[Kuwanon G inhibits growth, migration and invasion of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway].

OBJECTIVE: To investigate the effects of kuwanon G (KG) on proliferation, apoptosis, migration and invasion of gastric cancer cells and the molecular mechanisms. METHODS: The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay, by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67. The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit, Western blotting and TUNEL staining. The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase (MMP). The role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in KG-mediated regulation of gastric cancer cell proliferation, migration, and invasion was verified by Western blotting and rescue assay. RESULTS: KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner (P < 0.05). KG treatment also increased apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, down-regulated Bcl-2, lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells (P < 0.05). Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway, and IGF-1, an activator of the PI3K/AKT/mTOR pathway, reversed the effects of KG on proliferation, migration and invasion of gastric cancer cells (P < 0.05). CONCLUSION: KG inhibits proliferation, migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Assessment of noise pollution-prone areas using an explainable geospatial artificial intelligence approach.

This research aims to use the power of geospatial artificial intelligence (GeoAI), employing the categorical boosting (CatBoost) machine learning model in conjunction with two metaheuristic algorithms, the firefly algorithm (CatBoost-FA) and the fruit fly optimization algorithm (CatBoost-FOA), to spatially assess and map noise pollution prone areas in Tehran city, Iran. To spatially model areas susceptible to noise pollution, we established a comprehensive spatial database encompassing data for the annual average Leq (equivalent continuous sound level) from 2019 to 2022. This database was enriched with critical spatial criteria influencing noise pollution, including urban land use, traffic volume, population density, and normalized difference vegetation index (NDVI). Our study evaluated the predictive accuracy of these models using key performance metrics, including root mean square error (RMSE), mean absolute error (MAE), and receiver operating characteristic (ROC) indices. The results demonstrated the superior performance of the CatBoost-FA algorithm, with RMSE and MAE values of 0.159 and 0.114 for the training data and 0.437 and 0.371 for the test data, outperforming both the CatBoost-FOA and CatBoost models. ROC analysis further confirmed the efficacy of the models, achieving an accuracy of 0.897, CatBoost-FOA with an accuracy of 0.871, and CatBoost with an accuracy of 0.846, highlighting their robust modeling capabilities. Additionally, we employed an explainable artificial intelligence (XAI) approach, utilizing the SHAP (Shapley Additive Explanations) method to interpret the underlying mechanisms of our models. The SHAP results revealed the significant influence of various factors on noise-pollution-prone areas, with airport, commercial, and administrative zones emerging as pivotal contributors.

High-performance and ultra-wide bandwidth silicon TM polarizer with suppressed reflection utilizing a tailored contra-mode conversion Bragg grating.

We present a compact TM polarizer with high polarization extinction ratio (PER), low loss, and suppressed reflection over an ultra-wide bandwidth on a 220 nm silicon-on-insulator (SOI) platform. The device utilizes a contra-mode conversion Bragg grating (CMC-BG) with strong polarization dependence embedded in a multimode waveguide. Through a sophisticated grating design incorporating tailored chirping and apodization profiles to match modal properties, we have achieved, by simulation, a compact device footprint of 34.72 × 1.22 µm2 and an ultra-wide bandwidth of 346 nm with PER > 40 dB and an insertion loss (IL) < 1 dB, a 5-fold increase over our previous design. Particularly notable is the polarizer's ability to suppress reflection to <-15 dB across an extended bandwidth exceeding 450 nm. Experimental measurements confirm the excellent performance of the fabricated TM polarizer, with IL < 1.2 dB (0.5 dB) and PER > 30 dB over a bandwidth of 336 nm (268 nm).

[Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection].

Objective: To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). Methods: This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. Results: None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (ß [95% CI]: 4.4 [0.5-8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ2=4.133, P=0.023). Conclusions: In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

[Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022].

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

[Clinicopathological characteristics of gangliogliomas with anaplastic morphology].

Objective: To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity. Methods: Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling. Results: Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation. Conclusions: AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

[Accelerating the construction of digital and intelligentialized pathology and the prospects].

