Objective:To explore the causal relationship between human circulating inflammatory proteins and pressure injury (PI) mediated by human blood metabolites.Methods:This study employed a method of analysis based on mediated Mendelian randomization (MR). Genome-wide association study data of 91 human circulating inflammatory proteins (14 824 samples), 1 400 human blood metabolites (8 299 samples), and PI (467 794 samples) were retrieved. A significance threshold was established and single nucleotide polymorphisms (SNPs) were used as instrumental variables with the influence of weak instrumental variables excluded. Forward two-sample MR (TSMR) was employed to analyze the causal relationship between circulating inflammatory proteins and PI. The inverse variance weighted (IVW) method served as the primary approach, and the results were validated using the weighted median method, MR-Egger regression, weighted mode method, and simple mode method (the specific analytical methods were the same below). For the SNPs of selected circulating inflammatory proteins, sensitivity analysis was employed, including heterogeneity which was evaluated by the Cochran Q test, horizontal pleiotropy which was evaluated by the MR-Egger intercept test and MR-PRESSO outlier test, and reliability which was evaluated via leave-one-out analysis. Based on reverse TSMR analysis, the IVW method, MR-Egger regression, weighted median method, simple mode method, and weighted mode method were employed to evaluate whether a reverse causal relationship exists between PI and the selected circulating inflammatory proteins. Forward TSMR was employed to analyze the causal relationship between selected circulating inflammatory proteins and 1 400 blood metabolites and to select the blood metabolites. For the SNPs of selected circulating inflammatory proteins, sensitivity analysis was employed as before. Forward TSMR was employed to analyze the causal relationship between selected blood metabolites and PI. For the SNPs of selected blood metabolites, sensitivity analysis was employed as before (except for the leave-one-out analysis). Finally, the mediation effect values and mediation effect ratios of selected blood metabolites in the mediation effect between selected circulating inflammatory proteins and PI were calculated. Results:Five circulating inflammatory proteins and 59 blood metabolites were identified as meeting the exposure factor criteria, with the number of SNPs reaching the significance threshold ranging from 16 to 1 484. All the SNPs were confirmed as strong instrumental variables. The IVW method revealed significant causal relationships between interleukin-33 (IL-33), CUB domain-containing protein 1, IL-5, stem cell factor, and tumor necrosis factor and PI (with odds ratios of 1.29, 1.20, 1.25, 1.16, and 1.23, respectively, 95% confidence intervals of 1.07-1.55, 1.05-1.36, 1.04-1.51, 1.00-1.34, and 1.03-1.47, respectively, P<0.05). The weighted median method confirmed significant causal relationships between IL-33 and IL-5 and PI (with odds ratios of 1.37 and 1.37, respectively, 95% confidence intervals of 1.05-1.79 and 1.04-1.80, respectively, P<0.05). Among these, the most significant causal relationship was observed between IL-33 and PI ( P<0.01). The Cochran Q test indicated no significant heterogeneity in the SNPs of IL-33 which had significant causal relationship with PI ( Q=18.78, P>0.05). The MR-Egger intercept test (with intercept absolute value <0.001, P>0.05) and MR-PRESSO outlier test (with RSSobs value of 20.37, P>0.05) both indicated no significant horizontal pleiotropy in the SNPs of IL-33 which had significant causal relationship with PI. The leave-one-out analysis showed that the significant causal relationship between IL-33 and PI was reliable after removing the SNPs one by one. No significant reverse causal relationships were observed between PI and IL-33 through the IVW method, MR-Egger regression, weighted median method, simple mode method, or weighted mode method (with odds ratios of 1.00, 1.00, 1.00, 1.00, and 1.01, respectively, 95% confidence intervals of 0.98-1.02, 0.96-1.03, 0.97-1.03, 0.93-1.08, and 0.94-1.09, respectively, P>0.05). The IVW method revealed significant causal relationships between IL-33 and 59 blood metabolites (with odds ratios of 0.79-1.20, 95% confidence intervals lower limit range of 0.70-1.07 and upper limit range of 0.89-1.37, P<0.05). The MR-Egger regression and weighted median method confirmed significant causal relationships between IL-33 and 8 and 10 blood metabolites, respectively (with odds ratios of 0.63-1.70 and 0.82-1.21, respectively, 95% confidence intervals lower limit ranges of 0.43-1.29 and 0.70-1.14, respectively, 95% confidence intervals upper limit ranges of 0.94-2.25 and 