Association of Glymphatic and White Matter Impairment With the Postoperative Outcome of Pediatric Hydrocephalus.

BACKGROUND AND OBJECTIVES: Assessment of postoperative outcomes on pediatric hydrocephalus is critical for adjusting treatment strategies. The aim of this work was to investigate the ability of MRI metrics to predict postoperative outcomes. METHODS: A total of 55 children with hydrocephalus who underwent MRI and ventriculoperitoneal shunt surgery were prospectively enrolled. MRI was also performed at 6 months postoperatively in 33 of the 55 children. A total of 92 controls matched for age and sex were enrolled and divided into preoperative and postoperative control groups. We calculated the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, Evans index, and diffusion tensor imaging metrics. The ability of various metrics to predict postoperative outcomes was assessed using receiver operating characteristic curve analysis. RESULTS: The DTI-ALPS index was significantly lower in patients with hydrocephalus than in controls. The abnormal DTI-ALPS index trended toward the normal range after surgery. Patients with lower preoperative DTI-ALPS index, lower fractional anisotropy (FA), and higher radial diffusivity in association fibers had less favorable short-term outcomes. Patients with worse long-term outcomes had lower postoperative DTI-ALPS index, higher postoperative Evans index, and lower FA and higher radial diffusivity in association fibers. Predictive performance was better when the DTI-ALPS index and FA in association fibers were used in combination than when either of these metrics was used alone. CONCLUSION: The DTI-ALPS index and FA in association fibers provided complementary information for prognostic assessment after the ventriculoperitoneal shunt surgery on pediatric hydrocephalus. A combination of DTI-ALPS index and FA would improve our ability to predict postoperative outcomes in these patients.

Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single-center experience.

BACKGROUND: Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. METHODS: A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. RESULTS: The most common primary site was the testis (n = 10), followed by the ovaries (n = 7), mediastinum (n = 4), retroperitoneum (n = 3), pineal gland (n = 2), and sacrum/coccyx (n = 1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. CONCLUSIONS: Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

Predictive Value of GDF-15 and sST2 for Pulmonary Hypertension in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective: To confirm whether growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) are indicators of pulmonary hypertension in acute exacerbation of chronic obstructive pulmonary disease (AECOPD-PH). Methods: All patients admitted to the hospital with AECOPD between July 2020 and October 2021 were enrolled. The patients were then categorized into AECOPD and AECOPD-PH groups according to PH probability, and the differences in GDF-15 and sST2 serum levels in the AECOPD and AECOPD-PH groups were compared. Correlation analysis was carried out to explore the association between GDF-15 and sST2 serum levels and the length of hospital stay of patients with AECOPD-PH. Receiver operating characteristic curve analysis was used to assess the clinical significance of GDF-15 and sST2 in predicting patients with AECOPD-PH. Results: Included in this study were 126 patients with AECOPD, including 69 with AECOPD and 57 with AECOPD-PH. The serum levels of GDF-15 and sST2 in the AECOPD-PH group were significantly higher than those in the AECOPD group (P < 0.05). There was no significant correlation between the length of hospital stay in AECOPD-PH patients and GDF-15 and sST2 serum levels (P > 0.05). The area under the curves of GDF-15, sST2, and GDF-15 + sST2 for predicting AECOPD-PH and AECOPD-PH patients with poor prognosis were >0.60 and 0.70, respectively. The optimal cutoff values of GDF-15 and sST2 for predicting AECOPD-PH were 1125.33 pg/mL and 80.68 ng/mL and 1309.72 pg/mL and 59.10 ng/mL for predicting AECOPD-PH patients with poor prognosis, respectively. Conclusion: GDF-15 and sST2 levels may be useful in the prediction of AECOPD-PH.

High dose and hepatobiliary dysfunction are associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin: a retrospective study.

