The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective:To investigate the effects of melatonin(Mel)on inflammatory damage in the retina of rats with oxygen-induced retinopathy(OIR)and the molecular mechanisms.Methods:Healthy neonatal SD rats were di-vided into the sham group(Sham),the model group(OIR),and the melatonin treatment group(OIR+Mel).The OIR model was induced by alternating 50%/10%oxygen concentration exposure for 14 d.The OIR+Mel group was in-jected intraperitoneally with 10 mg-kg-1 melatonin.Hematoxylin-eosin(HE)staining was used to observe the morpho-logical changes in the retinal tissue;immunohistochemical staining was used to detect the expression of retinal cleaved-caspase-1 and IL-1β proteins;and immunofluorescence staining was used to detect the expression of cGAS-STING-NL-RP3 signaling molecules and gasdermin(GSDMD)in the microglia of the retina.Results:HE staining results showed that compared with the Sham group,the retinal cells in the OIR group were disorganized and the thickness of the inner retina was significantly thinner,and the retinal cells in the OIR+Mel group were more neatly arranged compared with those in the OIR group(P<0.05).Immunohistochemical staining results showed that the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR+Mel group decreased signifi-cantly compared with that of the OIR group(P<0.05).Immunofluorescence staining results showed that the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR+Mel group de-creased significantly compared with that in the OIR group(P<0.05);The number of Iba-1+/N-GSDMD+cells in-creased significantly in the OIR group compared with the Sham group,whereas the number of Iba-1+/N-GSDMD+cells in the OIR+Mel group was significantly less than that in the OIR group,but still more than that in the Sham group(P<0.05).Conclusion:Mel inhibits the pyroptosis of retinal microglia,thus attenuates retinal inflammatory injury in OIR rats,and its mechanism may be related to the cGAS-STING-NLRP3 signaling pathway.

Objective:To evaluate the impact of 131I therapy on salivary gland function in postoperative patients with differentiated thyroid cancer (DTC) using quantitative salivary gland scintigraphy (SGS). Methods:Sixty-four patients (23 males, 41 females, age (39.6±13.0) years) were recruited from the Third Affiliated Hospital, Sun Yat-Sen University, all of whom had undergone surgery for DTC between May 2014 and December 2023. SGS was conducted 3 d prior to and 3-6 months following 131I therapy. Salivary gland function parameters, including the uptake index (UI) and excretion fraction (EF) for both (right (R) and left (L)) parotid (P) and submandibular (S) glands (L-pUI, R-pUI, L-sUI, R-sUI, L-pEF, R-pEF, L-sEF, R-sEF), were measured. Patients were divided into two groups (group A: dose of first-time therapy (D f) ≤ 3700MBq; group B: D f>3700MBq) to analyze the characteristics of changes in salivary gland function between the two groups. The relationship between cumulative dose (D c) and salivary gland hypofunction was assessed. Data were analyzed using paired t test, Wilcoxon signed rank test, and χ2 test. The optimal threshold of D c for salivary gland hypofunction was determined through ROC curve analysis. Results:After the first therapy, L-pUI, R-pUI, L-sUI, and R-sUI significantly decreased compared with baseline values in group B ( n=38; t values: from -3.77 to -2.96, all P<0.01). In contrast, there were no significant differences in any salivary gland function parameters between pre-therapy and post-therapy assessments in group A ( n=26; t values: from -1.18 to 0.95, all P>0.05). Fifteen patients underwent therapy twice. After the second therapy, L-pUI, R-pUI, L-sUI, R-sUI, L-pEF, and R-pEF significantly decreased compared to baseline values ( t values: from -6.77 to -3.50, all P<0.01), and with a more pronounced reduction observed in L-pUI and R-pUI compared to the first therapy ( Z values: from -2.10 and -2.67, both P<0.05). The incidence of salivary gland hypofunction after the second therapy was higher than that after the first therapy (10/15 vs 21.9%(14/64); χ2=11.53, P=0.001). The incidence of salivary gland hypofunction was found to be related to D c ( χ2=24.35, P<0.001). Based on ROC curve analyses, patients were likely to experience salivary gland hypofunction when D c exceeded 5550MBq (AUC=0.80(95% CI: 0.69-0.89), P<0.001), with the sensitivity of 13/19, specificity of 91.1%(41/45), positive predictive value of 13/17, and negative predictive value of 87.2%(41/47). Conclusion:Some patients with DTC experience a decline in salivary gland function in the short term (3-6months) after undergoing postoperative therapy with 131I, and the degree and incidence of this decline display in a D c-related manner.

