Tracking the Cellular Degradation of Silver Nanoparticles: Development of a Generic Kinetic Model.

Understanding the degradation of nanoparticles (NPs) after crossing the cell plasma membrane is crucial in drug delivery designs and cytotoxicity assessment. However, the key factors controlling the degradable kinetics remain unclear due to the absence of a quantification model. In this study, subcellular imaging of silver nanoparticles (AgNPs) was used to determine the intracellular transfer of AgNPs, and single particle ICP-MS was utilized to track the degradation process. A cellular kinetic model was subsequently developed to describe the uptake, transfer, and degradation behaviors of AgNPs. Our model demonstrated that the intracellular degradation efficiency of AgNPs was much higher than that determined by mimicking testing, and the degradation of NPs was highly influenced by cellular factors. Specifically, deficiencies in Ca or Zn primarily decreased the kinetic dissolution of NPs, while a Ca deficiency also resulted in the retardation of NP transfer. The biological significance of these kinetic parameters was strongly revealed. Our model indicated that the majority of internalized AgNPs dissolved, with the resulting ions being rapidly depurated. The release of Ag ions was largely dependent on the microvesicle-mediated route. By changing the coating and size of AgNPs, the model results suggested that size influenced the transfer of NPs into the degradation process, whereas coating affected the degradation kinetics. Overall, our developed model provides a valuable tool for understanding and predicting the impacts of the physicochemical properties of NPs and the ambient environment on nanotoxicity and therapeutic efficacy.

Causal associations between dietary factors and colorectal cancer risk: a Mendelian randomization study.

Background: Previous epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive. Methods: We conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results. Results: MR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068-2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095-0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273-0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253-0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311-0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results. Conclusion: This study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention.

Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An Open-Label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label, randomized, nonplacebo-controlled clinical study. The numerical rating scale scores in the FMT group were slightly lower than the control group at 1 month (P > .05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < .001). Besides, compared with the control group, the Widespread Pain Index, Symptom Severity, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores were significantly lower in the FMT group at different time points (P < .001). After 6 months of treatment, there was a significant increase in serotonin (5-hydroxytryptamine) and gamma-aminobutyric acid levels (P < .001), while glutamate levels significantly decreased in the FMT group (P < .001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < .05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes in neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: FMT is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

A simultaneous strategy with multiple-signal amplification and self-calibration for ultrasensitive assay of miRNA-21 based on 3D MNPs-IL-rGO-AuNPs.

MicroRNA-21 (miRNA-21) is a significant biomarker for the development and progression of diverse cancers but is present in relatively low concentrations. Detecting such low-abundance molecules accurately can be challenging, especially in early-stage cancers where the concentration may be even lower. Herein, a self-calibration biosensing platform based on 3D novel MNPs-IL-rGO-AuNPs nanocomposites was successfully established for the ultrasensitive detection of miRNA-21. Duplex-specific nuclease (DSN) was introduced to recognize perfectly matched duplexes and trigger target recycling, enhancing the specificity and sensitivity of the biosensor. DSN-assisted target recycling, in conjunction with magnetic separation enrichment and high-performance MNPs-IL-rGO-AuNPs, collectively formed a multiple-signal amplification strategy. The obtained biosensor could output dual signals in both electrochemical and fluorescent modes, enabling self-correcting detection to enhance the accuracy. The obtained dual-mode biosensor prepared exhibited a wide detection range from 5 fM to 100 nM with a remarkably low LOD of 1.601 fM. It accomplished the sensitive evaluation of miRNA-21 in total RNA extracted from various human cancer cell lines and normal cell lines. Additionally, the greatly satisfactory outcomes in the analysis of human serum samples suggested that the proposed biosensor was a powerful screening candidate in early clinical diagnosis of cancer.

Remimazolam Dosing for Gastroscopy: A Randomized Noninferiority Trial.

BACKGROUND: Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. METHODS: This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. RESULTS: The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, -0.64%; 97.5% CI, -2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, -10.8%; 97.5% CI, -14.0% to -8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. CONCLUSIONS: This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.

