Novel mechanisms of Anshen Dingzhi prescription against PTSD: Inhibiting DCC to modulate synaptic function and inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Anshen Dingzhi prescription (ADP), documented in "Yi Xue Xin Wu", is a famous prescription for treating panic-related mental disorders such as post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which ADP intervened in PTSD-like behaviors. METHODS: A mouse model of single prolonged stress (SPS) was established to evaluate the ameliorative effects and mechanisms of ADP on PTSD. Behavioral tests were used to assess PTSD-like behaviors in mice; transmission electron microscopy was used to observe changes in the ultrastructure of hippocampal synapses, and western blot, immunofluorescence, and ELISA were used to detect the expression of hippocampal deleted in colorectal cancer (DCC) and downstream Ras-related C3 botulinum toxin substrate 1 (Rac1) - P21-activated kinase 1 (PAK1) signal, as well as levels of synaptic proteins and inflammatory factors. Molecular docking technology simulated the binding of potential brain-penetrating components of ADP to DCC. RESULTS: SPS induced PTSD-like behaviors in mice and increased expression of hippocampal netrin-1 (NT-1) and DCC on the 14th day post-modeling, with concurrent elevation in serum NT-1 levels. Simultaneously, SPS also decreased p-Rac1 level and increased p-PAK1 level, the down-stream molecules of DCC. Lentiviral overexpression of DCC induced or exacerbated PTSD-like behaviors in control and SPS mice, respectively, whereas neutralization antibody against NT-1 reduced DCC activation and ameliorated PTSD-like behaviors in SPS mice. Interestingly, downstream Rac1-PAK1 signal was altered according to DCC expression. Moreover, DCC overexpression down-regulated N-methyl-d-aspartate (NMDA) receptor 2A (GluN2A) and postsynaptic density 95 (PSD95), up-regulated NMDA receptor 2B (GluN2B) and increased neuroinflammatory responses. Administration of ADP (36.8 mg/kg) improved PTSD-like behaviors in the SPS mice, suppressed hippocampal DCC, and downstream Rac1-PAK1 signal, upregulated GluN2A and PSD95, downregulated GluN2B, and reduced levels of inflammatory factors NOD-like receptor protein 3 (NLRP3), nuclear factor kappa-B (NF-κB) and interleukin-6 (IL-6). Importantly, DCC overexpression could also reduce the ameliorative effect of ADP on PTSD. Additionally, DCC demonstrated a favorable molecular docking pattern with the potential brain-penetrating components of ADP, further suggesting DCC as a potential target of ADP. CONCLUSION: Our data indicate that DCC is a key target for the regulation of synaptic function and inflammatory response in the onset of PTSD, and ADP likely reduces DCC to prevent PTSD via modulating downstream Rac1-PAK1 pathway. This study provides a novel mechanism for the onset of PTSD and warrants the clinical application of ADP.

PTEN and P-4E-BP1 might be associated with postoperative recurrence of rectal cancer patients undergoing concurrent radiochemotherapy.

BACKGROUND: Local recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment. AIM: To find potential biomarkers of tumors for predicting postoperative recurrence. METHODS: In this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence. RESULTS: The expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy. CONCLUSIONS: This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.

Single-Image-Based Deep Learning for Segmentation of Early Esophageal Cancer Lesions.

Accurate segmentation of lesions is crucial for diagnosis and treatment of early esophageal cancer (EEC). However, neither traditional nor deep learning-based methods up to today can meet the clinical requirements, with the mean Dice score - the most important metric in medical image analysis - hardly exceeding 0.75. In this paper, we present a novel deep learning approach for segmenting EEC lesions. Our method stands out for its uniqueness, as it relies solely on a single input image from a patient, forming the so-called "You-Only-Have-One" (YOHO) framework. On one hand, this "one-image-one-network" learning ensures complete patient privacy as it does not use any images from other patients as the training data. On the other hand, it avoids nearly all generalization-related problems since each trained network is applied only to the same input image itself. In particular, we can push the training to "over-fitting" as much as possible to increase the segmentation accuracy. Our technical details include an interaction with clinical doctors to utilize their expertise, a geometry-based data augmentation over a single lesion image to generate the training dataset (the biggest novelty), and an edge-enhanced UNet. We have evaluated YOHO over an EEC dataset collected by ourselves and achieved a mean Dice score of 0.888, which is much higher as compared to the existing deep-learning methods, thus representing a significant advance toward clinical applications. The code and dataset are available at: https://github.com/lhaippp/YOHO.

