High-throughput microalgae sorting based on the deterministic lateral displacement technique.

Microalgae are a group of photosynthetic organisms that can grow autotrophically, performing photosynthesis to synthesize abundant organic compounds and release oxygen. They are rich in nutritional components and chemical precursors, presenting wide-ranging application prospects. However, potential contamination by foreign strains or bacteria can compromise their analytical applications. Therefore, the obtaining of pure algal strains is crucial for the subsequent analysis and application of microalgae. This study designed a deterministic lateral displacement (DLD) chip with dual input and dual outlet of equal width for the separation of Haematococcus pluvialis and Chlorella vulgaris. Optimal separation parameters were determined through a series of experiments, resulting in a purity of 99.80 % for Chlorella vulgaris and 94.58 % for Haematococcus pluvialis, with recovery rates maintained above 90 %, demonstrating high efficiency. This study provides a reliable foundation for future research and applications of microalgae, which holds considerable significance for the subsequent analysis and utilization of microalgae.

4D-QSAR, ADMET properties, and molecular dynamics simulations for designing N-substituted urea/thioureas as human glutaminyl cyclase inhibitors.

Human glutaminyl cyclase (hQC) inhibitors have great potential to be used as anti- Alzheimer's disease (AD) agents by reducing the toxic pyroform of ß-amyloid in the brains of AD patients. The four-dimensional quantitative structure activity relationship (4D-QSAR) model of N-substituted urea/thioureas was established with satisfying predictive ability and statistical reliability (Q2 = 0.521, R2 = 0.933, R2prep = 0.619). By utilizing the developed 4D-QSAR model, a set of new N-substituted urea/thioureas was designed and evaluated for their Absorption Distribution Metabolism Excretion and Toxicity (ADMET) properties. The results of molecular dynamics (MD) simulations, Principal component analysis (PCA), free energy landscape (FEL), dynamic cross-correlation matrix (DCCM) and molecular mechanics generalized Born Poisson-Boltzmann surface area (MM-PBSA) free energy calculations, revealed that the designed compounds were remained stable in protein binding pocket and compounds b ∼ f (-35.1 to -44.55 kcal/mol) showed higher binding free energy than that of compound 14 (-33.51 kcal/mol). The findings of this work will be a theoretical foundation for further research and experimental validation of urea/thiourea derivatives as hQC inhibitors.

Photoinduced Redox Cascade Reaction of Isatins and Aliphatic Carboxylic Acids to Access 6-Hydroxyindoloquinazolinones.

A visible-light-induced cascade reaction is described for the one-pot synthesis of 6-hydroxyindoloquinazolinones using isatins (or isatins and isatoic anhydrides) and aliphatic carboxylic acids. The method provides 36 desired products in 33-96% yield, exhibiting broad substrate scope and good functional group tolerance. This approach utilizes inexpensive and commercially available starting materials, enabling the direct construction of high-value complex structures under mild conditions without the need for photocatalyst, showcasing significant applicability and environmental friendliness.

Advances in polymeric nano-delivery systems targeting hair follicles for the treatment of acne.

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.

[Retracted] Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the certain of the cell proliferation assay data shown in Fig. 4C on p. 1444 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes, which had already been submitted for publication [Shi N, Shan B, Song Y, Chu H and Qian L: Circular RNA circ­PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR­3680­3p in esophageal squamous cell carcinoma. J Cell Biochem 120: 10021­10030, 2019]. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 21: 1439­1448, 2020; DOI: 10.3892/mmr.2020.10957].

Personalized and continuous care intervention affects rehabilitation, living quality, and negative emotions of patients with breast cancer.

