Tas2R activation relaxes airway smooth muscle by release of Gαt targeting on AChR signaling.

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor-mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gαt proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gαt released by Tas2R activation complexes with AChR and blocks the Gαq cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gαq-associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD.

Background signal suppression by opposite polarity subtraction for targeted DNP NMR spectroscopy on mixture samples.

A novel method for background signal suppression is introduced to improve the selectivity of dynamic nuclear polarization (DNP) NMR spectroscopy in the study of target molecules within complex mixtures. The method uses subtraction between positively and negatively enhanced DNP spectra, leading to an improved contrast factor, which is the ratio between the target and background signal intensities. The proposed approach was experimentally validated using a reverse-micelle system that confines the target molecules together with the polarizing agent, OX063 trityl. A substantial increase in the contrast factor was observed, and the contrast factor was optimized through careful selection of the DNP build-up time. A simulation study based on the experimental results provides insights into a strategy for choosing the appropriate DNP build-up time and the corresponding selectivity of the method. Further analysis revealed a broad applicability of the technique, encompassing studies from large biomolecules to surface-modified polymers, depending on the nuclear spin diffusion rate with a range of gyromagnetic ratios.

Dynamical analysis of a glucose-insulin regulatory system with insulin-degrading enzyme and multiple delays.

This paper investigates the dynamics of a glucose-insulin regulatory system model that incorporates: (1) insulin-degrading enzyme in the insulin equation; and (2) discrete time delays respectively in the insulin production term, hepatic glucose production term, and the insulin-degrading enzyme. We provide rigorous results of our model including the asymptotic stability of the equilibrium solution and the existence of Hopf bifurcation. We show that analytically and numerically at a certain value the time delays driven stability or instability occurs when the corresponding model has an interior equilibrium. Moreover, we illustrate the oscillatory regulation and insulin secretion via numerical simulations, which show that the model dynamics exhibit physiological observations and more information by allowing parameters to vary. Our results may provide useful biological insights into diabetes for the glucose-insulin regulatory system model.

Downregulation of circ-SFMBT2 blocks the development of gastric cancer by targeting the miR-885-3p/CHD7 pathway.

Accumulating evidence insists that circular RNAs (circRNAs) play important roles in the development of human cancers, including gastric cancer. This study aimed to investigate the role of circ-SFMBT2 and provide a potential mechanism to explain its function. The expression of circ-SFMBT2, miR-885-3p and chromodomain-helicase-DNA-binding protein 7 (CHD7) mRNA was determined by quantitative real-time PCR (qRT-PCR), and the protein level of CHD7 was determined by western blot. To investigate the function of circ-SFMBT2 in vitro, the effects of circ-SFMBT2 on cell viability, colony formation, apoptosis, migration and invasion were assessed using cell counting kit-8 assay, colony formation assay, flow cytometry assay, wounding healing assay and transwell assay, respectively. The indicators of oxidative stress were assessed using matched kits. Besides, the function of circ-SFMBT2 was also investigated in animal models. The relationship between miR-885-3p and circ-SFMBT2 or CHD7 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ-SFMBT2 and CHD7 were upregulated, whereas miR-885-3p was downregulated in gastric cancer tissues and cells. In functional assay, circ-SFMBT2 knockdown suppressed gastric cancer cell viability, colony formation ability, migration, invasion and oxidative stress but induced apoptosis, and circ-SFMBT2 downregulation also blocked tumor growth in vivo. In mechanism analysis, circ-SFMBT2 regulated CHD7 expression by sponging its target miRNA, miR-885-3p. Rescue experiments manifested that miR-885-3p inhibition reversed the effects of circ-SFMBT2 knockdown, and CHD7 overexpression abolished the antitumor role of miR-885-3p overexpression. Moreover, circ-SFMBT2 knockdown inactivated the Wnt/ß-catenin signaling pathway. Circ-SFMBT2 downregulation repressed the development of gastric cancer partially by controlling the miR-885-3p/CHD7 axis, which might be a novel strategy to inhibit gastric cancer progression.

CT-Guided Autologous Blood Patch for High-Level Cervical Cerebrospinal Fluid Leakage: Imaging Characteristics and Treatment Safety and Efficiency.

