Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults.

Objective: This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality. Methods: We included adult participants with available data for individual phenotypic age (PhenoAge) and Life's Essential 8 (LE8) scores from the National Health and Nutrition Examination Survey 2005-2010 (three cycles) and linked mortality records until 31 December 2019. Adjusted hazard ratios (HR) were estimated to evaluate the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks. Results: A 1-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% confidence interval, 1.04-1.05]) and cardiovascular (HR = 1.04 [95% confidence interval, 1.04-1.05]) mortality, independent of chronological age, demographic characteristics, and disease history. High level of LE8 (score: 80-100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36 and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all P < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure, and physical activity on all-cause mortality risk, respectively (all P < 0.05). Conclusion: Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.

Exploring the clinical implications of novel SRD5A2 variants in 46,XY disorders of sex development.

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2, and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.

G4LDB 3.0: a database for discovering and studying G-quadruplex and i-motif ligands.

Non-canonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have garnered significant research interest because of their unique structural properties and biological activities. Thousands of small molecules targeting G4/iM structures have been developed for various chemical and biological applications. In response to the growing interest in G4-targeting ligands, we launched the first G4 Ligand Database (G4LDB) in 2013. Here, we introduce G4LDB 3.0 (http://www.g4ldb.com), an upgraded version featuring extensive enhancements in content and functionality. The new version includes over 4800 G4/iM ligands and approximately 51 000 activity entries. Key upgrades include advanced search capabilities, dynamic knowledge graphs, enhanced data visualization, along with a new dynamic analysis function that automatically displays ligand structure clustering results and chemical space distribution. With these updates, G4LDB 3.0 further evolves into a comprehensive resource and valuable research tool. The significant improvements address the increasing demand for efficient data handling and user experience, highlighting the critical role of G4LDB in advancing research on G-quadruplexes and i-motifs.

TMCO1 promotes ferroptosis and ECM deposition in glaucomatous trabecular meshwork via ERK1/2 signaling.

Glaucoma, a leading cause of global blindness, is marked by irreversible retinal ganglion cells (RGCs) loss, elevated intraocular pressure (IOP), and extracellular matrix (ECM) deposition in the trabecular meshwork (TM). Transmembrane and coiled-coil domain protein 1 (TMCO1), implicated in calcium regulation, has potential links to primary open-angle glaucoma (POAG). Ferroptosis, an iron-dependent cell death mechanism driven by lipid peroxidation, is also observed in glaucoma. This study investigates the role of TMCO1 in POAG, focusing on its involvement in TM ECM deposition via ferroptosis induction and ERK1/2 phosphorylation inhibition. In both in vivo and in vitro models, we demonstrated that dexamethasone (DEX) stimulation upregulates TMCO1, leading to increased ECM deposition and ferroptosis in human trabecular meshwork cells (HTMCs). Furthermore, treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly reduced ECM deposition and ferroptosis in HTMCs. These findings establish TMCO1 as a critical regulator of ferroptosis and ECM deposition through the ERK/MAPK pathway, positioning it as a promising therapeutic target for glaucoma.

Association of dynamic hepatic metabolism with clinical outcomes in patients with severe Guillain-Barré syndrome: A prospective cohort study from multi-centers in China.

BACKGROUND AND AIMS: Little is known about the ability of serological biomarkers to monitor clinical outcomes in patients with Guillain-Barré syndrome (GBS). The objective of this study was to determine the associations of liver function, easily available and convenient biomarkers, with the clinical course and outcome of severe GBS in patients. METHODS: A prospective data collection was conducted in a cohort of 343 GBS patients from multi-centers between September 2019 and December 2023. Serum samples were obtained at four-time points for mechanical ventilation (MV) patients and two-time points for non-MV patients. The primary endpoint was the need for MV during hospitalization, while secondary outcomes included the ability to walk independently and the mortality at 26-week follow-up. RESULTS: (i) A total of 208 patients were eligible, of whom 50 required MV with a median (interquartile range) ventilation duration of 15 (8-27) days. (ii) Hypohepatia, as evidenced by reduced total protein (OR 0.913 [95% CI 0.862-0.967]) and albumin (0.775 [0.679-0.884]) 1 week after treatment, along with raised liver enzymes (2.732 [1.007-7.413]), was associated with the risk of MV after adjusting for confounders. (iii) After 26-week follow-up, patients with hypohepatia were less likely to regain independent walking and exhibited higher mortality in survival analysis (all log-rank p < .05). (iv) In a cross-sectional study spanning up to 4 years of follow-up, patients with prolonged MV (≥15 days) experienced a longer time to regain independent ambulation than those with shorter MV (167 [46-316] vs. 69 [24-106], p = .036). However, no relationships between liver function and prolonged MV were revealed. INTERPRETATION: Dynamically monitoring hepatic metabolism and promptly adjusting, it can aid the improvement of GBS in patients.

