Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes.

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

Advanced Hydrogels in Breast Cancer Therapy.

Breast cancer is the most common malignancy among women and is the second leading cause of cancer-related death for women. Depending on the tumor grade and stage, breast cancer is primarily treated with surgery and antineoplastic therapy. Direct or indirect side effects, emotional trauma, and unpredictable outcomes accompany these traditional therapies, calling for therapies that could improve the overall treatment and recovery experiences of patients. Hydrogels, biomimetic materials with 3D network structures, have shown great promise for augmenting breast cancer therapy. Hydrogel implants can be made with adipogenic and angiogenic properties for tissue integration. 3D organoids of malignant breast tumors grown in hydrogels retain the physical and genetic characteristics of the native tumors, allowing for post-surgery recapitulation of the diseased tissues for precision medicine assessment of the responsiveness of patient-specific cancers to antineoplastic treatment. Hydrogels can also be used as carrier matrices for delivering chemotherapeutics and immunotherapeutics or as post-surgery prosthetic scaffolds. The hydrogel delivery systems could achieve localized and controlled medication release targeting the tumor site, enhancing efficacy and minimizing the adverse effects of therapeutic agents delivered by traditional procedures. This review aims to summarize the most recent advancements in hydrogel utilization for breast cancer post-surgery tissue reconstruction, tumor modeling, and therapy and discuss their limitations in clinical translation.

[Clinical study of prone positioning in invasive respiratory support for neonatal respiratory distress syndrome]. / ä¿¯å§ä½åœ¨æ–°ç”Ÿå„¿å‘¼å¸çª˜è¿«ç»¼åˆå¾æœ‰åˆ›å‘¼å¸æ”¯æŒä¸­çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support. METHODS: A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital, involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS. The infants were randomly divided into a supine group (37 infants) and a prone group (40 infants). Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position, continuing in this cycle until weaning from the ventilator. The effectiveness and safety of the two approaches were compared. RESULTS: At 6 hours after enrollment, the prone group showed lower arterial blood carbon dioxide levels, inspired oxygen concentration, oxygenation index, rates of tracheal intubation bacterial colonization, and Neonatal Pain, Agitation and Sedation Scale scores compared to the supine group (P<0.05). There were no significant differences between the groups in terms of pH, arterial oxygen pressure, positive end-expiratory pressure, duration of mechanical ventilation, accidental extubation, ventilator-associated pneumonia, air leak syndrome, skin pressure sores, feeding intolerance, and grades II-IV intraventricular hemorrhage (P>0.05). CONCLUSIONS: Compared to supine positioning, prone ventilation effectively improves oxygenation, increases comfort, and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS, without significantly increasing adverse reactions.

Cadonilimab with chemotherapy in HER2-negative gastric or gastroesophageal junction adenocarcinoma: the phase 1b/2 COMPASSION-04 trial.

Treatment with anti-programmed cell death protein 1 (PD-1) therapy and chemotherapy prolongs the survival of patients with unresectable advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The benefit from anti-PD-1 therapy is enriched in patients with programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS)-positive or CPS-high tumors compared with patients with PD-L1 CPS-negative or CPS-low tumors. In this phase 1b/2 study, we evaluated the efficacy and safety of cadonilimab, a bispecific antibody targeting PD-1 and cytotoxic T-lymphocyte antigen-4, plus chemotherapy as first-line treatment in patients with human epidermal growth factor receptor 2-negative unresectable advanced or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was the recommended phase 2 dose (RP2D) for phase 1b and the objective response rate for phase 2. Secondary endpoints included disease control rate, duration of response, time to response, progression-free survival, overall survival (OS) and safety. The primary endpoint was met. No dose-limiting toxicities were observed during dose escalation in phase 1b; the recommended phase 2 dose was determined as 6 mg kg-1 every 2 weeks. The objective response rate was 52.1% (95% confidence interval (CI) = 41.6-62.5), consisting of complete and partial responses in 4.3% and 47.9% of patients, respectively. The median duration of response, progression-free survival and OS were 13.73 months (95% CI = 7.79-19.12), 8.18 months (95% CI = 6.67-10.48) and 17.48 months (95% CI = 12.35-26.55), respectively. The median OS in patients with a PD-L1 CPS ≥ 5 was 20.32 months (95% CI = 4.67-not estimable); in patients with a PD-L1 CPS < 1, the median OS reached 17.64 months (95% CI = 11.63-31.70). The most common treatment-related grade 3 or higher adverse events were decreased neutrophil count (19.1%), decreased platelet count (16.0%), anemia (12.8%) and decreased leukocyte count (8.5%). No new safety signal was identified. The current regimen showed promising clinical activity and manageable safety in patients with gastric or GEJ adenocarcinoma regardless of PD-L1 expression. Chinadrugtrials.org.cn registration: CTR20182027.

