Improving Three-Photon Fluorescence of Near-Infrared Quantum Dots for Deep Brain Imaging by Suppressing Biexciton Decay.

Three-photon fluorescence microscopy (3PFM) is a promising brain research tool with submicrometer spatial resolution and high imaging depth. However, only limited materials have been developed for 3PFM owing to the rigorous requirement of the three-photon fluorescence (3PF) process. Herein, under the guidance of a band gap engineering strategy, CdTe/CdSe/ZnS quantum dots (QDs) emitting in the near-infrared window are designed for constructing 3PF probes. The formation of type II structure significantly increased the three-photon absorption cross section of QDs and caused the delocalization of electron-hole wave functions. The time-resolved transient absorption spectroscopy confirmed that the decay of biexcitons was significantly suppressed due to the appropriate band gap alignment, which further enhanced the 3PF efficiency of QDs. By utilizing QD-based 3PF probes, high-resolution 3PFM imaging of cerebral vasculature was realized excited by a 1600 nm femtosecond laser, indicating the possibility of deep brain imaging with these 3PF probes.

Institutionally validated nomogram predicting prognosis for older patients with nonmetastatic nasopharyngeal carcinoma.

Aim: Older adult patients with nonmetastatic nasopharyngeal carcinoma (NPC) have poor outcomes relative to younger patients. The authors' group established a nomogram to predict the overall survival of older adults with NPC and inform patient management. Methods: Cases with NPC (n = 782) were enrolled in this study; clinical data in the Surveillance, Epidemiology, and End Results database from 2010 to 2015 served as the training cohort (n = 657), and patients from Jiangxi Cancer Hospital (n = 125) served as the external validation cohort. Results: Training and external validation cohort C-index, receiver operator characteristics curves and calibration curves showed that our nomogram has great predictive ability. Conclusions: Compared with tumor-node-metastasis staging, this nomogram can help clinicians better predict the prognosis of older adults with nonmetastatic NPC.

It is well known that more than 80% of newly diagnosed NPC patients are nonmetastatic. Older adult patients with nonmetastatic nasopharyngeal carcinoma have a poor chance of survival relative to younger patients. With the world's aging population, the treatment of older adults with nonmetastatic NPC has attracted more attention from clinicians. The use of the American Joint Committee on Cancer staging system alone has significant shortcomings in predicting survival outcomes. Therefore, the authors developed a predictive tool by combining more prognostic factors with a specific multivariable statistical model, including age, tumor stage, node stage and treatment type, which is helpful for clinicians to more accurately evaluate the prognosis of patients.

Limited recurrence distance of glioblastoma under modern radiotherapy era.

BACKGROUND: The optimal treatment volume for Glioblastoma multiforme (GBM) is still a subject of debate worldwide. The current study was aimed to determine the distances between recurring tumors and the edge of primary lesions, and thereby provide evidence for accurate target area delineation. METHODS: Between October 2007 and March 2019, 68 recurrent patients with GBM were included in our study. We measured the distance from the initial tumor to the recurrent lesion of GBM patients by expanding the initial gross tumor volume (GTV) to overlap the center of recurrent lesion, with the help of the Pinnacle Treatment Planning System. RESULTS: Recurrences were local in 47(69.1%) patients, distant in 12(17.7%) patients, and both in 9(13.2%) patients. Factors significantly influencing local recurrence were age (P = 0.049), sex (P = 0.049), and the size of peritumoral edema (P = 0.00). A total number of 91 recurrent tumors were analyzed. All local recurrences occurred within 2 cm and 94.8% (55/58) occurred within 1 cm of the original GTV based on T1 enhanced imaging. All local recurrences occurred within 1.5 cm and 98.3%(57/58) occurred within 0.5 cm of the original GTV based on T2-FLAIR imaging. 90.9% (30/33) and 81.8% (27/33) distant recurrences occurred >3 cm of T1 enhanced and T2-Flair primary tumor margins, respectively. CONCLUSIONS: The 1 cm margin from T1 enhanced lesions and 0.5 cm margin from T2-Flair abnormal lesions could cover 94.8 and 98.3% local recurrences respectively, which deserves further prospective study as a limited but effective target area.