Bibliometric Analysis of Hotspots and Frontiers of Immunotherapy in Pancreatic Cancer.

BACKGROUND: Pancreatic cancer is one of the most common malignant neoplasms with an increasing incidence, low rate of early diagnosis, and high degree of malignancy. In recent years, immunotherapy has made remarkable achievements in various cancer types including pancreatic cancer, due to the long-lasting antitumor responses elicited in the human body. Immunotherapy mainly relies on mobilizing the host's natural defense mechanisms to regulate the body state and exert anti-tumor effects. However, no bibliometric research about pancreatic cancer immunotherapy has been reported to date. This study aimed to assess research trends and offer possible new research directions in pancreatic cancer immunotherapy. METHODS: The articles and reviews related to pancreatic cancer immunotherapy were collected from the Web of Science Core Collection. CiteSpace, VOSviewer, and an online platform, and were used to analyze co-authorship, citation, co-citation, and co-occurrence of terms retrieved from the literature highlighting the scientific advances in pancreatic cancer immunotherapy. RESULTS: We collected 2475 publications and the number of articles was growing year by year. The United States had a strong presence worldwide with the most articles. The most contributing institution was Johns Hopkins University (103 papers). EM Jaffee was the most productive researcher with 43 papers, and L Zheng and RH Vonderheide ranked second and third, with 34 and 29 papers, respectively. All the keywords were grouped into four clusters: "immunotherapy", "clinical treatment study", "tumor immune cell expression", "tumor microenvironment". In the light of promising hotspots, keywords with recent citation bursts can be summarized into four aspects: immune microenvironment, adaptive immunotherapy, immunotherapy combinations, and molecular and gene therapy. CONCLUSIONS: In recent decades, immunotherapy showed great promise for many cancer types, so various immunotherapy approaches have been introduced to treat pancreatic cancer. Understanding the mechanisms of immunosuppressive microenvironment, eliminating immune suppression and blocking immune checkpoints, and combining traditional treatments will be hotspots for future research.

Engineering Isopropanol Dehydrogenase for Efficient Regeneration of Nicotinamide Cofactors.

Isopropanol dehydrogenase (IPADH) is one of the most attractive options for nicotinamide cofactor regeneration due to its low cost and simple downstream processing. However, poor thermostability and strict cofactor dependency hinder its practical application for bioconversions. In this study, we simultaneously improved the thermostability (433-fold) and catalytic activity (3.3-fold) of IPADH from Brucella suis via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H) by 1.23 × 106-fold. When these variants were employed in three typical bioredox reactions to drive the synthesis of important chiral pharmaceutical building blocks, they outperformed the commonly used cofactor regeneration systems (glucose dehydrogenase [GDH], formate dehydrogenase [FDH], and lactate dehydrogenase [LDH]) with respect to efficiency of cofactor regeneration. Overall, our study provides two promising IPADH variants with complementary cofactor specificities that have great potential for wide applications. IMPORTANCE Oxidoreductases represent one group of the most important biocatalysts for synthesis of various chiral synthons. However, their practical application was hindered by the expensive nicotinamide cofactors used. Isopropanol dehydrogenase (IPADH) is one of the most attractive biocatalysts for nicotinamide cofactor regeneration. However, poor thermostability and strict cofactor dependency hinder its practical application. In this work, the thermostability and catalytic activity of an IPADH were simultaneously improved via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H). The resultant variants show great potential for regeneration of nicotinamide cofactors, and the engineering strategy might serve as a useful approach for future engineering of other oxidoreductases.

