In-situ forming carboxymethyl chitosan hydrogel containing Paeonia suffruticosa Andr. leaf extract for mixed infectious vaginitis treatment by reshaping the micro-biota.

Mixed infectious vaginitis poses a serious threat to female reproductive health due to complex pathogenic factors, a long course and easy recurrence. Currently, antibiotic-based treatment methods are facing a crisis of drug resistance and secondary dysbiosis. Exploring effective drugs for the treatment of mixed vaginitis from Paeonia suffruticosa Andr., a natural traditional Chinese medicine with a long history of medicinal use, is a feasible treatment strategy. P. suffruticosa Andr. leaf extract (PLE) has significant anti-bacterial effects due to its rich content of polyphenols and flavonoids. The polyphenols in peony leaves have the potential to make carboxymethyl chitosan form in situ gel. In the current study, PLE and carboxymethyl chitosan were combined to develop another type of natural anti-bacterial anti-oxidant hydrogel for the treatment of mixed infectious vaginitis. Through a series of characterisations, CP had a three-dimensional network porous structure with good mechanical properties, high water absorption, long retention and a slow-release drug effect. The mixed infectious vaginitis mouse model induced by a mixture of pathogenic bacteria was used to investigate the therapeutic effects of CP in vivo. The appearance of the vagina, H&E colouring of the tissue and inflammatory factors (TNF-α, IL-6) confirm the good anti-vaginal effect of CP. Therefore, CP was expected to become an ideal effective strategy to improve mixed infection vaginitis due to its excellent hydrogel performance and remarkable ability to regulate flora.

The presence of a cribriform pattern is related to poor prognosis in lung adenocarcinoma after surgical resection: A meta-analysis.

OBJECTIVE: Previous studies reported that the cribriform pattern (CP) was associated with poor prognosis in lung adenocarcinoma (ADC) patients; therefore, a meta-analysis was performed to thoroughly evaluate the prognostic impact of cribriform pattern in postoperative ADC patients. METHODS: Eligible studies were retrieved from PubMed, Embase databases, and Web of Science until April 2023. Studies evaluating the effect of the cribriform pattern on the prognosis of postoperative ADC patients were included. Subsequently, subgroup analysis was conducted according to the proportion of the cribriform pattern, with disease-free survival (DFS) and/or overall survival (OS) as outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect estimates in the meta-analyses, which were performed with a random-effects model despite the heterogeneity. RESULTS: Nine studies published between 2015 and 2022 were included, with 4,289 ADC patients in total. The pooled results revealed a significantly poorer DFS (HR1.56, 95%CI 1.18-2.06, P = 0.11, I2 = 45%) and OS (HR2.11, 95%CI 1.63-2.72, P = 0.01, I2 = 56%) in patients with the cribriform pattern. Furthermore, the subgroup analysis showed that patients with a cribriform pattern (DFS: HR1.32, 95% CI 1.04-1.68 OS:HR2.30, 95% CI 1.55-3.39) and patients with a predominantly cribriform pattern (DFS:HR2.04, 95% CI 1.32--3.15 OS: HR1.92, 95% CI 1.41-2.61) were associated with poor prognosis. CONCLUSIONS: The presence of a cribriform pattern is related to poor prognosis in postoperative ADC patients, despite not being a main tumor component. However, the results should be confirmed by large-scale and prospective studies owing to the small sample and potential heterogeneity.

[Stellera chamaejasme against multidrug resistance of triple-negative breast cancer MDA-MB-231 cell through Nrf2].

