Cascaded multicore fiber interferometers for enhanced bending sensing based on the Vernier effect.

In this paper, cascaded modal interferometers constructed by strongly-coupled seven-core fiber (SC-SCF) with different lengths are demonstrated for enhanced bending sensing based on Vernier effect. The free spectral range (FSR) of a single SC-SCF interferometer is determined by the length of SC-SCF. Two SC-SCF interferometers with different FSRs are cascaded, in which, one functions as the sensor while the other functions as the reference. The wavelength shift of the envelope of the output spectrum is much larger than that of a single SC-SCF interferometer due to the Vernier effect. Therefore, enhanced sensing can be achieved. Experimental results show that the bending sensitivity of the proposed sensor is improved from -2.20 nm/m-1 (single SC-SCF interferometer) to 42.32 nm/m-1 (cascaded SC-SCF interferometers). The temperature response of the sensor is also investigated. Our proposed cascaded SC-SCF sensor has advantages of high sensitivity, ease of fabrication, and low cost. It is attractive for high precision bending sensing applications.

Laparoscopic left hemihepatectomy using augmented reality navigation plus ICG fluorescence imaging for hepatolithiasis: a retrospective single-arm cohort study (with video).

BACKGROUND: Laparoscopic left hemihepatectomy (LLH) has been shown to be an effective and safe method for treating hepatolithiasis primarily affecting the left hemiliver. However, this procedure still presents challenges. Due to pathological changes in intrahepatic duct stones, safely dissecting the hilar vessels and determining precise resection boundaries remains difficult, even with fluorescent imaging. Our team proposed a new method of augmented reality navigation (ARN) combined with Indocyanine green (ICG) fluorescence imaging for LLH in hepatolithiasis cases. This study aimed to investigate the feasibility of this combined approach in the procedure. METHODS: Between May 2021 and September 2023, 16 patients with hepatolithiasis who underwent LLH were included. All patients underwent preoperative 3D evaluation and were then guided using ARN and ICG fluorescence imaging during the procedure. Perioperative and short-term postoperative outcomes were assessed to evaluate the safety and efficacy of the method. RESULTS: All 16 patients successfully underwent LLH. The mean operation time was 380.31 ± 92.17 min, with a mean estimated blood loss of 116.25 ± 64.49 ml. ARN successfully aided in guiding hilar vessel dissection in all patients. ICG fluorescence imaging successfully identified liver resection boundaries in 11 patients (68.8%). In the remaining 5 patients (31.3%) where fluorescence imaging failed, virtual liver segment projection (VLSP) successfully identified their resection boundaries. No major complications occurred in any patients. Immediate stone residual rate, stone recurrence rate, and stone extraction rate through the T-tube sinus tract were 12.5%, 6.3%, and 6.3%, respectively. CONCLUSION: The combination of ARN and ICG fluorescence imaging enhances the safety and precision of LLH for hepatolithiasis. Moreover, ARN may serve as a safe and effective tool for identifying precise resection boundaries in cases where ICG fluorescence imaging fails.

A pilot study of virtual liver segment projection technology in subsegment-oriented laparoscopic anatomical liver resection when indocyanine green staining fails (with video).

BACKGROUND: Precision surgery for liver tumors favors laparoscopic anatomical liver resection (LALR), involving the removal of specific liver segments or subsegments. Indocyanine green (ICG)-negative staining is a commonly used method for defining resection boundaries but may be prone to failure. The challenge arises when ICG staining fails, as it cannot be repeated during surgery. In this study, we employed the virtual liver segment projection (VLSP) technology as a salvage approach for precise boundary determination. Our aim was to assess the feasibility of the VLSP to be used for the determination of the boundaries of the liver resection in this situation. METHODS: Between January 2021 and June 2023, 12 consecutive patients undergoing subsegment-oriented LALR were included in this pilot series. The VLSP technology was utilized to define the resection boundaries at the time of ICG-negative staining failure. Routine surgical parameters and short-term outcomes were evaluated to assess the safety of VLSP in this procedure. In addition, its feasibility was assessed by analyzing the accuracy between the predicted resected liver volume (PRLV) and actual resected liver volume (ARLV). RESULTS: Of the 12 enrolled patients, the mean operation time was 444.58 ± 101.70 min (range 290-570 min), with a mean blood loss of 125.00 ± 96.53 ml (range 50-400 mL). One patient (8.3%) was converted to laparotomy for subsequent parenchymal transection, four (33.3%) received blood transfusions and four (33.3%) had postoperative complications. All patients received an R0 resection. The Pearson correlation coefficient (r) between PRLV and ARLV was 0.98 (R2 = 0.96, p < 0.05), and the relative error (RE) was 8.62 ± 6.66% in the 12 patients, indicating agreement. CONCLUSION: Failure of intraoperative ICG-negative staining during subsegment-oriented LALR is possible, and VLSP may be an alternative to define the resection boundaries in such cases.

