One-stop hybrid operation versus microsurgery for treating brain arteriovenous malformation in children-a retrospective case series.

Background: Brain arteriovenous malformation (BAVM) is one of the most common causes of cerebral hemorrhage in children. The effectiveness of one-stop hybrid operation in the treatment of BAVM in adults has been widely confirmed, but there are few study for the case in children. The aim of this study was to retrospectively analyze of the role and significance of one-stop hybrid surgery versus microsurgery in the treatment of BAVM in children. Methods: A total of 57 children (≤18 years old) with BAVM who were admitted to The 900th Hospital and Fujian Children's Hospital between September 2018 and August 2022 were retrospectively analyzed. According to the inclusion and exclusion criteria, 38 patients were included, and they were divided into a microsurgical group (25 patients) and a hybrid operation group (13 patients) according to the treatment modality. The following clinical characteristics were observed: sex, age, initial symptoms, presence or absence of signs, Glasgow Coma Scale (GCS) score, Hunt-Hess grade, imaging characteristics such as the location of the BAVM, Spetzler-Martin (S-M) grade, presence of intraventricular hemorrhage, treatment and prognostic indicators such as intraoperative blood loss, operation time, imaging cure, postoperative complications, length of hospital stay, and 3- and 6-month modified Rankin score (mRS) after the operation. Results: The proportions of female patients (P=0.042), patients whose BAVM were located in the supratentorial region (P=0.034) and patients whose S-M grade was above grade III (P=0.003) were greater in the hybrid operation group than those in the microsurgical group. The intraoperative blood loss (P<0.001), operation time (P<0.001) and postoperative hospital stay (P=0.024) of patients in the microsurgical group were greater than those in the hybrid operation group. The presence of signs and the S-M grade may be relevant factors in predicting the surgical approach, and the probability of selecting a hybrid operation for each step of increasing the S-M grade was 3.046 times that of microsurgery. Conclusions: A one-stop hybrid operation is effective and safe for the treatment of BAVM in children. High S-M grades of BAVM are more suitable for hybrid operation.

Transport processes of dissolved and particulate nitrogen and phosphorus over urban road surface during rainfall runoff.

Nutrient pollutants serve as indicative pollutants in urban stormwater runoff, and usually coexist and transport in particulate and dissolved phase in runoff, which is complex and crucial for effective pollution control. In this study, nitrogen and phosphorus runoff samples were collected during various natural rainfall events to explore its transport process over urban road surface during rainfall runoff. The results showed that nitrogen mainly exists in the dissolved phase (mean proportion: 62.04 %), while phosphorus mainly exists in the particulate phase (mean proportion: 65.58 %). More nitrogen and phosphorus are present and transported in dissolved phase in initial rainfall runoff over urban roads. Nutrient concentration changes during rainfall events were influenced by factors such as rainfall intensity and surface runoff, resulting in multiple peaks. Transport rate peak and concentration peak did not coincide. The proportion of dissolved total nitrogen in the runoff process ranged mainly between 40 % and 80 %, and the proportion of dissolved ammonia was distributed between 60 % and 100 %. The proportion of dissolved phosphorus was more evenly distributed across each proportion interval. Influenced by the differences in phase proportions, first flush processes of nitrogen and phosphorus are not the same. Urban stormwater management measures should prioritize both the initial concentration peaks and the peaks in nutrient transport rates during rainfall. This approach is essential for enhancing the efficiency of stormwater pollutant collection and treatment.

Behavioral impairments and disrupted mitochondrial energy metabolism induced by polypropylene microplastics in zebrafish larvae.

