Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1α After Treatment: A Cell Regulation Study

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Comparison of New and Old Versions of Guidelines for Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Carcinoma in China from A Surgical Perspective / 肿瘤防治研究

The set of guidelines for the diagnosis and treatment of thyroid nodules and differentiated thyroid cancer (the second edition) was published in 2023 in China. Based on the first (2012) edition, the current set was revised jointly by nearly 100 experts in endocrinology, thyroid surgery, oncology, nuclear medicine, ultrasound medicine, and pathology from seven national societies for one year. The new version of the guideline is still divided into two parts, namely, thyroid nodules and differentiated thyroid cancer. The writing mode of asking clinical questions, explaining and giving recommendations is adopted, and a total of 117 recommendations are provided. This article aims to compare the variations in the differentiation of benign and malignant thyroid nodules and surgical treatment of differentiated thyroid cancer between the new and old versions from the perspective of surgery. The author's own understanding and experiences are also discussed.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Formulation and meaning of evidence-based and differentiated exercise prescription / 中华行为医学与脑科学杂志

Exercise is a crucial method for preventing and controlling chronic diseases, as well as promoting the health of Chinese residents.As guidelines for residents' exercise, traditional exercise prescriptions have limitations such as copying foreign experiences, uneven quality control, and general classification of population characteristics, which affect the applicability and practicality of their application in the Chinese population.A new model of exercise prescription is put forward and named evidence-based and differentiated exercise prescription.In terms of evidence selection, only studies based on Asian populations are selected.In terms of evidence quality control, standardized quality assessment processes are required.In terms of evidence application, accurate classification of candidate populations and personalized application of evidence are achieved.Evidence-based and differentiated exercise prescription provides scientific and accurate exercise prescription guidance for Chinese residents, realizes the integration of sports and medicine, which is conducive for the prevention and control of chronic diseases and the improvement of residents' health level.

Effects of discontinuation of levothyroxine sodium before radioactive iodine therapy after DTC on blood lipids and renal function in patients / 中华内分泌外科杂志

Objective:To investigate the effect of levothyroxine withdrawal before radioiodine therapy on blood lipids and renal function in patients with differentiated thyroid carcinoma (DTC) after operation.Methods:From Mar. 2020 to Apr. 2022, 214 patients with differentiated thyroid cancer were enrolled in the General Surgery Department, Linyi Central Hospital, Shandong Province. All patients stopped taking levothyroxine sodium after total thyroidectomy. The thyroid function index, blood lipid index and renal function index were measured and compared before and after drug withdrawal (before operation) and after drug withdrawal (before radioiodine treatment). The patients were divided into groups according to the duration of drug withdrawal (drug withdrawal group for 3 weeks, drug withdrawal group for 4 weeks), and the differences of thyroid function index, blood lipid index, and renal function index among patients with different drug withdrawal time were compared. The measurement data in accordance with normal distribution were compared between groups, and independent sample t-test was performed. Results:The levels of free thyroxin T4 (FT 4) and free triiodothyronine (FT 3) in DTC patients decreased significantly ( t=57.60, 71.74,all P<0.001), and the levels of thyroid-stimulating hormone (TSH) increased significantly ( t=102.15, P<0.001). After drug withdrawal, the serum lipid index [triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL) ] and renal function index [blood urea nitrogen (BUN), serum creatinine (SCR) ] of DTC patients increased significantly ( t=20.17, 42.50, 12.13, 30.73, 16.09, 43.73, all P<0.001). The levels of FT 3 and FT 4 in the 4-week group were significantly lower than those in the 3-week group ( t=7.75 and 10.07, both P<0.001), and TSH was significantly higher than that in the 3-week group ( t=26.46, P<0.001). The levels of TG, LDL, HDL, TC, BUN and Scr in the 4-week group were significantly higher than those in the 3-week group ( t=10.13, 10.29, 8.53, 11.47, 10.54, 8.55, all P<0.001). Correlation analysis showed that the levels of FT 3 and FT 4 in DCT patients were negatively correlated with the levels of TG, LDL, HDL, TC, BUN and Scr ( r=-0.256, -0.189, -0.249, -0.314, -0.352, -0.231, -0.342, -0.259, -0.304, -0.216, -0.391, -0.271, P=0.011, 0.029, 0.007, 0.004, 0.015, 0.036, 0.002, 0.009, 0.019, 0.017, 0.016, 0.003), and the levels of TSH were correlated with TG, LDL, HDL, TC and BUN Scr level was positively correlated ( r=0.257, 0.308, 0.219, 0.311, 0.251, 0.271, P=0.006, 0.013, 0.032, 0.004, 0.006, 0.014) . Conclusion:Stopping levothyroxine sodium before radioactive iodine treatment after DTC can easily lead to dyslipidemia and decreased renal function in patients, and the longer the withdrawal time is, the more obvious the changes of blood lipids and renal function in patients, and the withdrawal time should be shortened in clinical treatment.