Enantiomeric Neolignans and a Sesquiterpene from Solanum erianthum and Their Absolute Configuration Assignment.

One pair of new C-8-C-3'/C-7-O-C-4' linked neolignan enantiomers (1a/1b) and one new guaiane sesquiterpene (2) first featuring the 1(2),9(10)-conjugated double bond were isolated from the stems of Solanum erianthum (Solanceae). Their structures were characterized on the basis of extensive spectroscopic analyses, especially from their 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations of 1a/2b were rigorously elucidated by electronic circular dichroism (ECD) experiments combined with the reversed helicity rule for the 2,3-dihydrobenzo[b]furan chromophore, and compound 2 is the first report on the sterochemical assignment of a guaiane sesquiterpene by using the allylic axial chirality rule for the conjugated diene chromophore in combination with the calculated ECD spectrum.

Chemical and pharmacological progress on polyacetylenes isolated from the family apiaceae.

This review presents an up-to-date survey of natural polyacetylenes isolated from the family Apiaceae, and their biosynthesis and biological activities up to May 2013, with 107 references. A total of 103 polyacetylenes from 72 species of 41 genera of Apiaceae have been isolated so far, among which falcarinol-type polyacetylenes are most widely distributed.

Super-resolution based Nodule Localization in Thyroid Ultrasound Images through Deep Learning.

BACKGROUND: Currently, it is difficult to find a solution to the inverse inappropriate problem, which involves restoring a high-resolution image from a lowresolution image contained within a single image. In nature photography, one can capture a wide variety of objects and textures, each with its own characteristics, most notably the high-frequency component. These qualities can be distinguished from each other by looking at the pictures. OBJECTIVE: The goal is to develop an automated approach to identify thyroid nodules on ultrasound images. The aim of this research is to accurately differentiate thyroid nodules using Deep Learning Technique and to evaluate the effectiveness of different localization techniques. METHODS: The method used in this research is to reconstruct a single super-resolution image based on segmentation and classification. The poor-quality ultrasound image is divided into several parts, and the best applicable classification is chosen for each component. Pairs of high- and lowresolution images belonging to the same class are found and used to figure out which image is high-resolution for each segment. Deep learning technology, specifically the Adam classifier, is used to identify carcinoid tumors within thyroid nodules. Measures, such as localization accuracy, sensitivity, specificity, dice loss, ROC, and area under the curve (AUC), are used to evaluate the effectiveness of the techniques. RESULTS: The results of the proposed method are superior, both statistically and qualitatively, compared to other methods that are considered one of the latest and best technologies. The developed automated approach shows promising results in accurately identifying thyroid nodules on ultrasound images. CONCLUSION: The research demonstrates the development of an automated approach to identify thyroid nodules within ultrasound images using super-resolution single-image reconstruction and deep learning technology. The results indicate that the proposed method is superior to the latest and best techniques in terms of accuracy and quality. This research contributes to the advancement of medical imaging and holds the potential to improve the diagnosis and treatment of thyroid nodules.

Intravital observation of high-scattering and dense-labeling hepatic tissues using multi-photon fluorescence microscopy.

Achieving high-resolution and large-depth microscopic imaging in vivo under conditions characterized by high-scattering and dense-labeling, as commonly encountered in the liver, poses a formidable challenge. Here, through the optimization of multi-photon fluorescence excitation window, tailored to the unique optical properties of the liver, intravital microscopic imaging of hepatocytes and hepatic blood vessels with high spatial resolution was attained. It's worth noting that resolution degradation caused by tissue scattering of excitation light was mitigated by accounting for moderate tissue self-absorption. Leveraging high-quality multi-photon fluorescence microscopy, we discerned structural and functional alterations in hepatocytes during drug-induced acute liver failure. Furthermore, a reduction in indocyanine green metabolism rates associated with acute liver failure was observed using NIR-II fluorescence macroscopic imaging.

