The Global Incident Gastrointestinal Cancers Attributable to Suboptimal Diets From 1990 to 2018.

BACKGROUND & AIMS: The contribution of suboptimal diets to gastrointestinal (GI) cancer incidence globally remains unquantified, and we aimed to evaluate it. METHODS: Comprehensive meta-analyses and rigorous evidence-grading assessment identified the associations between suboptimal diets and 6 GI cancers and their subtypes. A comparative risk assessment model was used to estimate the proportional attributable burden and attributable rate of GI cancers to suboptimal diets by using the corroborative association estimates. In addition, correlation assessments with the Sociodemographic Index were carried out. RESULTS: In 2018, 21.5% (95% uncertainty interval, 19.1%-24.5%) of incident GI cancer cases globally were attributable to suboptimal diets, maintaining a relatively stable proportion since 1990 (22.4%; 19.7%-25.6%), whereas the absolute diet-attributable cases doubled from 580,862 (510,658-664,076) in 1990 to 1,039,877 (923,482-1,187,244) in 2018. Excessive processed meat consumption (5.9%; 4.2%-7.9%), insufficient fruit intake (4.8%; 3.8%-5.9%), and insufficient whole grain intake (3.6%; 2.8%-5.1%) were the most significant dietary risk factors in 2018, a shift from 1990 when the third major concern was insufficient nonstarchy vegetable intake. In addition, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in both 1990 (31.6%; 27.0%-37.4%) and 2018 (31.6%; 27.3%-36.5%), and a positive correlation (P < .001) between the Sociodemographic Index and the attributable GI cancer incidence was observed. CONCLUSIONS: Although the proportional attributable GI incidence remains relatively stable, the doubling of absolute cases from 1990 to 2018, along with the discrepancies among urbanicity and countries/regions, informs dietary priorities and more targeted preventive measures.

Salmonella Typhimurium alters galactitol metabolism under ciprofloxacin treatment to balance resistance and virulence.

Ciprofloxacin-resistant Salmonella Typhimurium (S. Typhimurium) causes a significant health burden worldwide. A wealth of studies has been published on the contributions of different mechanisms to ciprofloxacin resistance in Salmonella spp. But we still lack a deep understanding of the physiological responses and genetic changes that underlie ciprofloxacin exposure. This study aims to know how phenotypic and genotypic characteristics are impacted by ciprofloxacin exposure, from ciprofloxacin-susceptible to ciprofloxacin-resistant strains in vitro. Here, we investigated the multistep evolution of resistance in replicate populations of S. Typhimurium during 24 days of continuously increasing ciprofloxacin exposure and assessed how ciprofloxacin impacts physiology and genetics. Numerous studies have demonstrated that RamA is a global transcriptional regulator that prominently perturbs the transcriptional landscape of S. Typhimurium, resulting in a ciprofloxacin-resistant phenotype appearing first; the quinolone resistance-determining region mutation site can only be detected later. Comparing the microbial physiological changes and RNA sequencing (RNA-Seq) results of ancestral and selectable mutant strains, the selectable mutant strains had some fitness costs, such as decreased virulence, an increase of biofilm-forming ability, a change of "collateral" sensitivity to other drugs, and inability to utilize galactitol. Importantly, in the ciprofloxacin induced, RamA directly binds and activates the gatR gene responsible for the utilization of galactitol, but RamA deletion strains could not activate gatR. The elevated levels of RamA, which inhibit the galactitol metabolic pathway through the activation of gatR, can lead to a reduction in the growth rate, adhesion, and colonization resistance of S. Typhimurium. This finding is supported by studies conducted in M9 medium as well as in vivo infection models. IMPORTANCE: Treatment of antibiotic resistance can significantly benefit from a deeper understanding of the interactions between drugs and genetics. The physiological responses and genetic mechanisms in antibiotic-exposed bacteria are not well understood. Traditional resistance studies, often retrospective, fail to capture the entire resistance development process and typically exhibit unpredictable dynamics. To explore how clinical isolates of S. Typhimurium respond to ciprofloxacin, we analyzed their adaptive responses. We found that S. Typhimurium RamA-mediated regulation disrupts microbial metabolism under ciprofloxacin exposure, affecting genes in the galactitol metabolic pathways. This disruption facilitates adaptive responses to drug therapy and enhances the efficiency of intracellular survival. A more comprehensive and integrated understanding of these physiological and genetic changes is crucial for improving treatment outcomes.

Anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies show vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in dorsal motor nucleus of vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately 7 times more than cholinergic fibers in main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than these in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than WKY. Norepinephrine (NE) increased, and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of ß-receptors, M- or N-receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves, but not affected by stimulation of subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.

Enriched H3K27Me3 on BMP4 suppresses the osteoblastic differentiation potential of BMSCs in diabetes mellitus.

Diabetes mellitus has been widely acknowledged to have a negative effect on the osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). However, the underlying epigenetic mechanisms associated with this process remain to be elucidated. The goal of the present study was to investigate the effect of diabetes mellitus on the osteoblastic differentiation of BMSCs and assess the role of histone methylation in the observed phenomena. The osteoblastic differentiation ability of BMSCs was shown to be decreased in diabetes mellitus, as indicated by alkaline phosphatase activity and the mRNA levels of osteoblast-related genes. Furthermore, diabetes mellitus caused an increased expression of the histone methylase EZH2 and the levels of H3K27Me3 and decreased the expression of the histone demethylase KDM6B, as demonstrated by qRT-PCR and western blotting. Furthermore, immunofluorescence staining suggested that both EZH2 and H3K27Me3 were primarily localized in the nucleus. In addition, chromatin immunoprecipitation assays indicated an increased presence of H3K27Me3 on the promoter region of the BMP4 gene. In summary, in the present study, we demonstrated that the osteoblastic differentiation of BMSCs is dramatically reduced in diabetes mellitus. In addition, upregulation of EZH2 expression and downregulation of KDM6B expression may not be enough to eliminate transcriptional repression mediated by H3K27Me3 on the promoter region of the BMP4 gene during the osteoblastic differentiation of BMSCs in diabetes mellitus.

EptA of Riemerella anatipestifer mediates phenotypes involved in colistin resistance and virulence.

Colistin (polymyxin E) is a group of cationic antimicrobial cyclic peptides and is recognized as a last-resort defense against lethal infections with carbapenem-resistant pathogens. In addition to the plasmid-borne mobilized phosphoethanolamine (PEA) transferases, the functional expression of lipid A-modifying enzymes encoded on chromosomes has been attributed to intrinsic bacterial colistin resistance. However, the mechanisms of colistin resistance in Riemerella anatipestifer remain unknown. Herein, the GE296_RS09715 gene-encoded Lipid A PEA transferases (RaEptA) was identified in R. anatipestifer. Genetic and structural analyses revealed that the amino acid sequence of RaEptA shared 26.6%-33.1% similarities with the family of Lipid A PEA transferases (EptA) and MCR-like proteins and have defined 12 residues that contribute to the formation of phosphatidylethanolamine (PE)-recognizable cavities. Comparative analyses of colistin resistance in RA-LZ01 and RA-LZ01ΔRaEptA showed the level of colistin has fallen from 96 µg mL-1 down to 24 ~ 32 µg mL-1 . Site-directed mutagenesis assay of the PE-binding cavity and expression of the mutants reveals that K309-rRaEptA can remodel the surface of Escherichia coli and rendering it resistant to colistin, suggesting this point-mutation of P309K is necessary for EptA-mediated lipid A modification. Moreover, the virulence of RA-LZ01ΔRaEptA was attenuated compared with RA-LZ01 both in vivo and vitro. Taken together, the results represent the RaEptA involved in the colistin resistance and pathogenicity, and the P309K mutation might alter bacterial adaptation and increase the spread of colistin resistance from R. anatipestifer to other gram-negative bacteria. The findings of this study suggest another scenario for the spread of colistin resistance genes and should be considered by a wide audience.

