Differentiation of skin incision and laparoscopic trocar insertion via quantifying transient bradycardia measured by electrocardiogram.

Most surgical procedures involve structures deeper than the skin. However, the difference in surgical noxious stimulation between skin incision and laparoscopic trocar insertion is unknown. By analyzing instantaneous heart rate (IHR) calculated from the electrocardiogram, in particular the transient bradycardia in response to surgical stimuli, this study investigates surgical noxious stimuli arising from skin incision and laparoscopic trocar insertion, and their difference. Thirty-five patients undergoing laparoscopic cholecystectomy were enrolled in this prospective observational study. Sequential surgical steps including umbilical skin incision (11 mm), umbilical trocar insertion (11 mm), xiphoid skin incision (5 mm), xiphoid trocar insertion (5 mm), subcostal skin incision (3 mm), and subcostal trocar insertion (3 mm) were investigated. IHR was derived from electrocardiography and calculated by the modern time-varying power spectrum. Similar to the classical heart rate variability analysis, the time-varying low frequency power (tvLF), time-varying high frequency power (tvHF), and tvLF-to-tvHF ratio (tvLHR) were calculated. Prediction probability (PK) analysis and global pointwise F-test were used to compare the statistical performance between indices and the heart rate readings from the patient monitor. Analysis of IHR showed that surgical stimulus elicits a transient bradycardia, followed by the increase of heart rate. Transient bradycardia is more significant in trocar insertion than skin incision (p < 0.001 for tvHF). The IHR change quantifies differential responses to different surgical intensity. Serial PK analysis demonstrates de-sensitization in skin incision, but not in laparoscopic trocar insertion. Quantitative indices present the transient bradycardia introduced by noxious stimulation. The results indicate different effects between skin incision and trocar insertion.

ROS-scavenging lipid-based liquid crystalline as a favorable stem cell extracellular vesicles delivery vector to promote wound healing.

Wound management is a critical clinical challenge due to the dynamic and complex pathological characteristics of inflammation, proliferation, and matrix remodeling. To address this challenge, the regulation and management of this multi-stage pathological microenvironment may provide a feasible approach to wound healing. In this work, we synthesized a new lipid material (DA) with reactive oxygen species (ROS) scavenging effect to prepare DA-based liquid crystalline (DALC). Then, DALC was incorporated with adipose mesenchymal stem cells-derived extracellular vesicles (AMSC-EVs) to fabricate a novel scaffold dressing (EVs@DALC) for the treatment of the wound. DALC not only endowed EVs@DALC with ROS scavenging sites for relieving the oxidative stress and inflammation in the microenvironment of the wound site, but also facilitated cellular uptake and transfection of microRNA and growth factors contained in AMSC-EVs. Benefiting from DALC, AMSC-EVs effectively transferred microRNA and growth factors into the skin cells to induce cell proliferation and migration and accelerate angiogenesis. The results of wound healing effect in vivo indicate EVs@DALC achieved multi-stage pathological modulation for accelerating wound healing through alleviating inflammation, promoting cell proliferation and migration, and angiogenesis. Taken together, this work provides an effective strategy based on antioxidant lipid liquid crystalline delivering extracellular vesicles in treating skin wounds and paves a way for stem cell extracellular vesicles clinical translation.

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

Zwitterionic Injectable Hydrogel-Combined Chemo- and Immunotherapy Medicated by Monomolecular Micelles to Effectively Prevent the Recurrence of Tumor Post Operation.

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.

Differential influences of rest tremor on brain fiber architecture in essential tremor and Parkinson's disease.

BACKGROUND: Rest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear. METHODS: This study included 57 ET patients (40 without rest tremor (ETWR), 17 with rest tremor (ETRT)), 68 PD patients (34 without rest tremor (PDWR), 34 with rest tremor (PDRT)), and 62 normal controls (NC). Fixel-based analysis was used to evaluate the structural changes of white matter in rest tremor in these different diseases. RESULTS: The fiber-bundle cross-section (FC) of the right non-decussating dentato-rubro-thalamic tract and several fibers outside the dentato-rubro-thalamic pathway in ETWR were significantly higher than that in NC. The fiber density and cross-section of the left nigro-pallidal in PDWR is significantly lower than that in NC, while the FC of bilateral nigro-pallidal in PDRT is significantly lower than that in NC. CONCLUSION: ET patients with pure action tremor showed over-activation of fiber tracts. However, when superimposed with rest tremor, ET patients no longer exhibited over-activation of fiber tracts, but rather showed a trend of fiber tract damage. Except for the nigro-pallidal degeneration in all PD, PDRT will not experience further deterioration in fiber organization. These results provide important insights into the unique effects of rest tremor on brain fiber architecture in ET and PD.