This study aims to investigate the effect and mechanism of Stellera chamaejasme extract(SCL) on multidrug resistance(MDR) in breast cancer. Human triple-negative breast cancer cell line MDA-MB-231 and its adriamycin-resistant cell line MDA-MB-231/ADR were used in the experiment. Cell viability was detected by methyl thiazolyl tetrazolium(MTT) assay, and cell apoptosis was detected by DAPI staining and Annexin-V/Pi double staining. Western blot(WB) was used to detect the expression levels of Keap1, Nrf2, HO-1, Bcl-2, Bax, caspase-9, and caspase-3. Immunofluorescence staining was used to observe the distribution of Nrf2 in the cell, and flow cytometry was used to detect the level of reactive oxygen species(ROS) in the cell. The results showed that the resis-tance factor of SCL was 0.69, and that of adriamycin and paclitaxel was 8.40 and 16.36, respectively. DAPI staining showed that SCL could cause nuclear shrinkage and fragmentation of breast cancer cells. Annexin-V/Pi double staining showed that the average apoptosis rate of the drug-resistant cells was 32.64% and 50.29%, respectively under medium and high doses of SCL. WB results showed that SCL could significantly reduce the expression levels of anti-apoptotic proteins Bcl-2, caspase-9, and caspase-3 and significantly increase the expression level of pro-apoptotic protein Bax. Further studies showed that SCL could significantly promote the expression of Keap1, significantly inhibit the expression of Nrf2 and HO-1, and significantly reduce the expression level of Nrf2 in the nucleus. Correspondingly, flow cytometry showed that the intracellular ROS level was significantly increased. In conclusion, SCL can significantly inhibit the proliferation of MDA-MB-231 multidrug-resistant cells of triple-negative breast cancer and cause cell apoptosis, and the mechanism is related to inhibiting Keap1/Nrf2 signaling pathway, leading to ROS accumulation in drug-resistant cells and increasing the expression of apoptosis-related proteins.

Comprehensive Pan-Cancer Analysis of Connexin 43 as a Potential Biomarker and Therapeutic Target in Human Kidney Renal Clear Cell Carcinoma (KIRC).

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein-protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.

Local delivery of stem cell spheroids with protein/polyphenol self-assembling armor to improve myocardial infarction treatment via immunoprotection and immunoregulation.

Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.

Effect of subanesthetic dose of esketamine on postoperative pain in elderly patients undergoing laparoscopic gastrointestinal tumor Surgery:A prospective, double-blind, randomized controlled trial.

Purpose: Postoperative pain is prevalent and severe complication in elderly surgical patients. Multiple studies propose that a small dose of esketamine administered intraoperatively can alleviate postoperative pain and curtail opioid usage. We aimed to evaluate the impact of esketamine on postoperative acute pain among elderly patients with gastrointestinal tumors. Patients and methods: This is a prospective, parallel-group, randomized controlled trial. Ninety patients aged 60 and above, undergoing resection of gastrointestinal tumors, were randomly assigned to two groups: esketamine group (Group S, a single dose of 0.25 mg/kg and 0.1 mg/kg/h infusion) and control group (Group C, saline). Visual Analogue Scale (VAS) pain scores were the primary outcome. Remifentanil consumption, instances of rescue analgesia, delirium, sleep quality, postoperative recovery quality, serum levels of inflammatory cytokines, and adverse events within 72 h post-surgery were secondary outcomes, respectively. Results: Data of 87 of 99 eligible patients were analyzed. VAS scores at rest in Group S were lower than those in Group C at 6 h [1.2 (0.6, 1.6) vs 1.6 (1.0, 2.0), P = 0.003], 12 h [1.4 (1.0, 2.0) vs 2.0 (1.5, 2.0), P < 0.001], and 24 h [1.8 (1.3, 2.0) vs 2.2 (1.6, 2.6), P < 0.001] postoperatively. At 6 h post-surgery, VAS score during coughing was lower in Group S than Group C [2.0 (2.0, 2.3) vs 2.0 (2.0, 3.0), P = 0.009]. The instances of rescue analgesia were fewer in group S compared to group C (P = 0.007). Furthermore, the esketamine group showed improved sleep quality and QoR-15 score (P < 0.05) postoperatively. Conclusion: Intravenous administration of esketamine as an adjunct to general anesthesia can decrease the intensity of pain for 24 h without additional adverse effects after laparoscopic gastrointestinal tumor surgery.

A dual network cross-linked hydrogel with multifunctional Bletilla striata polysaccharide/gelatin/tea polyphenol for wound healing promotion.

