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 explore the data distribution characteristics of hydrogen and methane breath test (HMBT) in Chinese population and to evaluate its applicability for diagnosing small intestinal bacterial overgrowth (SIBO) in Chinese population.Methods:HMBT data of 18 634 individuals who underwent health check-up nationwide from March 2019 to september 2022 were retrospectively collected, which included the levels of hydrogen and methane at 0, 30, 60, and 90 min. After quality control and data cleaning, the final valid sample size was 12 654 cases, comprising 7 146 SIBO-negative cases and 5 508 SIBO-positive cases. In order to exclude confounding factors such as oral hygiene, the 12 654 cases were divided into D0 and D1 dataset, when the 0 min-value of hydrogen and methane were both lower than the 30 min-value, the 0 min-value was taken as the baseline, and induded into the D0 dataset (5 556 cases), and other situations were induded into the D1 dataset (7 098 cases). There were 2 879 SIBO-negative cases and 2 659 SIBO-positive cases in D0 dataset, and 4 249 SIBO-negative cases and 2 849 SIBO-positive cases in D1 dataset. The hydrogen and methane level at each testing time point in the SIBO-negative and SIBO-positive individuals, the difference between the peak gas level at 90 min and the baseline, and the distribution of time points at which peak level occurred were analyzed. Independent-sample t test and Mann-Whitney U test were used for statistical analysis. Results:The overall SIBO positive rate was 43.53% (5 508/12 654). In SIBO-positive cases the hydrogen level at 0, 30, 60, and 90 min were 9.41×10 -6 (5.01×10 -6, 21.90×10 -6), 11.34×10 -6 (6.13×10 -6, 22.94×10 -6), 18.16×10 -6 (11.03×10 -6, 29.37×10 -6) and 29.59×10 -6 (20.12×10 -6, 43.36×10 -6), respectively, and methane level were 9.13×10 -6 (7.12×10 -6, 12.03×10 -6), 9.23×10 -6 (8.07×10 -6, 12.03×10 -6), 10.21×10 -6 (9.02×10 -6, 13.01×10 -6), and 12.03×10 -6 (10.01×10 -6, 14.11×10 -6), respectively, which were higher than those of SIBO-negative cases (6.04×10 -6 (3.10×10 -6, 11.08×10 -6), 6.04×10 -6 (3.21×10 -6, 10.06×10 -6), 6.95×10 -6 (4.03×10 -6, 11.01×10 -6), 8.96×10 -6 (5.01×10 -6, 13.91×10 -6); 8.04×10 -6 (7.02×10 -6, 10.00×10 -6), 8.03×10 -6 (7.03×10 -6, 9.95×10 -6), 8.04×10 -6 (7.03×10 -6, 10.00×10 -6) 8.98×10 -6 (7.12×10 -6, 10.03×10 -6)], and the differences were statistically significant ( U=1.41×10 7, 1.09×10 7, 6.66×10 6, 4.14×10 6, 1.51×10 7, 1.23×10 7, 1.02×10 7, 8.86×10 6; all P<0.001). In both D0 and D1 datasets, the increase in hydrogen and methane of SIBO positive subgroup were higher than those of SIBO negative subgroup (22.39×10 -6(14.82×10 -6, 33.37×10 -6) vs. 4.82×10 -6(1.96×10 -6, 7.85×10 -6), 20.61×10 -6(7.87×10 -6, 31.44×10 -6) vs. 3.25×10 -6(0.79×10 -6, 7.88×10 -6); 3.98×10 -6(2.87×10 -6, 6.87×10 -6) vs. 1.95×10 -6(0.98×10 -6, 2.99×10 -6), 2.95×10 -6(0.98×10 -6, 4.93×10 -6) vs. 0.98×10 -6(0.00×10 -6, 1.99×10 -6)), and the differences were statistically significant( U=7.24×10 6, 9.72×10 6, 5.74×10 6, 8.27×10 6; all P<0.001). In both D0 and D1 datasets, hydrogen and methane concentrations peaked at 90 min. Conclusion:HMBT can be used for non-invasive diagnosis of SIBO in Chinese population, and the differences in hydrogen and methane concentrations at 90 min of the test have critical value for SIBO diagnosis.

