Investigating the progression of preeclampsia through a comprehensive analysis of genes associated with per- and polyfluoroalkyl substances.

Per- and Polyfluoroalkyl Substances (PFAS) are synthetic chemicals utilized in the production of various products that possess water and dirt-repellent properties. Exposure to PFAS has been linked to numerous diseases, such as cancer and preeclampsia (PE). However, whether PFAS contributes to the advancement of PE remains uncertain. In this study, we conducted an extensive bioinformatics analysis using the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) databases, leading us to discover a connection between PE and four specific PFAS. Moreover, further examination revealed that six genes associated with PFAS exhibited significant diagnostic potential for individuals with PE. By employing receiver operating characteristic (ROC) curves, our PFAS-related gene-based nomogram model demonstrated outstanding predictive efficacy for diagnosing PE. Immune infiltration analysis showed that six PFAS-related genes were significantly associated with the level of immune cell infiltration. The expression of PFAS-related genes in PE patients was confirmed by collecting clinical samples. This research has offered fresh perspectives on comprehending the impact of PFAS on PE, drawing attention to the connection between environmental factors and the risks and development of PE.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Advances of mesenchymal stem cells and their derived extracellular vesicles as a promising therapy for acute respiratory distress syndrome: from bench to clinic.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

Transcriptomic and Functional Analyses of Two Cadmium Hyper-Enriched Duckweed Strains Reveal Putative Cadmium Tolerance Mechanisms.

Cadmium (Cd) is one of the most toxic metals in the environment and exerts deleterious effects on plant growth and production. Duckweed has been reported as a promising candidate for Cd phytoremediation. In this study, the growth, Cd enrichment, and antioxidant enzyme activity of duckweed were investigated. We found that both high-Cd-tolerance duckweed (HCD) and low-Cd-tolerance duckweed (LCD) strains exposed to Cd were hyper-enriched with Cd. To further explore the underlying molecular mechanisms, a genome-wide transcriptome analysis was performed. The results showed that the growth rate, chlorophyll content, and antioxidant enzyme activities of duckweed were significantly affected by Cd stress and differed between the two strains. In the genome-wide transcriptome analysis, the RNA-seq library generated 544,347,670 clean reads, and 1608 and 2045 differentially expressed genes were identified between HCD and LCD, respectively. The antioxidant system was significantly expressed during ribosomal biosynthesis in HCD but not in LCD. Fatty acid metabolism and ethanol production were significantly increased in LCD. Alpha-linolenic acid metabolism likely plays an important role in Cd detoxification in duckweed. These findings contribute to the understanding of Cd tolerance mechanisms in hyperaccumulator plants and lay the foundation for future phytoremediation studies.

Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer.

Oncogenes are increasingly recognized as important factors in the development and progression of cancer. Holliday Junction Recognition Protein (HJURP) is a highly specialized mitogenic protein that is a chaperone protein of histone H3. The HJURP gene is located on chromosome 2q37.1 and is involved in nucleosome composition in the mitotic region, forming a three-dimensional crystal structure with Centromere Protein A (CENP-A) and the histone 4 complex. HJURP is involved in the recruitment and assembly of centromere and kinetochore and plays a key role in stabilizing the chromosome structure of tumor cells, and its dysfunction may contribute to tumorigenesis. In the available studies HJURP is upregulated in a variety of cancer tissues and cancer cell lines and is involved in tumor proliferation, invasion, metastasis and immune response. In an in vivo model, overexpression of HJURP in most cancer cell lines promotes cell proliferation and invasiveness, reduces susceptibility to apoptosis, and promotes tumor growth. In addition, upregulation of HJURP was associated with poorer prognosis in a variety of cancers. These properties suggest that HJURP may be a possible target for the treatment of certain cancers. Various studies targeting HJURP as a prognostic and therapeutic target for cancer are gradually attracting interest and attention. This paper reviews the functional and molecular mechanisms of HJURP in a variety of tumor types with the aim of providing new targets for future cancer therapy.

Dietary Leucine Improves Fish Intestinal Barrier Function by Increasing Humoral Immunity, Antioxidant Capacity, and Tight Junction.

