Clinical Characteristics of Adrenal Hemangioma.

Objective: Adrenal hemangioma (AH) is a rare, benign adrenal tumor often detected incidentally by imaging. This retrospective study aimed to investigate the clinical characteristics of AH, including clinical and diagnostic imaging features, to improve the recognition and understanding of AH. Methods: We retrospectively analyzed the medical records of patients diagnosed with AH at Peking Union Medical College Hospital between 2008 and 2022. Clinical manifestations, adrenal hormone levels, imaging findings, treatment approaches, and pathological results were collected and analyzed. Results: Of the 7140 adrenal tumor patients, 40 (0.56%) had AH confirmed postoperatively. The mean age at diagnosis was 53.9 years, with a female predominance. Most (70%) were asymptomatic and diagnosed incidentally. Misdiagnosis before surgery was common, most frequently as pheochromocytoma. Imaging characteristics, especially enhanced computed tomography, revealed distinct features based on tumor size. Surgery was the main treatment, with laparoscopic adrenalectomy preferred. Conclusion: This study elucidates the clinical characteristics of AH, including demographics, diagnostic challenges, and imaging features. AH often presents incidentally and is frequently misdiagnosed preoperatively. Recognizing distinct imaging characteristics and appropriate surgical management can enable accurate diagnosis and optimal treatment.

Intranasal G5-BGG/pDNA Vaccine Elicits Protective Systemic and Mucosal Immunity against SARS-CoV-2 by Transfecting Mucosal Dendritic Cells.

Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA (pSP), named G5-BGG/pSP complex, is developed to activate NALT and to promote both systemic and mucosal immune defense. G5-BGG/pSP could traverse mucosal barriers and deliver DNA to the target cells because of its superior nasal retention and permeability characteristics. The intranasal G5-BGG/pSP complex elicits robust antigen-specific immune responses, such as the notable production of IgG antibody against several virus variants. More importantly, it induces elevated levels of antigen-specific IgA antibody and a significant expansion of the lung-resident T lymphocyte population. Notably, the intranasal G5-BGG/pSP complex results in antigen expression and maturation of dendritic cells in nasal mucosae. These findings exhibit the potential of G5-BGG, a novel cationic material, as an effective gene carrier for intranasal vaccines to obtain robust systemic and mucosal immunity.

Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

PURPOSE: Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40 mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. METHODS: Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39 mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. RESULTS: Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1 week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36 months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. CONCLUSIONS: With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.

Effect of Isoflavones on Blood Lipid Alterations in Postmenopausal Females: A Systematic Review and Meta-Analysis of Randomized Trials.

The effects of isoflavones on postmenopausal female's blood lipid profile have yielded conflicting results in previous studies. Further investigation is necessary to determine the potential benefits of isoflavone therapy in managing cardiovascular health in this population. This meta-analysis aimed to assess the effects of isoflavones on blood lipid concentrations in postmenopausal females. A comprehensive search was conducted in major databases for randomized controlled trials published between 2000 and 2023. Eighteen studies were included in the analysis, which examined the impact of isoflavone intake on blood lipids in postmenopausal females. Isoflavone consumption resulted in a significant reduction in triacylglycerol (TG) concentrations (-12.50 mg/dL; 95% CI: -23.09, -1.91) and a modest increase in high-density lipoprotein cholesterol (HDL cholesterol) concentrations (1.83 mg/dL; 95% CI: 0.03, 3.64). Subgroup analysis showed that isoflavones significantly decreased TG (-15.79 mg/dL; 95% CI: -28.36, -3.22) and increased HDL cholesterol (2.49 mg/dL; 95% CI: 1.80, 3.19) in postmenopausal females under 65 y old. No significant effects were observed in females over 65 y old. Both low (≤80 mg/d) and high (>80 mg/d) doses of isoflavones exhibited TG-lowering effects, whereas only the high dose increased HDL cholesterol. Longer treatment duration (≥24 wk) was associated with a significant reduction in TG, whereas HDL cholesterol improvement occurred during the early period (<24 wk) of supplementation. The consumption of isoflavones resulted in a significant reduction in TG concentrations and an increase in HDL cholesterol concentrations among postmenopausal females under 65 y of age.

Incidence and risk factors of cancers in acromegaly: a Chinese single-center retrospective study.

