Solitary thyroid gland metastasis from rectal cancer: A case report and review of the literature.

BACKGROUND: Metastatic carcinoma of the thyroid gland is a rare encounter in clinical practice, but autopsy series showed that it is not so rare. Thyroid metastasis from colorectal cancer (CRC) is rare and has a poor prognosis. We herein report a rare case of solitary thyroid metastasis from rectal cancer combined with needle tract implantation after fine-needle aspiration (FNA) of the thyroid nodule and review the relevant literature. CASE SUMMARY: A 54-year-old woman with a history of TNM stage III CRC presented a 1.3 cm × 1.0 cm mass in the left thyroid gland. FNA and histological examination of the left thyroid lobe surgical specimen confirmed the diagnosis of isolated metastatic adenocarcinoma from the rectum. Needle tract implantation was observed in the neck 11 mo after the FNA examination. The 2.5-cm seeding lesion was successfully removed by surgery, and the patient recovered well. The literature relevant to this clinical condition, the diagnostic workup, spread pathway, and surgical management of these rare lesions is reviewed. CONCLUSION: For a patient with a thyroid mass and a history of CRC, metastatic thyroid carcinoma should be considered even if the patient has no evidence of other organ metastasis from CRC. FNA cytological examination of the thyroid mass is useful in the differential diagnosis between primary thyroid disease and metastatic thyroid carcinoma. Thyroid lobectomy of the gland containing the metastatic tumor is suggested in patients with metastatic carcinoma of the thyroid.

Integrated analysis of RNA-seq in hepatocellular carcinoma reveals competing endogenous RNA network composed of circRNA, lncRNA, and mRNA.

BACKGROUND: Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been hypothesized to have important roles in the etiology of hepatocellular carcinoma (HCC). However, the synergistic effect of circRNA and lncRNA in the pathogenesis of HCC has rarely been studied. METHODS: In this study, the Gene Expression Omnibus database was used to get the expression profiles of circRNAs, micro RNAs (miRNAs), lncRNAs, and messenger RNAs (mRNAs) in HCC tissues and normal tissues. The accession numbers for this database are GSE101728, GSE155949, and GSE108724. We found 291 differentially overexpressed lncRNAs and 541 differentially overexpressed mRNA in GSE101728, 30 differentially overexpressed circRNA in GSE155949, and 48 significantly downregulated miRNA in GSE198724. Meanwhile, based on Pearson correlation test, we established lncRNA-mRNA networks. We constructed lncRNA/circRNA-miRNA pairs through Starbase database prediction and identified the common miRNAs. The intersection of co-predicted miRNAs and the 48 significantly low expression miRNAs in GSE198724 were included in the following study. miRDB, Targetscan, miRwalk, and lncRNA-related mRNA jointly determined the miRNA-mRNA portion of the circRNA/lncRNA-miRNA-mRNA co-expression network. And, among 55 differentially expressed mRNA in circRNA/lncRNA-miRNA-mRNA network, CPEB3, EFNB3, FATA4, growth hormone receptor, GSTZ1, KLF8, MFAP4, PAIP2B, PHACTR3, PITPNM3, RPS6KA6, RSPO3, SLITRK6, SMOC1, STEAP4, SYT1, TMEM132E, TSPAN11, and ZFPM2 were intimately related to the prognosis of HCC patients in Kaplan-Meier plotter analysis (P < .05). CONCLUSION: We have discovered that the prognosis-related lncRNAs/circRNAs-miRNA-mRNA network plays a significant role in the pathogenesis of HCC. These findings may offer fresh perspectives for further research into the pathogenesis of HCC and the search for novel treatments for HCC.

Fine-Needle Pricking Test of the Parathyroid Gland during Thyroid Surgery in Predicting Parathyroid Function.

Background: Permanent hypoparathyroidism is a serious complication following total thyroidectomy plus central neck dissection (CND). How to evaluate the vascularization of the parathyroid gland in real time is a major concern of thyroid surgeons. This study aimed to evaluate the fine-needle pricking (FNP) test in predicting parathyroid gland function. Methods: The FNP test was performed in patients undergoing total thyroidectomy plus CND between January 1, 2014, and December 31, 2019, to visualize the vascularization of the parathyroid glands. Patients were classified according to the number of parathyroid glands preserved in situ with excellent vascularity (PGPIEV) demonstrated by FNP: group 0 (without PGPIEV), group 1 (with one PGPIEV), group 2 (with two PGPIEV), group 3 (with three PGPIEV), and group 4 (with four PGPIEV). Results: A total of 608 patients with four parathyroid glands underwent FNP testing during thyroidectomy. At least one PGPIEV was demonstrated by FNP testing in 581 patients who had intact parathyroid hormone (iPTH) levels in the normal range after the operation. The prevalence of hypocalcemia decreased from 77.8% in group 0 to 9.8% in group 4 (P < 0.001), and the incidence of hypoparathyroidism decreased from 44.4% in group 0 to 0% in groups 1-4 (P < 0.001). iPTH concentrations on postoperative day 1 were positively correlated with PGPIEV groups (increased from 14.58 ng/l in group 0 to 45.22 ng/l in group 4, P < 0.001). Conclusions: The FNP test is a safe and reliable method to predict parathyroid function. One PGPIEV demonstrated by the FNP test rules out the possibility of patients developing hypoparathyroidism.

