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Carbon nanotubes (CNTs), as potent reinforcements in composites, have demonstrated excellent strengthening effects when combined with copper in numerous recent studies. Challenges remain in the application of these composites and in fully leveraging the reinforcing capabilities of CNTs to achieve comprehensive performance enhancement. The performance of CNTs/Cu composites can be flexibly regulated owing to the unique structure and properties of CNTs. To achieve the fabrication of high-performance and diverse CNTs/Cu composites, a profound understanding of the reinforcement mechanisms of CNTs in the composites is essential, along with the consideration of key influencing factors on performance. This article provides a comprehensive overview of the reinforcement mechanisms of CNTs on the mechanical, electrical, and thermal properties of CNTs/Cu composites. Factors influencing the effectiveness of CNT reinforcement in composites are discussed, including the attributes and dispersion of CNTs, the architectures of composites, and the interface between CNTs and Cu. Furthermore, this study explores the role of CNTs in addressing the trade-off between high strength and high conductivity as well as between high strength and high ductility in the copper matrix.

Background Fibrinogen (FIB) is often elevated in children with Henoch Schonlein purpuric nephritis (HSPN), but the correlation between FIB and renal lesions has been less studied. Objective To explore the correlation between FIB in children with HSPN and the International Study Group on Pediatric Kidney Disease (ISKDC) pathology grading and micropathological changes in parts of renal units, and to clarify whether FIB can assess the severity of renal injury in children with HSPN. Methods In total, 922 children with HSPN who were hospitalized in the First Affiliated Hospital of Henan University of Chinese Medicine in the pediatric nephrology ward and underwent kidney biopsy at the same time from December 2017 to December 2022 were collected, and the clinical information, FIB and renal pathological information during renal biopsy were summarized, and based on the FIB level, the children were categorized into group A (low) 4.98 g/L. The correlation between FIB and ISKDC pathological grades, glomerular mesangial hyperplasia ratio, the crescentic bodies ratio and the nature of the glomerular lesions from acute to chronic was investigated by Spearman rank correlation analysis, and the prediction of FIB on the micropathological changes of renal units was analyzed by the subject's work characteristic (ROC) curve. Results Among 922 children with HSPN who had undergone renal biopsy, the FIB was (3.48±1.01) g/L. 113 cases in group A had a low FIB rate of 12.26%; 734 cases in group B had a standardized FIB rate of 79.61%; and 75 cases in group C had a high FIB rate of 8.13%. The ISKDC pathology classification was type Ⅱa in 173 cases (18.76%), type Ⅱb in 29 cases (3.15%), 466 cases (50.54%) of type Ⅲa, 232 cases (25.16%) of type Ⅲb, and 22 cases (2.39%) of type Ⅳ and above (including 2 cases of type Ⅳa, 18 cases of type Ⅳb, and 2 cases of type Ⅴ). The results of the Spearman's rank correlation analysis showed that the FIB and the grouping of the FIB of the children with HSPN were positively related to the renal pathology ISKDC grading (rs=0.146, P

Ratiometric DNA biosensors, which utilize DNA as the recognition element and integrate dual signals from diverse sensing platforms including fluorescence, electrochemistry, and surface-enhanced Raman scattering (SERS), have demonstrated remarkable proficiency in detecting a wide range of targets. In this review, we showcase the significant progress achieved by ratiometric biosensors. Firstly, ratiometric biosensors have made notable advancements in analyzing real samples. These include the analysis of pH values near cancer cells, quantification of miRNA in human cell lysates, detection of human telomerase RNA in cell extracts, and performing DNA logic-gated in situ bioimaging on cell membranes. Secondly, excellent sensitivity has been attained through the utilization of effective amplification methods such as RCA, HCR, and CHA, among others. Thirdly, the construction of stable reference signals has resulted in significantly improved precision for ratiometric biosensors. This breakthrough has overcome matrix effects, enabling reliable detection in real samples with high selectivity. This review provides a comprehensive overview of recent advancements in strategies employed by ratiometric DNA biosensors. We present three types of biosensors based on distinct sensing platforms: fluorescent, electrochemical, and SERS biosensors. Additionally, we discuss future directions and primary challenges in the development of ratiometric DNA biosensors.

A single nucleotide variant in mitochondrial DNA (mtDNA) 1555A>G is associated with drug-induced hearing loss. For the 1555A>G mutation site, 1555A wild-type and 1555G mutant-type plasmids were constructed, respectively. In this study, a PCR method based on the TaqMan amplification refractory mutation system was proposed to detect mtDNA 1555A>G. A common upstream primer, a common TaqMan probe, and two downstream allele-specific primers with mismatched bases were designed. One-step amplification and detection of the wild-type and mutant type at the 1555 site were realized for the deafness-related gene through two reactions. Based on this detection method, the minimum detection limit of the wild-type and mutant type detection systems for plasmids was 50 copies/μL. The minimum sensitivity for the detection of nucleic acids in real dried blood spot (DBS) samples was 0.1 ng/μL. In the normal DBS DNA sample, the detection limit of the mutation abundance reached 0.78%. The specificity of the detection method was 100%, and the coefficient of variation was less than 3.36%. This approach was validated using clinical DNA extracted from 113 DBS samples of newborns. Additionally, it showed 100% agreement with bi-directional Sanger sequencing. It can be used as an optional method for the clinical detection of deafness-related genes.

