Glioma is the most common primary central nervous system tumor,mainly derived from glial cells,with strong invasiveness,easy recurrence,and poor prognosis.Glioblastoma is a high-grade glioma with the highest degree of malignancy.The clinical treatment method is mainly surgical resection,supplemented by compre-hensive treatment such as radiotherapy,chemotherapy,and electric field therapy,but the treatment effect is not satisfactory.In recent years,with the rapid development of the field of tumor immunotherapy,CD73 is a novel immune checkpoint related to adenosine metabolism,which can promote tumor progression by inhibiting anti-tumor immune responses and promoting angiogenesis.This article systematically reviews the mechanism of action of CD73 and discusses its biological role and application in glioma,aiming to provide potential treatment options for glioma patients.

With the increase of its incidence,differentiated thyroid carcinoma(DTC)has become a global concern.Over the recent decades,the guidelines for the management of DTC have been kept updating along with the development of nuclear medicine theranostics and molecular biology.The present article will systematically expound on the 131I pre-treatment evaluation system based on the clinical practice of nuclear medicine theranostics,the latest evidence-based medical evidence,and guideline recommendations.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To investigate the value of cellular immune status before initial 131I treatment for predicting treatment response in young and middle-aged patients with papillary thyroid cancer (PTC). Methods:From March 2018 to April 2019, 150 young and middle-aged patients with PTC (46 males, 104 females, age (40.0±9.8) years) who underwent total thyroidectomy and neck lymph node dissection in the Affiliated Hospital of Qingdao University were enrolled retrospectively. All patients underwent radioablation 1-2 months after operation, and the serum lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD4/CD8) as well as natural killer (NK) cells were detected 1 d before the initial 131I treatment. Patients were divided into excellent response (ER) group and non-ER group according to the response of 6-12 months after 131I treatment. Clinicopathological characteristics, preablative stimulated thyroglobulin (psTg), initial 131I dose and lymphocyte subsets that might affect the response to 131I treatment were analyzed (independent-sample t test, Mann-Whitney U test, χ2 test, multiple logistic regression analysis). ROC curve analysis was used to evaluate the predictive value of significant factors for non-ER. Results:Of 150 patients, 84 cases were in ER group (56.00%), and 66 cases (44.00%) were in non-ER group. Age ( z=-2.86, P=0.004), M stage ( χ2=13.64, P<0.001), psTg ( z=-8.94, P<0.001), initial 131I dose ( z=-7.60, P<0.001), CD4 + ( t=2.50, P=0.014), CD4/CD8 ( z=-2.22, P=0.027) of the two groups were significantly different. Multivariate analysis showed that psTg (odds ratio ( OR)=1.27, 95% CI: 1.16-1.40, P<0.001) and CD4/CD8 ( OR=0.39, 95% CI: 0.15-0.99, P=0.048) were independent factors for predicting 131I treatment response. The cut-off values of psTg and CD4/CD8 for predicting non-ER were 6.78 μg/L and 1.67, respectively. Conclusions:Cellular immune status before initial 131I treatment may predict treatment response in young and middle-aged patients with PTC. It indicates non-ER response when Tg is higher than 6.78 μg/L and CD4/CD8 is lower than 1.67.

Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.

