BACKGROUND:Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS:In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS:Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION:Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING:None.

LINC01089 suppresses the malignant progression of breast, colorectal, and non-small cell lung cancers. However, the function of LINC01089 in thyroid cancer has not yet been elucidated. Here, The Cancer Genome Atlas (TCGA) database showed that LINC01089 expression is remarkably reduced in thyroid cancer tissues. Lower LINC01089 expression was correlated with higher tumor stage and regional lymph node metastasis. Furthermore, LINC01089 overexpression effectively blocked thyroid cancer cell proliferation, migration, and invasion. LINC01089 acted as a competing endogenous RNA for miR-27b-3p, thus inhibiting miR-27b-3p expression. miR-27b-3p overexpression promoted the proliferation, migration, and invasion of thyroid cancer, reversing the effect of LINC01089 overexpression on thyroid cancer. Fibulin-5 (FBLN5) was discovered as a target of miR-27b-3p in thyroid cancer. FBLN5 expression was found to be underexpressed in thyroid cancer and was enhanced and reduced by LINC00987 overexpression and miR-27b-3p overexpression, respectively. Furthermore, FBLN5 knockdown promoted the malignant progression of thyroid cancer cells by counteracting the effect of LINC00987. In conclusion, LINC01089 plays a tumor-suppressive role by binding miR-27b-3p to increase FBLN5 expression, confirming that LINC01089 has tremendous potential to become a therapeutic target for thyroid cancer treatment.

Effect of laparoscopic sleeve gastrectomy (LSG) on thyroid function of patients with obesity remains unclear. The aim of this study was to evaluate the changes in thyroid function before and after LSG in patients with obesity. Data was retrieved from a retrospectively collected database of patients with morbid obesity and normal thyroid function who received LSG. At 12 months after surgery, changes of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and intact parathyroid hormone (iPTH) were evaluated. In addition, the correlation between thyroid hormone levels and body mass index (BMI) and other metabolic indicators and anthropometric parameters were analyzed. Eighty-five patients were included in the study. The concentrations of FT3 (5.7 ± 0.7 vs 5.1 ± 0.6, p < 0.001) and TSH (2.2 ± 1.0 vs 1.9 ± 0.9, p = 0.002) significantly decreased 12 months postsurgery, while mean FT4 levels increased from12.0 ± 1.9 vs 12.4 ± 2.0 pmol/L (p = 0.013). Furthermore, mean iPTH decreased from 53.3 ± 48.3 to 38.7 ± 13.2 pg/mL (p = 0.011). Multiple stepwise regression analysis showed that changes in LDL levels were an independent factor contributing to changes in TSH levels (β = 0.362, p = 0.001). Moreover, TSH did not correlate with BMI. In this study, FT3, TSH, and iPTH were decreased in euthyroid patients with obesity after LSG, while FT4 was significantly increased. Changes in TSH were positively correlated with LDL, but no statistically significant correlation was found with BMI. Additionally, FT3, FT4, and iPTH were correlated with VB12, age, and BMI, respectively.

目的 利用对自体外周血来源的PBMC进行重编程为诱导多能干细胞(iPSCs),探讨在此基础上与NGF/Coll-H复合支架相结合修复兔喉返神经损伤的可能性.方法 新西兰大白兔随机分为5组:喉返神经单纯端-端吻合组、神经端端吻合-Coll-H支架治疗组、端端吻合-Coll-H-NGF治疗组、端端吻合-Coll-H-NGF-iPSCs治疗组以及假手术组.对比分析复合支架植入到喉返神经损伤部位的修复效果.结果 多项指标表明iPSCs/NGF/Coll-H复合支架的修复效果要显著高于其他组.结论 自体外周血来源的PBMC诱导的iPSCs与NGF/Coll-H复合支架相结合更有利于治疗喉返神经手术带来的损伤.

Neurons loss and axons degeneration after spinal cord injury (SCI) gradually give rise to result in functional motor and sensory impairment. A bridging biomaterial scaffold that allows the axons to grow through has been investigated for the repair of injured spinal cord. In this study, we introduced a silk fibroin (SF)-based neurobridge as scaffold enriched with/without nerve growth factor (NGF) that can be utilized as a therapeutic approach for spinal cord repair. NGF released from alginate (Alg) microspheres on SF scaffold (SF/Alg composites scaffolds) to the central lesion site of SCI significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons. This optimal multi-disciplinary approach of combining biomaterials, controlled-release microspheres and neurotrophic factors offers a promising treatment for the injured spinal cord.