Enhancing Surface Hydroxyl Group Modulation on Carbon Nitride Boosts the Effectiveness of Photodynamic Treatment for Brain Glioma.

The effectiveness of photodynamic therapy (PDT) in treating brain gliomas is limited by the solubility of photosensitizers and the production of reactive oxygen species (ROS), both of which are influenced by the concentration of photosensitizers and catalyst active sites. In this study, we developed a controllable surface hydroxyl concentration for the photosensitizer CN11 to address its poor water solubility issue and enhance PDT efficacy in tumor treatment. Compared to pure g-C3N4 (CN), CN11 exhibited 4.6 times higher hydrogen peroxide production under visible light, increased incidence of the n → π* electron transition, and provided more available reaction sites for cytotoxic ROS generation. These findings resulted in a 2.43-fold increase in photodynamic treatment efficacy against brain glioma cells. Furthermore, in vivo experiments conducted on mice demonstrated that CN11 could be excreted through normal cell metabolism with low cytotoxicity and high biosafety, effectively achieving complete eradication of tumor cells.

Preclinical imaging evaluation of a bispecific antibody targeting hPD1/CTLA4 using humanized mice.

BACKGROUND: The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. METHODS: First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. RESULTS: The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. CONCLUSIONS: The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice.

FBL Promotes LPS-Induced Neuroinflammation by Activating the NF-κB Signaling Pathway.

Purpose: Neuroinflammation occurs in response to central nervous system (CNS) injury, infection, stimulation by toxins, or autoimmunity. We previously analyzed the downstream molecular changes in HT22 cells (mouse hippocampal neurons) upon lipopolysaccharide (LPS) stimulation. We detected elevated expression of Fibrillarin (FBL), a nucleolar methyltransferase, but the associated proinflammatory mechanism was not systematically elucidated. The aim of this study was to investigate the underlying mechanisms by which FBL affects neuroinflammation. Methods: RT-real-time PCR, Western blotting and immunofluorescence were used to assess the mRNA and protein expression of FBL in HT22 cells stimulated with LPS, as well as the cellular localization and fluorescence intensity of FBL. BAY-293 (a son of sevenless homolog 1 (SOS1) inhibitor), SR11302 (an activator protein-1 (AP-1) inhibitor) and KRA-533 (a KRAS agonist) were used to determine the molecular mechanisms underlying the effect of FBL. AP-1 was predicted to be the target protein of FBL by molecular docking analysis, and validation was performed with T-5224 (an AP-1 inhibitor). In addition, the downstream signaling pathways of FBL were identified by transcriptome sequencing and verified by RT-real-time PCR. Results: LPS induced FBL mRNA and protein expression in HT22 cells. In-depth mechanistic studies revealed that when we inhibited c-Fos, AP-1, and SOS1, FBL expression decreased, whereas FBL expression increased when KRAS agonists were used. In addition, the transcript levels of inflammatory genes in the NF-kB signaling pathway (including CD14, MYD88, TNF, TRADD, and NFKB1) were elevated after the overexpression of FBL. Conclusion: LPS induced the expression of FBL in HT22 cells through the RAS/MAPK signaling pathway, and FBL further activated the NF-kB signaling pathway, which promoted the expression of relevant inflammatory genes and the release of cytokines. The present study reveals the mechanism by which FBL promotes neuroinflammation and offers a potential target for the treatment of neuroinflammation.

Semen promotes oocyte development in Sebastesschlegelii elucidating ovarian development dynamics in live-bearing fish.

In some vertebrates and invertebrates, semen release factors affecting female physiology and behavior. Here, we report that semen delivered to females is potentially beneficial for promoting oocyte development in a viviparous teleost, Sebastes schlegelii. 88% of mated ovaries develop normally and give birth to larval fish, whereas 61% of non-mated ovaries are arrested in the previtellogenic stage. Semen's significant role (p < 0.0001) in promoting oocyte development may involve remodeling follicular cells and regulating the expression of the extracellular matrix, which facilitates cell communication. Furthermore, the ovarian response to semen may influence the brain, affecting hormone release, follicular cell development and steroid production, and crucial for oocyte growth. This mechanism, which could potentially delay maternal investment in offspring until male genetic input occurs to avoid energy wastage, has not been previously described in teleosts. These findings enhance our understanding of ovarian development in viviparous fish, with broader implications for reproductive biology.

