RESUMEN
Background: Age-related kidney failure is often induced by a decrease in the bioavailability of tubular epithelial cells in elderly chronic kidney disease (CKD) patients. BRD4, an epigenetic regulator and a member of the bromodomain and extraterminal (BET) protein family, acts as a super-enhancer (SE) organizing and regulating genes expression during embryogenesis and cancer development. But the physiological function of BRD4 in normal cells has been less studied. This study aimed to research certain biological roles of BRD4 in the process of normal cell aging and discuss the potential mechanisms. Methods: In this study, we investigated the biological functions of BRD4 proteins in the aging of renal tubular cells. At first, we used a D-galactose (D-gal) and BRD4 inhibitor (Abbv-075) to replicate kidney senescence in vivo. D-gal and Abbv-075 were then used to measure the aging-related changes, such as changes in cell cycle, ß-galactosidase activity, cell migration, and p16 protein expression in vitro. At last, we knocked down and over-expressed BRD4 to investigate the aging-related physiological phenomena in renal tubular cells. Results: In vitro, D-gal treatment induced noticeable aging-related changes such as inducing cell apoptosis and cell cycle arrest, increasing ß-galactosidase activity as well as up-regulating p16 protein expression in primary human tubular epithelial cells. In the aging mice model, D-gal significantly induced renal function impairment and attenuated BRD4 protein expression. At the same time, the BRD4 inhibitor (Abbv-075) was able to mimic D-gal-induced cell senescence. In vivo, Abbv-075 also decreased kidney function and up-regulated p21 protein expression. When we knocked down the expression of BRD4, the senescence-associated ß-galactosidase (SA-ß-gal) activity increased dramatically, cell migration was inhibited, and the proportion of cells in the G0/G1 phase increased. Additionally, the knockdown also promoted the expression of the senescence-related proteins p16. When the renal tubular cells were overexpressed with BRD4, cell aging-related indicators were reversed in the D-gal-induced cell aging model. Conclusions: BRD4 appears to have an active role in the aging of renal tubular cells in vivo and in vitro. The findings also suggest that BRD4 inhibitors have potential nephrotoxic effects for oncology treatment. BRD4 may be a potential therapeutic biomarker and drug target for aging-related kidney diseases, which warrants additional studies.
RESUMEN
It has been demonstrated that microplastics (MPs) may be inadvertently ingested by aquatic animals, causing harm to their physiological functions and potentially entering the food chain, thereby posing risks to human food safety. To achieve an environmentally friendly and efficient reduction of MPs in freshwater environments, this experiment investigates the depuration effect of C. demersum on MPs using three common aquatic animals: Macrobrachium nipponense, Corbicula fluminea, and Bellamya aeruginosa as research subjects. The amounts of MPs, digestive enzyme activity, oxidative stress index, and energy metabolism enzyme activity in the digestive and non-digestive systems of three aquatic animals were measured on exposure days 1, 3, and 7 and on depuration days 1 and 3. The results indicated that the depuration effect of C. demersum and the species interaction were significant for the whole individual. Concerning digestive tissue, C. demersum was the most effective in purifying B. aeruginosa. When subjected to short-term exposure to MPs, C. demersum displayed a superior depuration effect. Among non-digestive tissues, C. demersum exhibited the earliest purifying effect on C. fluminea. Additionally, C. demersum alleviated physiological responses caused by MPs. In conclusion, this study underscores C. demersum as a promising new method for removing MPs from aquatic organisms.
Asunto(s)
Corbicula , Microplásticos , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo , Corbicula/metabolismo , Corbicula/efectos de los fármacos , Palaemonidae/metabolismo , Estrés Fisiológico , Estrés Oxidativo/efectos de los fármacos , Chlorophyceae/metabolismoRESUMEN
Background: Individuals with pre-existing chronic kidney disease (CKD) are at an increased risk of experiencing severe symptoms if infected with COVID-19. This report presents the case of a patient with CKD who contracted COVID-19 and subsequently experienced rapid deterioration of kidney function, hair loss, and spontaneous remission of facial warts. Case presentation: A 60-year-old Chinese man with a decade-long history of abnormal serum creatinine (Scr) levels and recently heightened fatigue sought treatment. The disease was previously managed and deemed resolved in 2020. However, when he contracted the novel coronavirus on December 20, 2022, he experienced persistent fatigue without other symptoms. In early January 2023, Scr levels was examined as more than 300 µmol/L. This was followed by hair loss, including eyebrows and lashes, and the spontaneous resolution of a longstanding facial wart. During this period, although the patient received kidney-protecting drugs and a lifestyle optimization, Scr increased continuously and the disease eventually progressed to the uremic stage. As the patient still had relatively abundant urine volume, the patient chose peritoneal dialysis treatment. At a two-month follow-up, he had adhered to the CAPD protocol without complications and his hair had begun to regrow. After eight months, his hair had mostly regrown, and his Scr levels kept stable. Conclusion: This case may represent the inaugural instance of CKD patients experiencing rapid deterioration of renal function, hair loss, and spontaneous remission of common warts. The underlying mechanisms of this unique phenomenon warrant further researches and debate.
