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Cholecystolithiasis combined with choledocholithiasis represents a prevalent disease. At present, regarding the management of the common bile duct (CBD), T-tube drainage (TTD) and primary duct closure (PDC) emerge as two prominent approaches for biliary tract repair after laparoscopic CBD exploration (LCBDE). Here, retrospective analysis was conducted on the clinical records of 157 patients who underwent LCBDE at our hospital between January 2019 and January 2022. All patients were categorized into the PDC group or the TTD group based on the chosen CBD treatment approach. A comparative assessment was made across demographic factors, preoperative conditions, surgical particulars, and postoperative complications. The results showed that PDC is recommended for patients with a limited number of small stones, particularly when the CBD is in the 10-15 mm diameter range.

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Intrahepatic cholangiocarcinoma (iCCA) is a hepatobiliary malignancy which accounts for approximately 5-10 % of primary liver cancers and has a high mortality rate. The diagnosis of iCCA remains significant challenges owing to the lack of specific and sensitive diagnostic tests available. Hence, improved methods are needed to detect iCCA with high accuracy. In this study, we evaluated the efficacy of serum amino acid profiling combined with machine learning modeling for the diagnosis of iCCA. A comprehensive analysis of 28 circulating amino acids was conducted in a total of 140 blood samples from patients with iCCA and normal individuals. We screened out 6 differentially expressed amino acids with the criteria of |Log2(Fold Change, FC)| > 0.585, P-value < 0.05, variable importance in projection (VIP) > 1.0 and area under the curve (AUC) > 0.8, in which amino acids L-Asparagine and Kynurenine showed an increasing tendency as the disease progressed. Five frequently used machine learning algorithms (Logistic Regression, Random Forest, Supporting Vector Machine, Neural Network and Naïve Bayes) for diagnosis of iCCA based on the 6 circulating amino acids were established and validated with high sensitivity and good overall accuracy. The resulting models were further improved by introducing a clinical indicator, gamma-glutamyl transferase (GGT). This study introduces a new approach for identifying potential serum biomarkers for the diagnosis of iCCA with high accuracy.

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The mechanism of neuropathic pain induced by nerve injury is complex and there are no effective treatment methods. P2X4 receptor expression is closely related to the occurrence of pain. Schwann cells (SCs) play a key protective role in the repair of peripheral nerve injury and myelin sheath regeneration. However, whether SCs can affect the expression of P2X4 receptor and play a role in pathological pain is still unclear. Therefore, this study investigated the effect of SCs on whether they can down regulate the expression of P2X4 receptor to affect pain. The results showed that in the neuropathic pain induced by sciatic nerve injury model, the expression of P2X4 receptor in spinal cord tissue was significantly increased and the pain sensation of rats was increased. While SCs transplantation could down regulate the expression of P2X4 receptors in spinal cord and increase the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats. These data indicate that SCs can reduce the expression of P2X4 receptors to alleviate neuropathic pain, indicating that SCs can mediate P2X4 receptor signalling as a new target for pain treatment.

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Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

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BACKGROUND: Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three-dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes. PURPOSE: This study aimed to introduce an individual curved-needle interstitial template (ICIT) created using 3D printing technology for high-dose-rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented. METHODS: Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D-printed according to the high-risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V100, V200, D90, and D98) and organs at risk (OARs) (D2cc) were recorded. RESULTS: All patients completed interstitial brachytherapy treatment with the 3D-printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center. CONCLUSION: The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility.

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OBJECT: Autologous CD19 chimeric antigen receptor T-cell therapy (CAR-T) significantly modifies the natural course of chemorefractory diffuse large B-cell lymphoma (DLBCL). However, 25% to 50% of patients with relapsed/refractory DLBCL still do not achieve remission. Therefore, investigating new molecular prognostic indicators that affect the effectiveness of CAR-T for DLBCL and developing novel combination therapies are crucial. METHODS: Data from 73 DLBCL patients who received CD19 CAR-T (Axi-cel or Relma-cel) were retrospectively collected from Shanghai Tongji Hospital of Tongji University, The Second Affiliated Hospital Zhejiang University School of Medicine, and The Affiliated People's Hospital of Ningbo University. Prior to CD19 CAR-T-cell transfusions, the patients received fludarabine and cyclophosphamide chemotherapy regimen. RESULTS: Our study revealed that relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) patients with both Double-expression (MYC > 40% and BCL2 > 50%) and TP53 alterations tend to have a poorer clinical prognosis after CAR-T therapy, even when CAR-T therapy is used in combination with other therapies. However, CAR-T therapy was found to be effective in patients with only TP53 alterations or DE status, suggesting that their prognosis is in line with that of patients without TP53 alterations or DE status. CONCLUSIONS: Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities.