The Clinical Significance of Detecting Blood Supply to the Inferior Parathyroid Gland Based on the "Layer of Thymus-Blood Vessel-Inferior Parathyroid Gland" Concept.

Objective: How to preserve the inferior parathyroid gland (IPTG) in situ during central neck dissection (CND) is the major concern of thyroid surgeons. The "layer of thymus-blood vessel-IPTG" (TBP layer) concept showed to be effective in preserving IPTG. The objective of this study was to identify the origin and course of blood supply to IPTG (IPBS) within the TBP layer and to take key points of operation during CND. Design: This is a retrospective control study. Participants. Patients who underwent thyroidectomy plus CND using the TBP layer concept and conventional technique between 2017 and 2019 were enrolled. Measurements. The origin and course of IPBS in relation to recurrent laryngeal nerve (RLN) and thymus and prevalence of hypoparathyroidism were detected. Results: A total of 71.3% of IPTGs (251 of 352) were supplied by ITA branches, defined as type A. Type A was further divided into Types A1 (branches of ITA, coursing laterally to the RLN (53.1%, 187 of 352)) and A2 (branches of ITA, traversing medially to the RLN (18.2%, 64 of 352)). Type A2 was more common on the right side than on the left side (P < 0.001). Fifty-five (15.6%) IPTG feeding vessels originated from the thymus or mediastinum. Nineteen (5.4%) IPTGs were supplied by branches of the superior thyroid artery. The incidence of transient hypoparathyroidism decreased from 45.7% to 3.6% (P < 0.001), in the TBP layer group compared with the conventional technique group. Conclusion: The origin and course of IPBS follow a definite pattern. This mapping and precautions help surgeons optimize intraoperative manipulations for better preservation of IPBS during CND.

Tough Adhesion of Freezing- and Drying-Tolerant Transparent Nanocomposite Organohydrogels.

Tough hydrogels with strong wet adhesion have drawn extensive attention for various applications. However, it is still challenging to achieve both excellent wet adhesion and freezing- and drying-tolerance in hydrogels. In this study, we present tough transparent nanocomposite organohydrogels based on the glycerol-water binary solvent system in the presence of Al(OH)3 nanoparticles as a cross-linker. The resultant organohydrogels exhibited excellent tensile strength (∼0.9 MPa), high transparency (97%), superior anti-drying and anti-freezing properties, and good ionic conductivity. In particular, polyacrylic acid (PAA) was chosen as the bridging polymer to endow the organohydrogels with strong wet adhesion. The interfacial adhesion energy exceeded 2200 J m-2, which was ascribed to the synergy of ionic coordination and hydrogen bonds between the nanoparticles and carboxyl groups in PAA chains. Interestingly, based on the strong wet adhesion, the transparent organohydrogels can be assembled into hydraulically driven soft variable-focus lenses with long-term ambient stability. This work will provide a new insight into controlled wet adhesion ̵of hydrogel and have great potential for hydrogel-based functional devices with long-term ambient stability.

Predicting non-small-volume central lymph node metastases (>5 or ≥2 mm) preoperatively in cN0 papillary thyroid microcarcinoma without extrathyroidal extension.