Spatial Distribution Analysis of Novel Texture Feature Descriptors for Accurate Breast Density Classification.

Breast density has been recognised as an important biomarker that indicates the risk of developing breast cancer. Accurate classification of breast density plays a crucial role in developing a computer-aided detection (CADe) system for mammogram interpretation. This paper proposes a novel texture descriptor, namely, rotation invariant uniform local quinary patterns (RIU4-LQP), to describe texture patterns in mammograms and to improve the robustness of image features. In conventional processing schemes, image features are obtained by computing histograms from texture patterns. However, such processes ignore very important spatial information related to the texture features. This study designs a new feature vector, namely, K-spectrum, by using Baddeley's K-inhom function to characterise the spatial distribution information of feature point sets. Texture features extracted by RIU4-LQP and K-spectrum are utilised to classify mammograms into BI-RADS density categories. Three feature selection methods are employed to optimise the feature set. In our experiment, two mammogram datasets, INbreast and MIAS, are used to test the proposed methods, and comparative analyses and statistical tests between different schemes are conducted. Experimental results show that our proposed method outperforms other approaches described in the literature, with the best classification accuracy of 92.76% (INbreast) and 86.96% (MIAS).

The Protective Effects of Hydrogen Sulfide New Donor Methyl S-(4-Fluorobenzyl)-N-(3,4,5-Trimethoxybenzoyl)-l-Cysteinate on the Ischemic Stroke.

In this paper, we report the design, synthesis and biological evaluation of a novel S-allyl-l-cysteine (SAC) and gallic acid conjugate S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-l-cysteinate (MTC). We evaluate the effects on ischemia-reperfusion-induced PC12 cells, primary neurons in neonatal rats, and cerebral ischemic neuronal damage in rats, and the results showed that MTC increased SOD, CAT, GPx activity and decreased LDH release. PI3K and p-AKT protein levels were significantly increased by activating PI3K/AKT pathway. Mitochondrial pro-apoptotic proteins Bax and Bim levels were reduced while anti-apoptotic protein Bcl-2 levels were increased. The levels of cleaved caspase-9 and cleaved caspase-3 were also reduced in the plasma. The endoplasmic reticulum stress (ERS) was decreased, which in turns the survival rate of nerve cells was increased, so that the ischemic injury of neurons was protected accordingly. MTC activated the MEK-ERK signaling pathway and promoted axonal regeneration in primary neurons of the neonatal rat. The pretreatment of MEK-ERK pathway inhibitor PD98059 and PI3K/AKT pathway inhibitor LY294002 partially attenuated the protective effect of MTC. Using a MCAO rat model indicated that MTC could reduce cerebral ischemia-reperfusion injury and decrease the expression of proinflammatory factors. The neuroprotective effect of MTC may be due to inhibition of the over-activation of the TREK-1 channel and reduction of the current density of the TREK1 channel. These results suggested that MTC has a protective effect on neuronal injury induced by ischemia reperfusion, so it may have the potential to become a new type of neuro-ischemic drug candidate.

Prognostic risk analysis related to radioresistance genes in colorectal cancer.

Background: Radiotherapy (RT) is one of the most important treatments for patients with colorectal cancer (CRC). Radioresistance is the crucial cause of poor therapeutic outcomes in colorectal cancer. However, the underlying mechanism of radioresistance in colorectal cancer is still poorly defined. Herein we established a radioresistant colorectal cancer cell line and performed transcriptomics analyses to search for the underlying genes that contribute to radioresistance and investigate its association with the prognosis of CRC patients. Methods: The radioresistant cell line was developed from the parental HCT116 cell by a stepwise increased dose of irradiation. Differential gene analysis was performed using cellular transcriptome data to identify genes associated with radioresistance, from which extracellular matrix (ECM) and cell adhesion-related genes were screened. Survival data from a CRC cohort in the TCGA database were used for further model gene screening and validation. The correlation between the risk score model and tumor microenvironment, clinical phenotype, drug treatment sensitivity, and tumor mutation status were also investigated. Results: A total of 493 different expression genes were identified from the radioresistant and wild-type cell line, of which 94 genes were associated with ECM and cell adhesion-related genes. The five model genes TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1 were identified for CRC radioresistance via screening using the best model. A ROC curve indicated that the AUC of the resulting prognostic model (based on the 5-gene risk score and other clinical parameters, including age, sex, and tumor stages) was 0.79, 0.77, and 0.78 at 1, 2, and 3 years, respectively. The calibration curve showed high agreement between the risk score prediction and actual survival probability. The immune microenvironment, drug treatment sensitivity, and tumor mutation status significantly differed between the high- and low-risk groups. Conclusions: The risk score model built with five radioresistance genes in this study, including TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1, showed favorable performance in prognosis prediction after radiotherapy for CRC.

Scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions: A biomechanical study.

BACKGROUND: Severe bony Bankart lesions are a difficult challenge in clinical treatment and research. The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures. While good results have been achieved, there are also complications such as coracoid fracture, bone graft displacement, and vascular and nerve injury. AIM: To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions. METHODS: Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used. When the humeral rotation angles were 0°, 30°, 60° and 90°, and the axial loads were 30 N, 40 N, and 50 N, the humerus displacement was studied by biomechanical experiments. RESULTS: When the angle of external rotation of the humerus was 0°, 30°, 60°, and 90°, with axial loads of 30 N, 40 N, and 50 N, the data of the normal control group, allograft pin repair group, and titanium alloy hollow screw repair group were compared with each other by the q-test, which showed that there were no statistically differences among the three groups (P > 0.05). CONCLUSION: The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability. The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.

Novel Texture Feature Descriptors Based on Multi-Fractal Analysis and LBP for Classifying Breast Density in Mammograms.

This paper investigates the usefulness of multi-fractal analysis and local binary patterns (LBP) as texture descriptors for classifying mammogram images into different breast density categories. Multi-fractal analysis is also used in the pre-processing step to segment the region of interest (ROI). We use four multi-fractal measures and the LBP method to extract texture features, and to compare their classification performance in experiments. In addition, a feature descriptor combining multi-fractal features and multi-resolution LBP (MLBP) features is proposed and evaluated in this study to improve classification accuracy. An autoencoder network and principal component analysis (PCA) are used for reducing feature redundancy in the classification model. A full field digital mammogram (FFDM) dataset, INBreast, which contains 409 mammogram images, is used in our experiment. BI-RADS density labels given by radiologists are used as the ground truth to evaluate the classification results using the proposed methods. Experimental results show that the proposed feature descriptor based on multi-fractal features and LBP result in higher classification accuracy than using individual texture feature sets.

Arthroscopic C-Shaped Release Around the Greater Trochanter for Gluteal Muscle Contracture.

OBJECTIVE: To investigate the outcomes of C-shaped release around the greater trochanter in gluteal muscle contracture under arthroscopy. METHODS: From December 2016 to January 2018, 185 patients with gluteal muscle contracture who treated under arthroscopy were reviewed, including 69 males and 116 females. All patients had a history of repeated intramuscular injection into the buttocks. The follow signs were positive in all the patients before surgery: squatting and crouching disability, difficulty in crossing the leg, Ober's sign positive, clicking sound during rotation of the hip. The C-shaped release around the greater trochanter under arthroscopy was performed in 96 cases (C-shaped release group) with an average age of 24.6 ± 4.9 years old, and conventional gluteal muscle contracture release under arthroscopy was performed in 89 cases (conventional release group) with an average age of 25.1 ± 5.0 years. The released tissues in the C-shaped release group: iliotibial band (ITB) about 5 cm distal to the proximal end of the greater trochanter, the contracture tissue near the posterior and superior of the greater trochanter, which depended on both intraoperative physical examination and arthroscopic observation. The released tissues in conventional release group: the contracture tissues in gluteal muscles according to observation under arthroscopy. The gluteal muscle contracture disability scale (GDS) and Visual analogue scale (VAS) were evaluated before surgery and at the last follow-up. RESULTS: The average release time after making arthroscopic operation space for each lower limb were 12.2 ± 3.2 min in the C-shaped release group, and 21.4 ± 6.1 min in the conventional release group (P = 0.000). All the patients were followed for at least of 2 years after operation. There was one case of wound hematoma in the C-shaped release group and five cases in the conventional release group(P = 0.079), abductor weakness (IV level)occurred in two patients in the C-shaped release group and five cases in the conventional release group (P = 0.208). GDS was 49.3 ± 17.3 (22 to 70) in theC-shaped release group and 48.1 ± 15.6 (23 to 69) in the conventional release group before surgery (P = 0.622), 91.7 ± 5.2 (83 to 100) in the C-shaped release group and 90.2 ± 6.1 (83 to 98) in the conventional release group (P = 0.073) with difference nearly significant at last follow-up. CONCLUSION: Arthroscopic C-shaped release around the greater trochanter had less operation time, acceptable complication occurrence, and it has an optimistic outcome for gluteal muscle contracture under arthroscope.

