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Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumor in Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples during July 2021 to August 2022. 2337 (82%) of the cohort possess genetic alterations including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%) and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF positive papillary thyroid cancer (PTC) patients tend to have elder age, smaller tumor size, less vascular invasion, more frequent tumor multifocality and significantly higher cervical lymph node metastatic rate. Mutation at RET gene codon 918 and 634 is strongly correlated with medullary thyroid cancer (MTC), However it did not display more invasive clinical characteristics. TERT positive patients are more likely to have elder age, larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating poor prognosis. Patients with TERT, RET/PTC1 and CHEK2 mutation are more susceptible to lateral lymph node metastasis. In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center., Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel., Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients., Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1526/coif). Z.T.K. is an employee from the Department of Bioinformatics, Zhejiang Shaoxing Topgen Biomedical Technology Co., Ltd. R.J.L. is an employee from the Department of Technology, Zhejiang Topgen Clinical Laboratory Co., Ltd. L.S.H. is an employee from Department of Bioinformatics, Zhejiang Shaoxing Topgen Biomedical Technology Co., Ltd. S.E.T. is an employee from AO Vector-Best, Novosibirsk, Russian Federation. The other authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Objective: The aim of this study was to investigate the effects of sodium hydrosulfide (NaHS) on Lipopolysaccharide (LPS)-induced cardiomyocyte injury in H9c2 cells., Methods: H9c2 cardiomyocytes cultivated with medium containing 10  μ g/mL LPS were used to recapitulate the phenotypes of those in sepsis. Two sequential experiments were performed. The first contained a control group, a LPS group, and a LPS + NaHS group, with the aim to assure the protective effects of NaHS on LPS-treated cardiomyocytes. The second experiment added a fourth group, the LPS + NaHS + miR-133a-3p inhibition group, with the aim to preliminarily explore whether miR-133-3p exerts a protective function downstream of NaHS. The adenosine triphosphate (ATP) kit was used to detect ATP content; real-time quantitative polynucleotide chain reaction (qPCR) was used to measure the levels of mammalian targets of rapamycin (mTOR), AMP-dependent protein kinase (AMPK), and miR-133a-3p, and Western blot (WB) was used to detect protein levels of mTOR, AMPK, myosin-like Bcl2 interacting protein (Beclin-1), microtubule-associated protein 1 light chain 3 (LC3I/II), and P62 (sequestosome-1, sqstm-1/P62)., Results: Compared with the control group, the expressions of miR-133a-3p ( P  < 0.001), P62 ( P  < 0.001), and the content of ATP ( P  < 0.001) decreased, while the expressions of Beclin-1 ( P  = 0.023) and LC3I/II ( P  = 0.048) increased in the LPS group. Compared with the LPS group, the expressions of miR-133a-3p ( P  < 0.001), P62 ( P  < 0.001), and the content of ATP ( P  < 0.001) in the NaHS + LPS group increased, while the expressions of Beclin-1 ( P  = 0.023) and LC3I/II ( P  = 0.022) decreased. Compared with the NaHS + LPS group, the expression levels of miR-133a-3p ( P  < 0.001), P62 ( P  = 0.001), and the content of ATP ( P  < 0.001) in the LPS + NaHS + miR-133a-3p inhibition group were downregulated, and the expression levels of Beclin-1 ( P  = 0.012) and LC3I/II ( P  = 0.010) were upregulated. The difference was statistically significant. There was no significant difference in the expression of AMPK and mTOR between groups., Conclusion: Our research demonstrated that NaHS relieved LPS-induced myocardial injury in H9c2 by promoting the expression of miR-133a-3p, inhibiting autophagy in cardiomyocytes, and restoring cellular ATP levels., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Yi-Mei Jin et al.)