BACKGROUND: Breast cancer is among the most common malignancies worldwide. With progress in treatment methods and levels, the overall survival period has been prolonged, and the demand for quality care has increased. AIM: To investigate the effect of individualized and continuous care intervention in patients with breast cancer. METHODS: Two hundred patients with breast cancer who received systemic therapy at The First Affiliated Hospital of Hebei North University (January 2021 to July 2023) were retrospectively selected as research participants. Among them, 134 received routine care intervention (routing group) and 66 received personalized and continuous care (intervention group). Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores, including limb shoulder joint activity, complication rate, and care satisfaction, were compared between both groups after care. RESULTS: SAS and SDS scores were lower in the intervention group than in the routing group at one and three months after care. The total FACT-B scores and five dimensions in the intervention group were higher than those in the routing group at three months of care. The range of motion of shoulder anteflexion, posterior extension, abduction, internal rotation, and external rotation in the intervention group was higher than that in the routing group one month after care. The incidence of postoperative complications was 18.18% lower in the intervention group than in the routing group (34.33%; P <0.05). Satisfaction with care was 90.91% higher in the intervention group than in the routing group (78.36%; P <0.05). CONCLUSION: Personalized and continuous care can alleviate negative emotions in patients with breast cancer, quicken rehabilitation of limb function, decrease the incidence of complications, and improve living quality and care satisfaction.

Fabrication of sea urchin shaped polyaniline-modified magnetic microporous organic network for efficient extraction of non-steroidal anti-inflammatory drugs from animal-derived food samples.

In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.

Recent Progress in Nonconventional Luminescent Macromolecules and their Applications.

Traditional π-conjugated luminescent macromolecules typically suffer from aggregation-caused quenching (ACQ) and high cytotoxicity, and they require complex synthetic processes. In contrast, nonconventional luminescent macromolecules (NCLMs) with nonconjugated structures possess excellent biocompatibility, ease of preparation, unique luminescence behavior, and emerging applications in optoelectronics, biology, and medicine. NCLMs are currently believed to produce inherent luminescence due to through-space conjugation of overlapping electron orbitals in solid/aggregate states. However, as experimental facts continue to exceed expectations or even overturn some previous assumptions, there is still controversy about the detailed luminous mechanism of NCLMs, and extensive studies are needed to further explore the mechanism. This Perspective highlights recent progress in NCLMs and classifies and summarizes these advances from the viewpoint of molecular design, mechanism exploration, applications, and challenges and prospects. The aim is to provide guidance and inspiration for the huge fundamental and practical potential of NCLMs.

A simultaneous impact of digital economy, environment technology, business activity on environment and economic growth in G7: Moderating role of institutions.

This study investigates the simultaneous influence of the digital economy, environmental technologies, business activity, and institutional quality on both the environment and economic growth in G7 economies from 1996 to 2020. The study provides an in-depth analysis to investigate the influence of institutional quality, particularly the regulatory environment, on business activity. Employing a rigorous methodology encompassing correlation analysis, long-term examination using Driscoll and regression estimators, and the utilization of various digital economy indicators such as internet usage and cell subscriptions, we uncover significant insights. The findings underscore the substantial impact of digital economies in mitigating carbon emissions and driving economic growth at an accelerated rate. Moreover, the study reveals that certain regulatory constraints on corporate operations can paradoxically facilitate carbon emission management while also fostering economic expansion. The study validates the presence of an inverted U-shaped Environmental Kuznets Curve (EKC) in G7 economies. This suggests that there is a specific point at which economic activities start to contribute more to carbon emissions. Moreover, the study highlights the importance of achieving a balance between economic growth driven by foreign direct investment and the goals of environmental sustainability. Environmental technology is becoming increasingly important in the regulation of emissions. Significantly, the study highlights the need to enhance the quality of implementing institutional regulations. It suggests that G7 economies can improve both environmental quality and economic growth by adopting superior regulatory methods. These findings are relevant for governments seeking economic growth and environmental protection. They suggest the need for specific policy actions to accomplish sustainable development goals.

A machine learning and drug repurposing approach to target ferroptosis in colorectal cancer stratified by sex and KRAS.