Abstract Background Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. Methods A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways’ activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein–protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. Results In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. Conclusion We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

In the human body, non-centrosymmetric biological structures exhibit piezoelectric effect across from microscopic biomolecular building blocks to macroscopic tissues and organs. However, the fabrication of piezoelectric devices from discarded natural tissues and organs has rarely been exploited for energy harvesting applications. Herein, the extracted human teeth were recycled as an active layer in a piezoelectric nanogenerator for power generation. Due to the piezoelectric effect of enamel and dentin, a human teeth-based sandwiched piezoelectric nanogenerator was fabricated, producing high and stable power outputs with an open-circuit voltage of approximately 0.9 V under an external force at 60 N. Furthermore, the high mechanical durability of the piezoelectric nanogenerator was also verified after 1600 pressing-and-releasing cycles without noticeable output degradation. Notably, for the first time, a light-emitting diode (LED) was illuminated by the human teeth-based piezoelectric device. This work exemplifies a sustainable strategy to recycle the extracted human teeth by fabricating a piezoelectric nanogenerator for energy harvesting, providing inspiration for converting waste into wealth toward green energy in bionanotechnology.

Aims: To identify and analyze genes closely related to the progression of nonalcoholic steatohepatitis (NASH) by employing a combination of single-cell RNA sequencing and machine-learning algorithms. Main methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed to find the cell population with the most significant differences between the Chow and NASH groups. This approach was used to validate the developmental trajectory of this cell population and investigate changes in cellular communication and important signaling pathways among these cells. Subsequently, high dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) was used to find the key modules in NASH. Machine learning analyses were performed to further identify core genes. Deep learning techniques were applied to elucidate the correlation between core genes and immune cells. The accuracy of this correlation was further confirmed using deep learning techniques, specifically Convolutional Neural Networks. Key findings: By comparing scRNA-seq data between the Chow and NASH groups, we have observed a notable distinction existing in the Kupffer cell population. Signaling interactions between hepatic macrophages and other cells were significantly heightened in the NASH group. Through subsequent analysis of macrophage subtypes and key modules, we identified 150 genes tightly associated with NASH. Finally, we highlighted the 16 most significant core genes using multiple iterations of machine learning. Furthermore, we pointed out the close relationship between core genes and immune cells. Significances: Using scRNA-seq analysis and machine learning, we can distinguish NASH-related genes from large genetic datasets, providing theoretical support in finding potential targets for the development of novel therapies.

Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

Abstract Background Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. Methods Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo. Results We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway. Conclusions This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis. Graphical Abstract

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

When the wind speed changes significantly in a permanent magnet synchronous wind power generation system, the maximum power point cannot be easily determined in a timely manner. This study proposes a maximum power reference signal search method based on fuzzy control, which is an improvement to the climbing search method. A neural network-based parameter regulator is proposed to address external wind speed fluctuations, where the parameters of a proportional-integral controller is adjusted to accurately monitor the maximum power point under different wind speed conditions. Finally, the effectiveness of this method is verified via Simulink simulation

To realize the industrial production of pure sour porridge, the traditional sour porridge from Hequ of Shanxi was used as the donor of lactic acid bacteria, which could be used to produce sour porridge under pure culture condition. Lactic acid bacteria were isolated from the sour porridge with CaCO3-MRS medium, and lactic acid bacteria with strong tolerance were screened through acid tolerance, bile salt tolerance and simulated gastrointestinal tolerance tests. The strains were identified by physiological and biochemical tests, 16S rDNA and pheS gene sequence. The results showed that strains L10, W10 and Y3 with strong tolerance were selected from 68 strains of lactic acid bacteria, the three strains of lactic acid bacteria were identified as Lactiplantibacillus plantarum. At aggregation assay, the self-agglutination rate of L10, W10 and Y3 were 48.86%, 30.14% and 27.63% respectively. Strains L10, W10 and Y3 were able to survive at MRS medium containing 1.0 mmol/L hydrogen peroxide. In free radical scavenging assays, the fermentation supernatant of L10 possessed the highest ability to scavenge the DPPH radical (95.27%), and the hydroxyl radical and superoxide anion scavenging ability of Y3 were the highest, which were 51.26% and 20.16% respectively. However, the DPPH radical scavenging ability of the intact cell suspension of W10 was the highest (27.53%), and the hydroxyl radical scavenging ability of Y3 was 24.83%, which was the highest among them. Therefore, the three strains of lactic acid bacteria screened from traditional sour porridge possessed the potential applications in the industrial production of pure sour porridge.

