The effects of gonadotropin-releasing hormone agonist on final adult height among girls with early and fast puberty.

Introduction: This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty. Methods: A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children's Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment. Results: The treatment group was significantly older at the time of inclusion(chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht)(PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH-PAH1≥5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year. Discussion: GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain.

COVID-19 risk perception and tourist satisfaction: A mixed-method study of the roles of destination image and self-protection behavior.

This study aimed to examine the effects of COVID-19 risk perception on negative destination image and self-protection behavior, and the resultant effects on tourist satisfaction. Hence, this study applied a continuous interpretive mixed-method design combining quantitative and qualitative analyses. A quantitative survey (n = 486) in the cities of Ningbo, Huangshan, and Chengdu, China, and 19 qualitative interviews were conducted online. The results of the quantitative study show that: (1) Risk perception and negative destination image are antecedent variables influencing tourist satisfaction, and (2) there are significant positive correlations between risk perception and negative destination image, risk perception and tourist self-protection behavior, and negative destination image and tourist self-protection behavior. Moreover, (3) negative destination image had a partial mediating effect between risk perception and satisfaction. Furthermore, to supplement the research data and expand the quantitative findings, this study further examined whether the above variables are related to tourist satisfaction, through in-depth interviews with tourists. The findings showed that COVID-19 risk perception, negative destination image, and self-protection behavior all affect tourist satisfaction. The findings provide valuable crisis management suggestions for the government and should contribute to the efforts of tourist destinations to build a healthy and safe image, thereby contributing to the sustainable development of tourism industries in the post-epidemic era.

Graves disease is more prevalent than Hashimoto disease in children and adolescents with type 1 diabetes.

Introduction: Autoimmune thyroid disease (AITD) is the most common associated autoimmune disorder in type 1 diabetes (T1D). Early detection of AITD is crucial to optimize glycemic control, growth, and intellectual development. In this prospective cohort study, we sought to characterize the prevalence, incident ages and risk factors of AITD in children and adolescents with T1D. Materials and methods: Patients with T1D diagnosed at ≤ 18 years at MacKay Children's Hospital, Taipei, from 1990 to 2019 underwent annual screening for AITD. Institutional Review Board-approved data on age, sex, and disease profile are collected. Statistical analysis was performed by using independent sample t test for continuous variables, chi-squared test for categorical variables, and Kaplan-Meier estimates of cumulative incidence of AITD were calculated. A p value of <0.05 was considered statistically significant. Results: We prospectively followed up 808 patients with T1D, 761 patients were included in the study. Of these patients, 197 (25.9%) of them had thyroid autoimmunity, meaning positivity of thyroid autoantibodies. Females had a higher prevalence of thyroid autoimmunity than males (59.9%, p = 0.012). Altogether, 5.5% patients developed AITD (4.1% had Graves disease; 1.4% had Hashimoto disease), at a mean age of 17.8 ± 8.5 years. The cumulative incidence of AITD at 30 years of disease duration was 0.29 in the total group and was significantly higher in females (0.39, n = 397) than in males (0.15, n = 364, p<0.001). Discussion: In Taiwan, the prevalence of AITD in pediatric population with T1D increases with age, a longer disease duration and female sex. For early detection of autoimmune thyroid disease in Taiwanese children and adolescents with T1D, an annual AITD screening program should be implemented.

Effectiveness of traditional Chinese medicine in treating gastrointestinal dysfunction in patients with acute stroke: a systematic review and meta-analysis of 16 randomized controlled trials.

BACKGROUND: Gastrointestinal dysfunction is one of the complications after stroke. If it is not treated in time, it will affect the rehabilitation process after stroke and reduce the quality of life of patients. In this study, we conducted a systematic review and meta-analysis of the reports on the treatment of gastrointestinal dysfunction after stroke with traditional Chinese medicine (TCM) in recent years to provide evidence for clinical diagnosis and treatment. METHODS: The clinical randomized controlled trials (RCTs) published in Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases from January 2010 to August 2021 were searched. After screening the qualified literatures, literature quality evaluation was performed. The software Stata 16.0 was used to analyze and compare the outcome indicators of TCM and conventional western medicine treatment, and the utility of TCM in the treatment of gastrointestinal disorders after stroke was comprehensively evaluated. RESULTS: A total of 16 studies were finally selected including a total of 1,589. Meta-analysis showed that TCM treatment of gastrointestinal disorders after stroke was more effective than conventional western medicine treatment [odds ratio (OR) =3.94; 95% confidence interval (CI): 2.63 to 5.89; P=0.000]. It was also shown that TCM can reduce the recovery time of bowel sounds and is superior to conventional western medicine [standard mean difference (SMD) =-1.92; 95% CI: -2.51 to -1.34; P=0.000]; reduce defecation and flatulence recovery time (SMD =-2.51; 95% CI: -3.41 to -1.61; P=0.000); increase gastrin level (SMD =0.80; 95% CI: 0.35 to 1.25; P=0.001); increase motilin level (SMD =2.27; 95% CI: 1.55 to 3.00; P=0.000); increase serum albumin level (SMD =0.72; 95% CI: 0.54 to 0.90; P=0.000); increase transferrin levels (SMD =1.11; 95% CI: 0.86 to 1.36; P=0.000); and it can increase serum prealbumin levels (SMD =1.50; 95% CI: 0.78 to 2.22; P=0.000). DISCUSSION: The use of TCM in the treatment of gastrointestinal dysfunction after stroke can effectively reduce symptoms, shorten the recovery time of bowel sounds, the first defecation and flatulence time, promote gastric motility and gastrointestinal hormone secretion, and improve the nutritional status of patients.