With the continuous development of informatization, digitalization and artificial intelligence technology, the working mode of the pathology department has gradually changed from the traditional manual check, paper circulation and physical carrier storage to the informatization process and digital storage. The traditional pathology discipline has ushered in unprecedented opportunities and challenges. Digital pathology department also emerge as the times require. Simultaneously, with the full integration of artificial intelligence technology in pathology department, the concept of "department of digital and intelligentialized pathology" was proposed. Based on information and digital technology, the digital intelligent pathology department integrates intelligent management system, optimizes the previous cumbersome management and workflow of the pathology department, develops advanced technologies such as intelligent material extraction, unmanned organization processing, artificial intelligence quality control, artificial intelligence diagnosis, and promotes the intelligent construction of the pathology department.

[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

[Correlation of 1p/16q loss of heterozygosity and 1p gain with clinicopathological characteristics and prognosis in Wilms tumor].

Objective: To investigate the relationship between 1p/16q loss of heterozygosity (LOH) and 1p gain in Wilms tumor and their clinicopathologic characteristics and prognosis. Methods: A total of 175 Wilms tumor samples received from the Department of Pathology, Beijing Children's Hospital from September 2019 to August 2022 were retrospectively analyzed. The histopathologic type and presence of lymph node involvement were evaluated by two pathologists. The clinical data including patients'gender, age, tumor location, preoperative chemotherapy, and tumor stage were summarized. Fluorescence in situ hybridization (FISH) was done to detect 1p/16q LOH and 1p gain and their correlation with the clinicopathological features and prognosis were analyzed. Results: Among the 175 samples, 86 cases (49.1%) were male and 89 (50.9%) were female. The mean age was (3.5±2.9) years, and the median age was 2.6 years. There were 26 (14.9%) cases with 1p LOH, 28 (16.0%) cases with 16q LOH, 10 (5.7%) cases of LOH at both 1p and 16q, and 53 (30.3%) cases with 1q gain. 1q gain was significantly associated with 1p LOH (P<0.01) and 16q LOH (P<0.01). There were significant differences (P<0.01) between 1q gain, 1p LOH and 16q LOH among different age groups. The rate of 16q LOH in the high-risk histopathological subtype (50.0%) was significantly higher than that in the intermediate-risk subtype (13.6%, P<0.05). The frequency of 1q gain, 1p LOH, and 16q LOH in children with advanced clinical stages (Ⅲ and Ⅳ) was significantly higher than that in children with early clinical stages (Ⅰ and Ⅱ). 1q gain, 1p LOH, and 16q LOH showed no significant correlation with gender, unilateral or bilateral disease, chemotherapy, or lymph node metastasis. The progression-free survival (PFS) time for patients with 1q gain and 1p LOH was significantly shorter than those without these aberrations (P<0.05). Additionally, the PFS time of patients with 16q LOH was slightly shorter than those with normal 16q, although the difference was not statistically significant. Patients with stage Ⅲ to Ⅳ disease exhibiting 1q gain or 1p LOH had a significantly higher relative risk of recurrence, metastasis, and mortality. Conclusions: 1p/16q LOH and 1q gain are associated with age, high-risk histological type, and clinical stage in Wilms tumor. 1q gain and 1p LOH are significantly correlated with the prognosis of Wilms tumor.

Local-field engineering in slot waveguide for fabricating on-chip Bragg grating filters with high reflectivity across a flat broadband.

On-chip Bragg gratings with high reflectivities have been found to have widespread applications in filters, resonators, and semiconductor lasers. However, achieving strong Bragg reflections with flat response across a broad bandwidth on the popular 220 nm silicon-on-insulator (SOI) platform still remains a challenge. In this paper, such a high performance device is proposed and fabricated, which is based on a slot waveguide with gratings etched on the inner sidewalls of the slot. By manipulating the local field in the slot region using a chirped and tapered grating-based mode transition, the device achieves a flat response with ultra-high reflection and low transmission for the TE mode across a broad operating bandwidth. Leveraging the ultra-high birefringence of the SOI waveguide, the device functions both as a TE slot waveguide reflector and a TM pass polarizer. Simulation results demonstrate that the device exhibits an ultra-high rejection of more than 50 dB and a reflectivity exceeding 0.99 for the TE mode across a 91 nm wavelength range, while maintaining a high transmittance of larger than 0.98 for the TM mode. Experimental results validate that the device performance is consistent with the simulation results. A fabricated device based on such a gratings exhibits a low insertion loss (<0.8 dB) and high polarization extinction ratio (>30 dB) over 100 nm bandwidth (1484 nm-1584 nm), demonstrating that the performance of the present design is competitive with that of the state-of-the-art SOI Bragg gratings.

An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Surveillance Strategies in Patients with Stage I, II, III or Resectable IV Melanoma Who Were Treated with Curative Intent.

AIMS: To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent. MATERIALS AND METHODS: This guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used. RESULTS: Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made. CONCLUSIONS: After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes.

[Determination of triclocarban and triclosan in urine by QuEChERS extraction and ultra-performance liquid chromatography-tandem mass spectrometry].

Objective: To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS. Methods: In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI(-)) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results: The linear ranges of TCC and TCS were 0.5-100.0 µg/L and 1.0-100.0 µg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 µg/L, and 0.5 and 1.0 µg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 µg/L. Conclusion: QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Osteoporosis is associated with depression among older adults: a nationwide population-based study in the USA from 2005 to 2020.

OBJECTIVES: The global prevalence of osteoporosis is rising, yet it is unclear whether people with osteoporosis have a higher risk of depression than those without osteoporosis. STUDY DESIGN: A cross-sectional study. METHODS: We used nationally representative data from the US National Health and Nutrition Examination Survey (NHANES) in 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2020. The diagnosis of osteoporosis was based on the bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a score ≥5 as depressive symptoms and a score ≥10 as probable depression. We used logistic regression models to evaluate the association between osteoporosis and depressive symptoms and probable depression. RESULTS: We included 11,603 adults (aged 50 years and older, 52.3% male) and observed 5.2% of them had osteoporosis. 31.9% of these osteoporotic people had depressive symptoms, and 10.0% had probable depression. Compared to participants without osteoporosis, those with osteoporosis were 1.73 times more likely to experience depressive symptoms (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.20-2.50) and 1.91 times more likely to experience probable depression (OR = 1.91, 95% CI 1.02-3.59), after adjusting for sex, age, race/ethnicity, education, marital status, family income, body mass index, smoking, physical activity, and alcohol abuse. Moderate-to-vigorous activities mediated the associations between osteoporosis and depression and depressive symptoms. CONCLUSIONS: Osteoporosis is an independent risk factor for depression. This study highlights the need to evaluate the mental well-being of patients with osteoporosis in clinical and primary health care.

[Anatomical study of the architecture of the cutaneous branch-chained blood vessels in the medial lower leg in adult].