Abstract Background CD24+CK19+/CD24+SOX9+ resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed. Results The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues. tdTom+ hepatocytes were isolated from ROSA26 tdTomato mice following AAV8-Tbg-Cre-mediated recombination, EpCAM+ biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and ALB/GFP−EpCAM− cells were isolated from Alb CreERT /R26 GFP mice. A cocktail of small molecules was used to convert the isolated cells into LPCs. These in vitro cultured LPCs with CD24 and SOX9 expression regained the ability to proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 (Lcn2) at high levels. Accordingly, endogenous Cd24a + Lcn2 + LPCs were identified by integration of sc-RNA-sequencing and pathological datasets of liver dysfunction which indicates that LPCs produced by ductular reactions might also originate from the resident LPCs. Transplantation of in-vitro cultured Cd24a + Lcn2 + LPCs into CCl4-induced fibrotic livers exacerbated liver damage and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response. Conclusions CD24+LCN2+ LPCs constituted the expanding ductular reaction and contributed to macrophage-mediated inflammation in chronic liver damage. The current findings highlight the roles of LPCs from distinct origins and expose the possibility of targeting LPCs in the treatment of chronic hepatic diseases. Graphical Abstract

The selective separation of small molecules at the sub-nanometer scale has broad application prospects in the field, such as energy, catalysis, and separation. Conventional polymeric membrane materials (e.g., nanofiltration membranes) for sub-nanometer scale separations face challenges, such as inhomogeneous channel sizes and unstable pore structures. Combining polymers with metal–organic frameworks (MOFs), which possess uniform and intrinsic pore structures, may overcome this limitation. This combination has resulted in three distinct types of membranes: MOF polycrystalline membranes, mixed-matrix membranes (MMMs), and thin-film nanocomposite (TFN) membranes. However, their effectiveness is hindered by the limited regulation of the surface properties and growth of MOFs and their poor interfacial compatibility. The main issues in preparing MOF polycrystalline membranes are the uncontrollable growth of MOFs and the poor adhesion between MOFs and the substrate. Here, polymers could serve as a simple and precise tool for regulating the growth and surface functionalities of MOFs while enhancing their adhesion to the substrate. For MOF mixed-matrix membranes, the primary challenge is the poor interfacial compatibility between polymers and MOFs. Strategies for the mutual modification of MOFs and polymers to enhance their interfacial compatibility are introduced. For TFN membranes, the challenges include the difficulty in controlling the growth of the polymer selective layer and the performance limitations caused by the “trade-off” effect. MOFs can modulate the formation process of the polymer selective layer and establish transport channels within the polymer matrix to overcome the “trade-off” effect limitations. This review focuses on the mechanisms of synergistic construction of polymer–MOF membranes and their structure–nanofiltration performance relationships, which have not been sufficiently addressed in the past.

Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16–24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FN ABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n = 335), 9.6% (n = 44), 2.8% (n = 13), 4.8% (n = 22), and 0.4% (n = 2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V–VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III–IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, P PV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients.Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0–24 h).Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0–24 h nor normalized AUCss, 0–24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = −0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0–24 h (r = −0.414, p = 0.049). Patients with AUCss, 0–24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0–24 h < 50 mg·h/L or patients with AUCss, 0–24 h 50–100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose.Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.

Abstract Background Human primary hepatocytes (PHCs) are considered to be the best cell source for cell-based therapies for the treatment of end-stage liver disease and acute liver failure. To obtain sufficient and high-quality functional human hepatocytes, we have established a strategy to dedifferentiate human PHCs into expandable hepatocyte-derived liver progenitor-like cells (HepLPCs) through in vitro chemical reprogramming. However, the reduced proliferative capacity of HepLPCs after long-term culture still limits their utility. Therefore, in this study, we attempted to explore the potential mechanism related to the proliferative ability of HepLPCs in vitro culture. Results In this study, analysis of assay for transposase accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) were performed for PHCs, proliferative HepLPCs (pro-HepLPCs) and late-passage HepLPCs (lp-HepLPCs). Genome-wide transcriptional and chromatin accessibility changes during the conversion and long-term culture of HepLPCs were studied. We found that lp-HepLPCs exhibited an aged phenotype characterized by the activation of inflammatory factors. Epigenetic changes were found to be consistent with our gene expression findings, with promoter and distal regions of many inflammatory-related genes showing increased accessibility in the lp-HepLPCs. FOSL2, a member of the AP-1 family, was found to be highly enriched in the distal regions with increased accessibility in lp-HepLPCs. Its depletion attenuated the expression of aging- and senescence-associated secretory phenotype (SASP)-related genes and resulted in a partial improvement of the aging phenotype in lp-HepLPCs. Conclusions FOSL2 may drive the aging of HepLPCs by regulating inflammatory factors and its depletion may attenuate this phenotypic shift. This study provides a novel and promising approach for the long-term in vitro culture of HepLPCs.

An industrial control process multiple-input multiple-output (MIMO) coupled system is analyzed in this study as an example of a Loss of Coolant Accident (LOCA) simulation system. Ordinary control algorithms can complete the steady state of the control system and even reduce the response time to some extent, but the entire system still consumes a large amount of energy after reaching the steady state. So a multivariable decoupled energy-saving control method is proposed, and a novel energy-saving function (economic function, Eco-Function) is specially designed based on the active disturbance rejection control algorithm. Simulations and LOCA simulation system tests show that the Eco-function algorithm can cope with the uncertainty of the multivariable system's internal parameters and external disturbances, and it can save up to 67% of energy consumption in maintaining the parameter steady state.

Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to “see” light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called “photoneuroendocrinology”, which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light’s beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin’s photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin’s unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.