Wound healing is a dynamic and complex biological process, and traditional biological excipients cannot meet the needs of the wound healing process, and there is an urgent need for a biological dressing with multifunctionality and the ability to participate in all stages of wound healing. This study developed tea polyphenol (TP) incorporated multifunctional hydrogel based on oxidized Bletilla striata polysaccharide (OBSP) and adipic acid dihydrazide modified gelatin (Gel-ADH) with antimicrobial, antioxidant hemostatic, and anti-inflammatory properties to promote wound healing. The composite OBSP, Gel-ADH, TP (OBGTP) hydrogels prepared by double crosslinking between OBSP, TP and Gel-ADH via Schiff base bonding and hydrogen bonding had good rheological and swelling properties. The introduction of TP provided the composite hydrogel with excellent antioxidant antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil). In the rat liver hemorrhage model and skin injury model, the OBGTP composite hydrogel had significant (p < 0.001) hemostatic ability, and had the ability to accelerate collagen deposition, reduce the expression of inflammatory factors, and promote rapid wound healing. In addition, OBGTP hydrogels had adhesive properties and good biocompatibility. In conclusion, OBGTP multifunctional composite hydrogels have great potential for wound healing applications.

Case report: Clinical complete response in advanced ALK-positive lung squamous cell carcinoma: a case study of successful anti-PD-1 immunotherapy post ALK-TKIs failure.

In patients with advanced lung adenocarcinoma (LADC) harboring the echinoderm microtubule-associated protein-like 4 (EML4) -anaplastic lymphoma kinase (ALK) rearrangement, targeted therapy typically demonstrates superior efficacy as an initial treatment compared to chemotherapy. Following resistance to ALK-tyrosine kinase inhibitors (TKIs), regimens incorporating platinum-based dual agents or combined with bevacizumab often show effectiveness. However, therapeutic alternatives become constrained after resistance develops to both TKIs and platinum-based therapies. Given that the majority of ALK-positive non-small cell lung carcinomas (NSCLC) are LADC, the benefits of TKIs for patients with ALK-positive lung squamous cell carcinoma (LSCC) and the optimal treatment strategy for these patients remain a subject of debate. In this case study, we report on a patient with advanced LSCC, in whom the EML4-ALK rearrangement was identified via ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction). The patient underwent oral treatment with crizotinib and alectinib, showing effectiveness in both first-line and second-line ALK-TKI therapies, albeit with limited progression-free survival (PFS). Subsequent resistance to second-generation TKI was followed by the detection of tumors in the left neck region via computed tomography (CT). Biopsy pathology revealed non-squamous cell carcinoma, and subsequent treatment with platinum-based double-drug therapy proved ineffective. Further analysis through next-generation sequencing (NGS) indicated ALK negativity but a high expression of programmed death-ligand 1 (PD-L1). Immunotherapy was then initiated, resulting in a PFS of over 29 months and clinical complete remission (cCR). This case underscores the potential benefit of ALK-TKIs in patients with ALK-positive LSCC. Resistance to second-generation TKIs may lead to ALK negativity and histological transformation, highlighting the necessity of repeated biopsies post-TKI resistance for informed treatment decision-making. As of November 2023, imaging studies continue to indicate cCR in the patient, with a survival time exceeding 47 months.

Association between Atopic Dermatitis and Colorectal Cancer: TET2 as a Shared Gene Signature and Prognostic Biomarker.

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.

Efficacy of dexmedetomidine combined with ropivacaine on postoperative analgesia and delirium in elderly patients with total knee arthroplasty.

This study aimed to investigate the impact of dexmedetomidine combined with ropivacaine on continuous femoral nerve block (CFNB) in postoperative analgesia and delirium in elderly patients with total knee arthroplasty (TKA). A total of 120 patients who undergone TKA were randomly assigned into group D + R (dexmedetomidine combined with ropivacaine) and group R (only ropivacaine), with 60 cases in each group. The pain scores at rest and exercise at 6 h, 12 h, 24 h, and 48 h postoperatively. The occurrence of delirium on Day 1, Day 2, and Day 3 postoperatively were measured, and the sleep quality was evaluated before surgery, the night of surgery, and 24 h postoperatively to observe the occurrence of postoperative complications. The Visual analogu scale (VAS) of group D + R at 12 h, 24 h, and 48 h postoperatively were lower than those of group R in both rest and exercise states. The incidence of postoperative delirium in group D + R was lower than that in group R on Day 1 and Day 2. Pittsburgh sleep quality index (PSQI) scores in group D + R were lower than those in group R. There was no significant difference in postoperative adverse reactions between the two groups. Dexmedetomidine combined with ropivacaine improves postoperative analgesia and sleep quality, and alleviates the occurrence of postoperative delirium in elderly patients with TKA.

