Single-cell and Bulk Transcriptomic Analyses Reveal a Stemness and Circadian Rhythm Disturbance-related Signature Predicting Clinical Outcome and Immunotherapy Response in Hepatocellular Carcinoma.

AIMS: Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response. BACKGROUND: Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells. OBJECTIVE: Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC. METHODS: The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature. RESULTS: A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts. CONCLUSIONS: In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.

A competitive-type photoelectrochemical aptasensor for 17 beta-estradiol detection in microfluidic devices based on a novel Au@Cd:SnO2/SnS2 nanocomposite.

A competitive-type photoelectrochemical (PEC) aptasensor coupled with a novel Au@Cd:SnO2/SnS2 nanocomposite was designed for the detection of 17ß-estradiol (E2) in microfluidic devices. The designed Au@Cd:SnO2/SnS2 nanocomposites exhibit high photoelectrochemical activity owing to the good matching of cascade band-edge and the efficient separation of photo-generated e-/h+ pairs derived from the Cd-doped defects in the energy level. The Au@Cd:SnO2/SnS2 nanocomposites were loaded into carbon paste electrodes (CPEs) to immobilize complementary DNA (cDNA) and estradiol aptamer probe DNA (E2-Apt), forming a double-strand DNA structure on the CPE surface. As the target E2 interacts with the double-strand DNA, E2-Apt is sensitively released from the CPE, subsequently increasing the photocurrent intensity due to the reduced steric hindrance of the electrode surface. The competitive-type sensing mechanism, combined with high PEC activity of the Au@Cd:SnO2/SnS2 nanocomposites, contributed to the rapid and sensitive detection of E2 in a "signal on" manner. Under the optimized conditions, the PEC aptasensor exhibited a linear range from 1.0 × 10-13 mol L-1 to 3.2 × 10-6 mol L-1 and a detection limit of 1.2 × 10-14 mol L-1 (S/N = 3). Moreover, the integration of microfluidic device with smartphone controlled portable electrochemical workstation enables the on-site detection of E2. The small sample volume (10 µL) and short analysis time (40 min) demonstrated the great potential of this strategy for E2 detection in rat serum and river water. With these advantages, the PEC aptasensor can be utilized for point-of-care testing (POCT) in both clinical and environmental applications.

SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma.

BACKGROUND: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. METHODS: Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. RESULTS: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. CONCLUSIONS: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

Cardiovascular safety of febuxostat versus allopurinol among the Asian patients with or without gout: A systematic review and meta-analysis.

The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.

Association between dietary antioxidant capacity and type 2 diabetes mellitus in Chinese adults: a population-based cross-sectional study.

BACKGROUND: Higher intakes of dietary antioxidants have been linked to a lower type 2 diabetes mellitus (T2DM) risk. However, few studies have comprehensively examined the overall dietary antioxidant capacity, assessed by dietary antioxidant quality scores (DAQS) and dietary total antioxidant capacity (DTAC), related to T2DM risk, especially in populations consuming relatively monotonous diets. This study aimed to evaluate the associations of DAQS, DTAC, and T2DM among rural Chinese adults. METHODS: Data from 12,467 participants from the Natural Population Cohort of Northwest China: Ningxia Project was analyzed. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. DAQS were calculated based on vitamins A, C, and E, zinc (Zn), and selenium (Se) intake. DTAC was estimated using the ferric-reducing ability of plasma assay. Logistic regression models were used to evaluate the associations of DAQS and DTAC with T2DM risk. Restricted cubic splines were used to assess potential non-linear relationships between DTAC and T2DM. RESULTS: T2DM was observed in 1,238 (9.9%) participants. After adjusting for confounders, compared to the lowest tertiles (T1) of DAQS, the odds ratios (ORs) for T2DM were 1.03 (95% CI 0.82-1.30) in T2 and 0.85 (95% CI 0.68-1.06) in T3 (P = 0.010). Compared to T1, the ORs for T2DM in the highest T3 were 0.78 (95% CI 0.67-0.91, P-trend = 0.008) for vitamin A, 1.34 (95% CI 1.15-1.56, P-trend < 0.001) for vitamin E, 0.83 (95% CI 0.71-0.97, P-trend = 0.007) for Se, and 0.86 (95% CI 0.74-1.01, P-trend = 0.033) for Zn. Compared to the lowest quartile(Q1) of DTAC, the OR in the highest Q4 was 0.96 (95% CI 0.80-1.17, P-trend = 0.024) for T2DM. A non-linear relationship was observed between DATC and T2DM. CONCLUSION: Higher DAQS and DATC were associated with a lower T2DM risk, suggesting that consuming antioxidant-rich foods may reduce the T2DM risk.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.