Research progress of exosomes as drug carriers in cancer and inflammation.

Extracellular vesicles (EVs) could be produced by most cells and play an important role in disease development. As a subtype of EVs, exosomes exhibit suitable size, rich surface markers and diverse contents, making them more appealing as potential drug carriers. Compared with traditional synthetic nanoparticles, exosomes possess superior biocompatibility and much lower immunogenicity. This work reviewed the most up-to-date research progress of exosomes as carriers for nucleic acids, proteins and small molecule drugs for cancer and inflammation management. The drug loading strategies and potential cellular uptake behaviour of exosomes are highlighted, trying to provide reference for future exosome design and application.

Exosomes are secreted by a variety of cells and play an important role in the process of inter-cell communication.This paper provides a comprehensive review focussing on the up-to-date applications of exosomes as carriers of nucleic acids, proteins and small molecule drugs for cancer and inflammation management.This paper briefly introduces the basic properties of exosomes, from definition, biogenesis to cellular uptake manners.Various strategies to enable exosomes to efficiently load cargoes are highlighted.Problems to be solved when using exosomes to deliver drugs are discussed.

The psychometric properties of Binge Eating Scale among overweight college students in Taiwan.

BACKGROUND: The Binge Eating Scale (BES) is a widely used measuring tool to assess binge eating problems in Western countries. However, the psychometric properties of such scales among cross-cultural youth groups are insufficient, and the factor structure continues to be debated; therefore, further research is needed. The aim of this study was to examine the properties of BES among overweight college students in Taiwan. METHODS: A cross-sectional design and convenience sampling were adopted to recruit 300 overweight students from five universities. A translated Traditional Chinese version of BES was used for the survey, and the validity of the scale was tested using the Confirmatory Factor Analysis (CFA) and Bulimic Investigatory Test, Edinburgh (BITE). The reliability was evaluated using internal consistency and test-retest reliability. RESULTS: The CFA results showed a reasonable model fit. The first-order two-factor model was consistent with that of the original BES and significantly correlated with the criterion of BITE score. Cronbach's α value, representing internal consistency reliability, and the intraclass correlation coefficient of repeated measures made one month apart were both 0.83, indicating good reliability and stability. Significant correlations were observed between the BES score and sex and BMI; however, no correlation was observed between BES scores and age. CONCLUSION: The BES presents sound psychometric properties, has good cross-cultural applicability, and can be used as a first-line screening tool by mental health professionals to identify the severity of binge eating behavior among overweight college students in Taiwan. It is recommended that participant diversity and obesity indicators be incorporated into the scale in the future to establish a universal psychometric tool.

The Binge Eating Scale (BES) is a screening tool that has been widely used to assess binge eating problems in Western countries. The current study aimed to test the validity and reliability properties of the BES among overweight college students in Taiwan. This research involved 300 overweight and obese college students while using a traditional Chinese-translated questionnaire in the survey and analyzed with subjective and scientific statistics methods afterward. The results indicated that BES has good cross-cultural applicability and can be used as a first-line measuring tool by mental health professionals to identify the severity of binge eating behavior among overweight or obese college students in Taiwan.

Salt sensitive purely zwitterionic physical hydrogel for prevention of postoperative tissue adhesion.

Abdominal adhesions are a class of serious complications following abdominal surgery, resulting in a complicated and severe syndrome and sometimes leading to a Gordian knot. Traditional therapies employ hydrogels synthesized using complicated chemical formulations-often with click chemistry or thermal responsive hydrogel. The complicated synthesis process and severe conditions limit the extent of the hydrogels' applications. In this work, poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) polymer was synthesized to self-assemble into physical hydrogels due to the inter- and intramolecular ion interactions. The strong static interaction bonding density has a substantial impact on the gelation and physicochemical properties, which is beneficial to clinical applications and offers a novel way to obtain the desired hydrogel for a specific biomedical application. Intriguingly, this PSBMA polymer can be customized into a transient network with outstanding antifouling capability depending on the ion concentration. As ion concentration increases, the PSBMA hydrogel dissociated completely, endowing it as a candidate for adhesion prevention. In the cecum-sidewall model, the PSBMA hydrogel demonstrated superior anti-adhesion properties than commercial HA hydrogel. Furthermore, we have demonstrated that this PSBMA hydrogel could inhibit the inflammatory response and encourage anti-fibrosis resulting in adhesion prevention. Most surprisingly, the recovered skins of cecum and sidewall are as smooth as the control skin without any scar and damage. In conclusion, a practical hydrogel was synthesized using a facile method based on purely zwitterionic materials, and this ion-sensitive, antifouling adjustable supramolecular hydrogel with great clinic transform potential is a promising barrier for preventing postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: The development of hydrogels with satisfactory coverage, long retention time, facile synthetic method, and good biocompatibility is vital for preventing peritoneal adhesions. Herein, we developed a salt sensitive purely zwitterionic physical hydrogel poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) hydrogel to effectively prevent postoperative and recurrent abdominal adhesions. The hydrogel was simple to synthesize and easy to use. In the cecum-sidewall model, PSBMA hydrogel could instantaneously adhere and fix on irregular surfaces and stay in the wound for more than 10 days. The PSBMA hydrogel could inhibit the inflammatory response, encourage anti-fibrosis, and restore smoothness to damaged surfaces resulting in adhesion prevention. Overall, the PSBMA hydrogel is a promising candidate for the next generation of anti-adhesion materials to meet clinical needs.