Selective Inhibition of Organic Cation Transporter 1 by Benzoylpaeoniflorin Attenuates Hepatic Lipid Accumulation through AMPK Activation.

Organic cation transporter 1 (OCT1) is a liver-specific transporter and plays an essential role in drug disposition and hepatic lipid metabolism. Therefore, inhibition of OCT1 may not only lead to drug-drug interactions but also represent a potential therapy for fatty liver diseases. In this study, we systematically investigated the inhibitory effect of 200 natural products on OCT1-mediated uptake of 4,4-dimethylaminostyryl-N-methylpyridinium (ASP+) and identified 10 potent OCT1 inhibitors. The selectivity of these inhibitors over OCT2 was evaluated using both in vitro uptake assays and in silico molecular docking analyses. Importantly, benzoylpaeoniflorin was identified as the most potent OCT1 inhibitor with the highest selectivity over OCT2. Additionally, benzoylpaeoniflorin prevented lipid accumulation in hepatocytes, with concomitant activation of AMPK and down-regulation of lipogenic genes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). To conclude, our findings are of significant value in understanding OCT1-based natural product-drug interactions and provide a natural source of OCT1 inhibitors which may hold promise for treating fatty liver diseases.

Management strategies of dental anxiety and uncooperative behaviors in children with Autism spectrum disorder.

BACKGROUND: Children with Autism spectrum disorder (ASD) was frequently experienced dental anxiety and uncooperative behaviors during dental treatment. Oral health care was necessary because of the poor oral hygiene and prevalent dental diseases in this population. AIM: In this systematic review, we evaluated the effectiveness and feasibility for pediatric dentist to manage the dental anxiety in children with ASD. DESIGN: PubMed, Embase, and Cochrane Library were systematically performed on the literature search. The date of eligible publications was from inception to January 2023. After that, the quality of eligible studies was assessed by the Newcastle Ottawa Scale (NOS). Review findings were summarized using the PRISMA Statement for reporting. RESULTS: A total of six studies were systematically evaluated according to the inclusion and exclusion criteria. Five studies were conducted to evaluate ASD Children's anxiety and uncooperative performance in the progressive oral examination, oral disease prophylaxis and fluoride application. The other one study evaluated the success rate of treatment in decayed permanent tooth treatment. In the included studies, four studies indicated that it was extremely necessary to reduce dental anxiety of ASD children to increase the cooperation in sensory-adapted dental environment (SADE). CONCLUSION: It is not always effective and feasible for pediatric dentist to manage the dental anxiety in children with autism during routine oral examination. Meanwhile, it is necessary for ASD children to conduct preoperative psychological assessment, to investigate parents' expectations and cooperation, and to determine whether to start corresponding dental treatment.

Sporadic hand, foot, and mouth disease cases associated with non-C4 enterovirus 71 strains in Xiamen, China, from 2009 to 2018.

Enterovirus 71 (EV71) has caused large hand, foot, and mouth disease (HFMD) epidemics among young children, and EV71 infection is the leading cause of severe HFMD cases and deaths. In mainland China, the prevalence and risk factors of non-C4 EV71 strains are still unclear. In this study, we monitored non-C4 strains over a 10-year HFMD epidemiological surveillance period in Xiamen. The 5'UTR and VP1 coding region of EV71 strains were amplified by RT-nested PCR and sequenced. Thirty-two non-C4 EV71 strains were identified during 2009-2018. This study provides important information about the prevalence of EV71 in China that will be applicable for development of vaccines and diagnostic reagents as well as establishment of policies for HFMD prevention and control.

Yinzhihuang Oral Liquid Ameliorates Hyperbilirubinemia Induced by δ-Aminolevulinic Acid and Novobiocin in Neonatal Rats.

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.

Effects of mouth breathing on facial skeletal development in children: a systematic review and meta-analysis.

BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SN-PP, PP-MP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, Overjet, Overbite, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 10 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: - 1.63, P < 0.0001), SNB (MD: - 1.96, P < 0.0001) in mouth-breathing children was lower than that in nasal-breathing children. ANB (MD: 0.90, P < 0.0001), 1. NA (MD: 1.96, P = 0.009), 1-NA (MD: 0.66, P = 0.004), and 1-NB (MD: 1.03, P < 0.0001) showed higher values in children with mouth breathing. In vertical direction, SN-PP (MD: 0.68, P = 0.0050), SN-OP (MD: 3.05, P < 0.0001), PP-MP (MD: 4.92, P < 0.0001) and SNGoGn (MD: 4.10, P < 0.0001) were higher in mouth-breathing individuals. In airway, SPAS (MD: - 3.48, P = 0.0009), PAS (MD: - 2.11, P < 0.0001), and C3-H (MD: - 1.34, P < 0.0001) were lower in mouth breathing group. CONCLUSIONS: The results showed that the mandible and maxilla rotated backward and downward, and the occlusal plane was steep. In addition, mouth breathing presented a tendency of labial inclination of the upper anterior teeth. Airway stenosis was common in mouth-breathing children. Trial registration crd-register@york.ac.uk, registration number CRD42019129198.

Effect of advanced glycation end products on autophagic ability in osteoblasts. / 晚期糖基化终末产物对成骨细胞自噬能力的影响.

OBJECTIVES: Excessive production of AGEs in diabetic patients will affect the normal function of osteoblasts, and this process may be related to autophagy of osteoblasts. This study aims to explore the effect of advanced glycation end products (AGEs) on autophagic activity during osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated and cultured in vitro, treated with different concentrations (0, 50, 100, 200, and 400 mg/L) of AGEs for different time (3, 6, 12, 24, 48, and 72 h). The proliferation activity was detected by CCK-8 method. The mRNA and protein expression levels of Beclin1 and LC3 in cells were detected by real-time PCR and Western blotting, respectively.The autophagic vacuoles were observed under the transmission electron microscope. The cells were treated with autophagy promoter rapamycin or autophagy inhibitor 3MA. After 7 days of osteogenic induction, we performed alkaline phosphatase (ALP) staining and real-time PCR to detect the mRNA expression levels of osteogenesis-related genes. RESULTS: In the low-concentration groups, the proliferation activity in BMSCs was increased (P<0.01), the mRNA and protein expressions of autophagy-related genes LC3 and Beclin1 were increased (both P<0.01). The number of autophagosome also was increased. In the high-concentration groups, the results were just the opposite. In the low-concentration groups, the ALP staining was deeper than that of the 0 mg/L AGEs group, and the mRNA expressions of the osteogenic related genes were increased (P<0.01). But the results were reversed in the presence of autophagy inhibitor 3MA. In the high-concentration groups, the ALP staining was lighter than that of the 0 mg/L AGEs group, and the mRNA expressions of the osteogenic related genes were decreased (P<0.01). After the addition of the autophagy promoter rapamycin, the results were reversed. CONCLUSIONS: Low concentration of AGEs can enhance the proliferative activity of BMSCs and promote osteogenic differentiation by accelerating autophagy. High concentration of AGEs can suppress the proliferation of BMSCs and inhibit osteogenic differentiation by reducing autophagy.

Comparison of odontoblast differentiation capacity between stem cells from human exfoliated deciduous teeth and dental pulp stem cells. / 人脱落乳牙牙髓干细胞与恒牙牙髓干细胞成牙本质分化能力的比较.