Polypropylene microplastics (PP-MPs) are emerging pollutant commonly detected in various environmental matrices and organisms, while their adverse effects and mechanisms are not well known. Here, zebrafish embryos were exposed to environmentally relevant concentrations of PP-MPs (0.08-50 mg/L) from 2 h post-fertilization (hpf) until 120 hpf. The results showed that the body weight was increased at 2 mg/L, heart rate was reduced at 0.08 and 10 mg/L, and behaviors were impaired at 0.4, 10 or 50 mg/L. Subsequently, transcriptomic analysis in the 0.4 and 50 mg/L PP-MPs treatment groups indicated potential inhibition on the glycolysis/gluconeogenesis and oxidative phosphorylation pathways. These findings were validated through alterations in multiple biomarkers related to glucose metabolism. Moreover, abnormal mitochondrial ultrastructures were observed in the intestine and liver in 0.4 and 50 mg/L PP-MPs treatment groups, accompanied by significant decreases in the activities of four mitochondrial electron transport chain complexes and ATP contents. Oxidative stress was also induced, as indicated by significantly increased ROS levels and significant reduced activities of CAT and SOD and GSH contents. All the results suggested that environmentally relevant concentrations of PP-MPs could induce disrupted mitochondrial energy metabolism in zebrafish, which may be associated with the observed behavioral impairments. This study will provide novel insights into PP-MPs-induced adverse effects and highlight need for further research.

Alterations in corpus callosum subregions morphology and functional connectivity in patients with adult-onset hypothyroidism.

BACKGROUND: Magnetic resonance imaging (MRI) brain abnormalities have been reported in the corpus callosum (CC) of patients with adult-onset hypothyroidism. However, no study has directly compared CC-specific morphological or functional alterations among subclinical hypothyroidism (SCH), overt hypothyroidism (OH), and healthy controls (HC). Moreover, the association of CC alterations with cognition and emotion is not well understood. METHODS: Demographic data, clinical variables, neuropsychological scores, and MRI data of 152 participants (60 SCH, 37 OH, and 55 HC) were collected. This study investigated the clinical performance, morphological and functional changes of CC subregions across three groups. Moreover, a correlation analysis was performed to explore potential relationships between these factors. RESULTS: Compared to HC, SCH and OH groups exhibited lower cognitive scores and higher depressive/anxious scores. Notably, rostrum and rostral body volume of CC was larger in the SCH group. Functional connectivity between rostral body, anterior midbody and the right precentral and dorsolateral superior frontal gyrus were increased in the SCH group. In contrast, the SCH and OH groups exhibited a decline in functional connectivity between splenium and the right angular gyrus. Within the SCH group, rostrum volume demonstrated a negative correlation with Montreal Cognitive Assessment and visuospatial/executive scores, while displaying a positive correlation with 24-item Hamilton Depression Rating Scale scores. In the OH group, rostral body volume exhibited a negative correlation with serum thyroid stimulating hormone levels, while a positive correlation with serum total thyroxine and free thyroxine levels. CONCLUSIONS: This study suggests that patients with different stages of adult-onset hypothyroidism may exhibit different patterns of CC abnormalities. These findings offer new insights into the neuropathophysiological mechanisms in hypothyroidism.

Interactions between intestinal microbiota and metabolites in zebrafish larvae exposed to polystyrene nanoplastics: Implications for intestinal health and glycolipid metabolism.

Previous studies have shown the harmful effects of nanoscale particles on the intestinal tracts of organisms. However, the specific mechanisms remain unclear. Our present study focused on examining the uptake and distribution of polystyrene nanoplastics (PS-NPs) in zebrafish larvae, as well as its toxic effects on the intestine. It was found that PS-NPs, marked with red fluorescence, primarily accumulated in the intestine section. Subsequently, zebrafish larvae were exposed to normal PS-NPs (0.2-25 mg/L) over a critical 10-day period for intestinal development. Histopathological analysis demonstrated that PS-NPs caused structural changes in the intestine, resulting in inflammation and oxidative stress. Additionally, PS-NPs disrupted the composition of the intestinal microbiota, leading to alterations in the abundance of bacterial genera such as Pseudomonas and Aeromonas, which are associated with intestinal inflammation. Metabolomics analysis showed alterations in metabolites that are primarily involved in glycolipid metabolism. Furthermore, MetOrigin analysis showed a significant correlation between bacterial flora (Pedobacter and Bacillus) and metabolites (D-Glycerate 2-phosphate and D-Glyceraldehyde 3-phosphate), which are related to the glycolysis/gluconeogenesis pathways. These findings were further validated through alterations in multiple biomarkers at various levels. Collectively, our data suggest that PS-NPs may impair the intestinal health, disrupt the intestinal microbiota, and subsequently cause metabolic disorders.