Direct visualization of immune status for tumor-infiltrating lymphocytes by rolling circle amplification.

The immune status of tumor-infiltrating lymphocytes (TILs) is essential for the effectiveness of cancer immunotherapies. However, due to the diversity of immune status in TILs, cellular heterogeneity, and the applicability to the clinic, it is still lacking effective strategies to meet clinical needs. We developed a novel immuno-recognition-induced method based on rolling circle amplification (RCA), namely immunoRCA, to in situ visualize the immune status of TILs in actual clinical samples. This developed immunoRCA method, in which, feature mRNAs were used as the biomarkers for the immune status of TILs, has a low fluorescence background, high sensitivity, and specificity. The immunoRCA was able to efficiently evaluate the immune status of CD8+ T cells regulated by activating or inhibiting factors, track the T cell type and immune status during in vitro expansion, and in situ visualize the number, location, and immune status of TILs in clinical specimens.

The Safety and Feasibility of Pulsed-Field Ablation in Atrioventricular Nodal Re-Entrant Tachycardia: First-in-Human Pilot Trial.

BACKGROUND: The incidence of atrioventricular conduction system damage during the catheter ablation procedure has long been a safety concern in patients with atrioventricular nodal re-entrant tachycardia (AVNRT). Pulsed-field ablation (PFA) with high tissue selectivity is a promising technique to address this problem in patients with AVNRT. OBJECTIVES: This study aimed to evaluate the safety and feasibility of PFA in patients with AVNRT. METHODS: This was an investigator-initiated, single-center, single-arm, prospective study performed in West China Hospital, Sichuan University. Patients diagnosed with AVNRT by electrophysiological examination were included and treated using PFA. The primary outcome was the ability to achieve acute ablation success. The secondary outcomes were ablation success after 6 months and safety incidents reported. RESULTS: A total of 30 patients with AVNRT with a mean age of 47.9 ± 13.9 years were included and underwent PFA. Acute ablation success was achieved in all patients. The skin-to-skin procedure time was 109.1 ± 32.1 minutes, and fluoroscopy time was 4.1 ± 0.9 minutes. A median of 8 (range: 6.5 to 11.0) PFA applications were delivered. The average distance of the closest ablation site to the His bundle was 6.5 ± 2.5 mm, with a minimum distance of 2.0 mm. All patients maintained sinus rhythm after 6 months. No adverse events occurred in any patient during the ablation or the 6-month follow-up. CONCLUSIONS: PFA showed favorable feasibility and safety in patients with AVNRT in this pilot study. Further study with larger population and longer follow-up time is warranted to verify the results.

The Influence of Scar Patterns After Reduction Mammoplasty on Eye Movement and Gaze Pattern: An Eye-Tracking Investigation.

BACKGROUND: Given that scars are acknowledged as the primary cause of postoperative dissatisfaction following reduction mammoplasty, it is imperative to comprehend the patient's visual perception of different scar patterns in order to enhance patient satisfaction. To achieve this, eye-tracking technology provides an unbiased method of evaluating how observers assess breast scars. METHODS: 58 participants (32 females and 26 males) between the ages of 19 and 82 years (mean age of 29.47 ± 10.98 years) were shown 18 color photographs, taken at 3 viewing angles (right 45° oblique, frontal and frontal view with arms raised), from 6 patients undergone reduction mammoplasty with the inverted T-scar technique (3 patients) or no-vertical-scar technique (3 patients). The images were presented to every participant for a fixed duration of 5 s each. Eye-tracking device was used to collect and analyze the gaze data of viewers. RESULTS: The nipple-areola complex (NAC) and the periareolar scar captured observers' gaze faster, had longer duration and more count of eye fixation than all other parts of breast scars, regardless of the viewing angle and scar pattern. Moreover, the scar region in the inverted T-scar pattern received greater and faster visual attraction of observer's gaze than the no-vertical-scar pattern. CONCLUSION: The NAC and the periareolar scar seem to be perceived as the most important regions for breast aesthetics. The findings can be helpful to assist plastic surgeons in determining the most appropriate technique for reduction mammoplasty, meanwhile underlining the importance of a fine periareolar scar and symmetric NAC for excellent aesthetic outcomes. This is to our best knowledge the first study using eye-tracking technology in evaluating reduction mammoplasty outcomes. This study explored the influence of different scar patterns after reduction mammoplasty on eye movements and gaze patterns among observers. The study have validated the significance of the NAC and the periareolar scar for breast aesthetics and revealed that the scar region in the inverted T-scar pattern may be judged less visually attractive than the no-vertical-scar pattern. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors  www.springer.com/00266 .