The ability to identify patients with aggressive papillary thyroid microcarcinoma (PTMC) from the low-risk patients is critical to planning proper management of PTMC. Lymph node metastases showed association with recurrence and low survival rate, especially in patients with >5 or ≥2 mm metastatic lymph nodes. Therefore, this study aimed to investigate the preoperatively predictive factors of non-small-volume (metastatic lymph nodes >5 or ≥2 mm in size) central lymph node metastases (NSVCLNM) in PTMC patients. A total of 420 patients with clinically node-negative (cN0) PTMC without extrathyroidal extension underwent thyroidectomy plus central neck dissection (CND) between January 2013 and December 2015, were retrospectively analyzed. Of the 420 patients, 33 (7.9%) had NSVCLNM. The 5-year recurrence-free survival was significantly less in cN0 PTMC patients with NSVCLNM, when compared with patients without NSVCLNM (80.8% vs 100%, P < .001). Multivariate logistic regression revealed age ≤36 years (P < .001), male sex (P = .002), ultrasonic tumor sizes of >0.65 cm (P < .001), and ultrasonic multifocality (P = .039) were independent predictive factors of NSVCLNM. A prediction equation (Y = 1.714 × age + 1.361 × sex + 1.639 × tumor size + 0.842 × multifocality -5.196) was developed, with a sensitivity (69.7%) and a specificity (84.0%), respectively, at an optimal cutoff point of -2.418. In conclusion, if the predictive value was >-2.418 according to the equation, immediate surgery including CND rather than active surveillance might be considered for cN0 PTMC patients.

Large-area superelastic graphene aerogels based on a room-temperature reduction self-assembly strategy for sensing and particulate matter (PM2.5 and PM10) capture.

Graphene aerogels are emerging low density and superelasticity macroscopic porous materials with various applications. However, it still remains a challenge to develop a versatile strategy under ambient conditions for fabricating large-area, high-performance graphene aerogels, which is crucial for their practical applications. Here, we report a novel room-temperature reduction self-assembly (RTRS) strategy to fabricate large-area graphene aerogels under ambient conditions. The strategy is based on using unique hydrazine hydrates as reducing agents to generate stable microbubbles beneficial for the formation of macroporous graphene hydrogels. Interestingly, the resultant hydrogel followed by a simple pre-freeze treatment can be naturally dried into graphene aerogels without noticeable volume shrinkage or structure cracking. Benefiting from the mild conditions, a large-area graphene aerogel with a diameter of up to 27 cm was prepared as an example. The as-formed aerogels exhibit a stable honeycomb-like coarse-pores structure, a low density of 3.6 mg cm-3 and superelasticity (rapidly recoverable from 95% compression) which are suitable for pressure/strain sensors. Moreover, the aerogel exhibits superior particulate matter adsorption efficiency (PM2.5: 93.7%, PM10: 96.2%) and good recycling ability. Importantly, the preparation process is cost-effective and easily scalable without the need for any special drying techniques and heating processes, which provides an ideal platform for mass production of graphene aerogels toward practical applications.

Strong Wet Adhesion of Tough Transparent Nanocomposite Hydrogels for Fast Tunable Focus Lenses.

Tough hydrogel adhesives that can bond strongly to wet surfaces have shown great potential in various applications. However, it still remains a challenge to develop the adhered hydrogels integrated with strong wet adhesion, high transparency, exceptional mechanical properties, and fast self-recovery. Herein, tough nanocomposite hydrogels demonstrating high tensile strength, high transparency, and fast self-recovery are reported. The strong wet adhesion between two tough hydrogel films can be realized by introducing chemical bridging across the hydrogel-hydrogel interface, while the interfacial adhesion energy and shearing adhesion strength are up to 2216 J m-2 and 385 N m-1, respectively. The strong adhesion and superior toughness of our hydrogels enable their reassembly capability to produce stretchable sealed balloons that can endure high air pressure without leakage. Most interestingly, the combination of excellent sealability and high transparency also allows our hydrogel balloons to turn into hydraulically driven fast tunable focus convex lenses, which is first reported here for hydrogel lenses. The hydrogel adhesives may open up the door to develop soft sealed containers and intelligent optical devices.

Water-Evaporation-Powered Fast Actuators with Multimodal Motion Based on Robust Nacre-Mimetic Composite Film.

Water evaporation as a source of energy to trigger moisture-responsive soft materials is an emerging field in a variety of energy-harvesting devices, which has attracted widespread attention. Here, we design and fabricate bioinspired nacrelike composite film actuators consisting of graphene oxide and sodium alginate, which demonstrate an obvious shrinkage in volume when their state transfers from wet to dry and the contractile stress is up to 42.3 MPa. Based on these features, the film actuators can show rapid and continuous movements under the water gradient. The flipping frequency of the actuators can reach up to 76 rounds min-1, which is much faster than those in previous reports. The film can flap back and forth quickly on water vapor even after loading a cargo that is 9 times its own weight. Moreover, high mobility with multimodal motion including blooming, stretching, folding, and twisting can also be achieved by modulating the shapes of films. Thus, film actuators may hold great potential in many fields, such as microrobots, artificial muscles, and sensors on grounds of their rapid response speed and adjustable motion models.

Highly Stretchable Room-Temperature Self-Healing Conductors Based on Wrinkled Graphene Films for Flexible Electronics.