Anesthetic management of thoracotomy for massive intrathoracic solitary fibrous tumor of the pleura: a case report.

BACKGROUNDS: Solitary fibrous tumor of the pleura (SFTP) is a rare thoracic tumor and usually asymptomatic. Massive SFTP may affect adjacent organs and tissues including pulmonary vasculature, bronchus and heart. A thoracotomy for massive SFTP is necessary in severe case. Therefore, it is important for anesthesiologists to understand the condition of patients with massive SFTP and develop an appropriate anesthetic management strategy. A 76-year-old woman with massive SFTP presented to our clinical center and was evaluated as requiring thoracotomy. She received multidisciplinary cooperation treatment from the radiology, cardiac, thoracic surgery and anesthetic teams. The perioperative management of anesthesiologists played a crucial role in the great prognosis of this woman. CONCLUSIONS: This case report demonstrates the importance of comprehensive and meticulous perioperative management and provides guidance to the multidisciplinary team on the potential risk and the rational treatment strategy of patients with massive SFTP during the perioperative period.

IRDC-Net: An Inception Network with a Residual Module and Dilated Convolution for Sign Language Recognition Based on Surface Electromyography.

Deaf and hearing-impaired people always face communication barriers. Non-invasive surface electromyography (sEMG) sensor-based sign language recognition (SLR) technology can help them to better integrate into social life. Since the traditional tandem convolutional neural network (CNN) structure used in most CNN-based studies inadequately captures the features of the input data, we propose a novel inception architecture with a residual module and dilated convolution (IRDC-net) to enlarge the receptive fields and enrich the feature maps, applying it to SLR tasks for the first time. This work first transformed the time domain signal into a time-frequency domain using discrete Fourier transformation. Second, an IRDC-net was constructed to recognize ten Chinese sign language signs. Third, the tandem CNN networks VGG-net and ResNet-18 were compared with our proposed parallel structure network, IRDC-net. Finally, the public dataset Ninapro DB1 was utilized to verify the generalization performance of the IRDC-net. The results showed that after transforming the time domain sEMG signal into the time-frequency domain, the classification accuracy (acc) increased from 84.29% to 91.70% when using the IRDC-net on our sign language dataset. Furthermore, for the time-frequency information of the public dataset Ninapro DB1, the classification accuracy reached 89.82%; this value is higher than that achieved in other recent studies. As such, our findings contribute to research into SLR tasks and to improving deaf and hearing-impaired people's daily lives.

Cu(I)/Cu(II) Released by Cu Nanoparticles Revealed Differential Cellular Toxicity Related to Mitochondrial Dysfunction.

Cu-based nanoparticles (NPs) have been increasingly fabricated, and different Cu species (i.e., Cu+ and Cu2+) of these NPs are tuned to achieve differential physicochemical properties. Although ion release is one of the major toxic mechanisms of Cu-based NPs, differences in cytotoxicity between released Cu(I) and Cu(II) ions are largely unknown. In this study, the A549 cells exhibited a lower tolerance to Cu(I) compared with Cu(II) accumulation. Bioimaging of labile Cu(I) indicated that the change of the Cu(I) level upon CuO and Cu2O exposure displayed different trends. We then developed a novel method to selectively release Cu(I) and Cu(II) ions within the cells by designing CuxS shells for Cu2O and CuO NPs, respectively. This method confirmed that Cu(I) and Cu(II) exhibited different cytotoxicity mechanisms. Specifically, excess Cu(I) induced cell death through mitochondrial fragmentation, which further led to apoptosis, whereas Cu(II) resulted in cell cycle arrest at the S phase and induced reactive oxygen species generation. Cu(II) also led to mitochondrial fusion, which was likely due to the influence of the cell cycle. Our study first uncovered the difference between the cytotoxicity mechanisms of Cu(I) and Cu(II), which could be greatly beneficial for the green fabrication of engineered Cu-based NPs.