Objective: To investigate the architecture of the cutaneous branch-chained blood vessels in the medial lower leg and provide the anatomical basis for design and clinical application of the cutaneous branch-chained flap from this region. Methods: The experimental research method was used. From March to May 2023, the anatomical study was conducted on the 5 voluntarily donated fresh adult (aged 50 to 70 years, all male) cadaveric specimens from Hangzhou Normal University School of Basic Medical Sciences. The fine anatomy under microscope was performed on each lower leg specimens of 5 corpses (1 lower leg specimen was conducted with digital radiography (DR) scan before fine anatomy), to observe, measure, and record the course of posterior tibial artery, quantity of perforator, the distance between the perforating point of each perforator and the medial condyle of tibia, the external diameter of posterior tibial artery perforator, the length of perforator pedicle, the horizontal distance between the posterior tibial artery perforator and the saphenous nerve, and the course of each perforator within superficial fascia after crossing the deep fascia and the distribution of the cutaneous branch-chains. The DR scan under the perfusion of barium sulfate was conducted in one lower leg specimen to observe the distribution of cutaneous branch-chained vascular network (hereinafter referred to as vascular chain) between perforators. Transparent skin specimen was made from one leg specimen after anatomy to observe the distribution of perforators and vascular chains between perforators. Results: In 5 lower leg specimens, the upper part of posterior tibial artery was located deep in soleus muscle, and the lower part was located between the medial edge of gastrocnemius muscle and flexor digitorum longus muscle. A total of 28 posterior tibial artery perforators were identified, with an average of 5.6 branches in each lower leg. The distance between the perforating point of perforator and the medial condyle of tibia ranged from 6.5 to 36.0 cm, mainly distributed at 22.0 (15.1, 28.1) cm from the medial condyle of tibia, in zones 3 to 6. The external diameters of perforators of posterior tibial arteries were 0.7-1.1 mm. The length of perforator pedicle was 1.0-4.5 cm, and the horizontal distance between the posterior tibial artery perforator and the saphenous nerve was 0.5-3.0 cm. The fine anatomy under microscope showed that the posterior tibial artery perforators had long upward and downward branches after crossing the deep fascia, and the ascending branches and descending branches were anastomosed longitudinally to form the nutrient cutaneous branch-chain in the medial lower leg. DR scan and transparent skin specimen both showed that longitudinal vascular chain was formed between the posterior tibial artery perforators, the transparent skin specimen also showed that longitudinal blood vessel chains included the direct connecting vessels in the adipose layer and the indirect connecting vessels in the subdermal layer. Conclusions: The cutaneous branch-chained vessels in the medial lower leg are constructed by posterior tibial artery perforators, direct connecting vessels, indirect connecting vessels, and traffic branches. The cutaneous branch-chained flap is reliable in terms of vascular anatomy, and can carry the saphenous nerve for partial restoration of its sensation, thus it is an ideal flap.

2†µm band four-wavelength-switchable narrow linewidth fiber laser enabled by fs-laser direct-written polarization-dependent parallel fiber Bragg gratings.

We propose and experimentally demonstrate a four-wavelength-switchable single-longitudinal-mode (SLM) narrow linewidth thulium-holmium co-doped fiber laser (THDFL) using two polarization-dependent parallel fiber Bragg gratings (PD-PFBGs). The PD-PFBGs, fabricated using femtosecond (fs) laser direct-writing technology in a standard single-mode fiber (SMF) via a point-by-point method, are used as a four-channel reflection filter. Two FBGs are inscribed in parallel in the fiber core along the axial direction and are uniquely positioned symmetrically on either side of the centerline. This configuration enables polarization-dependent multi-channel filtering capability, which further allows for polarization-control-based four-wavelength-switchable operations of the THDFL. SLM lasing is accomplished by utilizing a simple dual-ring sub-cavity filter. An exceptional output performance of the THDFL is achieved, including an optical signal-to-noise ratio (SNR) of >72 dB, maximum power and wavelength fluctuations of 0.350 dB and 0.024 nm, respectively, and a linewidth of <2 kHz, for all four single-wavelength operations lasing at ∼2000 nm. These performance indicators suggest that the THDFL can be applied in free-space optical communication, atmospheric monitoring, and Lidar.

[Liposome nanoparticles for targeted delivery of parthenolide induce colorectal cancer necroptosis to ameliorate tumor-infiltrating T cell exhaustion in mice].