Enhancing Total Optical Throughput of Microscopy with Deep Learning for Intravital Observation.

The significance of performing large-depth dynamic microscopic imaging in vivo for life science research cannot be overstated. However, the optical throughput of the microscope limits the available information per unit of time, i.e., it is difficult to obtain both high spatial and temporal resolution at once. Here, a method is proposed to construct a kind of intravital microscopy with high optical throughput, by making near-infrared-II (NIR-II, 900-1880 nm) wide-field fluorescence microscopy learn from two-photon fluorescence microscopy based on a scale-recurrent network. Using this upgraded NIR-II fluorescence microscope, vessels in the opaque brain of a rodent are reconstructed three-dimensionally. Five-fold axial and thirteen-fold lateral resolution improvements are achieved without sacrificing temporal resolution and light utilization. Also, tiny cerebral vessel dilatations in early acute respiratory failure mice are observed, with this high optical throughput NIR-II microscope at an imaging speed of 30 fps.

Gold-Nanorod-Assisted Live Cell Nuclear Imaging Based on Near-Infrared II Dark-Field Microscopy.

Dark-field microscopy offers several advantages, including high image contrast, minimal cell damage, and the absence of photobleaching of nanoprobes, which make it highly advantageous for cell imaging. The NIR-II window has emerged as a prominent research focus in optical imaging in recent years, with its low autofluorescence background in biological samples and high imaging SBR. In this study, we initially compared dark-field imaging results of colorectal cancer cells in both visible and NIR-II wavelengths, confirming the superior performance of NIR-II imaging. Subsequently, we synthesized gold nanorods with localized surface plasmon resonance (LSPR) absorption peaks in the NIR-II window. After bio-compatible modification, we non-specifically labeled colorectal cancer cells for NIR-II dark-field scattering imaging. The imaging results revealed a sixfold increase in SBR, especially in the 1425-1475 nm wavelength range. Finally, we applied this imaging system to perform dark-field imaging of cell nuclei in the NIR-II region and used GNRs for specific nuclear labeling in colorectal cancer cells. The resulting images exhibited higher SBR than non-specifically-labeled cell imaging, and the probe's labeling was precise, confirming the potential application of this system in photothermal therapy and drug delivery for cancer cells.

Near-Infrared Photothermal Manipulates Cellular Excitability and Animal Behavior in Caenorhabditis elegans.

Near-infrared (NIR) photothermal manipulation has emerged as a promising and noninvasive technology for neuroscience research and disease therapy for its deep tissue penetration. NIR stimulated techniques have been used to modulate neural activity. However, due to the lack of suitable in vivo control systems, most studies are limited to the cellular level. Here, a NIR photothermal technique is developed to modulate cellular excitability and animal behaviors in Caenorhabditis elegans in vivo via the thermosensitive transient receptor potential vanilloid 1 (TRPV1) channel with an FDA-approved photothermal agent indocyanine green (ICG). Upon NIR stimuli, exogenous expression of TRPV1 in AFD sensory neurons causes Ca2+ influx, leading to increased neural excitability and reversal behaviors, in the presence of ICG. The GABAergic D-class motor neurons can also be activated by NIR irradiation, resulting in slower thrashing behaviors. Moreover, the photothermal manipulation is successfully applied in different types of muscle cells (striated muscles and nonstriated muscles), enhancing muscular excitability, causing muscle contractions and behavior changes in vivo. Altogether, this study demonstrates a noninvasive method to precisely regulate the excitability of different types of cells and related behaviors in vivo by NIR photothermal manipulation, which may be applied in mammals and clinical therapy.

LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis.