This study attempted to evaluate the possible impact and mechanism of leucine (Leu) on fish intestinal barrier function. One hundred and five hybrid Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂ catfish were fed with six diets in graded levels of Leu 10.0 (control group), 15.0, 20.0, 25.0, 30.0, 35.0, and 40.0 g/kg diet for 56 days. Results showed that the intestinal activities of LZM, ACP, and AKP and contents of C3, C4, and IgM had positive linear and/or quadratic responses to dietary Leu levels. The mRNA expressions of itnl1, itnl2, c-LZM, g-LZM, and ß-defensin increased linearly and/or quadratically (p < 0.05). The ROS, PC, and MDA contents had a negative linear and/or quadratic response, but GSH content and ASA, AHR, T-SOD, and GR activities had positive quadratic responses to dietary Leu levels (p < 0.05). No significant differences on the CAT and GPX activities were detected among treatments (p > 0.05). Increasing dietary Leu level linearly and/or quadratically increased the mRNA expressions of CuZnSOD, CAT, and GPX1α. The GST mRNA expression decreased linearly while the GCLC and Nrf2 mRNA expressions were not significantly affected by different dietary Leu levels. The Nrf2 protein level quadratically increased, whereas the Keap1 mRNA expression and protein level decreased quadratically (p < 0.05). The translational levels of ZO-1 and occludin increased linearly. No significant differences were indicated in Claudin-2 mRNA expression and protein level. The transcriptional levels of Beclin1, ULK1b, ATG5, ATG7, ATG9a, ATG4b, LC3b, and P62 and translational levels of ULK1, LC3Ⅱ/Ⅰ, and P62 linearly and quadratically decreased. The Beclin1 protein level was quadratically decreased with increasing dietary Leu levels. These results suggested that dietary Leu could improve fish intestinal barrier function by increasing humoral immunity, antioxidative capacities, and tight junction protein levels.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study.

INTRODUCTION: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. METHODS: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. RESULTS: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. CONCLUSIONS: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Integrative analysis of differentially expressed mRNAs and proteins induced by PGC-1ß in breast cancer cells.

Breast cancer is one of the most frequent malignancies in females. The molecular mechanism of how breast cancer development and recurrence still need to be explored. Peroxisome gamma coactivator-1ß (PGC-1ß) was engaged in cancer energy metabolism and tumor genesis. However, the mechanisms of PGC-1ß in breast cancer have not been fully understood. In this study, PCG-1ß overexpressed and knockdown vectors were transferred into MCF-7 cells. With the association-quantitative connection analysis, the different expressions of mRNAs and proteins were examined. Additionally, the terms on differentially expressed mRNAs and proteins were enriched by GO and KEGG. Based on the results, 1872 differentially expressed genes were identified in the up-regulated of PGC-1ß group, and 1318 genes were found in the down-regulated of PGC-1ß cells. With the label-free technique, 221 differentially expressed proteins were screened in PGC-1ß up-regulated group, and 459 proteins were identified in PGC-1ß down-regulated group. Correlation analysis showed that 49 significantly expressed mRNA-protein pairs in OV vs CT groups and 25 paired in SI vs CT groups. Combined analysis of transcriptome and proteome demonstrated that PGC-1ß plays a important role in cancer energy metabolism and boosting the pace of chemical processes in the proliferation of breast cancer cells. Additional investigation about PGC-1ß and energy metabolism in cancer cells may shed fresh light on the growth and treatment of breast cancer cells.

Risk factors and outcomes associated with acute kidney injury following extracardiac total cavopulmonary connection: a retrospective observational study.

Background: Total cavopulmonary connection (TCPC) is an important operation for the treatment of complex congenital heart disease. Epidemiology and outcomes for pediatric patients with acute kidney injury (AKI) following extracardiac TCPC have not been well documented. This study investigates the prevalence, risk factors, and outcomes of AKI in children after extracardiac TCPC surgery. Methods: We retrospectively evaluated patients (age at surgery <18 years) who underwent extracardiac TCPC surgery between January 2008 and January 2020 in the Pediatric Cardiac Surgical Center of Fuwai Hospital, Beijing, China. AKI was defined according to the pediatric-modified risk, injury, failure, loss of function, and end-stage renal disease criteria. Results: A total of 377 pediatric patients were included in this study; 123 patients (32.6%) had some degree of AKI. Among the patients with AKI, 101 (82.1%) were diagnosed with AKI-risk (AKI-R), while 22 (17.9%) were diagnosed with acute kidney injury/failure (AKI/F) (16 with AKI, and 6 with AKF). Preoperative estimated creatinine clearance (OR: 1.039, 95% CI: 1.024-1.055, P<0.001), neutrophil-to-lymphocyte ratio (OR: 1.208, 95% CI: 1.128-1.294, P<0.001), and renal perfusion pressure (OR: 0.962, 95% CI: 0.938-0.986, P=0.002) on postoperative day (POD) 0 were significantly associated with AKI after TCPC. Having previously undergone a bidirectional Glenn was significantly associated with the severity of postoperative AKI (OR: 0.253, 95% CI: 0.088-0.731, P=0.011). Furthermore, AKI was associated with prolonged mechanical ventilation time, prolonged intensive care unit stay, and composite adverse outcome. Compared with non-AKI patients, the 10-year survival rate of patients with severe AKI was significantly lower (95.5% vs. 65.9%, P=0.009). Conclusions: Although the incidence of AKI was high in patients undergoing TCPC surgery, most cases were AKI-R. Severe AKI was significantly associated with early adverse outcomes and poor long-term survival.