Preso enhances mGluR1-mediated excitotoxicity by modulating the phosphorylation of mGluR1-Homer1 complex and facilitating an ER stress after traumatic brain injury.

Glutamate receptor (GluR)-mediated excitotoxicity is an important mechanism causing delayed neuronal injury after traumatic brain injury (TBI). Preso, as a core scaffolding protein of postsynaptic density (PSD), is considered an important regulator during excitotoxicity and TBI and combines with glutamate receptors to form functional units for excitatory glutamatergic neurotransmission, and elucidating the mechanisms of these functional units will provide new targets for the treatment of TBI. As a multidomain scaffolding protein, Preso directly interacts with metabotropic GluR (mGluR) and another scaffold protein, Homer. Because the mGluR-Homer complex plays a crucial role in TBI, modulation of this complex by Preso may be an important mechanism affecting the excitotoxic damage to neurons after TBI. Here, we demonstrate that Preso facilitates the interaction between metabotropic mGluR1 and Homer1 to activate mGluR1 signaling and cause excitotoxic neuronal injury and endoplasmic reticulum (ER) stress after TBI. The regulatory effect of Preso on the mGluR1-Homer1 complex is dependent on the direct association between Preso and this complex and also involves the phosphorylation of the interactive binding sites of mGluR1 and Homer1 by Preso. Further studies confirmed that Preso, as an adaptor of cyclin-dependent kinase 5 (CDK5), promotes the phosphorylation of the Homer1-binding site on mGluR1 by CDK5 and thereby enhances the interaction between mGluR1 and Homer1. Preso can also promote the formation of the mGluR1-Homer1 complex by inhibiting the phosphorylation of the Homer1 hinge region by Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα). Based on these molecular mechanisms, we designed several blocking peptides targeting the interaction between Preso and the mGluR1-Homer1 complex and found that directly disrupting the association between mGluR1 and scaffolding proteins significantly promotes the recovery of motor function after TBI.

Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles.

Ischemic stroke is a fatal and disabling disease worldwide and imposes a significant burden on society. At present, biological markers that can be conveniently measured in body fluids are lacking for the diagnosis of ischemic stroke, and there are no effective treatment methods to improve neurological function after ischemic stroke. Therefore, new ways of diagnosing and treating ischemic stroke are urgently needed. The neurovascular unit, composed of neurons, astrocytes, microglia, and other components, plays a crucial role in the onset and progression of ischemic stroke. Extracellular vesicles are nanoscale lipid bilayer vesicles secreted by various cells. The key role of extracellular vesicles, which can be released by cells in the neurovascular unit and serve as significant facilitators of cellular communication, in ischemic stroke has been extensively documented in recent literature. Here, we highlight the role of neurovascular unit-derived extracellular vesicles in the diagnosis and treatment of ischemic stroke, the current status of extracellular vesicle engineering for ischemic stroke treatment, and the problems encountered in the clinical translation of extracellular vesicle therapies. Extracellular vesicles derived from the neurovascular unit could provide an important contribution to diagnostic and therapeutic tools in the future, and more studies in this area should be carried out.

Lattice Rotation and Deformation Mechanisms under Tensile Loading in a Single-Crystal Superalloy with [001] Misorientation.

This study investigates how deviation angles close to the [001] orientation affect the tensile properties and deformation behavior of a nickel-based single-crystal superalloy at room temperature. The research focuses on samples with deviation angles of 3°, 8°, and 13° from the [001] orientation and examines their strength and ductility. We employed scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM) to explore the deformation micro-mechanisms at varying angles. Findings reveal that strength decreases and ductility increases as the deviation angle widens within the [001] vicinity. The study emphasizes that <110> octahedral slip-driven crystal slip and rotation are crucial for understanding tensile deformation. The deformation differences in samples at varying angles are attributed to the differential engagement of mechanisms. Specifically, at lower angles, reduced ductility and increased strength are due to short lattice rotation paths and work hardening causing superlattice stacking faults (SSFs) to slip in two directions on the {111} plane within the γ' phase. As the angles increase, the lattice rotation paths extend, and Shockley partial dislocations (a/6<112>) accumulate in γ channels. This process, involving SSFs moving in a single direction within the γ' phase, results in higher ductility and reduced strength.

[In vitro expression and functional analyses of the mutants p.R243Q, p.R241C and p.Y356X of the human phenylalanine hydroxylase]. / äººè‹¯ä¸™æ°¨é ¸ç¾ŸåŒ–é ¶çªå˜ä½“p.R243Q、p.R241C和p.Y356Xçš„ä½“å¤–è¡¨è¾¾åŠåŠŸèƒ½ç ”ç©¶.