Utility of Ultrasound-Guided Anesthetic Intra-articular Injection to Estimate the Outcome of Hip Arthroscopy in Patients with Femoroacetabular Impingement Syndrome.

OBJECTIVE: To investigate the effectiveness of ultrasound (US) guided intra-hip joint injection to estimate the outcome of hip arthroscopy in patients with femoroacetabular impingement (FAI) syndrome. METHODS: Patients with FAI syndrome (n = 60) were prospectively enrolled in our study. Before hip arthroscopy, a mix of 4 mL 2% lidocaine and 4 mL 1% ropivacaine were injected into the hip joint under the guidance of US. The clinical efficacy of the intra-articular injection was evaluated by comparing the visual analog scale (VAS) and international hip outcome tool 12 (iHOT-12) results before and after the injection. The outcome of hip arthroscopy was evaluated by iHOT-12, the modified Harris hip score (MHHS), and the patient's satisfaction 12 months after the operation. The outcome of intra-articular injection and hip arthroscopy were compared. Factors related to the outcomes of hip arthroscopy were evaluated. The correlation between the efficacy of intra-hip joint injection and arthroscopy was evaluated. RESULTS: The VAS of patients decreased from 11.3 ± 7.7 to 3.3 ± 4.5, and the iHOT-12 increased from 52.1 ± 23.2 to 84.1 ± 18.1 after intra-articular injection (all P < 0.001). The iHOT-12 score increased from 52.1 ± 23.2 to 78.9 ± 19.2, and the MHHS increased from 66.5 ± 6.8 to 81.6 ± 8.1 after hip arthroscopy (all P < 0.001). The satisfaction rate of arthroscopy, including very satisfied and effective patients, was 93.3%. Multi-variable logistic regression showed that only iHOT-12 improved value after injection was included in the regression formula of satisfaction, with the ß of -0.154, standard error of 0.071, Wald value of 4.720, and OR of 0.857 (95%CI 0.746-0.985) (P = 0.03). Significant correlation was detected between iHOT-12 scores after intra-articular anesthesia and at 12 months after arthroscopy (r = 0.784, P < 0.001). So was the iHOT-12 improved value (r = 0.781, P < 0.001) and the iHOT-12 improved ratio (r = 0.848, P < 0.001). If we had performed arthroscopy only on patients with post-injection iHOT-12 score improvement ≥10, the satisfaction rate of arthroscopy would have increased to 96.6%. CONCLUSIONS: US-guided intra-hip joint injection may provide a feasible way to estimate the outcome of hip arthroscopy in patients with FAI syndrome, and could be used as a method for indication selection of hip arthroscopy.

Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in ß-thalassemia.