INTRODUCTION: Epidural blood patches (EBPs) are rarely performed at the high-level cervical levels. The aim of the study was to investigate the imaging features, safety, and effectiveness of CT-guided percutaneous EBPs for high-level cervical cerebrospinal fluid (CSF) leakage. METHODS: Twenty-five patients with spontaneous high-level (C1-C3) CSF leakage on MRI and CT imaging, including 2 patients with intracranial epidural hematoma caused by CSF, were treated with EBP. Two needles were inserted into the C1-3 bilateral epidural space. The needle location was confirmed by injection of both 3-5mL sterile air and a diluted iodinated contrast agent to delineate its spatial diffusion. The patient's blood 11.1 ± 3.1 mL was slowly injected to make a patch; the distribution in epidural space was monitored with intermittent CT scanning. RESULTS: The typical manifestation of CSF leakage was the high signal outside the C1-3 cervical dura on MR T2W fat inhibition images and low density in cervical muscle space on CT images. Twenty patients suffered from headaches and were able to sit and walk 24 h after the operation. Four patients, with partial relief of headache and a small but persistent CSF leakage, were re-treated with EBS. One patient underwent a third operation because of a persistent CSF leakage on MRI. CONCLUSIONS: Imaging of water at the surrounding epidural space of high cervical level is a typical feature of dural rupture on both MRI and CT. CT-guided EBP is safe and efficient for the high-level cervical CSF leakage, especially for cases in which conservative treatments failed.

Iodine nutrition status and thyroid function of women at different phases of gestation in an iodine sufficient rural area.

BACKGROUND AND OBJECTIVES: This study was undertaken to evaluate the status of iodine nutrition and thyroid function of women at different phases of gestation in an iodine sufficient rural area. METHODS AND STUDY DESIGN: 215 pregnant women in different trimesters were consecutively enrolled in iodine sufficient rural areas of Yongjing county of Gansu province, China. The blood samples and random urine samples were collected from them, and serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxin (FT4), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and urinary iodine were measured. RESULTS: Median Urinary Iodine (MUI) of three groups of pregnant women (first, second and third trimester) were 190 µg/L, 153 µg/L and 145 µg/L respectively. With the increase of gestational age, the level of FT3 decreased. And the FT3 level in the first trimester was higher than those in the second and third trimester. There was a U-shaped curve seen between the TSH levels and the gestational age. The medians of TgAb and TPOAb appeared the lowest in the first trimester．Significant difference was seen in TgAb and TPOAb levels of the three groups of pregnant women. The incidence of thyroid function disorder was 1.86%, including subclinical hypothyroidism accounted for 1.40% and hypothyroidism accounted for 0.47%. The incidence of thyroid function disorder mainly appeared in the early pregnancy. Abnormal FT3, TSH, positive TgAb and TPOAb were mainly seen during early pregnancy. CONCLUSIONS: The levels of serum TSH and thyroid hormones fluctuate at the different phases of pregnancy. With the increase of gestational age, the incidence of iodine deficiency also increased. Abnormal thyroid hormones, TSH, positive TgAb and TPOAb were mainly existed in the early pregnancy.

Competitive Binding of Mg2+ and Na+ Ions to Nucleic Acids: From Helices to Tertiary Structures.

Nucleic acids generally reside in cellular aqueous solutions with mixed divalent/monovalent ions, and the competitive binding of divalent and monovalent ions is critical to the structures of nucleic acids because of their polyanionic nature. In this work, we first proposed a general and effective method for simulating a nucleic acid in mixed divalent/monovalent ion solutions with desired bulk ion concentrations via molecular dynamics (MD) simulations and investigated the competitive binding of Mg2+/Na+ ions to various nucleic acids by all-atom MD simulations. The extensive MD-based examinations show that single MD simulations conducted using the proposed method can yield desired bulk divalent/monovalent ion concentrations for various nucleic acids, including RNA tertiary structures. Our comprehensive analyses show that the global binding of Mg2+/Na+ to a nucleic acid is mainly dependent on its structure compactness, as well as Mg2+/Na+ concentrations, rather than the specific structure of the nucleic acid. Specifically, the relative global binding of Mg2+ over Na+ is stronger for a nucleic acid with higher effective surface charge density and higher relative Mg2+/Na+ concentrations. Furthermore, the local binding of Mg2+/Na+ to a phosphate of a nucleic acid mainly depends on the local phosphate density in addition to Mg2+/Na+ concentrations.

Divalent Ion-Mediated DNA-DNA Interactions: A Comparative Study of Triplex and Duplex.