RESUMEN
Background: Cervical cancer (CC) is a highly malignant gynecological cancer with a direct causal link to inflammation, primarily resulting from persistent high-risk human papillomavirus (HPV) infection. Given the challenges in early detection and mid to late-stage treatment, our research aims to identify inflammation-associated immune biomarkers in CC. Methods: Using a bioinformatics approach combined with experimental validation, we integrated two CC datasets (GSE39001 and GSE63514) in the Gene Expression Omnibus (GEO) to eliminate batch effects. Immune-related inflammation differentially expressed genes (DGEs) were obtained by R language identification. Results: This analysis identified 37 inflammation-related DEGs. Subsequently, we discussed the different levels of immune infiltration between CC cases and controls. Weighted gene co-expression network analysis (WGCNA) identified seven immune infiltration-related modules in CC. We identified 15 immune DEGs associated with inflammation at the intersection of these findings. In addition, we constructed a protein interaction network using the String database and screened five hub genes using "CytoHubba": CXC chemokine ligand 8 (CXCL8), CXC chemokine ligand 10 (CXCL10), CX3C chemokine receptor 1 (CX3CR1), Fc gamma receptors 3B (FCGR3B), and SELL. The expression of these five genes in CC was determined by PCR experiments. In addition, we assessed their diagnostic value and further analyzed the association of immune cells with them. Conclusions: Five inflammation- and immune-related genes were identified, aiming to provide new directions for early diagnosis and mid to late-stage treatment of CC from multiple perspectives.
RESUMEN
Background. Tripartite motif-containing 22 (TRIM22) is characterized by a canonical RING domain with ubiquitin E3 ligase activity and is closely associated with tumorigenesis. As a product of TRIM22 transcription, whether hsa_circ_TRIM22 has a function of regulating tumorigenesis is unclear. Thus, we aimed to explore the role and mechanism of hsa_circ_TRIM22 in human papillomavirus (HPV) 16 positive cervical cancer (CC). Methods. We collected HPV16-positive cervical tissues including chronic cervicitis, high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and CC, and along with CC cell lines to detect the hsa_circ_TRIM22 level using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Hsa_circ_TRIM22 was silenced using specific short hairpin ribonucleic acid (shRNA) in CC cell lines and functional assays were performed thereafter. Mechanistically, the targeting and regulatory relationship between hsa_circ_TRIM22 and miR-154-5p were confirmed using the luciferase report assay and rescue experiments. Results. We found hsa_circ_TRIM22 expression level was significantly higher in CC cells and tissues. Further, hsa_circ_TRIM22 knockdown inhibited migration, proliferation, invasiveness, enhanced apoptosis, and slowed the cell cycle. Mechanistically, hsa_circ_TRIM22 could bind miR-154-5p and prevent miR-154-5p from reducing the levels of Cullin2 (CUL2). Notably, the application of miR-154-5p inhibitor significantly rescued hsa_circ_TRIM22-mediated tumorigenesis. Conclusions. Our observations suggest hsa_circ_TRIM22 is upregulated in HPV16-positive CC and promotes CC progression by regulating the miR-154-5p/CUL2 axis, thereby serving as a promising candidate for diagnosis and treatments of CC.
RESUMEN
OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30â¯% of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37â¯mL/min/1.73â¯m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.