Whether coagulation dysfunction influences the onset and progression of diabetic peripheral neuropathy: A multicenter study in middle-aged and aged patients with type 2 diabetes.

BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (ß 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

Expressional respones of hsp70 genes against abiotic and entomopathgenic stresses in four different noctuid larval species (Lepidoptera: Noctidae).

Heat shock proteins (Hsps) are stress response proteins. In a previous study, host larval Hsp70s were identified as the structural proteins of virions of Heliothis virescens ascovirus 3h (HvAV-3h), an insect virus that mainly infects noctuid larvae. To investigate the response of hsp70s of healthy Mythimna separata, Spodoptera exigua, Spodoptera frugiperda, and Spodoptera litura larvae to various abiotic or entomopathogenic stresses, quantitative PCR was used to detect larval hsp70s expression patterns. Results showed distinct expression patterns of hsp70s in response to different abiotic stresses. Notably, Mshsp70 expression pattern resembled Slhsp70 under most treatments. In healthy larvae, no tissue tropism was observed concerning the relative expression of Mshsp70, Sfhsp70, and Slhsp70. After infection with HvAV-3h, the expression of hsp70s in all dissected tissues of all tested larval species increased. Significant differences were found in the fat bodies of M. separata, S. exigua, and S. litura as well as in the hemolymph of S. exigua and S. litura. Subsequent silencing of Slhsp70, resulted in a significant decrease in DNA replication levels of HvAV-3h in S. litura larvae at 24 and 72 h post RNA interference, indicating that Slhsp70 is necessary for DNA replication in HvAV-3h. These data can provide references for the studying on the stress response of noctuid larvae to different environmental factors.

Effects of Paclobutrazol on Reproductive and Vegetative Traits of Phalaenopsis Join Grace 'TH288-4'.

Phalaenopsis is the most popular potted plant worldwide. However, its typically long stalks often lead to increased shipping costs and risks. This study investigates the effectiveness of varying the concentration, timing, and frequency of paclobutrazol (PP333) applications on shortening the stalk of Phalaenopsis Join Grace 'TH288-4'. Concurrently, it also examines the potential for producing visually appealing and single-flower potted phalaenopsis products by means of truncation. Mature phalaenopsis plants were moved to a cool room in the seventh week to induce flowering. Four experimental groups were established based on different PP333 application schedules: the control (CK) group, with reverse osmosis water application in the second week; the T2 group, with a single application in the second week; the T2T3 group, with applications in both the second and third weeks; and the T7T8 group, with applications in the seventh and eighth weeks. The PP333 concentrations used were 250, 500, 750, and 1000 mg·L-1, applied as foliar sprays. The results showed that the shortest stalks, measured from the base to the first flower, were observed in the T2 group treated with PP333 at 750 mg·L-1 and in the T2T3 group with PP333 at 500, 750, and 1000 mg·L-1. These treatments resulted in stalk lengths of 19.18-22.17 cm, which are 67.2-71.6% shorter than the controls. PP333 application had minimal effect on the stalk diameter, pedicel length, flower width, length, and length/width ratio. However, root diameter was thicker in plants treated with PP333 compared with the control plants. For producing single-flower phalaenopsis, a foliar spray of 750 mg·L-1 PP333 is recommended approximately a month before moving the plants to cooler conditions, followed by truncation, retaining only the first flower. As a result, this study establishes a PP333 treatment protocol for phalaenopsis, offering a strategy to effectively shorten the stalks.

[Influence of different processing methods on volatile components of Atractylodis Rhizoma based on HS-GC-MS technology].