Ion-mediated interaction between DNAs is essential for DNA condensation, and it is generally believed that monovalent and nonspecifically binding divalent cations cannot induce the aggregation of double-stranded (ds) DNAs. Interestingly, recent experiments found that alkaline earth metal ions such as Mg2+ can induce the aggregation of triple-stranded (ts) DNAs, although there is still a lack of deep understanding of the surprising findings at the microscopic level. In this work, we employed all-atom dynamic simulations to directly calculate the potentials of mean force (PMFs) between tsDNAs, between dsDNAs, and between tsDNA and dsDNA in Mg2+ solutions. Our calculations show that the PMF between tsDNAs is apparently attractive and becomes more strongly attractive at higher [Mg2+], although the PMF between dsDNAs cannot become apparently attractive even at high [Mg2+]. Our analyses show that Mg2+ internally binds into grooves and externally binds to phosphate groups for both tsDNA and dsDNA, whereas the external binding of Mg2+ is much stronger for tsDNA. Such stronger external binding of Mg2+ for tsDNA favors more apparent ion-bridging between helices than for dsDNA. Furthermore, our analyses illustrate that bridging ions, as a special part of external binding ions, are tightly and positively coupled to ion-mediated attraction between DNAs.

Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA.

Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Co(NH3)6 (3+) (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive. However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become 'internal binding' into the deep major groove and consequently cannot form the evident ion-bridge between adjacent helices, while for B-form helices without deep grooves, Co-Hex would exhibit 'external binding' to strongly bridge adjacent helices. In addition, our further calculations show that, the PMF between A-RNAs could become strongly attractive either at very high [Co-Hex] or when the bottom of deep major groove is fixed with a layer of water.

[Experiment on pruning of Cistanche deserticola inoculated in artificial Haloxylon ammodendron forest].

At present, the objective of cutting and pruning Cistanche deserticola is to harvest in successive years and enhance the harvesting yield and quality of C. deserticola in the process of the artificial cultivating C. deserticola. An experiment was conducted focusing on cutting and pruning C. deserticola in artificial forests of Haloxylon ammodendron drip-irrigated with saline water at the hinter-land of the Taklimakan desert, according to different growth stages and lengths. The results were following: (1) The effect of cutting on C. deserticola was similar to that of pruning, which resulted in three kinds of morphological types, not related to the bloom and size of C. deserticola. (2) The growth forms were diversified after pruning. Among them, there had sprouting new body, died or maintaining life with no sprouting, mildewed on its surface layer, etc. However, some of new bodies were sprouting from the lower part of the old body. The death rate of bloomed C. deserticola was higher than that of the underground, and the death rate of the 40 cm in stubble height for C. deserticola was higher than those with the stubble height of 20 cm and 5 cm. (3) Most of the diameter of living C. deserticola after pruning was increasing, but some of them changed little. (4) The mildew and rot of C. deserticola and the broken of the roots of the H. ammodendron and the fallen of the point of the inoculated when it was dug, which would cause the death of the C. deserticola. On the other, the yield-increasing effect and the economic benefit of the techniques of the pruning of Cistanche would need further research and evaluate. Therefore, the application of this technique needs to be cautious.

PRECISION: A Physics-Constrained and Noise-Controlled Diffusion Model for Photon Counting Computed Tomography.

Recently, the use of photon counting detectors in computed tomography (PCCT) has attracted extensive attention. It is highly desired to improve the quality of material basis image and the quantitative accuracy of elemental composition, particularly when PCCT data is acquired at lower radiation dose levels. In this work, we develop a physics-constrained and noise-controlled diffusion model, PRECISION in short, to address the degraded quality of material basis images and inaccurate quantification of elemental composition mainly caused by imperfect noise model and/or hand-crafted regularization of material basis images, such as local smoothness and/or sparsity, leveraged in the existing direct material basis image reconstruction approaches. In stark contrast, PRECISION learns distribution-level regularization to describe the feature of ideal material basis images via training a noise-controlled spatial-spectral diffusion model. The optimal material basis images of each individual subject are sampled from this learned distribution under the constraint of the physical model of a given PCCT and the measured data obtained from the subject. PRECISION exhibits the potential to improve the quality of material basis images and the quantitative accuracy of elemental composition for PCCT.

CircSCUBE3 Reduces the Anti-gastric Cancer Activity of Anti-PD-L1.