Objective: To evaluate the long-term inhibition of malignant biliary tumor growth using paclitaxel (PTX)-covered polycaprolactone (PCL) electrospun membranes. Methods: A mixture of PCL, a material used to fabricate polymer stents, and PTX, a widely used chemotherapeutic agent, was synthesized by electrospinning. After preparing the drug-eluting membrane, drug release and fiber degradation were assessed in vitro under different pH conditions. The QBC939 cholangiocarcinoma cell line was cultured to establish a xenograft nude mouse model. Finally, the drug-eluting membrane was implanted into the mouse model, and the relative tumor inhibition rate was evaluated. Results: A new PTX-loaded PCL electrospun fiber membrane was developed. The drug release rate was about 20–40% in the 32-day release cycle, and the release quantity was between 20 and 170 mg. As pH decreased, the release rate increased significantly. The degradation rate of the fiber membranes in vitro was approximately 20–48%, and was positively correlated with the drug loading rate. In animal experiments, the growth of tumors in mice was suppressed using drug-eluting membranes. Conclusion: The PTX-loaded PCL electrospun fiber membrane enhanced the long-term drug release and exhibited excellent antitumor effects in vivo.

Abstract Background Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence. Methods We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson–Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end‐stage liver disease score. Results Majority of patients were male (69.4%) with a mean age of 55.40 ± 10.68 years. SATI had a U‐shaped association with mortality (P for non‐linearity 51.8 cm2/m2) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P = 0.052) and high versus moderate SATI groups (Gray's test, P = 0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR] = 1.66, 95% confidence interval [CI]: 0.992–2.78, P = 0.054) and was an independent predictor of death (sHR = 1.86, 95% CI: 1.059–3.28, P = 0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR = 1.6, 95% CI: 1–2.54, P = 0.049), and was an independent predictor of death (sHR = 2.007, 95% CI: 1.195–3.37, P = 0.0085). VATI had an irregularly shaped association with mortality (P for non‐linearity 40.2 cm2/m2) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P = 0.381) and high versus moderate VATI groups (Gray's test, P = 0.787). Competing risk analyses demonstrated that neither low (sHR = 1.27, 95% CI: 0.599–2.7, P = 0.53) nor high VATI (sHR = 0.848, 95% CI: 0.539–1.34, P = 0.48) was an independent predictor of death compared with moderate VATI. Conclusions Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients.

Traumatic injuries in the central nervous system, such as traumatic brain injury and spinal cord injury, are associated with tissue inflammation and the infiltration of immune cells, which simultaneously affect the self-renewal and differentiation of neural stem cells. However, the tissue repair process instigated by endogenous neural stem cells is incapable of restoring central nervous system injuries without external intervention. Recently, resident/peripheral immune cells have been demonstrated to exert significant effects on neural stem cells. Thus, the restoration of traumatic injuries in the central nervous system by the immune intervention in neural stem cells represents a potential therapeutic method. In this review, we discuss the roles and possible mechanisms of immune cells on the self-renewal and differentiation of neural stem cells along with the prognosis of central nervous system injuries based on immune intervention. Finally, we discuss remaining research challenges that need to be considered in the future. Further elucidation of these challenges will facilitate the successful application of neural stem cells in central nervous system injuries.

Abstract Background Although repeated cryopreservation is an occasional occurrence, the effect on perinatal outcomes is unclear. Therefore, the aim of this study was to evaluate the perinatal outcomes of singletons after embryo re-cryopreservation. Methods In this retrospective study, a total of 647 singleton live births after blastocyst freeze-thaw embryo transfer cycles were investigated. They were divided into two groups: vitrified-warmed blastocysts (once-vitrified group) and vitrified-warmed blastocysts derived from thawed cleaved embryos (re-vitrified group). Propensity score matching (PSM) was used to control for potential confounding factors. Results A total of 592 infants were included in the once-vitrified group, and 55 infants were included in the re-vitrified group. After PSM, 108 cases were generated for comparison. The median gestational age was 38 weeks for both groups, and the birthweights were comparable (3390.6 ± 601.5 g vs. 3412.8 ± 672.6 g, P > 0.05). The incidence of preterm birth (PTB) (20.4% vs. 16.7%), low birthweight (LBW) (3.7% vs. 7.4%), macrosomia (11.1% vs. 16.7%) and large for gestational age (LGA) (29.6% vs. 22.2%) were not significantly different between the two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect the occurrence of PTB (OR, 2.58 [95% CI, 0.77, 8.63]), LBW (OR, 0.83 [95% CI, 0.08, 8.29]), macrosomia (OR, 0.60 [95% CI, 0.13, 2.69]), or LGA (OR, 1.51 [95% CI, 0.53, 4.27]) (P > 0.05, for all). Conclusion Our findings demonstrate that double vitrification-warming procedures do not increase the risk of adverse neonatal outcomes compared with those of once-vitrified embryos.