PURPOSE: In clinical practice, the risk factors for pegylated liposomal doxorubicin-related hand-foot syndrome remain unclear. The purpose of this study was to determine the risk factors associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin. METHODS: This retrospective descriptive analysis included patients with lymphoma who received PLD treatment (≥ 2 cycles of chemotherapy) at our cancer centre and had complete follow-up data from January 2016 to February 2020. Clinical, laboratory data, as well as the occurrence of hand-foot syndrome (incidence, location, severity, impact on follow-up chemotherapy) were obtained. The primary end point was the incidence of hand-foot syndrome, which was classified according to the "Common Terminology Criteria for Adverse Events" (Version 4.0). A multivariate logistic regression analysis was used to identify risk factors for hand-foot syndrome in patients with lymphoma using doxorubicin liposomes. FINDINGS: A total of 167 patients met the inclusion criteria. 58 developed HFS, of which 45 occurred after the second course of chemotherapy. The multivariate logistic regression analysis revealed that a dose increase of pegylated liposomal doxorubicin and hepatobiliary dysfunction were significantly associated with an increased risk for hand-foot syndrome(dose intensity, OR = 6.479; 95% CI, 1.431-29.331 [P = 0.015]; history of gallstones, OR = 14.144, 95% CI, 1.512-132.346 [P = 0.020]; alanine aminotransferase, OR = 1.194, 95% CI, 1.056-1.350 [P = 0.005]; aspartate aminotransferase, OR = 1.162, 95% CI, 1.010-1.336 [P = 0.035]; and glutamine transpeptidase, OR = 1.092, 95% CI, 1.016-1.174 [P = 0.018]). IMPLICATIONS: These findings contribute to the risk assessment of patients with lymphoma before using pegylated liposomal doxorubicin. For patients with the above risk factors, preventive measures should be taken in advance to reduce the incidence of HFS.

Risk factors for pegylated liposomal doxorubicin-induced moderate to severe hand-foot syndrome in breast cancer patients: assessment of baseline clinical parameters.

BACKGROUND: Hand-foot syndrome (HFS) is a side effect of skin related to pegylated liposomal doxorubicin (PLD) application. Moderate to severe hand-foot syndrome (MSHFS) might have a serious impact on patients' quality of life and treatment. However, information on risk factors for the development of MSHFS is still limited. To analyze the risk factors for PLD-induced MSHFS in breast cancer patients and constructed a logistic regression prediction model. METHODS: We conducted a retrospective analysis of breast cancer patients who were treated with a PLD regimen in the Tumor Hospital of Harbin Medical University from January 2017 to August 2019. A total of 26 factors were collected from electronic medical records. Patients were divided into MSHFS (HFS > grade 1) and NMHFS (HFS ≤ grade 1) groups according to the NCI classification. Statistical analysis of these factors and the construction of a logistic regression prediction model based on risk factors. RESULTS: A total of 44.7% (206/461) of patients developed MSHFS. The BMI, dose intensity, and baseline Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels in the MSHFS group, as well as good peripheral blood circulation, excessive sweat excretion, history of gallstones, and tumour- and HER2-positive percentages, were all higher than those in the NMHFS group (P < 0.05). The model for predicting the occurrence of MSHFS was P = 1/1 + exp. (11.138-0.110*BMI-0.234*dose intensity-0.018*baseline ALT+ 0.025*baseline AST-1.225*gallstone history-0.681* peripheral blood circulation-1.073*sweat excretion-0.364*with or without tumor-0.680*HER-2). The accuracy of the model was 72.5%, AUC = 0.791, and Hosmer-Lemeshow fit test P = 0.114 > 0.05. CONCLUSIONS: Nearly half of the patients developed MSHFS. The constructed prediction model may be valuable for predicting the occurrence of MSHFS in patients.

The Role of Long Noncoding RNAs in Antiestrogen Resistance in Breast Cancer: An Overview and Update.

As a standard treatment, endocrine therapy has dramatically enhanced the prognosis of patients with estrogen receptor (ER)-positive breast cancer, which accounts for nearly 70% of all breast cancers. Antiestrogen drugs such as tamoxifen and aromatase inhibitors are the standard treatment options for ERα-positive breast cancer. However, acquired antiestrogen resistance is still the leading cause of disease recurrence and progression. Evidence has shown that long noncoding RNAs (lncRNAs) play an essential role in the development of antiestrogen resistance in ER-positive breast cancer and can serve as biomarkers or potential therapeutic targets. This review highlights the role of lncRNAs in the development of antiestrogen resistance in breast cancer.