PURPOSE: To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1). METHODS: A retrospective cohort including 1738 consecutive hospitalized patients with acromegaly in a single referral center between 2012 and 2020 (mean follow-up 4.3 years). A gender- and age-matched case-control study (280 patients from the cohort) was performed for risk factor analysis. RESULTS: One hundred thirteen malignancies (67 diagnosed after acromegaly) were observed. The overall newly-diagnostic cancer risk of acromegaly was higher than the general population (standardized incidence ratio (SIR) 2.81; 95% CI 2.18-3.57). The risk of thyroid cancer (n = 33, SIR 21.42; 95% CI 13.74-30.08) and colorectal cancer (n = 8, SIR 3.17; 95% CI 1.37-6.25) was elevated. In the overall cohort, IGF-1 (ULN: 1.27 vs. 0.94, p = 0.057), GH (1.30 vs. 1.00 ng/ml, p = 0.12), and disease-controlled rate (34.9% vs. 45.9%, p = 0.203) at the last visit did not reach significance between patients with and without post-diagnostic cancer. In the case-control study, GH (1.80 vs. 0.90 ng/ml, p = 0.018) and IGF-1 (ULN: 1.27 vs. 0.91, p = 0.003) at the last visit were higher in patients with post-diagnostic cancers, with a lower disease-controlled rate. Elder age was a risk factor for cancer. Other metabolic comorbidities and the size of pituitary tumors were similar. CONCLUSION: The risk of malignancies, especially thyroid cancer, was increased in patients with acromegaly in our center. More cancer screening should be considered when managing acromegaly, especially in patients with higher posttreatment GH and IGF-1.

Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center.

Background: Growth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported. Objectives: This study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center. Methods: We retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital's information system. Results: Based on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P <0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group. Conclusion: There are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA.

Clinical and Proteomic-Based Molecular Characterizations of Invasive and Noninvasive Somatotroph PitNETs.

INTRODUCTION: Somatotroph pituitary neuroendocrine tumours (PitNETs) are characterized by complex and variable biological behaviours with unpredictable patterns of growth and invasiveness. The molecular mechanisms and reliable predictors of biological markers of invasiveness remain unknown. METHODS: Seventy-two acromegaly patients were consecutively enrolled. Data-independent acquisition-based proteomics and ingenuity pathway analysis were conducted between invasive and noninvasive somatotroph PitNETs. The expression of selected biomarkers was verified in PitNET tissue, and its correlation with various clinical indicators and outcomes of these tumours was assessed. The invasive phenotypes of GH3 cells were validated in vitro. RESULTS: Patients with invasive somatotroph PitNETs were significantly younger at onset and diagnosis, with significantly higher secretion and faster growth and a lower long-term biochemical response rate than patients with noninvasive somatotroph PitNETs. Proteomic data were evaluated in a consecutively collected sample of 19 (10 invasive and 9 noninvasive somatotroph PitNETs) tumours and indicated a distinct proteomic pattern. The enriched and important pathways included IL-4, PDGF, PTEN, VEGF, PI3K/AKT, FAK, and other pathways that were significantly associated with tumour proliferation, migration, and invasion. High cathepsin Z (CTSZ) expression was found in invasive somatotroph PitNETs and significantly positively correlated with parameters of tumour invasion and growth. In Ctsz-overexpressing GH3 cells, cell proliferation, invasion, and migration were consequently increased. CONCLUSION: It is more difficult for patients with invasive somatotroph PitNETs to achieve remission than those with noninvasive somatotroph PitNETs, and proteomic data analysis has revealed the high expression of CTSZ as a contributing factor to invasive transformation and poor prognosis in somatotroph PitNETs for the first time.

Influence of lung cancer model characteristics on tumor targeting behavior of nanodrugs.

Evidence is mounting that there is a significant gap between the antitumor efficacy of nanodrugs in preclinical mouse tumor models and in clinical human tumors, and that differences in tumor models are likely to be responsible for this gap. Herein, we investigated the enhanced permeability and retention (EPR) effect in mouse lung cancer models with different tumor growth rates, volumes and locations, and analyzed the nanodrug tumor targeting behaviors limited by tumor vascular pathophysiological characteristics in various tumor models. The results showed that the fast-growing tumors were characterized by lower vascular tight junctions, leading to higher vascular paracellular transport activity and nanodrug tumor accumulation. The paracellular transport activity increased with the growth of tumor, but the vascular density and transcellular transport activity decreased, and as a result, the average tumor accumulation of passive targeting nanodrugs decreased. Orthotopic tumors were rich in blood vessels, but had low vascular transcellular and paracellular transport activities, making it difficult for nanodrug accumulation in orthotopic tumors via passive targeting strategies. The antitumor efficacy of passive targeting nanodrugs in various lung cancer-bearing mice validated the aforementioned nanodrug accumulation behavior, and nanodrugs based on the angiogenesis-tumor sequential targeting strategy achieved obviously improved efficacy in orthotopic lung cancer-bearing mice. These results suggest that the EPR effect varies in different tumor models and should not be used as a universal targeting strategy for antitumor nanodrugs. Besides, attention should be paid to the animal tumor models in the evaluation of nanodrugs so as to avoid exaggerating the antitumor efficacy.

The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible.