Recurrent laryngeal nerve (RLN) injury can result in unilateral or bilateral vocal cords paralysis, thereby causing a series of complications, such as hoarseness and dyspnea. However, the repair of RLN remains a great challenge in current medicine. This study aimed to develop human umbilical mesenchymal stem cells (HuMSCs) and nerve growth factor (NGF)-loaded heparinized collagen scaffolds (HuMSCs/NGF HC-scaffolds) and evaluate their potential in the repair of RLN injury. HuMSCs/NGF HC-scaffolds were prepared through incorporating HuMSCs and NGF into heparinized collagen scaffolds that were prefabricated by freeze-drying in a template. The resulting scaffolds were characterized by FTIR, SEM, porosity, degradation in vitro, NGF release in vitro and bioactivity. A rabbit RLN injury model was constructed to appraise the performance of HuMSCs/NGF HC-scaffolds for nerve injury repair. Electrophysiology, histomorphology and diagnostic proteins expression for treated nerves were checked after application of various scaffolds. The results showed that the composite scaffolds with HuMSCs and NGF were rather helpful for the repair of broken RLN. The RLN treated with HuMSCs/NGF HC-scaffolds for 8 weeks produced a relatively normal electromyogram, and the levels of calcium-binding protein S100, neurofilament and AchE pertinent to nerve were found to be close to the normal ones but higher than those resulted from other scaffolds. Taken together, HuMSCs/NGF HC-scaffolds exhibited a high score on the nerve injury repair and may be valuable for the remedy of RLN injury.

Dysregulation of microRNAs is involved in the initiation and progression of several human cancers, including breast cancer, as strong evidence of miRNAs acting as oncogenes or tumour suppressor genes has been found. This study was performed to investigate the biological functions of microRNA-421 (miR-421) in breast cancer and the underlying mechanisms. The expression level of miR-421 was detected in 50 pairs of surgical specimens and human breast cancer cell lines. The results showed that miR-421 is downregulated in breast cancer tissues and metastatic cell lines. In addition, the decrease in miR-421 levels was significantly associated with lymph node metastasis, recurrence/metastasis, or pTNM stage. Functions of miR-421 in cell migration and invasion were assessed through its silencing and overexpression. The results showed that miR-421 knockdown promotes invasion and metastasis in MCF-7 cells and its overexpression suppresses invasion and metastasis in MDA-MB-231 cells. The specific target genes of miR-421 were predicted by TargetScan algorithm and determined by dual luciferase reporter assay, quantitative reverse transcriptase PCR, and western blot analysis. miR-421 could suppress luciferase activity of the reporter containing 3′-untranslated region of metastasis associated 1 (MTA1), a potent oncogene. miR-421 overexpression or knockdown had no effect on the mRNA expression of MTA1, but it could modulate MTA1 protein level. Furthermore, MTA1 knockdown receded the effect of miR-421 inhibitor on invasion and metastasis of MCF-7 cells, and its overexpression receded the effect of miR-421 on invasion and metastasis of MDA-MB-231 cells. Our findings clearly demonstrate that miR-421 suppresses breast cancer metastasis by directly inhibiting MTA1 expression. The present study provides a new insight into the tumour suppressor roles of miR-421 and suggests that miR-421/MTA1 pathway is a putative therapeutic target in breast cancer.

Spinal cord injury (SCI) is a severe trauma for which no effective treatment is currently available. In this study, a composited treatment system was prepared using a silk fibroin/alginates/glial cell line-derived neurotrophic factor (SF/AGs/GDNF) scaffold seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) and the combined therapeutic effects of the composite scaffold to repair SCI rats were evaluated. The use of SF as a scaffold material could act as a biomimetic platform allowing neurons to properly accommodate and rebuild the target tissue. The SF/AGs/GDNF scaffold had the best sustained-release function and the AGs were the key determining factor in the controlled release of GDNF. After 8weeks of treatment, the hUCMSCs on SF/AGs/GDNF composite scaffolds could significantly enhance the scar expansion of spinal cord tissue and increased the number of surviving neurons. The combination of GDNF and hUCMSCs transplantation loaded on SF/AGs composite scaffolds exhibited better therapeutic and repair effects to the SCI of rats, compared with the SF/AGs group or GDNF alone on SF/AGs scaffolds. The composite scaffold, GDNF and stem cells could build a bioactive material to form the micro-environment of growth and repair of the neurons. These results may provide a theoretical basis and beneficial exploration for clinical treatment of SCI.

AIM: To isolate the active compounds of Centella asiatica and to investigate their effects on the apoptosis of mouse spleen lymphocytes.METHODS: Cold soak,polar extraction,silica gel column chromatography and Sephadex LH-20 column chromatography were performed to isolate the active compounds from Centella asiatica,which were identified by the assays of scavenging activity on 1,1-diphenyl-2-picrylhydrayl radical(DPPH·) and hydroxyl radical(OH·).Flow cytometry was performed to observe the effects of Centella asiatica extracts on the apoptosis of spleen lymphocytes in mice.RESULTS: Four extracts(B1,B2,B3 and B4) were obtained by the separating procedure.Among them,the extract B4 exerted a potent scavenging effect on both DPPH· and OH·.Quercetin was identified from the extract B4 by HPLC analysis.The mouse spleen lymphocytes with extract B4 treatment showed a significant rise in the level of apoptosis compared with control group.CONCLUSION: Centella asiatica extract B4 induces apoptosis of spleen lymphocytes,and quercetin is the major substance of extract B4.