Effects of light qualities on growth and physiological-biochemical traits of Scutellaria baicalensis.

Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem Ⅱ (ФPSⅡ), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.

IGF2BP3 enhances lipid metabolism in cervical cancer by upregulating the expression of SCD.

Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.

Dual-energy CT-based radiomics in predicting EGFR mutation status non-invasively in lung adenocarcinoma.

Objectives: Patients with epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD) can benefit from individualized targeted therapy. This study aims to develop, compare, analyse prediction models based on dual-energy spectral computed tomography (DESCT) and CT-based radiomic features to non-invasively predict EGFR mutation status in LUAD. Materials and methods: Patients with LUAD (n = 175), including 111 patients with and 64 patients without EGFR mutations, were enrolled in the current study. All patients were randomly divided into a training dataset (122 cases) and validation dataset (53 cases) at a ratio of 7:3. After extracting CT-based radiomic, DESCT and clinical features, we built seven prediction models and a nomogram of the best prediction. Receiver operating characteristic (ROC) curves and the mean area under the curve (AUC) values were used for comparisons among the models to obtain the best prediction model for predicting EGFR mutations. Results: The best distinguishing ability is the combined model incorporating radiomic, DESCT and clinical features for predicting the EGFR mutation status with an AUC of 0.86 (95 % CI: 0.79-0.92) in the training group and an AUC value of 0.83 (95 % CI: 0.73, 0.96) in the validation group. Conclusions: Our study provides a predictive nomogram non-invasively with a combination of CT-based radiomic, DESCT and clinical features, which can provide image-based biological information for targeted therapy of LUAD with EGFR mutations.

Dihydroartemisinin abolishes cisplatin-induced nephrotoxicity in vivo.

Dihydroartemisinin (DHA), a derivative of artemisinin which is primarily used to treat malaria in clinic, also confers protective effect on lipopolysaccharide-induced nephrotoxicity. While, the activities of DHA in cisplatin (CDDP)-caused nephrotoxicity are elusive. To investigate the role and underlying mechanism of DHA in CDDP-induced nephrotoxicity. Mice were randomly separated into four groups: normal, CDDP, and DHA (25 and 50 mg/kg were orally injected 1 h before CDDP for consecutive 10 days). All mice except the normal were single injected intraperitoneally with CDDP (22 mg/kg) for once on the 7th day. Combined with quantitative proteomics and bioinformatics analysis, the impact of DHA on renal cell apoptosis, oxidative stress, biochemical indexes, and inflammation in mice were investigated. Moreover, a human hepatocellular carcinoma cells xenograft model was established to elucidate the impact of DHA on tumor-related effects of CDDP. DHA reduced the levels of creatinine (CREA) (p < 0.01) and blood urea nitrogen (BUN) (p < 0.01), reversed CDDP-induced oxidative, inflammatory, and apoptosis indexes (p < 0.01). Mechanistically, DHA attenuated CDDP-induced inflammation by inhibiting nuclear factor κB p65 (NFκB p65) expression, and suppressed CDDP-induced renal cell apoptosis by inhibiting p63-mediated endogenous and exogenous apoptosis pathways. Additionally, DHA alone significantly decreased the tumor weight and did not destroy the antitumor effect of CDDP, and did not impact AST and ALT. In conclusion, DHA prevents CDDP-triggered nephrotoxicity via reducing inflammation, oxidative stress, and apoptosis. The mechanisms refer to inhibiting NFκB p65-regulated inflammation and alleviating p63-mediated mitochondrial endogenous and Fas death receptor exogenous apoptosis pathway.

PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma.