Purpose: This study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) in active and controlled acromegaly patients. Methods: This cross-sectional study involved 55 acromegaly patients from a tertiary hospital (23 males and 32 females, aged 45.0 ± 11.6 years). Firstly, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and markers for bone turnover were assessed. Next, we derived peripheral bone microstructure parameters and volumetric bone mineral density (vBMD) through HR-pQCT. These parameters were compared between acromegaly patients and 110 healthy controls, as well as between 27 active and 28 controlled acromegaly patients. Moreover, the relationship between GH/IGF-1 and bone microstructure parameters was analyzed through multiple linear regression. Results: As compared with healthy controls, acromegaly patients exhibited elevated cortical vBMD, reduced trabecular vBMD, and increased trabecular inhomogeneity in the distal radius and tibia. While controlled acromegaly patients had slower bone turnover, they did not necessarily have better bone microstructure relative to active patients in intergroup comparison. Nevertheless, multiple regression indicated that higher IGF-1 was associated with lower tibial stiffness and failure load. Additionally, males with higher IGF-1 typically had larger trabecular separation, lower trabecular number, and larger cortical pores in the radius. Moreover, patients with elevated GH typically had more porous cortical bone in the radius and fewer trabeculae in the tibia. However, the compromised bone strength in active patients was partially compensated by increased bone thickness. Furthermore, no significant linkage was observed between elevated GH/IGF-1 and the most important HR-pQCT parameters such as trabecular volumetric bone density. Conclusion: Acromegaly adversely affected bone quality, even in controlled patients. As the deterioration in bone microstructure due to prolonged GH/IGF-1 exposure was not fully reversible, clinicians should be aware of the bone fragility of acromegaly patients even after they had achieved biochemical remission.

Case Report: A Clinical and Genetic Analysis of Childhood Growth Hormone Deficiency With Familial Hypercholesterolemia.

Background: Growth hormone deficiency (GHD) is a developmental disorder in children characterized by low growth hormone (GH), short stature and unfavorable lipid profiles. Familial hypercholesteremia (FH) is an inborn disorder of low-density lipoprotein cholesterol (LDL-C) metabolism which results in premature cardiovascular events. The co-occurrence of GHD and FH, which may aggravate the hypercholesteremic condition in the affected individuals, had rarely been discussed in previous publication. Methods: This work reports two cases of GHD with FH, and explores the lipid profiles of GHD children and their therapeutic response to recombinant human growth hormone (rhGH). The diagnosis of GHD is based on low peak GH level (<7 ng/mL) in GH provocation test. FH is diagnosed by high LDL-C level (≥ 4 mmol/L) and confirmed genetic mutations in the LDL-C metabolic pathway. We also searched all previously published metabolic studies on GHD children as of December 31, 2020. Information on their LDL-C, duration and dose of rhGH treatment were retrieved and summarized. Results: The first case was a 5.3 year-old boy. His height was 103.6 cm (SDS = -2.29) and his peak GH in provocative test was 6.37 ng/mL. Additionally, his LDL-C was 4.80 mmol/L and he harbored a heterozygous mutation for the apolipoprotein B (APOB) gene (c.10579 C > T). The second case was a 9-year-old girl at the height of 117.3 cm (SDS = -2.91). Her GH peaked at 4.99 ng/mL in insulin-induced hypoglycemic test and 2.80 ng/mL in L-dopa test. Her LDL-C was 6.16 mmol/L, and she carried a mutated copy of the low-density lipoprotein receptor (LDLR) gene (c.809 G > A). Literature review indicated that GHD children suffered from higher baseline LDL-C, but it was significantly reduced after rhGH treatment. Conclusions: FH should be considered if a GHD child has remarkably elevated LDL-C that cannot be attributed to low GH level alone. Genetic mutations in the LDL-C metabolic pathway prevent the body from effectively metabolizing lipids, thereby resulting in early-onset hypercholesteremia and probably playing a negative role in children's growth.

Precipitate Evolution in 22Cr25NiWCuCo(Nb) Austenitic Heat-Resistant Stainless Steel during Heat Treatment at 1200 °C.

In this study, 22Cr25NiWCuCo(Nb) heat-resistant steel specimens with high Cr and Ni contents were adopted to investigate the effect of Nb content on thermal and precipitation behavior. Differential scanning calorimetry profiles revealed that the melting point of the 22Cr25NiWCuCo(Nb) steel specimens decreased slightly with the Nb content. After heat treatment at 1200 °C for 2 h, the precipitates dissolved in a Nb-free steel matrix. In addition, the Z phase (CrNb(C, N)) and MX (Nb(C, N), (Cr, Fe)(C, N), and NbC) could be observed in the Nb-containing steel specimens. The amount and volume fraction of the precipitates increased with the Nb content, and the precipitates were distributed heterogeneously along the grain boundary and inside the grain. Even when the heat treatment duration was extended to 6 h, the austenitic grain size and precipitates became coarser; the volume fraction of the precipitates also increased at 1200 °C. The Z phase, rather than the MX phase, became the dominant precipitates at this temperature.