Introduction: To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with medical treatments for women with heavy menstrual bleeding. Materials and methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant randomized controlled trials (RCTs) in November 2021. All meta-analyses were performed using the random-effects model. PROSPERO registration number: CRD42021295379. Results: A total of trials (with 14 references) reporting on 1,677 women were included in this systematic review. The majority of the included RCTs were rated with low-to-unclear risk of bias in selection, detection, attrition, reporting, and other bias. All RCTs were rated as high risk in performance bias because blinding was difficult to ensure in the compared groups. Results of meta-analyses revealed that the number of clinical responders was greater in the LNG-IUS group than that in the medical treatments group at both 6-month (steroidal: five RCTs; n = 490; risk ratio [RR]: 1.72 [1.13, 2.62]; I 2 = 92%; nonsteroidal: one RCT; n = 42; RR: 2.34 [1.31, 4.19]) and 12-month (steroidal: three RCTs; n = 261; RR: 1.31 [1.01, 1.71]; I 2 = 74%) endpoints, with no clear differences on number of dropouts, and the incidence of adverse events. Conclusion: Evidence indicates that LNG-IUS is superior to the medical treatments in short-term and medium-term clinical responses, blood loss control, compliance, and satisfaction. Meanwhile, frequency of adverse events related to LNG-IUS is acceptable. Systematic review registration: PROSPERO, identifier CRD42021259335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021295379.

Comparison of the Value of Conventional Ultrasound and Contrast-Enhanced Ultrasound-Guided Puncture Biopsy in Different Sizes of Peripheral Pulmonary Lesions.

Objective: To compare the clinical value of contrast-enhanced ultrasound and conventional ultrasound-guided puncture biopsy in peripulmonary lesions of different sizes. Materials and Methods: 110 patients with peripulmonary lesions were randomly divided into two groups: the conventional ultrasound-guided group and the contrast-enhanced ultrasound-guided group. The lesions in the two groups were further divided into two groups according to the size of the lesions, and the tissues taken after puncture biopsy were sent for pathological examination. The pathological results were compared with the postoperative pathological results and other examination results, and the complications were recorded at the same time. Results: In the conventional ultrasound group, the success rate of single puncture was 72.7% and the success rate of puncture was 80.0%; in the contrast group, the success rate of single puncture was 90.9% and the success rate of puncture was 94.6%. The difference between the two groups was statistically significant. There was no significant difference in needle bleeding and pneumothorax between the two groups. In the <30 mm group, there was no significant difference in the success rate of single puncture and the success rate of puncture between the two groups according to the size of the lesions. In the ≥30 mm group, the success rate of single puncture (97.1%) and puncture success rate (97.1%) in the contrast guidance group were higher than those in the conventional ultrasound guidance group (70.3%, 78.4%) and the difference was statistically significant (p < 0.05). Conclusion: Compared with conventional ultrasound, for peripheral pulmonary lesions guided by contrast-enhanced ultrasonography, especially when the maximum diameter of the lesion is ≥ 30 mm, needle biopsy has better guiding significance; for peripheral lung lesions with a maximum diameter of <30 mm, contrast-enhanced ultrasonography is compared with conventional ultrasound guidance. The puncture success rate was not significantly different.

The Transumbilical Laparoendoscopic Single-Site Extraperitoneal Approach for Pelvic and Para-Aortic Lymphadenectomy: A Technique Note and Feasibility Study.

