Expression and Clinical Significance of CLCA2 in Pan-Cancer / Expresión y Significado Clínico de CLCA2 en Pan-Cáncer

SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.

El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.

Frailty does not affect prognostic markers in patients with acute coronary syndrome: results from a Brazilian university hospital

OBJECTIVE: To evaluate frailty and its relationship with prognostic markers in hospitalized patients with acute coronary syndrome. METHODS: This cross-sectional study with a prospective variable analysis (prognostic markers) involved adults of both sexes aged ≥ 50 years with acute coronary syndrome. Patients with ≥ 3 of the following criteria were considered frail: 1) unintentional weight loss; 2) exhaustion (assessed by self-reported fatigue); 3) low handgrip strength; 4) low physical activity level; and 5) low gait speed. The included prognostic markers were: metabolic changes (lipid and glycemic profile), changes in inflammatory status (C-reactive protein), thrombolysis in myocardial infarction risk score, troponin level, angioplasty or surgery, hospitalization in the intensive care unit, length of hospital stay, and hospital outcome. RESULTS: The sample consisted of 125 patients, whose mean age was 65.5 (SD, 8.7) years. The prevalence of frailty was 48.00%, which was higher in women (PR = 1.55; 95%CI 1.08­2.22; p = 0.018) and patients with systemic arterial hypertension (PR = 2.18; 95%CI 1.01­5.24; p = 0.030). Frailty was not associated with age, cardiac diagnosis, or prognostic markers (p > 0.05). CONCLUSIONS: Frailty was highly prevalent in patients with acute coronary syndrome, affecting almost half of the sample, particularly women and patients with hypertension, irrespective of age. However, despite its high prevalence, frailty was not associated with markers of metabolic change or poor prognosis.

Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-up

Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.

Análise do perfil clínico e epidemiológico das internações por asma no período de 2020 a 2021 em um hospital do sul de Santa Catarina / Analysis of the clinical and epidemiological profile of hospitalizations due to asthma in the period 2020­2021 in a hospital in southern Santa Catarina, Brazil

INTRODUÇÃO: A asma brônquica é uma doença crônica inflamatória de alta frequência mundialmente, e em especial no Brasil, onde ocorreram mais de 100.000 internações por ano, segundo dados do DATASUS. Identificar pacientes em admissão hospitalar que poderão necessitar de leito em UTI ou uso de ventilação mecânica por conta de crises asmáticas é um desafio ao profissional de saúde, portanto, faz-se importante analisar variáveis clínicas que possam predispor agravos e avaliar pacientes mais vulneráveis, para que as condutas realizadas sejam efetivas e rápidas. OBJETIVO: Analisar o perfil clínico e epidemiológico de pacientes internados em um hospital do sul do Brasil e avaliar os preditores relacionados ao maior tempo de internação. MÉTODOS: Estudo epidemiológico observacional, do tipo transversal, que utilizou como fonte de informação dados secundários, os quais foram obtidos através de prontuários de pacientes internados em um hospital do sul do Brasil. RESULTADOS: Foram analisados 261 prontuários. Verificou-se que a população menor de 40 anos de idade teve maior prevalência, representando 57% das internações. Além disso, em relação a gênero e etnia, mulheres e caucasianos foram as populações com maiores taxas de hospitalização, sendo 63% e 87% das admissões hospitalares, respectivamente.A necessidade de internação em UTI foi encontrada em 1,1% dos casos (3 pacientes), cerca de 6,9% tiveram internações prolongadas (maiores de 3 dias), e 0,8% vieram à óbito (2 pacientes). Identificou-se que a baixa saturação de oxigênio e a alta frequência cardíaca tiveram relação significativa com internação prolongada. CONCLUSÃO: É importante analisar sinais vitais no momento das admissões hospitalares e o perfil epidemiológico dos pacientes para que as populações mais prevalentes e os fatores preditivos de desfechos mais graves possam ser acompanhados e a conduta a ser tomada seja adequada e efetiva.

