A screw algorithm for congenital C2-3 fusion with high-riding vertebral arteries: feasibilities and clinical outcomes of five different fixation techniques.

OBJECTIVE: To propose a screw algorithm and investigate the anatomical feasibilities and clinical outcomes of five distinct fixation methods for C2-3 fused vertebra with high-ridding vertebral arteries (VA) (HRVA) when the C2 pedicle screw placement is unfeasible. METHODS: Thirty surgical patients with congenital C2-3 fusion, HRVA, and atlantoaxial dislocation (AAD) were included. We designed a algorithm for alternative screw implantation into C2-3 fused vertebrae, including C2 pedicle screw with in-out-in (passing VA groove) technique (in-out-in screw), subfacetal screw, translaminar screw, lateral mass screw, C3 pedicle screw. VA diameter and position, C2 and C3 pedicles, superior facets, fused lamina, and fused lateral mass dimensions were evaluated for screw implantation indication. Implant failure, reduction loss, implant placement accuracy were investigated by computed tomography. RESULTS: A total of 5 VAs were identified as distant VAs; a total of 2 VAs were categorized as occlusive VAs. Sufficient dimension of lateral mass and lamina provided the broadest indications for screw implantation, while the distant or occlusive VA provided the most limited indications for in-out-in screw. The indications of five alternative methods ranged from narrowest to widest as follows: in-out-in screw, C3 pedicle screw, subfacetal screw, translaminar screw, lateral mass screw. The translaminar screws and the lateral mass screws increased the probability of implant failure. All patients who received in-out-in screws, C3 pedicle screws, and subfacetal screws achieved fusion. The accuracy ranged from lowest to highest as follows: C3 pedicle screw, lateral mass screw, in-out-in screw, subfacetal screw, translaminar screw. No translaminar screws deviated. CONCLUSIONS: The algorithm proved to be a valuable tool for screw selection in cases of C2-3 fused vertebrae with HRVAs. The subfacetal screw, boasting broad indications, a high fusion rate, and exceptional accuracy, stood as the primary preferred alternative.

Individualized C1-2 intra-articular three-dimensional printed porous titanium alloy cage for craniovertebral deformity.

BACKGROUND: Congenital craniovertebral deformity, including basilar invagination (BI) and atlantoaxial instability (AAI), are often associated with three-dimensional (3D) deformity, such as C1-2 rotational deformity, craniocervical kyphosis, C1 lateral inclination, among other abnormalities. Effective management of these conditions requires the restoration of the 3D alignment to achieve optimal reduction. Recently, 3D printing technology has emerged as a valuable tool in spine surgery, offering the significant advantage of allowing surgeons to customize the prosthesis design. This innovation provides an ideal solution for precise 3D reduction in the treatment of craniovertebral deformities. OBJECTIVE: This study aims to describe our approach to individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cages for the quantitative correction of craniovertebral junction deformities. METHODS: A retrospective analysis was conducted on patients with craniovertebral deformities treated at our institution using individualized 3D-printed porous titanium alloy cages. Preoperative CT data were used to construct models for 3D realignment simulations. Cage designs were tailored to the simulated joint morphology following computer-assisted realignment. Preoperative and postoperative parameters were statistically analyzed. RESULTS: Fourteen patients were included in the study, with a total of 28 3D-printed porous titanium alloy cages implanted. There were no cases of C2 nerve root resection or vertebral artery injury. All patients experienced symptom relief and stable implant fixation achieved in all cases. No implant-related complications were reported. CONCLUSION: The use of individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cage facilitates precise 3D realignment in patients with craniovertebral deformities, demonstrating effectiveness in symptom relief and stability.

Biomechanical differences of three cephalic fixation methods for patients with basilar invagination and atlantoaxial dislocation in the setting of congenital atlas occipitalization: a finite element analysis.