Rapid On-Site AI-Assisted Grading for Lung Surgery Based on Optical Coherence Tomography.

The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human-machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion's location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.

Multi-system diseases and death trajectory of metabolic dysfunction-associated fatty liver disease: findings from the UK Biobank.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. METHODS: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. RESULTS: Participants aged 59 (51-64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid-base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. CONCLUSIONS: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.

Enantioselective Oral Absorption of Molecular Chiral Mesoporous Silica Nanoparticles.

Inspired by the unique pharmacological effects of chiral drugs in the asymmetrical body environments, it is assumed that the chirality of nanocarriers is also a key factor to determine their oral adsorption efficiency, apart from their size, shape, etc. Herein, l/d-tartaric acid modified mesoporous silica nanoparticles (l/d-CMSNs) are fabricated via a one-pot cocondensation method, and focused on whether the oral adsorption of nanocarriers will be benefited from their chirality. It is found that l-CMSN performed better in the sequential oral absorption processes, including mucus permeation, mucosa bio-adhesion, cellular uptake, intestinal transport and gastrointestinal tract (GIT) retention, than those of the d-chiral (d-CMSN), racemic (dl-CMSN), and achiral (MSN) counterparts. The multiple chiral recognition mechanisms are experimentally and theoretically demonstrated following simple differential adsorption on biointerfaces, wherein electrostatic interaction is the dominant energy. During the oral delivery task, l-CMSN, which is proven to be stable, nonirritative, biocompatible, and biodegradable, is efficiently absorbed into the blood (1.72-2.05-fold higher than other nanocarriers), and helps the loaded doxorubicin (DOX) to achieve better intestinal transport (2.32-27.03-times higher than other samples), satisfactory bioavailability (449.73%) and stronger antitumor effect (up to 95.43%). These findings validated the dominant role of chirality in determining the biological fate of nanocarriers.

Oropharynx pain, discomfort, and economic impact of transesophageal echocardiography for planned radio-frequency catheter ablation in patients with atrial fibrillation: A cross-sectional survey study.

Background: To survey the unmet medical needs associated with atrium thrombus screening in Chinese patients with atrial fibrillation (AF) who underwent transesophageal echocardiography (TEE) for planned radio-frequency catheter ablation (RFCA). Methods: This cross-sectional survey study interviewed 300 patients who underwent their first TEE for planned RFCA. The surveyed information included patients' anxiety, oropharynx pain and discomfort, time expense, and patient satisfaction related to TEE examination. Patient preference for a new atrium thrombus screening technology, hospital length of stay (LOS) of RFCA, and hospital costs of RFCA in these surveyed patients were collected as well. Descriptive statistical methods were used to summarize the collected survey information. Results: Of the 300 interviewed patients, 36.3% reported anxiety before TEE examination, 58.6% reported oropharynx pain related to TEE, and 76.2% reported oropharynx discomforts, mainly including foreign body sensation (54.3%), dry heaves (33.8%), nausea (31.9%), and bleeding (22.9%). Even though 62.3% were satisfied with TEE, 84.3% preferred a new technology to replace TEE. Conducting outpatient TEE took more wait time (4.4 days vs. 0.1 days, p = 0.016) but led to significantly shorter hospital LOS (3.8 days vs. 6.4 days, p < 0.001) and significant lower hospital costs for RFCA (¥74,097 vs. ¥85,843, p < 0.001) than conducting inpatient TEE. Conclusions: Most AF patients experienced oropharynx pain and discomfort during or after TEE. Although more than half of AF patients were satisfied with TEE, most AF patients preferred a new technology to replace TEE for atrium thrombus screening. TEE was associated with economic impact on RFCA irrespective of TEE conducting settings.

