Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

OBJECTIVE: Reduce the number of false alarms and measurement time caused by movement interference by the sync waveform of the movement. METHODS: Vital signal monitoring system based on motion sensor was developed, which collected and processed the vital signals continuously, optimized the features and results of vital signals and transmitted the vital signal results and alarms to the interface. RESULTS: The system was tested in many departments, such as digestive department, cardiology department, internal medicine department, hepatobiliary surgery department and emergency department, and the total collection time was 1 940 h. The number of false electrocardiograph (ECG) alarms decreased by 82.8%, and the proportion of correct alarms increased by 28%. The average measurement time of non-invasive blood pressure (NIBP) decreased by 16.1 s. The total number of false respiratory rate measurement decreased by 71.9%. CONCLUSIONS False alarms and measurement failures can be avoided by the vital signal monitoring system based on accelerometer to reduce the alarm fatigue in clinic.
Humans ; Monitoring, Physiologic ; Electrocardiography ; Arrhythmias, Cardiac ; Blood Pressure ; Accelerometry ; Clinical Alarms

OBJECTIVE: To summarize the clinical and laboratory characteristics of patients with acute myeloid leukemia (AML) with inv(16)/t(16;16) (p13.1;q22), and to analyze the risk factors affecting the prognosis of the patients. METHODS: AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11⁺ admitted to the Department of Hematology, The First Affiliated Hospital of Soochow University from January 1, 2008 to October 30, 2019 were retrospective analyzed, the clinical and laboratory indicators, as well as treatment plans and efficacy evaluations of the patients were all recorded. Furthermore, related factors affecting the overall survival (OS) and event-free survival (EFS) of the patients were analyzed. RESULTS: Among 151 AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11⁺, the percentage of additional chromosomal abnormalities was about 27.8%, and the most common additional chromosomal abnormality was +22 (33/151, 21.8%), followed by +8 (11/151, 7.3%). There were 112 patients with perfect NGS examination, and the result showed the most common accompanying gene mutations were KIT mutation (34/112, 30.4%) and FLT3 mutation (23/112, 20.5%). Univariate analysis showed that factors affecting EFS included: NE≤0.5×10⁹/L (P=0.006) and combined K-RAS mutation (P=0.002); Factors affecting OS included: Age≥50 years old (P<0.001) and NE≤0.5×10⁹/L (P=0.016). Multivariate analysis showed that NE≤0.5×10⁹/L (P=0.019) was the risk factors affecting OS. The proportion of bone marrow eosinophilia (BME)≥10.00% (P=0.029) was the risk factors affecting EFS. CONCLUSION The prognosis for those newly diagnosed AML patients who were of advanced age, the high proportion of bone marrow eosinophils, K-RAS mutations, and agranulocytosis is poor. The treatment plans can be adjusted in the early stage to improve the prognosis of such patients.
Chromosome Inversion ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Myosin Heavy Chains/genetics* ; Oncogene Proteins, Fusion ; Prognosis ; Retrospective Studies

Objective:Pulse oximetry plethysmographic (POP) waveform to indicate the patient's perfusion status and the quality of resuscitation has been affirmed. The POP waveform is obtained by a non-invasive monitoring method, and its clinical feasibility during CPR is better than that of invasive monitoring technologies. This study aimed to analyze the three parameters derived from POP waveform: CPR quality index (CQI), perfusion index (PI), and chest compression fraction (CCF) in evaluating the CPR quality and ROSC possibility.Methods:A prospective descriptive study was conducted on 74 CPR patients who were divided into the ROSC group and non-ROSC group according to their resuscitation results. The clinical data were extracted from patient monitor, the distribution and changes of the three parameters during CPR were collected, and their value of evaluating resuscitation outcome were analyzed.Results:At the end stage of resuscitation, there were statistically significant differences in the three parameters between the two groups ( P<0.05). In addition, CQI was significantly more capable in evaluating the possibility of ROSC than PI and CCF ( P<0.05). Conclusions:CQI, PI and CCF derived from POP waveform can all be applied to evaluate CPR quality and ROSC possibility. CQI has higher prognosis value than PI and CCF.