BACKGROUND CONTEXT: In cases of basilar invagination-atlantoaxial dislocation (BI-AAD) complicated by atlas occipitalization (AOZ), the approach to cranial end fixation has consistently sparked debate, generally falling into two categories: C1-C2 fixation and occipitocervical fixation. Several authors believe that C1-C2 fixation carries a lower risk of fixation failure than occipitocervical fixation. PURPOSE: To study the biomechanical differences among 3 different cranial end fixation methods for BI-AAD with AOZ. STUDY DESIGN: This was a finite element analysis. PATIENT SAMPLE: A 35-year-old female patient diagnosed with congenital BI-AAD and AOZ. OUTCOME MEASURES: range of motion (ROM), peak von Mise stress (PVMS), cage micro-subsidence, cage micro-slippage METHOD: Four finite element models were constructed, including unstable group (BI-AAD with AOZ), C1 lateral mass screw group, occipital plate group, occipitocervical rod group. The flexion and extension (FE), lateral bending (LB) as well as axial rotation (AR) were simulated under a torque of 1.5 Nm. Parameters include C1-C2 ROM, PVMS on screw-rod construct, cage micro-subsidence, cage micro-slippage. RESULTS: The ROM of the C1 lateral mass screw group was smaller than that of the other fixation groups in LB and AR, but not FE. Compared with the occipitocervical rod group, the ROM in LB and AR of the occipital plate group was higher, but not in FE. The PVMS of C1 lateral mass screw group was significantly higher than that of the other groups. The ROM and PVMS of the occipitocervical rod group were in between the other 2 groups. Regarding the screws at the cranial end, the PVMS of the 4-screw occipitocervical rod group was significantly lower than that of the other groups. In general, the cage micro-motion follows the ascending order: C1 lateral mass group < occipitocervical rod group < occipital plate group. CONCLUSION: In cases of BI-AAD with AOZ, the C1 lateral mass screw group provided the least ROM and cage micro-motion, but the screw-rod PVMS was the largest. The advantage of occipital plate fixation lies in the lowest screw-rod PVMS, but the ROM and cage micro-motion is the highest. Four-screw fixation at the cranial end of occipitocervical rod group helps to reduce the PVMS and may prevent screw failure at the cranial end.

Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers.

Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.

Advancing precision medicine in gliomas through single-cell sequencing: unveiling the complex tumor microenvironment.

Glioblastoma (GBM) displays an infiltrative growth characteristic that recruits neighboring normal cells to facilitate tumor growth, maintenance, and invasion into the brain. While the blood-brain barrier serves as a critical natural defense mechanism for the central nervous system, GBM disrupts this barrier, resulting in the infiltration of macrophages from the peripheral bone marrow and the activation of resident microglia. Recent advancements in single-cell transcriptomics and spatial transcriptomics have refined the categorization of cells within the tumor microenvironment for precise identification. The intricate interactions and influences on cell growth within the tumor microenvironment under multi-omics conditions are succinctly outlined. The factors and mechanisms involving microglia, macrophages, endothelial cells, and T cells that impact the growth of GBM are individually examined. The collaborative mechanisms of tumor cell-immune cell interactions within the tumor microenvironment synergistically promote the growth, infiltration, and metastasis of gliomas, while also influencing the immune status and therapeutic response of the tumor microenvironment. As immunotherapy continues to progress, targeting the cells within the inter-tumor microenvironment emerges as a promising novel therapeutic approach for GBM. By comprehensively understanding and intervening in the intricate cellular interactions within the tumor microenvironment, novel therapeutic modalities may be developed to enhance treatment outcomes for patients with GBM.

RUVBL1/2 Blockade Targets YTHDF1 Activity to Suppress m6A-Dependent Oncogenic Translation and Colorectal Tumorigenesis.

The N6-methyladenosine (m6A) RNA-binding protein YTHDF1 is frequently overexpressed in colorectal cancer and drives chemotherapeutic resistance. To systematically identify druggable targets in colorectal cancer with high expression of YTHDF1, this study used a CRISPR/Cas9 screening strategy that revealed RUVBL1 and RUVBL2 as putative targets. RUVBL1/2 were overexpressed in primary colorectal cancer samples and represented independent predictors of poor patient prognosis. Functionally, loss of RUVBL1/2 preferentially impaired the growth of YTHDF1-high colorectal cancer cells, patient-derived primary colorectal cancer organoids, and subcutaneous xenografts. Mechanistically, YTHFD1 and RUVBL1/2 formed a positive feedforward circuit to accelerate oncogenic translation. YTHDF1 bound to m6A-modified RUVBL1/2 mRNA to promote translation initiation and protein expression. Coimmunoprecipitation and mass spectrometry identified that RUVBL1/2 reciprocally interacted with YTHDF1 at 40S translation initiation complexes. Consequently, RUVBL1/2 depletion stalled YTHDF1-driven oncogenic translation and nascent protein biosynthesis, leading to proliferative arrest and apoptosis. Ribosome sequencing revealed that RUVBL1/2 loss impaired the activation of MAPK, RAS, and PI3K-AKT signaling induced by YTHDF1. Finally, the blockade of RUVBL1/2 by the pharmacological inhibitor CB6644 or vesicle-like nanoparticle-encapsulated siRNAs preferentially arrested the growth of YTHDF1-expressing colorectal cancer in vitro and in vivo. Our findings show that RUVBL1/2 are potential prognostic markers and druggable targets that regulate protein translation in YTHDF1-high colorectal cancer. Significance: RUVBL1/2 inhibition is a therapeutic strategy to abrogate YTHDF1-driven oncogenic translation and overcome m6A dysregulation in colorectal cancer.