Asunto(s)
Cistatina C , Tasa de Filtración Glomerular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cistatina C/sangre , Adulto , Anciano , Creatinina/sangre , Pruebas de Función Renal/métodos , Pruebas de Función Renal/normas , China , Pueblo Asiatico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Riñón/fisiología , Curva ROC , Pueblos del Este de AsiaRESUMEN
Objective: To introduce laparoscopic neo-pancreaticogastrostomy (neo-PG) and investigate its application potential in total laparoscopic pancreaticoduodenectomy (TLPD). Materials and Methods: We performed a single-center prospective single-arm trial to evaluate the feasibility and safety of neo-PG for its initial application in TLPD. The first 50 patients who were operated by a single surgeon and who underwent TLPD with neo-PG at our institution were recruited. The pre/intra/postoperation data were collected and analyzed. Results: Twenty-nine male patients and 21 female patients from May 2022 to March 2023 were included. The mean operation time was 272.60 ± 47.30 minutes. The median PG time was 16 (15, 23) minutes. Six patients had delayed gastric emptying (DGE), and all underwent standard LPD. None of the patients had Grade B/C postoperative pancreatic fistula (POPF) or postoperative hemorrhage, or underwent reoperation. The median length of post-LPD hospital stay was 6 (6, 8) days. None of the patients died within 90 days after surgery. Nineteen cases were pathologically classified as pancreatic lesion, 6 cases as bile duct lesion, 18 cases as duodenal lesion, and 7 cases as ampullary lesion. Conclusion: The laparoscopic neo-PG is a simple, safe, and feasible pancreatic anastomosis that can be applied in TLPD. Pylorus-preserving LPD may decrease DGE rate. Further studies involving more surgeons are warranted to prove that our new technique may terminate POPF in TLPD.
Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Femenino , Humanos , Masculino , Anastomosis Quirúrgica/métodos , Laparoscopía/métodos , Fístula Pancreática , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20â¯% [P20] and ±30â¯% [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50⯵mol/L; ≥80 years, 54.41-96.43⯵mol/L. RIs for females were: 18-59 years, 40.42-69.73⯵mol/L; 60-79 years, 41.16-73.69⯵mol/L; ≥80 years, 46.50-73.20⯵mol/L. Q-values were set at 73.82⯵mol/L (0.84â¯mg/dL) for males and 53.80⯵mol/L (0.61â¯mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.
Asunto(s)
Creatinina , Minería de Datos , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Femenino , Creatinina/sangre , Adulto , Anciano , Valores de Referencia , Adolescente , Adulto Joven , Minería de Datos/métodos , Anciano de 80 o más Años , ChinaRESUMEN
Triple-negative breast cancer (TNBC) cells are in a more hypoxic and starved state than non-TNBC cells, which makes TNBC cells always maintain high autophagy levels. Emerging evidence has demonstrated that circular RNAs (circRNAs) are involved in the progress of tumorigenesis. However, the regulation and functions of autophagy-induced circRNAs in TNBC remain unclear. In our study, autophagy-responsive circRNA candidates in TNBC cells under amino acid starved were identified by RNA sequencing. The results showed that circEGFR expression was significantly upregulated in autophagic cells. Knockdown of circEGFR inhibited autophagy in TNBC cells, and circEGFR derived from exosomes induced autophagy in recipient cells in the tumor microenvironment. In vitro and in vivo functional assays identified circEGFR as an oncogenic circRNA in TNBC. Clinically, circEGFR was significantly upregulated in TNBC and was positively associated with lymph node metastasis. CircEGFR in plasma-derived exosomes was upregulated in breast cancer patients compared with healthy people. Mechanistically, circEGFR facilitated the translocation of Annexin A2 (ANXA2) toward the plasma membrane in TNBC cells, which led to the release of Transcription Factor EB (a transcription factor of autophagy-related proteins, TFEB) from ANXA2-TFEB complex, causing nuclear translocation of TFEB, thereby promoting autophagy in TNBC cells. Meanwhile, circEGFR acted as ceRNA by directly binding to miR-224-5p and inhibited the expression of miR-224-5p, which weakened the suppressive role of miR-224-5p/ATG13/ULK1 axis on autophagy. Overall, our study demonstrates the key role of circEGFR in autophagy, malignant progression, and metastasis of TNBC. These indicate circEGFR is a potential diagnosis biomarker and therapeutic target for TNBC.
Asunto(s)
Proteínas Relacionadas con la Autofagia , MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , MicroARNs/genética , ARN Circular/genética , Neoplasias de la Mama Triple Negativas/patología , Retroalimentación , Proliferación Celular/genética , Línea Celular Tumoral , Autofagia/genética , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismoRESUMEN
BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.