Objective:To report the follow-up status of patients participating phase Ⅲ clinical trial (ZGDD3) of Donafenib tosilate (abbreviated as Donafenib) in the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), and to explore its efficacy, safety and prognostic factors.Methods:This study was a randomized controlled trial, and the clinicopathological data and follow-up results of 29 patients (16 males, 13 females, age 40-68 years) who participated in the clinical trial ZGDD3 between August 2018 and March 2021 were analyzed. Patients were divided into Donafenib group and placebo group using the central dynamic randomization method with the ratio of 2∶1. Adverse reactions (AE) during the trial were observed. Independent-sample t test, Mann-Whitney U test and Fisher exact test were used to analyze the differences of baseline characteristics between the two groups. Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier method was used to draw the survival curve (log-rank test) and Cox regression analysis was used to analyze the prognostic factors. Results:There were 22 patients in Donafenib group and 7 patients in placebo group. There were no significant differences of baseline characteristics between the two groups ( t values: -0.68, Z values: from -1.47 to -0.56, all P>0.05). The follow-up was 32.07(21.07, 49.85) months. During the trial, drug-related AEs occurred in all patients in Donafenib group, mostly was grade Ⅰ-Ⅱ, no grade Ⅳ or Ⅴ AEs were found. The median PFS was significantly longer in Donafenib group than that in placebo group (13.23 vs 4.03 months; χ2=9.68, P=0.002), and the median OS was 55.00 and 24.30 months respectively ( χ2=2.07, P=0.150). Metastasis to less common sites was the independent risk factor for OS (hazard ratio ( HR)=6.789, 95% CI: 1.272-36.246, P=0.025). Conclusions:Donafenib shows good clinical application in the treatment of RAIR-DTC, demonstrating good safety and efficacy. Metastasis to less common sites is closely related to OS.

For differentiated thyroid cancer(DTC),which accounts for over 90%of cases and usually has a good prognosis,bone metastasis is not only the main threat to patients'survival and quality of life,but also a difficult problem that needs to be solved urgently in clinical diagnosis and treatment at this stage.Currently,existing clinical guidelines at home and abroad have not yet provided comprehensive management recommendations and precise diagnostic and treatment strategies for bone metastasis in thyroid cancer,making it imperative to promote the implementation of systematic and personalized diagnostic and treatment plans.Therefore,understanding epidemiological characteristics,clarifying the pathogenesis,mastering commonly used diagnostic techniques,exploring the latest treatment progress and evaluating treatment efficacy are crucial for the management of bone metastasis in thyroid cancer.In terms of pathogenesis,bone metastasis in thyroid cancer is mostly osteolytic,regulating the interaction between the bone microenvironment and cancer cells through the release of various cytokines,thus forming a vicious cycle of bone metastasis.Early identification of bone metastasis in DTC is crucial for improving patient prognosis.Its diagnosis can be based on clinical manifestations(such as bone pain,pathological fractures,spinal cord compression and hypercalcemia),laboratory tests(such as red blood cell and platelet counts,serum calcium/phosphorus and bone turnover markers),and imaging examination results[such as X-ray,computed tomography(CT),magnetic resonance imaging(MRI),single photon emission computed tomography(SPECT)/CT,and positron emission tomography(PET)/CT].The treatment of DTC bone metastasis involves multiple modalities,such as surgical treatment,interventional radiological treatment and external beam radiation therapy for local lesions,or the use of radionuclides(131I,89Sr and 153Sm),tyrosine kinase inhibitors(lenvatinib,sorafenib,etc.),or bone-targeting agents(including zoledronic acid,denosumab and 99Tc-methylene diphosphonate)to control the development of systemic bone metastasis.After the treatment of DTC bone metastasis,an efficacy evaluation should be conducted to guide subsequent treatment decisions and predict prognosis.With the increasingly mature multidisciplinary collaborative diagnosis and treatment model today,the diagnosis and treatment of bone metastatic DTC should include surgery,nuclear medicine,radiation and interventional therapy,external beam radiation therapy,medical oncology and clinical laboratory testing to ensure a comprehensive assessment of the patient's condition,make objective decisions on individualized treatment plans,and achieve the goal of preventing disease progression and alleviating symptoms.This article mainly reviewed the epidemiology,pathogenesis,diagnostic methods,treatment strategies and efficacy evaluation of bone metastasis,aiming to clarify the diagnostic and treatment thinking of bone metastasis in thyroid cancer,assist in clinical management,and provide useful references for clinicians to make rapid and accurate diagnosis and precise treatment decisions when facing patients with bone metastatic DTC.

