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Primary liver cancer represents a major health concern in China. The combina-tion of targeted therapy with immunotherapy has initiated a new era in liver cancer treatment. Currently, immunotherapy-based combinational therapies are widely applied across all stages of liver cancer care, with notable improvements in neoadjuvant therapy, conversion therapy, postopera-tive adjuvant therapy, and locoregional treatments. These advancements have significantly improved patient outcomes. However, whether it is combination of targeted therapy with immunotherapy or dual immunotherapy for liver cancer, the overall response rate still needs to be further improved. Another crucial challenge remains in accurately selecting patients who will stand to benefit from these treatments. Importantly, tackling both primary and acquired drug resistance also presents an urgent and critical clinical and scientific issue in this field. Advancements in understanding tumor biology, discovering novel therapeutic targets, fostering pharmaceutical innovation and development, and decoding the mechanisms of drug sensitivity and resistance are all equally vital for the future breakthroughs in liver cancer treatments. The authors elaborate on the innovative progress of clinical and translational therapy research for liver cancer, in order to provide reference for the academic community to carry out related research.
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Objective:To investigate the clinical value of muscle index changing value during neoadjuvant chemotherapy in predicting the prognosis of gastric cancer after radical gastrec-tomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 362 gastric cancer patients undergoing neoadjuvant chemotherapy combined with radical gastrectomy in 3 medical centers, including 163 cases in Fujian Medical University Union Hospital, 141 cases in the Affiliated Hospital of Qinghai University and 58 cases in St. Mary′s Hospital, from January 2010 to December 2017 were collected. There were 270 males and 92 females, aged from 26 to 79 years, with a median age of 61 years. Of 362 patients, 304 cases in Fujian Medical University Union Hospital and the Affiliated Hospital of Qinghai University were allocated into modeling group and 58 cases in St. Mary′s Hospital were allocated into validation group. Observation indicators: (1) changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy; (2) follow-up and survival of patients; (3) analysis of risk factor affecting prognosis of patients in modeling group; (4) construc-tion and comparison of prognostic prediction models; (5) evaluation of prognostic prediction models. Follow-up was conducted using outpatient examination, telephone interview and mail communication to detect postoperative survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Univariate and multivariate analysis were performed using the COX proportional hazard model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy: the subcutaneous adipose index, visceral adipose index, muscle index, carcinoem-bryonic antigen, CA19-9, body mass index, prognostic nutritional index and modified systemic inflammation score of 304 gastric cancer patients in the modeling group before neoadjuvant chemotherapy were 31.2 cm 2/m 2(range, 0.6?96.0 cm 2/m 2), 25.1 cm 2/m 2(range, 0.1?86.3 cm 2/m 2), 47.1 cm 2/m 2(range, 27.6?76.6 cm 2/m 2), 43.2 μg/L(range, 0.2?1 000.0 μg/L), 108.7(range, 0.6? 1 000.0)U/mL, 21.9 kg/m 2(range, 15.6?29.7 kg/m 2), 46.8(range, 28.6?69.0), 1.0±0.8, respectively. The above indicators of 304 gastric cancer patients in the modeling group before radical gastrec-tomy were 32.5 cm 2/m 2(range, 5.1?112.0 cm 2/m 2), 25.4 cm 2/m 2(range, 0.2?89.0 cm 2/m 2), 47.0 cm 2/m 2(range, 16.8?67.0 cm 2/m 2), 17.0 μg/L(range, 0.2?1 000.0 μg/L), 43.9 U/mL(range, 0.6?1 000.0 U/mL), 21.6 kg/m 2(range, 31.1?29.0 kg/m 2), 47.7(range, 30.0?84.0), 1.0±0.8, respectively. The changing value of above indicators of 304 gastric cancer patients in the modeling group during neoadjuvant chemotherapy were 1.4 cm 2/m 2(range, ?31.0?35.1 cm 2/m 2), 0.2 cm 2/m 2(range, ?23.5?32.6 cm 2/m 2), ?0.1 cm 2/m 2(range, ?18.2?15.9 cm 2/m 2), ?26.2 μg/L(range, ?933.5?89.9 μg/L), ?64.9 U/mL(range, ?992.1?178.6 U/mL), ?0.3 kg/m 2(range, ?9.7?7.1 kg/m 2), 0.9(range, ?27.1?38.2), 0.0±0.8, respec-tively. (2) Follow-up and survival of patients: 284 of 304 patients in the modeling group were followed up for 3 to 130 months, with a median follow-up time of 36 months. During follow-up, 130 cases died of tumor recurrence and metastasis