Prognostic value of PD-L1 and Siglec-15 expression in patients with nasopharyngeal carcinoma.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). Here, we aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in nasopharyngeal carcinoma (NPC) patients. We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescence staining in 182 NPC tissue samples. A significant correlation was identified between the PD-L1 and Siglec-15 expression (P = 0.000). Moreover, Kaplan-Meier survival curves showed that PD-L1 expression was associated with improved overall survival (OS) (P = 0.025) and Siglec-15 expression was associated with improved distant failure-free survival (D-FFS) (P = 0.048). Moreover, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of OS (P = 0.020) and D-FFS (P = 0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression had significant advantages regarding OS, compared to other groups (P = 0.037). PD-L1 and Siglec-15 may represent novel biomarkers for predicting the prognosis of NPC patients. Siglec-15 may be considered as a potential target for the development of therapeutics for NPC treatment in the future.

[Research advances in chemical constituents and pharmacological activities of Dendrobium plants].

Dendrobii Caulis are commonly used tonic Chinese medicinal materials with a long history of application. As demonstrated by pharmacological results, the chemical constituents and the extracts of Dendrobii Caulis have anti-inflammatory, antibacte-rial, antioxidant, and anti-tumor effects, and can also regulate immunity, lower blood pressure, and regulate blood sugar. The active ingredients contained are widely concerned by scholars. This paper comprehensively summarized the chemical constituents and pharmacological activities of Dendrobium plants reported so far. The chemical constituents isolated from Dendrobium plants are mainly alkaloids, sesquiterpenoids, flavonoids, fluorenones, coumarins, bibenzyls, phenanthrenes, lignans, steroids, phenols, and polysaccharides. This paper is expected to provide a reference for further research, development, and utilization of Dendrobium plants.

The lower threshold of hypothermic oxygen delivery to prevent neonatal acute kidney injury.

BACKGROUND: Oxygen delivery during cardiopulmonary bypass (CPB) is closely related to postoperative acute kidney injury (AKI). The value of critical indexed oxygen delivery (DO2i) is a key indicator to reflect oxygen supply in cardiovascular surgery. However, the target DO2i value for neonates undergoing hypothermic CPB remains unclear. METHODS: One hundred and twenty-six consecutive newborns (≤28 days) undergoing arterial switch operations were retrospectively divided into two groups according to AKI occurrence. Baseline characteristics, intraoperative variables, and clinical outcomes were collected. Multivariate logistic regression analysis and receiver-operating characteristic curve were performed to investigate the association between DO2i and AKI. RESULTS: Neonates in the no-AKI group (n = 67) had significantly higher nadir bypass flow and DO2i during the hypothermic phase compared with the AKI group (n = 59). AKI group had remarkably higher incidences of hepatic dysfunction and peritoneal dialysis requirement compared with newborns without AKI. Mixed venous oxygen saturation (SvO2) was comparable between the two groups. Base excess (BE)(P = 0.011) value during the hypothermic phase of the AKI group was higher than the no-AKI group. Multivariate analysis showed that hypothermic DO2i was negatively associated with AKI. The cut-off value of hypothermic DO2i was 269 mL min-1 m-2. CONCLUSIONS: The importance of hypothermic DO2i should be highlighted, even when SvO2 was satisfactory. A lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of postoperative AKI. IMPACT: The key message of our article is that the lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of AKI after on-pump hypothermic cardiovascular surgery. The critical DO2i value for neonates undergoing hypothermic CPB remains unclear, and our study may add new evidence for this matter based on the 6-year experience of our center. In this study, the lowest critical value of DO2i in neonatal hypothermic CPB is determined for the first time, which provides a reference for intra-CPB management strategy to improve the postoperative outcomes of newborns.

