Morphological variation and expressed sequence tags-simple sequence repeats-based genetic diversity of Aspergillus cristatus in Chinese dark tea.

Introduction: Aspergillus cristatus is a homothallic fungus that is used in the natural fermentation process of Chinese Fuzhuan tea and has been linked to the production of bioactive components. However, not much is known about the variations present in the fungus. To understand the variation of the dominant microorganism, A. cristatus, within dark tea, the present study investigated the genetic and morphological diversity of 70 A. cristatus collected across six provinces of China. Methods: Expressed sequence tags-simple sequence repeats (EST-SSR) loci for A. cristatus were identified and corresponding primers were developed. Subsequently, 15 specimens were selected for PCR amplification. Results: The phylogenetic tree obtained revealed four distinct clusters with a genetic similarity coefficient of 0.983, corresponding to previously identified morphological groups. Five strains (A1, A11, B1, D1, and JH1805) with considerable differences in EST-SSR results were selected for further physiological variation investigation. Microstructural examinations revealed no apparent differentiation among the representative strains. However, colony morphology under a range of culture media varied substantially between strains, as did the extracellular enzymatic activity (cellulase, pectinase, protease, and polyphenol oxidase); the data indicate that there are differences in physiological metabolic capacity among A. cristatus strains. Discussion: Notably, JH1805, B1, and A11 exhibited higher enzymatic activity, indicating their potential application in the production of genetically improved strains. The findings provide valuable insights into species identification, genetic diversity determination, and marker-assisted breeding strategies for A. cristatus.

Comparison of 1-stage and 2-stage Managements for Common Bile Duct Stones and Gallstones (CBDS): A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS). METHODS: This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups. RESULTS: Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05). CONCLUSIONS: Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.

Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas.

OBJECTIVE: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

Steroid profiling in adrenal disease.

The measurement of steroid hormones in blood and urine, which reflects steroid biosynthesis and metabolism, has been recognized as a valuable tool for identifying and distinguishing steroidogenic disorders. The application of mass spectrometry enables the reliable and simultaneous analysis of large panels of steroids, ushering in a new era for diagnosing adrenal diseases. However, the interpretation of complex hormone results necessitates the expertise and experience of skilled clinicians. In this scenario, machine learning techniques are gaining worldwide attention within healthcare fields. The clinical values of combining mass spectrometry-based steroid profiles analysis with machine learning models, also known as steroid metabolomics, have been investigated for identifying and discriminating adrenal disorders such as adrenocortical carcinomas, adrenocortical adenomas, and congenital adrenal hyperplasia. This promising approach is expected to lead to enhanced clinical decision-making in the field of adrenal diseases. This review will focus on the clinical performances of steroid profiling, which is measured using mass spectrometry and analyzed by machine learning techniques, in the realm of decision-making for adrenal diseases.

Reference intervals for LC-MS /MS measurements of plasma renin activity, aldosterone, angiotensin II, and 24-hour urinary aldosterone in Northern Chinese Han population.

BACKGROUND: Examination of aldosterone to Renin Ratio (ARR) and plasma aldosterone concentration (PAC) or 24-h urinary aldosterone excretion (24-h UALD) was the necessary tests in confirmatory tests for primary aldosteronism (PA). We developed a combined liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for plasma renin activity (PRA), PAC, and angiotensin II (Ang II) and investigated their reference intervals (RIs) in northern Chinese Han population. The RIs of 24-h UALD excretion were also studied using LC-MS/MS. METHODS: A total of 309 healthy volunteers were recruited in 3 cities in China. PRA, PAC, Ang II, and 24-h UALD were measured using the laboratory-developed LC-MS/MS. Multiple linear regression and the variance component model were applied to determine if the RI needed to be split. The RIs of PRA, PAC, and Ang II were determined using the nonparametric percentile method. RESULTS: The laboratory-developed LC-MS/MS method was verified and showed good performance. Standard deviation ratio (SDR) sex for PAC and SDR region for Ang II are 0.466 and 0.407, respectively, indicating that the RIs of PAC and Ang II must be divided by sex and region, respectively. In addition, the SDR 24hUK for 24-h UALD is 0.579, indicating that the RI of 24-h UALD must be partitioned by urine potassium. CONCLUSION: RIs were established for tests related to the renin-angiotensin-aldosterone system in the apparently healthy northern Chinese Han population by the LC-MS/MS method.

Leukadherin-1 inhibits NLRP3 inflammasome by blocking inflammasome assembly.