Value of monitoring serum t-PINP/β-CTX ratio and 25 (OH) D levels in the prevention and treatment of osteoporosis after surgery for differentiated thyroid cancer in elderly women / 中华内分泌外科杂志

Objective:To investigate the level change of serum total n-terminal propeptide of type Ⅰ precollagen (t-PINP) /type Ⅰ collagen carboxy-terminal peptide (beta-CTX) ratio, 25-hydroxyvitamin D (25-hydroxyvitamin D, 25 (OH) ) ratio, and 25-hydroxyvitamin D in elderly women with differentiated thyroid cancer (DTC) after surgery and its value in the prevention and treatment of osteoporosis (OP) .Methods:From Jan. 2020 to May. 2021, 112 elderly female postoperative DTC patients treated with thyroid stimulating hormone (TSH) suppression in Department of Endocrinology of Wenzhou Hospital of Integrative Medicine were collected for a prospective study, and the incidence of OP after 1 year of treatment was counted, and according to the incidence of OP, they were divided into incidence group ( n=78) and non-incidence group ( n=34). The general information, thyroid parameters [TSH, free triiodothyronine (FT3), free thyroxine (FT4) ], bone mineral density (BMD), and serum t-titrosine (BMD) were compared between the two groups. SPSS22.0 software was used, and the counting data was described by examples χ2 test. Grade data was expressed in u, Ridit test was used, measurement data was described in mean±standard deviation ( ±s), t test was used, Pearson correlation coefficient model was used to analyze postoperative thyroid index and serum t-PINP/β- Correlation between CTX ratio and 25 (OH) D level, and serum t-PINP after 1 year of treatment was analyzed through interaction/β- The role of CTX ratio and 25 (OH) D level in OP occurrence. Results:The incidence of OP after 1 year of TSH suppression treatment in 112 elderly female post-DTC patients in this study was 69.64% (78/112) ; serum TSH levels (0.63±0.19) mIU/ml after 1 year of treatment in patients who developed OP were lower than those in patients who did not develop OP (0.81±0.22) mIU/ml, and serum FT3 (6.15±1.71) pmol/ml and FT4 levels (24.63±4.28) pmol/ml were higher than those of patients without OP (4.32±1.29) pmol/ml and (20.36±3.70) pmol/ml ( t1=4.391, t2=5.581, t3=5.050,all P<0.05) .Serum t-PINP/β-CTX ratio (130.27±18.09) and 25 (OH) D level (20.18±4.15) ng/ml after 1 year of treatment in patients with OP were lower than those in patients without OP (148.56±20.37) and (23.36±4.36) ng/ml ( t1=4.733, t2=3.672, both P<0.05) ; serum TSH levels were positively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels, and serum FT3 and FT4 levels were negatively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels after 1 year of treatment in patients with OP ( P<0.05) ; low serum t-PINP/β-CTX ratio after 1 year of treatment expression, and low 25 (OH) D levels showed a positive interaction in OP occurrence in a superphase multiplicative model ( P<0.05) . Conclusion:Serum t-PINP/β-CTX ratio and 25 (OH) D level are closely associated with the occurrence of OP after DTC in elderly women, and postoperative monitoring can help prevent and treat OP.