and 9 cases died of non-tumor causes. The 5-year overall survival rate was 54.6%. Fifty-two of 58 patients in the validation group were followed up for 2 to 91 months, with a median follow-up time of 29 months. During follow-up, 21 cases died with the 5-year overall survival rate of 63.8%. (3) Analysis of risk factor affecting prognosis of patients in modeling group: results of univariate analysis showed that the postoperative pathological type and postoperative pathological staging were related factors affecting 5-year overall survival rate [ hazard ratio=1.685, 2.619, 95% confidence interval(CI): 1.139?2.493, 1.941?3.533, P<0.05] and 5-year progression free rate survival of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.468, 2.577, 95% CI: 1.000?2.154, 1.919?3.461, P<0.05). Results of multivariate analysis showed that the postoperative pathological type and postoperative pathological staging were independent influencing factors for 5-year overall survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.508, 2.287, 95% CI: 1.013?2.245, 1.691?3.093, P<0.05) and the postoperative patholo-gical staging was an independent influencing factor for 5-year progression free survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio= 2.317,95% CI: 1.719?3.123, P<0.05). (4) Construction and comparison of prognostic prediction models: the area under curve (AUC) of prognostic prediction model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value for 304 gastric cancer patients in the modeling group were 0.549(95% CI: 0.504?0.593), 0.501(95% CI: 0.456?0.546), 0.566(95% CI: 0.521?0.610), 0.519(95% CI: 0.474?0.563), 0.588(95% CI: 0.545?0.632), 0.553(95% CI: 0.509?0.597), 0.539(95% CI: 0.495?0.584). The AUC of prognostic prediction model of muscle index changing value was 0.661(95% CI: 0.623?0.705) with significant differences to the AUC of prognostic predic-tion model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value, respectively ( Z=3.960, 5.326, 3.353, 4.786, 2.455, 3.448, 3.987, P<0.05). The optimum cut-off value was 0.7 cm 2/m 2 for prognostic prediction model of muscle index changing. Kaplan-Meier survival curve showed there were significant differences of overall survival and progression free survival for gastric cancer patients with subcutaneous adipose index changing value <0.7 cm 2/m 2 and ≥0.7 cm 2/m 2 in the modeling group ( χ2 =27.510, 21.830, P<0.05). The nomogram prognostic prediction model was cons-tructed based on 3 prognostic indicators including muscle index change value combined with postoperative pathological type and postoperative pathological staging and the AUC of nomogram prognostic prediction model were 0.762(95% CI: 0.708?0.815) and 0.788(95% CI: 0.661?0.885) for the modeling group and the validation group, respectively. The AUC of postoperative pathological staging prognostic prediction model were 0.706(95% CI: 0.648?0.765) and 0.727(95% CI: 0.594?0.835)for the modeling group and the validation group, respectively. There were significant differences of the AUC between the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging and the postoperative pathological staging prognostic prediction model in the modeling group and the validation group, respectively ( Z=3.522, 1.830, P<0.05). (5) Evaluation of prognostic prediction models: the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging showed that patients with score of 0-6 were classified in the low risk group, patients with score of >6 and ≤10 were classified in the moderate-low risk group, patients with score of >10 and ≤13 were classified in the moderate-high risk group and patients with score of >13 were classified in the high risk group. Kaplan-Meier survival curve showed there were significant differences of the overall survival between the low risk group, moderate-low risk group, moderate-high risk group and high risk group patients in the modeling group and the validation group, respectively ( χ2 =75.276, 14.989, P<0.05). Results of decision making curve showed the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging had better clinical utility than the postoperative pathological staging prognostic prediction model in the modeling group and the validation group. Conclusions:The muscle index changing value of gastric cancer patient during neoadjuvant chemotherapy can be used as a prognostic indicator for gastric cancer patient prognosis after radical gastrectomy. The risk score of the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging can be used to evaluate the survival and prognosis of gastric cancer patients after radical gastrectomy.