Objective - To investigate the effect of lung flora dysbiosis on the process of pulmonary fibrosis and lung epithelial （ ） Methods - mesenchymal transition EMT in mice with silicosis. Male C57BL/6 mice of specific pathogen free grade were ， ， ， （ ） randomly divided into the blank control group silicosis model group solvent control group vancomycin VM + ampicillin （ ） ， （ ） （ ） ， AMP group metronidazole MNZ + neomycin NEO group and mixed treatment group 12 mice in each group. Except for ， ， the blank control group which was given 20.0 µL of 0.9% NaCl solution the other five groups of mice were dosed with 20.0 µL of silica dust suspension at a mass concentration of 250.0 g/L using a single tracheal drip to establish the silicosis mouse model. ： The intranasal drip method was used to treat silicosis mice in each group as following mice in the solvent control group were - ； ； given double distilled water mice in the VM+AMP group were given VM at a mass concentration of 0.5 g/L and AMP at 1.0 g/L ； mice in the MNZ+NEO group were given MNZ at a mass concentration of 1.0 g/L and NEO at 1.0 g/L mice in the mixed ， treatment group were given the same doses of the four antibiotics mentioned above all in a drip volume of 50.0 µL. Silicosis ， ， mice were treated seven days and half an hour before silica dusting and 7 14 and 21 days after silica dusting. Mouse lungtissue was collected aseptically 28 days after silica dusting. Hematoxylin eosin and Masson trichrome staining methods were - used to observe the pathological changes. Western blotting was used to detect the relative protein expression of α smooth muscle （ - ）， - （ - ） （ ） actin α SMA E cadherin E CAD and vimentin VIM . Immunohistochemistry was used to detect the relative expression of - - E CAD and VIM. Real time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of （Col1a2） Results collagen type Ⅰ alpha 2 mRNA in lung tissues. The histopathological results showed that the alveoli of the ， blank control group were thin and structurally intact with few surrounding infiltrating inflammatory cells and no abnormal ， distribution of collagen fibers. The alveoli of the silicosis model group were structurally disorganized with a large number of ， ， infiltrating inflammatory cells thickened alveolar walls and cellular fibrous nodules with abundant blue collagen deposit. In the ， ， VM+AMP group MNZ+NEO group and the mixed treatment group the inflammation and fibrosis were reduced with diferent degrees in the lung tissues compared to the silicosis model group and the solvent control group. The relative expression levels of - ， Col1a2 α SMA VIM protein and mRNA in lung tissues of mice in the silicosis model group were higher than those in the blank （ P ）， -CAD control group all <0.05 and the relative expression levels of E protein were lower than those in the blank control （P ） - ， Col1a2 group <0.05 . The relative expression levels of α SMA VIM protein and mRNA in lung tissues of mice in the MNZ+ （ P ）， -CAD NEO group and the mixed treatment group were lower all <0.05 and the relative expression levels of E protein were （P ）， Conclusion higher <0.05 when compared with the silicosis model group and the solvent control group. Pulmonary fibrosis ， - was reduced in silicosis mice with interventions in lung flora where anaerobic and gram negative bacteria affected pulmonary fibrosis and dysbiosis of the lung flora affected pulmonary EMT.

