Selective fluorescence detection of acetylsalicylic acid, succinic acid and ascorbic acid based on a responsive lanthanide metal fluorescent coordination polymer.

A fluorescent sensor for highly selective and ultrasensitive detection of acetylsalicylic acid (ASA), succinic acid (SA), and ascorbic acid (AA) was reported. The water-soluble fluorescent ligand salicylic acid (Sal) was generated through catalyzing ASA by the hydrolase activity of zeolitic-imidazolate framework-8 (ZIF-8) or natural esterase (Est). The Sal can coordinate with 2-methylimidazole (2-MIm) and Ln(III) to form a fluorescent lanthanide coordination polymer (LCP), which has a fluorescence emission peak with the maximum wavelength at 412 nm (the excitation wavelength at 300 nm). Therefore, the detection of ASA can be achieved through the fluorescence intensity changes of LCPs in the system, which has comparable sensitivity and good selectivity (linear range of 0.031-1.00 mM and LODs of 11.72 and 3.22 µM) as compared to a direct reaction between Est/ZIF-8 and ASA for detecting ASA (linear range of 0.05-1.20 mM and limits of detection (LODs) of 4.43 and 4.58 µM). Furthermore, upon the addition of SA and AA, the fluorescence intensity of the reaction system can be enhanced and weakened through changing the energy resonance transfer pathways and affecting the enzymatic reaction process, respectively, realizing their sensitive and selective fluorescence detection. The established fluorescent sensors can work well in a wide linear range of SA concentrations from 0 to 2.50 mM (Est-based reaction system) and 0 to 1.50 mM (ZIF-8-based reaction system) with the LODs of 0.032 and 0.028 mM, respectively. The linear ranges of AA concentrations are from 0.0078 to 0.25 mM (Est-based reaction system) and 0.0078 to 0.13 mM (ZIF-8-based reaction system) with the LODs of 2.54 and 3.80 µM, respectively. The established sensors were successfully used in the detection of SA in rabbit plasma, with a recovery of 84.0%-98.7%. Additionally, the contents of ASA in Aspirin Enteric-Coated tablets and AA in vitamin C tablets were also determined by the developed methods.

[Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM). METHODS: Two newborns with CNM diagnosed clinically at Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects, and their clinical data was collected. Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: Patient 1 was a male neonate and Patient 2 was a 20-day-old male infant. Both newborns had featured difficulty in breathing and swallowing. WES revealed that both had harbored hemizygous variants of the MTM1 gene, which were verified by Sanger sequencing. Patient 1 had harbored a c.1261A>G variant. Based on the ACMG guidelines, it was rated as pathogenic (PVS1+PM2_Supporting+PP3). Patient 2 harbored a c.342delT variant, which was also rated as pathogenic (PVS1+PM2_Supporting+PP3). CONCLUSION: The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.

Association of ACTN4 Gene Mutation with Primary Nephrotic Syndrome in Children in Guangxi Autonomous Region, China.

Objective: To investigate the association between ACTN4 gene mutation and primary nephrotic syndrome (PNS) in children in Guangxi Autonomous Region, China. Methods: The high-throughput sequencing technology was used to sequence ACTN4 gene in 155 children with PNS in Guangxi Autonomous Region in China, with 98 healthy children serving as controls. Twenty-three exon-specific capture probes targeting ACTN4 were designed and used to hybridize with the genomic DNA library. The targeted genomic region DNA fragments were enriched and sequenced. The protein levels of ACTN4 in both case and control groups were quantified using ELISA method. Results: Bioinformatics analysis revealed five unique ACTN4 mutations exclusively in patients with PNS, including c.1516G>A (p.G506S) on one exon in 2 patients, c.1442 + 10G>A at the splice site in 1 patient, c.1649A>G (p.D550G) on exon in 1 patient, c.2191-4G>A at the cleavage site in 2 patients, and c.2315C>T (p.A772V) on one exon in 1 patient. The c.1649A>G (p.D550G) and c.2315C>T (p.A772V) were identified from the same patient. Notably, c.1649A>G (p.D550G) represents a novel mutation in ACTN4. In addition, three other ACTN4 polymorphisms occurred in both case and control groups, including c.162 + 6C>T (1 patient in case group and 2 patients in control group), c.572 + 11G>A (1 patient in case group and 2 patients in control group), and c.2191-5C>T (4 patients in the case group and 3 patients in control group). The serum ACTN4 concentration in the case group was markedly higher, averaging 544.7 ng/mL (range: 264.6-952.6 ng/mL), compared with 241.20 ng/mL (range: 110.75-542.35 ng/mL) in the control group. Conclusion: Five ACTN4 polymorphisms were identified among children with PNS in Guangxi Autonomous Region, China, including the novel mutation c.1649A>G. The lower serum levels of α-actinin-4 in the case group suggest that this protein might play a protective role in PNS.