Aberrant activation of the NLRP3 inflammasome has been implicated in the occurrence and development of many inflammatory diseases, and thus potent inhibitors of the NLRP3 inflammasome should be explored. An antitumor agent, Leukadherin-1 (LA-1), tested in phase 1/2 clinical trials, has been reported to exert anti-inflammatory properties by blocking the NF-κB pathway. However, the effects of LA-1 on the NLRP3 inflammasome have not been conclusively determined. In this study, we found that at lower doses (below 1 µM) ex vivo, LA-1 blocked NLRP3 inflammasome activation without affecting NF-κB signaling. Accordingly, 1 mg/Kg LA-1 strongly inhibited the release of NLRP3-dependent cytokine, but only slightly inhibited NLRP3-independent-cytokines secretion in endotoxemia and alleviated NLRP3-dependent peritonitis in vivo. Mechanistically, LA-1 had no effects on ion flux or mitochondrial injury. Instead, it inhibited NLRP3 inflammasome assembly by suppressing ASC oligomerization, blocking NLRP3 self-assembly, and reducing interactions of NLRP3 with ASC and NEK7. Therefore, LA-1 inhibits NLRP3 inflammasome activation, implying that it is a potential treatment option for NLRP3-associated diseases.

Renal arteriovenous fistula complicated with malignant hypertension: a case report.

Renal arteriovenous fistula (RAVF) is a rare vascular disease and is usually presented with severe hypertension. Renin-angiotensin-aldosterone system (RAAS) activation was proposed to play a key role in RAVF-induced hypertension but the data was inconsistent. We reported a case of RAVF presented as malignant hypertension, which was detected by contrast-enhanced ultrasonography and successfully managed by interventional embolization. A 35-year-old male was presented with a headache and blurred vision. His blood pressure was up to 220/110 mmHg, with significantly elevated serum creatinine and proteinuria. Hypertensive target organ impairments were noted. A RAVF was detected by contrast-enhanced renal ultrasonography. He underwent renal artery angiography and renal arteriovenous fistula embolization. RAAS activation was also evaluated by separate renal vein sampling. The patient's blood pressure and target-organ damage improved after RAVF embolization and blood pressure control. This is a rare case of renal arteriovenous fistula with malignant hypertension. Contrast-enhanced ultrasonography can be useful for diagnosis.

Extraventricular neurocytoma at the sellar region: Report of 8 cases and literature review.

BACKGROUND: Extraventricular neurocytoma at the sellar region (EVNSR) is an exceedingly rare tumor. Given the paucity of specificity and its peculiar nature, our study aimed to characterize the clinical, imaging, and pathological features, including treatment and clinical outcomes of this tumor. METHOD: Eight patients with pathologically confirmed EVNSR at Beijing Tiantan Hospital from 2012 to 2020 were retrospectively analyzed. Additionally, 7 cases from the prior detailed literature were also retrieved. FINDINGS: Among the 8 patients from Beijing Tiantan Hospital, 2 males and 6 females with an average age of 45.3 (range, 8-61). Vision impairment and headache were the most common complaints at presentation. Preoperative diagnoses were pituitary adenoma (n = 6), meningioma (n = 1), and oligodendroglioma (n = 1). Treatment included subtotal tumor resection (n = 3), partial resection (n = 5), adjuvant therapy covered radiotherapy (n = 2), and gamma knife surgery (n = 3). The clinical outcomes of these 8 cases were stable (n = 5), survival after progression (n = 1), and death after recurrence (n = 2). CONCLUSIONS: EVNSRs are extremely rare tumors, and most have benign prognoses after appropriate treatment. Due to the unique location, total removal of the tumor is challenging; And adjuvant radiation therapy for eligible patients is recommended. Regular imaging review is also advised. Future studies with more patients are needed to elucidate the biological nature of EVNSRs.

An automated magnetic bead extraction method for measuring plasma metanephrines and 3-methoxytyramine using liquid chromatography tandem mass spectrometry.