BMSC-Derived Exosomes Alleviate Sepsis-Associated Acute Respiratory Distress Syndrome by Activating the Nrf2 Pathway to Reverse Mitochondrial Dysfunction.

Type II alveolar epithelial cell (AECII) apoptosis is one of the most vital causes of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that bone mesenchymal stem cell-derived exosomes (BMSC-exos) can effectively reduce sepsis-induced ARDS. However, the function and molecular mechanism of BMSC-exos in sepsis-induced AECII apoptosis remain to be elucidated. In the present study, a more significant number of AECII apoptosis, high mitochondrial fission p-Drp1 protein levels, and low levels of mitochondrial biogenesis-related PGC1α, Tfam, and Nrf1 proteins accompanied with ATP content depression were confirmed in AECIIs in response to sepsis. Surprisingly, BMSC-exos successfully recovered mitochondrial biogenesis, including the upregulated expression of PGC1α, Tfam, Nrf1 proteins, and ATP contents, and prohibited p-Drp1-mediated mitochondrial fission by promoting Nrf2 expression. However, the aforementioned BMSC-exo reversal of mitochondrial dysfunction in AECIIs can be blocked by Nrf2 inhibitor ML385. Finally, BMSC-exos ameliorated the mortality rate, AECII apoptosis, inflammatory cytokine storm including HMGB1 and IL-6, and pathological lung damage in sepsis mice, which also could be prevented by ML385. These findings reveal a new mechanism of BMSC-exos in reversing mitochondrial dysfunction to alleviate AECII apoptosis, which may provide novel strategies for preventing and treating sepsis-induced ARDS.

Cell cycle-dependent Cu uptake explained the heterogenous responses of Chlamydomonas to Cu exposure.

Growing evidence suggested that microorganisms exhibited heterogeneous sensitivity to toxicants, but their underlying mechanisms remain largely unknown. The asynchronous cell cycle progression in natural population implies the connection between cell cycle and heterogeneity. Here, the heterogenous responses of Chlamydomonas reinhardtii upon Cu stress were confirmed with the aid of a fluorometric probe for imaging Cu(I), implying the connection with cell cycle. Our results further indicated that the increase of labile Cu(I) was related to the cell division, leading to the fluctuation of labile Cu(I) with diurnal cycle and cell cycle, respectively. However, lack of Cu mainly influenced the cell division. We demonstrated that G2/M phase was the critical stage requiring high Cu quota during cell division. Specifically, algae at G2/M phase required 10-fold of Cu quota compared with that at G1 phase, which was related to the mitochondrial replication. Eventually, the heterogeneous Cu uptake ability of algae at different cell phases led to the heterogeneous responses to Cu exposure. Overall, Cu could influence the cell cycle through mediating the cell division, and in turn algae at different cell phases exhibited different Cu sensitivities. This study firstly uncovered the underlying mechanisms of heterogeneous Cu sensitivity for phytoplankton, which could help to evaluate the potential ecological risks of Cu.

In Situ Tracking of Crystal-Surface-Dependent Cu2O Nanoparticle Dissolution in an Aqueous Environment.

Metal-oxide-based nanoparticles (MONPs) such as Cu2O NPs have attracted growing attention, but the potential discharges of MONPs have raised considerable concern of their environmental fate including their dissolution behavior. The impacts of morphology on MONP dissolution are largely uncertain due to the lack of in situ tracking techniques. In this study, we combined a series of in situ technologies including liquid-cell transmission electron microscopy and fluorescence probes to reveal the in situ dissolution process of Cu2O NPs in freshwater. Our results suggest that cubic Cu2O NPs exhibit a higher dissolution quantity compared with spherical NPs of the same surface area. The difference was mainly related to the crystal surface, while other factors such as particle size or aggregation status showed minor effects. Importantly, we demonstrated the simultaneous growth of new small NPs and the dissolution of pristine Cu2O NPs during the dissolution of Cu2O NPs. Cubic Cu2O NPs became much less soluble under O2-limited conditions, suggesting that O2 concentration largely affected the dependence of dissolution on the NP morphology. Our findings highlight the potential application of in situ techniques to track the environmental fates of MONPs, which would provide important information for assessing the ecological risks of engineered NPs.