Design, synthesis and biological evaluation of novel 1,2,4a,5-tetrahydro-4H-benzo[b][1,4]oxazino[4,3-d][1,4]oxazine-based AAK1 inhibitors with anti-viral property against SARS-CoV-2.

Coronavirus entry into host cells hinges on the interaction between the spike glycoprotein of the virus and the cell-surface receptor angiotensin-converting enzyme 2 (ACE2), initiating the subsequent clathrin-mediated endocytosis (CME) pathway. AP-2-associated protein kinase 1 (AAK1) holds a pivotal role in this pathway, regulating CME by modulating the phosphorylation of the µ subunit of adaptor protein 2 (AP2M1). Herein, we report a series of novel AAK1 inhibitors based on previously reported 1,2,4a,5-tetrahydro-4H-benzo[b] [1,4]oxazino[4,3-d] [1,4]oxazine scaffold. Among 23 synthesized compounds, compound 12e is the most potent one with an IC50 value of 9.38 ± 0.34 nM against AAK1. The in vitro antiviral activity of 12e against SARS-CoV-2 was evaluated using a model involving SARS-CoV-2 pseudovirus infecting hACE2-HEK293 host cells. The results revealed that 12e was superior in vitro antiviral activity against SARS-CoV-2 entry into host cells when compared to SGC-AAK1-1 and LX9211, and its activity was comparable to that of a related and reference compound 8. Mechanistically, all AAK1 inhibitors attenuated AAK1-induced phosphorylation of AP2M1 threonine 156 and disrupted the direct interaction between AP2M1 and ACE2, ultimately inhibiting SARS-CoV-2 infection. Notably, compounds 8 and 12e exhibited a more potent effect in suppressing the phosphorylation of AP2M1 T156 and the interaction between AP2M1 and ACE2. In conclusion, novel AAK1 inhibitor 12e demonstrates significant efficacy in suppressing SARS-CoV-2 infection, and holds promise as a potential candidate for developing novel antiviral drugs against SARS-CoV-2 and other coronavirus infections.

Discovery of plant-derived anti-tumor natural products: Potential leads for anti-tumor drug discovery.

Natural products represent a paramount source of novel drugs. Numerous plant-derived natural products have demonstrated potent anti-tumor properties, thereby garnering considerable interest in their potential as anti-tumor drugs. This review compiles an overview of 242 recently discovered natural products, spanning the period from 2018 to the present. These natural products, which include 69 terpenoids, 42 alkaloids, 39 flavonoids, 21 steroids, 14 phenylpropanoids, 5 quinolines and 52 other compounds, are characterized by their respective chemical structures, anti-tumor activities, and mechanisms of action. By providing an essential reference and fresh insights, this review aims to support and inspire researchers engaged in the fields of natural products and anti-tumor drug discovery.

Design, synthesis and anti-tumor efficacy evaluation of novel 1,3-diaryl propane-based polyphenols obtained from Claisen rearrangement reaction.

Polyphenols such as resveratrol, honokiol and nordihydroguaiaretic acid are widely existing in nature products or synthetic compounds with interesting biological activities. Inspired by their structural feature, a total of 49 1,3-diaryl propane-based polyphenols were designed and synthesized through Claisen rearrangement reaction. New compounds were initially assessed for their anti-proliferative activities against various cancer cell lines (PC-3, U87MG, U251, HCT116) at a concentration of 50 µM, and the results guided the SAR of this series of compounds. Further screening of selected compounds against seven cancer cell lines (three additional colon cancer cell lines namely COLO205, HT29 and SW480 were chosen) led to the identification of two advanced leads 2t and 3t with IC50 values ranging from 8.2 ± 0.1 to 19.3 ± 1.9 µM. Both compounds also showed promising anti-proliferative activities against COLO205 in dose- and time-dependent manners. Furthermore, 2t and 3t exhibited good anti-tumor efficacy in COLO205 xenografted mice model with TGI values ranging from 38% to 58%. These results warrant the further investigation of this series of compounds.

An ultrasonographic study of gouty arthritis: Synovitis and its relationship to clinical symptoms: A retrospective analysis.