0.97-1.42, respectively, P values all <0.05). Among these, the most significant causal relationship was observed between blood metabolite X-12798 and IL-33 (with odds ratio of 0.79, 95% confidence interval of 0.70-0.89, P<0.05). The Cochran Q test indicated no significant heterogeneity in the SNPs of IL-33 which had significant causal relationship with blood metabolite X-12798 ( Q=24.94, P>0.05). The MR-Egger intercept test (with intercept absolute value of 0.012, P>0.05) and MR-PRESSO outlier test (with RSSobs value of 27.45, P>0.05) both indicated no significant horizontal pleiotropy in the SNPs of IL-33 which had significant causal relationship with blood metabolite X-12798. The leave-one-out analysis showed that the significant causal relationship between IL-33 and blood metabolite X-12798 was reliable after removing the SNPs one by one. The IVW method revealed significant causal relationship between blood metabolite X-12798 and PI (with odds ratio of 0.92, 95% confidence interval of 0.84-0.99, P<0.05). The MR-Egger regression and weighted median method both confirmed significant causal relationship between blood metabolite X-12798 and PI (with odds ratios of 0.87 and 0.89, respectively, 95% confidence intervals of 0.77-0.98 and 0.80-0.99, respectively, P<0.05). The Cochran Q test indicated no significant heterogeneity in the SNPs of blood metabolite X-12798 which had significant causal relationship with PI ( Q=23.45, P>0.05). The MR-Egger intercept test (with intercept absolute value of 0.015, P>0.05) and MR-PRESSO outlier test (with RSSobs value of 26.01, P>0.05) both indicated no significant horizontal pleiotropy in the SNPs of blood metabolite X-12798 which had significant causal relationship with PI. The mediation effect value was 0.02 and the mediation effect ratio was 8.27%. Conclusions:Significant causal relationships are observed among human circulating inflammatory proteins, blood metabolites, and PI, with the association between circulating inflammatory protein IL-33 and PI being mediated by blood metabolite X-12798.

Objective:To explore the causal relationship between human circulating inflammatory proteins and pressure injury (PI) mediated by human blood metabolites.Methods:This study employed a method of analysis based on mediated Mendelian randomization (MR). Genome-wide association study data of 91 human circulating inflammatory proteins (14 824 samples), 1 400 human blood metabolites (8 299 samples), and PI (467 794 samples) were retrieved. A significance threshold was established and single nucleotide polymorphisms (SNPs) were used as instrumental variables with the influence of weak instrumental variables excluded. Forward two-sample MR (TSMR) was employed to analyze the causal relationship between circulating inflammatory proteins and PI. The inverse variance weighted (IVW) method served as the primary approach, and the results were validated using the weighted median method, MR-Egger regression, weighted mode method, and simple mode method (the specific analytical methods were the same below). For the SNPs of selected circulating inflammatory proteins, sensitivity analysis was employed, including heterogeneity which was evaluated by the Cochran Q test, horizontal pleiotropy which was evaluated by the MR-Egger intercept test and MR-PRESSO outlier test, and reliability which was evaluated via leave-one-out analysis. Based on reverse TSMR analysis, the IVW method, MR-Egger regression, weighted median method, simple mode method, and weighted mode method were employed to evaluate whether a reverse causal relationship exists between PI and the selected circulating inflammatory proteins. Forward TSMR was employed to analyze the causal relationship between selected circulating inflammatory proteins and 1 400 blood metabolites and to select the blood metabolites. For the SNPs of selected circulating inflammatory proteins, sensitivity analysis was employed as before. Forward TSMR was employed to analyze the causal relationship between selected blood metabolites and PI. For the SNPs of selected blood metabolites, sensitivity analysis was employed as before (except for the leave-one-out analysis). Finally, the mediation effect values and mediation effect ratios of selected blood metabolites in the mediation effect between selected circulating inflammatory proteins and PI were calculated. Results:Five circulating inflammatory proteins and 59 blood metabolites were identified as meeting the exposure factor criteria, with the number of SNPs reaching the significance threshold ranging from 16 to 1 484. All the SNPs were confirmed as strong instrumental variables. The IVW method revealed significant causal relationships between interleukin-33 (IL-33), CUB domain-containing protein 1, IL-5, stem cell factor, and tumor