The progression of gastric cancer (GC) is closely related to tumor immune escape. The research, therefore, studied the impact of possible circRNAs on the immune escape of GC tumors and the underlying mechanisms. Here, to explore circRNAs that may affect GC, the differential circRNAs in six normal gastric mucosal tissues and six GC samples (GSM2005868-GSM2005879) were analyzed through the bioinformatics website circmine, and hsa_circ_0076092 (circSCUBE3) was identified as the research object. In vitro assays revealed the functions of circSCUBE3 and its downstream miRNA/mRNA axis in GC cells. The effect of circSCUBE3 against PD-1 anti-tumor activity was evaluated in vivo. The relationship between circSCUBE3 and miR-744-5p, miR-744-5p, and SLC7A5 was identified by RNA immunoprecipitation and dual-luciferase reporter experiments. The effect of SLC7A5 on GC immune escape by regulating PD-L1 expression was assessed by co-culture system and flow cytometry. CircSCUBE3 was up-regulated in human GC tissues and GC cell lines. circSCUBE3 was associated with poor prognosis in GC patients. Functional experiments reported that circSCUBE3 knockdown could suppress GC immune escape. Mechanistically, circSCUBE3 bound to miR-744-5p, which further targeted SLC7A5, and SLC7A5 can affect GC immune escape by regulating PD-L1. Furthermore, in vivo assay manifested that circSCUBE3 attenuated the anti-tumor effect of PD-L1. Our study revealed the importance of the circSCUBE3/miR-744-5p/SLC7A5 axis in GC immune escape and anti-PD-1 resistance.

Low-dose CT fluoroscopy-guided interventional minimally invasive robot.

Background: This study aimed to assess the feasibility, safety, and accuracy of a low-dose CT fluoroscopy-guided remote-controlled robotic real-time puncture procedure. Methods: The study involved two control groups with Taguchi method: Group A, which underwent low-dose traditional CT-guided manual puncture (blank control), and Group B, which underwent conditional control puncture. Additionally, an experimental group, Group C, underwent CT fluoroscopy-guided remote-controlled robotic real-time puncture. In a phantom experiment, various simulated targets were punctured, while in an animal experiment, attempts were made to puncture targets in different organs of four pigs. The number of needle adjustments, puncture time, total puncture operation time, and radiation dose were analyzed to evaluate the robot system. Results: Successful punctures were achieved for each target, and no complications were observed. Dates were calculated for all parameters using Taguchi method. Conclusion: The low-dose CT fluoroscopy-guided puncture robot system is a safe, feasible, and equally accurate alternative to traditional manual puncture procedures.

Deep learning-based accurate diagnosis and quantitative evaluation of microvascular invasion in hepatocellular carcinoma on whole-slide histopathology images.

BACKGROUND: Microvascular invasion (MVI) is an independent prognostic factor that is associated with early recurrence and poor survival after resection of hepatocellular carcinoma (HCC). However, the traditional pathology approach is relatively subjective, time-consuming, and heterogeneous in the diagnosis of MVI. The aim of this study was to develop a deep-learning model that could significantly improve the efficiency and accuracy of MVI diagnosis. MATERIALS AND METHODS: We collected H&E-stained slides from 753 patients with HCC at the First Affiliated Hospital of Zhejiang University. An external validation set with 358 patients was selected from The Cancer Genome Atlas database. The deep-learning model was trained by simulating the method used by pathologists to diagnose MVI. Model performance was evaluated with accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve. RESULTS: We successfully developed a MVI artificial intelligence diagnostic model (MVI-AIDM) which achieved an accuracy of 94.25% in the independent external validation set. The MVI positive detection rate of MVI-AIDM was significantly higher than the results of pathologists. Visualization results demonstrated the recognition of micro MVIs that were difficult to differentiate by the traditional pathology. Additionally, the model provided automatic quantification of the number of cancer cells and spatial information regarding MVI. CONCLUSIONS: We developed a deep learning diagnostic model, which performed well and improved the efficiency and accuracy of MVI diagnosis. The model provided spatial information of MVI that was essential to accurately predict HCC recurrence after surgery.

Flexible Piezoresistive Sensors Based on PPy Granule-Anchored Multilayer Fibrous Membranes with a Wide Operating Range and High Sensitivity.