INTRODUCTION: Bronchial asthma is a chronic inflammatory disease with a high worldwide frequency, especially in Brazil, where more than 100,000 asthma-related hospitalizations occur annually according to DATASUS data. Identifying patients upon hospital admission who may require an ICU bed or mechanical ventilation due to an asthma attack is a challenge for healthcare professionals. It is important to analyze clinical variables that may predispose to deterioration and evaluate more vulnerable patients to ensure that effective interventions are instituted promptly. OBJECTIVE: To analyze the clinical and epidemiological profile of patients admitted due to asthma in a hospital in southern Brazil and evaluate predictors of longer hospital stay. METHODS: Observational epidemiological study with a cross-sectional design.The source of information were secondary data obtained from medical records of patients admitted to a hospital in southern Brazil. RESULTS: Overall, 261 medical records were analyzed.Patients were predominantly under the age of 40, representing 57% of hospitalizations. In terms of gender and ethnicity, most patients were female (63%) and white (87%).Three patients (1.1%) required ICU admission, approximately 6.9% had prolonged hospitalizations (>3 days), and 2 (0.8%) died. Low oxygen saturation and elevated heart rate correlated significantly with prolonged hospitalization. CONCLUSION: Vital signs at the time of hospital admission and the epidemiological profile of patients should be analyzed, so that the most prevalent populations and predictors of severe outcomes can be monitored, and appropriate and effective measures can be taken.

Utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer / Usefulness of the qSOFA score for predicting hospital mortality in cancer patients

Resumen Antecedentes: El quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) es una puntuación propuesta para identificar de forma rápida a pacientes con mayor probabilidad de morir. Objetivo: Describir la utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer. Material y métodos: Estudio transversal realizado entre enero de 2021 y diciembre de 2022. La mortalidad hospitalaria fue la variable dependiente. Se calculó el área bajo la curva ROC (ABC) para determinar la capacidad discriminativa de qSOFA para predecir mortalidad hospitalaria. Resultados: Se incluyeron 587 pacientes con cáncer. La puntuación qSOFA < 1 obtuvo una sensibilidad de 57.2 %, una especificidad de 78.5 %, un valor predictivo positivo de 55.4 % y un valor predictivo negativo de 79.7 %. El ABC de qSOFA para predecir mortalidad hospitalaria fue de 0.70. La mortalidad hospitalaria de los pacientes con qSOFA de 2 y 3 puntos fue de 52.7 y 64.4 %, respectivamente. La mortalidad hospitalaria fue de 31.9 % (187/587). Conclusión: qSOFA mostró capacidad discriminativa aceptable para predecir mortalidad hospitalaria en pacientes con cáncer.

Abstract Background: The quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) is a score that has been proposed to quickly identify patients at higher risk of death. Objective: To describe the usefulness of the qSOFA score to predict in-hospital mortality in cancer patients. Material and methods: Cross-sectional study carried out between January 2021 and December 2022. Hospital mortality was the dependent variable. The area under the ROC curve (AUC) was calculated to determine the discriminative ability of qSOFA to predict in-hospital mortality. Results: A total of 587 cancer patients were included. A qSOFA score higher than 1 obtained a sensitivity of 57.2 %, specificity of 78.5 %, a positive predictive value of 55.4 % and negative predictive value of 79.7 %. The AUC of qSOFA for predicting in-hospital mortality was 0.70. In-hospital mortality of patients with qSOFA scores of 2 and 3 points was 52.7 and 64.4 %, respectively. In-hospital mortality was 31.9 % (187/587). Conclusions: qSOFA showed acceptable discriminative ability for predicting in-hospital mortality in cancer patients.