The volatile components of Atractylodis Rhizoma have obvious pharmacological effects and are considered to be the main dry components of Atractylodis Rhizoma. The differences of different processed products of Atractylodis Rhizoma were analyzed from the perspective of volatile oil changes to explain the reasons for dryness reduction and efficacy increase of Atractylodis Rhizoma after processing. HS-GC-MS technology was used to obtain the volatile components of raw Atractylodis Rhizoma, bran-fried Atractylodis Rhizoma, roasted Atractylodis Rhizoma, and rice-water processed Atractylodis Rhizoma under four different processes, and then SIMCA software was used to analyze the volatile oil components of Atractylodis Rhizoma and its different processed products. A total of 87 volatile components were identified in the HS-GC-MS results. A total of 76 volatile components were identified in raw products; 79 volatile components were identified in bran-fried Atractylodis Rhizoma; 70 volatile components were identified in Zhangbang rice-water processed Atractylodis Rhizoma; 81 volatile components were identified in roasted Atractylodis Rhizoma; 78 volatile components were identified in Hunan rice-water processed Atractylodis Rhizoma; 73 volatile components were identified in Jilin rice-water processed Atractylodis Rhizoma, and 77 volatile components were identified in Shanghai rice-water processed Atractylodis Rhizoma. Through multivariate statistical analysis, it was found that there were significant differences between the processed products of Atractylodis Rhizoma. Then, a total of 28 significant differential components between the symbiotic products and the six processed products were established by the OPLS-DA model. Among them, 11 volatile components that generally increased significantly after processing were α-pinene, phellandrene,(1S)-(+)-3-carene, o-isopropyltoluene, D-limonene, α-ocimene, α-isoterpinene, silphiperfol-5-ene,silphinene, γ-alkenyl, and germacrene B, which may be related to their synergistic effect. Five volatile components that generally decreased significantly after processing were ß-elemene, 1-methyl-4-(6-methylhept-5-en-2-yl) cyclohexa-1, 3-diene, ß-selinene,ß-sesquiphellandrene, and atractylon, which may be related to their dryness.

Nobiletin, an activator of the pyruvate kinase isozyme M1/M2 protein, upregulated the glycolytic signalling pathway and alleviated depressive-like behaviour caused by artificial light exposure at night in zebrafish.

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway.

Controlling factors of iron plaque formation and its adsorption of cadmium and arsenic throughout the entire life cycle of rice plants.

Iron (Fe) plaque, which forms on the surface of rice roots, plays a crucial role in immobilizing heavy metal(loids), thus reducing their accumulation in rice plants. However, the principal factors influencing Fe plaque formation and its adsorption capacity for heavy metal(loid)s throughout the rice plant's lifecycle remain poorly understood. Thus, this study investigated the dynamics of Fe plaque formation and its ability to adsorb cadmium (Cd) and arsenic (As) across different growth stages, aiming to identify the key drivers behind these processes. The findings reveal that the rate of radial oxygen loss (ROL) and the abundance of plaque-associated microbes are the primary drivers of Fe plaque formation, with their relative importance ranging from 1.4% to 81%. Similarly, the adsorption of As by Fe plaque is principally determined by the rate of ROL and the quantity of Fe plaque, with subsequent effects from the total Fe in rhizospheric soil, arsenate-reducing bacteria, and organic matter-degrading bacteria. The relative importance of these factors ranges from 6.0% to 11.7%. By contrast, the adsorption of Cd onto Fe plaque is primarily affected by competition for adsorption sites with ammonium in soils and the presence of organic matter-degrading bacteria, contributing 25.5% and 23.5% to the adsorption process, respectively. These findings provide significant insights into the development of Fe plaque and its absorption of heavy metal(loid)s throughout the lifecycle of rice plants.

Prevalence and Antibiotic Resistance Patterns of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Hospital Setting: A Retrospective Study from 2018 to 2022.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections.

Screening of herbal extracts binding with vascular endothelial growth factor by applying HerboChip platform.

BACKGROUND: Traditional Chinese medicine (TCM) has been hailed as a rich source of medicine, but many types of herbs and their functions still need to be rapidly discovered and elucidated. HerboChip, a target-based drug screening platform, is an array of different fractions deriving from herbal extracts. This study was designed to identify effective components from TCM that interact with vascular endothelial growth factor (VEGF) as a target using HerboChip. METHODS: Selected TCMs that are traditionally used as remedies for cancer prevention and wound healing were determined and extracted with 50% ethanol. Biotinylated-VEGF was hybridized with over 500 chips coated with different HPLC-separated fractions from TCM extracts and straptavidin-Cy5 was applied to identify plant extracts containing VEGF-binding fractions. Cytotoxicity of selected herbal extracts and their activities on VEGF-mediated angiogenic functions were evaluated. RESULTS: Over 500 chips were screened within a week, and ten positive hits were identified. The interaction of the identified herbal extracts with VEGF was confirmed in cultured endothelial cells. The identified herbs promoted or inhibited VEGF-mediated cell proliferation, migration and tube formation. Results from western blotting analysis demonstrated the identified herbal extracts significantly affected VEGF-triggered phosphorylations of eNOS, Akt and Erk. Five TCMs demonstrated potentiating activities on the VEGF response and five TCMs revealed suppressive activities. CONCLUSIONS: The current results demonstrated the applicability of the HerboChip platform and systematically elucidated the activity of selected TCMs on angiogenesis and its related signal transduction mechanisms.