TCF21 inhibits tumor-associated angiogenesis and suppresses the growth of cholangiocarcinoma by targeting PI3K/Akt and ERK signaling.

Tumor-associated angiogenesis plays a critical role in the pathogenesis of cholangiocarcinoma (CCA). In this study, we examined the biological effects and molecular mechanisms of transcription factor 21 (TCF21) on CCA-associated angiogenesis. TCF21 expression was compared between 15 pairs of peritumor normal tissues and CCA tissues and also between normal bile duct epithelial cells and two CCA cell lines (QBC-939 and TFK-1) using real-time PCR and Western blot. With the use of both CCA cell lines as the model system, we stably expressed TCF21 by lentiviral transduction (Lv-TCF21). In vivo, we monitored xenograft growth from different CCA cells, measured tumor-associated angiogenesis by histological analysis, and determined the expressions and circulatory levels of VEGFA and PDGF-BB by immunohistochemistry and ELISA, respectively. In vitro, we assessed the effects of conditioned medium collected from different CCA cells on the viability, migration, and tube formation of endothelial cells and explored the significance of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), as well as ERK1/2 signaling in this process. TCF21 was significantly downregulated in CCA tissues or cell lines. Ectopic expression of TCF21 in CCA cells inhibited xenograft growth or tumor-associated angiogenesis in vivo and targeted the expression and secretion of proangiogenic factors, VEGFA and PDGF-BB. In vitro, the conditioned medium collected from Lv-TCF21 CCA cells significantly reduced the viability, migration, and tube formation of endothelial cells. On the molecular level, the targeting of PI3K/Akt and ERK1/2 signaling mediated the anti-angiogenic activity of TCF21. TCF21 presents growth-inhibitory and anti-angiogenic activities, and thus the elevation of TCF21 expression may provide therapeutic benefits for CCA. NEW & NOTEWORTHY Transcription factor 21 (TCF21) is downregulated in cholangiocarcinoma (CCA) tissues or cells. TCF21 inhibits the growth of xenografts derived from CCA cells. TCF21 suppresses in vivo tumor-associated angiogenesis. TCF21 targets expression and production of proangiogenic factors from CCA cells. The targeting of phosphatidylinositol 3-kinase/protein kinase B and ERK1/2 signaling mediates the anti-angiogenesis of TCF21.

Efficacy and safety of chemotherapy with or without targeted therapy in biliary tract cancer: A meta-analysis of 7 randomized controlled trials.

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis. The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87; 95% CI: 1.37-2.57; P=0.000), but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63; 95% CI:-0.45-1.72; P=0.26] and overall survival (OS) (MD=-0.67; 95% CI:-2.54-1.20; P=0.49). In the sub analysis, better ORR was obtained with the addition of EGFR (OR=1.75; 95% CI: 1.20-2.56; P=0.004) and VEGFR (OR=2.5; 95% CI: 1.28-4.87; P=0.007) targeted therapy. Furthermore, the sub analysis of EGFR target showed an significant improvement on PFS (MD=1.36; 95% CI: 0.29-2.43; P=0.01). No significant differences were observed in the incidences of neutropenia (OR=1.37; 95% CI: 0.89-2.12), thrombocytopenia (OR=1.40; 95% CI: 0.83-2.39), anemia (OR=1.21; 95% CI: 0.62-2.38), peripheral neuropathy (OR=1.52; 95% CI: 0.81-2.88), increased AST/ALT (OR=1.40; 95% CI: 0.82-2.39) as well as fatigue (OR=1.65; 95% CI: 0.96-2.84) in either of the treatment groups. In conclusion, better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present meta-analysis without the cost of increased unacceptable toxicities, but regretfully not for the OS. The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS. Otherwise, there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone. Given the paucity of favorable data, we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

Efficacy and Safety of Chemotherapy with or without Targeted Therapy in Biliary Tract Cancer: A Meta-analysis of 7 Randomized Controlled Trials / 华中科技大学学报（医学）（英德文版）

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.