Liquid chromatography tandem mass spectrometry (LC-MS/MS) is used routinely in clinical diagnostics; however, automating the sample pretreatment is challenging. We established and evaluated an automated method based on the magnetic bead extraction principle (MBE) to measure normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT). The target analytes were extracted, purified, and concentrated using different solvents and chemical bond-modified magnetic beads transferred via a magnetic bar. The linearity, recovery, matrix effect, and precision of MBE were evaluated thoroughly, and compared with traditional solid-phase extraction (SPE) using 131 plasma samples. The chromatography peaks of metanephrines and 3-MT, extracted via MBE, are symmetrical, without interfering peaks. The linearity was excellent with correlation coefficient (r) > 0.99. The MBE exhibited good reproducibility with within-run coefficient variations (CVs) of 1.96-2.00%, 4.06-5.75%, and 3.89-4.90% for MN, NMN, and 3-MT, respectively. The total CVs for MN, NMN, and 3-MT were 1.96-2.80%, 5.12-5.75%, and 5.44-6.27%, respectively. The relative recoveries for MN, NMN, and 3-MT varied between 93.5 and 107.4%, whereas their biases were all within 10%. The results for MN, NMN, and 3-MT extracted via MBE compared with SPE exhibited excellent correlation, with r > 0.99; the mean bias% for MN, NMN, and 3-MT were small (-2.9%, -3.2%, and -3.2%, respectively). In conclusion, the automated MBE method for measuring plasma metanephrines and 3-MT can be applied in future routine clinical diagnostics, and the MBE principle may indicate a new era for LC-MS/MS in clinical application.

Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing ß-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Evaluation of bone metabolism-associated biomarkers in Tibet, China.

AIM: To measure and evaluate the distribution and possible contributing factors of seven bone metabolism-associated biomarkers in Tibet, a plateau province of China. METHODS: A total of 1615 individuals were recruited from Tibet at three different altitudes. The levels and possible contributing factors of serum calcium, serum phosphorus, ALP, 25OHD, PINP, CTX, and PTH were evaluated. RESULTS: In total, 1246 Tibetan adults (males: n = 543) were eventually enrolled in this study. Multiple linear regression recognized age, sex, altitude, and BMI as the major effect factors. The levels of ALP, PINP, and CTX in males continuously decreased with age; however, those in females increased after approximately 39 years of age. Males had higher 25OHD levels (23.9 vs. 15.4 ng/ml) but lower levels of serum phosphorus (1.12 vs. 1.19 mmol/L) and PTH (41.3 vs. 47.4 pg/ml) than females. Before the age of 50, males had higher levels of calcium, ALP, PINP, and CTX than females, and the opposite trend was observed after the age of 50. The highest levels of serum calcium and phosphorus and the lowest levels of PINP and CTX were found in the Shigatse/Lhasa region, suggesting a better bone metabolism status. Compared with reports from plain areas of China, significantly higher levels of PINP (65.3 vs. 49.36 ng/ml) and CTX (0.46 vs. 0.37 ng/ml) were recorded in Tibetan adults. CONCLUSION: A more active bone turnover status was found in Tibetan adults than in individuals from the plain areas of China.

Analytical and Clinical Performance of a Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Gastrin Subtypes G34 and G17 in Serum.

BACKGROUND: Two major forms of gastrin, gastrin-17 (G17) and gastrin-34 (G34), exist in blood. However, conventional immunoassay methods can only quantify total gastrin or G17 alone. Here, we aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify G17 and G34 simultaneously. METHODS: Serum samples were prepared by anion-exchange solid-phase extraction. The analytical performance of the LC-MS/MS method was validated and the method was compared to chemiluminescence immunoassay (CLIA) and radioimmunoassay (RIA). The G17 and G34 concentrations in 245 serum samples from healthy controls, individuals with gastrinoma, and individuals with other diseases were analyzed. RESULTS: The total runtime of the LC-MS/MS method was 6 min. No substantial matrix effect was observed with internal standard correction. The intraassay coefficients of variation (CVs) for G17 and G34 were 4.0%-14.2% and 4.4%-10.4%, respectively, and total CVs were 5.2%-14.1% and 4.6%-12.4%, respectively. The correlation coefficient between LC-MS/MS and CLIA was 0.87, and between LC-MS/MS and RIA was 0.84. The G17+G34 concentrations for 87.5% of individuals with gastrinoma were higher than the 95th percentile of healthy controls (18.1 pg/mL), whereas the concentrations for individuals with other diseases and gastrinoma overlapped. Based on the Youden indices calculated for G17+G34, G34, and G17, the most specific biomarker was G17 (96.9% clinical specificity at 209.8 pg/mL) for gastrinoma. CONCLUSIONS: This method should aid in the diagnosis of diseases associated with increased gastrin concentrations.

Dexmedetomidine inhibits unstable motor network in patients with primary motor area gliomas.