CARDIOPULMONARY BYPASS-DERIVED PLASMA EXOSOMAL HMGB1 CONTRIBUTES TO ALVEOLAR EPITHELIAL CELL NECROPTOSIS VIA mtDNA/CGAS/STING PATHWAY.

ABSTRACT: Our previous study confirmed that cardiopulmonary bypass (CPB) leads to acute lung injury (ALI) via inducing high-mobility group box 1 (HMGB1) release. Recent research showed that HMGB1 promotes pulmonary injury mainly via exosomes transport. Currently, alveolar epithelial cell (AEC) necroptosis has been demonstrated to be involved in ALI. However, it is unknown whether exosomal inflammatory cytokine HMGB1 promotes ALI by inducing AEC necroptosis, and its underlying mechanisms remain elusive. Here, a prospective cohort study was carried out, in which plasma samples from 21 CPB patients were isolated at four specific time points: pre-CPB, 2, 12, and 24 h after initiation of CPB. Plasma exosomes were extracted via ultra-high-speed centrifugation and cocultured with AEC cell line-A549 cells at increasing concentrations of 50, 100, and 150 µg/mL. Then, HMGB1 antagonist-Box A and mtDNA deficiency ethidium bromide (EtBr) were applied to explore the underlying role of exosomal HMGB1 and cytoplasm mitochondrial DNA in AEC. Western blot analysis showed that plasma exosomal HMGB1 expression gradually increased and peaked at 24 h after CPB. Twenty-four-hour treatment of CPB-derived exosomes at 150 µg/mL for 24 h could induce necroptosis by promoting mitochondrial fission and further elevating cytoplasm mtDNA levels in A549 cells, which was successfully blocked by Box A or EtBr. Most importantly, EtBr significantly inhibited cytoplasm mtDNA downstream guanosine monophosphate (GMP)-AMP synthase (cGAS)/stimulator of interferon gene (STING) signal pathway. Collectively, these data demonstrate that CPB-derived plasma exosomal HMGB1 contributes to AEC necroptosis through the mtDNA/cGAS/STING pathway.

Intravenous Lidocaine Significantly Reduces the Propofol Dose in Elderly Patients Undergoing Gastroscopy: A Randomized Controlled Trial.

Objective: Propofol-based sedation has been widely used for gastroscopy, but the risk of respiratory suppression in elderly patients should not be overlooked. Intravenous (IV) lidocaine during surgery can reduce the demand for propofol and the incidence of cardiopulmonary complications. We examined whether IV lidocaine reduces the dose of propofol and the occurrence of adverse events during gastroscopy in elderly patients. Methods: We conducted a prospective, single-center, double-blind randomized controlled trial in elderly patients aged ≥65 years with ASA I-II. Subjects were randomly assigned to the lidocaine group (Group L, n=70), who received IV 1.5 mg kg-1 lidocaine followed by a continuous infusion of 4 mg kg-1 h-1 lidocaine, or the normal saline group (Group N, n=70), who received an equal volume of saline in the same way. Results: IV lidocaine reduced the total and maintenance propofol dose in Group L (p<0.001), with no significant effect on the induction dose. The incidence of intraoperative hypoxia (p=0.035), emergency airway management events (p=0.005), duration of gastroscopy (p<0.05), consciousness recovery time (p<0.001), and postoperative pain (p=0.009) were all reduced in Group L. Patient (p=0.025) and gastroscopist (p=0.031) satisfaction was higher in Group L. Intraoperative hemodynamic parameters, the respiratory rate, the incidence of sedation-related events and anesthesiologist satisfaction were similar between the two groups. Conclusion: IV lidocaine can significantly reduce the amount of propofol, the incidence of hypoxia and postoperative pain during gastroscopy in elderly patients, with a higher patient and gastroscopist satisfaction.