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Objective:To investigate the relationship of mitochondrial DNA (mtDNA) copy number with clinicopathologic characteristics and its influence on the prognosis of hepatocellular carcinoma (HCC) patients.Methods:The retrospective case-control study was conducted. The clinicopathological data of 71 HCC patients undergoing surgical treatment in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University from March to June 2011 were collected. There were 61 males and 10 females, aged from 26 to 80 years, with a median age of 55 years. The mtDNA copy number of tumor tissues and adjacent normal tissues were measured for all patients. Observation indicators: (1) the mtDNA copy number of tumor tissues and adjacent normal tissues and relationship between the mtDNA copy number and clinicopathological characteristics of HCC patients; (2) follow-up; (3) related factors for the prognosis of HCC patients. Follow-up using outpatient examination or telephone interview was conducted to detect postoperative survival of patients up to September 2019. Measurement data with normal distribution were described as Mean± SD, and comparison between groups was analyzed using independent samples t test or the matched samples t test. Measurement data with skewed distribution were described as M(range). Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Univariate and multivariate analyses were conducted using the COX regressional model. Variables with P<0.10 in the univariate analysis were included for the multivariate analysis. Survival rates were calculated using the Kaplan-Meier method, and Log-rank test was used for survival analysis. Results:(1) The mtDNA copy number of tumor tissues and adjacent normal tissues and relationship between the mtDNA copy number and clinicopathological characteristics of HCC patients: of 71 HCC patients, the mtDNA copy number was 0.85±0.08 in tumor tissues, versus 1.16±0.08 in adjacent normal tissues, showing a significant difference between them ( t=2.96, P<0.05). Of 71 HCC patients, 48 cases were mtDNA-low and 23 cases were mtDNA-high. Cases with tumor capsule as integrity or not-integrity, cases with or without microvascular (MVI) in mtDNA-low and mtDNA-high patients were 20, 28, 21, 27 and 16, 7, 4, 19, respectively, showing significant differences ( χ2=4.84, 4.74, P<0.05). (2) Follow-up: 71 patients were followed up for 2.1 to 85.3 months, with a median follow-up time of 47.8 months. The 1-, 3-, 5-year overall survival rates of 71 HCC patients were 87.3%, 64.7, 37.4%, respectively. Moreover, the 1-, 3-, 5-year overall survival rates were 81.2%, 50.0%, 29.2% of the mtDNA-low patients, versus 95.7%, 86.5%, 54.7% of the mtDNA-high patients, showing a significant difference between the two groups ( χ2=5.86, P<0.05). (3) Related factors for the prognosis of HCC patients. Results of univariate analysis showed that the number of tumor, portal vein tumor thrombus, MVI, Barcelona Clinic Liver Cancer stage, mtDNA copy number were related factors for the prognosis of HCC patients ( hazard ratios=2.211, 2.911, 3.899, 3.587, 0.440, 95% confidence intervals as 1.024?4.777, 1.485?5.704, 2.115?7.186, 1.615?7.966, 0.223?0.871, P<0.05). Results of multivariate analysis showed that MVI and mtDNA copy number were independent influencing factors for the prognosis of HCC patients ( hazard ratios=2.754, 0.437, 95% confidence intervals as 1.374?5.521, 0.205?0.932, P<0.05). Conclusions:The mtDNA copy number of HCC patients is related with tumor capsule and MVI. The mtDNA copy number and MVI are independent influencing factors for the prognosis of HCC patients.