Background: Nowadays, lymphadenectomy could be performed by the transperitoneal or extraperitoneal approach. Nevertheless, each approach has its own advantages and disadvantages. Under these circumstances, we developed a transumbilical laparoendoscopic single-site (TU-LESS) extraperitoneal approach for lymphadenectomy. In this research, the primary goal is to demonstrate the feasibility of the novel approach in systematic lymphadenectomy and present the surgical process step-by-step. Methods: Between May 2020 and June 2021, patients who had the indications of systematic lymphadenectomy underwent lymphadenectomy via the TU-LESS extraperitoneal approach. This new approach was described in detail, and the clinical characteristics and surgical outcomes were collected and analyzed. Results: Eight patients with gynecological carcinoma were included in the research, including four with high-risk endometrial cancer and four with early-stage ovarian cancer. The TU-LESS extraperitoneal approach for pelvic and para-aortic lymphadenectomy was successfully performed in all patients without conversion. In all, a median of 26.5 pelvic lymph nodes (range 18-35) and 18.0 para-aortic lymph nodes (range 7-43) were retrieved. There was a median of 166.5 min of surgical time (range 123-205). Patients had speedy recoveries without complications. All patients had positive pain responses after surgery, as well as satisfactory cosmetic and body image outcomes. Conclusion: Our initial experience showed that it is feasible to perform systematic lymphadenectomy with the TU-LESS extraperitoneal approach. And this new approach may provide a new measure or a beneficial supplement for lymphadenectomy in gynecologic cancer.

Identification of rare thalassemia variants using third-generation sequencing.

Routine PCR, Sanger sequencing, and specially designed GAP-PCR are often used in the genetic analysis of thalassemia, but all these methods have limitations. In this study, we evaluated a new third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in subjects with no variants identified by routine PCR, Sanger sequencing, and specially designed GAP-PCR. Hemoglobin testing and routine PCR tests for 23 common variants were performed for 3,033 subjects. Then, Sanger sequencing and specially designed GAP-PCR were performed for a subject with no variants identified by routine PCR, no iron deficiency, and positive hemoglobin testing. Finally, the new CATSA method was conducted for the subjects with no variants identified by Sanger sequencing and specially designed GAP-PCR. In the 49 subjects tested by CATSA, eight subjects had variants identified. Sanger sequencing and independent PCR confirmed the CATSA result. In addition, it is the first time that Hb Lepore was identified in Hunan Province. In total, traditional methods identified variants in 759 of the 3,033 subjects, while CATSA identified additional variants in eight subjects. CATSA showed great advantages compared to the other genetic testing methods.

Is a high-risk clinical target volume required? Evaluation of the dosimetric feasibility based on T staging.

Background: Clinical target delineation is a primary focus in the field of radiotherapy. This study aimed to investigate whether high-risk clinical target volume can be removed in nasopharyngeal carcinoma patients with different T stages. Materials and methods: We designed a test plan without the high-risk clinical target volume for 111 nasopharyngeal carcinoma patients and further compared the test plans with the treatment plans in the parameters of planning target volumes and the radiation dose to normal organs. Results: Our data showed that when high-risk clinical target volume was abnegated, target coverage, conformity indices, and homogeneity indices of planning target volumes and doses of normal organs were not influenced in the T4 nasopharyngeal carcinoma patients, and more than 95% of the high-risk planning target volume area could still be covered by the 60 Gy dose line. However, only some T1-3 patients achieved the ideal dose coverage, and even fewer after induction chemotherapy (62.8% vs. 41.2%, p = 0.018). Gross tumor volume was positively correlated with the target coverage of the original high-risk planning target volume in the test-plan (p = 0.0001). Gross tumor volume can be used to predict whether the target coverage of high-risk planning target volume is more than 95% (area under the curve = 0.868). Conclusion: Omitting high risk clinical target volume can be considered in patients with T4 nasopharyngeal carcinoma according to physical evaluations. However, this approach is only suitable for a specific subset of T1-3 patients.

Hot-Band-Absorption-Induced Anti-Stokes Fluorescence of Aggregation-Induced Emission Dots and the Influence on the Nonlinear Optical Effect.