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

Background/aim: Acute exogenous lipoid pneumonia (AELP) is a rare disorder caused by intake of lipid formulations and is often underdiagnosed. Meanwhile, the mechanism of AELP is still underlying. MCC950, was previously found to significantly suppress the release of inflammatory cytokines IL-18 and IL-1β. However, the effect of MCC950 on AELP induced by sewing machine oil has not been reported., Materials and Methods: The NLRP3, NF-[Formula: see text]B p65, caspase-1 and IL-1β expression in lung tissues were compared between a rat model of AELP and control rats using western blotting and real-time quantitative assay. Moreover, haematoxylin and eosin (H&E) staining was performed to elucidate the mechanisms by which MCC950 ameliorates sewing machine oil-induced AELP in vivo., Results: MCC950 reduced the expression of NF-[Formula: see text]B p65 in the lung samples of the treatment group and further down-regulated the NLRP3 and caspase-1 levels while inhibited the production of IL-1β. Besides, decreases in inflammatory cell infiltration in the lung were shown using H&E staining., Conclusion: MCC950 ameliorates sewing machine oil-induced acute exogenous lipoid pneumonia in rats through inhibition of the NF-[Formula: see text]B/NLRP3 inflammasome pathway., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the &quot;five principles&quot; of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.

As typical persistent organic pollutants, polybrominated diphenyl ethers (PBDEs) have aroused high environmental concern due to their toxicity and recalcitrant degradation. Herein, we report the enhanced photoreduction degradation of polybromodiphenyl ethers with Fe 3 O 4 -g-C 3 N 4 under visible light irradiation (>420 nm). A series of high activity photocatalysts Fe 3 O 4 -g-C 3 N 4 (named FeOCN- x ) have been synthesized by an in situ growth method. The characterization of the prepared FeOCN- x nanocomposites has been examined by SEM, TEM, ultraviolet-visible diffuse reflectance spectroscopy, a vibrating sample magnetometer, X-ray diffraction, X-ray photoelectron spectroscopy and Brunauer-Emmer-Teller surface area analysis. FeOCN- x hybrids all exhibit good magnetic separation properties with the saturation magnetization at 300 K varying from 0.4 to 6.3 emu g -1 . Under visible light irradiation, FeOCN- x hybrids show enhanced photocatalytic activity for the debromination of PBDEs compared with g-C 3 N 4 . Among all the hybrids, FeOCN-4 with a 4 wt% Fe 3 O 4 content gives the highest reaction rate, which is 6.7 times as high as that in pure g-C 3 N 4. The FeOCN- x nanocomposites not only exhibit good photostability, but could also be easily recovered by magnetism. The results of the kinetic isotope effects (KIE) and the trapping agent experiments show that the rate determining step in the degradation reaction of PBDEs with FeOCN- x is the rate of electron accumulation in the conductive band. A possible photoreductive mechanism has been proposed. This study shows that the easily magnetically separable recycled photocatalyst FeOCN- x , with high visible light activity, could be an excellent candidate for dealing with halogen pollutants., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cinnamaldehyde (CA), the primary chemical component of the Chinese traditional herb Cinnamomum cassia, is an effective cytotoxic agent against various human cancers. Our previous study indicated that CA could trigger apoptosis in three kinds of non-small cell lung cancer (NSCLC) cells. However, CA mechanism of action in NSCLC has not been unveiled completely. Herein, we showed that a novel circular RNA hsa&#95;circ&#95;0043256 was upregulated in NSCLC cells in response to CA treatment, as detected by microarray and real-time PCR. Hsa&#95;circ&#95;0043256 could inhibit cell proliferation and induce apoptosis, while hsa&#95;circ&#95;0043256 knock-down could promote cell proliferation and restrain apoptosis induced by CA. Bioinformatics analysis predicted that hsa&#95;circ&#95;0043256 could work as a miR-1252 sponge, which could in turn directly