OBJECTIVES: To explore the difference in odontoblast differentiation capacity between stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs), and to examine the expression level of ephrinB1 in odontoblast differentiation of these stem cells. METHODS: The stems cells were divided into a SHED group and a DPSCs group. After odontoblast differentiation induction, the above 2 groups were also randomly divided into a 3 d group and a 7 d group, respectively.The calcium deposition was detected by alkaline phosphatase (ALP) staining and alizarin red staining.The mRNA and protein expressions of ephrinB1, dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) were detected by real-time PCR and Western blotting. RESULTS: ALP staining and alizarin red staining showed that there was stronger mineralization capacity in the SHED group than that in the DPSCs group. The relative mRNA and protein expressions of DMP-1, DSPP, and ephrinB1 in the SHED group were higher than those in the DPSCs group except for the protein expression of DMP-1 in the SHED 3 d group (all P<0.05). CONCLUSIONS: SHED has stronger odontoblast differentiation capacity than DPSCs. In addition, ephrinB1 may be involved in the processes of odontoblast differentiation in the SHED and DPSCs.

Biflavonoids from Juniperus oblonga inhibit organic anion transporter 3.

Organic anion transporters (OATs in humans, Oats in rodents) play an important role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. Their ligand recognition is also important for drug therapy and development. In this study, the n-butanol and dichloromethane soluble fractions of Juniperus oblonga were found to inhibit OAT3 in vitro and three biflavonoids were found to be responsible for this activity. One of these compounds, amentoflavone exhibited stronger inhibition than probenecid, a known strong inhibitor of OAT3. Biological characterization of amentoflavone in vivo also showed inhibition of Oat3. Preliminary observations of structure-activity relationships suggest that the biflavonoids are more potent inhibitors of this transporter than their corresponding monomer, and that methylation of even a single hydroxyl group results in a substantial decrease in activity. This greater potency of the biflavonoids may indicate the need for a more in-depth investigation of the distribution of biflavonoids in plants used as foodstuffs and herbal medicines, due to their potential for causing interactions with OAT3 substrate drugs.

Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial.

BACKGROUND: N-acetylcysteine is a classic mucolytic agent. This study aimed to investigate the efficacy of N-acetylcysteine on reducing the risk of exacerbations in bronchiectasis patients. METHODS: A prospective, randomized, controlled trial was conducted between April 1, 2014 and December 31, 2016 in five general hospitals in Shandong Province, China. Adult bronchiectasis patients with at least two exacerbations in the past year were potentially eligible. Patients were randomly assigned to receive oral N-acetylcysteine (600 mg, twice daily, 12 months) or on-demand treatment. RESULTS: A total of 161 patients were eligible for randomization (81 to the N-acetylcysteine group and 80 to the control group). During the 12-month follow-up, the incidence of exacerbations in the N-acetylcysteine group was significantly lower than that in the control group (1.31 vs. 1.98 exacerbations per patient-year; risk ratio, 0.41; 95% CI, 0.17-0.66; P = 0.0011). The median number of exacerbations in the N-acetylcysteine group was 1 (0.5-2), compared with 2 (1-2) in the control group (U = - 2.95, P = 0.003). A total of 24.7% of the N-acetylcysteine group patients and 11.3% of the control group patients remained exacerbation-free throughout the 12-month follow-up (χ2 = 4.924, P = 0.026). Compared with the control group, the volume of 24-h sputum in the N-acetylcysteine group was significantly reduced (t = - 3.091, P = 0.002). Additionally, the N-acetylcysteine group showed a significant improvement in the quality of life. No severe adverse events were reported in the intervention group. CONCLUSION: The long-term use of N-acetylcysteine is able to reduce the risk of exacerbations for bronchiectasis patients in Shandong Province, China. The results of this study should be verified in a larger randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02088216) (Registered date: March 5, 2014).

[Study on the Expression of KDM6B of Osteoblast in Diabetic Environment].