Background and Aims: Joint pain is the main symptom of acute attacks in patients with gout, which if not managed properly, can develop into chronic gout. The aim of this study was to investigate the correlation between ultrasound (US) features of gouty arthritis (GA) and its clinical manifestations to provide a basis for diagnosing and evaluating the disease. Methods: We retrospectively analyzed 182 sites in 139 patients with GA diagnosed by the Rheumatology and Immunology Department. Degree of pain was evaluated using the visual analog scale (VAS). Patients with GA were divided into active and inactive arthritis groups. Statistical differences between the two groups and the correlation between US features and clinical manifestations of the affected joints in patients with GA were analyzed. Results: The groups had statistical significance in joint effusion, power Doppler ultrasonography (PDS), double contour sign, and bone erosion (p = 0.02, 0.001, 0.04, 0.04, respectively). Correlation analysis in this study showed that joint effusion and PDS were positively correlated with degree of pain (r s = 0.275, 0.269; p < 0.001, <0.001, respectively). Additionally, PDS was positively correlated with synovitis, joint effusion, bone erosion, and aggregates (r s = 0.271, 0.281, 0.222, 0.281; p < 0.001, <0.001, 0.003, <0.001, respectively). Conclusions: Pathological US features, such as joint effusion, synovitis, PDS and bone erosion were more likely to be detected in GA with clinical signs and symptoms. PDS was positively correlated with joint effusion and synovitis, pain was closely related to PDS and joint effusion, which suggested that the clinical symptoms of GA were related to inflammation, reflecting the patient's condition to some extent. Therefore, musculoskeletal US is a useful clinical tool for managing patients with GA and can provide a reliable reference for diagnosing and treating GA.

Augmented Reality Navigation System and Indocyanine Green Fluorescence Imaging Make Laparoscopic Right Anterior Sectionectomy More Precisely and Safely.

BACKGROUND: Laparoscopic right anterior sectionectomy (LRAS) is an attractive surgical option for tumors in the right anterior section (RAS), which can remove tumor-bearing segments while sparing more normal liver tissue1. However, the definition of the resection plane, the guidance during the resection, and the protection of the right posterior hepatic duct are still the key points of this procedure2. Our center attempted to use augmented reality navigation system and indocyanine green fluorescence (ICG) imaging technology to solve these difficulties3, and reported this in LRAS for the first time. METHODS: A 47-year-old female was admitted to our institution for a tumor in the RAS. Therefore, LRAS was performed. First, a virtual liver segment projection combined with the ischemic line caused by the occlusion of RAS blood flow was used to mark the RAS boundary, and it was confirmed using the ICG negative staining. Then, during the parenchymal transection, the precise resection plane was guided assisted by the ICG fluorescence imaging system. In addition, the right anterior Glissonean pedicle (RAGP) was divided using a linear stapler after confirming the spatial relationship of the bile duct using ICG fluorescence imaging. RESULTS: The operation lasted 360 min with 100 mL of intraoperative blood loss. There were no postoperative complications, and the patient was discharged after 8 days. CONCLUSION: The augmented reality navigation system plus ICG imaging can make LRAS more precisely and safely.

Microwave-assisted rapid synthesis of chiral oxazolines.

Chiral oxazoline compounds play an extremely important role in asymmetric synthesis and drug discovery. Herein a simpler, greener and more efficient microwave-assisted protocol to rapidly access chiral oxazolines is developed using aryl nitriles or cyano-containing compounds and chiral ß-amino alcohols as starting materials. The reaction proceeds smoothly in the presence of a recoverable heterogeneous catalyst in either concentrated solution or under solvent-free conditions. The advantages of this method include rapidness, convenience, environmental protection, high atom economy, and excellent yields. The protocol should find wider application in the community in the future.

Deep learning based on carotid transverse B-mode scan videos for the diagnosis of carotid plaque: a prospective multicenter study.