Intestinal T-cell lymphomas NOS presenting as a polypoidal lesion: A case report.

RATIONALE: Intestinal T-cell lymphomas are exceedingly rare diseases. Intestinal T-cell lymphoma NOS, as a "wastebasket" category, is difficult to diagnosis. Endoscopy can identify abnormal mucosa in most patients at a reasonably early stage. Therefore, it is crucial to increase the understanding of endoscopists in terms of the endoscopic characteristics of ITCL. PATIENT CONCERNS: A 74-year-old male alone with wasting as the major complaint, had multiple polypoid lesions in the large intestine. The patient then had endoscopic care. DIAGNOSES: Only 1 polypoid lesion on white-light endoscopy in the sigmoid colon was pathologically diagnosed as intestinal T-cell lymphomas, not otherwise specified (ITCL-NOS). INTERVENTIONS: The patient underwent intensity-reduced CHOP therapy. OUTCOMES: The patient is still with controlled disease but developed chemotherapy-related side effects. LESSONS: In the individual with unexplained anemia and waste, endoscopy should not be delayed. For each of polypoid lesion on white-light endoscopy, the endoscopist need to remain cautious, because every lesion in the same patient can exhibit the independence of histopathological features. Meanwhile, we suggest that endoscopists should routinely observe the terminal ileum, even take biopsy samples if necessary.

Probing microscale crystallization phenomena: Transforming waste slags into riches.

Metal smelting and combustion of solid fuels produce significant quantities of waste slag, leading to issues such as land occupation and environmental pollution. Understanding and controlling the microscale crystallization phenomena of these slags during thermal treatment is crucial for transforming waste slags into materials suitable for carbon capture or glass ceramics. Previous research has primarily focused on macroscopic crystallization behaviors, significantly advancing the utilization of waste slags in cement clinker production. However, macroscopic results are inadequate for precisely controlling the microscale crystallization behaviors of waste slags. Here, we employed the single hot thermocouple technique to visually explore crystal growth modes, shapes, sizes, numbers, and translational rates of the crystal growth front in a representative blast furnace slag under various isothermal temperatures. The results revealed that crystals exhibited five modes as the isothermal temperature gradually increased, including equiaxed, equiaxed & columnar, columnar, columnar & planar, and planar. Moreover, the translational rate of the crystal growth front increased from 0.011 µm·s-1 to 43.7 µm·s-1 with an increase in the isothermal temperature. Simultaneously, the number of crystals decreased from around 104 to 100 µm-2. On this basis, correlations between microscale crystallization behaviors and isothermal temperature were established to fill the current gap.

Profiling the Gut Microbiota in Obese Children with Formula Feeding in Early Life and Selecting Strains against Obesity.

Formula feeding, obesity and the gut microbiota are closely related. The present investigation explored the profiles of the intestinal microbiota in obese children over 5 years old with formula feeding in early life. We identified functional bacteria with anti-obesity potential through in vitro and in vivo experiments, elucidating their mechanisms. The results indicated that, in the group of children over 5 years old who were fed formula in early life, obese children exhibited distinct gut microbiota, which were characterized by diminished species diversity and reduced Bifidobacterium levels compared to normal-weight children. As a result, Lactobacillus acidophilus H-68 (H-68) was isolated from the feces of the N-FF group and recognized as a promising candidate. H-68 demonstrated the ability to stimulate cholecystokinin (CCK) secretion in STC-1 cells and produce bile salt hydrolase. In vivo, H-68 promoted CCK secretion, suppressing food intake, and regulated bile acid enterohepatic circulation, leading to increased deoxycholic acid and lithocholic acid levels in the ileum and liver. This regulation effectively inhibited the diet-induced body weight and body fat gain, along with the liver fat deposition. In conclusion, H-68 was recognized for its prospective anti-obesity impact, signifying an auspicious pathway for forthcoming interventions targeted at averting pediatric obesity in formula-fed children.

miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Predicting the 90-day prognosis of stereotactic brain hemorrhage patients by multiple machine learning using radiomic features combined with clinical features.