Safety and Efficacy of Paxlovid in Pediatric Intensive Care Unit Patients with COVID-19.

INTRODUCTION: Paxlovid (nirmatrelvir/ritonavir) has received endorsement from several guidelines for treating COVID-19 in adults, but its use in children is still uncertain. OBJECTIVES: This study aimed to evaluate the safety and effectiveness of paxlovid in pediatric patients in the pediatric intensive care unit (PICU). METHODS: A retrospective analysis was performed on children with COVID-19. The children who received paxlovid comprised the paxlovid group; otherwise, they were referred to as the control group. RESULTS: A total of 31 children were enrolled, with 12 and 19 participants assigned to the paxlovid and control groups, respectively. Approximately 35% had received vaccination against the novel coronavirus. The control group exhibited a significantly lower mean age in comparison to the paxlovid group (p < 0.001). However, no significant differences were observed between the groups in terms of other baseline data and biochemical indexes at admission. However, on the fifth day of drug administration, the paxlovid group exhibited a statistically significant decrease in temperature compared to the control group (p < 0.05). Additionally, the paxlovid group exhibited a significantly shorter conversion time to negativity for novel coronary genes in the respiratory tract (9.5 days) compared to the control group (16 days, p < 0.05). The administration of paxlovid did not result in any observed adverse reactions. Merely two patients exhibited a transient elevation in liver enzyme levels. CONCLUSION: The application of paxlovid in critically ill pediatric patients with COVID-19 can effectively control symptoms and promote virus clearance, demonstrating efficacy and a relatively low-risk profile.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery.

BACKGROUND: Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM: To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS: This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein ß (S-100ß) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS: There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P > 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P < 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P < 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P < 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P < 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P < 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P < 0.05). Marked elevations in serum levels of VEGF, TGF-ß1, TNF-α, and S-100ß were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P < 0.05). CONCLUSION: TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-ß1, TNF-α, and S-100ß levels. This scheme also reduced POCD and had a high safety profile.

Rapid redox-response featured visual ascorbic acid sensor based on simple-assembled europium metal-organic framework.

A facile, fast and visible sensing platform for ascorbic acid (AA) detection has been developed based on self-assembled hydrangea-like europium metal-organic framework (HL-EuMOF). HL-EuMOF was synthesized through a simple one-step mixing process with Eu3+ and 1, 10-phenanthroline-2, 9-dicarboxylic acid at room temperature, which exhibited excellent properties including strong red fluorescence, long decay lifetime (548.623 µs) and good luminescent stability. Based on the specific redox reaction between Fe3+ and AA, the HL-EuMOF@Fe3+ was fabricated with "turn-off" response for AA, where the resulting Fe2+ displayed effective fluorescence quenching ability toward HL-EuMOF. The sensor demonstrated low detection limit (31.94 nM), rapid response time (30 s) and high selectivity. Integration of smartphone-assisted RGB analysis with HL-EuMOF@Fe3+ permitted convenient and visible quantitative determination of AA level. This approach also presented good detection performances in complex human serum and beverage samples, which could provide a valuable tool for AA detection in biomedical research and food industry.

Hidradenitis suppurativa and cardiovascular diseases: A bidirectional Mendelian randomization study.

BACKGROUND: Prior investigation has indicated a link between Hidradenitis suppurativa (HS) and cardiovascular diseases (CVDs), yet the causal relationship (CR) between these conditions remains unresolved. METHODS: This investigation utilized bidirectional Mendelian randomization (MR) analysis to determine the CR between HS and CVDs. Genetic instruments for both conditions were sourced from genome-wide association studies (GWAS). The GWAS summary data for CVD comprised coronary artery disease (CAD), myocardial infarction (MI), coronary atherosclerosis (CA), ischemic stroke (IS), and chronic heart failure (CHF). Four new approaches were added to the inverse variance weighted (IVW) method for the main analysis: weighted median, weighted MR-Egger, simple mode, and weighted mode. The validity of the causal conclusions was verified by sensitivity tests that included leave-one-out analysis, heterogeneity, and pleiotropy. RESULTS: HS and CAD (OR = 1.024; 95%CI: 1.002-1.046, P = 0.033), MI (OR = 1.001; 95%CI: 1.000-1.002, P = 0.033), and CA (OR = 1.001; 95%CI: 1.000-1.002, P = 0.022) were identified to have a positive CR, according to the IVW analysis. Conversely, no significant association was identified between HS and either IS or CHF. Furthermore, the bidirectional analysis indicated no reverse causation between these diseases. CONCLUSION: The findings of this study suggest a potential CR between HS and CAD, MI, and CA. Additional research is warranted to elucidate the biological mechanisms underlying these associations.