Engineered Cell Elongation Promotes Extracellular Electron Transfer of Shewanella Oneidensis.

To investigate how cell elongation impacts extracellular electron transfer (EET) of electroactive microorganisms (EAMs), the division of model EAM Shewanella oneidensis (S. oneidensis) MR-1 is engineered by reducing the formation of cell divisome. Specially, by blocking the translation of division proteins via anti-sense RNAs or expressing division inhibitors, the cellular length and output power density are all increased. Electrophysiological and transcriptomic results synergistically reveal that the programmed cell elongation reinforces EET by enhancing NADH oxidation, inner-membrane quinone pool, and abundance of c-type cytochromes. Moreover, cell elongation enhances hydrophobicity due to decreased cell-surface polysaccharide, thus facilitates the initial surface adhesion stage during biofilm formation. The output current and power density all increase in positive correction with cellular length. However, inhibition of cell division reduces cell growth, which is then restored by quorum sensing-based dynamic regulation of cell growth and elongation phases. The QS-regulated elongated strain thus enables a cell length of 143.6 ± 40.3 µm (72.6-fold of that of S. oneidensis MR-1), which results in an output power density of 248.0 ± 10.6 mW m-2 (3.41-fold of that of S. oneidensis MR-1) and exhibits superior potential for pollutant treatment. Engineering cellular length paves an innovate avenue for enhancing the EET of EAMs.

Characterization of extreme rainfall changes and response to temperature changes in Guizhou Province, China.

Different geographical zones have regional heterogeneity in underlying earth surface structure and microclimate which result in different evolution trends and their response to climate change varies in extreme rainfalls in these zones. In the Guizhou province of China, there are complex landforms, which lead to spatial redistribution of rainfall, frequent extreme rainfall, and disasters high risk of geologic disasters. Research on extreme climate in Guizhou mostly paid attention to its spatio-temporal characteristics and modeling, but lack of analysis on its characteristics of extreme rainfall variability and response to temperature changes under different subsurface conditions. This study investigated the characteristics of the extreme rainfall spatiotemporal and recurrence periods in Guizhou province and discussed the relationship between the response of extreme rainfall to temperature change. Daily rainfall data from 1990 to 2020 and 2021-2100 at 31 meteorological observation stations throughout the province were collected to calculate extreme precipitation. This research had the following results. (1) Both historical and future periods show an upward trend in extreme rainfall in Guizhou province, with a spatial distribution pattern of "high in the south and low in the north, high in the east and low in the west" and "high in the southeast and low in the northwest", respectively; the spatial distribution of extreme rainfall under each recurrence period is consistent with the non-recurrence period. (2) Both historical and future periods show an upward trend in temperature in Guizhou province, with a spatial distribution consistent with that of the extreme rainfall in the corresponding period. (3) The change in extreme rainfall intensity with increasing temperature is almost always greater than the C-C rate for different periods and underlying earth surface structure; Extreme rainfall has a Hook response structure to temperature change, and the climate response structure shifts to the right with climate warming. The results of the study can provide a basis for decision-making on regional disaster prevention and mitigation in the context of temperature change.

Fucoxanthin Attenuates Angiogenesis by Blocking the VEGFR2-Mediated Signaling Pathway through Binding the Vascular Endothelial Growth Factor.

Fucoxanthin, a dietary carotenoid, is predominantly found in edible brown algae and is commonly consumed worldwide. Fucoxanthin has been shown to possess beneficial health activities such as antidiabetic, anti-inflammatory, antimutagenic, and antiobesity; however, the effects of fucoxanthin on VEGF-mediated angiogenesis and its possible binding with VEGF are unknown. Here, different lines of evidence supported the suppressive roles of fucoxanthin in VEGF-mediated angiogenesis. In human umbilical vein endothelial cells, fucoxanthin remarkedly suppressed VEGF-mediated cell proliferative, migration, and invasive abilities, as well as tube formation, without cytotoxicity. In addition, fucoxanthin inhibited the subintestinal vessel formation of zebrafish in vivo. In signaling cascades, fucoxanthin was proposed to interact with VEGF, thus attenuating VEGF's functions in activating the VEGF receptor and its related downstream signaling, i.e., phosphorylations of MEK and Erk. Fucoxanthin also significantly blocked VEGF-triggered ROS formation. Furthermore, the outcomes of applying fucoxanthin in cancer cells were identified, which included (i) inhibiting VEGF-mediated cell proliferation and migration and (ii) inhibiting NF-κB translocation via limiting MMP2 expression. These lines of investigations supported the antiangiogenic roles of fucoxanthin, as well as reviewing its signaling mechanisms, in blocking the VEGF-triggered responses. The results would benefit the potential development of fucoxanthin for the prevention and treatment of angiogenesis-related diseases.