target a vital negative regulator of Canonical Wnt signaling, Itchy E3 ubiquitin protein ligase (ITCH), as validated by dual-luciferase assay. Western blot results further confirmed that hsa&#95;circ&#95;0043256 could upregulate ITCH expression, whereas miR-1252 could partially abolish this effect. Interestingly, hsa&#95;circ&#95;0043256 knock-down could weaken Wnt/β-catenin pathway inhibition induced by CA. Finally, we discovered that CA induced apoptosis and meanwhile upregulated hsa&#95;circ&#95;0043256 expression in vivo. Immunohistochemical analysis revealed that ITCH expression was positively association with hsa&#95;circ&#95;0043256 levels. Above all, we characterized a new mechanism mediated by hsa&#95;circ&#95;0043256/miR-1252/ITCH axis in CA function against NSCLC, providing a novel insight into lung cancer therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Efficient modulation of aberrant vascular endothelial growth factor (VEGF) and its receptor-1 (Flt-1) expressions have become a potential therapeutic strategy for hematologic malignancies including myeloid leukemia. In this study, we explored the safety and efficacy of chitosan nanoparticle siRNA-VEGF and Flt-1 in leukemic U973 cells., Methods: Cell transfection efficiencies were analyzed by fluorescence microscope, quantitative Real Time PCR; cell growth inhibitory rates were analyzed by CCK-8 assays and flow cytometry., Results: siRNA-coated chitosan nanosphere transfection led to 65%, Lipofectamine 2000 to 50% and adenovirus to 90% transfection efficiencies. Three days after transfection of U973 cells, the siRNA induced gene silencing rates of VEGF and Flt-1 were 68% and 65% in the adenovirus, 45% and 43% in the chitosan nanoparticle group. The cell growth inhibitory rates were 34.73% for VEGF and 27.61% for Flt-1 silencing in the adenovirus and 27.04% for VEGF and 21.49% for Flt-1 silencing in the chitosan nanoparticle group., Conclusion: Chitosan nanoparticle siRNA technology can effectively inhibit the expression of VEGF and its receptor in leukemic cells, which led to suppression of their proliferation. Though less efficient than adenoviruses, their non-viral properties suggest that chitosan nanoparticle siRNA complex gene silencing is suitable for further trials., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To study the relationship between the intraoperative hypothermia and the residual neuromuscular of single intubation dose of vecuronium., Methods: The designed patients were from July to December in 2009. There are 36 male and 44 female cases. Their age was 19 to 59 years. The induction and sustaining are routine method. There were no additional muscle relaxant. Intraoperative nasopharyngeal temperature (T) < 36°C for the intraoperative hypothermia (LBT group) or non-intraoperative hypothermia group (NBT group). The patients turn back the PACU with tracheal intubation. Measured TOFr immediately after extubation., Results: The incidence of residual neuromuscular single intubation dose of vecuronium was 28.7%. The incidence of postoperative residual neuromuscular was 43.2% (16/37) in the LBT group. The incidence of postoperative residual neuromuscular was 16.3% (7/43) in the NBT group. LBT group compared with the NBT group the incidence of postoperative residual neuromuscular was significant differences (P < 0.05)., Conclusion: The incidence of residual neuromuscular increases. When patients in the surgery exist low body temperature.

EPLERENONE [SYSTEMATIC NAME: 7α-(methoxy-carbon-yl)-3-oxo-9α,11-ep-oxy-17α-pregn-4-ene-21,17-carbolactone], an aldo-sterone receptor antagonist, crystallizes from ethanol as a monosolvate, C(24)H(30)O(6)·C(2)H(6)O. The eplerenone mol-ecule has two five-membered rings, three six-membered rings and one three-membered ring. Both five-membered rings display envelope conformations, while the three six-membered rings assume envelope (cyclohexene), half-chair (cyclohexane sharing one edge with epoxy) and chair (other cyclohexane) conformations. The solvent mol-ecule is disordered equally over two sites. It is linked to the eplerenone mol-ecule by hydrogen bonds.