Objective To investigate the value of individualized thyroid stimulating hormone (TSH) inhibition therapy in postoperative patients with differentiated thyroid carcinoma.Methods The medical record and follow-up data of the 556 patients with differentiated thyroid carcinoma after total or neartotal thyroidectomy were retrospectively reviewed.Patients were divided into two groups:Group A (304 cases) received TSH suppression therapy without risk assessment.Group B (252 cases) were given TSH suppression therapy in accord with risk assessment of both differentiated thyroid cancer recurrence risk stratification condition and the side effects of TSH suppression therapy risk stratification.Results The 3-year non-recurrence and (or) non-metastasis rate in group B was 99.2％ which was higher than 96.8％ in group A (P =0.044).The hospitalization rate caused by postoperative cardiovascular events or other morbidities in group B decreased 89％ than that in group A.Conclusions Individualized TSH suppression therapy can significantly decrease the recurrence and metastasis rate as well as concurrent morbidities caused by unnecessary TSH inhibition.

BACKGROUND:CT-guided percutaneous intervention and rehabilitation techniques are both classic programs for diagnosis and treatment of lumbar disc herniation. Is the combination of CT-guided percutaneous intervention and rehabilitation techniques preferential y used for treatment of lumbar disc herniation?
OBJECTIVE:To evaluate the curative effect of CT-guided interventional injection combined with rehabilitation integration treatment for lumbar disc herniation and to analyze prognostic factors.
METHODS:Eighty-eight patients with lumbar disc herniation were subjected to CT-guided interventional injection combined with rehabilitation integration treatment from May 2010 to May 2013. Injection medicine consisted of betamethasone, tanshinone Ⅱ A sulfonate, neurotropin, normal saline and iohexol. Rehabilitation integration treatment included traction, manipulation, acupuncture, transcutaneous electrical nerve stimulation and thermal magnon. Macnab criteria and Chinese version of Oswestry low back pain disability questionnaire were used to assess the curative effects in comparison with the 112 patients receiving only CT-guided interventional injection that were reported previously. The prognostic factors, such as age, disease course time and herniation type of target segment were testified by correlation analysis.
RESULTS AND CONCLUSION:Total y 77 patients were completely fol owed up for 1 year. There were excellent outcomes in 64 cases, while favorable outcomes in 7 cases, fair outcomes in 5 case, poor outcome in 1 case, with a better outcome rate of 92%.There was a significantly decreased trend in Oswestry disability Index scores at 1, 6, 12 months during the fol ow-ups (P<0.01). No severe complications occurred in al the included patients. The curative effects were improved in term of better outcomes rate compared with the 112 patients receiving only CT-guided interventional injection, but there was no significant difference (P>0.05). The young group (≤ 45 years) had better outcomes than the older group (>45 years;P<0.01). In addition, disease course time and herniation type of target segment were not statistical y significant risk factors predicting clinical results (P>0.05). These findings indicate that CT-guided interventional injection combined with rehabilitation integration treatment could relieve lower back pain and radical leg pain effectively and decrease life disability level.

OBJECTIVES: To investigate the effects of PLK1 inhibitors on osimertinib-resistant non-small cell lung carcinoma (NSCLC) cells and the anti-tumor effect combined with osimertinib. METHODS: An osimertinib resistant NCI-H1975 cell line was induced by exposure to gradually increasing drug concentrations. Osimertinib-resistant cells were co-treated with compounds from classical tumor pathway inhibitor library and osimertinib to screen for compounds with synergistic effects with osimertinib. The Gene Set Enrichment Analysis (GSEA) was used to investigate the activated signaling pathways in osimertinib-resistant cells; sulforhodamine B (SRB) staining was used to investigate the effect of PLK1 inhibitors on osimertinib-resistant cells and the synergistic effect of PLK1 inhibitors combined with osimertinib. RESULTS: Osimertinib-resistance in NCI-H1975 cell (resistance index=43.45) was successfully established. The PLK1 inhibitors GSK 461364 and BI 2536 had synergistic effect with osimertinib. Compared with osimertinib-sensitive cells, PLK1 regulatory pathway and cell cycle pathway were significantly activated in osimertinib-resistant cells. In NSCLC patients with epidermal growth factor receptor mutations treated with osimertinib, PLK1 mRNA levels were negatively correlated with progression free survival of patients (R=－0.62, P<0.05), indicating that excessive activation of PLK1 in NSCLC cells may cause cell resistant to osimertinib. Further in vitro experiments showed that IC₅₀ of PLK1 inhibitors BI 6727 and GSK 461364 in osimertinib-resistant cells were lower than those in sensitive ones. Compared with the mono treatment of osimertinib, PLK1 inhibitors combined with osimertinib behaved significantly stronger effect on the proliferation of osimertinib-resistant cells. CONCLUSIONS PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; ErbB Receptors/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; Mutation ; Cell Line, Tumor

Objective: To investigate the feasibility of echocardiography-guided closed-chest repeated intraventricular blood sampling in mice, and to clarify the maximum blood volume that can be collected by this method, and whether the method can be used for long-term repeated blood collection in mice. Methods: Twenty-four male C57BL/6J mice (10-14 weeks old) were divided into the terminal experiment group (n=4, for investigating the maximum blood amount that could be sampled at one time), the repeated 0.5 ml blood collection group (n=10, sampling 0.5 ml whole blood each time, once every two days for consecutive 4 weeks), and the repeated 0.75 ml blood collection group (n=10, sampling 0.75 ml whole blood each time, once every two days for consecutive 4 weeks). High-frequency echocardiography was used to display the largest section of the left ventricle, guiding the insulin syringe needle through the thorax into the left ventricle for blood collection. In the repeated 0.5 ml blood collection group, echocardiography was used to detect the cardiac structure and function before blood collection, three minutes after blood collection, and one week after the last (the 14th) blood collection. Results: We successfully performed echocardiography-guided closed-chest intraventricular blood sampling, with an average operating time (88±19)s per mouse, and a maximum blood volume (1.43±0.11)ml per mouse. In the repeated 0.5 ml blood collection group, heart rate, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension and left ventricular posterior wall end-diastolic thickness remained uncganged before the first blood collection and after 4 weeks of repeated blood collection (all P>0.05). No death in the repeated 0.5 ml blood collection group. However, in the 0.75 ml blood collection group, two mice died before the end point. Conclusions The echocardiography-guided closed-chest intraventricular blood sampling is a safe, minimally invasive, convenient and efficient method, and can be used repeatedly for long-term blood collection in mice.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation