The relationships between obesity and epilepsy: A systematic review with meta-analysis.

OBJECTIVE: There is ongoing debate regarding the association between epilepsy and obesity. Thus, the aim of this study was to examine the correlation between epilepsy and obesity. METHOD: This study adhered to the PRISMA guidelines for systematic reviews and meta-analyses. On The Prospero website, this study has been successfully registered (CRD42023439530), searching electronic databases from the Cochr-ane Library, PubMed, Web of Sciences and Embase until February 10, 2024.The search keywords included "Epilepsy", "Obesity", "Case-Control Studies", "cohort studies", "Randomized Controlled Trial" and "Cross-Sectional Studies". The medical subject headings(MeSH) of PubMed was utilized to search for relevant subject words and free words, and a comprehensive search strategy was developed. Two reviewers conducted article screening, data extraction and bias risk assessment in strict accordance with the predefined criteria for including and excluding studies. The predefined inclusion criteria were as follows: 1) Inclusion of case-control, cohort, randomized controlled trial, and cross-sectional studies; 2) Segregation of subjects into epileptic patients and healthy controls; 3)Obesity as the outcome measure; 4) Availability of comprehensive data; 5) Publication in English. The exclusion criteria were as follows: 1) Exclusion of animal experiments, reviews, and other types of studies; 2) Absence of a healthy control group; 3) Incomplete data; 4) Unextractable or unconvertible data; 5) Low quality, indicated by an Agency for Healthcare Research and Quality(AHRQ) score of 5 or lower,or a Newcastle-Ottawa Scale (NOS) score less than 3. The subjects included in the study included adults and children, and the diagnostic criteria for obesity were used at different ages. In this study, obesity was defined as having a body mass index(BMI) of 25 kg/m2 or higher in adults and being above the 85th percentile of BMI for age in children. We used obesity as an outcome measure for meta-analysis using RevMan, version 5.3. RESULTS: A meta-analysis was conducted on a total of 17 clinical studies, which involved 5329 patients with epilepsy and 480837 healthy controls. These studies were selected from a pool of 1497 articles obtained from four electronic databases mentioned earlier. Duplicate studies were removed based on the search strategies employed. No significant heterogeneity was observed in the outcome measure of obesity in epileptic patients compared with healthy controls(p = 0.01,I2 = 49%). Therefore, a fixed effects model was utilized in this study. The findings revealed a significant difference in obesity prevalence between patients with epilepsy and healthy controls(OR = 1.28, 95%CI: 1.20-1.38, p<0.01). CONCLUSION: The results of this meta-analysis indicate that epilepsy patients are more prone to obesity than healthy people, so we need to pay attention to the problem of post-epilepsy obesity clinically. Currently, there is a scarcity of largescale prospective studies. Additional clinical investigations are warranted to delve deeper into whether obesity is a comorbidity of epilepsy and whether obesity can potentially trigger epilepsy.

Functional cure induced by tenofovir alafenamide plus peginterferon-alpha-2b in young children with chronic hepatitis B: a case series study.

BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Nonlinear association between the triglyceride-glucose index and diabetes mellitus in overweight and obese individuals: a cross-sectional retrospective analysis.

BACKGROUND: The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. METHODS: This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. RESULTS: Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98-7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52-25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76-8.48,), more significant in individuals with a BMI of 24-28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83-9.02), and increased with age (OR = 8.15, 95% CI: 7.25-9.17) (all P for interaction < 0.001). CONCLUSION: Among overweight or obese individuals, a higher TyG index is associated with an elevated risk of diabetes, especially when TyG is > 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24-28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

Curing of chronic hepatitis C combined with coronavirus disease 2019 in a couple over 85 years old: a case series study.

Introduction: Data on the management of patients aged more than 85 years with chronic hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequential infections are lacking. Methods: The current study described the management of an older couple aged more than 85 years with these above-mentioned two diseases treated with 12 weeks of sofosbuvir/velpatasvir (Epclusa®) and 5 days of nirmatrelvir/ritonavir (Paxlovid®) sequentially. The effectiveness and safety profiles were closely monitored during therapy and till 9 months posttreatment. Results: In late March 2023, the husband with the main complaint of repeated gingival bleeding and asymptomatic wife were 86 and 85 years old, and had HCV RNA levels of 91,800 and 6,630,000 IU/mL, respectively. On the fourth day of sofosbuvir/velpatasvir treatment, the husband had a moderate headache, and the wife had severe headache and moderate fever and dizziness. We then found that their SARS-CoV-2 test results were positive. After careful consideration, the expert panel decided to treat the couple with oral nirmatrelvir/ritonavir (300 mg/100 mg, twice daily) beginning on the fifth day of sofosbuvir/velpatasvir treatment for 5 days. During the 5 days of nirmatrelvir/ritonavir treatment, the patient's symptoms and signs gradually improved, and the patient was negative for SARS-CoV-2 RNA on the fifth day of nirmatrelvir/ritonavir therapy. Meanwhile, the husband's HCV RNA was not detectable after one week of sofosbuvir/velpatasvir treatment till posttreatment month 9, and his ALT level was normal beginning at week 1 of sofosbuvir/velpatasvir treatment. Moreover, the wife's HCV RNA was not detectable after week 4 of sofosbuvir/velpatasvir treatment till posttreatment month 9. Notably, no other symptoms or signs occurred during the treatment or follow-up period, and other serum biochemical parameters remained stable until 9 months after the discontinuation of sofosbuvir/velpatasvir treatment. Conclusion: The older couple aged more than 85 years with chronic HCV and SARS-CoV-2 sequential infection were safely cured by the sofosbuvir/velpatasvir and nirmatrelvir/ritonavir sequential treatment. Discussion: This study suggested that old age should not be a barrier to HCV/SARS-CoV-2 treatment. Given that the proportion of older HCV-infected patients is increasing, clinical trials of direct-acting antiviral agents should include older HCV-infected individuals.

Self-Assembled Peptide Hydrogels Loaded with Umbilical Cord-Derived Mesenchymal Stem Cells Repairing Injured Endometrium and Restoring Fertility.

Endometrial injury is a major cause of infertility and recurrent miscarriage. However, no clinically available methods currently exist to effectively repair the damaged endometrium. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for promoting tissue regeneration, yet a biocompatible scaffold capable of delivering MSCs and supporting their growth is needed. Herein, the study reports a peptide hydrogel scaffold, self-assembled from a peptide IVK8-RGD consisting of an ionic complementary peptide sequence IEVEIRVK and a bioactive sequence RGD, to load umbilical cord-derived mesenchymal stem cells (UC-MSCs). This peptide forms a hydrogel under the physiological condition through self-assembly, and the peptide hydrogel exhibits injectability and adhesiveness to uterus, making it suitable for endometrial repair. Importantly, this hydrogel supports the adhesion and proliferation of UC-MSCs in a 3D environment. In vivo experiments using rats with endometrial injury have shown that treatment with IVK8-RGD hydrogel loaded with UC-MSCs effectively restores endometrial thickness, inhibits fibrosis, and facilitates angiogenesis through activating Raf/MEK/ERK pathway, leading to significantly improved fertility and live birth rate. These findings demonstrate the potential of the UC-MSCs-loaded hydrogel in repairing damaged endometrium and may address the unmet clinical needs of treating recurrent miscarriage and infertility induced by endometrial damage.

Identification of BAF60b as a chromatin remodeling checkpoint of diet-induced fatty liver disease.

Overnutrition has gradually become the primary causative factor of nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. Here, we identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complex and is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, while transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of PPARγ expression. Mechanistically, through motif analysis of liver ATAC-Seq and multiple validation experiments, we identified CCAAT/enhancer-binding protein ß (C/EBPß) as the transcription factor that interacts with BAF60b to suppress PPARγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work uncovers hepatic BAF60b as a negative regulator of liver steatosis through C/EBPß dependent chromatin remodeling.

Erythroid-intrinsic activation of TLR8 impairs erythropoiesis in inherited anemia.

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Nonlinear association between atherogenic index of plasma and type 2 diabetes mellitus in overweight and obesity patients: evidence from Chinese medical examination data.

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.

Identifying popular, rejected and neglected children in Chinese preschool: An exploratory study on the educational application of spatial positioning data.

Amidst the rapid advancement of Internet of Things (IoT) technology and the burgeoning field of Multimodal Learning Analytics (MMLA), this study employs spatial positioning technology as a case study to investigate the potential of multimodal data in assessing children's social development. This study combines the spatial positioning data of preschool children collected during free play sessions in natural educational settings and the spatial metrics constructed based on observational studies to establish and validate a sociometric status Decision Tree classification model. The findings suggest that the model can overall accurately identify children with three distinct sociometric statuses, albeit with some variability in efficacy across different sociometric groups and age groups. Notably, the model demonstrates a high hitting rate in identifying the potentially neglected children, providing valuable support for educators in understanding and fostering children's developmental needs. This study also highlights the advantages of emerging technology and multimodal data application in child development assessment.

A meta-analysis of the effects of ketamine on suicidal ideation in depression patients.

The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is particularly important. Ketamine has been shown to reduce suicidal ideation rapidly, but the strength of the effect is unclear and there is little evidence-based medical evidence to support this. We systematically searched all articles published on PubMed, Cochrane Library, Web of Science, CNKI and EMBASE. Stata 15 and R 4.1.3 were used for meta-analysis, and odds ratios were calculated in fixed effects or random effects models based on the heterogeneity test results. Our search resulted in 505 articles; we analyzed 14 studies, which included 1,380 participants. The 14 studies included 10 randomized controlled trial (RCT) studies and 4 single-arm studies. Our study suggests that, ketamine has a significant therapeutic effect on suicidal ideation throughout the treatment cycle. We performed network meta-analyses(NMA) and pairwise meta-analyses to compare the efficacy of ketamine in the reduction of suicidal ideation. There was a significant reduction in suicidal ideation within the first day after treatment (NMA ketamine day1 RR = 10.02, 95%CI = 4.24 to 23.68). In repeated treatment, the degree of recovery of suicidal ideation after the last dose was significantly greater than that after the first dose (RR = 0.56, 95%CI = 0.51 to 0.62). Recovery of suicidal ideation was also significantly better in the treatment end point than in the placebo group at the same time point (NMA ketamine day26 RR = 4.29, 95%CI = 1.41 to 13.08). This is the first network meta-analysis to demonstrate the role of ketamine in the alleviation of suicidal ideation. Our network meta-analysis also compared the effects of different drugs at different time points, which was not done in previous studies. This is of great reference significance for future drug research andrational drug use.

Targeting lipid peroxidation-associated ferroptosis suppresses lung carcinoma progression by regulating cell cycle arrest.

Lung carcinoma is a frequently encountered cancerous growth that affects the respiratory tract and has a high occurrence rate globally. In light of the ongoing worldwide health emergency, the significance of efficient therapeutic agents and strategies is of utmost importance. A meticulous control of the cell cycle is crucial for comprehending the pathophysiology and molecular causes of lung cancer, as well as for the formulation of efficacious therapeutic medicines. The mechanism by which cells synchronize cell cycle with cell survival and death is still not fully understood. In this study, we demonstrate that the halting of the cell cycle has a strong inhibitory impact on ferroptosis, a specific type of controlled cell death triggered by excessive lipid peroxidation at the membranes of cells. Ferroptosis is halted through the mechanism of cell cycle arrest, which involves the deposition of intracellular lipids mediated by diacylglycerol acyltransferase (DGAT). Excessive amounts of polyunsaturated fatty acids (PUFAs) are stored as triacylglycerols (TAGs) within inactive cells. As a result, inhibiting DGAT causes a rearrangement of PUFAs from TAGs to phospholipids and makes arrested cells more susceptible to ferroptosis. We demonstrate that certain lung cancer cells that are resistant to antimitotic drugs and have a slow-cycling behavior exhibit an increase in lipid droplets. Furthermore, we find that the growth of tumors resistant to 5-fluorouracil, lorlatinib, and docetaxel can be effectively suppressed by a combination treatment involving the use of ferroptosis inducers and DGAT inhibitors, which induces ferroptosis. Collectively, these findings demonstrate the involvement of cell cycle arrest in conferring resistance to ferroptosis and propose a potential therapeutic approach for addressing the challenge of slow-cycling malignancies that exhibit resistance to ferroptosis.

Construction of mechanically robust and recyclable catalytic hydrogel based on hydroxypropyl cellulose-supported by montmorillonite/ionic liquid with different anions for pollutants(4-NP, MB, CR, Rhb) degradation.

Dye wastewater poses a serious threat to the environment and human health, necessitating sustainable degradation methods. In this study, Na-based Montmorillonite (MMT) was exfoliated using different ionic liquids ([C16MIM][Cl], [C16MIM][BF4], [C16MIM][PF6]), and silver nanoparticles (Ag NPs) were green-synthesized using hydroxypropyl cellulose (HPC). The HPC significantly enhanced the dispersion of MMT in the hydrogel. By introducing lauryl methacrylate (LMA), a hydrophobic associative network was constructed in PAM/LMA/HPC/MMT@ILs&Ag NPs hydrogel. This hydrogel demonstrated outstanding mechanical properties, with a stress of 833.21 kPa, strain of 3300 %, and toughness of 14.36 MJ/m3. It also exhibited excellent catalytic activity, with a rate constant of 0.83 min-1 for 4-nitrophenol degradation at 28 °C. The effects of temperature and catalyst concentration on the catalytic reaction were systematically investigated. This study presents a simple green synthesis approach for Ag NPs using HPC, achieving superior mechanical performance and stable MMT dispersion in aqueous solutions.

One-step of ionic liquid-assisted stabilization and dispersion: Exfoliated graphene and its applications in stimuli-responsive conductive hydrogels based on chitosan.

Conductive hydrogels, as novel flexible biosensors, have demonstrated significant potential in areas such as soft robotics, electronic devices, and wearable technology. Graphene is a promising conductive material, but its dispersibility in aqueous solutions exists difficulties. Here, we discover that untreated graphene, after exfoliation by different ionic liquids, can disperse well in aqueous solutions. We investigate the impact of four ionic liquids with varying alkyl chain lengths ([Bmim]Cl, [Omim]Cl, [Dmim]Cl, [Hmim]Cl) on the dispersibility of grapheme, and a dual physically cross-linked network hydrogel structure is designed using acrylamide (AM), acrylic acid (AA), methyl methacrylate octadecyl ester (SMA), ionic liquid@graphene (ILs@GN), and chitosan (CS). Notably, SMA, CS, AA and AM act as dynamic cross-linking points through hydrophobic interactions and hydrogen bonding, playing a crucial role in energy dissipation. The resulting hydrogel exhibits outstanding stretchability (2250 %), remarkable toughness (1.53 MJ/m3) in tensile deformation performance, high compressive strength (1.13 MPa), rapid electrical responsiveness (response time âˆ¼ 50 ms), high electrical conductivity (12.11 mS/cm), and excellent strain sensing capability (GF = 12.31, strain = 1000 %). These advantages make our composite hydrogel demonstrate high stability in extensive deformations, offering repeatability in pressure and strain and making it a promising candidate for multifunctional sensors and flexible electrodes.

Association between liver fat level and risk of hypertension: evidence from a Chinese health examination dataset.

BACKGROUND: Hypertension development is predominantly influenced by inflammation, excessive fat deposition, and metabolic irregularities. Among these factors, liver fat accumulation is a critical metabolic disorder. However, the quantification of liver fat levels and its associated risk for hypertension incidence remain ambiguous. This project is designed to explore the association between liver fat levels and the risk of hypertension in a healthy population. METHODS: This cross-sectional study involved 4955 participants from the Health Management Center at Henan Provincial People's Hospital who were surveyed between February 2020 and February 2023. Participants were categorized into four groups based on liver fat quartiles. Subgroup analyses, restricted cubic spline regression models, and logistic regression were utilized to assess the association between liver fat levels and hypertension risk. The relationships between liver fat levels and inflammatory markers were examined using multiple linear regression models. Additionally, a mediation analysis was conducted to explore the role of inflammatory factors in the relationship between liver fat and hypertension risk. RESULTS: Participants with hypertension exhibited greater liver fat levels than did those without hypertension. An increased risk of hypertension was associated with elevated liver fat levels, even after adjusting for other covariates [Q4 vs. Q1 in model II: odds ratio (OR = 1.28), 95% confidence interval (CI) = 1.04-1.59, P = 0.022; P for trend = 0.039]. A nonlinear relationship was observed between liver fat level and hypertension risk, with a notable increase in hypertension risk occurring at liver fat levels greater than 8.65%. Additionally, a positive correlation was found between inflammatory markers and liver fat levels. A mediation effect of 4.76% was noted, linking hypertension risk and liver fat levels through neutrophils. CONCLUSION: Liver fat levels exceeding 8.65% significantly elevated the risk of hypertension. Inflammatory factors serve as crucial mediators of the relationship between liver fat and hypertension.

Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

Targeting BIRC5 as a therapeutic approach to overcome ASXL1-associated decitabine resistance.

Hypomethylating agents (HMAs) are widely employed in the treatment of myeloid malignancies. However, unresponsive or resistant to HMAs occurs in approximately 50 % of patients. ASXL1, one of the most commonly mutated genes across the full spectrum of myeloid malignancies, has been reported to predict a lower overall response rate to HMAs, suggesting an essential need to develop effective therapeutic strategies for the patients with HMA failure. Here, we investigated the impact of ASXL1 on cellular responsiveness to decitabine treatment. ASXL1 deficiency increased resistance to decitabine treatment in AML cell lines and mouse bone marrow cells. Transcriptome sequencing revealed significant alterations in genes regulating cell cycle, apoptosis, and histone modification in ASXL1 deficient cells that resistant to decitabine. BIRC5 was identified as a potential target for overcoming decitabine resistance in ASXL1 deficient cells. Furthermore, our experimental evidence demonstrated that the small-molecule inhibitor of BIRC5 (YM-155) synergistically sensitized ASXL1 deficient cells to decitabine treatment. This study sheds light on the molecular mechanisms underlying the ASXL1-associated HMA resistance and proposes a promising therapeutic strategy for improving treatment outcomes in affected individuals.