Effect of silver on microstructure and antibacterial property of 2205 duplex stainless steel.

In this study, 2205 duplex stainless steel (DSS) was employed to enhance the antibacterial properties of material through silver doping. The results demonstrated that silver-doped 2205 DSS produces an excellent bacteria-inhibiting effect against Escherichia coli and Staphylococcus aureus. The antibacterial rates were 100% and 99.5%, respectively. Because the mutual solubility of silver and iron is very low in both the solid and liquid states, a silver-rich compound solidified and dispersed at the ferrite/austenite interface and the ferrite, austenite, and secondary austenite phases in silver-doped 2205 DSS. Doping 2205 DSS with silver caused the Creq/Nieq ratio of ferrite to decrease; however, the lower Creq/Nieq ratio promoted the rapid nucleation of γ2-austenite from primary α-ferrite. After 12h of homogenisation treatment at 1200 °C, the solubility of silver in the γ-austenite and α-ferrite phases can be increased by 0.10% and 0.09%, respectively. Moreover, silver doping was found to accelerate the dissolution of secondary austenite in a ferrite matrix during homogenisation.

Implicit trust between the Uyghur and the Han in Xinjiang, China.

Trust is a vital lubricant that increases the sense of security in social interactions. In this study, we investigated the intergroup trust between the Uyghur and the Han, the two largest ethnic groups in Xinjiang, China, with a Go/No-Go Association Task. Specifically, we instructed Uyghur and Han participants to respond to ethnic faces (Uyghur vs. Han) and trust/distrust words and measured the strength of the automatic associations between the faces and words for both in-group and out-group pairs. As expected, both ethnic groups showed implicit in-group trust and out-group distrust, but the Han group demonstrated stronger in-group trust and out-group distrust toward the Uyghur than the Uyghur group toward the Han. However, the magnitude of distrust of the Han toward the Uyghur was small to medium as compared with that reported by other intergroup relationship research. In addition, participant geographic location was associated with out-group distrust. These findings offer implications for developing effective strategies to encourage trust between conflicting groups.

Thermal stability of TiAlN and nanocomposite TiAlSiN thin films.

TiAlN and TiAlSiN coatings were synthesized by a cathodic arc deposition process. Titanium, Ti50Al50 alloy and AlSi (88 at.% of Al and 12 at.% of Si) alloy targets were adopted as the cathode materials. X-ray diffraction analyses revealed that Ti0.5Al0.5N and Ti49Al0.44Si0.07N possess a B1-NaCl crystal structure. The lattice constants of the Ti0.5Al0.5N and Ti0.49Al0.44Si0.07N calculated from XRD pattern were 0.418 nm and 0.422 nm, respectively. For the high temperature oxidation test, the coated samples were annealed at 900 degrees C in air atmosphere for 2 hours. In this study, the deposited Ti0.5Al0.5N had completely transformed to TiO2 and Al2O3, and Ti0.49Al0.44Si0.07N remained the as-deposited structure after oxidation treatment. It indicated that Ti0.49Al0.44Si0.07N possesses superior oxidation resistance than Ti0.5Al0.5N, due to the amorphous SiNx phase existed in the nanocomposite structure. The different oxidation mechanisms of Ti50Al50N and Ti0.49Al0.44Si0.07N at high temperature of 900 degrees C are developed in this study.

Microstructure characterization of multilayered TiSiN/CrN thin films.

Monolayered TiSiN and multilayered TiSiN/CrN coatings were synthesized by a cathodic arc deposition process. The chromium and Ti/Si (80/20 at.%) alloy targets were adopted as the cathode materials, altering the ratio of cathode current (I[TiSi]/I[Cr]) to obtain various multilayer periodic thicknesses of multilayered TiSiN/CrN coatings. X-ray diffraction and TEM analyses showed that all the deposited monolayered TiSiN and multilayered TiSiN/CrN films possessed the B1-NaCl structure. In this study, it was shown that the multilayer periods (Lambda) of the TiSiN/CrN deposited at I[TiSi]/I[Cr] cathode current ratios of 1.8, 1.0, and 0.55 were 8.3 nm, 6.2 nm, and 4.2 nm, respectively, with multilayer periodic thicknesses decreasing with smaller I[TiSi]/I[Cr] cathode current ratios. An amorphous phase was found at the boundaries of the TiN/CrN column grains. In addition, the multilayered TiSiN/CrN coatings displayed a lamellar structure that was well-defined and nonplanar between each TiN and CrN layer.