Objective To explore the mediating effect of empowerment ability between type D personality and self-management behavior of patients with diabetes mellitus(DM).Methods A total of 738 patients with type 2 diabetes mellitus(T2DM)hospitalized in the Department of Endocrinology of three tertiary hospitals in Hainan Province from December 2022 to May 2023 were selected and divided into Type D personality(Type D,n=104)group and T2DM group(n=634).The general data,biochemical indexes,scores of negative emotion(NA),social inhibition(SI),empowerment ability,and scale of DM self-management activities(SDSCA)were compared between the two groups,and the correlation between type D personality,empowerment ability and self-management ability was analyzed.The mediating effect model was used to analyze the mediating effect of empowerment ability on the four self-management behaviors of patients with type D personality,and the chain mediating effect model was used to analyze the relationship between type D personality,empowerment ability,self-management behaviors and HbA1c.Results Compared with the T2DM group,HbA1c,proportion of rural residence,proportion of complications≥3,proportion of education level of junior high school or above,proportion of monthly income<3000 yuan,and NA and SI scores were significantly higher in the Type D group(P<0.05).The empowerment ability and scores of healthy diet,regular exercise,blood glucose monitoring and medication compliance were lower in the Type D group than in the T2DM group(P<0.05).Spearman correlation analysis showed that the empowerment ability score was positively correlated with the scores of healthy diet,regular exercise,blood glucose monitoring and medication compliance(P<0.05).NA and SI scores were negatively correlated with empowerment ability score,healthy diet,regular exercise,blood glucose monitoring and medication compliance(P<0.05).The results of model analysis with empowerment ability as the mediating variable showed that type D personality had direct,indirect and total effects on regular exercise,blood glucose monitoring,medication compliance and SDSCA total score(P<0.05),and indirect and total effects on regular diet score(P<0.05).The mediating effect of empowerment ability was significant(Bootstrap CI did not include 0).The chain mediating effect analysis showed that type D personality could indirectly affect HbA1c through empowerment ability,healthy diet(γ=0.389,95%CI 0.206～0.591),and medication compliance(γ=0.149,95%CI 0.040～0.265),and the effect proportion was 39.4%and 14.1%,respectively.Conclusions Type D personality can indirectly influence self-management behavior through the mediating effect of empowerment,and simultaneously affecting HbA1c through the chain effect of empowerment,diet,and medication behavior.

Objective To explore the mediating effect of empowerment ability between type D personality and self-management behavior of patients with diabetes mellitus(DM).Methods A total of 738 patients with type 2 diabetes mellitus(T2DM)hospitalized in the Department of Endocrinology of three tertiary hospitals in Hainan Province from December 2022 to May 2023 were selected and divided into Type D personality(Type D,n=104)group and T2DM group(n=634).The general data,biochemical indexes,scores of negative emotion(NA),social inhibition(SI),empowerment ability,and scale of DM self-management activities(SDSCA)were compared between the two groups,and the correlation between type D personality,empowerment ability and self-management ability was analyzed.The mediating effect model was used to analyze the mediating effect of empowerment ability on the four self-management behaviors of patients with type D personality,and the chain mediating effect model was used to analyze the relationship between type D personality,empowerment ability,self-management behaviors and HbA1c.Results Compared with the T2DM group,HbA1c,proportion of rural residence,proportion of complications≥3,proportion of education level of junior high school or above,proportion of monthly income<3000 yuan,and NA and SI scores were significantly higher in the Type D group(P<0.05).The empowerment ability and scores of healthy diet,regular exercise,blood glucose monitoring and medication compliance were lower in the Type D group than in the T2DM group(P<0.05).Spearman correlation analysis showed that the empowerment ability score was positively correlated with the scores of healthy diet,regular exercise,blood glucose monitoring and medication compliance(P<0.05).NA and SI scores were negatively correlated with empowerment ability score,healthy diet,regular exercise,blood glucose monitoring and medication compliance(P<0.05).The results of model analysis with empowerment ability as the mediating variable showed that type D personality had direct,indirect and total effects on regular exercise,blood glucose monitoring,medication compliance and SDSCA total score(P<0.05),and indirect and total effects on regular diet score(P<0.05).The mediating effect of empowerment ability was significant(Bootstrap CI did not include 0).The chain mediating effect analysis showed that type D personality could indirectly affect HbA1c through empowerment ability,healthy diet(γ=0.389,95%CI 0.206～0.591),and medication compliance(γ=0.149,95%CI 0.040～0.265),and the effect proportion was 39.4%and 14.1%,respectively.Conclusions Type D personality can indirectly influence self-management behavior through the mediating effect of empowerment,and simultaneously affecting HbA1c through the chain effect of empowerment,diet,and medication behavior.