Flexible conductors are emerging soft materials for diverse electrical applications. However, it still remains a great challenge to fabricate high-performance soft conductors that are highly conductive, largely stretchable, and rapid room-temperature self-healable. Here, we design and fabricate flexible conductive bilayer composite films composed of healable elastomeric substrates and wrinkled graphenes. The elastomeric substrates, obtained by a facile bulk copolymerization of N-isopropylacrylamide and 2-methoxyethyl acrylate, show fast room-temperature self-healing efficiency of up to 96%, imparted by the reversible hydrogen bonds. Importantly, the substrates also display strong interfacial adhesion crucial to the formation of stable bilayer composite films based on a prestrain route. The synergy between self-healing of the substrates and wrinkled structures of graphene is endowed to the composite films for mechanical and electrical healing. By adjusting the prestrain ratio of the substrates, the composite films could display the tunable stretchability, conductivity, and self-healing. The optimal bilayer composite film exhibits a high conductivity of 126 S cm-1, a large stretchability of 300%, and rapid room-temperature self-healing. Moreover, it is demonstrated that the composite films are strain-sensitive and can be used as strain sensors to monitor stretching deformation and human motion. These prominent demonstrations suggest a great potential of the bilayer composite films in next-generation wearable electronics.

Tough and electro-responsive hydrogel actuators with bidirectional bending behavior.

Electro-responsive hydrogel actuators have gained much attention because of their fast response, low power consumption and easy modulation. However, such hydrogel actuators suffer from poor mechanical properties and restricted bending direction, which limit their practical applications. Herein, we report a nanocomposite hydrogel actuator with a combination of high mechanical tensile strength (2 MPa) and automatic bidirectional bending behavior in response to electric signals. The resulting hydrogel, crosslinked by aluminum hydroxide nanoparticles, shows rapid bending behavior and could be cyclically actuated up to ten times in an electric field. Furthermore, the hydrogel demonstrates bidirectional bending actuation, which was ascribed to the difference in diffusion coefficients and concentrations of cations and anions within the gel network. Moreover, the direction and magnitude of the bending behavior could be tuned by composition variation. The hydrogel actuators developed in this study may have great potential in soft robotics, artificial muscles and tissue engineering.

A self-healable and tough nanocomposite hydrogel crosslinked by novel ultrasmall aluminum hydroxide nanoparticles.

Self-healing hydrogels like tissues or organs which are repaired automatically in response to damage show great promise. However, it remains a challenge to develop novel functional nanoparticles as crosslinkers to prepare tough and self-healing nanocomposite hydrogels. Here, we report the preparation of water-soluble ultrasmall aluminum hydroxide nanoparticles with a diameter of 2-3 nm through a simple sol-gel method. Furthermore, a tough nanocomposite hydrogel is prepared by the in situ copolymerization of acylamide and 2-acrylamido-2-methyl propane sulfonic acid in the presence of aluminum hydroxide nanoparticles. The resulting hydrogels exhibit high compressive strength of 18.9 MPa and an elongation at break of ∼2100%. Importantly, the Al-NC gel displayed a high self-healing efficiency of 86% without any external stimulus at room temperature. Moreover, we found an interesting multi-hierarchical porous morphology of the Al-NC gel depending on the contents of the aluminum hydroxide nanoparticles. The tough nanocomposite hydrogel might provide a novel promising avenue for designing advanced self-healable soft materials for various biomedical applications.

Bio-inspired layered chitosan/graphene oxide nanocomposite hydrogels with high strength and pH-driven shape memory effect.

The layered nanocomposite hydrogel films containing chitosan (CS) and graphene oxide (GO) have been prepared by water evaporation induced self-assembly and subsequent physical cross-linking in alkaline solution. The layered CS/GO hydrogel films obtained have a nacre-like brick-and-mortar microstructure, which contributes to their excellent mechanical properties. The tensile strength and elongation at break of the hydrogel films with 5wt% GO are 5.35MPa and 193.5%, respectively, which are comparable to natural costal cartilage. Furthermore, the CS/GO hydrogel films exhibited pH-driven shape memory effect, and this unique phenomenon is mainly attributed to the reversible transition of partial physically cross-linking corresponding to hydrogen bondings and hydrophobic interactions between CS polymer chains due to pH changing.

Isoglycyrrhizinate Magnesium Enhances Hepatoprotective Effect of FK506 on Ischemia-Reperfusion Injury Through HMGB1 Inhibition in a Rat Model of Liver Transplantation.

BACKGROUND: Ischemia-reperfusion injury after liver transplantation (LT) impairs graft function and affects prognosis of recipients. Isoglycyrrhizinate magnesium (Iso) is a hepatoprotective drug usually used after liver injury. In this study, we intended to explore whether Iso alone have protective effect after ischemia-reperfusion injury in a rat model of liver transplantation. We also aimed to study whether Iso could enhance the hepatoprotective effect of FK506 (tacrolimus) and underlying mechanism. METHODS: Rats after LT were treated with different concentration of FK506 with or without, Iso or lower-dose FK506 plus Iso. Alanine transaminase, aspartate transaminase, and albumin level were measured after 48 hours, 72 hours, and 7 days. A cell ischemic/reperfusion model was established to further study the mechanism of hepatoprotective effect of FK506 and Iso. RESULTS: Iso treatment alone had no effect on liver grafts after LT, but lower-dose FK506 + Iso was better for maintenance of liver function than lower-dose FK506 alone at 48 hours, 72 hours, and 7 days after LT. In terms of mechanism, FK506 induced autophagy which resulted in significantly reduced apoptosis and maintained proliferative potential. However, autophagy induced by FK506 also lead to high-mobility group box (HMGB) 1 release from nuclei, resulting in hepatocyte injury through triggering of p38 phosphorylation and chemokine release. Iso effectively inhibited the release of HMGB1 and downstream inflammatory cytokines. CONCLUSIONS: Iso could inhibit release of HMGB1 by FK506 and enhance the hepatoprotective effect of FK506 in rat LT. Combining Iso with FK506 would be promising for the patients after LT.

Cytokine production of papillary thyroid carcinoma coexisting with Hashimoto's thyroiditis.

In the tumor microenvironment coexisting with Hashimoto's thyroiditis (HT), cytokines secreted by the tumor cells, stroma cells, or immune cells play a critical role in the regulation of tumor growth, invasion, and metastasis. The present study aims to understand cytokine production from cancerous tissues (CT), para-cancerous tissues (PT), and serum in patients with papillary thyroid carcinoma (PTC) with or without accompanying HT. Using a multiplexed human cytokine assay, we found that nine cytokines, including Interleukin-1alpha (IL-1α), Interleukin-1beta (IL-1ß), Interleukin-12p70 (IL-12p70), Interleukin-8 (IL-8), Interferon-inducible protein-10 (IP-10), Monocyte chemoattractant protein-1 (MCP-1), Macrophage inflammatory protein-1alpha (MIP-1α), Macrophage inflammatory protein-1beta (MIP-1ß), and soluble E-selectin (sE-Selectin), showed significantly higher expression in para-cancerous tissues of HT+PTC compared with HT-PTC (P<0.05). In addition, H&E staining showed immune cell infiltration in PT but not in CT. Moreover para-cancerous tissues of HT+PTC patients produced more Interferon-alpha (IFN-α) (P=0.048) and Interferon-gamma (IFN-γ) (P=0.004) compared with cancerous tissues, and production of Intercellular cell adhesion molecule-1 (ICAM-1) was significantly higher in CT than PT both in HT+PTC (P=0.001) and HT-PTC (P=0.012) patients. To conclude, autoimmune HT was found to affect the cytokine profiles in patients with PTC by stimulating secretion of Th1-type cytokines and chemokines, but further studies are needed to determine the significance of these findings and to reveal the exact mechanism of the interactions between chemokines and cytokines in the pathogenesis of HT and PTC.

Clinical implication of Keap1 and phosphorylated Nrf2 expression in hepatocellular carcinoma.

In this paper, variation tendency of phosphorylated Nrf2, as the activated form of native Nrf2, was studied in 107 primary hepatocellular carcinoma (HCC) specimens treated by curative hepatectomy. Moreover, the coexpression of oxidative stress markers Keap1 and pNrf2, and their association with pathological features were also evaluated based on those specimens. The results showed that preserved cytoplasmic Keap1 expression of cancer cells was observed in 59 HCCs, while reduced Keap1 expression was determined in remaining 48 ones. With regarding to nuclear pNrf2 expression, 75 HCCs were defined as high and the other 32 ones as low. There was a significant association between Keap1 and pNrf2 expression in HCCs. Higher pNrf2 expression was observed, at a more substantial proportion, in those specimens with reduced Keap1 expression, compared to those with preserved Keap1 expression. The subset with higher pNrf2 and reduced Keap1 expression was defined as pNrf2+ Keap1- . According to the analysis of prognosis, this subset was significantly associated with poor 5-year overall survival and worse disease-free survival in HCCs, indicating that pNrf2 and Keap1 were two-functional biomolecules, not only the oxidative stress markers but also biomarkers for prognosis of HCCs.