Asunto(s)
Enfermedades Renales Quísticas , Riñón , Humanos , Tasa de Filtración Glomerular , Estudios Transversales , Factores de Riesgo , Enfermedades Renales Quísticas/epidemiología , China/epidemiologíaRESUMEN
BACKGROUND: Peripheral blood-derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. MATERIALS AND METHODS: Pure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK cells and cytokine secretion by NK cells were examined using flow cytometry. NK cell antitumor activity in vitro was assessed using lactate dehydrogenase (LDH) cytotoxicity assay and an Incucyte real-time imaging system. Additionally, the function of SNK cells against ascites caused by ovarian cancer in NOD-Prkdc(em26Cd52)il2rg(em26Cd22)/Nju (NCG) mice was determined. In a further investigation of the differences between PBNK and SNK, the mRNA of both cells was sequenced and analyzed. RESULTS: Human peripheral blood mononuclear cells showed selective NK cell expansion upon cytokine activation and culture. Both SNK and PBNK cells expressed activation markers, but at different levels, and SNK cells secreted more cytokines related to cytotoxicity than PBNK cells did. Accordingly, SNK cells exhibited strong antitumor activity ex vivo and improved NCG mice survival after intraperitoneal ovarian cancer transplantation. Mechanistically, SNK cells expressed more genes associated with nucleotide metabolism, fatty acid, and ATP metabolism than PBNK cells. CONCLUSION: SNK cells derived from peripheral blood mononuclear cells have sufficiently activated mature characteristics and high antitumor activity, rendering them a highly promising and essential therapeutic approach for cancer treatment.
Asunto(s)
Leucocitos Mononucleares , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Ratones Endogámicos NOD , Células Asesinas Naturales , CitocinasRESUMEN
BACKGROUND: Equations based on serum creatinine (SCr) have been extensively applied to estimate glomerular filtration rate (GFR), but their performance is debatable. In 2021, the European Kidney Function Consortium (EKFC) published one novel SCr-based formula, which combined the feature of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and full age spectrum (FAS) equations, but its potential applications remain unknown. We seek to assess the appropriateness of the three equations in Chinese adults. METHODS: A total of 3,692 participants (median age, 54 years) were included. Reference GFR (rGFR) was measured by the 99mTc-DTPA renal dynamic imaging method. Estimated GFR (eGFR) was calculated by the CKD-EPI, FAS, and EKFC equations. Correlation coefficients and Bland-Altman analysis were adopted to evaluate their validity. The performance was assessed in subgroups according to age, sex, rGFR, and SCr, considering the bias, accuracy, and precision. RESULTS: The average rGFR was 74.2 mL/min/1.73 m2. eGFR by EKFC showed a relatively stronger correlation with rGFR (R = 0.749) and a larger area under the receiver operating characteristic curve (0.902). EKFC was significantly less biased and exhibited the highest P30 in the entire population (bias = 3.61, P30 = 73.3%). It also performed well in all analyzed subgroups, especially in participants with normal or slightly impaired renal function (rGFR≥60 mL/min/1.73 m2), and low SCr. CONCLUSIONS: Compared to the other two SCr-based formulas, EKFC performed better in the Chinese. Thus, it might serve as a good alternative, until a more suitable formula is developed for the Chinese population.
Asunto(s)
Cistatina C , Insuficiencia Renal Crónica , Adulto , Humanos , Persona de Mediana Edad , Tasa de Filtración Glomerular , Riñón/diagnóstico por imagen , Insuficiencia Renal Crónica/epidemiología , Creatinina , ChinaRESUMEN
Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates. Methods: The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results: Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions: ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.