OBJECTIVES: Accurate detection of carotid plaque using ultrasound (US) is essential for preventing stroke. However, the diagnostic performance of junior radiologists (with approximately 1 year of experience in carotid US evaluation) is relatively poor. We thus aim to develop a deep learning (DL) model based on US videos to improve junior radiologists' performance in plaque detection. METHODS: This multicenter prospective study was conducted at five hospitals. CaroNet-Dynamic automatically detected carotid plaque from carotid transverse US videos allowing clinical detection. Model performance was evaluated using expert annotations (with more than 10 years of experience in carotid US evaluation) as the ground truth. Model robustness was investigated on different plaque characteristics and US scanning systems. Furthermore, its clinical applicability was evaluated by comparing the junior radiologists' diagnoses with and without DL-model assistance. RESULTS: A total of 1647 videos from 825 patients were evaluated. The DL model yielded high performance with sensitivities of 87.03% and 94.17%, specificities of 82.07% and 74.04%, and areas under the receiver operating characteristic curve of 0.845 and 0.841 on the internal and multicenter external test sets, respectively. Moreover, no significant difference in performance was noted among different plaque characteristics and scanning systems. Using the DL model, the performance of the junior radiologists improved significantly, especially in terms of sensitivity (largest increase from 46.3 to 94.44%). CONCLUSIONS: The DL model based on US videos corresponding to real examinations showed robust performance for plaque detection and significantly improved the diagnostic performance of junior radiologists. KEY POINTS: • The deep learning model based on US videos conforming to real examinations showed robust performance for plaque detection. • Computer-aided diagnosis can significantly improve the diagnostic performance of junior radiologists in clinical practice.

A Questionnaire-Based Ensemble Learning Model to Predict the Diagnosis of Vertigo: Model Development and Validation Study.

BACKGROUND: Questionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders. OBJECTIVE: This study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo. METHODS: In this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation. RESULTS: A total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation. CONCLUSIONS: The questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.

Ensemble learning for the early prediction of neonatal jaundice with genetic features.

BACKGROUND: Neonatal jaundice may cause severe neurological damage if poorly evaluated and diagnosed when high bilirubin occurs. The study explored how to effectively integrate high-dimensional genetic features into predicting neonatal jaundice. METHODS: This study recruited 984 neonates from the Suzhou Municipal Central Hospital in China, and applied an ensemble learning approach to enhance the prediction of high-dimensional genetic features and clinical risk factors (CRF) for physiological neonatal jaundice of full-term newborns within 1-week after birth. Further, sigmoid recalibration was applied for validating the reliability of our methods. RESULTS: The maximum accuracy of prediction reached 79.5% Area Under Curve (AUC) by CRF and could be marginally improved by 3.5% by including genetic variant (GV). Feature importance illustrated that 36 GVs contributed 55.5% in predicting neonatal jaundice in terms of gain from splits. Further analysis revealed that the main contribution of GV was to reduce the false-positive rate, i.e., to increase the specificity in the prediction. CONCLUSIONS: Our study shed light on the theoretical and practical value of GV in the prediction of neonatal jaundice.

Clinicopathological and prognostic value of circulating tumor cells in esophageal carcinoma: a meta-analysis.

BACKGROUND: The associations between circulating tumor cells (CTCs) in peripheral blood and prognosis of patients with esophageal carcinoma (EC) have been investigated by a number of studies, but the results are not consistent. Therefore, this study aimed to explore this controversial subject. METHODS: A literature database search was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs) were retained as the effect measures. If necessary, subgroup analyses and metaregression should also be performed to clarify the heterogeneity. RESULTS: Thirty-three studies, containing 3,236 patients with EC, were included in this meta-analysis. The results showed that overall survival (OS) (HR =2.14; 95% CI, 1.73-2.65) and progression-free survival (PFS) (HR =2.29; 95% CI, 1.69-3.11) were worse in CTCs-positive patients. CTC positivity is also significantly associated with depth of infiltration (RR =1.42; 95% CI, 1.10-1.82, P=0.21) and tumor-node-metastasis (TNM) stage (RR =1.36; 95% CI, 1.09-1.69, P=0.22). However, there was no significant relationship between CTC-positive and distant metastasis (RR =1.58; 95% CI, 1.00-2.50, P=0.65). CONCLUSIONS: Detection of CTCs had prognostic value for EC patients. Positive CTC is associated with poor prognosis and some prognostic factors, such as depth of infiltration and TNM stage, but not related to metastasis.

Osimertinib for EGFR-mutant lung cancer with central nervous system metastases: a meta-analysis and systematic review.

BACKGROUND: Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR)TKI. Osimertinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Osimertinib is used to treat a certain type of non-small cell lung cancer. We review some of the main challenges in targeting EGFR, including lack of central nervous system penetration with most tyrosine kinase inhibitors, activity of osimertinib penetrating blood-brain barrier and the efficacy of osimertinib. METHODS: Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, we conducted a systematic literature search in the databases PubMed, EMBASE, ISI Web of Science database on January 30, 2020, searching for studies investigating the osimertinib efficacy on patients with CNS metastases in EGFR-mutant non-small cell lung cancer (NSCLC). And Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence. RESULTS: The pooled results showed that the overall response rate (ORR) and disease control rate (DCR) were 70% and 92%, respectively, in patients with T790M mutations. The efficacy of osimertinib was confirmed by the median progression free survival (PFS). In untreated advanced EGFR-mutated NSCLC with CNS metastases patients, the pooled ORR and DCR of osimertinib were 71% and 93%, respectively. And the combined median PFS, achieved by osimertinib, was 12.21 months. Above data proved that osimertinib has well activity in disease control, especially in first line. CONCLUSIONS: This meta-analysis confirmed that in treatment-naive advanced NSCLC CNS metastases harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity.