Investigation of myocardial protection during pediatric CPB: Practical experience in 100 Chinese hospitals.

Many measures have been proposed for myocardial protection in pediatric congenital heart surgeries, but little data is available for China. This study investigates myocardial protection strategies in pediatric cardiopulmonary bypass (CPB) throughout China. Online questionnaires were delivered to 100 hospitals in 27 provinces. The number of yearly on-pump pediatric cardiovascular surgeries in these hospitals varied greatly. About 91.0% of respondents believe that each surgery should have at least two perfusionists, while only 64.0% of hospitals actually met this requirement. For pediatric patients, crystalloid cardioplegia was more prevalent than blood-based cardioplegia. Histidine-tryptophan-ketoglutarate solution and St. Thomas crystalloid solution were dominant among crystalloid cardioplegia. Del Nido cardioplegia and St. Thomas blood-based cardioplegia ranked the top two in the popularity of blood-based cardioplegia. Dosages varied among different kinds of cardioplegia. In the choice of different cardioplegia, perfusionists mainly focused on myocardial protective effect and cost. Hypothermia of cardioplegia solution was maintained by ice buckets in 3/4 of the hospitals in this survey. In conclusion, the essence of myocardial protection management during pediatric CPB was cardiac arrest induced by cardioplegia under systemic hypothermia. However, there is no uniform standard for the type of cardioplegia, or dosages. Therefore, well-designed multicenter randomized controlled trials are warranted to provide tangible evidence for myocardial protection of cardioplegia in pediatric CPB.

Comparable prognosis in different neonatal histidine-tryptophan-ketoglutarate dosage management.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion. METHODS: A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg < HTK ≤ 60 mL/kg) and a high-dose (HD) group (n = 83, HTK >60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias. RESULTS: The SD group had a higher weight (3.7 ±â€Š0.4 vs. 3.4 ±â€Š0.4 kg, P < 0.0001), a lower proportion of complete transposition of the great artery (69.8% vs. 85.5%, P = 0.022), a lower cardiopulmonary bypass (CPB) time (123.5 [108.0, 136.0] vs. 132.5 [114.8, 152.5] min, P = 0.034), and a lower aortic x-clamp time (82.9 ±â€Š27.1 vs. 95.5 ±â€Š26.0 min, P = 0.005). After PSM, 44 patients were assigned to each group; baseline characteristics and CPB parameters between the two groups were comparable. There were no significant differences in peri-CPB blood product consumption after PSM (P > 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups. CONCLUSIONS: In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion.

A circular RNA, circSMARCA5, inhibits prostate cancer proliferative, migrative, and invasive capabilities via the miR-181b-5p/miR-17-3p-TIMP3 axis.

SMARCA5 (circSMARCA5) is involved in the occurrence of different cancers, but its role in prostate cancer carcinogenesis and metastatic transformation remains elusive. Thus, we evaluated the circSMARCA5 functional relevance in prostate cancer and its associated molecular mechanism. First, circSMARCA5 expression and function in this cancer were evaluated. To determine the miR-181b-5p/miR-17-3p target and clarify how circSMARCA5 regulates the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis, RNA immunoprecipitation, biotin-coupled microRNA capture, luciferase reporter, Western blot, and quantitative real-time PCR assays were employed. In primary and metastatic prostate cancer tissues, circSMARCA5 was significantly downregulated compared with normal controls. Functionally, circSMARCA5 exhibited a suppressive effect on prostate cancer cells' metastasis and growth. At the molecular level, circSMARCA5 could affect the tissue inhibitor of metalloproteinases 3 (TIMP3) expression through miR-181b-5p or miR-17-3p interactions. Moreover, lysine acetyltransferase 5 (KAT5) induced circSMARCA5 biogenesis and regulated the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis. These results suggested that targeting circSMARCA5-miR-181b-5p-TIMP3 and circSMARCA5-miR-17-3p-TIMP3 axis might be a novel therapeutic strategy for prostate cancer.

Primary malignant teratoma of the kidney: a rare case report and literature review.