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As a typical natural photosensitizer, hypocrellin B (HB) offers the advantages of high molar extinction coefficient, high phototoxicity, low dark toxicity, and fast metabolism in vivo. However, the lack of tumor specificity hinders its clinical applications. Herein, we designed and synthesized a glutathione (GSH) responsive photosensitizer based on HB. The 7 - nitro - 2,1,3 - benzoxadiazole (NBD) covalently connected to HB not only served as a fluorescence quenching group but also as a GSH activating group. The photosensitizer HB-NBD showed almost no fluorescence and singlet oxygen generation as a result of the photoinduced electron transfer between HB and NBD. The designed photosensitizer HB-NBD can be activated by GSH in solutions and cancer cells, and then obtain recuperative fluorescence and photosensitive activity.

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High-voltage dual ion battery (DIB) is promising for stationary energy storage applications owing to its cost-effectiveness, which has been a hot topic of research in rechargeable battery fields. However, it still suffers from rapid battery failure caused by the severe solvent co-intercalation and electrolyte oxidation. To address these bottlenecks, herein a functional electrolyte additive hexafluoroglutaric anhydride (HFGA) is presented based on a Helmholtz plane regulation strategy. It is demonstrated that the HFGA can precisely enter into the Helmholtz plane and positively regulate anion solvation behaviors near the graphite electrode surface owing to its considerable H-F affinity with ethyl methyl carbonate (EMC), thus alleviating EMC-related co-intercalation and oxidation decomposition during DIB charging. Meanwhile, HFGA can copolymerize with the presence of PF5 at the Helmholtz plane to participate in forming a CF2-rich CEI layer with excellent PF6- permselectivity, conducive to achieving PF6- de-solvation and simultaneously suppressing electrolyte oxidation decomposition. By virtue of such beneficial effects, the graphite cathode enables a 5.5 V DIB with a prominent capacity retention of 92% and a high average Coulombic efficiency exceeding 99% within 2000 cycles, demonstrating significantly enhanced electrochemical reversibility. The Helmholtz plane regulation strategy marks a milestone in advancing DIB technologies.

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Deciphering the intricate cell-state transitions orchestrating immune adaptation over time stands as a cornerstone for advancing biological understanding. However, the lack of empirical in vivo genomic technologies capable of capturing cellular dynamics has posed a significant challenge. In response to this gap, a groundbreaking study introduces Zman-seq, a single-cell technology that records transcriptomic dynamics across time by incorporating time stamps into circulating immune cells, enabling their tracking in tissues for extended periods. The application of Zman-seq in glioblastoma research has successfully unraveled the cell state and molecular trajectories underlying the dysfunctional immune microenvironment. Understanding the temporal aspects of cell-state transitions during immune responses is pivotal for advancing our knowledge in biology. The emergence of Zman-seq addresses the current limitations in empirical in vivo genomic technologies, offering a revolutionary approach to studying the dynamics of immune cells over time. This highlight comprehensively explores the implications of Zman-seq in resolving cell-state transitions and molecular trajectories within the dysfunctional immune microenvironment in different types of immunotherapy. This technique has particular potential for chimeric antigen receptor T-cell therapy, overriding drug resistance, clinical medication optimization, and facilitating drug development. In particular, this article discusses potential strategies for improving the efficacy of clinical treatments.

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INTRODUCTION: Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection, especially in children and older people. However, no effective treatment is currently available. Type I interferons (IFNs) are a group of cytokines that help regulate the activity of the immune system. GB05, human IFNα1b inhalation solution, was developed under US Food and Drug Administration (FDA) standard guidelines to combat RSV infection. This randomized, double-blind, placebo-controlled, dose-escalation phase I trial evaluated the safety, tolerability, and pharmacokinetics of nebulized GB05. METHODS: A total of 35 eligible healthy Chinese adult volunteers were enrolled in this study. In the single ascending dose (SAD) study, volunteers were randomized into 0.2, 0.6, 1.2, and 1.8 million IU of GB05 or placebo. In the multiple ascending dose (MAD) study, volunteers received 1.2 or 1.8 million IU of GB05 or placebo for four consecutive days. Safety, tolerability, immunogenicity, and plasma pharmacokinetics were assessed for all groups. RESULTS: All adverse events were mild or moderate and resolved spontaneously. The most common adverse event was decreased white blood cell count (8.6% in SAD and 10% in MAD). No serious adverse events, deaths, or adverse events that reached the termination criteria occurred during the study. In SAD, the maximum concentration and area under the curve increased across the dose range of 1.2-1.8 million IU in a non-linear relationship. The maximum plasma concentration after GB05 nebulization (1.06 IU/ml in the 1.8 million IU group) reflected a low concentration in the blood, suggesting a better lung uptake of GB05 and reduced incidence or risks of adverse events. In MAD, a steady state was reached after continuous administrations of twice daily for 3 days. CONCLUSIONS: Overall, nebulized GB05 exhibited satisfactory safety, tolerability, and favorable pharmacokinetic (PK) profiles in healthy adult volunteers, supporting further clinical investigation in patients infected with respiratory syncytial virus. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06277167.

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How well autistic children can imitate movements and how their brain activity synchronizes with the person they are imitating have been understudied. The current study adopted functional near-infrared spectroscopy (fNIRS) hyperscanning and employed a task involving real interactions involving meaningful and meaningless movement imitation to explore the fundamental nature of imitation as a dynamic and interactive process. Experiment 1 explored meaningful and meaningless gesture imitation. The results revealed that autistic children exhibited lower imitation accuracy and behavioral synchrony than non-autistic children when imitating both meaningful and meaningless gestures. Specifically, compared to non-autistic children, autistic children displayed significantly higher interpersonal neural synchronization (INS) in the right inferior parietal lobule (r-IPL) (channel 12) when imitating meaningful gestures but lower INS when imitating meaningless gestures. Experiment 2 further investigated the imitation of four types of meaningless movements (orofacial movements, transitive movements, limb movements, and gestures). The results revealed that across all four movement types, autistic children exhibited significantly lower imitation accuracy, behavioral synchrony, and INS in the r-IPL (channel 12) than non-autistic children. This study is the first to identify INS as a biomarker of movement imitation difficulties in autistic individuals. Furthermore, an intra- and interindividual imitation mechanism model was proposed to explain the underlying causes of movement imitation difficulties in autistic individuals.

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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic diseases caused by a combination of many factors, including genetics, environment, and immunity. AAV is characterized by predominantly small-vessel involvement and has a variety of clinical manifestations. Small-vessel lesions of the kidneys and lungs are common, and lesions of medium-sized arteries may also present, but the involvement of large arteries and their primary branches is very rare. This report delineates two instances of AAV with large arterial involvement, one case presenting with lesions of the aortic valve and the other with lesions of the pulmonary artery. The first case involved a 57-year-old man with no underlying diseases. Transthoracic echocardiography showed thickening of the left and right coronary valves of the aortic valve with enhanced echogenicity, moderate echogenic masses were seen on both valve leaflets, and the leaflets had restricted opening and poor closure. Blood tests showed positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-myeloperoxidase (MPO) antibodies. The patient's aortic valve thickening virtually disappeared after treatment with hormones combined with immunosuppressive agents. The second case involved a 60-year-old woman whose transthoracic echocardiography and CT (computed tomography) angiography of the pulmonary arteries showed wall thickening of the main pulmonary artery and the proximal left and right pulmonary arteries, leading to luminal stenosis. Blood tests showed positive cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) and anti-proteinase 3 (PR 3) antibodies. The patient's pulmonary artery wall thickening reduced after receiving hormones in combination with immunosuppression but she died of heart failure during subsequent treatment. The patient had been diagnosed with tuberculosis six months earlier and had been poorly treated with anti-tuberculosis therapy. The involvement of large arteries in AAV is a rare and critical condition with rapid progression and a high mortality rate. Early recognition of this type of AAV and aggressive immunosuppressive therapy may facilitate the reversal of the vascular lesion and a reduction in the risk of patient death.

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The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.

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Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice.

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In crowdsourcing scenarios, we can obtain each instance's multiple noisy labels from different crowd workers and then infer its unknown ground truth via a ground truth inference method. However, to the best of our knowledge, the existing ground truth inference methods always attempt to aggregate multiple noisy labels into a single consensus label as the ground truth. In this article, we aim to explore a new strategy, i.e., label selection, which directly selects the label of the highest quality worker as the ground truth. To this end, we propose a label consistency-based ground truth inference (LCGTI) method. In LCGTI, we argue that high-quality workers should have a low bias with other workers in labeling the same instances and a low variance with themselves in labeling similar instances. To estimate the bias, we calculate the label consistency of different workers on the same instances. To estimate the variance, we calculate the label consistency of the same worker on similar instances. Finally, we combine these two components to calculate the labeling quality of each worker on the inferred instance and perform label selection instead of label aggregation to achieve inference. The experimental results on 34 simulated and two real-world datasets show that LCGTI significantly outperforms all the other state-of-the-art label aggregation-based ground truth inference methods.

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Over the past decades, cancer immunotherapy has encountered challenges such as immunogenicity, inefficiency, and cytotoxicity. Consequently, exosome-based cancer immunotherapy has gained rapid traction as a promising alternative. Exosomes, a type of extracellular vesicles (EVs) ranging from 50 to 150 nm, are self-originating and exhibit fewer side effects compared to traditional therapies. Exosome-based immunotherapy encompasses three significant areas: cancer vaccination, co-inhibitory checkpoints, and adoptive T-cell therapy. Each of these fields leverages the inherent advantages of exosomes, demonstrating substantial potential for individualized tumor therapy and precision medicine. This review aims to elucidate the reasons behind the promise of exosome-based nanoparticles as cancer therapies by examining their characteristics and summarizing the latest research advancements in cancer immunotherapy.

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Spinel cobalt oxides (Co3O4) have emerged as a promising class of catalysts for the electrochemical nitrate reduction reaction (eNO3RR) to ammonia, offering advantages such as low cost, high activity, and selectivity. However, the specific role of crystallographic facets in determining the catalysts' performance remains elusive, impeding the development of efficient catalysts. In this study, we have synthesized various Co3O4 nanostructures with exposed facets of {100}, {111}, {110}, and {112}, aiming to investigate the dependence of the eNO3RR activity on the crystallographic facets. Among the catalysts tested, Co3O4 {111} shows the best performance, achieving an ammonia Faradaic efficiency of 99.1 ± 1.8% with a yield rate of 35.2 ± 0.6 mg h-1 cm-2 at -0.6 V vs RHE. Experimental and theoretical results reveal a transformation process in which the active phases evolve from Co3O4 to Co3O4-x with oxygen vacancy (Ov), followed by a Co3O4-x-Ov/Co(OH)2 hybrid, and finally Co(OH)2. This process is observed for all facets, but the formation of Ov and Co(OH)2 is the most rapid on the (111) surface. The presence of Ov significantly reduces the free energy of the *NH2 intermediate formation from 1.81 to -0.53 eV, and plentiful active sites on the densely reconstructed Co(OH)2 make Co3O4 {111} an ideal catalyst for ammonia synthesis via eNO3RR. This work provides insights into the understanding of the realistic active components, offers a strategy for developing highly efficient Co-based spinel catalysts for ammonia synthesis through tuning the exposed facets, and helps further advance the design and optimization of catalysts in the field of eNO3RR.

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Sodium bis(fluorosulfonyl)imide (NaFSI) electrolytes are renowned for their superior physicochemical and electrochemical properties, making them ideal for high-performance sodium-ion batteries (SIBs). However, severe oxidative dissolution of aluminum current collectors (commonly known as Al corrosion) in NaFSI-based electrolytes occurs at high potentials. To address this challenge, aiming to understand the Al corrosion mechanism and develop strategies to inhibit corrosion, we propose dual-salt electrolytes using 0.8 mol L-1 (M) NaFSI and 0.2 M of a second fluorine-containing sodium salt dissolved in EC/PC solutions (1:1, v/v) to construct an insoluble deposits layer on the Al. Dual-salt electrolytes adopting a second sodium salt capable of passivating the Al collector have been extensively investigated through various techniques, such as cyclic voltammetry, scanning electron microscopy, chronoamperometry, X-ray photoelectron spectroscopy, and charge-discharge tests. Our findings demonstrate that introducing sodium difluoro(oxalato)borate (NaDFOB) into the NaFSI electrolytes inhibits Al corrosion, which is attributed to the formation of insoluble deposits of Al-F (AlF3) and B-F containing polymers. Moreover, the capacity retention of Na||Na3V2(PO4)3 (NVP) cells using the NaFSI-NaDFOB dual-salt electrolyte reaches 99.2% along with a Coulombic efficiency over 99.3% at a 1 C rate after 200 cycles. This research provides a practical solution for passivating Al collectors in SIBs with NaFSI electrolytes and promotes the development of sodium batteries with long calendar lifetimes.

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Fe-MOFs of mixed valence was synthesized by a solvothermal method via the in-situ reduction of ethylene glycol (EG) pre-coordination with the proper ratio of Fe2+/Fe3+ between 0.83 and 2.46. Synchronously with copper introduction, the Fe/Cu MOFs of mixed valence (Fe/Cu-MVMOFs) was then one pot acquired to remarkably improve the affinity of Fe2+ and Cu+ to H2O2 and promote the conversion efficiency of Fe2+/Fe3+ via the electron transfer among Fe-Cu bimetal clusters (XPS and XRD). Hence, the maximum reaction rate of H2O2 with Fe/Cu-MVMOFs reached 16.65 M·s-1, along with Km as low as 0.0479 mM. H2O2 and glutathione (GSH) were efficiently detected, ranging from 0.25 to 60 µM and from 0.2 to 40 µM, respectively. The investigation of catalyzation selectivity and practical serum detection by Fe/Cu-MVMOFs illustrated the efficacy and efficiency, denoting Fe/Cu-MVMOFs as the promising peroxidase candidate.