Objective:To observe the effect of liraglutide on the correlation between nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) infl ammasome and nonalcoholic fatty liver disease (NAFLD).Methods:Thirty-nine NAFLD cases (group N) and thirty-nine healthy subjects (group C) were selected from the physical examination center, and their general data were collected to determine the serum levels of NLRP3, IL-1β, and IL-18. The differences and correlations were analyzed between the two sets of indicators. Thirty male SD rats were randomly divided into normal (NC, n=10) and high-fat diet group (HF, n=20). The normal group were fed with normal diet and high-fat diet group were fed with high-fat diet. After 12 weeks of feeding, HF group was randomly divided into HF group ( n=10) and liraglutide group (100L, n=10), and were given 0.5 ml/kg sterile isotonic saline and 100 g/kg liraglutide subcutaneously twice a day, respectively. Four weeks later, serum biochemical indicators, liver NLRP3 infl ammasome protein expression, and infl ammatory cytokine conditions were detected in each group. Statistical analysis was performed using t test, oneway analysis of variance (ANOVA) or χ2 test. Results:There were no statistically signifi cant differences between N and C group in terms of age, gender, diastolic blood pressure, glycosylated hemoglobin, mean platelet volume, erythrocyte distribution width, serum low-density lipoprotein cholesterol (HDL-Ch), total cholesterol, and total bileacid. Compared with group C, group N had elevated systolic blood pressure, body mass index (BMI), fasting blood glucose, blood creatinine, alkaline phosphatase (ALP), NLRP3, interleukin (IL)-1β, IL-18, TG, blood uric acid, γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and white blood cell counts, while HDL-Ch and total bilirubin were depleted than group C, and the difference was statistically significant ( P< 0.05). NLRP3 was positively correlated with systolic blood pressure, BMI, fasting blood glucose, serum creatinine, IL-1β, IL-18, triglycerides, serum uric acid, GGT, ALT, AST, but negatively correlated with total bilirubin and HDL-Ch, and the difference was statistically signifi cant. Compared with NC group, HF group had significantly increased body mass, liver mass, serum biochemical indicators (triglycerides, AST, ALT), liver NLRP3 inflammasome protein expression, and inflammatory cytokines. After treatment with liraglutide, 100L group indicators were signifi cantly decreased when compared to HF group. Conclusion:Compared with healthy subjects, the infl ammation-related indicators, body mass, blood lipids and liver function-related indicators are signifi cantly changed in patients with NAFLD, which is also consistent with the results of rat model study. Liraglutide treatment had improved NAFLD to certain extent in NAFLD rats, so NLRP3 regulation may be one of the mechanisms to improve liver inflammation and steatosis.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective: To investigate the clinicopathological characteristics, treatment and prognosis of head and neck carcinosarcoma. Methods: The clinical data of 14 patients with head and neck carcinosarcoma treated in the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2020 were retrospectively analyzed, including 11 males and 3 females, with age range from 30 to 72 years old. Clinicopathological characteristics, treatments and follow-up results of patients were evaluated. Kaplan-Meier method was used to estimate the cumulative survival rate. Results: Histopathological examination showed the co-existence of malignant epithelial and mesenchymal components in all cases. Immunohistochemical staining of 13 cases showed cytokeratin and epithelial membrane antigens were positively expressed in the epithelial areas, whereas vimentin was positive in the malignant mesenchymal tissue area. Among 14 cases, 5 cases were treated with surgery, 3 cases with surgery and radiotherapy, and 6 cases with surgery, radiotherapy and chemotherapy. The follow-up time was 2-81 months, with a median follow-up time of 22.5 months. Except for one patient who was lost to follow-up in 21 months after treatment, among the remaining 13 patients, 4 patients had recurrence, 8 patients died, and 5 patients had a tumor-free survival. The Kaplan-Meier analysis showed that the 1, 3, and 5-year cumulative survival rates of 14 patients with head and neck carcinosarcoma were 64.3%, 57.1%, and 42.9%, respectively. Conclusions: Carcinosarcoma of the head and neck is rare in clinic, histopathological and immunohistochemical examinations are important basis for diagnosis, and surgery is a preferred treatment. Carcinosarcoma of the head and neck has a poor prognosis, and patients should be followed up for a long time.
Adult ; Aged ; Carcinosarcoma/therapy* ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies