwent surgery, age (OR = 5.29, 95%CI: 1.37-20.33, P = 0.015) and peri-hepatic packing (PHP) (OR = 5.54, 95%CI: 1.43-21.487, P = 0.013) were independently associated with death. CONCLUSIONS: AAST grading ≥ III and multiple organ injury were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death. Among patients with ASST ≥ III and who underwent surgery, age and PHP were independently associated with death.
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Accidentes , Hígado , Heridas y Lesiones , China , Estudios Transversales , Femenino , Hospitales , Humanos , Hígado/lesiones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros Traumatológicos , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/etiología , Heridas y Lesiones/terapiaRESUMEN
To deal with the problem of multitarget tracking with measurement origin uncertainty, the paper presents a multitarget tracking algorithm based on Adaptive Network Graph Segmentation (ANGS). The multitarget tracking is firstly formulated as an Integer Programming problem for finding the maximum a posterior probability in a cost flow network. Then, a network structure is partitioned using an Adaptive Spectral Clustering algorithm based on the Nyström Method. In order to obtain the global optimal solution, the parallel A* search algorithm is used to process each sub-network. Moreover, the trajectory set is extracted by the Track Mosaic technique and Rauchâ»Tungâ»Striebel (RTS) smoother. Finally, the simulation results achieved for different clutter intensity indicate that the proposed algorithm has better tracking accuracy and robustness compared with the A* search algorithm, the successive shortest-path (SSP) algorithm and the shortest path faster (SPFA) algorithm.
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BACKGROUND: The etiological factor for intrahepatic cholangiocarcinoma (ICC) is not clear. Although it has been widely accepted that intrahepatic biliary tree stone is associated with increased risk of ICC, the role of extrahepatic biliary tree stone in the incidence of ICC is controversial. In the present study we aim to evaluate the association between pre-existing choledocholithiasis and cholecystolithiasis and the risk of ICC. METHODS: PubMed, Embase, and Web of Science were searched to identify cohort and case-control studies on the association between choledocholithiasis or cholecystolithiasis and the risk of ICC. Studies that met the inclusion criteria were subjected to a meta-analysis performed with Stata statistical software. Either a fixed or random effect model was used, depending on the heterogeneity within the studies. Egger's test was performed to assess publication bias. RESULTS: Seven case-control studies met our inclusion criteria. Of the 123,771 participants, 4763 (3.85 %) were patients with ICC, and 119,008 were tumor-free controls. The presence of pre-existing bile duct stones (choledocholithiasis alone or choledocholithiasis accompanied by hepatolithiasis) was associated with the risk of ICC (odds ratio [OR] 17.64, 95 % confidence interval [CI] 11.14-27.95). Even the presence of choledocholithiasis alone (in the absence of hepatolithiasis) was associated with a high risk of ICC (OR 11.79, 95 % CI 4.17-33.35). Cholecystolithiasis may possibly contributed to the incidence of ICC (OR 2.00, 95 % CI 1.16-3.42), with large heterogeneity within studies (I (2) = 78.5 %). CONCLUSIONS: Bile duct stones including choledocholithiasis are important risk factors for ICC. Careful surveillance of patients with extrahepatic biliary tree stone should be considered.
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Neoplasias de los Conductos Biliares/patología , Conductos Biliares/patología , Colangiocarcinoma/patología , Colelitiasis/patología , Neoplasias de los Conductos Biliares/epidemiología , Colangiocarcinoma/epidemiología , Colangiocarcinoma/etiología , Colelitiasis/complicaciones , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Factores de RiesgoRESUMEN
In this paper, the robust adaptive optimal tracking control problem is addressed for the disturbed unmanned helicopter based on the time-varying gain extended state observer (TVGESO) and adaptive dynamic programming (ADP) methods. Firstly, a novel TVGESO is developed to tackle the unknown disturbance, which can overcome the drawback of initial peaking phenomenon in the traditional linear ESO method. Meanwhile, compared with the nonlinear ESO, the proposed TVGESO possesses easier and rigorous stability analysis process. Subsequently, the optimal tracking control issue for the original unmanned helicopter system is transformed into an optimization stabilization problem. By means of the ADP and neural network techniques, the feedforward controller and optimal feedback controller are skillfully designed. Compared with the conventional backstepping approach, the designed anti-disturbance optimal controller can make the unmanned helicopter accomplish the tracking task with less energy. Finally, simulation comparisons demonstrate the validity of the developed control scheme.