Objective To compare the risk of mortality in patients with cirrhosis with and without the associated acute kidney injury (AKI).Methods We performed a systematic search in the PubMed, Embase, and Scopus databases for observational studies that were done on patients with cirrhosis. Eligible studies reported AKI in patients with cirrhosis and compared mortality among patients with and without AKI. We used a random-effects model, using STATA version 16.0, for deriving pooled effect sizes that were reported as odds ratio (OR) with 95% confidence intervals (CIs).Results Thirty-two studies were included. In patients with cirrhosis, AKI was significantly associated with higher in-hospital mortality (OR 5.92), and mortality at 30 days (OR 4.78), 90 days (OR 4.34), and at 1 year follow-up (OR 4.82) compared to patients without AKI.Conclusions AKI is associated with an increased risk of mortality in patients with cirrhosis. Careful monitoring to identify the development of AKI and early prompt management is necessary.

Summary: The liver is the main site of colorectal cancer (CRC) metastasis. Tumor-associated macrophages (TAMs) play a key role in tumor metastasis. Therefore, modulating the function of tumor-associated macrophages is a potential therapeutic strategy to control tumor metastasis. We found in vivo experiments that the activation of STING inhibited CRC liver metastasis in model mice and affected the macrophage phenotype in the tumor microenvironment. Mechanistically, STING affects TAM polarization and regulates macrophage function through IRG1. And STING activates IRG1 to promote the nuclear translocation of TFEB, affecting the ability of macrophages to suppress tumor metastasis.Therefore, this study highlights the critical role of the STING-IRG1 axis on TAM reprogramming and its role in the process of tumor liver metastasis, which may provide a promising therapeutic strategy for CRC liver metastasis.

Numerous linear grooves have long been recognized as covering the surface of Phobos, but the mechanisms of their formation are still unclear. One possible mechanism is related to the largest crater on Phobos, the Stickney crater, whose impact ejecta may slide, roll, bounce, and engrave groove-like features on Phobos. When the launch velocity is higher than the escape velocity, the impact ejecta can escape Phobos. A portion of these high-velocity ejecta are dragged by the gravitational force of Mars, fall back, and reimpact Phobos. In this research, we numerically test the hypothesis that the orbital ejecta of the Stickney crater that reimpact Phobos could be responsible for a particular subset of the observed grooves on Phobos. We adopt impact hydrocode iSALE-2D (impact-Simplified Arbitrary Lagrangian Eulerian, two-dimensional) to simulate the formation of the Stickney crater and track its impact ejecta, with a focus on orbital ejecta with launch velocities greater than the escape velocity of Phobos. The launch velocity distribution of the ejecta particles is then used to calculate their trajectories in space and determine their fates. For orbital ejecta reimpacting Phobos, we then apply the sliding boulder model to calculate the ejecta paths, which are compared with the observed groove distribution and length to search for causal relationships. Our ejecta trajectory calculations suggest that only ~1% of the orbital ejecta from the Stickney crater can reimpact Phobos. Applying the sliding boulder model, we predict ejecta sliding paths of 9−20 km in a westward direction to the east of the zone of avoidance, closely matching the observed grooves in that region. The best-fit model assumes an ejecta radius of ~150 m and a speed restitution coefficient of 0.3, consistent with the expected ejecta and regolith properties. Our calculations thus suggest the groove class located to the east of the zone of avoidance may have been caused by reimpact orbital ejecta from the Stickney crater.

Abstract Background Aiming at the poor quality of small lectures due to the lack of lecturing skills of the clinical teachers in residency standardized training, the Teaching and Training Department of Shanghai East Hospital set up a continuous improvement project of lecturing skills for the clinical teachers to search for effective ways to improve lecture quality, then the effect was evaluated. Methods Based on the ADDIE model of training design, the department conducted the project in accordance with a process of analysis, design, development, implementation and evaluation. A special course “Clinical Teacher Presentation Training” (CTPT) was developed to convey and train the 5 key behaviors in presentation to improving lecture quality of the clinical teachers. Ninety-nine clinical teachers who give lectures to the residents were recruited as subjects for the project. Adopted the model of “intensive training + practice transference” to strengthen lecturing skills, and applied the Kirkpatrick Four Levels to evaluate the effect of the project from multi-role and multi-stage. Results The training satisfaction of the CTPT course from the subjects reaches 100%. The subjects have a high degree of knowledge acquisition through CTPT and the knowledge of the 5 key behaviors has been actually used in their lectures at the stage of practice transference. Comparing the data before training and after transference, it is found that the average increasing of the subjects’ 5 key behavior scores made by teaching secretaries is 14.12 points (14.12%) and that of the subjects’ self-efficacy scores is 9.31 points (9.31%); the performance values were modeling based on the scores from different types of evaluators and increased by an average of 12.61 points (12.61%); and the star ratings of the overall performance increased by an average of 1.17 points (23.4%). The results showed statistically difference (P

Monitoring the spatial distribution characteristics of heavy metal pollution and evaluating its potential risks in the soil is essential for promoting regional socioeconomic development and maintaining the safety of the ecological environment. In this study, a representative coal mining region in Tai’an City, Chinas was selected as the study area, eight typical heavy metal elements (HMEs), i.g. Cu, Pb, Zn, Cd, Cr, As, Hg, Ni in the topsoil (0–20 cm) of 59 randomly generated sample sites were measured and monitored through sampling, testing and statistical analysis, and their spatial distribution patterns were analyzed accordingly. The single factor pollution index（SFPI) method, comprehensive pollution index (CPI) method and potential ecological hazard index (PEHI) method were employed to systematically computed and analyzed the single factor, comprehensive pollution and potential ecological risks of the selected HMEs in the soil. Results found that: (1) the average measured content of these elements all exceeded the referenced background value. The Cr element pollution was the lowest (3.39%), while the pollution of Ni, Cd and Hg elements were the highest (86.44%, 83.05 % and 81.36%, respectively). (2) The comprehensive pollution level was above mild pollution at all sample sites, and the comprehensive pollution was mainly ranged in the mild pollution level (59.32%); The moderate pollution level of comprehensive potential ecological risk accounted for 64.41%, and the spatial distribution was annular from northwest to southeast. (3) The values of potential ecological risk index indicated that Hg and Cd were the main pollution elements in this coal mining region, and Cd had the highest pollution rate. The findings of this study can be used to evaluate the pollution in other coal regions, and provide reference for the decision-making of soil heavy metal pollution control.

Capsaicinoids, mostly from chili peppers, are widely used in daily life. Capsaicinoids are considered to be markers for the identification of illegal cooking oil (ICO), which is a serious threat to public health. The identification of capsaicinoids can help reveal food-related fraud, thereby safeguarding consumers’ health. Here, a novel and ultrasensitive method was established with a signal amplification strategy for the detection of capsaicinoids. AuNPs@Fe3O4 nanocomposites were functionalized with 4-aminothiophenol (4-atp). After diazotization, 4-atp on AuNPs@Fe3O4 reacted with capsaicinoids and formed capsaicinoids-azo-atp-AuNPs@Fe3O4. Ultimately, capsaicinoids-azo-atp-AuNPs@Fe3O4 was dropped onto the surface of a screen-printed carbon electrode (SPCE) and detected via the differential pulse voltammetry (DPV) method. AuNPs@Fe3O4 nanocomposites increased the specific surface area of the electrode. Moreover, the diazotization–coupling reaction enriched the analytes on the electrode surface. Liquid–liquid extraction was used for sample pretreatment. Under a pH value of 9.0 and concentration of 0.20 mol/L for the supporting electrolyte, the linearity of capsaicinoids in ICO is from 0.10 to 10.00 ng/mL, and the limit of detection (S/N = 3) is 0.05 ng/mL. This method is ultra-sensitive, reliable, and cost-effective for the detection of capsaicinoids. Herein, this method provides a promising tool for the identification of ICO.

Herein, we report the development of a drug delivery system (DDS) that can be very efficiently targeted to a breast cancer site by both aptamer and external magnetic field to achieve chemo-photothermal-starvation combination effects. Cancer starvation agent glucose oxidase was chemically attached to synthesized iron oxide nanoparticles (NPs) which were entrapped inside PLGA polymer along with Doxorubicin. To achieve photothermal property, the surface of the developed DDS was coated with polydopamine (PDA) to which aptamer was conjugated so that the DDS can be targeted by both external magnet and aptamer. The final size of the aptamer decorated DDS was 185.2 ​± ​3 ​nm. Upon NIR (near-infrared) laser irradiation, the DDS can raise the suspension's temperature over 50 ​°C within 10 ​min. Accelerated drug release was achieved in acidic conditions (pH 5.5) in the presence of laser irradiation due to both pH sensitivity and photothermal effect. Efficient dual targeting along with laser irradiation could reduce in vitro viability of MDA-MB-231 ​cells to 9.1 ​± ​2.3% resulting in a synergistic effect, whereas the same group could inhibit 90.6 ​± ​2.7% tumor growth showing the best therapeutic effect in a mouse model. The obtained results suggest that the developed DDS is an effective tool to treat various cancers by combination therapy.

Traditional walkers are commonly used for the elderly in social life, which solves the basic problem of walking, but it is difficult to ensure safety when a fall occurs, and the human-computer interaction is poor. The image recognition method or the IMU sensor method fixed on the user, such as a wearable watch, is used by most of the current fall detection methods. Wearable sensors require the user’s wearing operation, which is a little troublesome, and the detection accuracy is related to the way of wearing. The image recognition method requires a high-priced camera and a fixed installation position, which is unable to adapt to outdoor activities. We investigated a low-cost method of mounting the sensor on the body of the walker. We propose in this paper an improved fall detection method, namely Precondition and Limit Threshold SPRT (PLT-SPRT), and a novel fall detection system on the smart walker based on PLT-SPRT. The signals of the upper and lower limb sensors are fused based on the Kalman filter algorithm, and the admittance control parameters are obtained through the system identification method. In this study, the improved sequential probability ratio test algorithm is used to set the null hypothesis and the alternative hypothesis, construct the likelihood ratio and optimize the decision function, which is used to judge whether falls occur. The system is simulated by Matlab software, the user intention after fusion is more accurate, and the optimized decision function is judged accurately. Verified by the embedded system based on STM32 of the smart walker equipment in the real world, it can accurately identify the fallen state, with low detection delay, and the fallen state is detected about 160ms earlier than the traditional threshold-based detection algorithm, at the same time, the accuracy is higher than 94.9%, which meets the high real-time requirements of fall detection and is the ideal solution for smart walkers.