Correlation between serum SOST, DKK-1 levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery / 中华内分泌外科杂志

Objective:To investigate the correlation between serum recombinant sclerostin (SOST) and dickkopf-related protein 1 (DKK-1) levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery.Methods:A total of 110 patients diagnosed with osteoporosis after differentiated thyroid cancer surgery were recruited as the study group, and another 110 patients without osteoporosis diagnosed after differentiated thyroid cancer surgery were recruited as the control group. The general data, bone mineral density, serum SOST, DKK-1 levels and bone metabolism indicators N-terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BALP), beta-isomerized C-telopeptide (β-CTX), 25-hydroxyvitamin D3 [25- (OH) D3] levels were compared between the two groups. The correlation between serum SOST, DKK-1 levels and bone metabolism indexes was analyzed, and the risk factors affecting the formation of osteoporosis were explored.Results:The T value of bone mineral density in the study group (-3.27±0.92) was significantly lower than that in the control group (-1.23±0.27, t=22.32, P<0.001). The serum SOST (15.84±1.34, t=32.53, P<0.001) and DKK-1 (5.96±1.40, t=4.82, P<0.001) levels in the study group were significantly higher than those in the control group (SOST: 10.24±1.21, DKK-1: 5.05±1.40). The serum PINP (40.95±9.84, t=7.59, P<0.001), BALP (23.14±5.26, t=5.06, P<0.001) and β-CTX (1.07±0.54, t=4.96, P<0.001) in the study group were significantly higher than those in the control group (31.48±8.64, 19.64±4.99, 0.78±0.29), and the 25- (OH) D3 level (13.68±4.49) was significantly lower than that of the control group (18.31±5.72, t=6.68, P<0.001). Serum SOST was positively correlated with PINP ( r=0.33, P=0.001), BALP ( r=0.23, P=0.016) and β-CTX ( r=0.19, P=0.046), but not with 25- (OH) D3 ( r=-0.09, P=0.349). Serum DKK-1 was positively correlated with PINP ( r=0.19, P=0.044), BALP ( r=0.26, P=0.007) and β-CTX ( r=0.21, P=0.028), but not with 25- (OH) D3 ( r=-0.16, P=0.088). Serum SOST and DKK-1 levels were independent risk factors for osteoporosis (all P<0.05) . Conclusion:Serum SOST and DKK-1 levels are independent risk factors for the formation of osteoporosis, which are significantly positively correlated with bone metabolism indexes PINP, BALP, and β-CTX in patients with osteoporosis after differentiated thyroid cancer surgery.

Relationship between UE and CEUS indexes and the expression of invasion genes and proliferation genes in differentiated thyroid cancer tissue / 中华内分泌外科杂志