Hot-band absorption (HBA)-induced anti-Stokes fluorescence (ASF) with longer-wavelength excitation is one effective pathway to deep penetration and low autofluorescence in intravital fluorescence imaging, raising demands for fluorophores with broad spectra, high absorption, and strong emission. However, typical fluorescent dyes display some emission quenching when their concentration is increased in order to obtain brighter fluorescence. In this work, the HBA-induced ASF of aggregation-induced emission (AIE) dots is reported. BPN-BBTD dots were synthesized and confirmed with a fluorescence enhancement and a considerable ASF intensity. In addition, the mechanism of ASF and the HBA process of BPN-BBTD dots were carefully validated and discussed. To obtain the full advantages of the long-wavelength excitation and the short fluorescence lifetime in deep-tissue bioimaging, a large-depth ASF confocal microscopic imaging of in vivo cerebral vasculature was conducted under the excitation of a 980 nm continuous wave laser after intravenous injection of BPN-BBTD dots. Meanwhile, the 3D structure of the cerebrovascular network was successfully reconstructed.

Retrospective Analysis of a Modified Irrigation Method for Nasopharyngeal Carcinoma Patients With Post-Radiation Nasopharyngeal Necrosis.

PURPOSE: Post-radiation nasopharyngeal necrosis (PRNN) is one of the most serious late effects of nasopharyngeal carcinoma (NPC) after radiotherapy. Standard conservative treatments are not always effective, and this study sought to investigate the feasibility of modified nasopharyngeal irrigation in the treatment of PRNN. METHODS: Between September 2011 and September 2018, 113 NPC patients with pathologically or radiologically diagnosed PRNN were analyzed retrospectively. All patients received the traditional conservative treatments of debridement of the necrotic tissues guided by an endoscope and systematic antibiotic therapy partly guided by culture results. The patients were divided into two groups according to the irrigation method used: traditional and modified groups. Modified irrigation used an irrigation device made by our hospital, guided by endoscopy, while the patients in the traditional irrigation group used a nasopharyngeal irrigation pot to wash the nasopharynx by themselves each day. RESULTS: Survival was affected by ICA (internal carotid artery) exposure, necrosis grade, and re-irradiation, but only ICA exposure and re-irradiation were found to be independent prognostic factors. The modified irrigation had a significantly more positive effect on the recovery rates of patients with mild- and moderate-grade PRNN than did traditional irrigation. The 2-year overall survival (OS) of the 113 patients was 68.4%. The modified irrigation was associated with better OS in the mild- and moderate-grade groups, in the one-course radiotherapy group, and in the low-risk group (according to the 2017 system). CONCLUSIONS: More intense modified irrigation under the physicians control may be an effective treatment for PRNN, especially mild- and moderate-grade, one-course radiotherapy, or low-risk PRNN.

Microbial etiology, susceptibility profile of postradiation nasopharyngeal necrosis patients with nasopharyngeal carcinoma.

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is important for clinical doctors to realize this problem in order to cope with this severe clinical situation. The aim of our study was to assess the bacteriology of PRNN and to demonstrate the antimicrobial susceptibility pattern that should guide the clinicians towards more appropriate antibiotic use. METHODS: Sixty-nine NPC patients with PRNN in our department between March 2013 and December 2017 were retrospectively enrolled. Pathogenic culture and drug sensitivity test were performed in these 69 NPC patients with PRNN. The infection rate of Pathogens and the sensitivity of the drugs were analyzed based on these results. RESULTS: Sixty-nine NPC patients with PRNN were enrolled in our study. Pathogens were identified in 58 (84%) patients. Of the 58 patients, Staphylococcus aureus was isolated in 34 (58.6%) patients. And the second most common group of bacterial isolates was Pseudomonas aeruginosa. Antibiotic sensitivity showed that Levofloxacin was the highest (88.5%), followed by Ciprofloxacin (85.2%) and Gentamicin (80.3%). The only pathologic fungus was Candidaalbicans, about 6.8%. The positive rates of bacterial and fungal culture in PRNN patients were not significantly different from the patients' gender, age, stage, number of radiotherapy courses (P>0.05), but the cure rate was statistically higher in culture-negative patients in comparison with culture-positive patients (63.6% vs 20.7%, P=0.011). CONCLUSION: Our results provide an overall picture of the microbiology and drug susceptibility patterns for NPC patients with PRNN and could help implement guidelines for more rational treatment and improve therapeutic outcome.