Cell-Type-Dependent Dissolution of CuO Nanoparticles and Efflux of Cu Ions following Cellular Internalization.

CuO nanoparticles (NPs) show promising applications in biosensors, waste treatment, and energy materials, but the growing manufacture of CuO NPs also leads to the concerns for their potential environmental and health risks. However, the cellular fates of CuO NPs such as Cu ion dissolution, transformation, and efflux remain largely speculative. In the present study, we for the first time combined the gold-core labeling and Cu ion bioimaging technologies to reveal the intracellular fates of CuO NPs in different cells following cellular internalization of NPs. We demonstrated that the dissolution rate of CuO NPs depended on the cell type. Following CuO dissolution, limited transformation of Cu(II) to Cu(I) occurred within the cellular microenvironment. Instead, Cu(II) was rapidly eliminated from the cells, and such rapid efflux in different cells was highly dependent on the GSH-mediated pathway and lysosome exocytosis. The labile Cu(I) level in the two cancerous cell lines was immediately regulated upon Cu exposure, which explained their tolerance to Au@CuO NPs. Overall, our study demonstrated a very rapid turnover of Cu in the cells following CuO internalization, which subsequently determined the cellular toxicity of CuO. The results will have important implications for assessing the health risk of CuO NPs.

Curcumol inhibits the growth of xenograft-tumors in mice and the biological activities of pancreatic cancer cells by regulating the miR-21-5p/SMAD7 axis.

Anti-cancer effects of curcumol on various cancers have been reported previously. This study focused on investigating the role of curcumol in pancreatic cancer from the molecular perspective. The survival of pancreatic cancer patients with high or low expression of miR-21-5pand the target gene of miR-21-5pwere analyzed by bioinformatics. MiR-21-5p expression in cancer tissues was analyzed by RT-qPCR. Anxenograft-tumor BALB/c nude mice model was established and pancreatic cancer cells were cultured. Later, the mice and cells were further treated with curcumol. The tumor size and weightas well as mice body weight were recorded. The viability, proliferation, migration, and invasion of the cells were evaluated by MTT, colony formation, and transwell assays, respectively. The expressions of molecules in the xenograft-tumor tissues or cells were detected by immunohistochemical assay, Western blot, or RT-qPCR. MiR-21-5p was high-expressed in pancreatic cancer tissues and patients with high expression of miR-21-5p had poor survival. Curcumol inhibited the xenograft-tumor size, tumor weight, and PCNA and miR-21-5p expressions while promoting Cleaved caspase-3 expression in xenograft-tumor tissues. Curcumol inhibited the viability, proliferation, migration, invasion, and miR-21-5p expression, but increased SMAD7 expression in cancer cells. MiR-21-5p overexpression reversed the effect of curcumol on cancer cells, and decreased the E-cadherin expression while elevating the expressions of PCNA, N-cadherin, Vimentin, p-SMAD2, and p-SMAD3 in curcumol-treated cells. The overexpression of SMAD7, a target gene of miR-21-5p, reversed the effect of miR-21-5p on curcumol-treated cells. Curcumol inhibited growth of xenograft-tumors and the biological activities of pancreatic cancer cells by regulating the miR-21-5p/SMAD7 axis.

Potential application of Au core labeling for tracking Ag nanoparticles in the aquatic and biological system.