Teratomas originate from pluripotent cells and can differentiate along one or more embryonic germ lines. Renal teratoma is infrequent and malignant renal teratoma is even rarer. Experience in the diagnosis and treatment of this uncommon malignancy is seriously limited. In this report, we described the case of a 64-year-old female who complained of right flank pain for 4 months. Computed tomography (CT) revealed a hypodense mass (50 mm in maximum diameter) with slow contrast enhancement and obscure boundary located in the lower pole of the right kidney. CT also showed multiple retroperitoneal lymphadenectasis. Retroperitoneal laparoscopic right radical nephrectomy along with regional lymphadenectomy was successfully performed, and postoperative pathological examination confirmed malignant teratoma of the kidney. After surgery, the patient received adjuvant chemotherapy with BEP (bleomycin, etoposide, and cisplatin) protocol. At the 6-month follow-up, pulmonary and liver metastases were discovered by CT and the patient refused any further treatment. Unfortunately, she died at 16 months postoperatively. Although primary renal malignant teratoma is extremely rare, this kind of tumor should be taken into consideration. Currently, there is no therapeutic standard consensus for this disease and the prognosis remains unclear. Early detection and surgical intervention is critical, and more research on postoperative adjuvant therapy should be performed.

Outcomes and factors associated with early mortality in pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation.

Mortality and morbidity of children received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support after cardiac surgery remain high despite remarkable advances in medical management and devices. The purpose of this study was to describe outcomes and risk factors of applying VA-ECMO in the surgical pediatric population. We retrospectively analyzed 85 consecutive pediatric patients (aged <18 years) who received postcardiotomy VA-ECMO from January 2010 to December 2018. Median (IQR) age at ECMO implantation in this cohort was 12.7 (6.4, 43.2) months, median weight was 8.5 (6.0, 12.8) kg, mean ECMO duration was 143.2 ± 81.6 hours and mean hospital length of stay was 48.4 ± 32.4 days. Seventy-five patients (88.2%) were indicated for postcardiotomy cardiogenic shock. The successful ECMO weaning rate was 70.6% and in-hospital mortality was 52.9%. The most common diagnosis was transposition of great arteries (n = 18, 21.2%), while acute kidney injury occurred most often (n = 64, 75.3%). Multivariate logistic regression analysis showed that thrombocytopenia, hemolysis, and nosocomial infection were positively correlated with in-hospital mortality. Multivariate Cox proportional hazard regression analysis presented that thrombocytopenia significantly increased the 180-day mortality in patients with successful weaning. Therefore, multiple factors had adverse effects on prognosis. Patient selection and procedures from ECMO implantation to weaning need to be closely monitored and performed in a timely manner to improve outcome.

Negative emotions and their management in Chinese convalescent cervical cancer patients: a qualitative study.

OBJECTIVE: The aim of the study was to understand the experience of negative emotions and coping styles of patients with cervical cancer during the rehabilitation period. METHODS: A descriptive qualitative research method was used. Purposive sampling was used to recruit participants. Semi-structured interviews were conducted with 18 cervical cancer patients and the data were analysed using content analysis. RESULTS: The analysis identified three relevant themes. Theme 1: Negative emotions in convalescent cervical cancer patients mainly comprised fear of recurrence, worries about sex and feelings of inferiority. Theme 2: Patients used positive and negative coping styles to manage negative emotions. Theme 3: Patients expressed a strong need for rehabilitation information. CONCLUSIONS: Patients with cervical cancer exhibited negative emotions during the rehabilitation period. To help these patients, medical staff should develop an understanding of their needs by communicating more with patients and providing them with targeted care to help them return to society more quickly.

HeLa Cell-Derived Paclitaxel-Loaded Microparticles Efficiently Inhibit the Growth of Cervical Carcinoma.