RESUMEN
Background: The aim of this study was to review clinical features of adolescent malignant germ cell tumors (MGCTs) in Beijing and analyze the peculiar characteristics of this age group. Methods: Clinical characteristics, pathological presentations, and survival outcomes of 34 patients were analyzed retrospectively. Results: Of 34 patients, 12 girls and 22 boys, 18 (52.9%) had an extra-cranial tumor, including one testicular tumor, five ovarian tumors, one sacrococcygeal tumor, and 11 mediastinal tumors. Histologically, we found immature teratomas (n = 6), yolk sac tumors (n = 5), mixed malignant tumors (n = 5), an embryonic carcinoma (n = 1), and seminoma (n = 1). Three-year event-free survival (EFS) and overall survival (OS) were 48.8% and 62.9%, respectively. Another 16 (47.1%) patients had an intracranial tumor, including nine in the pineal region, five in the suprasellar region, one in basal ganglia, and one in cerebellopontine. All patients had localized disease and an excellent outcome with 3-year EFS and OS of 93.7% and 100%, respectively. Conclusions: Adolescent MGCTs are rare with a strong dependence on gender, and the mediastina and pineal region are the most common tumor locations. The prognosis is promising compared with that of other adolescent tumors and MGCTs in other age groups. MGCTs in mediastina have a tendency to companion with other hematological malignancies, and the prognosis is extremely poor in these patients.
RESUMEN
BACKGROUND: Triple-positive breast cancer (TPBC) is highly invasive and lacks well-established treatment strategies, especially in patients with advanced stage disease. This study aimed to explore the efficacy of everolimus in patients with metastatic TPBC (mTPBC) in a multicenter real-world setting. METHODS: A total of 2518 cancer patients who received everolimus-based therapy were enrolled from three cancer institutes in China from 2014 to 2022. Their clinicopathological characteristics were collected from medical records. The indicators for the efficacy of everolimus were progression-free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR). RESULTS: We collected 79 HER2-enriched patients that were treated with everolimus-based therapy, 43 of whom were mTPBC. The most commonly used therapeutic combinations was everolimus plus endocrine therapy (18/43, 41.9%). Among all combinations, everolimus plus chemotherapy plus trastuzumab developed the longest PFS of 10.9 months (95% CI: 1.5-20.3). Seventeen patients (32.6%) with mTPBC received everolimus as frontline treatment (1 L/2 L/3 L, FL), and 26 patients (67.4%) as backline treatment (>3 L, BL). Among all the population, the median PFS for everolimus was 4.5 months (range: 3.0-6.0), ORR was 30.2%, and CBR was 48.8%. PFSFL of 10.9 months was significantly longer than 4.0 months for PFSBL (p = 0.003, HR = 0.31, 95% CI: 0.14-0.67). ORRFL was 41.2%, showing no significance compared to ORRBL of 23.1% (one-sided p = 0.11). CBRFL was observed better of 76.5% versus CBRBL of 46.2% (one-sided p = 0.026). CONCLUSION: Everolimus as frontline treatment achieves clinical benefits for Chinese patients with mTPBC, which may provide some references for the management of Chinese mTPBC patients.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Everolimus/uso terapéutico , Receptor ErbB-2 , Trastuzumab/uso terapéutico , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
INTRODUCTION: To investigate the application potential of single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures ("1 + 2" PJ) in total laparoscopic pancreaticoduodenectomy (TLPD). Explore the advantages of "1 + 2" PJ over the traditional double-layer interrupted duct-to-mucosa pancreaticojejunostomy (traditional PJ). METHODS: We retrospectively collected the clinical data of 184 patients who were admitted in our department from Oct 2019 to Oct 2022, including 95 cases who underwent TLPD with "1 + 2" PJ and 89 cases who underwent TLPD with traditional PJ. The pre/intra/postoperation data were analyzed and compared. RESULTS: The "1 + 2" PJ procedures were successfully performed in all the 95 cases. When compared with the traditional PJ group, there were no statistically significant variations between the pre-operative and pathological data. However, the "1 + 2" PJ group had a shorter operation time (235 (210, 300) minutes vs. 310 (270, 360) minutes in the traditional PJ group, P < 0.001), shorter pancreaticojejunostomy time (15 (10, 20) minutes vs. 50 (45, 55) minutes in the traditional PJ group, P < 0.001), lower pancreatic fistula (both grade B/C) rate (4.21% vs. 12.34% in the traditional group, P = 0.044), and abdominal infection rate (2.11% vs. 8.99% in the traditional group, P = 0.044), as well as reduced hospital stay (11 (9, 15) days vs. 13 (11, 15) days in the traditional PJ group, P = 0.013). In the "1 + 2" PJ group, the median diameter of the pancreatic duct was 3 (3, 4) mm; 82 cases (86.31%) had a normal pancreatic texture, while nine (9.47%) cases had a hard texture, and seven (7.37%) cases had a soft texture; the median intraoperative blood loss was 200 (100, 400) mL and 19 cases (20.00%) needed intraoperative transfusion; eight cases (8.4%) developed postoperative complications, including four cases (4.2%) of pancreatic fistula (including both grade B/C), one case (1.1%) of bile leakage, three cases (3.2%) of delayed gastric emptying, three cases (3.2%) of postoperative hemorrhage, two cases (2.1%) of abdominal infection, and one case (1.1%) of reoperation; the median hospital stay was 13 (8, 17) days; 25 cases were pathologically classified as pancreatic cancer, 35 cases as bile duct cancer, 23 cases as duodenal cancer, and 12 cases as ampullary cancer. CONCLUSION: Single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures is a feasible and safe procedure that can be applied in TLPD.
Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Laparoscopía , Humanos , Pancreatoyeyunostomía/efectos adversos , Fístula Pancreática/etiología , Fístula Pancreática/cirugía , Pancreaticoduodenectomía/métodos , Estudios Retrospectivos , Neoplasias del Conducto Colédoco/cirugía , Complicaciones Posoperatorias/etiología , Membrana Mucosa/cirugía , Laparoscopía/efectos adversos , Suturas/efectos adversosRESUMEN
BACKGROUND: Identifying age-related trend of estimated glomerular filtration rate (eGFR) is necessary to assess whether kidney function is healthily aging. This study aimed to investigate the application of CKD-EPI, FAS, and Xiangya equations for the aging estimation of eGFR in the healthy Chinese individuals. METHODS: A total of 36,911 healthy individuals were enrolled in this study. We grouped every ten years to observe the trend of eGFR with aging and investigated decline rate of it by general linear regression analysis in each age-groups. Agreement between equations was determined by intraclass correlation coefficient (ICC) and Bland-Altman plot. We calculated reference interval in each age-group. We further analyzed above statistical indicators in males and females. RESULTS: The eGFR by CKD-EPI, and Xiangya equation started to decline from the age of 18. Whereas eGFR by FAS equation remained stable under 40 years, then decreased more rapidly. Compared with males, the females had a higher level but a faster decline rate of eGFR with aging. Agreement analysis revealed good agreement between CKD-EPI and FAS equations (ICC 0.818-0.920). Agreement between Xiangya and CKD-EPI or FAS equations was poor to moderate in most of the population under 70 years old (ICC 0.282-0.786), but good in individuals above 70 years (ICC 0.769-0.881). CONCLUSIONS: The trend of eGFR with aging was different by CKD-EPI, FAS, and Xiangya equations in the healthy Chinese. It may be necessary to take these equations- or age-related differences into consideration when assessing kidney function in primary health care and clinical practice.
Asunto(s)
Tasa de Filtración Glomerular , Insuficiencia Renal Crónica , Anciano , Femenino , Humanos , Masculino , Envejecimiento , Creatinina , Insuficiencia Renal Crónica/epidemiología , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Hypoxia is one of most typical features in the tumor microenvironment of solid tumor and an inducer of endoplasmic reticulum (ER) stress, and HIF-1α functions as a key transcription factor regulator to promote tumor angiogenesis in the adaptive response to hypoxia. Increasing evidence has suggested that hypoxia plays an important regulatory role of ER homeostasis. We previously identified TMTC3 as an ER stress mediator under nutrient-deficiency condition in esophageal squamous cell carcinoma (ESCC), but the molecular mechanism in hypoxia is still unclear. METHODS: RNA sequencing data of TMTC3 knockdown cells and TCGA database were analyzed to determine the association of TMTC3 and hypoxia. Moreover, ChIP assay and dual-luciferase reporter assay were performed to detect the interaction of HIF-1α and TMTC3 promoter. In vitro and in vivo assays were used to investigate the function of TMTC3 in tumor angiogenesis. The molecular mechanism was determined using co-immunoprecipitation assays, immunofluorescence assays and western blot. The TMTC3 inhibitor was identified by high-throughput screening of FDA-approved drugs. The combination of TMTC3 inhibitor and cisplatin was conducted to confirm the efficiency in vitro and in vivo. RESULTS: The expression of TMTC3 was remarkably increased under hypoxia and regulated by HIF-1α. Knockdown of TMTC3 inhibited the capability of tumor angiogenesis and ROS production in ESCC. Mechanistically, TMTC3 promoted the production of GTP through interacting with IMPDH2 Bateman domain. The activity of Rho GTPase/STAT3, regulated by cellular GTP levels, decreased in TMTC3 knockdown cells, whereas reversed by IMPDH2 overexpression. Additionally, TMTC3 regulated the expression of VEGFA through Rho GTPase/STAT3 pathway. Allopurinol inhibited the expression of TMTC3 and further reduced the phosphorylation and activation of STAT3 signaling pathway in a dose-dependent manner in ESCC. Additionally, the combination of allopurinol and cisplatin significantly inhibited the cell viability in vitro and tumor growth in vivo, comparing with single drug treatment, respectively. CONCLUSIONS: Collectively, our study clarified the molecular mechanism of TMTC3 in regulating tumor angiogenesis and highlighted the potential therapeutic combination of TMTC3 inhibitor and cisplatin, which proposed a promising strategy for the treatment of ESCC.