OBJECTIVE: To investigate the ability of osteogenic differentiation and the expression of histone demethylases KDM6B in bone marrow mesenchymal stem cells (BMSCs) in diabetic environment. METHODS: Diabetic model rats was successfully established, and BMSCs from diabetic model rats and normal rats were isolated and cultured for further study. When cultured cells, we added high concentration of glucose and advanced glycosylation products (AGE) in the medium to imitating the diabetic environment. BMSCs were divided into 6 groups: diabetes group (derived from diabets SD rats), normal group (derived from normal SD rats), high glucose group (30 mmol/L D-glucose), normal glucose group (5.5 mmol/L D-glucose), AGE group (AGE 300 µg/mL) and BSA group (BSA 300 µg/mL). BMSCs in diabetes group were derived from diabetes SD rats, while others were derived from normal SD rats. After 7 d of osteogenic induction, the cells were examined the ability of osteogenic differentiation by alkaline phosphatase (ALP) staining, the transcription levels of Runt-related transcription factor 2 (Runx2) and KDM6B were determined by RT-PCR, and the expression levels of H3K27Me3 protein were examined by Western bolt. RESULTS: Compared with the control groups, the numbers of ALP stained cells and the mRNA levels of Runx2 and KDM6B in diabetes group, high glucose group and AGE group were all decreased (P < 0.05), while H3K27Me3 protein expression levels were all increased (P < 0.05). CONCLUSION: The ability of osteogenic differentiation of BMSCs in diabetic environment was weakened, and the expression of Runx2 mRNA was inhibited, which may be related to the increased expression of H3K27Me3 after the inhibition of KDM6B expression.

A Prospective Trial of Nebulized Amikacin in the Treatment of Bronchiectasis Exacerbation.

BACKGROUND: Pseudomonas aeruginosa is the most common pathogenic bacteria in bronchiectasis (BE) patients. The availability and security of nebulized amikacin treatment are unknown. OBJECTIVE: The purpose of this study was to explore the efficiency and adverse effects of nebulized amikacin treatment for 2 weeks, administered as intravenous therapy during exacerbation of BE patients infected with P. aeruginosa. METHODS: A total of 143 patients with exacerbation of BE were screened between January 2013 and March 2016 at five tertiary hospitals in Shandong Province, China. The BE patients were diagnosed by high-resolution computed tomography scans, and all of them were confirmed to be infected with P. aeruginosa after sputum culture test. Seventy-four patients were assigned to the intervention group and received amikacin nebulization (0.2 g) treatment twice daily for 2 weeks along with intravenous antibiotic therapy. Sixty-nine patients were assigned to the control group and received standard antibiotic therapy alone. The primary outcome was the rate of bacterial eradication from the sputum, and the secondary outcomes were drug resistance and adverse effects. RESULTS: The bacterial eradication rate of sputum in the intervention group (51.4%) was significantly higher compared to that in the control group (23.2%) (χ2 = 14.211, p = 0.030). Drug sensitivity testing showed that there were 5 drug-resistant cases in the intervention group and 7 in the control group, which was not significantly different. Three patients dropped out of the trial due to adverse effects. None of the patients hat renal injury. CONCLUSIONS: Nebulized amikacin treatment is a safe treatment for exacerbation of BE and significantly increases the bacterial eradication rate of sputum.

[Detection and analysis technologies for single biological nanoparticles].

In recent years, nanoscale detection has played an increasingly important role in the research on viruses, exosomes, small bacteria, and organelles. The small size and complex biological natures of these particles, with the smallest known virus particle measuring only 17 nm in diameter and exosomes ranging from 30 nm to 150 nm in size, pose challenges to the classical large-scale (typically micron-scale) characterization methods, which has become a major obstacle in the research. The emergence of nanoscale detection and analysis technologies has filled the gap of optical microscopy, a conventional technique in this field. These technologies enable the sensitive and robust detection of objects that exceed the lower limit of optical detection, revealing the molecular composition and biological roles simultaneously. Currently, several commercialized instruments based on nanotechnology have emerged, providing complete single-particle detection solutions and achieving unique functionality based on their respective technological advantages. However, it is inevitable that these technologies have limitations in terms of application and detection capabilities, as they continue to evolve. This paper offers a thorough overview of the principles, advantages, limitations, and future development trends of several mainstream commercial instruments, aiming to serve researchers in selecting and utilizing these technologies.

Isolation, characterization and SARS-CoV-2 3CL protease inhibitory activity of a new methylsulfinyl-butanyl derivative from Raphani Semen.