The human genome harbors 14,000 duplicated or retroposed pseudogenes. Given their functionality as regulatory RNAs and low conservation, we hypothesized that pseudogenes could shape human-specific phenotypes. To test this, we performed co-expression analyses and found that pseudogene exhibited tissue-specific expression, especially in the bone marrow. By incorporating genetic data, we identified a bone-marrow-specific duplicated pseudogene, HBBP1 (η-globin), which has been implicated in ß-thalassemia. Extensive functional assays demonstrated that HBBP1 is essential for erythropoiesis by binding the RNA-binding protein (RBP), HNRNPA1, to upregulate TAL1, a key regulator of erythropoiesis. The HBBP1/TAL1 interaction contributes to a milder symptom in ß-thalassemia patients. Comparative studies further indicated that the HBBP1/TAL1 interaction is human-specific. Genome-wide analyses showed that duplicated pseudogenes are often bound by RBPs and less commonly bound by microRNAs compared with retropseudogenes. Taken together, we not only demonstrate that pseudogenes can drive human evolution but also provide insights on their functional landscapes.

Specific Gene Co-variation Acts Better Than Number of Concomitant Altered Genes in Predicting EGFR-TKI Efficacy in Non-small-cell Lung Cancer.

BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.

The gas-phase formation of tin dioxide nanoparticles in single droplet combustion and flame spray pyrolysis.

Tin dioxide (SnO2) nanoparticles synthesized via flame spray pyrolysis (FSP) have promising applications for gas sensors. The formation of SnO2 nanoparticles in the gas-phase has been investigated using single droplet combustion and FSP. Precursor solutions of Tin (II) 2-ethylhexanoate dissolved in Xylene with varying Sn concentrations were selected as the precursor-solvent system. The selected precursor-solvent system has its stability and ability to synthesize homogeneous nanoparticles, compared to metal nitrate based precursor solutions. The precursor-solvent system was studied using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and thermogravimetric analysis (TGA). The SnO2 nanoparticles were characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), and transmission electron microscopy (TEM). Droplet surface micro-explosions were observed during the single droplet combustion of the precursor solutions. It is because of the heterogeneous vapor-phase nucleation, which is beneath the liquid droplet surface and caused by precursor thermal decomposition. The results show that the size of nanoparticles obtained both from FSP and single droplet combustion increases with increasing metal-precursor concentration. The TEM images of the particles from such droplet combustion reveal two types of nanoparticles with different sizes and morphologies. The current work provides fundamental understanding of precursor decomposition and particle formation during single droplet combustion, which help in-depth understanding of the flame spray pyrolysis.

Pretracheal-laryngeal lymph nodes in frozen section predicting contralateral paratracheal lymph nodes metastasis.

BACKGROUND: There has been an ongoing debate concerning the predictors of contralateral paratracheal lymph nodes metastasis (LNM) in unilateral papillary thyroid cancer (PTC). This study aimed to explore the value of pretracheal-laryngeal lymph nodes (LNs) in frozen section in predicting contralateral paratracheal LNM. METHODS: A total of 242 patients with unilateral PTC were enrolled in this prospective study. Patients who underwent total thyroidectomy and bilateral central lymph nodes dissection (LND) were divided into two groups according to positive or negative contralateral paratracheal LNs. Patients' demographics and clinicopathological features were compared between the two groups. Validity indexes and consistency of pretracheal-laryngeal LNs in frozen sections were calculated. RESULTS: LNM rates in central, ipsilateral paratracheal, pretracheal-laryngeal, and contralateral paratracheal regions were 55.37%, 47.03%, 23.55% and 14.05%, respectively. Only pretracheal-laryngeal LNM, regardless of whether detected in frozen or paraffin sections, were independent risk factors for contralateral paratracheal LNM (OR = 2.707; 95% CI 1.062-6.902; P = 0.037 in frozen section; OR = 3.072; 95% CI 1.248-7.560; P = 0.015 in paraffin section). The sensitivity, specificity, false-negative rate, false-positive rate, accuracy rate, and Kappa value of pretracheal-laryngeal LNM in frozen sections for predicting pretracheal-laryngeal LNM were 87.72%, 100%, 12.28%, 0%, 97.11% and 0.916 respectively, while those for predicting contralateral paratracheal LNM were 85,29%, 89.90%, 14.71%, 10.10%, 89.22%, and 0.618 respectively. CONCLUSION: Pretracheal-laryngeal LNs in frozen section accurately predicted contralateral paratracheal LNM, which could allow the identification of patients who can benefit from an extended central LND.