OBJECTIVES: To study the in vitro expression of three phenylalanine hydroxylase (PAH) mutants (p.R243Q, p.R241C, and p.Y356X) and determine their pathogenicity. METHODS: Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein. Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells. Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants, and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay. RESULTS: Bioinformatics analysis predicted that all three mutants were pathogenic. The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control (P>0.05), while the mRNA expression level of the p.Y356X mutant significantly decreased (P<0.05). The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control (P<0.05). The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control (P<0.05), while there was no significant difference between the p.R243Q mutant and the wild type control (P>0.05). CONCLUSIONS: p.R243Q, p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells, with p.R241C and p.Y356X mutants also affecting the function of PAH protein. These three PAH mutants are to be pathogenic.

Nuclear translocation of metabolic enzyme PKM2 participates in high glucose-promoted HCC metastasis by strengthening immunosuppressive environment.

Although some cohort studies have indicated a close association between diabetes and HCC, the underlying mechanism about the contribution of diabetes to HCC progression remains largely unknown. In the study, we applied a novel HCC model in SD rat with diabetes and a series of high glucose-stimulated cell experiments to explore the effect of a high glucose environment on HCC metastasis and its relevant mechanism. Our results uncovered a novel regulatory mechanism by which nuclear translocation of metabolic enzyme PKM2 mediated high glucose-promoted HCC metastasis. Specifically, high glucose-increased PKM2 nuclear translocation downregulates chemerin expression through the redox protein TRX1, and then strengthens immunosuppressive environment to promote HCC metastasis. To the best of our knowledge, this is the first report to elucidate the great contribution of a high glucose environment to HCC metastasis from a new perspective of enhancing the immunosuppressive microenvironment. Simultaneously, this work also highlights a previously unidentified non-metabolic role of PKM2 and opens a novel avenue for cross research and intervention for individuals with HCC and comorbid diabetes.

Biochar derived from alkali-treated sludge residue regulates anaerobic digestion: Enhancement performance and potential mechanisms.

Biochar produced from bio-wastes has been widely used to promote the performance of anaerobic digestion. Waste activated sludge (WAS) is considered as a kind of popular precursor for biochar preparation, but the abundant resources in WAS were neglected previously. In this study, the roles of biochar prepared from raw, pretreated, and fermented sludge on anaerobic digestion were investigated. That is, parts of carbon sources and nutrients like polysaccharides, proteins, and phosphorus were firstly recovered after sludge pretreatment or fermentation, and then the sludge residuals were used as raw material to prepare biochar. The methane yield improved by 22.1% with adding the biochar (AK-BC) prepared by sludge residual obtained from alkaline pretreatment. Mechanism study suggested that the characteristics of AK-BC like specific surface area and defect levels were updated. Then, the conversion performance of intermediate metabolites and electro-activities of extracellular polymeric substances were up-regulated. As a result, the activity of electron transfer was increased with the presence of AK-BC, with increase ratio of 21.4%. In addition, the electroactive microorganisms like Anaerolineaceae and Methanosaeta were enriched with the presence of AK-BC, and the potential direct interspecies electron transfer was possibly established. Moreover, both aceticlastic and CO2-reducing methanogenesis pathways were improved by up-regulating related enzymes. Therefore, the proposed strategy can not only obtain preferred biochar but also recover abundant resources like carbon source, nutrients, and bioenergy.

Designing transparent piezoelectric metasurfaces for adaptive optics.

Simultaneously generating various motion modes with high strains in piezoelectric devices is highly desired for high-technology fields to achieve multi-functionalities. However, traditional approach for designing multi-degrees-of-freedom systems is to bond together several multilayer piezoelectric stacks, which generally leads to cumbersome and complicated structures. Here, we proposed a transparent piezo metasurface to achieve various types of strains in a wide frequency range. As an example, we designed a ten-unit piezo metasurface, which can produce high strains (ε3 = 0.76%), and generate linear motions along X-, Y- and Z-axis, rotary motions around X-, Y- and Z-axis as well as coupled modes. An adaptive lens based on the proposed piezo metasurface was demonstrated. It can realize a wide range of focal length (35.82 cm ~ ∞) and effective image stabilization with relatively large displacements (5.05 µm along Y-axis) and tilt angles (44.02' around Y-axis). This research may benefit the miniaturization and integration of multi-degrees-of-freedom systems.

Self-Healing Hydrogen-Bonded Organic Frameworks for Low-Concentration Ammonia Capture.