The entering of silver nanoparticles (Ag NPs) in natural environments constantly increases due to their widespread production and application. While the environmental behavior, impacts, and fate of Ag NPs were critically assessed, the main challenge represents continuous tracking and quantification of Ag NPs in environmental and biological matrices. A group of labeled Ag NPs with gold cores (Au@Ag NPs) was developed for distinguishing between pristine Ag NPs and their other forms, and we comprehensively compared their physicochemical properties, environmental behavior, and biological effects with unlabeled Ag NPs. The electron transfer process from the Au core to the Ag shell gradually decreased with the increase of Ag shell thickness, then the inhibition of Ag+ release induced by the Au core was gradually alleviated, but the generation of superoxide radicals was intensified sharply. Then, the effect of the Au core on the dissolution capacity and free radicals' generation significantly altered the biological toxicity of Ag NPs, and the influence degree was related to the test organism's species. Nevertheless, the Au core retained the surface properties of Ag NPs, leading to the uptake of Au@Ag NPs, entirely consistent with the behavior of unlabeled Ag NPs. These findings confirmed that Au core labeling provides new opportunities for tracking Ag NPs in environmental and biological systems, and the exposure conditions and test organisms should be carefully assessed before employing the Au core labeling technology.

Clinical Effects and Safety of the Use of Methylene Blue for the Treatment of Lumbar Facet Joint Syndrome.

BACKGROUND: Lumbar facet joint syndrome (LFJS) has been suggested to be a main source of low back pain. Methylene blue (MB), an inhibitor of nitric oxide synthesis with potential analgesic and anti-inflammatory properties, has been widely applied for a variety of pain-related diseases. However, no studies have been conducted on the treatment of LFJS patients using MB. OBJECTIVES: The purpose of this study was to evaluate the therapeutic effects of intra-articular injection of MB on LFJS patients. STUDY DESIGN: A prospective, randomized, controlled clinical trial. SETTING: Department of pain, Shanghai East Hospital. METHODS: A total of 120 eligible patients with LFJS were randomly divided into an MB group and a control group. Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the pre-operation and post-operation states of the patients, and adverse events were recorded. The patients participating in this study were followed up for a period of 6 months. RESULTS: A total of 104 patients were followed up for the entire 6 months period. The control group included 51 patients, and the MB group included 53 patients. In both groups, the NRS scores, ODI scores, PHQ-9 scores, and PSQI scores decreased at different time points after treatment, compared to baseline. Moreover, the NRS scores were significantly lower than that of the control group at 3 months and 6 months after operation (P < 0.05). The ODI, PSQI, and PHQ-9 scores of the MB group were also respective significantly lower than that of the control group at 3 months and 6 months after operation (P < 0.05). As for the clinical efficacy, the total effective treatment rate of the MB group was significantly higher than that of the control group at 6 months after the procedure (P < 0.05). On the first day after operation, the incidence of hyperglycemia in patients with diabetes in the MB group was significantly lower than that of the control group (P < 0.05). LIMITATIONS: Firstly, the patients enrolled were recruited from a single center, and the sample size was small. Secondly, the patients were only followed-up for a period of 6 months after treatment. Thirdly, double blinding was not used in the design of this research study. CONCLUSION: Ultrasound-guided intra-articular MB injection is a safe and effective therapy for patients with LFJS. Intra-articular injection with MB can significantly reduce pain intensity, improve patient lumbar function, pain-related depression and sleep quality, increase total effective rate with no severe adverse side effects.

Combining Ozonated Autohemotherapy with Pharmacological Therapy for Comorbid Insomnia and Myofascial Pain Syndrome: A Prospective Randomized Controlled Study.

Objective: To examine the efficacy and safety of ozonated autohemotherapy (O3-AHT) combined with pharmacological therapy for comorbid insomnia and myofascial pain syndrome (MPS). Materials and Methods: One hundred and eighteen patients were randomly divided into two groups: the control group (N = 50) and the O3-AHT group (N = 53). Patients in both groups were given the same pharmacological management for three weeks. Patients in the O3-AHT group were treated with ozonated autohemotherapy (the concentration of ozone was 20 µg/ml in the first week, 30 µg/ml in the second week, and 40 µg/ml in the third week) combined with pharmacological therapy. Primary (the insomnia severity index (ISI) and visual analogue scale (VAS)) and secondary outcomes (the Epworth sleepiness scale (ESS), polysomnography data, the anxiety and preoccupation about sleep questionnaire (APSQ), the beck depression index (BDI), and the multidimensional fatigue inventory (MFI)) were examined at pretreatment, posttreatment, 1 month, and 6 months. Results: Fifty patients in the control group and fifty-three patients in the O3-AHT group completed the study. In both groups, insomnia and pain symptoms were relieved significantly compared with pretreatment. Compared with the control group, the O3-AHT group had significantly improved sleep quality, pain, and negative mood at different time points. No adverse complications were observed in either group. Conclusion: Compared with pharmacological therapy alone, ozonated autohemotherapy combined with pharmacological therapy can ameliorate insomnia, reduce pain intensity, improve negative mood, and alleviate fatigue more effectively without serious adverse complications.