Thyroid cancer is the most common malignant tumor of the endocrine system and head and neck region,mainly including papillary thyroid cancer(PTC),follicular thyroid cancer(FTC),medullary thyroid cancer(MTC)and anaplastic thyroid cancer(ATC).Over the past few decades,the global incidence of thyroid cancer has risen rapidly,nearly doubling in some developed countries.Geographically,thyroid cancer incidence is higher in economically developed regions.Although the fastest increase in incidence has been observed in high-income countries,certain middle-income countries have also reported significant growth.Demographically,the incidence rate is notably higher in women than in men.In China,the incidence of thyroid cancer has increased significantly in recent years,while the mortality rate has remained stable at a low level.Urban areas report higher incidence rates than rural areas,and eastern coastal regions have higher rates compared to central and western regions.The etiology of thyroid cancer is multifaceted,with major risk factors including genetic predisposition,radiation exposure,iodine intake levels,endocrine disruptions,environmental and lifestyle factors.Among these,radiation exposure(particularly ionizing radiation during childhood)is a recognized critical risk factor.In addition,both insufficient and excessive iodine intake can disrupt thyroid function,thereby increasing disease risk.Genetic factors,such as familial clustering and gene(BRAF,RET/PTC,etc.)mutations,have been widely studied,while environmental pollution and modern lifestyles may also contribute to disease onset.Therefore,it is beneficial to conduct early screening for people with a family history of thyroid cancer,reduce unnecessary medical radiation exposure and conduct intervention on lifestyle-related risk factors such as obesity to prevent and control thyroid cancer.Most patients with thyroid cancer have a favorable prognosis.The main factors influencing the prognosis include pathological typing(PTC has a relatively better prognosis,while MTC and ATC have poorer prognoses),clinical staging(patients at TNM stages Ⅰ and Ⅱ have better prognoses,while those at stages Ⅲ and Ⅳ have worse ones),physiological factors(the overall prognosis of females is superior to that of males),genetic factors and environmental factors.Understanding the epidemiological trends and identifying factors influencing the onset and prognosis of thyroid cancer are essential for its prevention,treatment and health management.Future research should focus on identifying high-risk populations and developing targeted interventions to prevent and control thyroid cancer,reduce its disease burden,improve quality of life for patients,and lower healthcare costs.