Variáveis Clínicas e Laboratoriais na Admissão Hospitalar são Preditores de Fibrilação Atrial Nova em Pacientes Internados com Pneumonia por COVID-19 / Clinical and Laboratory Data Up on Hospital Admission are Predictors of New-Onset Atrial Fibrillation in Patients Hospitalized Due to COVID-19 Pneumonia

Resumo Fundamento Fibrilação atrial nova (FAN) ocorre em pacientes internados por COVID-19. Há controvérsias quanto ao valor preditivo de dados clínicos e laboratoriais à admissão hospitalar para ocorrência de FAN. Objetivos Analisar, à admissão hospitalar, variáveis com potencial preditivo para ocorrência de FAN em pacientes com pneumonia por COVID-19. Método Estudo observacional, retrospectivo, caso-controle. Foram avaliados prontuários eletrônicos de pacientes consecutivos ≥ 60 anos, hospitalizados com pneumonia por COVID-19 entre 1º de março e 15 de julho de 2020. Comparações feitas pelos testes `t' de Student ou qui-quadrado. Foi empregado modelo de risco proporcional de Cox para identificação de preditores de FAN. Considerou-se o valor de p < 0,05 como estatisticamente significativo. Resultados Entre 667 pacientes internados por COVID-19, 201 (30,1%) foram incluídos. FAN foi documentada em 29 pacientes (14,4%) (grupo 1). Grupo 2 foi composto por 162 pacientes que não apresentaram FAN. Dez pacientes excluídos por estarem em FA na admissão hospitalar. Houve diferenças entre os grupos 1 e 2, respectivamente, no tempo de permanência em UTI (11,1±10,5 dias vs. 4,9±7,5 dias; p=0,004), necessidade de ventilação invasiva (82,9% e 32,7%; p<0,001) e mortalidade hospitalar (75,9% vs. 32,1%; p<0,001). No modelo de Cox, idade > 71 anos (hazard ratio [HR]=6,8; p<0,001), leucometria ≤ 7.720 cels.μL-1 (HR=6,6; p<0,001), natremia ≤ 137 mEq.L-1 (HR=5,0; p=0,001), escore SAPS3 > 55 (HR=5,6; p=0,002) e desorientação (HR=2,5; p=0,04) foram preditores independentes de FAN. Conclusões FAN é uma arritmia comum em idosos hospitalizados com pneumonia por COVID-19. Parâmetros clínicos e laboratoriais avaliados na admissão são preditores de FAN durante internação.

Abstract Background New-onset atrial fibrillation (NOAF) occurs in patients hospitalized due to COVID-19. It is still unknown whether clinical and laboratory data assessed upon hospital admission have predictive value for NOAF. Objectives To analyze, upon hospital admission, variables with predictive potential for the occurrence of NOAF in patients with COVID-19 pneumonia. Methods Observational, retrospective, case-control study. Electronic medical reports of consecutive patients, 60 years of age or older, hospitalized due to COVID-19 pneumonia between March 1st and July 15th, 2020, were reviewed. Non-paired Student or chi-squared tests compared variables. A Cox proportional hazard model was employed to identify independent predictors of NOAF. P value < 0.05 was considered statistically significant. Results Among 667 patients hospitalized due to COVID-19, 201 (30.1%) fulfilled the inclusion criteria. NOAF was documented in 29 patients (14.4%), composing group 1. Group 2 was composed of 162 patients without NOAF. Ten patients were excluded due to the AF rhythm upon hospital admission. In groups 1 and 2, there were differences in overall in-hospital survival rate (24.1 % vs. 67.9%; p<0.001), length of stay in ICU (11.1 ± 10.5 days vs. 4.9 ± 7.5 days; p=0.004) and need for mechanical ventilation rate (82.9% vs. 32.7%; p<0.001). In the Cox model, age > 71 y/o (HR=6.8; p<0.001), total leukocyte count ≤ 7,720 cels.μL-¹ (HR=6.6; p<0.001), serum [Na+] ≤ 137 mEq.L-¹ (HR=5.0; p=0.001), SAPS3 score > 55 (HR=5.6; p=0.002), and disorientation (HR=2.5; p=0.04) on admission were independent predictors of NOAF. Conclusion NOAF is a common arrhythmia in elderly hospitalized patients with COVID-19 pneumonia. Clinical and laboratory parameters evaluated on admission have a predictive value for the occurrence of NOAF during hospitalization.