Objective:To explore the data distribution characteristics of hydrogen and methane breath test (HMBT) in Chinese population and to evaluate its applicability for diagnosing small intestinal bacterial overgrowth (SIBO) in Chinese population.Methods:HMBT data of 18 634 individuals who underwent health check-up nationwide from March 2019 to september 2022 were retrospectively collected, which included the levels of hydrogen and methane at 0, 30, 60, and 90 min. After quality control and data cleaning, the final valid sample size was 12 654 cases, comprising 7 146 SIBO-negative cases and 5 508 SIBO-positive cases. In order to exclude confounding factors such as oral hygiene, the 12 654 cases were divided into D0 and D1 dataset, when the 0 min-value of hydrogen and methane were both lower than the 30 min-value, the 0 min-value was taken as the baseline, and induded into the D0 dataset (5 556 cases), and other situations were induded into the D1 dataset (7 098 cases). There were 2 879 SIBO-negative cases and 2 659 SIBO-positive cases in D0 dataset, and 4 249 SIBO-negative cases and 2 849 SIBO-positive cases in D1 dataset. The hydrogen and methane level at each testing time point in the SIBO-negative and SIBO-positive individuals, the difference between the peak gas level at 90 min and the baseline, and the distribution of time points at which peak level occurred were analyzed. Independent-sample t test and Mann-Whitney U test were used for statistical analysis. Results:The overall SIBO positive rate was 43.53% (5 508/12 654). In SIBO-positive cases the hydrogen level at 0, 30, 60, and 90 min were 9.41×10 -6 (5.01×10 -6, 21.90×10 -6), 11.34×10 -6 (6.13×10 -6, 22.94×10 -6), 18.16×10 -6 (11.03×10 -6, 29.37×10 -6) and 29.59×10 -6 (20.12×10 -6, 43.36×10 -6), respectively, and methane level were 9.13×10 -6 (7.12×10 -6, 12.03×10 -6), 9.23×10 -6 (8.07×10 -6, 12.03×10 -6), 10.21×10 -6 (9.02×10 -6, 13.01×10 -6), and 12.03×10 -6 (10.01×10 -6, 14.11×10 -6), respectively, which were higher than those of SIBO-negative cases (6.04×10 -6 (3.10×10 -6, 11.08×10 -6), 6.04×10 -6 (3.21×10 -6, 10.06×10 -6), 6.95×10 -6 (4.03×10 -6, 11.01×10 -6), 8.96×10 -6 (5.01×10 -6, 13.91×10 -6); 8.04×10 -6 (7.02×10 -6, 10.00×10 -6), 8.03×10 -6 (7.03×10 -6, 9.95×10 -6), 8.04×10 -6 (7.03×10 -6, 10.00×10 -6) 8.98×10 -6 (7.12×10 -6, 10.03×10 -6)], and the differences were statistically significant ( U=1.41×10 7, 1.09×10 7, 6.66×10 6, 4.14×10 6, 1.51×10 7, 1.23×10 7, 1.02×10 7, 8.86×10 6; all P<0.001). In both D0 and D1 datasets, the increase in hydrogen and methane of SIBO positive subgroup were higher than those of SIBO negative subgroup (22.39×10 -6(14.82×10 -6, 33.37×10 -6) vs. 4.82×10 -6(1.96×10 -6, 7.85×10 -6), 20.61×10 -6(7.87×10 -6, 31.44×10 -6) vs. 3.25×10 -6(0.79×10 -6, 7.88×10 -6); 3.98×10 -6(2.87×10 -6, 6.87×10 -6) vs. 1.95×10 -6(0.98×10 -6, 2.99×10 -6), 2.95×10 -6(0.98×10 -6, 4.93×10 -6) vs. 0.98×10 -6(0.00×10 -6, 1.99×10 -6)), and the differences were statistically significant( U=7.24×10 6, 9.72×10 6, 5.74×10 6, 8.27×10 6; all P<0.001). In both D0 and D1 datasets, hydrogen and methane concentrations peaked at 90 min. Conclusion:HMBT can be used for non-invasive diagnosis of SIBO in Chinese population, and the differences in hydrogen and methane concentrations at 90 min of the test have critical value for SIBO diagnosis.