[Research progress on the epigenetic mechanisms of inverse relationship between Alzheimer's disease and cancer onset].

Alzheimer's disease (AD) is currently the most prevalent neurodegenerative disease in the aging population. It is characterized by massive deposition of extracellular ß-amyloid peptide and formation of intracellular neurofibrillary tangles. Cancer is also an age-related disease. Some epidemiological studies have shown an inverse relationship between AD and the onset of various types of cancers, that is, the risk of cancer in patients with AD is reduced, and vice versa. Epigenetic mechanisms play important roles in the development of AD and cancer. In this article, we will review the recent research advances on the epigenetic mechanisms of AD and cancer onset, and provide new ideas for rethinking the relevance of AD and cancer with a "holistic concept".

Isthmic Papillary Thyroid Carcinoma Presents a Unique Pattern of Central Lymph Node Metastasis.

PURPOSE: Treatment protocols for occult central lymph node metastasis (LNM) associated with papillary thyroid cancer (PTC) located in the isthmus are debatable. We aimed to analyze the pattern of occult central LNM in isthmic PTC, including risk factors for bilateral paratracheal LNM. PATIENTS AND METHODS: Consecutive patients with PTC were recruited to this study. All patients underwent total thyroidectomy and prophylactic bilateral central neck dissection. The clinicopathologic features and distribution of central LNM were compared between the two groups, and risk factors for bilateral paratracheal LNM were analyzed. RESULTS: A total of 174 patients with PTC were enrolled in this study, of whom 87 patients had isthmic PTC (study group) and 87 patients had lobe-originating PTC (control group). The two groups had comparable demographics and tumor features. There were higher frequencies of pretracheal LNM (P =0.001) and bilateral paratracheal LNM (P = 0.002) in the isthmic PTC group. Bilateral paratracheal LNM was significantly associated with age <55 years (P = 0.037), capsular invasion (P = 0.034), tumor location (isthmus) (P < 0.001), BRAF gene mutation (P = 0.013), and pretracheal LNM (P < 0.001). Isthmus location (odds ratio [OR]: 4.116, 95% confidence interval [CI]: 1.264-13.433, P = 0.019) and pretracheal LNM (OR: 3.422, 95% CI: 1.214-9.642, P = 0.020) were independent risk factors for bilateral paratracheal LNM. CONCLUSION: Because of its unique anatomic location, isthmic PTC differs from PTC in the lobe with respect to pretracheal and bilateral paratracheal LNM, even in patients of comparable age, sex, tumor size, extrathyroidal extension, BRAF mutation, and pathologic TNM staging. The isthmus location was found to be an independent risk factor for bilateral paratracheal LNM. This information may contribute to the development of an appropriate surgical protocol for isthmic PTC.

Genomic consequences of population decline in critically endangered pangolins and their demographic histories.

Pangolins are among the most critically endangered animals due to heavy poaching and worldwide trafficking. However, their demographic histories and the genomic consequences of their recent population declines remain unknown. We generated high-quality de novo reference genomes for critically endangered Malayan (Manis javanica, MJ) and Chinese (M. pentadactyla, MP) pangolins and re-sequencing population genomic data from 74 MJs and 23 MPs. We recovered the population identities of illegally traded pangolins and previously unrecognized genetic populations that should be protected as evolutionarily distinct conservation units. Demographic reconstruction suggested environmental changes have resulted in a population size fluctuation of pangolins. Additionally, recent population size declines due to human activities have resulted in an increase in inbreeding and genetic load. Deleterious mutations were enriched in genes related to cancer/diseases and cholesterol homeostasis, which may have increased their susceptibility to diseases and decreased their survival potential to adapt to environmental changes and high-cholesterol diets. This comprehensive study provides not only high-quality pangolin reference genomes, but also valuable information concerning the driving factors of long-term population size fluctuations and the genomic impact of recent population size declines due to human activities, which is essential for pangolin conservation management and global action planning.