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Laser fragmentation in liquids has emerged as a promising green chemistry technique for changing the size, shape, structure, and phase composition of colloidal nanoparticles, thus tuning their properties to the needs of practical applications. The advancement of this technique requires a solid understanding of the mechanisms of laser-nanoparticle interactions that lead to the fragmentation. While theoretical studies have made impressive practical and mechanistic predictions, their experimental validation is required. Hence, using the picosecond laser fragmentation of Au nanoparticles in water as a model system, the transient melting and fragmentation processes are investigated with a combination of time-resolved X-ray probing and atomistic simulations. The direct comparison of the diffraction profiles predicted in the simulations and measured in experiments has revealed a sequence of several nonequilibrium processes triggered by the laser irradiation. At low laser fluences, in the regime of nanoparticle melting and resolidification, the results provide evidence of a transient superheating of crystalline nanoparticles above the melting temperature. At fluences about three times the melting threshold, the fragmentation starts with evaporation of Au atoms and their condensation into small satellite nanoparticles. As fluence increases above five times the melting threshold, a transition to a rapid (explosive) phase decomposition of superheated nanoparticles into small liquid droplets and vapor phase atoms is observed. The transition to the phase explosion fragmentation regime is signified by prominent changes in the small-angle X-ray scattering profiles measured in experiments and calculated in simulations. The good match between the experimental and computational diffraction profiles gives credence to the physical picture of the cascade of thermal fragmentation regimes revealed in the simulations and demonstrates the high promise of the joint tightly integrated computational and experimental efforts.
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Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.
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Previous studies have demonstrated that Eyes Absent 4 (EYA4) influences the proliferation and migration of tumor cells. Notably, studies have established that EYA4 can also limit tumor sensitivity to chemotherapeutic agents. The objective of this study was to investigate the effect of EYA4 in conferring drug resistance in osteosarcoma (OS). Bioinformatics, histological, and cellular analyses revealed that the expression level of EYA4 was higher in OS tissues than in healthy tissues/cells and in resistant tissues/cells compared with sensitive tissues/cells. In vitro and in vivo experiments demonstrated that EYA4 knockdown increased the sensitivity of OS to doxorubicin (DOX). Conversely, overexpression of EYA4 decreased the sensitivity of OS to DOX. Exploration of the resistance mechanism exposed that EYA4 facilitates DNA double-strand break (DSB) repair, a typical mode of DNA damage repair (DDR). Subsequently, our findings indicated that EYA4 could directly interact with histone H2AX to activate the DDR pathway. Taken together, our observations indicated that EYA4 may serve as a target molecule for reversing drug resistance in OS patients.
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Antibióticos Antineoplásicos , Neoplasias Óseas , Daño del ADN , Reparación del ADN , Doxorrubicina , Resistencia a Antineoplásicos , Ratones Desnudos , Osteosarcoma , Doxorrubicina/farmacología , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Osteosarcoma/patología , Osteosarcoma/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Reparación del ADN/efectos de los fármacos , Reparación del ADN/fisiología , Ratones , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Transactivadores/genética , Transactivadores/metabolismo , Femenino , Ratones Endogámicos BALB C , Masculino , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Background: T lymphocytes, integral to the adaptive immune system, wield pivotal influence in bolstering anti-tumor responses, and are strictly regulated by ubiquitination modification. The objective of this investigation was to devise a novel prognostic and immunotherapeutic efficacy predictor for hepatocellular carcinoma patients utilizing T cell-related ubiquitination genes (TCRUG). Method: The single-cell RNA sequencing (scRNA-seq) data and bulk RNA data of HCC patients are derived from the GEO database and TCGA database. Based on the processing of scRNA-seq, T cell marker genes are obtained and TCRUG is obtained. Further combined with WGCNA, differential analysis, univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis to filter and screen TCRUG. Finally construct a riskscore for predicting the prognosis of HCC patients, the predictive effect of which is validated in the GEO dataset. In addition, we also studied the correlation between riskscore and immunotherapy efficacy. Finally, the oncogenic role of UBE2E1 in HCC was explored through various in vitro experiments. Result: Based on patients' scRNA-seq data, we finally obtained 3050 T cell marker genes. Combined with bulk RNA data and clinical data from the TCGA database, we constructed a riskscore that accurately predicts the prognosis of HCC patients. This riskscore is an independent prognostic factor for HCC and is used to construct a convenient column chart. In addition, we found that the high-risk group is more suitable for immunotherapy. Finally, the proliferation, migration, and invasion abilities of HCC cells significantly decreased after UBE2E1 expression reduction. Conclusion: This study developed a riskscore based on TCRUG that can accurately and stably predict the prognosis of HCC patients. This riskscore is also effective in predicting the immune therapy response of HCC patients.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Linfocitos T , Ubiquitinación , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Pronóstico , Biomarcadores de Tumor/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , InmunoterapiaRESUMEN
Key Clinical Message: In conclusion author highlights the tumor cell genetic testing or molecular pathological diagnosis plays a key role in the individualized treatment of PSC, which could benefit patients with advanced PSC. Abstract: An uncommon form of non-small-cell lung cancer (NSCLC) with a poor prognosis is pulmonary sarcomatoid carcinoma (PSC). Surgical resection is currently the preferred treatment, but guidelines for adjuvant chemotherapy have not yet been established, especially for the advanced stage. The development of molecular subgroups in the field of tumors may be advantageous to advanced PSC patients with the ongoing progress of genomics and immunology. A 54-year-old man presented to Xishan People's Hospital of Wuxi City with recurrent intermittent dry cough with fever for 1 month. Further examinations suggested the diagnosis of PSC occupying almost the entire right interlobar fissure area combined with malignant pleural effusion (Stage IVa). Pathological examination confirmed the diagnosis of PSC with ROS1 overexpressing via genetic testing. However, after three cycles of chemo-, antiangiogenetic- and immunochemical therapy, the lesion was localized, and pleural effusion disappeared, the patient subsequently received an operation which was performed as R0 resection. Unfortunately, the patient became deteriorated quickly followed by extensive metastatic nodules in the thoracic cavity. Although the patient continued to receive chemo- and immunochemical-therapy, it did not limit the progress of the tumor, leading to widespread metastasis, and eventually died of multiple organ failure. For PSC patients with Stage IVa, chemo-, antiangiogenetic- and immunochemical-therapy performs well in clinical efficacy, and comprehensive panel-based genetic testing may offer PSC patients a somewhat better prognosis. However, blindly implementing surgical treatment may bring harm to the patient and affect long-term survival. It's essential to know the surgical indications precisely by NSCLC guidelines.
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Key Clinical Message: For potentially resectable HCC, a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used. Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. The best treatment for HCC is radical surgical resection, but 70%-80% of patients are ineligible for surgery. Although conversion therapy is an established treatment strategy for various solid tumors, there is no uniform protocol for treating HCC. In this case, we present a 69-year-old male patient diagnosed with massive HCC with Barcelona clinical liver cancer (BCLC) stage B. Because of the insufficient volume of the future liver remnant, we believed radical surgical resection was temporarily impossible. Therefore, the patient received conversion therapy, including four cycles of transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC-Folfox), lenvatinib (8 mg orally once a day), and tislelizumab (an anti-PD-1 antibody, 200 mg intravenously once every 3 weeks). Fortunately, the patient achieved a good treatment response (smaller lesions and improved liver function) and underwent radical surgery finally. There was no clinical evidence of recurrence at 6 months of follow-up. For potentially resectable HCC, this case reveals that a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used.
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Objective: Although laparoscopic repair has been widely carried out and promoted due to its minimally invasive advantages, open surgery is still popular compared to elderly patients. This study aims to compare the outcomes of laparoscopic (LIHR) vs open repair of inguinal hernias (OIHR) in elderly patients. Methods: A retrospective analysis of the database was performed to identify elderly patients, from January 2021 through December 2022, who underwent surgery for an inguinal hernia. After a 1:1 propensity score matching (PSM) with a caliper of 0.1 was conducted to balance potential bias, binary logistic regressions were used for categorical and continuous outcomes. Results: After PSM, 78 pairs of elderly patients were enrolled in this study, and there were no significant differences in baseline between LIHR and OIHR groups. Compared to OIHR, univariable and multivariable logistic regression analysis showed that LIHR was independently affected for reducing intraoperative hemorrhage (OR = 0.06, 95% CI: 0.02-0.18, P < 0.001) and shortening postoperative hospitalization time (OR = 0.29, 95% CI: 0.15-0.57, P < 0.001) in elderly patients. Furthermore, LIHR (OR = 0.28, 95% CI: 0.14-0.57, P < 0.001) and age (OR = 0.89, 95% CI: 0.82-0.96, P = 0.002) were independent affecting factors for relieving postoperative pain. Meanwhile, no obvious differences were detected in postoperative complications [LIHR 7.7% (6/78) vs OIHR 14.1% (11/78), P = 0.199]. Conclusion: LIHR was closely associated with reducing intraoperative hemorrhage and shortening postoperative hospitalization time. Whilst LIHR and age were independently affecting factors for relieving postoperative pain.