MicroRNA-153-3p enhances the sensitivity of chronic myeloid leukemia cells to imatinib by inhibiting B-cell lymphoma-2-mediated autophagy.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease caused by abnormal DNA replication of bone marrow stem cells and chemotherapy resistance is a major obstacle to the effective treatment of patients with CML. Imatinib (IM), a tyrosine kinase inhibitor (TKI), is a first-line drug clinically used for CML. Mounting evidence has indicated that the dysregulation of microRNAs (miRNAs) is associated with the chemoresistance of CML. In this study, miR-153-3p, which had been implicated with numerous types of tumors, was identified to be downregulated in IM-resistant CML cells. Upregulation of miR-153-3p significantly increased IM sensitivity and decreased the survival rate of IM-resistant CML cells, whereas downregulation of miR-153-3p attenuated these effects in IM-resistant CML cells. Upregulated miR-153-3p could decrease the autophagy caused by IM in IM-resistant CML cells. Dual-luciferase reporter assays confirmed that Bcl-2 is a direct target of miR-153-3p. Bcl-2 restoration reversed the increased sensitivity to IM induced by miR-153-3p-mimic transfection in IM-resistant CML cells. The results of the present study showed that dysregulated miR-153-3p may target Bcl-2 to promote the development of IM resistance and attenuate IM-induced apoptosis in CML. Therefore, miR-153-3p upregulation combined with IM treatment may serve as a promising therapeutic strategy for patients with low sensitivity.

Evaluation of differential qPE9-1/DEP1 protein domains in rice grain length and weight variation.

BACKGROUND: qPE9-1/DEP1, encoding a G protein γ subunit, has multiple effects on plant architecture, grain size, and yield in rice. The qPE9-1 protein contains an N-terminal G gamma-like (GGL) domain, a putative transmembrane domain, and a C-terminal cysteine-rich domain. However, the roles of each domain remain unclear. RESULTS: In the present study, we focused on the genetic effects of different domains of qPE9-1 in the regulation of grain length and weight. We generated a series of transgenic plants expressing different truncated qPE9-1 proteins through constitutive expression and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 strategies. Phenotypic analysis indicated that the complete or long-tailed qPE9-1 contributed to the elongation of grains, while the GGL domain alone and short-tailed qPE9-1 led to short grains. The long C-terminus of qPE9-1 including two or three C-terminal von Willebrand factor type C domains effectively repressed the negative effects of the GGL domain on grain length and weight. qPE9-1-overexpressing lines in a Wuxianggeng 9 (carrying a qpe9-1 allele) background showed increased grain yield per plant, but lodging occurred in some years. CONCLUSIONS: Manipulation of the C-terminal length of qPE9-1 through genetic engineering can be used to generate varieties with various grain lengths and weights according to different requirements in rice breeding. The genetic effects of qPE9-1/qpe9-1 are multidimensional, and breeders should take into account other factors including genetic backgrounds and planting conditions in the use of qPE9-1/qpe9-1.

The Spermine Synthase OsSPMS1 Regulates Seed Germination, Grain Size, and Yield.

Polyamines, including putrescine, spermidine, and spermine, play essential roles in a wide variety of prokaryotic and eukaryotic organisms. Rice (Oryza sativa) contains four putative spermidine/spermine synthase (SPMS)-encoding genes (OsSPMS1, OsSPMS2, OsSPMS3, and OsACAULIS5), but none have been functionally characterized. In this study, we used a reverse genetic strategy to investigate the biological function of OsSPMS1 We generated several homozygous RNA interference (RNAi) and overexpression (OE) lines of OsSPMS1 Phenotypic analysis indicated that OsSPMS1 negatively regulates seed germination, grain size, and grain yield per plant. The ratio of spermine to spermidine was significantly lower in the RNAi lines and considerably higher in the OE lines than in the wild type, suggesting that OsSPMS1 may function as a SPMS. S-Adenosyl-l-methionine is a common precursor of polyamines and ethylene biosynthesis. The 1-aminocyclopropane-1-carboxylic acid (ACC) and ethylene contents in seeds increased significantly in RNAi lines and decreased in OE lines, respectively, compared with the wild type. Additionally, the reduced germination rates and growth defects of OE lines could be rescued with ACC treatment. These data suggest that OsSPMS1 affects ethylene synthesis and may regulate seed germination and plant growth by affecting the ACC and ethylene pathways. Most importantly, an OsSPMS1 knockout mutant showed an increase in grain yield per plant in a high-yield variety, Suken118, suggesting that OsSPMS1 is an important target for yield enhancement in rice.