BACKGROUND: Sedative agents such as dexmedetomidine have been found to transiently exacerbate or unmask limb motor dysfunction in patients with eloquent area brain gliomas. The present study aims to investigate whether dexmedetomidine can inhibit motor plasticity in patients with glioma via fMRI. METHODS: 21 patients with brain glioma were prospectively recruited between September 2017 and December 2018. Patients were classified into pre-M1 (primary motor cortex) group (n=9), post-M1 group (n=6), and non-eloquent group (control group) (n=6) according to the tumor position related to M1. The hand movement task-fMRI and resting state fMRI (rs-fMRI) were performed before and after sedation using dexmedetomidine. The lateralization index (LI) of activation voxels and magnitude and the functional connectivity (FC) of motor network were compared before and after sedation and among different groups. RESULTS: Permanent postoperative motor deficit of the upper limb was found in 5 of 6 patients in the pre-M1 group, and none in other groups (P < .01). Task-fMRI showed the LI of activation volume and activation magnitude at M1 significantly increased only in the pre-M1 group after sedation (P < .05). Rs-fMRI showed 60.0% (27 of 45) FCs of motor network decreased in pre-M1 group after sedation (p[FDR] < .05); whereas there was no FC reduction in post-M1 and control groups (p[FDR] > .05). CONCLUSIONS: In patients with eloquent area gliomas, dexmedetomidine can inhibit the unstable compensative motor plasticity on both task- and rs-fMRI. fMRI may be a promising method for elucidating the effect of sedative agents on motor plasticity.

Plasma or serum, which is the better choice for the measurement of metanephrines?

Measurement of metanephrines (MNs: metanephrine [MN] and normetanephrine [NMN]) is recommended for the initial biochemical diagnosis of pheochromocytoma and paraganglioma. Despite some drawbacks, plasma is commonly used for sampling. Here, we determined the feasibility of using serum, as an alternative to plasma, by comparing MNs in plasma and serum and evaluating the stability of MNs in serum. MNs obtained from serum, EDTA plasma, and heparin plasma were measured using LC-MS/MS immediately or after storage at 4 °C for 24 h, 72 h, and 7 days, and at -80 °C for 7 days, after sample collection. The differences between sample stability at given time points were compared using one-way ANOVA and Students' paired t-test, and the mean percent deviation was compared with total change limit (TCL). No significant difference was observed in MN and NMN between serum and EDTA plasma, and the mean percent deviation of the results obtained from serum compared to that from EDTA plasma was within the TCL. However, the difference of MN between EDTA plasma and heparin plasma exceeded the TCL. Both MNs in EDTA plasma and heparin plasma showed a significant decreasing trend at 4 °C with time (p < .01), while those in serum were relatively stable, with the mean percent deviation not exceeding the TCL at any time point or temperature. In conclusion, MNs measurement did not significantly differ between EDTA plasma and serum when measured immediately after collection, and MNs in serum were more stable than that in plasma.

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

Experimental Treatment of SIV-Infected Macaques via Autograft of CCR5-Disrupted Hematopoietic Stem and Progenitor Cells.

Hematopoietic stem cell (HSC)-based gene therapy targeting CCR5 represents a promising way to cure human immunodeficiency virus type 1 (HIV-1) infection. Yet the preclinical animal model with transplantation of autologous CCR5-ablated HSCs remains to be optimized. In this study, four Chinese rhesus macaques of simian immunodeficiency virus (SIV) chronic infection were given long-term antiretroviral therapy (ART), during which peripheral CD34+ hematopoietic stem and progenitor cells (HSPCs) were purified and infected with CCR5-specific CRISPR/Cas9 lentivirus (three monkeys) or GFP lentivirus (one monkey). After non-myeloablative conditioning, the CCR5-modified or GFP-labeled HSPCs were autotransplanted to four recipients, and ART was withdrawn following engraftment. All of the recipients survived the process of transplantation. The purified CD34+ HSPCs harbored an undetectable level of integrated SIV DNA. The efficiency of CCR5 disruption in HSPCs ranges from 6.5% to 15.6%. Animals experienced a comparable level of hematopoietic reconstuction and displayed a similar physiological homeostasis Despite the low-level editing of CCR5 in vivo (0.3%-1%), the CCR5-disrupted cells in peripheral CD4+ Effector Memory T cell (TEM) subsets were enriched 2- to 3-fold after cessation of ART. Moreover, two of the three treated monkeys displayed a delayed viral rebound and a moderately recovered immune function 6 months after ART withdrawal. This study highlights the importance of improving the CCR5-editing efficacy and augmenting the virus-specific immunity for effective treatment of HIV-1 infection.

Establishing reference intervals for urine and serum iodine levels: A nationwide multicenter study of a euthyroid Chinese population.