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Resumen Las dificultades del aprendizaje constituyen una de las principales causas de fracaso escolar; su aparición temprana puede evidenciarse en las habilidades gnósico-práxicas que soportan los procesos de lectura y escritura. Objetivo: Describir las habilidades gnósicas y práxicas en niños escolares, de 9 a 12 años de edad, asociadas a la presencia o no de dificultades en la lectura y/o la escritura. Participantes: 53 niños de una institución pública del municipio de Sabaneta-Colombia, divididos en dos grupos, uno compuesto por 16 niños con dificultades en la lectura y/o escritura y, el otro, por 37 niños sin dificultades en estos procesos. Resultados: La comparación intergrupos evidenció diferencias estadísticas (valor p y tamaño del efecto) significativas en aspectos cruciales para el proceso de lectura y escritura: la formación de imágenes visoconstruccionales y la velocidad, la planeación y la coordinación motora, evaluadas a partir de las tareas gnósico-práxicas de Sucesión de números y letras (WISC-IV) y Tapping (BANETA). Adicionalmente, se hallaron diferencias estadísticas en las subpruebas de Esterognosia, y correlaciones significativas entre Tapping y la velocidad al escribir palabras (BANETA). Conclusión: Las habilidades gnósico-práxicas no son plenamente los procesos predominantes en las diferencias intergrupos, si bien las habilidades motoras se vinculan con los procesos de aprendizaje y las dificultades que en ellos puedan presentarse, como lo sugieren las correlaciones dadas entre la subprueba de velocidad motora y el proceso de escritura. Adicionalmente, la velocidad de procesamiento y la memoria operativa se presentan como procesos transversales a las habilidades gnósico-práxicas y de lectura y escritura.
Abstract Learning disabilities constitute one of the main causes of school failure; their early manifestation may be evidenced in the gnosis-praxis skills that support reading and writing processes. Objective: To describe the performance of gnosis-praxis skills in school children (aged from 9 to 12 years old), associated to the existence or not of reading and/or writing difficulties. Participants: 53 children of a public school in Sabaneta - Colombia, divided into two groups, one consisting of 16 children with difficulties in reading and/or writing and, the other, by 37 children without difficulties in these processes. Results: The intergroup comparison showed significant statistical differences , in crucial aspects for reading and writing process: the visoconstructional image formation, speed, planning and motor coordination, obtained from the gnosis - praxis tasks of Letter-Number Sequencing (WISC-IV) and Tapping (BANETA). Additionally, statistical differences were found in the subtests of Stereognosis (BANETA) and significant correlations between Tapping and the speed rate in writing words. Conclusion: Gnosis - praxis skills are not the predominant processes in intergroup differences, even though motor skills are linked to learning process and the difficulties they may arise, as suggested by the correlations given between the motor speed subtest and the writing process. In addition, processing speed and operational memory are shown as crosscutting processes in gnosis-praxis, reading and writing skills.
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Objective To investigate the cause, diagno sis and treatment of acute acalculous cholecystitis(AAC).Method 32 cases of AAC which were treated from 1990 to 2000 were analyzed retrosp ective ly.Results 25 cases were diagnosed by B-ultrasonograph ,th e positive rate of diagnosis was 88.0%(22/25),7 cases were diagnosed by CT,6 c ases were definitely diagnosed(85.7%).All of them underwent operations, cholec ystectomy was performed in 29 patients,cholecystostomy in 2, subtotal cholecyste ctomy in 1 .Of them 31 were cured and one died.Conclusions The cause of AAC is very complication, the preoperative diagnosis is difficult, it is easy to be misdiagnosed. Surgeon should pay more attention to AAC. B-ultra sonograph is the first choice of the diagnosis of AAC,CT can give a hand to diag nosis. The early operation resection is the most effective method.