BackgroundEarly identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome.ObjectiveTo establish a risk prediction model for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).MethodsThe derivation cohort was from a meta-analysis. Risk factors and the corresponding risk ratio (RR) were extracted. Only risk factors with statistical significance were included in the model and were scored by their weightings. An external cohort were used to validate this model. The outcome was the occurrence of DPN.ResultsA total of 95,604 patients with T2DM from 18 cohorts were included. Age, smoking, body mass index, duration of diabetes, hemoglobin A1c, low HDL-c, high triglyceride, hypertension, diabetic retinopathy, diabetic kidney disease, and cardiovascular disease were enrolled in the final model. The highest score was 52.0. The median follow-up of validation cohort was 4.29 years. The optimal cut-off point was 17.0, with a sensitivity of 0.846 and a specificity of 0.668, respectively. According to the total scores, patients from the validation cohort were divided into low-, moderate-, high- and very high-risk groups. The risk of developing DPN was significantly increased in moderate- (RR 3.3, 95% CI 1.5–7.2, P = 0.020), high- (RR 15.5, 95% CI 7.6–31.6, P < 0.001), and very high-risk groups (RR 45.0, 95% CI 20.5–98.8, P < 0.001) compared with the low-risk group.ConclusionA risk prediction model for DPN including 11 common clinical indicators were established. It is a simple and reliable tool for early prevention and intervention of DPN in patients with T2DM.

BackgroundThyroid Cancer (TC) is the most common malignant disease of endocrine system, and its incidence rate is increasing year by year. Early diagnosis, management of malignant nodules and scientific treatment are crucial for TC prognosis. The first aim is the construction of a classification model for TC based on risk factors. The second aim is the construction of a prediction model for metastasis based on risk factors.MethodsWe retrospectively collected approximately 70 preoperative demographic and laboratory test indices from 1735 TC patients. Machine learning pipelines including linear regression model ridge, Logistic Regression (LR) and eXtreme Gradient Boosting (XGBoost) were used to select the best model for predicting deterioration and metastasis of TC. A comprehensive comparative analysis with the prediction model using only thyroid imaging reporting and data system (TI-RADS).ResultsThe XGBoost model achieved the best performance in the final thyroid nodule diagnosis (AUC: 0.84) and metastasis (AUC: 0.72-0.77) predictions. Its AUCs for predicting Grade 4 TC deterioration and metastasis reached 0.84 and 0.97, respectively, while none of the AUCs for Only TI-RADS reached 0.70. Based on multivariate analysis and feature selection, age, obesity, prothrombin time, fibrinogen, and HBeAb were common significant risk factors for tumor progression and metastasis. Monocyte, D-dimer, T3, FT3, and albumin were common protective factors. Tumor size (11.14 ± 7.14 mm) is the most important indicator of metastasis formation. In addition, GGT, glucose, platelet volume distribution width, and neutrophil percentage also contributed to the development of metastases. The abnormal levels of blood lipid and uric acid were closely related to the deterioration of tumor. The dual role of mean erythrocytic hemoglobin concentration in TC needs to be verified in a larger patient cohort. We have established a free online tool (http://www.cancer-thyroid.com/) that is available to all clinicians for the prognosis of patients at high risk of TC.ConclusionIt is feasible to use XGBoost algorithm, combined with preoperative laboratory test indexes and demographic characteristics to predict tumor progression and metastasis in patients with TC, and its performance is better than that of Only using TI-RADS. The web tools we developed can help physicians with less clinical experience to choose the appropriate clinical decision or secondary confirmation of diagnosis results.

AimsTo develop a feasible and effective nurse-manager dualistic intervention program to support nurses coping with burnout symptoms.BackgroundPerson-organization combined interventions were recommended as the most effective approach for reducing burnout symptoms. However, few interventions have been developed in the nursing field.MethodsThe Medical Research Council, United Kingdom (MRC UK), Framework for Development and Evaluation of Complex Interventions, was employed for nurse-manager dualistic intervention program development. The following three steps were followed for developing the dualistic intervention program: (1) identifying the evidence base by conducting extensive reviews of the relevant literature and a mixed study; (2) identifying/developing a theory by selecting the job demands-resources model and proposing the theoretical framework for intervention development; and (3) modifying the process and outcomes of the nurse-manager dualistic intervention program.ResultsThe intervention program consists of six group sessions over 9 weeks. Researchers/managers are supposed to deliver the program. The main contents of the intervention are (1) inception (session 1); (2) discovery (session 2); (3) dream (session 3); (4) design (session 4); (5) destiny (session 5); and (6) keep (session 6). The emphasis of the intervention is on helping nurses dealing with burnout symptoms.ConclusionFollowing the guidance of the MRC framework, a feasible and potentially effective nurse-manager dualistic intervention program was developed for nurses coping with burnout. Future studies are needed to model the intervention and assess the effects and replicability of the intervention.

Abstract Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5′,6,6′-tetrachloro1,1′,3,3′-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.