Predicting the Efficacy of Repeated Shockwave Lithotripsy for Treating Patients with Upper Urinary Tract Calculi Using an Artificial Neural Network Model.

PURPOSE: To establish a prediction model for repeated shockwave lithotripsy (SWL) efficacy to help choose an appropriate treatment plan for patients with a single failed lithotripsy, reducing their treatment burden. PATIENTS AND METHODS: The clinical records and imaging data of 304 patients who underwent repeat SWL for upper urinary tract calculi (UUTC) at the Urology Centre of Shiyan People's Hospital between April 2019 and April 2023 were retrospectively collected. This dataset was divided into training (N = 217; 146 males [67.3%] and 71 females [32.7%]) and validation (N = 87; 66 males [75.9%] and 21 females [24.1%]) sets. The overall predictive accuracy of the models was calculated separately for the training and validation. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. The normalized importance of each independent variable (derived from the one-way analyses) in the input layer of the artificial neural network (ANN) model for the dependent variable (success or failure in repeat SWL) in the output layer was plotted as a bar chart. RESULTS: This study included 304 patients, of whom 154 (50.7%) underwent successful repeat SWL. Predictive models were constructed in the training set and assessed in the validation set. Fourteen influencing factors were selected as input variables to build an ANN model: age, alcohol, body mass index, sex, hydronephrosis, hematuria, mean stone density (MSD), skin-to-stone distance (SSD), stone heterogeneity index (SHI), stone volume (SV), stone retention time, smoking, stone location, and urinary irritation symptom. The model's AUC was 0.852 (95% confidence interval (CI): 0.8-0.9), and its predictive accuracy for stone clearance in the validation group was 83.3%. The order of importance of the independent variables was MSD > SV > SSD > stone retention time > SHI. CONCLUSION: Establishing an ANN model for repeated SWL of UUTC is crucial for optimizing patient care. This model will be pivotal in providing accurate treatment plans for patients with an initial unsuccessful SWL treatment. Moreover, it can significantly enhance the success rate of subsequent SWL treatments, ultimately alleviating patients' treatment burden.

Clinical and imaging characteristics of growing skull fractures in children.

Growing skull fracture (GSF) is an uncommon form of head trauma among young children. In prior research, the majority of GSFs were typically classified based on pathophysiological mechanisms or the duration following injury. However, considering the varying severity of initial trauma and the disparities in the time elapsed between injury and hospital admission among patients, our objective was to devise a clinically useful classification system for GSFs among children, grounded in both clinical presentations and imaging findings, in order to guide clinical diagnosis and treatment decisions. The clinical and imaging data of 23 patients less than 12 years who underwent GSF were retrospectively collected and classified into four types. The clinical and imaging characteristics of the different types were reviewed in detail and statistically analyzed. In all 23 patients, 5 in type I, 7 in type II, 8 in type III, and 3 in type IV. 21/23 (91.3%) were younger than 3 years. Age ≤ 3 years and subscalp fluctuating mass were common in type I-III (P = 0.026, P = 0.005). Fracture width ≥ 4 mm was more common in type II-IV (P = 0.003), while neurological dysfunction mostly occurred in type III and IV (P < 0.001).Skull "crater-like" changes were existed in all type IV. 10/12 (83.3%) patients with neurological dysfunction had improved in motor or linguistic function. There was not improved in patients with type IV. GCS in different stage has its unique clinical and imaging characteristics. This classification could help early diagnosis and treatment for GCS, also could improve the prognosis significantly.

Structural and Functional Alterations of Hippocampal Subfields in Patients With Adult-Onset Primary Hypothyroidism.

CONTEXT: Hypothyroidism is often associated with cognitive and emotional dysregulation; however, the underlying neuropathological mechanisms remain elusive. OBJECTIVE: The study aimed to characterize abnormal alterations in hippocampal subfield volumes and functional connectivity (FC) in patients with subclinical hypothyroidism (SCH) and overt hypothyroidism (OH). METHODS: This cross-sectional observational study comprised 47 and 40 patients with newly diagnosed adult-onset primary SCH and OH, respectively, and 53 well-matched healthy controls (HCs). The demographics, clinical variables, and neuropsychological scale scores were collected. Next, the hippocampal subfield volumes and seed-based FC were compared between the groups. Finally, correlation analyses were performed. RESULTS: SCH and OH exhibited significant alterations in cognitive and emotional scale scores. Specifically, the volumes of the right granule cell molecular layer of the dentate gyrus (GC-ML-DG) head, cornu ammonis (CA) 4, and CA3 head were reduced in the SCH and OH groups. Moreover, the volumes of the right molecular layer head, CA1 body, left GC-ML-DG head, and CA4 head were lower in SCH. In addition, the hippocampal subfield volumes decreased more significantly in SCH than OH. The seed-based FC decreased in SCH but increased in OH compared with HCs. Correlation analyses revealed thyroid hormone was negatively correlated with FC values in hypothyroidism. CONCLUSION: Patients with SCH and OH might be at risk of cognitive decline, anxiety, or depression, and exhibited alterations in volume and FC in specific hippocampal subfields. Furthermore, the reduction in volume was more pronounced in SCH. This study provides novel insights into the neuropathological mechanisms of brain impairment in hypothyroidism.

Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.

Dysregulation of anti-apoptotic and pro-apoptotic protein isoforms arising from aberrant splicing is a crucial hallmark of cancers and may contribute to therapeutic resistance. Thus, targeting RNA splicing to redirect isoform expression of apoptosis-related genes could lead to promising anti-cancer phenotypes. Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. In this study, through RT-PCR and Western Blot analysis, we found that BCLX pre-mRNA is aberrantly spliced in GBM cells with a favored splicing of anti-apoptotic Bcl-xL. Modulation of BCLX pre-mRNA splicing using splice-switching oligonucleotides (SSOs) efficiently elevated the pro-apoptotic isoform Bcl-xS at the expense of the anti-apoptotic Bcl-xL. Induction of Bcl-xS by SSOs activated apoptosis and autophagy in GBM cells. In addition, we found that ionizing radiation could also modulate the alternative splicing of BCLX. In contrast to heavy (carbon) ion irradiation, low energy X-ray radiation-induced an increased ratio of Bcl-xL/Bcl-xS. Inhibiting Bcl-xL through splicing regulation can significantly enhance the radiation sensitivity of 2D and 3D GBM cells. These results suggested that manipulation of BCLX pre-mRNA alternative splicing by splice-switching oligonucleotides is a novel approach to inhibit glioblastoma tumorigenesis alone or in combination with radiotherapy.

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

Carrier systems of radiopharmaceuticals and the application in cancer therapy.

Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier. Herein, different types of carriers of radiopharmaceuticals and the characteristics are briefly described. Subsequently, we review radiolabeled monoclonal antibodies (mAbs) and their derivatives, and novel strategies of radiolabeled mAbs and their derivatives in the treatment of lymphoma and colorectal cancer. Furthermore, this review outlines radiolabeled peptides, and novel strategies of radiolabeled peptides in the treatment of neuroendocrine neoplasms, prostate cancer, and gliomas. The emphasis is given to heterodimers, bicyclic peptides, and peptide-modified nanoparticles. Last, the latest developments and applications of radiolabeled nucleic acids and small molecules in cancer therapy are discussed. Thus, this review will contribute to a better understanding of the carrier of radiopharmaceuticals and the application in cancer therapy.

HER2/ ERBB2 Immunohistochemical Expression and Copy Number Status in Ovarian Mucinous Tumors.

Primary mucinous ovarian carcinoma (MOC) is a rare ovarian epithelial cancer, which is often refractory to chemotherapy. HER2-targeting therapy is being increasingly considered in gynecologic malignancies. Although there have been limited studies examining the HER2 status of such tumors, the criteria for HER2 expression scoring have not been standardized for MOC as it has for other sites. This study aimed to survey immunohistochemical HER2 expression patterns in MOC and its precursor, mucinous borderline tumor in correlation with fluorescence in situ hybridization (FISH). Immunohistochemistry (IHC) for HER2 was performed on 12 cases of MOC and 15 mucinous borderline tumors, including 7 with intraepithelial carcinoma. HER2 expression was quantified using the gastric/gastroesophageal carcinoma protocol. Cases were considered 3+ if the tumor cells displayed strong complete or basolateral/lateral membranous staining in ≥10% of tumor cells. Cases (2+) had weak to moderate staining in ≥10% of tumor cells. Cases (1+) had faint staining in ≥10% of tumor cells. Cases considered 0 had no staining or faint staining in <10% of tumor cells. HER2 expression was also quantified with the endometrial serous carcinoma protocol, which uses a 30% tumor cell positivity cutoff. FISH for HER2 was performed on all 3+ and 2+ and a subset of 1+ cases. Of the MOC cases, 25% were 3+ and 1 mucinous borderline tumor with intraepithelial carcinoma had 3+ staining. All 3+ IHC MOC cases had >30% basolateral membranous staining. HER2 amplification was confirmed by FISH on all 3+ IHC cases and in one 2+ IHC case of MOC. Up to 25% of mucinous ovarian tumors showed HER2 IHC overexpression with an excellent correlation between IHC and FISH using the HER2 scoring protocol for either gastric/gastroesophageal carcinoma or uterine serous carcinoma.

Joint denoising and interpolating network for low-dose cone-beam CT reconstruction under hybrid dose-reduction strategy.

Cone-beam computed tomography (CBCT) is generally reconstructed with hundreds of two-dimensional X-Ray projections through the FDK algorithm, and its excessive ionizing radiation of X-Ray may impair patients' health. Two common dose-reduction strategies are to either lower the intensity of X-Ray, i.e., low-intensity CBCT, or reduce the number of projections, i.e., sparse-view CBCT. Existing efforts improve the low-dose CBCT images only under a single dose-reduction strategy. In this paper, we argue that applying the two strategies simultaneously can reduce dose in a gentle manner and avoid the extreme degradation of the projection data in a single dose-reduction strategy, especially under ultra-low-dose situations. Therefore, we develop a Joint Denoising and Interpolating Network (JDINet) in projection domain to improve the CBCT quality with the hybrid low-intensity and sparse-view projections. Specifically, JDINet mainly includes two important components, i.e., denoising module and interpolating module, to respectively suppress the noise caused by the low-intensity strategy and interpolate the missing projections caused by the sparse-view strategy. Because FDK actually utilizes the projection information after ramp-filtering, we develop a filtered structural similarity constraint to help JDINet focus on the reconstruction-required information. Afterward, we employ a Postprocessing Network (PostNet) in the reconstruction domain to refine the CBCT images that are reconstructed with denoised and interpolated projections. In general, a complete CBCT reconstruction framework is built with JDINet, FDK, and PostNet. Experiments demonstrate that our framework decreases RMSE by approximately 8 %, 15 %, and 17 %, respectively, on the 1/8, 1/16, and 1/32 dose data, compared to the latest methods. In conclusion, our learning-based framework can be deeply imbedded into the CBCT systems to promote the development of CBCT. Source code is available at https://github.com/LianyingChao/FusionLowDoseCBCT.