Prognostic awareness and prognostic information preferences among advanced cancer patients in Kenya

Background: Cancer is the third leading cause of death in Kenya. Yet, little is known about prognostic awareness and preferences for prognostic information. Aim: To assess the prevalence of prognostic awareness and preference for prognostic information among advanced cancer patients in Kenya. Setting: Outpatient medical oncology and palliative care clinics and inpatient medical and surgical wards of Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. Methods: The authors surveyed 207 adults with advanced solid cancers. The survey comprised validated measures developed for a multi-site study of end-of-life care in advanced cancer patients. Outcome variables included prognostic awareness and preference for prognostic information. Results: More than one-third of participants (36%) were unaware of their prognosis and most (67%) preferred not to receive prognostic information. Increased age (OR = 1.04, 95% CI: 1.02, 1.07) and education level (OR: 1.18, CI: 1.08, 1.30) were associated with a higher likelihood of preference to receive prognostic information, while increased symptom burden (OR= 0.94, CI: 0.90, 0.99) and higher perceived household income levels (lower-middle vs low: OR= 0.19; CI: 0.09, 0.44; and upper middle- or high vs low: OR= 0.22, CI: 0.09, 0.56) were associated with lower odds of preferring prognostic information. Conclusion: Results reveal low levels of prognostic awareness and little interest in receiving prognostic information among advanced cancer patients in Kenya. Contribution: Given the important role of prognostic awareness in providing patient-centred care, efforts to educate patients in Kenya on the value of this information should be a priority, especially among younger patients.

The correlation between YAP nuclear expression and tumor size with prognosis of epithelial ovarian cancer / 安徽医科大学学报

Objective To investigate the correlation between Yes-associated protein(YAP)nuclear expression and tumor size with prognosis of patients with epithelial ovarian cancer(EOC)and to study the role of YAP in EOC.Methods 120 patients with EOC were selected as the experimental group,including 38 patients with early stage(Ⅰ+Ⅱ)EOC and 8 2 patients with advanced stage(Ⅲ+Ⅳ)EOC.3 0 normal ovarian tissues obtained from patients with uterine leiomyoma were enrolled as the control group.Immunohistochemical(IHC)assay was em-ployed to determine YAP expression and sub-location.The relationship between YAP expression and the pathologi-cal parameters of the 120 patients with EOC was analyzed,so as to the prognosis of these patients.EOC cells(C13K and OV2008)were cultured with varying initial cell volumes.Ki67 expression and cell proliferation were tested by immunofluorescence and cloning assay respectively.YAP expression at mRNA and protein levels were de-tected by q-PCR and Western blot respectively when the cell conference of EOC cells reached to low(60％)and high(90％)cell density.Results The YAP nuclear expression was significantly higher in the EOC group com-pared to the control group(P＜0.05).The average diameter of stage Ⅰ+Ⅱ EOC was larger than that of stage Ⅲ+Ⅳ EOC(P＜0.01).The high nuclear expression of YAP was positively associated with pathological grade,clinical stage and the level of Ca125＞1 000 IU/ml,while negatively correlated with tumor size(all P＜0.05).Survival analyses showed that smaller tumor size(＜10 cm)and higher YAP nuclear expression were negatively as-sociated with the 3-year overall survival rate of EOC patients(P＜0.01).C13K and OV2008 cells cultured in the low density group exhibited a high number of clone formation,high Ki67 and YAP expression(P＜0.01).The down-regulation of YAP expression could decrease the cell viability of EOC cells in the low-and high-density groups(P＜0.05).Conclusion Higher level of YAP nuclear expression and smaller tumour size are inversely associated with the clinical prognosis of patients with EOC.Inhibiting YAP nuclear expression leads to a decrease in the prolif-eration capacity of EOC cells.