Objective:To study the diagnostic value of ultrasonic elastography (UE) CEUS in differentiated thyroid cancer (DTC) and its correlation with invasive gene and proliferative gene expression in DTC tissue.Methods:100 DTC patients who were treated in the Ultrasound Department of Zhuji People’s Hospital of Zhejiang Province from Jan. 2019 to Jan. 2022 were retrospectively selected and included in the TC group, and 100 thyroid adenoma patients who were treated during the same period were included in the thyroid adenoma group. UE and CEUS tests were performed on all patients, and the expression levels of proliferative and invasive genes in tumor tissues were measured. Time to peak (TTP) , average time of contrast medium passage (MTT) and peak intensity (PI) were recorded. DTC patients were divided into groups according to the blue area ratio, elastic ratio of lesions, optimal ROC truncation value of TTP, MTT and PI, that is, elastic value > 1.66, blue area ratio > 51.21%, PI≤17.11dB, MTT≤36.39s, TTP≤18.90s were group A, and vice president was Group B. SPSS 19.0 was used for data analysis, and P < 0.05 was considered to be statistically significant. Results:The blue area ratio and elastic ratio of lesions in TC group were higher than those in thyroid adenoma group ( P < 0.05) , while TTP, MTT and PI in TC group were lower than those in thyroid adenoma group ( P < 0.05) . There were statistically significant differences in blue area ratio, elastic ratio of lesions, TTP, MTT and PI among TC groups with different clinical stages, capsule invasion and lymph node metastasis ( P<0.05) . ROC curve was drawn. The AUC of DTC combined with blue area ratio, elastic ratio of lesions, TTP, MTT and PI was the highest, the specificity of combined detection was 86.37%, and the detection sensitivity was 80.16%. Compared with thyroid adenoma group, Xklp2 target protein (TPX2) , chemokine receptor 4, CXCR4) and polymetalloproteinase-9 (ADAM9) gene expression levels were higher, but TDCD4 gene expression levels were lower ( P<0.05) . The expression levels of TPX2, CXCR4 and ADAM9 genes in group A were higher than those in group B ( P<0.05) , and the programmed death factor 4 (PDCD4) gene in group A was lower than that in group B ( P<0.05) . According to Pearson linear analysis, the blue area ratio and elastic ratio of lesions were positively correlated with the expression levels of TPX2, ADAM9 and CXCR4 genes in DTC tissues, and inversely correlated with the expression levels of PDCD4 genes in DTC tissues ( P<0.05) . The expression levels of TPX2, ADAM9 and CXCR4 genes in TTP, MTT and PI were inversely proportional to the expression levels of PDCD4 genes in DTC patients ( P<0.05) . Conclusion:The combination of blue area ratio, elastic ratio of lesions, TTP, MTT and PI has good diagnostic value for DTC, and the blue area ratio, elastic ratio of lesions, TTP, MTT and PI are correlated with the expression levels of invasive genes and proliferating genes in tumor tissues.

Rediscussion of the reoperation of differentiated thyroid cancer / 国际外科学杂志

The treatment concept and standardization of primary surgery for patients with differentiated thyroid cancer vary among different regions and different treatment centers in the same region, resulting in different reoperation rates for patients. Intraoperative experience, preoperative evaluation, surgical approach, and procedure may all influence the success rate of reoperation. In order to reduce the risk of surgery and complications, reoperation should be treated standardized, while combining the current diagnosis and treatment techniques to provide individualized treatment options for reoperation patients, under the premise of ensuring efficacy, to broaden the indications of surgery, make large incisions into small incisions, and change traditional open surgery into minimally invasive surgery, improve the quality of life of patients and confidence in coping with social stress. This paper will summarize the main content of preoperative assessment at the time of reoperation in patients with differentiated thyroid cancer, analyze the notes and rationally developing a surgical plan for patients, in the hope of attracting the same emphasis and normalizing the reoperation treatment, so as to achieve reoperation of the tumor R0 resection.

Current status of diagnosis and treatment of senile differentiated thyroid cancer / 国际外科学杂志

As the elderly population continues to rise, the issue of disease diagnosis and treatment in the elderly population is becoming a hot topic of concern. Differentiated thyroid cancer is the most common endocrine malignancy in the world, and patients with differentiated thyroid cancer in the elderly have a worse clinical prognosis and higher risk of recurrence and metastasis. Moreover, due to the special characteristics and complexity of the elderly population, patients with differentiated thyroid cancer in the advanced age group have special features in terms of morbidity, preoperative diagnosis, treatment options, and postoperative management compared with other populations. This article reviews the current status of diagnosis and treatment of differentiated thyroid cancer in the elderly, taking into account the findings and opinions of domestic and international studies.