Objective:To analyze the clinical and genetic features of four children with pediatric acute liver failure (PALF) caused by neuroblastoma-amplified sequence ( NBAS) gene variant, as well as the correlation between clinical phenotype and genotype. Methods:The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology, Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acute liver failure (PALF) were retrospectively analyzed. The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords " NBAS," "neuroblastoma amplified sequence," "SOPH," "short stature with optic nerve atrophy and Pelger Hu?t anomaly," "liver failure," and "neuroblastoma amplified sequence" indexed in the CNKI database, Wanfang Data Knowledge Service Platform, and PubMed database. The clinical features and gene mutation characteristics of domestic patients were summarized. Results:The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months. All patients developed PALF within 1-2 days after the onset of fever, with symptoms such as vomiting, convulsions, and mental depression or confusion, accompanied by a sharp increase in transaminases, elevated bilirubin and blood ammonia, hyperlactatemia, and hepatomegaly. The PALF gradually improved, and three pediatric patients showed extrahepatic manifestations following antipyretic, fluid replacement, and other symptomatic supportive treatment. Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF. Genetic testing identified eight kinds of NBAS gene variants sites. Family testing validated compound heterozygous variants, which included four missense variants, one nonsense variants, and three frameshift mutations. A literature study revealed that out of 51 Chinese patients with NBAS gene variants, 98.0% (50/51) had liver involvement, and 37 cases showed PALF. A total of 61 mutation sites were identified, with c.3596G>A (45.1%, 23/51) as a hotspot variants. Conclusions:PALF caused by NBAS gene variant has obvious clinical and genetic characteristics, and there is a correlation between genotype and clinical phenotype. The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.

Objective:To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases.Methods:Relevant studies were retrieved from PubMed,EMBASE,Cochrane,Web of Science,Sinomed,CNKI and Wanfang data-bases.The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies,and relevant data were extracted.meta-analysis was performed using RevMan 5.4 and RStudio software,and forest plots were generated.Results:Six randomized con-trolled trials(RCTs)were included.Compared with the control group,denosumab significantly reduced the risk of skeletal-related e-vents(HR=0.78,95％CI:0.62-0.93).In terms of safety,denosumab did not increase the risk of total adverse events,severe adverse events and the adverse events higher than CTC grade 3.Conclusion:Denosumab can delay the time to first skeletal-related event with good safety.However,due to the limitations of this study,further high-quality,large-sample,multicenter RCTs are needed to confirm these findings.

Objective:To investigate the diagnostic value of umbilical cord blood lactic acid and base excess for multi-organ dysfunction following neonatal asphyxia.Methods:A retrospective analysis was conducted on the clinical data of 244 patients at high risk for perinatal asphyxia who received treatment at Dongyang People's Hospital from January 2021 to December 2023.Based on the presence of organ dysfunction, the infants were divided into three groups: a single organ dysfunction group (Group A, n = 55), a multi-organ dysfunction group (Group B, n = 16), and a no organ dysfunction group (Group C, n = 173). Lactic acid levels and base excess values were compared among the three groups. Receiver operating characteristic curves were used to validate the predictive value of lactic acid and base excess values for organ dysfunction. Results:There were no statistically significant differences in general data among the three groups ( P > 0.05). In Group B, the lactic acid level was 15.10 (13.85, 16.83) mmol/L, and the base excess value was 9.80 (6.65, 15.18) mmol/L. In Group A, the lactic acid level was 7.70 (6.25, 11.70) mmol/L, and the base excess value was 5.70 (3.85, 9.60) mmol/L. In Group C, the lactic acid level was 6.80 (4.30, 9.00) mmol/L, and the base excess value was 4.00 (3.00, 6.50) mmol/L. The lactic acid level and base excess value in Group B were significantly higher than those in both Group A and Group C. Additionally, the lactic acid level and base excess value in Group A were significantly greater than those in Group C ( t = 2.60, 20.19, 2.95, 1.92, all P < 0.05). Receiver operating characteristic curve analysis revealed that the combined assessment of base excess value and lactic acid level was more effective than evaluating each parameter individually in predicting the presence of organ damage and multiple organ dysfunction syndrome. Additionally, the detection of base excess value was found to be superior to the measurement of lactic acid level. The areas under the curve values for the combined assessment of base excess value and lactic acid level for the presence of organ damage and multiple organ dysfunction syndrome were 0.694 and 0.856, respectively. In comparison, the AUC values for base excess value detection were 0.678 and 0.846, while the AUC values for lactic acid level measurement were 0.633 and 0.797, respectively. Conclusions:Umbilical cord blood lactic acid and base excess are correlated with organ dysfunction following neonatal asphyxia, and both parameters have clinical value in assessing organ damage.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.