CONTEXT: Urinary iodine (UI) is commonly used for evaluating iodine status, whereas serum iodine (SI) is more closely correlated with bioavailable iodine. However, no reliable reference intervals (RIs) for clinical use are available. We aimed to establish RIs for SI, UI, and a ratio of UI to urinary creatinine (U-Cre) applicable to the Chinese population. METHODS: This multicenter cross-sectional study enrolled 930 apparently healthy adults from six representative cities in China (Beijing, Dongying, Guiyang, Urumqi, Shenzhen, and Qiqihar) in 2017. Thyroid ultrasonography and thyroid function tests, including antithyroid antibody tests, were performed to exclude individuals with latent thyroid diseases. An iodine intake-related questionnaire survey was performed. SI and UI were measured using inductively coupled plasma-mass spectrometry. Possible influencing factors of iodine levels were evaluated using multiple regression analysis. RESULTS: Post-exclusion, the final analysis included 894 individuals. Seafood intake frequency was positively correlated with SI (standardized partial regression coefficient = 0.23) but not with UI and UI/U-Cre. SI was positively correlated with serum TT4 (Spearman correlation coefficient: 0.40), TT3 (0.23), and FT4 (0.18). SI and UI showed no age- or sex-specific variations. Significantly higher UI/U-Cre values were observed in Qiqihar than in Beijing, Guizhou, and Shenzhen. Shenzhen showed the lowest UI levels among all evaluated cities. With application of latent abnormal values exclusion procedurere, the RIs for SI, UI, and UI/U-Cre in the population were 36.0-79.3 µg/L, 19-385 µg/L, 22-450 µg/g, respectively. CONCLUSIONS: We established RIs for UI and SI among healthy Chinese individuals with no thyroid nodule or dysfunction.

Validation of an improved liquid chromatography tandem mass spectrometry method for rapid and simultaneous analysis of plasma catecholamine and their metabolites.

Catecholamines [dopamine (DA), epinephrine (E), and norepinephrine (NE)] and their metabolites [metanephrine (MN), normetanephrine (NMN), and 3-methoxytyramine (3-MT)] are functionally important in humans. Their overexpression can indicate the presence of neuroendocrine tumors. Accurate and rapid quantitation of catecholamines and their metabolites may function in differential diagnosis of neuroendocrine tumors. Herein, we diluted 200 µL plasma using isotope labelled internal standards (IS), and extracted using solid phase extraction. The performance of isotope diluted liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) was evaluated and applied to quantify the level of catecholamines and metabolites in clinical samples from 73 apparently healthy adults. The total analysis time of the ID-LC-MS/MS method was 4 min. The improved method was highly sensitive, with a limit of quantification (LOQ) for MN, NMN, 3-MT, and E of 1 pg/mL, a LOQ for DA of 5 pg/mL, and for NE of 10 pg/mL. After correction using IS, no significant matrix effects were observed. Good reproducibility was obtained, with total CVs of 3.2-13.1% (DA), 4.8-10.0% (E), 6.2-6.9% (NE), 3.8-7.9% (MN), 4.1-8.8% (NMN), 3.4-8.9% (3-MT). Recoveries were in the range of 91.1-109.7% for the six analytes. Also, the mean concentration of catecholamines were as follows: MN, 22.9 ±â€¯7.2 pg/mL; NMN, 41.4 ±â€¯17.2 pg/mL; 3-MT, 2.34 ±â€¯2.01 pg/mL; DA, 10.2 ±â€¯4.6 pg/mL; E, 29.3 ±â€¯14.2 pg/mL and NE 427.0 ±â€¯190.6 pg/mL. A reliable ID-LC-MS/MS method for the determination of catecholamines and their metabolites using small volumes of plasma was verified. This method is rapid, simple, and may serve as an essential diagnostic tool for neuroendocrine tumors in clinical practice.

Caspase-11 signaling enhances graft-versus-host disease.

Acute graft-versus-host disease (GVHD) remains a major obstacle for the wider usage of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an effective therapy for hematopoietic malignancy. Here we show that caspase-11, the cytosolic receptor for bacterial endotoxin (lipopolysaccharide: LPS), enhances GVHD severity. Allo-HSCT markedly increases the LPS-caspase-11 interaction, leading to the cleavage of gasdermin D (GSDMD). Caspase-11 and GSDMD mediate the release of interleukin-1α (IL-1α) in allo-HSCT. Deletion of Caspase-11 or Gsdmd, inhibition of LPS-caspase-11 interaction, or neutralizing IL-1α uniformly reduces intestinal inflammation, tissue damage, donor T cell expansion and mortality in allo-HSCT. Importantly, Caspase-11 deficiency does not decrease the graft-versus-leukemia (GVL) activity, which is essential to prevent cancer relapse. These findings have major implications for allo-HSCT, as pharmacological interference with the caspase-11 signaling might reduce GVHD while preserving GVL activity.