OBJECTIVE: To investigate the mechanism of parthenolide for inducing necroptosis and ameliorating CD8+ T cell exhaustion in colorectal cancer (CRC) and construct liposome nanoparticles for targeted delivery of parthenolide. METHODS: The inhibitory effect of parthenolide on proliferation of different CRC cell lines was examined using CCK8 assay, and ROS LDH detection and Western blotting were used to analyze the cell death pathways. In a mouse model bearing subcutaneous MC38 cell xenografts, the effects of 5 and 15 mg/kg parthenolide on tumor growth and CD8+ T cell depletion were observed. In a mouse model bearing orthotopic CRC cell xenograft in the ileocecal region, free parthenolide (100 µg/mL) or low (100 µg/mL) and high doses (200 µg/mL) of liposome nanoparticles loaded with parthenolide were injected via the tail vein, and the changes in CD8 expression in the xenografts were analyzed using immunohistochemistry. RESULTS: Treatment with parthenolide dose-dependently lowered the viability of the CRC cell lines SW480, DLD1, HCT116 and MC38 cells, and its effect was obviously antagonized by Nec-1. Immunoblotting analysis showed that parthenolide treatment resulted in increased RIP3 and MLKL phosphorylation in the CRC cells. In the mouse model bearing subcutaneous xenografts, parthenolide treatment at the high dose, but not at the low dose, significantly increased the number of infiltrating CD3+ CD8+ T cells and PD1hiTIM3+ T cell percentage (P<0.01) and lowered the percentage of PD1loTIM3- T cells in the tumor tissue (P<0.01). In the mouse models bearing orthotopic CRC xenograft, intravenous injection of the liposomes loaded with parthenolide, especially at the high dose, significantly increased CD8 expression in the tumor tissue (P<0.01). CONCLUSION: Parthenolide induces necroptosis in CRC and increases infiltrating CD8+ T cells to ameliorate CD8+ T cell exhaustion in the tumor. Liposome nanoparticles for targeted delivery of parthenolide produce stronger, anti-tumor effect.

EVALUATION OF PRE-ABLATION NLR AND LMR AS PREDICTORS OF DISTANT METASTASES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

Objective: This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods: A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results: The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cut-off value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion: This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

[Study the involvement of Langerin in mediating epicutaneous sensitization of atopic dermatitis-like mouse model].

Objective: To explore the role of Langerin in mediating epicutaneous sensitization of atopic dermatitis (AD) in mouse model. Methods: Mice were topically treated with calcipotriol (MC903) plus ovalbumin (OVA) on the ears to establish AD mouse models, and mice were divided into wild-type control group, wild-type AD group, Langerin knockout control group, and Langerin knockout AD group. Changes of lesion were daily observed. Infiltration of inflammatory cells, mRNA expression of Tslp, Il4, Il13, Il17a, and Il22, levels of serum total IgE, OVA-specific IgE (sIgE), OVA sIgG1 and OVA sIgG2a, proportion of regulatory T (Treg) cells in cervical draining lymph nodes were evaluated at the end of model preparation. Results: Skin tumidness and thickness, dermal inflammatory cells infiltration, the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 in wild-type AD groups were higher than those in wild-type control groups, with (1.80±0.66, 1.64±0.25, 1.71±0.54, 2.41±0.23, 2.49±0.32) and (0.53±0.45, 0.85±0.29, 0.73±0.50, 0.72±0.25, 0.56±0.29), respectively (all P<0.05). In addition, the levels of serum total IgE, OVA sIgE and OVA sIgG1 in wild-type AD groups were higher than those in wild-type control groups, with [(1 216.00±572.70) ng/ml, (597.00±538.30) ng/ml, 1.59±0.09] and [(24.22±35.04) ng/ml, (20.01±41.71) ng/ml, 1.16±0.03], respectively (all P<0.05). In Langerin knockout mice, compared to wild-type mice, skin erythema, skin tumidness, epidermal thickening, inflammatory cell infiltration were more obvious; the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 were upregulated with (8.19±6.44, 2.53±0.69, 2.82±0.73, 3.94±1.32, 3.80±1.43) (all P<0.05); the levels of serum total IgE, OVA sIgE and OVA sIgG1 were significantly increased with (2 508.00±657.10) ng/ml, (1 808.00±470.70) ng/ml, (1.73±0.09) (all P<0.05); the number of CD4+CD25+CD127-Treg cells were decreased significantly with (13.25±0.96)% and (15.31±1.47)%, respectively (P<0.05). Conclusion: Langerin is involved in mediating epicutaneous sensitization of the AD mouse model and plays a negative immunoregulatory role.