Advances in the application of single-cell sequencing technology in diagnosis and prognostic assessment of acute leukemia / 白血病·淋巴瘤

Currently, single-cell multi-omics technologies including single-cell DNA sequencing (scDNA-seq) and single-cell RNA sequencing (scRNA-seq) have been used to reveal the heterogeneity of malignant tumor cells, elucidate their pathogenesis, drug resistance and recurrence mechanisms, which provide new strategies for the diagnosis and prognostic assessment of malignant tumors. This article reviews the application of single-cell sequencing technology in the diagnosis and prognostic assessment of acute leukemia based on the progress reported at the 65th American Society of Hematology Annual Meeting.

Human immunodeficiency virus-associated Hodgkin lymphoma: a clinical analysis of 22 cases / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics, therapeutic efficacy and prognosis of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma.Methods:A retrospective case series study was conducted. The clinical data of 22 HIV-associated Hodgkin lymphoma patients in Chongqing University Cancer Hospital from December 2013 to June 2022 were retrospectively analyzed. Their clinical features, laboratory results, treatment, and prognosis were analyzed. Kaplan-Meier method was used to perform survival analysis.Results:The age [ M ( Q1, Q3)] of 22 patients was 44 years old (36 years old, 53 years old); 18 cases were male, 4 cases were female; clinical staging was stage Ⅲ in 5 patients and stage Ⅱ in 17 patients. All 22 patients were infected with HIV through sexual transmission, with 10 cases transmitted through man sex with man and 12 cases transmitted through heterosexual transmission. Nine patients were found to be infected with HIV at the time of diagnosis of lymphoma, and 13 patients presented with lymphoma at 22.2 months (12.3 months, 38.4 months) after diagnosis of HIV infection. Of the 22 patients, 3 abandoned treatment; 19 patients were treated with antiretroviral therapy combined with ABVD regimen chemotherapy, 9 patients had complete remission, and 10 patients had partial remission. After follow-up of 46.8 months (24.8 months, 64.5 months), the 5-year progression-free survival rate was 83.9%, and the 5-year overall survival rate was 89.5%. Conclusions:HIV-associated Hodgkin lymphoma exhibits an invasive process in clinical practice, and standardized antiretroviral therapy combined with ABVD regimen chemotherapy can lead to long-term survival for patients.

Level of serum lipoprotein a in patients with diffuse large B-cell lymphoma and its impact on prognosis / 白血病·淋巴瘤

Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.

Analysis of clinicopathological features, therapeutic efficacy, prognosis and mutation in 11 patients with cardiac diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.

Predictive value of controlling nutritional status score in the prognosis of patients with advanced diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Analysis on correlation between PDK 1 and Ki-67 expression levels with survival and prognosis of patients with ovarian serous carcinoma / 重庆医学