Hypertensive Intracerebral Hemorrhage (HICH) is one of the most common types of cerebral hemorrhage with a high mortality and disability rate. Currently, preoperative non-contrast computed tomography (NCCT) scanning-guided stereotactic hematoma removal has achieved good results in treating HICH, but some patients still have poor prognoses. This study collected relevant clinical and radiomic data by retrospectively collecting and analyzing 432 patients who underwent stereotactic hematoma removal for HICH from January 2017 to December 2020 at the Liuzhou Workers Hospital. The prognosis of patients after 90 days was judged by the modified Rankin Scale (mRS) scale and divided into the good prognosis group (mRS ≤ 3) and the poor prognosis group (mRS > 3). The 268 patients were randomly divided into training and test sets in the ratio of 8:2, with 214 patients in the training set and 54 patients in the test set. The least absolute shrinkage and selection operator (Lasso) was used to screen radiomics features. They were combining clinical features and radiomic features to build a joint prediction model of the nomogram. The AUCs of the clinical model for predicting different prognoses of patients undergoing stereotactic HICH were 0.957 and 0.922 in the training and test sets, respectively, while the AUCs of the radiomics model were 0.932 and 0.770, respectively, and the AUCs of the combined prediction model for building a nomogram were 0.987 and 0.932, respectively. Compared with a single clinical or radiological model, the nomogram constructed by fusing clinical variables and radiomic features could better identify the prognosis of HICH patients undergoing stereotactic hematoma removal after 90 days.

LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase.

The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.

N6-Methyladenosine Reader YTHDF1 Promotes Stemness and Therapeutic Resistance in Hepatocellular Carcinoma by Enhancing NOTCH1 Expression.

N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic modification in mRNA and has been shown to play important roles in cancer biology. As the m6A reader YTHDF1 has been reported to promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated the clinical significance of YTHDF1 using human HCC samples and found that YTHDF1 was significantly upregulated in HCCs with high stemness scores and was positively associated with recurrence and poor prognosis. Analysis of HCC spheroids revealed that YTHDF1 was highly expressed in liver cancer stem cells (CSC). Stem cell-specific conditional Ythdf1 knockin (CKI) mice treated with diethylnitrosamine showed elevated tumor burden as compared with wild-type mice. YTHDF1 promoted CSCs renewal and resistance to the multiple tyrosine kinase inhibitors lenvatinib and sorafenib in patient-derived organoids and HCC cell lines, which could be abolished by catalytically inactive mutant YTHDF1. Multiomic analysis, including RNA immunoprecipitation sequencing, m6A methylated RNA immunoprecipitation sequencing, ribosome profiling, and RNA sequencing identified NOTCH1 as a direct downstream of YTHDF1. YTHDF1 bound to m6A modified NOTCH1 mRNA to enhance its stability and translation, which led to increased NOTCH1 target genes expression. NOTCH1 overexpression rescued HCC stemness in YTHDF1-deficient cells in vitro and in vivo. Lipid nanoparticles targeting YTHDF1 significantly enhanced the efficacy of lenvatinib and sorafenib in HCC in vivo. Taken together, YTHDF1 drives HCC stemness and drug resistance through an YTHDF1-m6A-NOTCH1 epitranscriptomic axis, and YTHDF1 is a potential therapeutic target for treating HCC. SIGNIFICANCE: Inhibition of YTHDF1 expression suppresses stemness of hepatocellular carcinoma cells and enhances sensitivity to targeted therapies, indicating that targeting YTHDF1 may be a promising therapeutic strategy for liver cancer.

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA. METHODS: RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment. RESULTS: A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway. CONCLUSIONS: The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.

Profiles of Intestinal Flora in Breastfed Obese Children and Selecting Functional Strains Against Obesity.

SCOPE: Breast milk has the potential to prevent childhood obesity by providing probiotics, but there are still instances of obesity in breastfed children. METHODS AND RESULTS: This study investigates the difference in intestinal flora structure between breastfed children with obesity (OB-BF) and normal-weight breastfed children (N-BF). Building upon this foundation, it employs both cell and mouse models to identify an antiobesity strain within the fecal matter of N-BF children and explore its underlying mechanisms. The results reveal a reduction in lactobacillus levels within the intestinal flora of OB-BF children compared to N-BF children. Consequently, Lactobacillus plantarum H-72 (H-72) is identified as a promising candidate due to its capacity to stimulate glucagon-like peptide-1 (GLP-1) secretion in enteroendocrine cells (ECCs). In vivo, H-72 effectively increases serum GLP-1 concentration, reduces food intake, regulates the expression of genes related to energy metabolism (SCD-1, FAS, UCP-1, and UCP-3), and regulates gut microbiota structure in mice. Moreover, the lipoteichoic acid of H-72 activates toll-like receptor 4 to enhanced GLP-1 secretion in STC-1 cells. CONCLUSIONS: L. plantarum H-72 is screened out for its potential antiobesity effect, which presents a potential and promising avenue for future interventions aimed at preventing pediatric obesity in breastfed children.