necrosis factor and PI (with odds ratios of 1.29, 1.20, 1.25, 1.16, and 1.23, respectively, 95% confidence intervals of 1.07-1.55, 1.05-1.36, 1.04-1.51, 1.00-1.34, and 1.03-1.47, respectively, P<0.05). The weighted median method confirmed significant causal relationships between IL-33 and IL-5 and PI (with odds ratios of 1.37 and 1.37, respectively, 95% confidence intervals of 1.05-1.79 and 1.04-1.80, respectively, P<0.05). Among these, the most significant causal relationship was observed between IL-33 and PI ( P<0.01). The Cochran Q test indicated no significant heterogeneity in the SNPs of IL-33 which had significant causal relationship with PI ( Q=18.78, P>0.05). The MR-Egger intercept test (with intercept absolute value <0.001, P>0.05) and MR-PRESSO outlier test (with RSSobs value of 20.37, P>0.05) both indicated no significant horizontal pleiotropy in the SNPs of IL-33 which had significant causal relationship with PI. The leave-one-out analysis showed that the significant causal relationship between IL-33 and PI was reliable after removing the SNPs one by one. No significant reverse causal relationships were observed between PI and IL-33 through the IVW method, MR-Egger regression, weighted median method, simple mode method, or weighted mode method (with odds ratios of 1.00, 1.00, 1.00, 1.00, and 1.01, respectively, 95% confidence intervals of 0.98-1.02, 0.96-1.03, 0.97-1.03, 0.93-1.08, and 0.94-1.09, respectively, P>0.05). The IVW method revealed significant causal relationships between IL-33 and 59 blood metabolites (with odds ratios of 0.79-1.20, 95% confidence intervals lower limit range of 0.70-1.07 and upper limit range of 0.89-1.37, P<0.05). The MR-Egger regression and weighted median method confirmed significant causal relationships between IL-33 and 8 and 10 blood metabolites, respectively (with odds ratios of 0.63-1.70 and 0.82-1.21, respectively, 95% confidence intervals lower limit ranges of 0.43-1.29 and 0.70-1.14, respectively, 95% confidence intervals upper limit ranges of 0.94-2.25 and 0.97-1.42, respectively, P values all <0.05). Among these, the most significant causal relationship was observed between blood metabolite X-12798 and IL-33 (with odds ratio of 0.79, 95% confidence interval of 0.70-0.89, P<0.05). The Cochran Q test indicated no significant heterogeneity in the SNPs of IL-33 which had significant causal relationship with blood metabolite X-12798 ( Q=24.94, P>0.05). The MR-Egger intercept test (with intercept absolute value of 0.012, P>0.05) and MR-PRESSO outlier test (with RSSobs value of 27.45, P>0.05) both indicated no significant horizontal pleiotropy in the SNPs of IL-33 which had significant causal relationship with blood metabolite X-12798. The leave-one-out analysis showed that the significant causal relationship between IL-33 and blood metabolite X-12798 was reliable after removing the SNPs one by one. The IVW method revealed significant causal relationship between blood metabolite X-12798 and PI (with odds ratio of 0.92, 95% confidence interval of 0.84-0.99, P<0.05). The MR-Egger regression and weighted median method both confirmed significant causal relationship between blood metabolite X-12798 and PI (with odds ratios of 0.87 and 0.89, respectively, 95% confidence intervals of 0.77-0.98 and 0.80-0.99, respectively, P<0.05). The Cochran Q test indicated no significant heterogeneity in the SNPs of blood metabolite X-12798 which had significant causal relationship with PI ( Q=23.45, P>0.05). The MR-Egger intercept test (with intercept absolute value of 0.015, P>0.05) and MR-PRESSO outlier test (with RSSobs value of 26.01, P>0.05) both indicated no significant horizontal pleiotropy in the SNPs of blood metabolite X-12798 which had significant causal relationship with PI. The mediation effect value was 0.02 and the mediation effect ratio was 8.27%. Conclusions:Significant causal relationships are observed among human circulating inflammatory proteins, blood metabolites, and PI, with the association between circulating inflammatory protein IL-33 and PI being mediated by blood metabolite X-12798.

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.

The poor prognosis of refractory thyroid cancer is the critical factor affecting the survival of patients with thyroid cancer. At present, multi-kinase inhibitors, surgery, particle implantation and other therapeutic methods are commonly used in clinical practice, which can improve the prognosis of patients to some extent, but the overall efficacy is still unsatisfactory. In recent years, immunotherapy has shown high efficacy, safety and reliability in the treatment of many tumors. In this article, the mechanism, current situation, method and prospect of immunotherapy in patients with refractory thyroid cancer are presented.