AIM: Tumor cell-derived microparticles (MP) can function as a targeted delivery carrier for anti-tumor drugs. Here, we aimed to generate paclitaxel-loaded microparticles (MP-PTX) from HeLa cells and examined its therapeutic potential on human cervical carcinoma. METHODS: MP-PTX was generated from HeLa cells by ultraviolet radiation and subsequent centrifugation. The particle size, drug loading rate, and stability of MP-PTX were examined in vitro. Flow cytometry and the MTT assay were performed to test the inhibitory effect of MP-PTX using different cell lines. Immunodeficient mice bearing HeLa cervical carcinoma were treated with 0.9% normal saline, MP, paclitaxel (PTX) (2.5 mg/kg), or MP-PTX (PTX content identical to PTX group) every day for 6 consecutive days. Tumor volume and animal survival were observed. Micro 18F-FDG PET/CT was performed to monitor the therapeutic efficacy. The proliferation activity of cells and microvessel density in tumor tissues were determined by immunohistochemical staining using Ki-67 and CD31, respectively. RESULTS: Dynamic laser scattering measurements showed that the particle size of MP-PTX was 285.58 ± 2.95 nm and the polydispersity index was 0.104 ± 0.106. And the particle size of MP-PTX was not change at 4°C for at least one week. More than 1% of PTX in the medium could be successfully encapsulated into HeLa cell-derived MP. When compared with PTX, MP-PTX treatment significantly increased apoptosis of tumor cells and reduced their proliferation. In addition, MP-PTX showed lower toxicity to normal human umbilical vein endothelial cells (HUVEC) than PTX. In vivo studies further demonstrated that MP-PTX treatment significantly inhibited the growth of cervical carcinoma, prolonged the survival of tumor-bearing mice, and reduced the toxicity of PTX. Immunohistochemical staining revealed that MP-PTX treatment led to decreased Ki-67 positive tumor cells and decreased microvessel density in tumor tissues. CONCLUSION: Our results demonstrated that HeLa-derived MP-PTX significantly enhanced the anti-cancer effects of PTX with reduced toxicity, which may provide a novel strategy for the treatment of cervical carcinoma.

Proline­rich polypeptide­1 decreases cancer stem cell population by targeting BAFF chromatin­remodeling complexes in human chondrosarcoma JJ012 cells.

Chondrosarcoma is the second most common primary malignant bone tumor and is resistant to chemotherapy and radiation. Inadequate treatment response and poor prognosis requires novel therapeutic approaches. Proline­rich polypeptide­1 (PRP­1), synthesized by brain neurosecretory cells, has demonstrated antitumor properties in JJ012­cells; however, its underlying molecular mechanism remains unclear. The present study aimed to investigate the epigenetic regulation by which PRP­1 inhibits chondrosarcoma cancer stem cell (CSC) proliferation and to elucidate additional CSC biomarkers in human chondrosarcoma other than ALDH1A1. Human chondrosarcoma JJ012­cells were treated with PRP­1 prior to performing an Aldefluor™ assay and fluorescence­activated cell sorting in order to determine aldehyde dehydrogenase (ALDH) expression levels and isolate ALDHhigh and ALDHlow cell populations. ALDH is an established marker of CSCs in several neoplasms, including chondrosarcoma. The cells were collected and lysed for gel electrophoresis, followed by western blot analysis. The Aldefluor™ assay was used to assess the expression levels of well­established CSC biomarkers, including CD133, CD4, CD10, CD144, CD177, CD221, CD271, leucine­rich repeat­containing G protein­coupled receptor 5, SOX2 and B lymphoma Mo­MLV insertion region 1 homolog (BMI­1), within the ALDHhigh population of JJ012 cells. The results confirmed that ALDHA1 was the biomarker for chondrosarcoma CSCs. PRP­1 was demonstrated to inhibit the ALDHhigh population colony and sarcosphere formation; 5 µg/ml PRP­1 was indicated to be the optimum concentration in eliminating colonies formed by JJ012 cells (92%, P<0.001) and by the ALDHhigh CSC­population (80.5%, P<0.001) in the clonogenic dose­response assay. Spheroid growth unequivocally decreased with an increase in PRP­1 dose. In order to determine the molecular mechanism by which PRP­1 decreased the CSC population, the regulation of the mammalian Switch/sucrose non­fermenting (SWI/SNF) complex, also referred to as BRG1­associated factor (BAF) complex, which either activates or represses transcription, thus acting as an oncogene or tumor suppressor in human cells, was analyzed. PRP­1 was demonstrated to decrease the expression levels of BRG, BAF170 and BRM; therefore, in JJ012 cells, these key players of the SWI/SNF (BAF) complex served an oncogenic role. The results of the present study demonstrated that PRP­1 targets chromatin­remodeling complexes; therefore, future efforts will be directed towards determining the interconnection between CSC maintenance, self­renewal capacity and BAF complexes.