Antagonistic Activity of Streptomyces alfalfae 11F against Fusarium Wilt of Watermelon and Transcriptome Analysis Provides Insights into the Synthesis of Phenazine-1-Carboxamide.

Streptomyces alfalfa strain 11F has inhibitory effects on many phytopathogenic fungi and improves the establishment and biomass yield of switchgrass. However, the antagonistic effects of strain 11F on Fusarium wilt of watermelon and its secondary metabolites that contribute to its biocontrol activity are poorly understood. We evaluated the antagonistic and growth-promoting effects of strain 11F and conducted a transcriptome analysis to identify the metabolites contributing to antifungal activity. Strain 11F had marked inhibitory effects on six fungal pathogens. The incidence of Fusarium wilt of watermelon seedlings was decreased by 46.02%, while watermelon seedling growth was promoted, as indicated by plant height (8.7%), fresh weight (23.1%), and dry weight (60.0%). Clean RNA-sequencing data were annotated with 7553 functional genes. The 2582 differentially expressed genes (DEGs) detected in the Control vs. Case 2 comparison were divided into 42 subcategories of the biological process, cellular component, and molecular function Gene Ontology categories. Seven hundred and forty functional genes (55.47% of the DEGs) were assigned to Kyoto Encyclopedia of Genes and Genomes metabolic pathways, reflecting the complexity of the strain 11F metabolic regulatory system. The expression level of the gene phzF, which encodes an enzyme essential for phenazine-1-carboxylic acid (PCA) synthesis, was downregulated 3.7-fold between the 24 h and 48 h fermentation time points, suggesting that strain 11F can produce phenazine compounds. A phenazine compound from 11F was isolated and identified as phenazine-1-carboxamide (PCN), which contributed to the antagonistic activity against Fusarium oxysporum f. sp. niveum. PCA was speculated to be the synthetic precursor of PCN. The downregulation in phzF expression might be associated with the decrease in PCA accumulation and the increase in PCN synthesis in strain 11F from 24 to 48 h. Streptomyces alfalfae 11F protects watermelon seedlings from Fusarium wilt of watermelon and promotes seedling growth. The transcriptome analysis of strain 11F provides insights into the synthesis of PCN, which has antifungal activity against F. oxysporum f. sp. niveum of watermelon.

Evidence of Bariatric Surgery Benefits Cardiac Function in Non-HFpEF Patients with Obesity: a Meta-Analysis.

BACKGROUND/OBJECTIVE: Nowadays, increasing clinical evidence on metabolic and weight-loss effects of bariatric surgery on improving cardiac structure in obese patients, but its application in improving the cardiac function of HF (heart failure) patients remains controversial. The objective of this meta-analysis was to assess the effects of BS on cardiac function by quantifying the changes of LVEF (left ventricular ejection fraction) and NYHA (New York Heart Association classification) after operations in non-HFpEF (heart failure and preserved ejection fraction) patients. METHODS: Articles were searched using PubMed and Embase from inception to December 9, 2022, and the Minors scale was used for quality assessments. The included patients should be non-HFpEF and clinically severely obese, and their pre-operative and post-operative values of LVEF or NYHA should be reported. RESULT: Nine studies involving 146 patients were eventually included with a final result showing that the cardiac functional parameters were improved in non-HFpEF patients. After a weighted mean follow-up time of 15.8 months, the mean NYHA decreased by 0.59 (I2 = 0; 95% CI 0.27 ~ 0.92; p = 0.003), and the mean LVEF increased by 7.49% (I2 = 0; 95% CI - 9.99 ~ - 4.99; p < 0.00001). CONCLUSION: Bariatric surgery offers beneficial cardiac effects on non-HFpEF patients with obesity but failed to show a significant improvement in the pooled analysis for the changes of cardiac parameters. The improving degree may be related to the baseline BMI, the extent of BMI loss, and the baseline age. Future studies should focus on finding out the influencing factors of effectivenesses and defining the suitable crowd.