The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine 2,3-dioxygenase 1 (IDO1), a prospective target for immunotherapy. PABPC1L was markedly upregulated in RCC, and high PABPC1L expression correlated with unfavorable prognosis and resistance to ICB. PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. PABPC1L enhanced the stability of JAK2 mRNA, leading to increased JAK2-STAT1 signaling that induced IDO1 expression. Additionally, PABPC1L-induced activation of the JAK2-STAT1 axis created a positive feedback loop to promote PABPC1L transcription. Conversely, loss of PABPC1L diminished IDO1 expression, mitigated cytotoxic T-cell suppression, and enhanced responsiveness to anti-PD-1 therapy in patient-derived xenograft models. These findings reveal the crucial role of PABPC1L in facilitating immune evasion in RCC and indicate that inhibiting PABPC1L could be a potential immunotherapeutic approach in combination with ICB to improve patient outcomes. SIGNIFICANCE: PABPC1L functions as a key factor in renal cell carcinoma immune evasion, enhancing IDO1 and impeding T-cell function, and represents a potential target to enhance the efficacy of immune checkpoint blockade therapy.

Rational design of antibodies and development of a novel method for (1-3)-ß-D glucan detection as an alternative to Limulus amebocyte lysate assay.

With advances in medicine, increasing medical interventions have increased the risk of invasive fungal disease development. (1-3)-ß-D glucan (BDG) is a common fungal biomarker in serological tests. However, the scarcity of Limulus resources for BDG detection poses a challenge. This study addresses the need for an alternative to Limulus amebocyte lysate by using BDG mutant antibody for chemiluminescence detection. The wild-type BDG antibody was obtained by immunizing rabbits. An optimal V52HI/N34L Y mutant antibody, which has increased 3.7-fold of the testing efficiency compared to the wild-type antibody, was first achieved by mutating "hot-spot" residues that contribute to strong non-covalent bonds, as determined by alanine scanning and molecular dynamics simulation. The mutant was then applied to develop the magnetic particle chemiluminescence method. 574 clinical samples were tested using the developed method, with a cutoff value of 95 pg/mL set by Limulus amebocyte lysate. The receiver operating characteristic curve demonstrated an area under the curve of 0.905 (95% CI: 0.880-0.929). Chemiluminescence detected an antigen concentration of 89.98 pg/mL, exhibiting a sensitivity of 83.33% and specificity of 89.76%. In conclusion, the results showed a good agreement with Limulus amebocyte lysate and demonstrated the feasibility of using BDG mutant antibodies for invasive fungal disease diagnosis. The new method based on chemiluminescence for detecting BDG could shorten the sample-to-result time to approximately 30 min, rescue Limulus from being endangered and is resource efficient in terms of equipment and the non-use of a skilled technician.

Comparison of the efficacy of fish oil and probiotic supplementation on glucose and lipid metabolism in patients with type 2 diabetes: a systematic review and network meta-analysis.

BACKGROUND: Abnormalities in glucose and lipid metabolism contribute to the progression and exacerbation of type 2 diabetes mellitus (T2DM). Fish oil and probiotics are dietary supplements that have the potential to improve glucose and lipid metabolism. However, their efficacy remains unclear in T2DM patients. METHODS: PubMed, Embase, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) on the efficacy of fish oil or probiotic supplementation in T2DM patients from the database inception to December 13, 2023. Primary outcome indicators encompassed glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR) and blood lipid profile (triglyceride (TG) and total cholesterol (TC). Secondary outcome indicators included inflammatory markers such as tumor necrosis factor -α (TNF-α) and adipocytokine (including leptin and adiponectin). The R software was used for statistical analysis, and GraphPad Prism was used for figure rendering. RESULTS: A total of 60 RCTs involving 3845 T2DM patients were included in the analysis. The results showed that the probiotics (Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, etc.) were more effective in reducing HOMA-IR than fish oil (Surca = 0.935). Bifidobacterium demonstrated the highest efficacy in reducing HbA1c levels (Surca = 0.963). Regarding lipid metabolism, fish oil was superior to probiotics in lowering TG and TC levels (Surca values of 0.978 and 0.902, respectively). Furthermore, fish oil outperformed probiotics in reducing TNF-α (Surca = 0.839) and leptin (Surca = 0.712), and increasing adiponectin levels (Surca = 0.742). Node-splitting analysis showed good consistency (P > 0.05 for direct, indirect, and network comparison across various interventions). CONCLUSIONS: In T2DM patients, fish oil was more effective than probiotics in regulating lipid metabolism. Probiotics outperformed fish oil in regulating glucose metabolism particularly; specifically, Bifidobacterium showed higher efficacy in reducing blood glucose.

Computational Design of Peptide Assemblies.