The employment of flexible piezoresistive sensors has sparked growing interest within the realm of wearable electronic devices, specifically in the fields of health detection and e-skin. Nevertheless, the advancement of piezoresistive sensors has been impeded by their limited sensitivity and restricted operating ranges. Consequently, it is imperative to fabricate sensors with heightened sensitivity and expanded operating ranges through the utilization of the appropriate methodologies. In this paper, piezoresistive sensors were fabricated utilizing electrospun polyvinylidene fluoride/polyacrylonitrile/polyethylene-polypropylene glycol multilayer fibrous membranes anchored with polypyrrole granules as the sensing layer, while electrospun thermoplastic polyurethane (TPU) fibers were employed as the flexible substrate. The sensitivity of the sensor is investigated by varying the fiber diameter of the sensing layer. The experimental findings reveal that a concentration of 14 wt % in the spinning solution exhibits high sensitivity (996.7 kPa-1) within a wide working range (0-10 kPa). This is attributed to the favorable diameter of the fibers prepared at this concentration, which facilitates the uniform in situ growth of pyrrole. The highly deformable TPU flexible fibers and multilayer sensing layer structure enable different linear responses across a broad pressure range (0-1 MPa). Furthermore, the sensor demonstrates good cyclic stability and can detect human movements under different pressures. These results suggest that the piezoresistive sensor with a wide operating range and high sensitivity has significant potential for future health monitoring and artificial intelligence applications.

Effects of n-pentanol/biodiesel blend fuels on combustion and conventional and unconventional emission characteristics of diesel engine.

The use of n-pentanol/biodiesel as a diesel engine fuel is one of the important ways to reduce fossil fuel consumption and lower diesel engine emissions. The objective of this work was to investigate the mechanism of the effect of different n-pentanol blending ratios (0%, 10%, 20%, and 30%) on the combustion and emission performance of a common rail diesel engine. Tests were conducted on a four-cylinder supercharged intercooled diesel engine at 1540 r/min with brake mean effective pressures of 0.289, 0.578, and 0.867 MPa. The results showed that with the increase of the n-pentanol blending ratio, the ignition delay was prolonged, the combustion duration was shortened, and the heat release center was shifted forward. The combustion process at medium and high loads was improved. When the blending ratio of n-pentanol reached 20%, the blended fuel showed better combustion characteristics at all three loads, and the peak in-cylinder pressure of the blended fuel increased by 13.74%, 1.95%, and 5.26% at the three loads, respectively, compared with that of pure biodiesel. With the increase of the n-pentanol blending ratio, HC, CH2O, CH4, and CH3CHO emissions increased at all three loads. Soot emission was reduced by 25.86%, 19.71%, and 31.59% at three loads when the n-pentanol blending ratio was 30%. C2H4 emissions increased with the increase of n-pentanol blending ratio at the low-load condition and showed a decreasing tendency at the medium and high loads. At high load conditions, NOx emissions increased with increasing n-pentanol blending ratio, and CO emissions decreased with increasing n-pentanol blending ratio.

Utilization of water-based drilling cuttings from offshore oil development to manufacture lightweight aggregates: a case study in the Bohai oil field, China.

Offshore water-based drilling cuttings (OWDC) are by-products of offshore oil-well drilling, whose effective management has become an urgent environmental and engineering issue. This study investigated the feasibility of recycling OWDC from the Bohai oilfield in China as a raw material for manufacturing lightweight aggregates (LWA). The effects of OWDC content (0-50%), preheating temperature (300-500 °C), and sintering temperature (1050-1200 °C) on the physical-mechanical performance of the resulting LWA were investigated through single-factor experiments. The microstructural and expansion mechanism analyses were determined based on X-ray diffraction analysis, scanning electron microscopy, and energy-dispersive X-ray spectrometric microanalysis. The results showed that under the optimum preparation conditions (mass ratio of OWDC and fly ash at 50:50, preheating at 400 °C for 30 min, and sintering at 1150 °C for 30 min), the OWDC-based LWA could meet the requirements of Chinese standard GB/T 17431.1-2010. The incorporation of OWDC lowered the aggregate melting points and promoted dense structure formation inside the aggregates due to the presence of flux agents (e.g., Na2O and K2O). Besides, OWDC additions promoted the formation of the liquid phase and gases inside the pellets, which was beneficial to the expansion behavior and lightweight performance of the aggregates. However, OWDC also had a negative effect on the compressive strength of the aggregates owing to the formation of enlarged pores. Furthermore, the results of the environmental performance tests indicated that the LWA were safe for the environment. This study provides a reference for recycling water-based drilling cuttings from offshore oilfields and contributes to the circular economy.