Objective:To explore the clinical pathological characteristics and initial 131I curative responses of familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC). Methods:A total of 66 FDTC patients (19 males, 47 females, age (39.8±11.7) years) and 1 701 SDTC patients (442 males, 1 259 females, age (40.9±11.3) years) who underwent 131I therapy in Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2010 and August 2018 were retrospectively enrolled. The clinical pathological characteristics, preablative stimulated thyroglobulin (ps-Tg), preablative stimulated thyroglobulin antibody (ps-TgAb) and response to initial therapy (excellent response, indeterminate response, biochemical incomplete response, structural incomplete response) of two groups were analyzed and compared. The clinical pathological parameters included age, gender, pathological type, tumour maximum diameter, bilateral, multifoci, nodules goiter, thyroiditis, thyroid membrane invasion, lymph node metastasis (LNM), invasion of the surrounding soft tissues, distant metastasis, TNM staging and American Thyroid Association (ATA) risk stratification (low-risk, intermediate-risk, high-risk). χ2 test or Fisher exact test and independent-sample t test were used to compare the data between two groups. Results:Comparing with SDTC group, FDTC group showed higher proportion of bilateral foci (45.5%(30/66) vs 31.2%(530/1 701); χ2=5.999, P=0.010), thyroid membrane invasion (43.9%(29/66) vs 26.6%(452/1 701); χ2=9.672, P=0.002) and distant metastasis (15.2%(10/66) vs 6.2%(105/1 701); χ2=8.418, P=0.004). There was a statistical difference in risk stratification between two groups (high-risk: 18.2%(12/66) vs 9.2%(156/1 701); intermediate-risk: 68.2%(45/66) vs 72.7%(1 237/1 701); low-risk: 13.6%(9/66) vs 18.1%(308/1 701); χ2=6.898, P=0.030). But the tumor maximum diameter of FDTC group was smaller than that of SDTC group ((1.24±0.74) vs (1.50±0.92) cm; t=-2.275, P=0.020). There were no significant differences in other clinical pathological parameters between FDTC group and SDTC group ( t=-0.804, χ2 values: 0.101-5.359, all P>0.05). There were no significant differences between two groups in the postoperation ps-Tg, ps-TgAb levels and the response to initial therapy after 131I treatment ( χ2 values: 0.059-1.915, all P>0.05). Conclusions:The FDTC group displays distinct characteristics as increased aggressiveness at diagnosis. But after accurately treatment, there is no significant difference in the response to therapy between two groups.

At the end of December 2019, acute respiratory infectious diseases caused by a new type of coronavirus were prevalent in Wuhan and other cities of China. Different from radiology examinations, the protocols of nuclear medical imaging examinations are complicated, in which more workplaces and staff are needed, resulting more complex management of patients and higher protection requirements. Combined with the characteristics of SPECT and PET imaging procedures, this paper puts forward some suggestions on the protective process of imaging examinations for patients with confirmed or suspected novel coronavirus infection. The main purpose is to protect medical staff from virus infection, effectively reduce the risk of virus transmission during the examination process, and ensure the medical quality and safety.