Outcomes and prognostic factors of differentiated thyroid cancer with bone metastasis / 中国辐射卫生

@#<b>Objective</b> To investigate the outcomes and prognostic factors of differentiated thyroid cancer (DTC) with bone metastasis. <b>Methods</b> A retrospective study was conducted on 108 DTC patients with bone metastasis who were treated in the Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier survival curves were generated. Log-rank test and Cox proportional hazards model were used to screen the prognostic factors. The correlation between treatment and prognosis was analyzed. <b>Results</b> The median overall survival was 70 months. The 5-, 10-, 15-, and 20-year overall survival rates were 54.4%, 24.3%, 9.8%, and 4.3%, respectively. Univariate analysis showed improved prognosis in patients with single bone metastasis, without skeletal-relatedevents (SREs), and without cervical lymph node metastasis (<i>P </i>= 0.003-0.019). Patients who received combined treatments (<i>P</i> < 0.001) or ¹³¹I treatment alone (<i>P</i> = 0.109) showed better prognosis than those without ¹³¹I treatment. Multivariate analysis identified single bone metastases, SREs, and treatmentas independent prognostic factors. <b>Conclusion</b> In DTC patients with bone metastasis, good prognosis is significantly associated with single bone metastases, absence of SREs, and ¹³¹I therapy in combination with other therapeutic approaches.

Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma / 中国医学科学院学报

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Progress on Targeted Therapy of Radioiodine-refractory Differentiated Thyroid Cancer / 肿瘤防治研究

Targeted therapy has brought revolutionary breakthroughs for radioiodine-refractory differentiated thyroid cancer. New targeted drugs have prolonged the survival of patients with advanced differentiated thyroid cancer. Multiple tyrosine kinase inhibitors, represented by sorafenib and lenvatinib, have remarkably improved the progression-free survival of patients. Novel tyrosine kinase inhibitors targeting BRAF and RET mutation have also achieved remarkable curative effects, greatly enriching the treatment methods for thyroid cancer. This article reviews the latest research progress on targeted therapy in radioiodine-refractory differentiated thyroid cancer.

Incidence, recurrence and mortality among Filipinos with differentiated thyroid cancer: A systematic review / Journal of the ASEAN Federation of Endocrine Societies

Background@#The majority of thyroid malignancies are differentiated thyroid carcinomas (DTCs). We examined the incidence, disease extent, recurrence and disease-specific mortality (DSM) of DTC among Filipinos residing in the Philippines and Filipino immigrants.@*Methodology@# In accordance with the 2020 PRISMA statement, we performed a systematic literature search in MEDLINE, Google Scholar, EBSCO, Cochrane and Clinicaltrials.gov for the period January 1, 1980 until January 27, 2022. Pooled incidence rate ratio and pooled proportions of disease extent, recurrence and DSM were determined.@*Results@#Literature search yielded 1,852 studies. Out of 26 articles retrieved, nine retrospective case controls and cohorts were included. Incidence of DTC was significantly higher in female Filipino immigrants compared with non-Hispanic whites (NHW). Distant metastases and recurrence were more common among Filipinos and Filipino immigrants compared with NHW. Limited data showed higher DSM in Filipino immigrants and NHW than Filipinos, which may be influenced by reporting bias.@*Conclusion@#This review supports the trend of increased incidence and recurrence of DTC among Filipinos, although case registries are essential to confirm these findings. In the setting of the newly released Philippine guidelines for DTC, prospective studies with active long-term follow-up will help detect any changes in the outcomes of DTC among Filipinos.