CD44-Targeted Photoactivatable Polymeric Nanosystem with On-Demand Drug Release as a "Photoactivatable Bomb" for Combined Photodynamic Therapy-Chemotherapy of Cancer.

Nowadays, the combined use of chemotherapy and photodynamic therapy (PDT) remains the most popular strategy for cancer treatment with high theraprutic efficacy. However, targeted therapy with the on-demand release of drugs is what most clinical treatments lack, leading to heavy side effects. Herein, a new CD44-targeted and red-light-activatable nanosystem, Ru-HA@DOX nanoparticles (NPs), was developed by conjugating hydrophilic biodegradable hyaluronic acid (HA) and hydrophobic photoresponsive ruthenium (Ru) complexes, which could encapsulate the chemotherapeutic drug doxrubicin (DOX). Ru-HA@DOX NPs can selectively accumulate at the tumor through the enhanced permeability and retention (EPR) effect and CD44-mediated endocytosis, thus avoiding off-target toxicity during circulation. After 660 nm of irradiation at the tumor site, Ru-HA@DOX NPs, as a "photoactivatable bomb", was split via the photocleavable Ru-N coordination bond to fast release DOX and produce singlet oxygen (1O2) for PDT. In general, Ru-HA@DOX NPs retained its integrity before irradiation and possessed minimal cytotoxicity, while under red-light irradiation, Ru-HA@DOX NPs showed significant cytotoxicity due to the release of DOX and production of 1O2 at the tumor. Chemotherapy-PDT of Ru-HA@DOX NPs resulted in a significant inhibition of tumor growth in A549-tumor-bearing mice and reduced the cardiotoxicity of DOX. Therefore, this study offers a novel CD44-targeted drug-delivery system with on-demand drug release for synergistic chemotherapy-PDT.

The same heterozygous Col4A4 mutation triggered different renal pathological changes in Chinese family members.

Background: Mutations in the collagen components of the glomerular basement membrane (GBM) often lead to hereditary glomerulonephritis. Previous studies have identified that autosomal dominant mutations of Col4A3, Col4A4 or Col4A5 are associated with thin basement membrane nephropathy (TBMN), Alport syndrome and other hereditary kidney diseases. However, the genetic mutations underlying other glomerulonephritis types have not been elucidated. Methods: In this study, we investigated a Chinese family with hereditary nephritis using the methods of genetic sequencing and renal biopsy. Genomic DNA was extracted from peripheral blood of the proband and her sister, and subsequently was performed genetic sequencing. They were found to have the similar mutation sites. Other family members were then validated using Sanger sequencing. The proband and her sister underwent renal puncture biopsies, and experienced pathologists performed PAS, Masson, immunofluorescence, and immunoelectron microscopic staining of the kidney tissue sections. Results: Through genetic sequencing analysis, we detected a novel heterozygous frameshift mutation c.1826delC in the COL4A4 (NM_000092.4) gene coding region, and 1 hybrid missense variation c.86G>A (p. R29Q) was also detected in the TNXB (NM_019105.6) gene coding region in several members of this Chinese family. Interestingly, we found that the same mutations caused different clinical features and distinct pathological changes in individual family members, which confirmed that pathological and genetic testing are crucial for the diagnosis and treatment of hereditary kidney diseases. Conclusion: In this study, we found a novel heterozygous mutation in Col4A4 and co-mutations of the TNXB gene in this Chinese family. Our study indicated that the same Col4A4 mutated variants produced different pathological and clinical changes in different family members. This discovery may provide novel insights into the study of hereditary kidney disease. In addition, new genetic biology techniques and renal biopsy of individual family members are essential.