Indisulam exerts anticancer effects via modulation of transcription, translation and alternative splicing on human cervical cancer cells.

Indisulam is a synthetic sulfonamides drug with anticancer activity in various tumors. However, the effect and molecular mechanism of indisulam have still not been studied in human cervical cancer. We treated human cervical cancer cell lines (HeLa and C33A) with indisulam, evaluated its efficacy, and investigated its molecular targets. Indisulam inhibited tumor growth and induced RBM39 degradation in a dose-dependent manner. RNA-seq and proteomics analysis revealed that indisulam disrupted transcriptional regulation pathways related to mRNA splicing and apoptosis. More importantly, indisulam caused mis-splicing of RNA transcripts including p73 isoforms ΔNp73 and TAp73 which have opposite roles in apoptosis regulation. Indisulam increased TAp73 expression and triggered mitochondrial apoptosis independent of p53 status in HeLa cells. In summary, our data suggests that indisulam has therapeutic potential in cervical cancer, representing an attractive strategy in p53-disrupted cancers and should be further investigated.

Alterations in Gray Matter Morphology and Functional Connectivity in Adult Patients with Newly Diagnosed Untreated Hypothyroidism.

Background: Untreated adult hypothyroidism may be associated with cognitive and emotional impairment, but the precise underlying neuropathological mechanism is unknown. We investigated the brain morphological and functional abnormalities associated with cognition and emotion in hypothyroidism. Methods: This is a cross-sectional observational study. Forty-four newly diagnosed adult hypothyroid patients and 54 well-matched healthy controls (HCs) were enrolled. All participants underwent three-dimensional T1-weighted imaging and resting-state functional magnetic resonance imaging (MRI). Morphological and seed-based functional connectivity (FC) analyses were performed to compare the intergroup differences. Neuropsychological tests, including the Montreal Cognitive Assessment (MoCA) Scale, 24-item Hamilton Depression Rating Scale (HAMD-24), and Hamilton Anxiety Rating Scale (HAMA) were administered. Thyroid function test and blood lipid levels were measured. Correlations were computed between neuropsychological and biochemical measures with neuroimaging indices. Sensitive morphological or functional neuroimaging indicators were identified using receiver operating characteristic (ROC) analysis. Results: Compared with HCs, hypothyroid patients demonstrated lower total and subdomain scores on the MoCA and higher HAMD-24 and HAMA scores. Morphological analysis revealed the hypothyroid patients had significantly reduced gray matter (GM) volumes in the right superior frontal gyrus, superior temporal gyrus, left dorsolateral superior frontal gyrus, middle frontal gyrus, and supplementary motor area as well as significantly increased GM volumes in the bilateral cerebellar Crus I and left precentral gyrus. Furthermore, seed-based FC analysis of hypothyroid patients showed increased FC between the right cerebellar Crus I and left precentral gyrus, triangular part of the inferior frontal gyrus, and angular gyrus of the inferior parietal lobe. The language scores of the MoCA were positively correlated with Jacobian values of the left supplementary motor area (r = 0.391, p = 0.046) and precentral gyrus (r = 0.401, p = 0.039). ROC analysis revealed FC value between cerebellar Crus I and angular gyrus could differentiate groups with relatively high accuracy (sensitivity: 75%, specificity: 77.8%, area under the curve: 0.794 [CI 0.701-0.888], p < 0.001). Conclusions: Untreated adult-onset hypothyroidism may be associated with impaired cognition and anxiety or depression. GM morphological alterations and FC of the cerebellum with subregions of the frontal and parietal lobes may represent key neuropathological mechanisms underlying the cognitive deterioration and mood dysregulation observed in hypothyroid adults. Clinical Trial Registration Number: chiCTR2000028966.