Practice of two methods in occupational health risk grading and classification management in petroleum refining enterprises / 环境与职业医学

Background Most of the studies on grading and classification of occupational health compre-hensive risks for specific employers still remain in the establishment and description of methodology, and practical application studies are rarely reported. Objective To explore the application of an occupational disease hazards comprehensive risk assessment method issued by the National Disease Control and Prevention Bureau in conjunction with the National Health Commission and a self-developed occupational health grading and classification method in petroleum refining enterprises, and to provide practical experience for the implementation of differentiated law enforcement by relevant regulatory authorities. Methods Two occupational health grading and classification methods were practiced in three petroleum refining enterprises in Guangdong Province. The occupational hazards comprehensive risk assessment method was provided by the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement of the National Disease Control and Prevention Bureau and the National Health Commission. The principle was to derive the occupational health risk level according to nature of occupational hazards, exposure level, and number of workers exposed to them in an employer, and then to classify them into Class A, Class B, and Class C by combining with local occupational health management status level. The occupational health grading and classification method was self-developed according to available domestic and foreign occupational health risk assessment methods. Its principle was to calculate the risk level of each workstation in an employer based on published carcinogenicity classification or LD50/LC50 of chemical toxicants, level of noise, exposure parameters such as exposure level and exposure frequency, estimate the comprehensive risk Ro of the target employer by the Romanian comprehensive risk calculation method, and then calculate a comprehensive risk Ro' weighted by the occupational health management index of the target employer and classify it into class A, class B, and class C. Finally, assessment results, scope of application, inquired indicators, advantages,disadvantages and professional competence requirements of the two grading and classification methods were compared. Results The occupational hazards that were evaluated in three enterprises in this study were benzene, toluene, xylene, gasoline, hydrogen sulfide, and noise. The exposure levels of benzene, toluene, xylene, and gasoline were all below 10% OEL (occupational exposure limit), and hydrogen sulfide and noise were disqualified. Occupational hazards such as benzene and hydrogen sulfide were serious occupational hazards in the three enterprises, and the number of workers exposed was 461, 912, and 224, respectively; the HRs (hazard ratings) of benzene, toluene, xylene, gasoline, hydrogen sulfide, and noise were level 5, 3, 2, 3, 5, and 3 respectively. The occupational health management status of the three enterprises was graded as B, A, and B, respectively by the occupational disease hazards comprehensive risk assessment method. The occupational health management index of the three enterprises was graded as B, A, and A, respectively by the occupational health grading and classification method. The comprehensive risk assessment results showed that two enterprises classified into as the highest class C and one into class B by the occupational disease hazards comprehensive risk assessment method, while all three enterprises were classified into class B by the occupational health grading and classification method. Conclusion The two grading and classification methods are not consistent in the evaluation results of petroleum refining enterprises, and there are differences in the evaluation scope, indicators to be collected, and professionalism. It is recommended that occupational health regulators should fully consider the advantages and disadvantages of the two methods and choose the appropriate assessment method according to the actual regulatory purpose.

Analysis and suggestions on the development trend of drug innovation in China / 中国药科大学学报

@#In order to comprehensivehy evaluate the stage of China in the global drug innovation, to further optimize the environment for drug innovation in China, and to unleash the vitality of drug innovation, this article mainly analyzes through comparison China''s situation of drug innovation in global competition from such perspectives as the current situation of the global drug R&D innovation market, R&D investment, product pipeline, policy support, and development trends, combined with the characteristics of China''s drug innovation development.It can be seen that China''s pharmaceutical innovation is faced with such practical problems as lagging behind some developed countries in terms of innovation development, companies bunching into research and development innovation, sudden research and development rush, and excessive dependence on capital markets for pharmaceutical innovation.Accordingly, this paper puts forward suggestions on continuously improving China''s new drug innovation environment, rationally selecting differentiated competition and new tracks, reasonably formulating drug innovation development strategies, guiding capital to return to innovative research and development, and constructing a "double cycle" strategy for drug innovation.

Radioiodine (131I) treatment decision-making for low- and intermediate-risk differentiated thyroid cancer

ABSTRACT Objective: The purpose of this study was to investigate the effect and influencing factors of post-surgical radioactive iodine (RAI) therapy for patients with low- and intermediate-risk differentiated thyroid cancer (DTC). Subjects and methods: A retrospective analysis of 423 low- and intermediate-risk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People's Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediate-risk. Results: The excellent response (ER) rate for low- and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [131I], and pretreatment stimulated-Tg (pre-Tg) levels between the low- and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Conclusion: Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.