Comparison of the clinical outcomes of patients with stage IA-IIA2 cervical adenocarcinoma and squamous cell carcinoma after radical hysterectomy: A propensity score-matched real-world analysis.

OBJECTIVE: To compare the pathological findings and survival outcomes of patients with 2009 FIGO stage IA-IIA2 cervical cancer between groups with adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using the Chinese Cervical Cancer Clinical (FOUR-C) study database. METHODS: Patients from 2004 to 2018 with cervical ADC and SCC who underwent radical hysterectomy were identified through the FOUR-C database. Propensity score matching (PSM) was conducted to balance baseline clinicopathological characteristics. The Kaplan-Meier method and Cox regression analysis were used to evaluate the prognostic effect of ADC on the 5-year overall survival (OS). RESULTS: We identified 1611 (9.8%) patients with ADC and 14 894 (90.2%) patients with SCC. Compared with SCC, ADC was significantly associated with an increased risk of death (odds ratio [OR] 1.40, 95% CI 1.12-1.74) and disease progression (OR 1.34, 95% CI 1.14-1.57). ADC had a greater propensity for lymph node metastasis, uterine corpus invasion, perineural invasion, and ovarian metastases than SCC (P < 0.05). After 1:2 PSM, significant differences were still observed between these two histology subtypes (OS: OR 1.43, 95% CI 1.10-1.86; DFS: OR 1.45, 95% CI 1.19-1.76). The subgroup analysis further showed a worse prognosis for patients with ADC than for patients with SCC among patients with any of the high- or intermediate- risk factors (OR 1.60, 95% CI 1.21-2.12), but no significant differences were observed for the patients with no risk factors (OR 0.71, 95% CI 0.32-1.58). CONCLUSION: ADC is an independent prognostic factor for shorter survival in surgically treated patients with cervical cancer presenting intermediate- or high-risk factors but does not affect survival outcomes in patients without any risk factors.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Alterations in cellular metabolism under different grades of glioma staging identified based on a multi-omics analysis strategy.

Glioma is a type of brain tumor closely related to abnormal cell metabolism. Firstly, multiple combinatorial sequencing studies have revealed this relationship. Genomic studies have identified gene mutations and gene expression disorders related to the development of gliomas, which affect cell metabolic pathways. In addition, transcriptome studies have revealed the genes and regulatory networks that regulate cell metabolism in glioma tissues. Metabonomics studies have shown that the metabolic pathway of glioma cells has changed, indicating their distinct energy and nutritional requirements. This paper focuses on the retrospective analysis of multiple groups combined with sequencing to analyze the changes in various metabolites during metabolism in patients with glioma. Finally, the changes in genes, regulatory networks, and metabolic pathways regulating cell metabolism in patients with glioma under different metabolic conditions were discussed. It is also proposed that multi-group metabolic analysis is expected to better understand the mechanism of abnormal metabolism of gliomas and provide more personalized methods and guidance for early diagnosis, treatment, and prognosis evaluation of gliomas.

Identification of M5c regulator-medicated methylation modification patterns for prognosis and immune microenvironment in glioma.

Glioma is a common intracranial tumor and is generally associated with poor prognosis. Recently, numerous studies illustrated the importance of 5-methylcytosine (m5C) RNA modification to tumorigenesis. However, the prognostic value and immune correlation of m5C in glioma remain unclear. We obtained RNA expression and clinical information from The Cancer Genome Atlas (TCGA) and The Chinese Glioma Genome Atlas (CGGA) datasets to analyze. Nonnegative matrix factorization (NMF) was used to classify patients into two subgroups and compare these patients in survival and clinicopathological characteristics. CIBERSORT and single-sample gene-set algorithm (ssGSEA) methods were used to investigate the relationship between m5C and the immune environment. The Weighted correlation network analysis (WGCNA) and univariate Cox proportional hazard model (CoxPH) were used to construct a m5C-related signature. Most of m5C RNA methylation regulators presented differential expression and prognostic values. There were obvious relationships between immune infiltration cells and m5C regulators, especially NSUN7. In the m5C-related module from WGCNA, we found SEPT3, CHI3L1, PLBD1, PHYHIPL, SAMD8, RAP1B, B3GNT5, RER1, PTPN7, SLC39A1, and MXI1 were prognostic factors for glioma, and they were used to construct the signature. The great significance of m5C-related signature in predicting the survival of patients with glioma was confirmed in the validation sets and CGGA cohort.