Background and purpose:As one of the first-line treatment methods for differentiated thyroid cancer(DTC),131I treatment is an important therapeutic approach for most patients with medium-high recurrence risk DTC after total or near-total thyroidectomy.Risk stratification and real-time dynamic assessment before 131I treatment after surgery are important steps in deciding on 131I treatment,enabling individualized treatment.This retrospective study aimed to explore the role of diagnostic whole body scan(DxWBS)in the decision-making of treatment for DTC after surgery and before 131I therapy.Methods:DTC patients who underwent pre-ablation evaluation were included.Patients were divided into low,medium and high sTg groups based on their pre-131I treatment stimulated thyroglobulin(sTg)levels(＜1 ng/mL,1 ng/mL≤sTg＜10 ng/mL,sTg≥10 ng/mL).The concordance rates of DxWBS and post treatment whole body scan(RxWBS)in each patient of the whole cohort were compared.The lesion detection rate between DxWBS and RxWBS in different sTg level groups was also explored.The"thyroid stunning effect"by DxWBS was evaluated by RxWBS.Through these analyses,the role of DxWBS in 131I treatment decision-making and its predicting treatment objectives were assessed.This study was approved by the Ethics Committee of Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences(ethics number:JS-2151).Results:A total of 91 patients were included.The low,medium and high sTg groups accounted for 15.4%(14/91),34.1%(31/91)and 50.5%(46/91)of the patients,respectively.Comparison of DxWBS and RxWBS results in the same patients in each sTg group showed no evidence of a stunning effect on 131I treatment.The overall concordance rate between DxWBS and RxWBS was 89.0%(81/91);In different sTg level groups was 100.0%(14/14),90.3%(28/31),84.8%(39/46)respectively.Taking sTg levels into consideration,DxWBS accurately predicted the need for total thyroidectomy,with a 100%(20/20)agreement with RxWBS.Among the 71 patients who received adjuvant therapy and/or remnant ablation due to suspected elevated Tg or high recurrence risk stratification or the iodine-avid metastatic lesions identified by DxWBS,87.5%(63/71)showed only residual thyroid tissue by DxWBS;Through the purpose verification by RxWBS and single photon emission computed tomography(SPECT)/CT,only 12.7%(9/71)of cases were verified as adjuvant or tumoricidal treatment due to iodine-avid cervical lymph node and/or lung metastasis identified by RxWBS,87.3%(62/71)were residual thyroid ablation.In the medium and high sTg group,the overall detection rate of functional cervical lymph node metastasis by DxWBS and RxWBS was 5.5%(5/91).For the detection of functional lung metastases,the overall detection rate of DxWBS was slightly lower than that of RxWBS(3.3%vs 5.5%).This indicates that DxWBS can be used to accurately pre-judge the purposes of 131I treatment,particularly for thyroid ablation and adjuvant therapy.Conclusion:DxWBS did not induce"thyroid stunning"effect.Integrating DxWBS as a theranostic tool into the real-time decision-making and evaluation system of 131I treatment,as well as with sTg and other biochemical indicators,may help to bridge the limitations of static evaluations based on pathology and clinical data,and provides a clear understanding and more precise objectives of 131I treatment.

Objective:To investigate the effects of melatonin(Mel)on inflammatory damage in the retina of rats with oxygen-induced retinopathy(OIR)and the molecular mechanisms.Methods:Healthy neonatal SD rats were di-vided into the sham group(Sham),the model group(OIR),and the melatonin treatment group(OIR+Mel).The OIR model was induced by alternating 50%/10%oxygen concentration exposure for 14 d.The OIR+Mel group was in-jected intraperitoneally with 10 mg-kg-1 melatonin.Hematoxylin-eosin(HE)staining was used to observe the morpho-logical changes in the retinal tissue;immunohistochemical staining was used to detect the expression of retinal cleaved-caspase-1 and IL-1β proteins;and immunofluorescence staining was used to detect the expression of cGAS-STING-NL-RP3 signaling molecules and gasdermin(GSDMD)in the microglia of the retina.Results:HE staining results showed that compared with the Sham group,the retinal cells in the OIR group were disorganized and the thickness of the inner retina was significantly thinner,and the retinal cells in the OIR+Mel group were more neatly arranged compared with those in the OIR group(P<0.05).Immunohistochemical staining results showed that the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR+Mel group decreased signifi-cantly compared with that of the OIR group(P<0.05).Immunofluorescence staining results showed that the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR+Mel group de-creased significantly compared with that in the OIR group(P<0.05);The number of Iba-1+/N-GSDMD+cells in-creased significantly in the OIR group compared with the Sham group,whereas the number of Iba-1+/N-GSDMD+cells in the OIR+Mel group was significantly less than that in the OIR group,but still more than that in the Sham group(P<0.05).Conclusion:Mel inhibits the pyroptosis of retinal microglia,thus attenuates retinal inflammatory injury in OIR rats,and its mechanism may be related to the cGAS-STING-NLRP3 signaling pathway.