A mussel-inspired, antibacterial, antioxidant, injectable composite hydrogel for the sustain delivery of salvianolic acid B for the treatment of frozen shoulder.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Epidemiology, risk factors, and vaccine effectiveness for SARS-CoV-2 infection among healthcare workers during the omicron pandemic in Shanghai, China.

Background: The COVID-19 pandemic has exposed healthcare workers (HCWs) to serious risk of infection. The aims of our study were to investigate the epidemiological characteristics and risk factors of SARS-CoV-2 infection among HCWs, and evaluate the vaccine effectiveness (VE) during the Omicron pandemic in Shanghai, China. Methods: Active surveillance of COVID-19 was performed among HCWs who worked in Shanghai General Hospital from December 2022 to January 2023. A case-control study was conducted by questionnaire survey to analyse the infection-related risk factors. A retrospective cohort study was explored to evaluate VE against primary infection. Results: During the Omicron outbreak, 2,008 of 2,460 (81.6%) HCWs were infected with SARS-CoV-2. The infection rate was higher in women, younger age groups, nurses and medical technicians. Among the 1,742 participants in the questionnaire, 1,463 (84.0%) were tested positive, and 95.1% of them developed symptoms. Most of the infections (53.0%) were acquired outside the hospital. The risk factors associated with higher odds of infection were working in the emergency department (aOR 3.77, 95% CI 1.69-8.38) and medical examination area (aOR 2.47, 95% CI 1.10-5.51). The protective factors associated with lower odds of infection were previous infection with SARS-CoV-2 (aOR 0.01, 95% CI 0-0.07) and receiving four doses of vaccines (aOR 0.40, 95% CI 0.17-0.97). For frontline HCWs, those who had oral-nasal exposure to coworkers were more likely to be infected (aOR 1.74, 95% CI 1.21-2.51). In VE analysis, the risk of primary infection was lower in HCWs who received the emergency heterologous booster (the fourth dose) during the epidemic (aHR 0.25, 95% CI 0.15-0.40), resulting in an adjusted-VE of 75.1%. Conclusions: In response to future pandemic, it is important for public health policies to aim at protecting HCWs through risk-differentiated infection control measures, strengthening personal protection and recommending vaccination to vulnerable individuals before the arrival of Omicron wave.

Associations of E-proteinoid 3 receptor genetic polymorphisms with salt sensitivity, longitudinal blood pressure changes, and hypertension incidence in Chinese adults.

The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Amino acid metabolic reprogramming in the tumor microenvironment and its implication for cancer therapy.

Amino acids are essential building blocks for proteins, crucial energy sources for cell survival, and key signaling molecules supporting the resistant growth of tumor cells. In tumor cells, amino acid metabolic reprogramming is characterized by the enhanced uptake of amino acids as well as their aberrant synthesis, breakdown, and transport, leading to immune evasion and malignant progression of tumor cells. This article reviews the altered amino acid metabolism in tumor cells and its impact on tumor microenvironment, and also provides an overview of the current clinical applications of amino acid metabolism. Innovative drugs targeting amino acid metabolism hold great promise for precision and personalized cancer therapy.

Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD.

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most common liver disease worldwide. The progression to fibrosis, occurring against a backdrop of hepatic steatosis and inflammation, critically determines liver-related morbidity and mortality. Inflammatory processes contribute to various stages of MAFLD and thought to instigate hepatic fibrosis. For this reason, targeting inflammation has been heavily nominated as a strategy to mitigate liver fibrosis. Lipopolysaccharide binding protein (LBP) is a secreted protein that plays an established role in innate immune responses. Here, using adoptive transfer studies and tissue-specific deletion models we show that hepatocytes are the dominant contributors to circulating LBP. In a murine model of MAFLD, hepatocyte-specific deletion of LBP restrained hepatic inflammation and improved liver function abnormalities, but not measures of fibrosis. Human studies, including genetic evidence, corroborate an important role for LBP in hepatic inflammation with minimal impact on fibrosis. Collectively, our data argues against the idea that targeting hepatic inflammation is a viable approach to reducing fibrosis.