Objective:To investigate the correlation between 131I uptake and therapeutic efficacy in metastatic differentiated thyroid carcinoma (DTC). Methods:The clinical data of 138 patients with metastatic DTC (42 males, 96 females, age range: 8-74 years) treated with 131I in nuclear medicine departments of 31 centers all over China were retrospectively analyzed. The lesional 131I uptake was quantitatively analyzed with target-to-nontarget (T/NT) ratio through the regions of interest in metastatic lesions confirmed by either planar or tomographic 131I SPECT/CT imaging. The efficacies of 131I treatment on the metastatic DTC were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progress disease (PD) based on the change of the lesion diameter before and after the treatment. Factors which may affect therapeutic efficacy were assessed by the univariate (Kruskal-Wallis rank sum test, χ2 test and one-way analysis of variance) and binary logistic regression analyses. The receiver operating characteristic (ROC) curve of lesional T/NT ratio to predict the ineffectiveness of 131I therapy was performed. Results:A total of 1 165 efficacies were evaluated. The planar imaging results ( n=653) showed that there was no statistically significant difference of T/NT ratio among CR, PR, SD and PD groups ( χ2=4.15, P>0.05). The tomographic imaging results ( n=512) suggested CR, PR, SD and PD in 7.6%(39/512), 65.8%(337/512), 22.9%(117/512), and 3.7%(19/512) of individuals, respectively, and the T/NT ratio among the four groups was significantly different ( χ2=30.46, P<0.01). The univariate analysis also showed that age, stimulated thyroglobulin(sTg), 131I dose were the factors affecting therapeutic efficacy ( F or χ2 values: 2.561, 7.095 and 8.799, all P<0.05). Furthermore, binary logistic regression analysis revealed that older patients (odds ratio ( OR)=1.034, P=0.022) or patients with lower lesional T/NT ( OR=1.086, P=0.006) had a higher probability of ineffectiveness. The area under ROC curve for T/NT ratio to predict ineffectiveness was 0.726, and the cut-off value was 6.2, with a sensitivity of 78.7%(107/136) and a specificity of 73.1%(275/376). Conclusions:131I therapy is an effective treatment for metastatic DTC. The age at the time of metastatic diagnosis and the lesional T/NT ratio are independent influential factors for ineffectiveness of 131I therapy. When the leisonal T/NT ratio is lower than 6.2, the inefficiency of 131I is higher.

Objective:To evaluate the effects of different sphere volumes, target background ratio (T/B) and post-processing correction techniques on the quantitative results of 99Tc m SPECT/CT. Methods:Six spheres with different diameters (37, 28, 22, 17, 13, 10 mm) in National Electrical Manufacturers Association International Electrotechnical Commission (NEMA IEC) models were filled with a mixture of 0.54 MBq/ml 99Tc m and iodixanol. The mixture iodine content was about 0.3%(135 mg), which led to different T/B (32∶1, 16∶1, 8∶1, 4∶1) by changing the radioactivity concentration of the cylinder. Routine imaging was performed on different T/B phantoms which were scanned by SPECT/CT. The CT threshold method was used for the delineation of volume of interest (VOI). Then the same processing correction technique and ordered-subsets expectation maximization (OSEM) parameters were used to calculate the radioactivity concentrations of different spheres, and further compared with the true values, and the accuracies were calculated. Pearson correlation analysis was applied to evaluate the relationships between sphere volume, T/B and quantitative results. The sphere with T/B of 32∶1 and diameter of 37 mm were processed by 3 correction techniques (CT attenuation correction (CTAC)+ scatter correction (SC)+ resolution recovery (RR); CTAC+ SC; CTAC+ RR). One-way analysis of variance and the least significant difference t test were used to analyzed the effects of 3 correction techniques on the quantitative results and image contrasts. Results:There were significant relationships between the sphere volumes, T/B and the quantitative accuracy ( r values: 0.757, 0.409, both P<0.05). There were significant differences of 3 correction techniques on the quantitative results and image contrast ( F values: 139.665 and 38.905, both P<0.001). Among them, the quantitative error of CTAC+ SC+ RR was lower than that of CTAC+ SC ((9.63±8.82)% vs (38.89±2.17)%; P<0.001), and similar to that of CTAC+ RR ((8.70±6.64)%; P>0.05). The quantitative error of CTAC+ RR was lower than that of CTAC+ SC ( P<0.001). The image contrast of CTAC+ SC+ RR was higher than that of CTAC+ SC ((93.45±0.91)% vs (92.41±0.25)%; P<0.001) and the image contrast of CTAC+ SC was higher than that of CTAC+ RR ((91.37±0.87)%; P<0.001). Conclusions:The larger sphere volume and the higher T/B, the more quantitative accuracy. The volume has a more significant effect on quantitative accuracy than T/B. Choosing the appropriate correction technique is helpful to quantitative accuracy improvement. It is suggested to use CTAC+ SC+ RR in quantitative processing.

At the end of December 2019, acute respiratory infectious diseases caused by a new type of coronavirus were prevalent in Wuhan and other cities of China. Different from radiology examinations, the protocols of nuclear medical imaging examinations are complicated, in which more workplaces and staff are needed, resulting more complex management of patients and higher protection requirements. Combined with the characteristics of SPECT and PET imaging procedures, this paper puts forward some suggestions on the protective process of imaging examinations for patients with confirmed or suspected noval coronavirus infec- tion. The main purpose is to protect medical staff from virus infection, effectively reduce the risk of virus transmission during the examination process, and ensure the medical quality and safety.