Optimizing alginate dressings with allantoin and chemical modifiers to promote wound healing.

Wound healing requires diverse functionalities in dressings, and conventional materials often fall short in water absorption and moisture regulation. Natural sodium alginate is popular in wound dressings due to its excellent film-forming ability, biocompatibility, ionic crosslinking, and pH responsiveness. However, it has limitations in physical stability and solubility in aqueous environments. This study enhanced alginate dressings by incorporating allantoin and treating with calcium chloride and citric acid to improve physicochemical properties and mechanical performance. Treatments for S2 to S5 prevented dissociation and maintained integrity, with suitable water absorption (363 %-442 %) and water vapor transmission rates (612.53-715.39 g × m2 × day-1). The treatments also improved tensile strength (44.90-55.19 MPa). S2 had the highest migration ratio (52.71 %) of L929 cells and wound healing rates for mice skin (86.6 %), indicating that calcium chloride treatment is beneficial. All dressings (S1 to S5) exhibited low cytotoxicity against L929 cells and low hemolysis ratios, indicating good biocompatibility. Higher allantoin content improved wound healing efficacy. This study provides valuable insights for the design and development of alginate dressings in wound repair, expanding allantoin's application in wound healing.

Brain Delivery of Protein Therapeutics by Cell Matrix-Inspired Biomimetic Nanocarrier.

Protein therapeutics are anticipated to offer significant treatment options for central nervous system (CNS) diseases. However, the majority of proteins are unable to traverse the blood-brain barrier (BBB) and reach their CNS target sites. Inspired by the natural environment of active proteins, the cell matrix components hyaluronic acid (HA) and protamine (PRTM) are used to self-assemble with proteins to form a protein-loaded biomimetic core and then incorporated into ApoE3-reconstituted high-density lipoprotein (rHDL) to form a protein-loaded biomimetic nanocarrier (Protein-HA-PRTM-rHDL). This cell matrix-inspired biomimetic nanocarrier facilitates the penetration of protein therapeutics across the BBB and enables their access to intracellular target sites. Specifically, CAT-HA-PRTM-rHDL facilitates rapid intracellular delivery and release of catalase (CAT) via macropinocytosis-activated membrane fusion, resulting in improved spatial learning and memory in traumatic brain injury (TBI) model mice (significantly reduces the latency of TBI mice and doubles the number of crossing platforms), and enhances motor function and prolongs survival in amyotrophic lateral sclerosis (ALS) model mice (extended the median survival of ALS mice by more than 10 days). Collectively, this cell matrix-inspired nanoplatform enables the efficient CNS delivery of protein therapeutics and provides a novel approach for the treatment of CNS diseases.

Heart Rate Variability Parameter Changes in Patients With Acute Ischemic Stroke Undergoing Intravenous Thrombolysis.

Background Autonomic dysfunction has been revealed in patients with acute ischemic stroke and is associated with poor prognosis. However, autonomic nervous system function assessed by heart rate variability (HRV) and its relationship with clinical outcomes in patients undergoing intravenous thrombolysis (IVT) remain unknown. Methods and Results Patients who did and did not undergo IVT between September 2016 and August 2021 were prospectively and consecutively recruited. HRV values were measured at 1 to 3 and 7 to 10 days after stroke to assess autonomic nervous system function. A modified Rankin scale score ≥2 at 90 days was defined as an unfavorable outcome. Finally, the analysis included 466 patients; 224 underwent IVT (48.1%), and 242 did not (51.9%). Linear regression showed a positive correlation of IVT with parasympathetic activation-related HRV parameters at 1 to 3 days (high frequency: ß=0.213, P=0.002) and with both sympathetic (low frequency: ß=0.152, P=0.015) and parasympathetic activation-related HRV parameters (high frequency: ß=0.153, P=0.036) at 7 to 10 days after stroke. Logistic regression showed HRV values and autonomic function within 1 to 3 and 7 to 10 days after stroke were independently associated with 3-month unfavorable outcomes after adjusting for confounders in patients who underwent IVT (all P<0.05). Furthermore, addition of HRV parameters to conventional risk factors significantly improved risk-predictive ability of 3-month outcome (the area under the receiver operating characteristic curve significantly improved from 0.784 [0.723-0.846] to 0.855 [0.805-0.906], P=0.002). Conclusions IVT positively affected HRV and autonomic nervous system activity, and autonomic function assessed by HRV in acute stroke phase was independently associated with unfavorable outcomes in patients undergoing IVT.

Recombinant High-Density Lipoprotein Boosts the Therapeutic Efficacy of Mild Hypothermia in Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to neuropsychiatric symptoms and increased risk of neurodegenerative disorders. Mild hypothermia is commonly used in patients suffering from severe TBI. However, its effect for long-term protection is limited, mostly because of its insufficient anti-inflammatory and neuroprotective efficacy and restricted treatment duration. Recombinant high-density lipoprotein (rHDL), which possesses anti-inflammatory and antioxidant activity and blood-brain barrier (BBB) permeability, was expected to potentially strengthen the therapeutic effect of mild hypothermia in TBI treatment. To test this hypothesis and optimize the regimen for combination therapy, the efficacy of mild hypothermia plus concurrent or sequential rHDL on oxidative stress, inflammatory reaction, and cell survival in the damaged brain cells was evaluated. It was found that the effect of combining mild hypothermia with concurrent rHDL was modest, as mild hypothermia inhibited the cellular uptake and lesion-site-targeting delivery of rHDL. In contrast, the combination of mild hypothermia with sequential rHDL more powerfully improved the anti-inflammatory and antioxidant activities, promoted nerve cell survival and BBB restoration, and ameliorated neurologic changes, which thus remarkably restored the spatial learning and memory ability of TBI mice. Collectively, these findings suggest that rHDL may serve as a novel nanomedicine for adjunctive therapy of TBI and highlight the importance of timing of combination therapy for optimal treatment outcome.