Effects of cue and instructor demonstration on the learning of Chinese characters for Chinese as a second language beginners.

This study purports to investigate the effects of cue and instructor demonstration on Chinese as a second language (CSL) beginners' Chinese character learning performance, cognitive load, learning motivation and attitude. In the current research, 100 CSL beginners were randomly assigned to four experimental groups, i.e., instructor demonstration cued character, instructor demonstration non-cued character, non-instructor demonstration cued character and non-instructor demonstration non-cued character. Participants were instructed to watch an instructional video and subsequently complete a post-test and a questionnaire. The results show that (1) in the presence of instructor demonstration, the cued characters can noticeably reduce CSL beginners' cognitive load and enhance their learning attitudes towards character learning, enabling them to achieve better performance in character stroke but not in radical and structure, and (2) in the presence of cued characters, the instructor demonstration can noticeably reduce CSL beginners' cognitive load and increase their learning motivation and attitudes towards character learning but can not improve their character learning performance. The findings have significant implications for educators and instructional designers of Chinese and other non-alphabetic languages, such as Kanji and Hangul.

Dietary effects of vitamin C on antioxidant capacity, intestinal microbiota and the resistance of pathogenic bacteria in cultured Silver pomfret (Pampus argenteus).

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively. The four diets were fed to juvenile P. argenteus (average initial weight: 4.68 ± 0.93 g) for 6 weeks. The results showed that the activity of SOD (superoxide dismutase) and CAT (catalase) increased significantly while that of MDA (malondialdehyde) decreased significantly in group tjl3 compared to vitamin group tjl0. At the genus level, groups tjl0, tjl6, and tjl12 contained the same dominant microbial community, Stenotrophomonas, Photobacterium, and Vibrio, whereas group tjl3 was dominated by Stenotrophomonas, Delftia, and Bacteroides. Among the fish fed with a basic diet containing 300 mg of vitamin C/kg, the intestines exhibited a notable abundance of probiotic bacteria, including lactic acid bacteria (Lactobacillus) and Bacillus. The abundance of Aeromonas in groups tjl3 and tjl6 was lower than that of the vitamin C-free supplemental basic diet group, whereas Aeromonas was not detected in group tjl12. In addition, a causative agent of the disease outbreak in cultured P. argenteus, Photobacterium damselae subsp. Damselae (PDD) was the dominant microbiota community in groups tjl0, tjl6 and tjl12, whereas the abundance of PDD in group tjl3 was the lowest among the diets. Taken together, the diets supplied with vitamin C could influence the composition microbial community of P. argenteus. The low level of vitamin C (300 mg of vitamin C/kg per basic diet) supplementation could not only improve the antioxidant capacity but also resist the invasion of pathogenic bacteria.

Navß2 Intracellular Fragments Contribute to Aß1-42-Induced Cognitive Impairment and Synaptic Deficit Through Transcriptional Suppression of BDNF.

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.

Long-term burden and increasing trends of body mass index are linked with adult hypertension through triglyceride-glucose index: A 30-year prospective cohort study.

BACKGROUND AND AIMS: Insulin resistance (IR) has previously been associated with hypertension, and obesity is a risk factor for IR and hypertension. There is likely an association between body mass index (BMI) and risk for hypertension through the triglyceride-glucose (TyG) index but this relationship remains uncharacterized. METHODS AND RESULTS: This study is based on the Hanzhong Adolescent Hypertension Cohort, which is an ongoing prospective study established in 1987. The TyG index was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. The total area under the curve (AUCt) and incremental AUC (AUCi) were calculated as the long-term burden and trend of BMI, respectively. We found that BMI AUCt and BMI AUCi were significantly associated with the risk of adult hypertension, both without (RR = 1.30/1.31 for BMI AUCt/AUCi) and with (RR = 1.25/1.26 for BMI AUCt/AUCi) the inclusion of the TyG index as a covariate. Importantly, mediation analysis revealed that the TyG index mediated the BMI AUCt-SBP association (19.3%), the BMI AUCt-DBP association (22.7%), the BMI AUCi-SBP association (18.5%) and the BMI AUCi-DBP association (21.3%). Furthermore, the TyG index had a significant mediating effect of 15.9% on the BMI AUCt-hypertension association and 14.9% on the BMI AUCi-hypertension association. CONCLUSION: These findings suggest that the TyG index plays an important mediating role in the association between the cumulative burden and increasing trends of BMI originating in childhood and the risk of hypertension in midlife. We emphasize that early weight management has the potential to reduce the burden of hypertension caused by IR. TRIAL REGISTRATION: The study was clinically registered at the ClinicalTrials.gov (NCT02734472) and approved by the Academic Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2015LSL-047).