Combination Chemotherapy of Lung Cancer - Co-Delivery of Docetaxel Prodrug and Cisplatin Using Aptamer-Decorated Lipid-Polymer Hybrid Nanoparticles.

PURPOSE: Lung cancer is the leading cause of cancer mortality worldwide. Drug resistance is the major barrier for the treatment of non-small cell lung cancer (NSCLC). The aim of this research is to develop an aptamer-decorated hybrid nanoparticle for the co-delivery of docetaxel prodrug (DTXp) and cisplatin (DDP) and to treat lung cancer. MATERIALS AND METHODS: Aptamer-conjugated lipid-polymer ligands and redox-sensitive docetaxel prodrug were synthesized. DTXp and DDP were loaded into the lipid-polymer hybrid nanoparticles (LPHNs). The targeted efficiency of aptamer-decorated, DTXp and DDP co-encapsulated LPHNs (APT-DTXp/DDP-LPHNs) was determined by performing a cell uptake assay by flow cytometry-based analysis. In vivo biodistribution and anticancer efficiency of APT-DTXp/DDP-LPHNs were evaluated on NSCLC-bearing mice xenograft. RESULTS: APT-DTXp/DDP-LPHNs had a particle size of 213.5 ± 5.3 nm, with a zeta potential of 15.9 ± 1.9 mV. APT-DTXp/DDP-LPHNs exhibited a significantly enhanced cytotoxicity (drug concentration causing 50% inhibition was 0.71 ± 0.09 µg/mL), synergy antitumor effect (combination index was 0.62), and profound tumor inhibition ability (tumor inhibition ratio of 81.4%) compared with the non-aptamer-decorated LPHNs and single drug-loaded LPHNs. CONCLUSION: Since the synergistic effect of the drugs was found in this system, it would have great potential to inhibit lung tumor cells and in vivo tumor growth.

Pursuing for the better lung cancer therapy effect: Comparison of two different kinds of hyaluronic acid and nitroimidazole co-decorated nanomedicines.

Lung cancer remains the leading cause of cancer associated deaths worldwide. Compared with traditional chemotherapy for non-small cell lung cancer (NSCLC), specific targeted therapies are better choices for advanced patients to improve their survival. In this study, we attempted to fabricate Nitroimidazoles (NI) and Hyaluronic acid (HA) co-decorated, cisplatin (DDP) loaded polymeric nanoparticles (PNPs) (NI/HA-DDP-PNPs) and lipid-polymer hybrid nanoparticles (LPNs) (NI/HA-DDP-LPNs) for the facilitated drug delivery at lung tumor regions (hypoxic regions). In vitro cytotoxicity and cellular uptake; In vivo anti-tumor activity and in vivo tissue biodistribution of PNPs and LPNs were evaluated and compared in lung carcinoma cells and xenograft. Hydrodynamic size of NI/HA-DDP-LPNs was 185.6 ± 4.7 nm, which is larger than that of NI/HA-DDP-PNPs (136.7 ± 3.5 nm). The zeta potential of NI/HA-DDP-PNPs (-31.2 ± 2.7 mV) was more negative than NI/HA-DDP-LPNs (-22.3 ± 2.1 mV). The peak plasma concentration (Cmax) achieved from NI/HA-DDP-PNPs and NI/HA-DDP-LPNs was 35.2 ± 1.6 and 37.3 ± 1.7 µg/mL. The half-life (T1/2) of NI/HA-DDP-PNPs and NI/HA-DDP-LPNs was 12.03 ± 0.75 and 11.78 ± 0.89 h. Area Under Curve (AUC) of NI/HA-DDP-PNPs and NI/HA-DDP-LPNs showed no significant difference while greater than other groups. NI/HA-DDP-LPNs exhibited excellent antitumor effect against drug-resistant human lung cancer A549/DDP cells in vitro and in vivo, better than that of NI/HA-DDP-PNPs. Considering that the low toxicity of NI/HA-DDP-LPNs and NI/HA-DDP-PNPs, NI/HA-DDP-LPNs could be a more promising system for lung cancer targeted therapy.