[Clinical application of penile biological vibration threshold for precise use of 5% lidocaine cream to treat hypersensitive premature ejaculation].

OBJECTIVE: This study aimed to evaluate the efficacy and safety of applying 5% lidocaine cream to the sensitive area of the glans penis after its precise localization under the penile biological vibration threshold test for the treatment of primary premature ejaculation. METHODS: Eighty patients diagnosed with primary premature ejaculation in an outpatient setting were included in this study. They were randomly scored into two groups. Group 1 (n = 40) was given 1 ml of 5% lidocaine cream on demand. They were instructed to apply the lidocaine cream evenly in a circular pattern to the glans penis without precise application to the sensitive area of the glans penis. The treatment lasted for a total of 4 weeks. Group 2 (n = 40) had a penile biological vibration threshold test performed to detect loci with a lower threshold. They were instructed to apply 1 ml of 5% lidocaine cream to the sensitive loci on the glans penis for 4 weeks. Lidocaine cream was applied topically or uniformly to the glans penis 20 minutes before planned intercourse in both groups .The efficacy and side effects before and after treatment were evaluated by the intravaginal ejaculation latency (IELTs) before and after treatment, combined with the Arabic Index of Premature Ejaculation and IIEF-5 score. RESULTS: After treatment, IELTs in both groups were significantly improved compared with those before treatment(P<0.05);The Arab premature ejaculation index and IIEF-5 score of the precise smear group are higher than those of the uniform smear group(P<0.05). CONCLUSION: This study infers that applying lidocaine according to the threshold of penile and glans vibration has a positive effect and fewer adverse event reports compared with the traditional method of using surface anesthetics, which is worthy of clinical promotion.

Traditional chinese medicine to prevent and treat diabetic erectile dysfunction.

Diabetic erectile dysfunction (DED) is one of the most common complications of diabetes mellitus. However, current therapeutics have no satisfactory effect on DED. In recent years, traditional Chinese medicine (TCM) has shown good effects against DED. By now, several clinical trials have been conducted to study the effect of TCM in treating DED; yet, the underlying mechanism is not fully investigated. Therefore, in this review, we briefly summarized the pathophysiological mechanism of DED and reviewed the published clinical trials on the treatment of DED by TCM. Then, the therapeutic potential of TCM and the underlying mechanisms whereby TCM exerts protective effects were summarized. We concluded that TCM is more effective than chemical drugs in treating DED by targeting multiple signaling pathways, including those involved in oxidation, apoptosis, atherosclerosis, and endothelial function. However, the major limitation in the application of TCM against DED is the lack of a large-scale, multicenter, randomized, and controlled clinical trial on the therapeutic effect, and the underlying pharmaceutical mechanisms also need further investigation. Despite these limitations, clinical trials and further experimental studies will enhance our understanding of the mechanisms modulated by TCM and promote the widespread application of TCM to treat DED.

Identification and functional analysis of LncRNA-XIST ceRNA network in prostate cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) play a functional role in the progression of prostate cancer (PCa). However, the molecular mechanism, expression, or function of the lncRNA XIST in PCa is not well understood. Therefore, the major goal of this study was to investigate the involvement of XIST in PCa. METHODS: We used the The Cancer Genome Atlas (TCGA) database to conduct a pan-cancer bioinformatics analysis of XIST and identified that it may play an important role in prostate cancer. This finding was verified using clinical samples and in vitro assays. Finally, we constructed an XIST ceRNA network for prostate cancer. RESULTS: Our in vitro and in vivo results showed that the XIST gene expression level was higher in PCa derived cells and tissues compared to that in normal cells and tissues. XIST gene expression level was positively correlated with the invasion and proliferation of tumour cells. Furthermore, the downregulation of XIST inhibited the growth of subcutaneous 22Rv1 xenografts in nude mice. In addition, we constructed a XIST ceRNA network. Consistent with previous studies, we found that the role of XIST is mediated through via sponges, such as miRNA -96-5p, miRNA -153-3p, and miRNA-182-5p. CONCLUSION: High expression level of XIST can lead to enhanced carcinogenicity in PCa. Therefore, XIST has the potential to be used as a prognostic marker and may become a new research focus for the treatment of PCa.

On blind separability based on the temporal predictability method.

This letter discusses blind separability based on temporal predictability (Stone, 2001 ; Xie, He, & Fu, 2005 ). Our results show that the sources are separable using the temporal predictability method if and only if they have different temporal structures (i.e., autocorrelations). Consequently, the applicability and limitations of the temporal predictability method are clarified. In addition, instead of using generalized eigendecomposition, we suggest using joint approximate diagonalization algorithms to improve the robustness of the method. A new criterion is presented to evaluate the separation results. Numerical simulations are performed to demonstrate the validity of the theoretical results.