The landscape of sex differences in Colorectal Cancer (CRC) has not been well characterized with respect to the mechanisms of action for oncogenes such as KRAS. However, our recent study showed that tumors from male patients with KRAS mutations have decreased iron-dependent cell death called ferroptosis. Building on these findings, we further examined ferroptosis in CRC, considering both sex of the patient and KRAS mutations, using public databases and our in-house CRC tumor cohort. Through subsampling inference and variable importance analysis (VIMP), we identified significant differences in gene expression between KRAS mutant and wild type tumors from male patients. These genes suppress (e.g., SLC7A11 ) or drive (e.g., SLC1A5 ) ferroptosis, and these findings were further validated with Gaussian mixed models. Furthermore, we explored the prognostic value of ferroptosis regulating genes and discovered sex- and KRAS-specific differences at both the transcriptional and metabolic levels by random survival forest with backward elimination algorithm (RSF-BE). Of note, genes and metabolites involved in arginine synthesis and glutathione metabolism were uniquely associated with prognosis in tumors from males with KRAS mutations. Additionally, drug repurposing is becoming popular due to the high costs, attrition rates, and slow pace of new drug development, offering a way to treat common and rare diseases more efficiently. Furthermore, increasing evidence has shown that ferroptosis inhibition or induction can improve drug sensitivity or overcome chemotherapy drug resistance. Therefore, we investigated the correlation between gene expression, metabolite levels, and drug sensitivity across all CRC primary tumor cell lines using data from the Genomics of Drug Sensitivity in Cancer (GDSC) resource. We observed that ferroptosis suppressor genes such as DHODH , GCH1 , and AIFM2 in KRAS mutant CRC cell lines were resistant to cisplatin and paclitaxel, underscoring why these drugs are not effective for these patients. The comprehensive map generated here provides valuable biological insights for future investigations, and the findings are supported by rigorous analysis of large-scale publicly available data and our in-house cohort. The study also emphasizes the potential application of VIMP, Gaussian mixed models, and RSF-BE models in the multi-omics research community. In conclusion, this comprehensive approach opens doors for leveraging precision molecular feature analysis and drug repurposing possibilities in KRAS mutant CRC.

Does Serum Uric Acid Mediate Relation between Healthy Lifestyle and Components of Metabolic Syndrome?

A healthy lifestyle is related to metabolic syndrome (MetS), but the mechanism is not fully understood. This study aimed to examine the association of components of MetS with lifestyle in a Chinese population and potential mediation role of serum uric acid (SUA) in the association between lifestyle behaviors and risk of components of MetS. Data were derived from a baseline survey of the Shaanxi urban cohort in the Regional Ethnic Cohort Study in northwest China. The relationship between components of MetS, healthy lifestyle score (HLS), and SUA was investigated by logistic or linear regression. A counterfactual-based mediation analysis was performed to ascertain whether and to what extent SUA mediated the total effect of HLS on components of MetS. Compared to those with 1 or less low-risk lifestyle factors, participants with 4-5 factors had 43.6% lower risk of impaired glucose tolerance (OR = 0.564; 95%CI: 0.408~0.778), 60.8% reduction in risk of high blood pressure (OR = 0.392; 95%CI: 0.321~0.478), 69.4% reduction in risk of hypertriglyceridemia (OR = 0.306; 95%CI: 0.252~0.372), and 47.3% lower risk of low levels of HDL cholesterol (OR = 0.527; 95%CI: 0.434~0.641). SUA mediated 2.95% (95%CI: 1.81~6.16%) of the total effect of HLS on impaired glucose tolerance, 14.68% (95%CI: 12.04~18.85%) on high blood pressure, 17.29% (95%CI: 15.01~20.5%) on hypertriglyceridemia, and 12.83% (95%CI: 10.22~17.48%) on low levels of HDL cholesterol. Increased HLS tends to reduce risk of components of MetS partly by decreasing the SUA level, which could be an important mechanism by which lifestyle influences MetS.

Unsupervised Domain Adaptation for Low-Dose CT Reconstruction via Bayesian Uncertainty Alignment.