Objective To analyze the relationship between the expression levels of pyruvate dehydro-genase kinase 1(PDK 1)and Ki-67 with the survival and prognosis of the patients with ovarian serous carci-noma(OSC).Methods The cancer tissues of 93 patients with OSC treated by surgery in this hospital from January 2000 to June 2020 were collected,and the expression levels of PDK1 and Ki-67 in the tissues were de-tected by immunohistochemistry.The relationship between the expression levels of PDK1 and Ki-67 with the clinicopathological characteristics of the patients with OSC was analyzed by the single factor and binary logis-tic regression model.The relationship between the PDK1 and Ki-67 expression levels with the recurrence and platinum resistance within 3 years was analyzed.The Kaplan-Meier survival curve was adopted to analyze the effect of PDKI and Ki-67 expression levels on the survival and prognosis in the patients with OSC.Results The expression levels of PDK1 and Ki-67 were related with the International Federation of Gynecology and Obstetrics(FIGO)stage,tissue differentiation level,lymphatic metastasis,ascites formation and positive asci-tes(P＜0.05).The high expression of PDK1 was a risk factor for the late FIGO stage(Ⅲ-Ⅳ),lymphatic metastasis and ascites positive in the patients with OSC(P＜0.05);the high expression of Ki-67 was a risk factor for the late FIGO stage(Ⅲ-Ⅳ)and ascites formationin in the patients with OSC(P＜0.05).The re-currence rate and platinum resistance rate within 3 years in the patients with PDKi and Ki-67 high expressions were significantly higher than those in the patients with low expressions(P＜0.05).The progression-free survival(PFS),overall survival(OS)and 5-year survival rate in the patients with high PDK1 and Ki-67 ex-pressions were significantly lower than those in the patients with low expressions(P＜0.05).Conclusion The expression levels of PDK 1 and Ki-67 play an important role in judging the survival and prognosis of the patients with OSC.

Analysis of the efficacy and prognosis of radiotherapy in acute leukemia with extramedullary infiltration / 重庆医学

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Early stratification of in-hospital mortality risk in adult septic shock patients and development of a simplified scoring system / 重庆医学

Objective To analyze the independent factors impacting the in-hospital prognosis of patients with septic shock,and to construct a simplified scoring system and evaluate its predictive value.Methods A retrospective analysis was carried out on 247 patients with septic shock admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from January 2021 to July 2022,among whom 122 patients survived and 125 died.Univariate analysis and multivariate Cox proportional hazard regression model were used to screen the independent factors affecting in-hospital mortality of septic shock patients.The best cut-off value was ob-tained by using the receiver operating characteristics(ROC)curve,and the continuous variables were conver-ted into binary variables and assigned.Finally,a simplified scoring system was established,and its predictive efficacy for hospital death in septic shock patients was verified.Results The results of multivariate Cox pro-portional hazard regression model showed that the Glasgow coma scale(GCS)score(HR=0.929,95%CI:0.875-0.985,P=0.014),quick sequential organ failure assessment(qSOFA)score(HR=1.475,95%CI:1.094-1.989,P=0.011),lactate level(HR=1.096,95%CI:1.049-1.145,P<0.001),procalcitonin level(HR=1.009,95%CI:1.000-1.018,P=0.048),and albumin level(HR=0.958,95%CI:0.922-0.996,P=0.029)were identified as independent influencing factors for in-hospital mortality in patients with septic shock.The ROC curve showed that the simplified scoring system,based on GCS score,qSOFA score,lactate,procalcitonin,and albumin levels,exhibited an area under the curve and 95%CI of 0.866(0.822-0.910),with an optimal cutoff value of 2.5.The sensitivity and specificity were 80.0%and 78.7%,respectively.Con-clusion The simplified scoring system,based on early assessments of GCS score,qSOFA score,lactate,pro-calcitonin,and albumin levels,demonstrates substantial predictive value for in-hospital mortality in patients with septic shock.

Expression and clinical significance of phosphorylated FGFR1Y654 in esophageal squamous cell carcinoma / 陆军军医大学学报