A dual-sensitive nanoparticle-mediated deepening synergistic therapy strategy involving DNA damage and ICD stimuli to treat triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy, remains difficult. To solve this puzzle, a deepening synergistic therapy strategy of DNA damage and immunogenic cell death (ICD) stimuli was proposed. We engineered a doxorubicin (DOX) and 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) prodrug polymer, and encapsulated chlorin e6 (Ce6) to obtain the hyaluronidase (HAase) and H2O2 dual-sensitive responsive nanoparticles (Ce6/HDP NPs). The NPs displayed efficient intratumoral accumulation and cellular internalization properties due to the active targeting of the hyaluronic acid (HA). The dual DNA damage of the chemotherapy and ROS production directly caused tumor cell apoptosis. The strong ICD stimuli, which were induced by ROS production and GSH depletion, generated an amplified immunogenicity to activate tumor immunotherapy in vivo. In this manner, the NPs could significantly inhibit primary tumor, abscopal tumor, pulmonary metastasis and recurrent tumor in a subcutaneous 4T1 tumor model, with effective biosafety. This study has provided a promising deepening synergistic therapy strategy against TNBC.

Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation.

Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

Injectable Zwitterionic Physical Hydrogel with Enhanced Chemodynamic Therapy and Tumor Microenvironment Remodeling Properties for Synergistic Anticancer Therapy.

Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO2/DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO2/DOX). Next, M/CuO2/DOX and the stimulator of interferon genes (STING) agonist 2',3'-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO2/DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO2/DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8+ T cell infiltration, and preventing postoperative recurrence and metastasis.

Research progress in tumor targeted immunotherapy.

INTRODUCTION: Compared with traditional cancer treatment methods, tumor-targeted immunotherapy can combine targeted therapy and immunotherapy with long-lasting responses to achieve synergistic therapy, which brings hope to the complete cure of cancer. AREAS COVERED: This review summarizes the newest and most up-to-date advances in tumor-targeted immunotherapy, including tumor-associated macrophages (TAMs) targeted immunotherapy, regulatory T (Treg) cells targeted immunotherapy, tumor-associated fibroblasts (TAFs) targeted immunotherapy and immune checkpoints targeted immunotherapy. EXPERT OPINION: Immunotherapy can restore anti-tumor immunity in the tumor microenvironment and produce a lasting immune surveillance effect. Smart multifunctional nano delivery system can effectively combine targeted therapy with immunotherapy, which has attracted extensive attention. With the deepening of research, more and more tumor-targeted immunotherapy enter into the clinical trial phases, especially antibodies and inhibitors. Tumor-targeted immunotherapy is a promising approach for conquering cancer and bringing hope for human health.

Phlebosclerotic colitis: A case report and review of the literature.

Phlebosclerotic colitis (PC) is a rare but potentially life-threatening disease. The initial presentation may include non-specific symptoms, such as vomiting, constipation and abdominal pain; however, intestinal stenosis, gangrene and perforation may occur without appropriate management. The present report describes the case of a 56-year-old male with abdominal pain and constipation. Imaging studies revealed thread-like calcifications involving almost the entire colon, which had markedly progressed over a three-year period, and changes consistent with colonic ischemia. Angiography revealed decreased blood flow in the mesenteric veins. The patient underwent emergent subtotal colectomy, and pathological examination revealed gangrene of the colon and calcifications of the mesenteric veins. The patient's postoperative course was uneventful. In conclusion, PC is a potentially life-threatening condition that may be diagnosed by the presence of serpentine calcifications on imaging studies. Management depends on the severity of the disease, ranging from close follow-up to prompt surgical intervention.