Objective:To evaluate the impact of 131I therapy on salivary gland function in postoperative patients with differentiated thyroid cancer (DTC) using quantitative salivary gland scintigraphy (SGS). Methods:Sixty-four patients (23 males, 41 females, age (39.6±13.0) years) were recruited from the Third Affiliated Hospital, Sun Yat-Sen University, all of whom had undergone surgery for DTC between May 2014 and December 2023. SGS was conducted 3 d prior to and 3-6 months following 131I therapy. Salivary gland function parameters, including the uptake index (UI) and excretion fraction (EF) for both (right (R) and left (L)) parotid (P) and submandibular (S) glands (L-pUI, R-pUI, L-sUI, R-sUI, L-pEF, R-pEF, L-sEF, R-sEF), were measured. Patients were divided into two groups (group A: dose of first-time therapy (D f) ≤ 3700MBq; group B: D f>3700MBq) to analyze the characteristics of changes in salivary gland function between the two groups. The relationship between cumulative dose (D c) and salivary gland hypofunction was assessed. Data were analyzed using paired t test, Wilcoxon signed rank test, and χ2 test. The optimal threshold of D c for salivary gland hypofunction was determined through ROC curve analysis. Results:After the first therapy, L-pUI, R-pUI, L-sUI, and R-sUI significantly decreased compared with baseline values in group B ( n=38; t values: from -3.77 to -2.96, all P<0.01). In contrast, there were no significant differences in any salivary gland function parameters between pre-therapy and post-therapy assessments in group A ( n=26; t values: from -1.18 to 0.95, all P>0.05). Fifteen patients underwent therapy twice. After the second therapy, L-pUI, R-pUI, L-sUI, R-sUI, L-pEF, and R-pEF significantly decreased compared to baseline values ( t values: from -6.77 to -3.50, all P<0.01), and with a more pronounced reduction observed in L-pUI and R-pUI compared to the first therapy ( Z values: from -2.10 and -2.67, both P<0.05). The incidence of salivary gland hypofunction after the second therapy was higher than that after the first therapy (10/15 vs 21.9%(14/64); χ2=11.53, P=0.001). The incidence of salivary gland hypofunction was found to be related to D c ( χ2=24.35, P<0.001). Based on ROC curve analyses, patients were likely to experience salivary gland hypofunction when D c exceeded 5550MBq (AUC=0.80(95% CI: 0.69-0.89), P<0.001), with the sensitivity of 13/19, specificity of 91.1%(41/45), positive predictive value of 13/17, and negative predictive value of 87.2%(41/47). Conclusion:Some patients with DTC experience a decline in salivary gland function in the short term (3-6months) after undergoing postoperative therapy with 131I, and the degree and incidence of this decline display in a D c-related manner.

Objective:To report the follow-up status of patients participating phase Ⅲ clinical trial (ZGDD3) of Donafenib tosilate (abbreviated as Donafenib) in the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), and to explore its efficacy, safety and prognostic factors.Methods:This study was a randomized controlled trial, and the clinicopathological data and follow-up results of 29 patients (16 males, 13 females, age 40-68 years) who participated in the clinical trial ZGDD3 between August 2018 and March 2021 were analyzed. Patients were divided into Donafenib group and placebo group using the central dynamic randomization method with the ratio of 2∶1. Adverse reactions (AE) during the trial were observed. Independent-sample t test, Mann-Whitney U test and Fisher exact test were used to analyze the differences of baseline characteristics between the two groups. Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier method was used to draw the survival curve (log-rank test) and Cox regression analysis was used to analyze the prognostic factors. Results:There were 22 patients in Donafenib group and 7 patients in placebo group. There were no significant differences of baseline characteristics between the two groups ( t values: -0.68, Z values: from -1.47 to -0.56, all P>0.05). The follow-up was 32.07(21.07, 49.85) months. During the trial, drug-related AEs occurred in all patients in Donafenib group, mostly was grade Ⅰ-Ⅱ, no grade Ⅳ or Ⅴ AEs were found. The median PFS was significantly longer in Donafenib group than that in placebo group (13.23 vs 4.03 months; χ2=9.68, P=0.002), and the median OS was 55.00 and 24.30 months respectively ( χ2=2.07, P=0.150). Metastasis to less common sites was the independent risk factor for OS (hazard ratio ( HR)=6.789, 95% CI: 1.272-36.246, P=0.025). Conclusions:Donafenib shows good clinical application in the treatment of RAIR-DTC, demonstrating good safety and efficacy. Metastasis to less common sites is closely related to OS.