Gradual Increase in Birefringence of Antimony Oxalates through Precise Tuning of the Sb3+/[C2O4]2- Ratio.

Birefringent crystals play a crucial role in modulating and controlling the polarization of light in the optical communication and laser industries. Recently, adopting appropriate strategies to enhance the birefringence of crystals has become a prominent area of research focus. Herein, four UV antimony oxalate birefringent crystals, namely, K5Sb2(C2O4)5.5·3H2O, BaSb(C2O4)2.5·3H2O, Na4Sb2O(C2O4)4·6H2O, and Na3Sb(C2O4)2F2·2H2O, have been successfully synthesized. These compounds feature a similar zero-dimensional (0D) cluster structure and share the same functional groups, including π-conjugated [C2O4]2- groups and Sb3+-based distorted polyhedra with stereochemically active lone pairs (SCALPs). Interestingly, we achieved a stepwise increase in birefringence by precisely controlling the Sb3+/[C2O4]2- ratio, ultimately resulting in the compound Na3Sb(C2O4)2F2·2H2O exhibiting a large birefringence (0.21@546 nm). Additionally, we confirmed that the synergistic effects between the π-conjugated [C2O4]2- groups and the distorted polyhedra based on Sb3+ are responsible for the excellent optical properties observed in the reported compounds.

Analgesic treatment for refractory cancer pain caused by gastric cancer bone metastasis: A case report and literature review.

RATIONALE: Patients with bone metastasis-associated cancer pain often experience a complex mix of pain types. Consequently, the use of multimodal combination therapy is essential. While monitoring for common adverse reactions in pain treatment, it is also crucial to be vigilant for the rare but serious serotonin syndrome. PATIENT CONCERNS: A 53-year-old female with metastatic gastric cancer was hospitalized due to severe, uncontrolled thoracic and cervical pain. During the titration of her cancer pain medication, she developed serotonin syndrome. DIAGNOSES: He was diagnosed with refractory cancer pain and serotonin syndrome. INTERVENTIONS: The complete process of cancer pain medication in a patient with gastric cancer and bone metastasis was analyzed, with a primary focus on the selection of analgesic medications, adjustment of opioid dosages, and prevention and treatment of medication-associated adverse reactions. OUTCOMES: The patient's cancer pain was well controlled, with the prompt management of adverse reactions. Furthermore, by adjusting the medication regimen, intolerable adverse reactions were prevented. LESSONS: In clinical settings, personalized analgesic regimens must be developed for patients with cancer pain to enhance patient compliance with medication, prevent the occurrence of severe adverse reactions, and improve the overall quality of life of patients with cancer. Healthcare professionals should pay increased attention to ADRs associated with opioid medications, whereas pharmacists should assist them in promptly identifying ADRs.

Effects of different anesthesia methods on labor process and postpartum serum estrogen and progesterone levels in primiparas with painless labor.

OBJECTIVE: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor. METHODS: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods. RESULTS: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05). CONCLUSION: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone.

Developing AAV-delivered nonsense suppressor tRNAs for neurological disorders.

Adeno-associated virus (AAV)-based gene therapy is a clinical stage therapeutic modality for neurological disorders. A common genetic defect in myriad monogenic neurological disorders is nonsense mutations that account for about 11% of all human pathogenic mutations. Stop codon readthrough by suppressor transfer RNA (sup-tRNA) has long been sought as a potential gene therapy approach to target nonsense mutations, but hindered by inefficient in vivo delivery. The rapid advances in AAV delivery technology have not only powered gene therapy development but also enabled in vivo preclinical assessment of a range of nucleic acid therapeutics, such as sup-tRNA. Compared with conventional AAV gene therapy that delivers a transgene to produce therapeutic proteins, AAV-delivered sup-tRNA has several advantages, such as small gene sizes and operating within the endogenous gene expression regulation, which are important considerations for treating some neurological disorders. This review will first examine sup-tRNA designs and delivery by AAV vectors. We will then analyze how AAV-delivered sup-tRNA can potentially address some neurological disorders that are challenging to conventional gene therapy, followed by discussing available mouse models of neurological diseases for in vivo preclinical testing. Potential challenges for AAV-delivered sup-tRNA to achieve therapeutic efficacy and safety will also be discussed.