Association of benzodiazepine and Z-hypnotic use with cardiovascular disease risk: insights from a prospective study of 10 million people in China.

AIM: To assess the association between Benzodiazepines (BZDs) or Z-hypnotic use and cardiovascular diseases (CVD) incidence in residents in Beijing, China. METHODS: We included 2,415,573 individuals with a prescription record for BZDs or Z-hypnotics in the Beijing Medical Claim Data for Employees database during 2010-2017, and 8,794,356 non-users with other prescriptions for the same period. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional risk models for 712,850 exposed and 712,850 unexposed participants who were matched 1:1 by propensity score. RESULTS: BZDs or Z-hypnotics users had a higher risk of CVD than non-users, with an HR of 1.11 (95% CI: 1.10, 1.13). Compared with non-users, those who used them for less than 3 months had the lowest risk of CVD, and those for more than 5 years had the highest risk, with HRs of 0.50 (0.48, 0.51) and 1.78 (1.72, 1.83), respectively. The risk of CVD was relatively low in those who used only one of the long-acting BZDs, short-acting BZDs, or Z-hypnotics compared to unexposed individuals. Individuals exposed to all three types of drugs had the highest risk, 2.33 (2.22, 2.44) times that of non-users. Users below the median dose had a lower risk of CVD compared to non-users, whereas users exceeding the median dose had an increased risk. CONCLUSION: BZD or Z-hypnotic use in general was nominally associated with an elevated risk of CVD. However, for short-term, single-type, and low-to-moderate-dose users, not only did this elevated risk disappear, but drug use also demonstrated a protective effect.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

[Research pro gress on historical processing evolution, chemical constituents,and pharmacological effects of Plantaginis Semen].

Plantaginis Semen is a traditional Chinese medicine(TCM) commonly used in clinical practice in China, which has the effects of clearing heat, inducing diuresis for treating stranguria, draining dampness and relieving diarrhea, brightening eyes, and eliminating phlegm. Plantaginis Semen has a long history of processing. In the Han Dynasty, there were records of stir-frying, and then processing with wine, processing with salt water, processing with rice water, and other processing methods appeared. Plantaginis Semen after processing can weaken the cold nature of the drug, suitable for clinical application. Modern research has shown that the main chemical constituents of Plantaginis Semen are phenylethanol glycosides, cyclic enol ether terpenes, polysaccharides, and flavonoids, with diuretic, anti-inflammatory, hypoglycemic, hypolipidemic, antioxidant, and other pharmacological effects. This article reviewed the materia medica, medicine books, and related literature in various dynasties and analyzed the historical processing evolution, chemical constituents, and pharmacological effects of Plantaginis Semen, so as to provide a reference for the relevant research on Plantaginis Semen.

Mechanoimmune-Driven Backpack Sustains Dendritic Cell Maturation for Synergistic Tumor Radiotherapy.

Cell backpacks present significant potential in both therapeutic and diagnostic applications, making it essential to further explore their interactions with host cells. Current evidence indicates that backpacks can induce sustained immune responses. Our original objective was to incorporate a model antigen into the backpacks to promote dendritic cell maturation and facilitate antigen presentation, thereby inducing immune responses. However, we unexpectedly discovered that both antigen-loaded backpacks and empty backpacks demonstrated comparable abilities to induce dendritic cell maturation, resulting in nearly identical potency in T-cell proliferation. Our mechanistic studies suggest that the attachment of backpacks induces mechanical forces on dendritic cells via opening the PIEZO1 mechanical ion channel. This interaction leads to the remodeling of the intracellular cytoskeleton and facilitates the production of type I interferons by dendritic cells. Consequently, the mechano-immune-driven dendritic cell backpacks, when combined with radiotherapy, induce a robust antitumor effect. This research presents an avenue for leveraging mechanotransduction to enhance combination immunotherapeutic strategies, potentially leading to groundbreaking advancements in the field.