Acupoint Catgut Embedding as Adjunctive Therapy for Patients With Gallstones.

AIMS OF THIS STUDY: A randomized clinical trial was undertaken to investigate the efficacy of acupoint catgut embedding (ACE) as adjunctive therapy to tauroursodeoxycholic acid (TUDCA) therapy on gallbladder emptying and clinical symptoms in patients with gallstone disease. MATERIALS AND METHODS: Between August 2018 and January 2019, 70 patients with gallstones in our hospital were enrolled in this prospective clinical trial. All the patients were randomly divided into the ACE group (ACE+TUDCA treatment for 8 wk) and the Sham group (Sham ACE+TUDCA treatment for 8 wk). In the ACE group, all the patients were nightly given ACE every 2 weeks, and in 2 groups, every patient took TUDCA 500 mg at bedtime. The parameters about gallbladder emptying were detected by ultrasound before and after the treatment, and the clinical symptom scores were recorded at the same time points. RESULTS: A total of 63 patients with gallstone disease were included in our study, with 33 patients in the ACE group and 30 patients in the Sham group. In the ACE group, the empty volume (EV) and gallbladder ejection fraction (GBEF) were improved after treatment (P<0.05). Almost every symptom score (except symptom 7, P=0.15) and total score were decreased (P<0.05). In the Sham group, the symptom 1, 2, 4, 5 scores, and total score were significantly decreased (P<0.05). Moreover, the residual volume in the ACE group was significantly lower than in the Sham group (P=0.008). The EV and GBEF in the ACE group were higher than that in the Sham group (P<0.05). The score of symptom 6 in the ACE group was lower than that in the Sham group (P=0.008). CONCLUSION: ACE therapy could more effectively improve the gallbladder emptying with a shorter treatment course. Therefore, ACE+TUDCA therapy might be a time-saving treatment for gallstones.

Cu-based nanoparticle toxicity to zebrafish cells regulated by cellular discharges.

Cellular transport of metal nanoparticles (NPs) is critical in determining their potential toxicity, but the transformation of metal ions released from the internalized NPs is largely unknown. Cu-based NPs are the only metallic-based NPs that are reported to induce higher toxicity compared with their corresponding ions, likely due to their unique cellular turnover. In the present study, we developed a novel gold core to differentiate the particulate and ionic Cu in the Cu2O microparticles (MPs), and the kinetics of bioaccumulation, exocytosis, and cytotoxicity of Au@Cu2O MPs to zebrafish embryonic cells were subsequently studied. We demonstrated that the internalized MPs were rapidly dissolved to Cu ions, which then undergo lysosome-mediated exocytosis. The uptake rate of smaller MPs (130 nm) was lower than that of larger ones (200 nm), but smaller MPs were dissolved much quickly in cells and therefore activated the exocytosis more quickly. The rapid release of Cu ions resulted in an immediate toxic action of Cu2O MPs, while the cell deaths mainly occurred by necrosis. During this process, the buffering ability of glutathione greatly alleviated the Cu toxicity. Therefore, although the turnover of intracellular Cu at a sublethal exposure level was hundred times faster than the basal values, labile Cu(I) concentration increased by only 2 times at most. Overall, this work provided new insights into the toxicity of copper NPs, suggesting that tolerance to Cu-based NPs depended on their ability to discharge the released Cu ions.