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Objectives: Although laparoscopic inguinal hernia repair (LIHR) has been widely accepted for treating inguinal hernia, the procedure remains very technical and challenging. The present study aimed to assess the effect of LIHR in relation to operation time, intraoperative hemorrhage and postoperative hospitalization. Methods: A total of 503 patients with inguinal hernia admitted at the Wuxi Rehabilitation Hospital between June 2019 and July 2021 were included in this retrospective cohort study. Binary logistic and linear regressions were used for categorical and continuous outcomes, respectively. The learning curve was drawn by cumulative sum analysis. Results: Multivariate logistic regression analysis identified LIHR as an independent factor associated with prolonging operation time (odd ratio [OR] = 1.750, 95% confidence interval [CI]: 1.215-2.520, p = 0.003) and decreasing intraoperative hemorrhage levels (OR = 0.079, 95 CI: 0.044-0.142, p < 0.001). Multivariate linear regression identified LIHR (Coefficient = -0.702, 95% CI: [-1.050] to [-0.354], p < 0.001) as an independent factor for shortening postoperative hospitalization time. After learning curve, LIHR (OR = 1.409, 95% CI: 0.948 to 2.094, p = 0.090) no longer resulted as a risk factor prolonging operation time. Conclusions: LIHR is an important independent predictive factor for decreasing intraoperative hemorrhage levels and shortening postoperative hospitalization time. Additionally, LIHR does not prolong operation time after the learning curve.
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Background: Edmondson-Steiner (E-S) grade is a pathological indicator of the degree of hepatocellular carcinoma (HCC) differentiation, and E-S grade III-IV is a poor prognostic factor for HCC patients. Predicting poorly differentiated HCC has essential significance for clinical decision-making. Although some studies have developed predictive models based on magnetic resonance imaging (MRI) and radiomics, radiomic features that require specific software for analysis are impractical for clinical work. This study aims to develop a novel and user-friendly nomogram model to predict E-S grade III-IV. Patients and Methods: Medical data on patients meeting the inclusion criteria were obtained from the Nanjing Drum Tower Hospital HCC database (January 2020 to December 2022). Univariate analysis was used to screen for risk factors associated with E-S grade III-IV. A novel nomogram was established based on the subsequent multivariate logistic regression analysis. The performance of the established model was evaluated through diagnostic ability, calibration, and clinical benefits. Results: Overall, 240 HCC patients were included in this study. Among them, 103 were highly differentiated (E-S grade I-II) HCC and 137 were poorly differentiated (E-S grade III-IV) HCC. A nomogram model that integrated alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb), aspartate aminotransferase to lymphocyte ratio index (ALRI), and macrovascular invasion was established. The novel model had a good diagnostic performance with an area under the curve (AUC) value of 0.763. Meanwhile, the model had a diagnostic accuracy of 72.5%, a sensitivity of 78.1%, and a specificity of 65.1%. The calibration curve showed good calibration of the nomogram model (mean absolute error = 0.043), and the decision curve analysis (DCA) demonstrated that the clinical benefit was provided. Conclusion: Our developed nomogram model could successfully predict E-S grade III-IV in HCC patients, which may be helpful in clinical decision-making.
RESUMEN
Background: The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope of surgical resection. It also affects the long-term efficacy of systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and γ-glutamyl transferase to platelet ratio (GPR), are less accurate in predicting cirrhosis in HCC patients. We aimed to build a novel decision tree model to improve diagnostic accuracy of liver cirrhosis. Patients and Methods: The Mann-Whitney U test, χ2 test, and multivariate logistic regression analysis were used to identify independent cirrhosis predictors. A decision tree model was developed using machine learning algorithms in a training cohort of 141 HCC patients. Internal validation was conducted in 99 HCC patients. The diagnostic accuracy and calibration of the established model were evaluated using receiver operating characteristic (ROC) and calibration curves, respectively. Results: Sex and platelet count were identified as independent cirrhosis predictors. A decision tree model integrating imaging-reported cirrhosis, APRI, FIB-4, and GPR was established. The novel model had an excellent diagnostic performance in the training and validation cohorts, with area under the curve (AUC) values of 0.853 and 0.817, respectively. Calibration curves and the Hosmer-Lemeshow test showed good calibration of the novel model. The decision curve analysis (DCA) indicated that the decision tree model could provide a larger net benefit to predict liver cirrhosis. Conclusion: Our developed decision tree model could successfully predict liver cirrhosis in HCC patients, which may be helpful in clinical decision-making.