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Iodine accumulation represents a differentiation marker of thyroid cancer (TC) and a cornerstone of benefits from 131I therapy. However, dedifferentiation phenotypes occur in nearly 70% of recurrent or metastatic TCs driven by oncogenic mutations such as B-Raf proto-oncogene, serine/threonine kinase (BRAF), telomerase reverse transcriptase (TERT) promoters, and tumor proten p53 (TP53). Beyond genetic alterations, epigenetics, autophagy, tumor microenvironment and other pathways are also involved in the dedifferentiation of TC and the tolerance to 131I therapy. Targeting the above-mentioned pathways has potential to improve the malignant phenotype of TC and restore sensitivity to 131I therapy, which is of great clinical significance. Based on the relevant mechanisms of dedifferentiation, this paper elaborates on the progress of preclinical experiments and clinical studies related to differentiation therapies of TC.
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Objective:To explore the risk factors for early trauma-induced coagulopathy (TIC) following severe trauma in the elderly patients.Methods:A case-control study was used to analyze the clinical data of 317 elderly patients with severe trauma admitted to Second Affiliated Hospital of Zhejiang University School of Medicine between February 2015 and November 2020. There were 212 males and 105 females, aged 65-96 years [(72.6±6.8)years]. The patients were divided into TIC group ( n=32) and non-TIC group ( n=285) using the international normalised ratio (INR)>1.5 as the reference standard. Sex, age, trauma sites, injury severity score (ISS), Glasgow coma scale (GCS), first body temperature on admission, shock index(SI), first laboratory results of arterial blood gas, routine blood and coagulation, blood transfusion, usage of blood product, hospitalization days and clinical outcomes were compared between the two groups. Univariate and multivariate Logistic regression analysis were used to identify the risk factors for early TIC in patients with severe trauma. Results:Differences in sex, age, injuries to the face, chest and abdomen, GCS, first body temperature and hospitalization days were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in the ratio of injuries to head, neck and extremities, ISS, SI, pH value, base excess (BE), lactate, hemoglobin (Hb), platelet (PLT) count (first detection, lowest level), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrinogen (FIB), blood transfusion and usage of blood product and clinical outcomes (all P<0.05). According to the univariate analysis, injuries to the head, neck and extremities, ISS, first body temperature, SI, pH value, BE, lactate, Hb, PLT, APTT, TT and FIB were correlated with the occurrence of early TIC (all P<0.05). Multiple Logistic regressions analysis showed that SI ( OR=1.54, 95% CI 1.10-2.17, P<0.05), PLT ( OR=0.67, 95% CI 0.49-0.91, P<0.05) and FIB ( OR=0.56, 95% CI 0.40-0.78, P<0.01) were significantly correlated with the occurrence of early TIC. Conclusion:For elderly patients with severe trauma, higher SI, lower PLT count and lower concentration of FIB are independent risk factors for the incidence of early TIC.
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Objective:To investigate the value of hypocalcaemia for predicting trauma-induced coagulopathy (TIC) in elderly trauma patients.Methods:The clinical data of elderly trauma patients in emergency ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to September 2020 were retrospectively analyzed, including age, sex, site of injury, injury severity score (ISS), Glasgow coma scale (GCS), admission arterial blood gas analysis (Ca 2+, K +), venous blood biochemical electrolyte (Ca 2+, K +, Na +); international normalized ratio (INR), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), use of blood products, length of stay, length of stay in ICU, total cost, and clinical prognosis. Receiver operating characteristic (ROC) curves and multivariate logistic regression analysis were performed to estimate the contribution of hypocalcaemia to triggering TIC in elderly trauma patients. Results:Totally 371 elderly trauma patients were included with a mean age of (72.5±6.8) years, and 248 (66.8%) were male. ISS score of the TIC group was higher than that of the non-TIC group [25(20, 34) vs. 21(16, 29)]. Compared with the non-TIC group, the incidence of chest injury, abdominal injury and limb injury were significantly higher , while the incidence of head and neck injury were significantly lower in the TIC group (all P<0.05). The biochemical blood calcium in the TIC group was significantly lower than that in the non-TIC group [(1.97±0.19) mmol/L vs. (2.15±0.16) mmol/L, P<0.001], but there was no significant difference in blood gas calcium between the two groups. The APTT value of the TIC group [(47.6±21.8) s vs. (33.8±4.1) s], PT value [(18.0±3.9) s vs. (13.7±0.8) s] were significantly higher than that of the non-TIC group, and FIB level was significantly lower than that of the non-TIC group[(1.7±0.8) g/L vs. (2.8±0.9) g/L] (all P<0.01). The utilization rate of blood products and the total cost in the TIC group were higher than that in the non-TIC group, while the recovery rate in the TIC group was lower than that in the non-TIC group (69.8% vs. 86.4%, P<0.001). Multivariate logistic regression analysis showed that hypocalcaemia was an independent risk factor for TIC in elderly trauma patients ( OR=5.830, 95% CI: 3.295-10.314). The area under ROC curve of correlation between biochemical calcium and TIC was 0.779 (95% CI: 0.728-0.831). The optimal diagnostic cut-off value was 2.06 mmol/L. Conclusions:The decrease of biochemical serum calcium level is an independent risk factor for TIC in elderly trauma patients. Positive correction of TIC in elderly trauma patients contributes to continuous improvement of clinical prognosis.
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Due to the limited efficacy of traditional therapies, the risk of death in patients with advanced thyroid cancer remains high. In recent years, targeted chemotherapy has shown prospective effects on inhibiting the growth of thyroid cancer and prolonging progression-free survival in these patients, but also brings some clinical confusion. Consequently, this paper reviewed the application status and clinical problems of targeted chemotherapy in thyroid cancer. In addition, treatment strategies of thyroid cancer and the future perspectives were also presented.
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Objective To evaluate therapeutic effects of Sini decoction (SND) on hypothyroidism based on serum meta-bonomics method .Methods Twenty-four rats were randomly divided into three groups including sham group ,surgery-induced hypothyroid model group and SND-treated group .The SND-treated group was given SND for 4 weeks .After 4 weeks ,the ser-um samples of each rat were collected and analyzed by UHPLC-Q-TOFMS ,pattern recognition analysis of metabolomics differ-ences among the groups and therapeutic effects of SND were evaluated .Results Total of 9 metabolites were identified through serum metabonomics analysis .It was showed that there was a possible mechanism that hypothyroidism was mainly involved in citrate cycle ,phenylalanine metabolism ,sphingolipid metabolism and phospholipid metabolism and the damage of hypothyroid-ism was reversed by SND .Conclusion SND administration could provide satisfactory effects on hypothyroidism through par-tially regulating the perturbed citrate cycle ,phenylalanine metabolism and phospholipid metabolism .