With the ongoing development of peptide self-assembling materials, there is growing interest in exploring novel functional peptide sequences. From short peptides to long polypeptides, as the functionality increases, the sequence space is also expanding exponentially. Consequently, attempting to explore all functional sequences comprehensively through experience and experiments alone has become impractical. By utilizing computational methods, especially artificial intelligence enhanced molecular dynamics (MD) simulation and de novo peptide design, there has been a significant expansion in the exploration of sequence space. Through these methods, a variety of supramolecular functional materials, including fibers, two-dimensional arrays, nanocages, etc., have been designed by meticulously controlling the inter- and intramolecular interactions. In this review, we first provide a brief overview of the current main computational methods and then focus on the computational design methods for various self-assembled peptide materials. Additionally, we introduce some representative protein self-assemblies to offer guidance for the design of self-assembling peptides.

Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation.

ABBREVIATIONS: AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid - Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.

Preparation and characterization of a novel composite acellular matrix/hyaluronic acid thermosensitive hydrogel for interstitial cystitis/bladder pain syndrome.

Bladder mucosa damage that causes harm to the interstitium is a recognized pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). The intravesical instillation of drugs is an important second-line therapy, but it is often necessary to use drugs repeatedly in the clinic because of their short residence time in the bladder cavity, which alters the therapeutic effect. To overcome this drawback, this study developed a novel composite acellular matrix/hyaluronic acid (HA) thermosensitive hydrogel (HA-Gel) using rabbit small intestinal submucosa extracellular matrix (ECM) as the thermosensitive material and HA as the drug component and examined its composition, microstructure, thermodynamic properties, temperature sensitivity, rheological properties, biocompatibility, drug release, hydrogel residue, and bacteriostatic properties. The study showed HA-Gel was liquid at temperatures of 15-37.5°C and solid at 37.5-50°C, its swelling rate decreased with increasing temperature, and its lower critical solution temperature occurred at approximately 37.5°C. This property made the hydrogel liquid at room temperature convenient for intravesical perfusion and turned into a solid about 1 min after entering the body and rising to body temperature to increase its residence time. Subsequent experiments also proved that the gel residue time of HA-Gel in vivo and the drug release time of HA in vivo could reach more than 5 days, which was significantly higher than that of HA alone, and it had good biocompatibility and antibacterial properties. Therefore, this hydrogel possesses the proper characteristics to possibly make it an ideal dosage form for IC/BPS intravesical instillation therapy.

Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12.

To investigate the effect of chromium and iron on glucose metabolism via the PI3K/Akt/GLUT4 signaling pathway. Skeletal muscle gene microarray data in T2DM (GSE7014) was selected using Gene Expression Omnibus database. Element-gene interaction datasets of chromium and iron were extracted from comparative toxicogenomics database (CTD). Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID online tool. Cell viability, insulin-stimulated glucose uptake, intracellular reactive oxygen species (ROS) level, and protein expression level were measured in C2C12 cells. The bioinformatics research indicated that PI3K/Akt signaling pathway participated in the effects of chromium and iron associated with T2DM. Insulin-stimulated glucose uptake level was significantly higher in chromium picolinate (Cr group) and lower in ammonium iron citrate (FA group) than that for the control group (P < 0.05); chromium picolinate + ammonium iron citrate (Cr + FA group) glucose uptake level was higher than that for the FA group (P < 0.05). Intracellular ROS level was significantly higher in the FAC group than that for the control group (P < 0.05), and that for the Cr + FA group was lower than that for the FA group (P < 0.05). p-PI3K/PI3K, p-Akt/Akt, and GLUT4 levels were significantly lower in the FA group than that for the control group (P < 0.05), and the Cr + FA group had higher levels than the FA group (P < 0.05). Chromium might have a protective effect on iron-induced glucose metabolism abnormalities through the ROS-mediated PI3K/Akt/GLUT4 signaling pathway.

Interaction of estradiol and vitamin D with low skeletal muscle mass among middle-aged and elderly women.