Discovery of a High-Efficient Algicidal Bacterium against Microcystis aeruginosa Based on Examinations toward Culture Strains and Natural Bloom Samples.

Harmful cyanobacterial blooms occur worldwide and pose a great threat to aquatic ecosystems and public health. The application of algicidal bacteria represents an eco-friendly strategy for controlling harmful cyanobacterial blooms; thus, searching for a high efficiency of algicidal bacteria has been becoming an important and continuous task in science. Herein, we identified a bacterial strain coded Streptomyces sp. HY with a highly algicidal activity, and investigated its algicidal efficiency and mechanism against Microcystis aeruginosa. The strain HY displayed high algicidal activity toward Microcystis aeruginosa cells, with a removal rate of 93.04% within 2 days via indirect attack. Streptomyces sp. HY also showed the ability to lyse several genera of cyanobacterial strains, including Dolichospermum, Pseudanabaena, Anabaena, and Synechocystis, whereas it showed a minor impact on the green alga Scenedesmus obliquus, demonstrating its selectivity specially for targeting cyanobacteria. Its algicidal mechanism involved damages to the photosynthesis system, morphological injury of algal cells, oxidative stress, and dysfunction of the DNA repair system. Furthermore, HY treatment reduced the expression levels of genes (mcyB and mcyD) related to microcystin biosynthesis and decreased the total content of microcystin-leucine-arginine by 79.18%. Collectively, these findings suggested that the algicidal bacteria HY is a promising candidate for harmful cyanobacterial bloom control.

A novel PTEN mutant caused by polymorphism in cis-regulatory elements is involved in chemosensitivity in breast cancer.

Phosphatase and tensin homolog (PTEN) is one of the most important tumor suppressor genes. Although studies have shown the association between cancer and genetic polymorphisms of PTEN, the underlying molecular mechanisms of breast cancer (BC) chemosensitivity that results from PTEN polymorphism is still unclear. This study aims to investigate potential links between PTEN polymorphisms in cis-regulatory elements and BC chemosensitivity in the Chinese population. A total of 172 BC patients who received neoadjuvant chemotherapy were included in the study, including 104 chemosensitive cases and 68 chemoresistant cases. The results showed a significant association between the rs786204926 polymorphism and BC chemosensitivity. Logistic multivariate regression analysis showed that age, lymph node metastasis, and the rs786204926 genotype were risk factors for BC chemoresistance. The G allele of rs786204926 is more prone to increasing the risk of chemosensitivity in BC. Additionally, analysis using Alamut Visual showed a preference of the G allele of rs786204926 to produce a novel PTEN mutant with an insertion of 18 bases from intron 4. While the transcriptional level of PTEN remained similar in chemosensitivity and chemoresistant samples, its protein level changed significantly. Interestingly, there were significant differences in both transcription and protein levels of the novel PTEN mutant between the two groups. Furthermore, we found that the mutant was more susceptible to dephosphorylation compared with wildtype PTEN, leading to chemosensitivity through the PI3K-AKT signaling pathway. These findings indicate that novel PTEN mutants caused by polymorphisms in cis-regulatory elements may be involved in BC chemosensitivity.

[Treatment experience of neck tumor surgeries involving carotid artery].

Objective:To investigate surgical treatment of carotid artery diseases in neck tumor surgery. Methods:A retrospective analysis of the clinical data on carotid artery treatment was conducted in the five cases of neck tumor surgeries treated at Department of Surgical Oncology, the First Peoples Hospital of Lanzhou from March 2010 to May 2020. Surgical methods, including carotid artery resection and ligation, tumor-involved artery resection and vascular reconstruction, and tumor peeling and carotid rupture repairing were used, respectively. Results:Five cases were successfully operated on. One case of carotid artery ligation was followed by intermittent dizziness and decreased contra-lateral limb strength after the surgery. The remaining patients exhibited no neurological complications. A patient with cervical low-grade myofibroblastoma developed into lung metastases 8 months after the surgery. Another patient with cervical lymph node metastases in papillary thyroid cancer developed into lung metastases 24 months after the surgery. Conclusion:Currently, surgical methods for clinical treatment of diseased carotid arteries include carotid artery resection and ligation, simple tumor peeling, tumor invasion artery resection and vascular reconstruction, and interventional therapy. Each surgical method has its own advantages and disadvantages. Therefore, the choice of treatment depends on the patient's specific conditions, physician's clinical experience, and the equipment available.