Course and predictors of supportive care needs among colorectal cancer survivors with ostomies: a longitudinal study.

PURPOSE: Although there is a growing emphasis on supportive care for cancer patients, those with colorectal cancer (CRC) who have ostomies require special attention in terms of their physical, psychological, spiritual, and social needs. However, there has been a lack of significant progress in meeting the supportive care needs of CRC survivors with ostomies. To bridge this gap, we conducted a prospective longitudinal study to track the trends in supportive care needs among CRC survivors with ostomies and identify any predictors over 6-month period. METHODS: A prospective longitudinal study was conducted at the wound and stoma clinic of Dalian University Affiliated Xinhua Hospital, focusing on CRC survivors with ostomies. A total of 143 participants completed self-report questionnaires on the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34-C (Mandarin)) and stoma complications at the first, third, and sixth month after surgery. ANOVA with repeated measure was utilized to assess the course of supportive care needs, with Generalized Estimating Equation (GEE) applied to identify predictors of SCNS. RESULTS: The supportive care needs and five dimensions scores were statistically significant at three time points (P < 0.05). The ratings of patients at the first, third, and sixth month after surgery revealed a decreasing trend in the scores for patient care and support, psychological needs, physical and daily living needs, and health system and information needs. However, the score for sexual needs showed an increased tendency. Higher levels supportive care needs were generally connected with a short duration after ostomy, high income level, resident medical insurance, spouse caregiver, other chronic disease, and stoma complications. CONCLUSIONS: Survivors' supportive care needs showed a dynamic trend over 6 months after surgery. Through three rounds, the primary needs were health system and information needs. It is recommended to integrate interdisciplinary health professionals and establish a comprehensive support and care system to effectively meet the diverse needs at different stages. Priority should be given to individuals with ostomies during the first and third month after surgery, particularly those with higher income levels, employee medical insurance, spouse caregivers, other chronic diseases, and stoma complications.

Establishment and validation of multiclassification prediction models for pulmonary nodules based on machine learning.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. This study aimed to establish novel multiclassification prediction models based on machine learning (ML) to predict the probability of malignancy in pulmonary nodules (PNs) and to compare with three published models. METHODS: Nine hundred fourteen patients with PNs were collected from four medical institutions (A, B, C and D), which were organized into tables containing clinical features, radiologic features and laboratory test features. Patients were divided into benign lesion (BL), precursor lesion (PL) and malignant lesion (ML) groups according to pathological diagnosis. Approximately 80% of patients in A (total/male: 632/269, age: 57.73 ± 11.06) were randomly selected as a training set; the remaining 20% were used as an internal test set; and the patients in B (total/male: 94/53, age: 60.04 ± 11.22), C (total/male: 94/47, age: 59.30 ± 9.86) and D (total/male: 94/61, age: 62.0 ± 11.09) were used as an external validation set. Logical regression (LR), decision tree (DT), random forest (RF) and support vector machine (SVM) were used to establish prediction models. Finally, the Mayo model, Peking University People's Hospital (PKUPH) model and Brock model were externally validated in our patients. RESULTS: The AUC values of RF model for MLs, PLs and BLs were 0.80 (95% CI: 0.73-0.88), 0.90 (95% CI: 0.82-0.99) and 0.75 (95% CI: 0.67-0.88), respectively. The weighted average AUC value of the RF model for the external validation set was 0.71 (95% CI: 0.67-0.73), and its AUC values for MLs, PLs and BLs were 0.71 (95% CI: 0.68-0.79), 0.98 (95% CI: 0.88-1.07) and 0.68 (95% CI: 0.61-0.74), respectively. The AUC values of the Mayo model, PKUPH model and Brock model were 0.68 (95% CI: 0.62-0.74), 0.64 (95% CI: 0.58-0.70) and 0.57 (95% CI: 0.49-0.65), respectively. CONCLUSIONS: The RF model performed best, and its predictive performance was better than that of the three published models, which may provide a new noninvasive method for the risk assessment of PNs.

Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.