A new compound named raphanised A (1), along with two known methylsulfinyl -butanyl derivatives (2-3) and seven known indole derivatives (4-10), were isolated from the Raphani Semen. Among the indole derivatives, 5 was identified as a new natural product, and 4, 6, 7, 8, 9, 10 were isolated from the genus of Raphanus for the first time. Their structures were elucidated based on the NMR and HR-EI-MS analysis. Additionally, the inhibitory activity of methylsulfinyl-butanyl derivatives 1-3 on SARS CoV-2 3CL protease was evaluated. The results showed that 1-3 exhibited inhibition of SARS-CoV-2 3CL protease activity at concentrations ranging from 3.3 to 30 µM.

Management of small cell lung cancer complicated with paraneoplastic Cushing's syndrome: a systematic literature review.

Paraneoplastic Cushing's syndrome (PCS) is a rare, but clinically important feature of small cell lung cancer (SCLC) that is associated with even worse prognosis. To identify key considerations in comprehensive management of SCLC patients complicated with PCS, we conducted a systematic review of relevant reports on PubMed and Web of Science, focusing on SCLC with PCS cases. The systematic review analyzed 61 reports published between 1985 and 2022 with a total of 157 SCLC patients included. Out of the 157 patients, 132 (84.1%) patients across 58 (95.1%) reports were diagnosed with ectopic Cushing's syndrome. The immunohistochemical (IHC) staining for adrenocorticotropic hormone (ACTH) was performed on 30 (19.1%) patients across 22 (36.1%) reports and demonstrated encouraging performance. For treatment, chemotherapy and ketoconazole were utilized in 50 (81.97%) and 24 (39.34%) reports, respectively. Regarding cause of death, infection and cancer were equally frequent, each being recorded in 17 (27.87%) reports. To conclude, the majority of PCS cases in SCLC patients were caused by ectopic hormone secretion. In order to make a differential diagnosis, it is recommended to utilize IHC staining for a specific hormone such as ACTH or corticotropin-releasing hormone. In the comprehensive treatment of SCLC with PCS patients, effective management of hypercortisolism and potent safeguarding against infection play two crucial roles. Ultimately, further confirmations are required regarding the specificity and accuracy of IHC staining technique as well as the efficacy and safety of immunotherapy in the treatment of SCLC with PCS patients.

Development and validation of the prognostic model based on autophagy-associated genes in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. Many studies suggest that autophagy may be related to disease progression and prognosis in IPF. However, the mechanisms involved have not been fully elucidated. Methods: We incorporated 232 autophagy-associated genes (AAGs) and two datasets, GSE28042 and GSE27957, from the GEO database. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression were used to construct the autophagy-associated prognostic model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functions of these autophagy-associated genes. CIBERSORT algorithm was used to calculate the immune cell infiltration between patients in the high-risk score and low-risk score groups. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to explore the mRNA expression of five genes in the autophagy-associated risk model. Results: We constructed a 5-autophagy-associated genes signature based on Univariate Cox analysis and LASSO regression. In our autophagy-associated risk model, IPF patients in the high-risk group demonstrated a poor overall survival rate compared to patients in the low-risk group. For 1-, 2-, and 3-year survival rates, the AUC predictive value of the AAG signature was 0.670, 0.787, and 0.864, respectively. These results were validated in the GSE27957 cohort, confirming the good prognostic effect of our model. GO and KEGG pathway analyses enriched immune-related pathways between the high-risk and low-risk groups. And there was also a significant difference in immune cell infiltration between two groups. And the results of qRT-PCR showed that the expression levels of FOXO1, IRGM, MYC, and PRKCQ were significantly decreased in the Peripheral Blood Mononuclear Cell (PBMC) of IPF patient samples. Conclusion: Our study constructed and validated an autophagy-associated risk model based on MYC, MAPK1, IRGM, PRKCQ, and FOXO1. And those five genes may influence the progression of IPF by regulating immune responses and immune cells.