The self-healing behavior has been extensively used in intelligent sensing systems capable of molecular recognition. However, most rigid crystalline frameworks, once collapsed under external stimuli like pressure, heat, or vacuum, could hardly recover to their crystalline phases under ambient conditions. Here, we report the self-healing of a new microporous hydrogen-bonded organic framework, FDU-HOF-3 (FDU = Fudan University), for ammonia (NH3) capture and compared it with the established mesoporous HOF-101. With the introduction of low-concentration NH3 into the pores, the HOFs became disordered but were then simply heated under a vacuum to return to their original crystalline states after NH3 removal. Close characterizations revealed that the repeatable self-healing behavior of these HOFs was achieved due to the COOH-NH3 acid-base interactions accompanied by the breaking and regeneration of complementary COOH-COOH hydrogen bonds. FDU-HOF-3 showed a record-capturing capability for low-concentration NH3 (8.13 mmol/g at 25 mbar) among all HOFs and displayed a quick photocurrent decrease after exposure to 250 ppm NH3 for less than 10 s. These self-healing HOFs were used to capture and release NH3 for over 10 cycles without any decrease in the adsorption capacities.

Montelukast Sodium to Prevent and Treat Bronchopulmonary Dysplasia in Very Preterm Infants: A Quasi-Randomized Controlled Trial.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, p = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, p = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.

Causal association of gut microbiota and esophageal cancer: a Mendelian randomization study.

Introduction: Despite the growing body of evidence, the link between the gut microbiota and different types of tumors, such as colorectal, gastric, and liver cancer, is becoming more apparent. The gut microbiota can be used as a reference for evaluating various diseases, including cancer, and can also act as risk factors or preventive factors. However, the specific connection between the gut microbiota and the advancement of esophageal cancer has yet to be investigated. Therefore, the aim of this research is to clarify the possible causal influence of intestinal microorganisms on the vulnerability to esophageal cancer through the utilization of Mendelian randomization (MR) studies. Methods: In this study, we employed a two-sample Mendelian randomization approach to evaluate the unbiased causal association between 150 different gut microbiota types and the occurrence of esophageal cancer. Following the selection from the IEU GWAS database and SNP filtration, we utilized various MR statistical techniques on the suitable instrumental variables. These included IVW methods, employing inverse variance weighting. Additionally, we performed a range of sensitivity analyses to confirm the heterogeneity and pleiotropy of the instrumental variables, thus ensuring the reliability of the outcomes. Results: The increased likelihood of developing esophageal cancer is linked to the genetically predicted high levels of Gordonibacter, Oxalobacter, Coprobacter, Veillonella, Ruminiclostridium 5, Ruminococcus 1, and Senegalimasilia genera. Conversely, a decreased risk of esophageal cancer is associated with the high abundance of Turicibacter, Eubacterium oxidoreducens group, Romboutsia, and Prevotella 9 genera. No heterogeneity and pleiotropy were detected in the sensitivity analysis. Discussion: We found that 11 types of gut microbial communities are associated with esophageal cancer, thereby confirming that the gut microbiota plays a significant role in the path.

Kinase D-interacting Substrate of 220 kDa Is Overexpressed in Gastric Cancer and Associated With Local Invasion.

BACKGROUND/AIM: Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning protein (ARMS), is a transmembrane scaffold protein. Deregulated Kidins220 has been observed in various malignancies including melanoma, glioma, neuroblastoma, prostate cancer, pancreatic cancer, and ovarian cancer. MATERIALS AND METHODS: In the current study, Kidins220 expression was determined at transcript and protein levels. A Kidins220 knockdown cell model was established to identify its role in cellular functions including cell cycle, proliferation, and invasion. Cell signalling was analysed by protein array and the TCGA gastric cancer cohort. RESULTS: Kidins220 transcript levels were significantly increased in gastric tumours, compared with adjacent normal tissues. More advanced tumours (TNMIII and TNMIV) exhibited higher protein levels of Kidins220 compared with early-stage tumours (TNMI and TNMII). Increased expression of Kidins220 in gastric cancer was associated with poorer overall survival. Loss of Kidins220 promoted cell invasion and adhesion of gastric cancer and correlated to epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) signalling. Knockdown of Kidins220 promoted proliferation of gastric cancer cells with an increased population at the G2/M phase. CONCLUSION: Our study identified increased expression of Kidins220 in gastric cancer, which is associated with disease progression and poor prognosis. However, Kidins220 presented an inhibitory effect on the proliferation, invasion, and adhesion through a regulation of EMT, MMP and cell cycle.