Low-dose computed tomography (LDCT) image reconstruction techniques can reduce patient radiation exposure while maintaining acceptable imaging quality. Deep learning (DL) is widely used in this problem, but the performance of testing data (also known as target domain) is often degraded in clinical scenarios due to the variations that were not encountered in training data (also known as source domain). Unsupervised domain adaptation (UDA) of LDCT reconstruction has been proposed to solve this problem through distribution alignment. However, existing UDA methods fail to explore the usage of uncertainty quantification, which is crucial for reliable intelligent medical systems in clinical scenarios with unexpected variations. Moreover, existing direct alignment for different patients would lead to content mismatch issues. To address these issues, we propose to leverage a probabilistic reconstruction framework to conduct a joint discrepancy minimization between source and target domains in both the latent and image spaces. In the latent space, we devise a Bayesian uncertainty alignment to reduce the epistemic gap between the two domains. This approach reduces the uncertainty level of target domain data, making it more likely to render well-reconstructed results on target domains. In the image space, we propose a sharpness-aware distribution alignment (SDA) to achieve a match of second-order information, which can ensure that the reconstructed images from the target domain have similar sharpness to normal-dose CT (NDCT) images from the source domain. Experimental results on two simulated datasets and one clinical low-dose imaging dataset show that our proposed method outperforms other methods in quantitative and visualized performance.

Construction of Near-Infrared Probes with Remarkable Large Stokes Shift Based on a Novel Purine Platform for the Visualization of mtG4 Upregulation during Mitochondrial Disorder in Somatic Cells and Human Sperms.

G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange (PATO) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder.

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

[Effects of different exercise modes on neuromuscular junction and metabolism of skeletal muscle-related proteins in aging rats].

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.

High-dimensional mediation analysis for continuous outcome with confounders using overlap weighting method in observational epigenetic study.

BACKGROUND: Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it's an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. METHODS: In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. RESULTS: Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. CONCLUSIONS: The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.

Construction of early warning classification of risk in bladder spasm and its intervention plans guided by the rate adjustment card of continuous bladder irrigation after transurethral resection of the prostate (TURP): development and usability study.

Background: Benign prostatic hyperplasia (BPH) is the most common benign disease causing voiding dysfunction in middle-aged and elderly men. the current "gold standard" for surgical treatment is transurethral resection of the prostate (TURP). Continuous bladder irrigation (CBI) is routinely given for 3 to 5 days after operation. However, this may induce bladder spasm. Bladder spasm not only brings physical and mental pain to patients, delaying the postoperative recovery process, but it also increases the medical economic burden. Therefore, it is important to take active measures to effectively warn and deal with bladder spasm. The color of the drainage fluid is an important indicator and requires close observation during CBI, as it can reflect real-time postoperative bleeding. When the color of drainage fluid is abnormal, effective measures should be undertaken. Grading nursing intervention divides patients into different conditions according to their possible changes, and then recommends targeted nursing intervention. Existing studies have formulated CBI programs from the perspective of quantifying the relationship between drainage fluid color and irrigation speed, but have yet to incorporate bladder spasm prevention and control levels or design corresponding grading nursing intervention programs according to different drainage fluid colors. This study aimed to construct the risk warning classification and intervention plan of bladder spasm under the guidance of CBI speed adjusting card after TURP. Methods: Based on the rate adjustment card of CBI after TURP, we formulated the first draft of an early warning classification of risk in bladder spasm and its intervention plans by combining methods suggested from a literature search with semi-structured interviews and results from 2 rounds of correspondence inquiries with 28 experts by the Delphi method. We further screened and revised grading standards and measures. Results: The positive coefficients of experts in 2 rounds of correspondence inquiries were both 100%, the authority coefficients were both 0.952, and the Kendall harmony coefficients were 0.238 and 0.326, respectively (P<0.01). In the second round of correspondence inquiries, the coefficient of variation of expert opinions was 0.000-0.154, and the coefficient of variation of all items was <0.25. Finally, a 3-level risk warning classification standard and 23 nursing measures for CBI complicated by bladder spasm was constructed. Conclusions: The early warning classification of risk in bladder spasm and its intervention plans guided by rate adjustment card of CBI after TURP are scientific and feasible, and can provide a basis and guidance for effective and standardized CBI in patients after TURP.

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation.

Background: Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance. Methods: We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects. Results: 30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV. Conclusion: 30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.