ObjectiveThe aim of this study is to explore efficacy and safety for radiofrequency ablation (RFA) among cases attacked by large benign solid thyroid nodules, mainly focusing on volume reduction, complication rate, and thyroid function.Methods and materialsFrom June 2015 to November 2019, 24 patients with 25 large benign solid thyroid nodules (more than 25 ml) underwent single or sequential RFA in our institution. Eleven nodules achieved complete ablation after single RFA, whereas the other 14 nodules received sequential RFA. Volume reduction in large nodules was evaluated. Following single or sequential RFA, all patients received clinical and ultrasound evaluations, and the median follow-up duration among them was 23.5 months. Technical success, complication rate, and recurrence rate were assessed as well.ResultsIn single RFA group, volume reduction ranged from 62.6% to 99.4% (mean ± SD, 93.6 ± 9.9%) 6 months after RFA. In sequential RFA group, volume reduction ranged from 30.6% to 92.9% (mean ± SD, 67.4 ± 17.8%) after the first RFA and was between 83.4% and 98.4% (mean ± SD, 94.8± 3.8%) 6 months after the second RFA. The concentrations of FT3 and FT4 increased slightly 1 day after RFA and returned to normal level 1 month after.ConclusionsSingle or sequential RFA is safe and effective in treating large benign solid thyroid nodules (more than 25 ml) that cause obvious compressive symptoms. Hence, compression symptoms and cosmetic conditions could be effectively improved through single or sequential RFA without marginal recurrence.

BackgroundThe incidence of papillary thyroid carcinoma (PTC) has rapidly increased in recent years. Microwave ablation (MWA) was proposed as an alternative treatment for PTC. This study aimed to investigate the efficacy and safety of MWA by exploring the postoperative pathology results of post-ablation lesions in patients with PTC.MethodsThis study retrospectively analyzed data from 12 patients who underwent thyroid surgery after MWA treatment for primary PTC between January 2015 and November 2021 in six hospitals.ResultsThe average age of the 12 patients (8 female) was 45.3 ± 9.7 years. There was one patient with PTC (size > 1 cm) and 11 patients with micro-PTC (size ≤ 1 cm), of which eight patients had unifocal micro-PTC and three patients had multifocal micro-PTC. A total of 17 tumor foci with mean size of 6.2 ± 2.6 mm were treated by MWA. The median interval time between MWA and surgery was 6.6 months (range: 0.4–21.9 months). Intraoperatively, adherence to the anterior cervical muscle group was observed in three cases (3/12). Upon postoperative pathologic examination, all the post-ablation lesions of the eight unifocal micro-PTC and two multifocal micro-PTC showed no residual carcinomas. Outside the ablation zone, PTCs were detected in three cases, including two of the eight patients with unifocal micro-PTC and one of the three patients with multifocal micro-PTC. Cervical lymph node metastases were detected in seven patients (7/12).ConclusionMWA was feasible for the treatment of primary unifocal low-risk micro-PTC (T1aN0M0) with good efficacy and safety. However, the use of MWA for treating PTC (size > 1 cm) and multifocal micro-PTC remains controversial.

In this study, it was aimed to exploit no chemical drug to treat cancer by starvation-immunotherapy combination. We used PD-L1 siRNA to down-regulate checkpoint protein PD-L1 on cancer cell surfaces, and IFN-γ was used as an immunomodulatory agent to activate the innate immune system. When PD-L1 siRNA, IFN-γ, and glucose oxidase (GOx) were co-delivered to the tumor microenvironment (TME) by a pH-sensitive drug delivery system (DDS), starvation-immunotherapy combinedly resulted in significant tumor volume reduction in a mouse model. The DDS was prepared by using PLGA polymer whose surface was coated with chitosan. IFN-γ, siRNA, and GOx entrapment efficiencies were 93.5 ± 3.1%, 65.1 ± 2.6%, and 66.2 ± 3.3%, respectively. Moreover, the size of the DDS was well below 200 nm, allowing easy sterilization and tumor accumulation by the enhanced permeability and retention (EPR) effect. In vitro pH-dependent release study indicated that in acidic pH, the developed DDS can show accelerated drug release. In a mouse model and in acidic TME, the DDS resulted in the best therapeutic effect due to pH-dependent drug release compared to unmodified DDS and free drug. Our findings reflect that high efficiency in colon cancer treatment is achieved by combination therapy over the studied monotherapies.

ObjectiveSurvivors of critical illness may experience short- and long-term physical function impairments. This review aimed to identify the risk factors for physical function impairments from the current literature.Data SourcesA systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews guideline was performed.Study SelectionThe risk factors reported in all human studies reporting physical function impairments in children admitted to the pediatric intensive care unit (PICU) were reviewed and categorized. Two investigators independently screened, evaluated, and selected studies for inclusion. Data from eligible studies were extracted by one investigator, and another investigator reviewed and verified the data. A systematic narrative approach was employed to review and summarize the data.ResultsA total of 264 studies were found to be eligible, with 19 studies meeting the inclusion criteria. Children admitted to the PICU experienced physical function impairments during their stay, which can last for years. The studies varied primarily in the measurement timing and tools used. The most frequently reported risk factors for physical function impairments were age, race or ethnicity, a pre-admission chronic condition, sex, disease severity, duration or the presence of mechanical ventilation, and admission diagnosis.ConclusionsPhysical function impairments may be persistent in PICU survivors. To prevent these impairments in critically ill patients, pediatricians should pay attention to modifiable risk factors, such as the duration of mechanical ventilation. Future studies need to promote a combination of standardized measures for the detection and prevention of physical function impairments.