Objective To explore the relationship between p-FGFR1Y654 expression and clinical pathological characteristics of esophageal squamous cell carcinoma patients and its prognostic value.Methods Tumor tissue samples from 103 cases of esophageal squamous cell carcinoma and 58 normal esophageal tissues were surgically collected in the General Hospital of Western Theater between January 2017 and July 2020.The expression of p-FGFR1Y654 in the tissues was detected using immunohistochemical assay,and its correlation with relevant clinicopathological parameters and prognosis was analyzed.Results The expression of p-FGFR1Y654 in esophageal squamous cell carcinoma tissues was significantly higher than that in normal tissue(P＜0.01).Its expression level was closely related to overall survival(OS,P＜0.05),but not related to age,gender,tumor stage or tumor size.Multivariate COX regression analysis showed that N-stage was identified as an independent prognostic factor for recurrence free survival(RFS)in esophageal squamous cell carcinoma patients.Survival analysis indicated that patients with low expression of p-FGFR1Y654 had significantly higher RFS and OS than those with high expression(P=0.032,95％CI:1.08～4.65;P=0.004,95％CI:2.14-11.51).Conclusion p-FGFR1Y654 is highly expressed in esophageal squamous cell carcinoma tissue,and is associated with poor prognosis in these patients.p-FGFR1Y654 may be a potential therapeutic target for esophageal squamous cell carcinoma.

Remodeling characteristics and construction of a survival prediction model based on enhancers and regulome in intestinal type gastric cancer / 陆军军医大学学报

Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer,analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis.Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers.Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications.Based on the distribution characteristics of H3K27ac,the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored.The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses.Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues.Compared with normal gastric mucosa,the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer.A total of 8847 enhancers with increased activity in intestinal type gastric cancer were identified,accounting for 8.3%of all enhancers,which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells.A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers,which was able to predict the overall survival of patients.Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer.These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC,E2F3 and other genes.A prognosis model based on enhancer target genes is constructed.

Prognostic significance of lactate dehydrogenase in salvage intensity-modulated radiotherapy for locally recurrent nasopharyngeal carcinoma before treatment / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the prognostic value of pre-treatment serum lactate dehydrogenase(LDH)levels in patients with locally recurrent nasopharyngeal carcinoma(NPC)treated with salvage intensity-modulated radiotherapy(IMRT)and to determine its association with rT staging.METHODS The records of 97 patients with locally relapsed and non-metastatic NPC who received salvage IMRT treatment in our center from January 2018 to April 2022 were collected,including 51 patients who died,18 patients with distant metastases,30 patients with local failure,and 67 patients with prognostic adverse events(death,distant tumors/local metastases).Clinical data,local failure-free survival(LFFS),distant metastasis-free survival(DMFS)and overall survival(OS)were obtained from all patients,and the relationship between LDH and the prognosis of salvage IMRT therapy in NPC patients was analyzed.RESULTS The serum LDH level before salvage IMRT was significantly higher in the death[221.25(178.24,339.13)U/L vs.124.82(79.0,159.50)U/L,Z=-5.122],local failure[230.75(170.89,394.50)U/L vs.157.85(91.78,216.95)U/L,Z=-3.442],distant metastasis[261.62(153.55,465.50)U/L vs.168.98(101.75,237.75)U/L,Z=-2.478]and poor prognosis group[220.05(167.20,506.16)U/L vs.93.45(69.95,154.35)U/L,Z=-6.018],and all P<0.05.Serum LDH levels were divided into dichotomous variables according to median values(≥177.50 U/L vs.<177.50 U/L),the Cox univariate model found that the hazard ratios of LDH affecting LFFS,DMFS,OS and toxic-related death(TRD)were 3.759(1.660-8.558),4.217(1.383-12.861),3.226(1.715-6.069),3.363(1.750-6.463),P<0.05.LDH remained an independent prognostic factor for LFFS,DMFS,OS,and TRD in multivariate regression analysis(P<0.05).Compared with patients with LDH<177.50 U/L,more patients in the LDH≥177.50 U/L group had local progression-related death,and the no LFFS stage,no DMFS stage and OS were shorter in the LDH≥177.50 U/L group(log rank=11.624,7.559,14.758),P<0.05.In predicting overall survival,adding LDH to the rT stage is preferable to the rT stage alone.CONCLUSION LDH is an important factor in predicting LFFS,DMFS,OS,and TRD after saving IMRT in patients with locally relapsed,non-metastatic NPC,and the value of LDH combined with rT staging in predicting overall survival is high.