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Alopurinol , Cisplatino/farmacología , Neoplasias Esofágicas/genética , Guanosina Trifosfato , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular , Factor de Transcripción STAT3/genética , Proteínas Portadoras , Proteínas de la MembranaRESUMEN
Spiroplasma eriocheiris is one of the major pathogenic bacteria in crustaceans, featuring high infectivity, rapid transmission, and an absence of effective control strategies, resulting in significant economic losses to the aquaculture industry. Research into virulence-related factors provides an important perspective to clarify how Spiroplasma eriocheiris is pathogenic to shrimps and crabs. Therefore, in this study, isobaric tags for relative and absolute quantitation (iTRAQ) technology was utilized to undertake a differential proteomic analysis of high- and low-virulence Spiroplasma eriocheiris strains at different growth phases. A total of 868 differentially expressed proteins (DEPs) were obtained, of which 31 novel proteins were identified by proteogenomic analysis. There were 62, 61, 175, and 235 DEPs between the log phase (YD) and non-log phase (YFD) of the high-virulence strain, between the log phase (CD) and non-log phase (CFD) of the low-virulence strain, between YD and CD, and between CFD and YFD, respectively. All the DEPs were compared with virulence protein databases (MvirDB and VFDB), and 68 virulence proteins of Spiroplasma eriocheiris were identified, of which 12 were involved in a total of 21 metabolic pathways, including motility, chemotaxis, growth, metabolism and virulence of the bacteria. The results of this study form the basis for further research into the molecular mechanism of virulence and physiological differences between high- and low-virulence strains of Spiroplasma eriocheiris, and provide a scientific basis for a detailed understanding of its pathogenesis.
Asunto(s)
Braquiuros , Spiroplasma , Animales , Proteómica/métodos , Virulencia , Spiroplasma/genética , Braquiuros/microbiologíaRESUMEN
Background: Soft-tissue sarcomas during infancy are rare and understudied. With no data on this specific condition, we performed a retrospective study of infant-onset sarcomas based on a multi-institutional cohort in Beijing, China, collected over the past decade. We reviewed infantile soft-tissue sarcomas' clinical characteristics, treatments, and outcomes. Materials and Methods: The patients with soft-tissue sarcoma diagnosed from 0 to 12 months in four primary children's hospitals in Beijing from January 2010 to December 2019 were evaluated. Results: Fifty-one patients were enrolled, including 31 males and 20 females. The median age at the diagnosis was five months (range, 0-12), and seven (13.7%) patients were diagnosed in the first month of their life. Histologically, twenty-five patients were diagnosed with rhabdomyosarcoma (RMS), six were diagnosed with extraosseous Ewing sarcoma (EES), and twenty were diagnosed with nonrhabdomyosarcoma soft-tissue sarcoma (NRSTS). The treatment principles and details of RMS focused on reference to the Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols. For EES and NRSTS, chemotherapy was prescribed according to children's oncology group protocols. The five-year EFS/OS rates of RMS were 26.4% ± 19.5%/56.2 ± 17.8%, the five-year EFS/OS rate of EES was 50% ± 20.4%, and the five-year EFS/OS of NRSTS was 85.2% ± 9.8%/100%. Conclusions: Infant-onset soft-tissue sarcoma is heterogeneous. The primary location of the abdominal or pelvic cavity of RMS and EWS was at a later stage and had a poorer prognosis. Multimodal therapy resulted in successful disease control for the majority of patients. Standardization of treatment protocols will facilitate care for such challenging conditions.