BACKGROUND: Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together. METHODS: Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer. Bivariate logistic regression and multiplicative interaction analyses were used to assess the impact of estradiol level and vitamin D status on low SMM, as well as the combined impact of estradiol and low vitamin D status on low SMM. RESULTS: A total of 287 (9.49%) participants had low SMM, which had lower levels of estradiol and vitamin D concentration than normal SMM group. While, after adjusting the confounding variables, these correlations were maintained in estradiol Q1, Q2, Q3 and vitamin D Q1. Furthermore, the significant combined effect of the highest quartile of estradiol concentrations and non-vitamin D deficiency, and interactions between vitamin D Q1 and estradiol Q2, vitamin D Q1 and estradiol Q3, vitamin D Q2 and estradiol Q1, vitamin D Q3 and estradiol Q3 on low SMM were stably reflected (P for interaction < 0.05). CONCLUSIONS: Estradiol and vitamin D were interrelated with low SMM in middle-aged and elderly women. Combination of estradiol and vitamin D supplements should be encouraged for middle-aged and elderly women who are at risk of muscle atrophy or experiencing muscle atrophy.

The Efficacy and Safety of Parecoxib Multimodal Preemptive Analgesia in Artificial Joint Replacement: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Postoperative pain after artificial joint replacement is intense and remains an unsolved problem. Some studies have shown that parecoxib can provide better analgesia in postoperative multimodal analgesia, however, doubts arise about whether its multimodal preemptive analgesia can reduce postoperative pain. OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the impact of preoperative injection of parecoxib on postoperative pain in patients undergoing artificial joint replacement. STUDY DESIGN: Systematic review and meta-analysis. SETTING: Embase, PubMed, Cochrane Library, CNKI, VIP, Wangfang databases were searched to identify relevant randomized controlled trials. The last search was in May 2022. METHODS: Randomized controlled trials of efficacy and adverse reactions of intra-operative and postoperative injection of parecoxib in artificial joint replacement were collected. The primary outcome was postoperative visual analog scale scores and the secondary outcomes included cumulative postoperative opioid consumption and incidence of adverse reactions. Using the Cochrane systematic review method to screen the studies, evaluate the quality of the included studies, and extract feature information, RevMan 5.4 software performs a meta-analysis of the corresponding research indicators. RESULTS: In total, nine studies were involved in the meta-analysis with 667 patients. The trial and control group were given the same dose of parecoxib or placebo at the same time point before and after surgery. The results showed that compared with the control group, the trial group is associated with substantially reduced visual analog scale scores in 24, 48 h at rest (P < 0.05), visual analog scale scores in 24, 48, 72 h at movement (P < 0.05), dose of opioid need in trial group is notably lower than that in control group (P < 0.05), but shows no obvious effect on visual analog scale scores in 72 h at rest, and adverse events (P > 0.05). LIMITATIONS: The major limitation of this meta-analysis relates to some low-quality studies. CONCLUSIONS: Our results support parecoxib multimodal preemptive analgesia in reducing postoperative acute pain in hip and knee replacement patients, and reduces cumulative opioid consumption without increasing the risk of adverse drug events. Its multimodal preemptive analgesia is safe and effective in hip and knee replacement. PROSPERO REGISTRATION: CRD42022379672.

Safety and efficacy of percutaneous electrocoagulation haemostasis in the treatment of grade IV haemorrhagic cystitis after allogeneic haematopoietic stem cell transplantation in children: a retrospective analysis.

BACKGROUND: To investigate the efficacy and safety of endoscopic electrocoagulation haemostasis via a percutaneous transhepatic approach for the treatment of grade IV haemorrhagic cystitis (HC) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 14 children with severe HC, who were admitted to Hebei Yanda Hospital between July 2017 and January 2020, were analysed retrospectively. There were nine males and five females, with an average age of 8.6 years (range: 3 to 13 years). After an average of 39.6 (7 to 96) days of conservative treatment in the hospital's haematology department, the bladders of all patients were filled with blood clots. A small 2-cm incision was made in the suprapubic area to enter the bladder and quickly clear the blood clots, and a percutaneous transhepatic approach to electrocoagulation and haemostasis was performed. RESULTS: In the 14 children, a total of 16 operations were performed, with an average operation time of 97.1 (31 to 150) min, an average blood clot of 128.1 (80 to 460) mL and an average intraoperative blood loss of 31.9 (20 to 50) mL. There were three cases of postoperative bladder spasm remission after conservative treatment. During the follow-up period of 1 to 31 months, one patient improved after one operation, 11 patients were cured after one operation, and two patients were cured after recurrent haemostasis by secondary electrocoagulation, four of whom died of postoperative non-surgical blood-related diseases and severe lung infections. CONCLUSION: Percutaneous electrocoagulation haemostasis can quickly remove blood clots in the bladders of children after allo-HSCT with grade IV HC. It is a safe and effective minimally invasive treatment.