Objective:To investigate the effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer (DTC) who were evaluated as indeterminate response (IDR) after surgery and before 131I therapy. Methods:A total of 281 DTC patients (89 males, 192 females, age (38.4±10.2)years ) assessed as IDR before 131I therapy and after total or near-total thyroidectomy in the Department of Nuclear Medicine of Peking Union Medical College Hospital from April 2009 to March 2022 were retrospectively analyzed. Patients were divided into 131I therapy group ( 131I group) and just thyroid stimulating hormone (TSH) suppressive therapy group (TSH group) according to whether receiving 131I therapy, and the efficacies of two groups at the end of follow-up were compared. Subgroup analysis was conducted in different risk stratifications (low-risk, moderate-risk and high-risk), positive thyroglobulin antibody (TgAb) group (TgAb≥115 kU/L) and negative TgAb group (TgAb<115 kU/L). For patients with positive TgAb, the duration and rate for TgAb declining to negative level under the 2 regimens were compared. Independent-sample t test, Mann-Whitney U test, χ2 test and Fisher exact test were performed to compare the differences between groups. Results:Median follow-up time was 39(6-146) months. There was no statistical difference between patients in 131I group and TSH group in baseline characteristics, and the efficacies at the end of follow-up was similar between the 2 groups ( χ2=6.50, P=0.075). For low-, moderate- and high-risk stratification, there were also no statistical differences of response to 2 regimens ( P=0.221; χ2=4.21, P=0.223; χ2=3.01, P=0.274). Similar results were showed for patients with positive and negative TgAb ( n=50, n=231; χ2=4.02, P=0.242; χ2=3.14, P=0.341). For patients with positive TgAb, the duration and rate for TgAb declining to negative level were not statistically different either between 2 regimens (71.0%(22/31) vs 14/19, χ2=0.04, P=0.836; 7.0(5.0, 9.3) vs 7.0(5.0, 7.3) months, z=-0.89, P=0.375). Conclusion:For DTC patients assessed as IDR after surgery, 131I therapy may not provide more benefit than follow-up with TSH suppressive therapy.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To analyze the relationship between serologically biochemical response and the disease progression trend and prognosis evaluated by traditional structural imaging in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated by apatinib.Methods:A retrospective study was performed on apatinib-treated (phase Ⅱ) patients ( n=19; 9 males, 10 females; age 46.0 (41.0, 57.5) years) with locally advanced/metastatic RAIR-DTC in Peking Union Medical College Hospital from March 2016 to June 2022. The relationships between serum thyroglobulin (Tg) and response evaluation criteria in solid tumors (RECIST) 1.1 structural imaging efficacy evaluation and disease progression trend were analyzed. The relationships between change of Tg after dose adjustment and the change of maximum diameter of target lesions in structure imaging were also discussed. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze the data. Results:During the median 49.41 months follow-up, the baseline Tg was 363.20(13.08, 2 490.50) μg/L. The Tg time-to-response was 0.47(0.47, 0.98) months, which was 1.80 (1.30, 1.90) months for RECIST 1.1. After 2, 4 and 8 weeks of initial treatment, the median Tg of the whole cohort decreased by 38.68%, 64.70% and 78.94%, respectively. After 8 weeks, the reducing degree of maximum diameter of target lesions was 33.48%. According to the best response, patients were divided into two groups: partial response (PR) group ( n=15) and stable disease (SD) group ( n=4). The median decreasing degree of Tg in PR group and that in SD group were 87.00% and 28.79%, and the reducing degree of maximum diameter of target lesions in corresponding groups were 45.00% and 21.22%. According to the final efficacy evaluation, patients were further divided into two groups: progressive disease (PD) group ( n=13) and non-PD (including PR and SD) group ( n=5). The median increasing degree of Tg in PD group was higher than that in non-PD group (381.55% vs 175.43%; U=10.00, P=0.037). The increasing degree of Tg and that of the maximum diameter of target lesions were 167.31% and 2.14% after the 1st adjustment, which were 231.06% and 9.73% after the 2nd adjustment. The differences of changes in Tg and maximum diameter of target lesions before and after the 1st dose adjustment were statistically significant ( z values: -3.06 and -2.23, P values: 0.002 and 0.026). Conclusion:During the apatinib treatment of RAIR-DTC, Tg can reflect the therapeutic effect of apatinib earlier than traditional imaging (RECIST 1.1), indicating the disease progression trend more sensitively.

Poor dietary habit is an important cause of the global prevalence of metabolic associated fatty liver disease (MAFLD), and the adjustment of dietary pattern is the cornerstone of MAFLD management. In recent years, a large number of new dietary intervention methods have been proposed and applied in the treatment of MAFLD, including calorie restrict diet, low-carbohydrate diet, low-glycemic index diet, low free sugar diet, intermittent fasting pattern, high protein diet, and Mediterranean diet, and these new methods have different effects in clinical practice. This article introduces the treatment concepts and practical methods of these new dietary treatment strategies and the evidence of their benefits in the treatment of MAFLD in China and globally, so as to provide a new perspective for clinicians to guide patients to achieve individualized nutritional therapy.

Background: Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods: Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results: There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. Conclusion A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.