Differentiating pediatric cystic nephroma from common renal multicystic lesions: A case report

Pediatric cystic nephroma is a rare, clinically benign, renal tumor. Pediatric renal cystic lesions are complex. Imaging findings and tumor appearance are often nonspecific, and careful pathological examination is necessary. We discuss diagnosis of pediatric cystic nephroma and how to differentiate it from multicystic dysplastic kidney and cystic partially differentiated nephroblastoma.

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups – Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades.Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Riesgo de recurrencia y factores de riesgo de invasión del cáncer diferenciado de tiroides / Risk of recurrence and risk factors for invasion of differentiated thyroid cancer

Introducción: El cáncer diferenciado de tiroides (CDT) se encuentra representado por el carcinoma papilar y el carcinoma folicular. Comprende la gran mayoría (>90%) de todos los cánceres de tiroides. Objetivos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Materiales y métodos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Resultados: El 87% fueron del sexo femenino. La edad media fue de 43±14 años. Predominó el riesgo de recurrencia bajo en el 49% de los pacientes, seguido del riesgo intermedio (33%) y riesgo alto (18%). El tamaño tumoral ˃1cm confiere mayor riesgo de ser estratificado como riesgo de recurrencia intermedio/alto (OR 5,7 IC 95% 3,6-9). El sexo masculino representó mayor riesgo de invasión ganglionar (OR 2,8 IC 95% 1,2-6,6); la edad ≥55 años lo fue en la invasión vascular (OR 2,1 IC 95% 1,1-4,1); el tamaño >1cm constituyó un mayor riesgo de manera significativa de invasión capsular (OR 10,5 IC 95% 6,5-17), invasión ganglionar (OR 10,2 IC 95% 3,8-26,9), invasión vascular (OR 30,7 IC 95% 4,2-224) e invasión de tejido peritiroideo (OR 5,2 IC 95% 3,3-8,2). Conclusión: El riesgo de recurrencia inicial más frecuente fue el riesgo bajo. El sexo masculino, la edad ≥55años y el tamaño >1cm constituyen factores de riesgo de invasión a estructuras vecinas.

Introduction: Differentiated thyroid cancer (DTC) is represented by papillary carcinoma and follicular carcinoma. It comprises the vast majority (> 90%) of all thyroid cancers. Objectives: Stratify the risk of initial recurrence of patients with DTC. Relate age, sex, and tumor size to the risk of recurrence, capsular, nodal, vascular, and perithyroid tissue invasion. Materials and methods: Observational, descriptive, retrospective, cross-sectional study with an analytical component. A total of 432 patients with a diagnosis of DTC from Hospital de Clínicas, Instituto de Previsión Social and Instituto Nacional del Cáncer between 2011 and 2015 were included. Results: 87% were female. The mean age was 43 ± 14 years. Low recurrence risk predominated in 49% of patients, followed by intermediate risk (33%) and high risk (18%). Male sex, age ≥55 years and tumor size ˃1cm confer a higher risk of being stratified as intermediate / high recurrence risk, but only size> 1cm was significantly (OR 5.7 95% CI 3.6-9). Male sex represented a higher risk of lymph node invasion (OR 3.1 95% CI 1.4-2.8) and vascular invasion (OR 2.3 95% CI 1.1-4.8); age ≥55 years was in the vascular invasion (OR 2.6 95% CI 1.4-4.9); size> 1cm constituted a significantly higher risk of capsular invasion (OR 10.7 95% CI 6.7-17.3), nodal invasion (OR 10.5 95% CI 4-27.7), vascular invasion (OR 33 95% CI 4.5-244) and invasion of perithyroid tissue (OR 5.1 95% CI 3.2-8.1). Conclusion: The most frequent initial recurrence risk was low risk. Male sex, age ≥55 years, and size> 1cm are risk factors for invasion of neighboring structures.